Pulse perfusion index (PI) reflects blood perfusion. It has been reported that PI can be used to evaluate the effect of nerve block, but currently, it is mainly focused on awake adults. In pediatric general anesthesia, it has been reported that PI can evaluate the effect of the sacral block. Still, there is a lack of relevant research on the impact of brachial plexus blocks. Our objective is to assess the prediction effects of PI on the success of supraclavicular brachial plexus block in pediatric patients under sevoflurane or propofol general anesthesia.This is a mono-center, parallel, 2-arm randomized superiority trial. One hundred four children aged 1 month to 12 years who undergo upper limb surgery will be enrolled in this study. According to anesthesia induction and maintenance medication, they will be divided into sevoflurane and propofol groups. The PI values of the index and little finger will be recorded on the blocked and non-blocked sides of supraclavicular brachial plexus block (SCB) in all children. The primary outcome is to assess the effects of PI on the success of supraclavicular brachial plexus block in pediatric patients under sevoflurane or propofol general anesthesia. The secondary outcome includes mean arterial blood pressure (MAP), heart rate (HR), and correlation between baseline PI and 10 min after SCB (PI ratio).This trial will provide evidence on the changes in PI after SCB in sevoflurane or propofol anesthesia in children. SCB may lead to changes in PI values under sevoflurane or propofol anesthesia. After the children wake up at the end of the surgery, the changes in PI values on the block side and non-block side may be helpful to judge the effect of nerve block when excluding the influence of anesthetics.NCT04216823. Registered on 15 July 2020.ClinicalTrials.gov  Fractures are common diseases in the growth and development of children . NaranjeBrachial plexus block (BCB) has a long history of being used for anesthesia and postoperative analgesia in upper limb surgery , 5. TherCurrently, studies found that PI can be used to evaluate the effect of nerve block primarily focused on awake adults , 17. Xu This study aims to describe the role of PI in evaluating the predictive effect of SCB in children under general anesthesia with sevoflurane and propofol. Meanwhile, whether PI could predict the success of SCB by reflecting the impact of ulnar nerve block.This is a parallel, 2-arm randomized superiority trial . Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology acting as the sponsor. Pediatric upper limb surgery cases will be collected in Tongji Hospital from May 2020 to December 2022. Children were divided into propofol and sevoflurane groups by the random number table method. PI values of the index finger and little finger in the blocked and non-blocked sides will be recorded in all children. Analyzing the possible relationship of the changes in PI values with complete block, partial block, and block failure in each group. A comparative analysis of sevoflurane and propofol block cases will determine whether PI can better judge the effect of supraclavicular brachial plexus block in which general anesthesia in children. The flowchart of this study is presented in Fig. According to literature reports , the proAge from 1 month to 12 yearsASA class I–IIElective upper extremity surgery in childrenSign the informed consent, and agree to participateEligibility criteria:Refusal by family membersChildren with abnormal behavior, including internalizing problems and externalizing problemsInflection at the puncture siteOther regional anesthesia contraindicationsChildren are allergic to known ingredients of experimental drugsExclusion criteria:After selection, the patient is found not to meet the selection or exclusion criteria.Children experienced severe adverse reactions or exacerbations during the clinical study.Withdrawal criteria:Prior to the commencement of the clinical study, the investigator will discuss the trial with the children and children’s guardian, including the research nature, the purpose of the study, possible benefits and risks, and the rights and obligations of the subject. The guardian signed the consent form, and the children who meet the eligibility criteria were randomly assigned to the sevoflurane group (SEV group) or propofol group (PRO group) in a 1:1 allocation. A computer-generated randomization schedule will allocate subjects. Allocations were maintained on a secure website accessed just before the procedure begin.After screening the child as a qualified subject and giving informed consent, a sealed opaque envelope containing a card with the computer-generated assignment number  will be opened by an anesthesia assistant who was not involved in the study. Anesthesiologists unblinded to the grouping of subjects are responsible for anesthesia management and nerve block according to the predetermined anesthesia.PO2). SEV group: Inhalation of sevoflurane (5%-8%) for induction of anesthesia, sufentanil 0.2 μg/kg, penehyclidine hydrochloride 0.01mg/kg, dexamethasone 0.1 mg/kg. Place the laryngeal mask, and maintain anesthesia with 1.0 MAC value of sevoflurane + 50% oxygen. PRO group: propofol 3 mg/kg, sufentanil 0.2 μg/kg, penehyclidine hydrochloride 0.01 mg/kg, dexamethasone 0.1 mg/kg are given for anesthesia induction. Place the laryngeal mask, and propofol 3 mg/kg/h is given for anesthesia maintenance. Then, all children will be placed supine with their heads tilted to the opposite side. Under ultrasound guidance, an experienced anesthesiologist will use an in-plane needle to block the supraclavicular nerve and give 0.25% ropivacaine 0.4 ml/kg.The children will be given a slow intravenous bolus of 0.1 mg/kg midazolam for sedation during the waiting period. After entering the operating room, routinely monitor the electrocardiogram (ECG), heart rate (HR), blood pressure (BP), respiration rate (RR), and pulse oxygen saturation  Assessment of restlessness and delirium during the recovery period and 30 min in PACU. (2) Postoperative pain score. Postoperative complications: nausea and vomiting, neurological dysfunction, Horner syndrome, respiratory depression, etc.The secondary outcome includes mean arterial blood pressure (MAP), heart rate (HR), and PI ratio (correlation between baseline PI and 10min after SCB). The age, gender, ASA classification, BMI, anesthesia time, operation time, anesthesia recovery time, duration of stay in PACU, and duration of postoperative hospital stay will be recorded.Complete block: There is no significant fluctuation of the HR, BP, and RR during the operation . Partial block: When a non-single nerve innervates the surgical site, there is a specific innervated area that causes HR, BP, and RR fluctuations , while there is no significant fluctuation in operation in other innervated area. Block failure: Operation in any innervated area caused substantial changes in HR, BP, and RR. For partial block and failure of block, a single dose of sufentanil (0.01 μg/kg) and a pump of 0.1–0.2 μg/kg/min remifentanil for supplementary analgesia.Record the PI values of the index finger and little finger on blocked and non-blocked sides in all children. Data collection and completion will be carried out by two research assistants blinded to the grouping of subjects. The clinical trial supervisors will periodically review the quality of data entry to ensure the authenticity and reliability of the program. This data supervision committee has no conflict of interest in the study. All information related to the study will be stored securely.t-test, analysis of variance, or rank-sum test will be used for comparison between groups of continuous variables. A logistic regression model will be used to analyze the influencing factors of anesthesia effect and complications, and stepwise regression will be used to screen independent variables. If data were missing, patients would be excluded from the specific analysis.Analyses will be performed using SPSS statistical software (version 19.0). Categorical variables are represented by frequency, and continuous variables are represented by mean ± standard deviation or median [interquartile range]. Chi-square test or Fisher test will be used for comparison between groups of classified variables, and There is no audit in the study.All children undergoing ultrasound-guided supraclavicular brachial plexus block for anesthesia can improve postoperative pain, reduce the use of postoperative analgesics, and promote recovery. In addition, the study will also benefit children undergoing upper limb surgery in the future.This study is observational. The possible adverse risks are all inherent complications and risks in surgery and anesthesia, and no additional adverse reactions and risks are added. Once any risk of harm is identified, the principal investigator will intervene to minimize potential harm. If there is any damage, the research team will provide appropriate compensation if necessary.Any possible protocol modification during the trial will require formal protocol modification. The Ethics Committee will conduct a comprehensive assessment and review of the subjects’ risks and inform all members after the new protocol is approved.The trial results will be published in the Clinical Trial Registry database or presented to the public as a publication upon completion of the entire clinical trial.PI has been used to evaluate the effect of brachial plexus, sciatic nerve, stellate ganglion in adults, and sacral canal block in children –20. SebaThe pediatric nerve block is mainly performed under sedation or general anesthesia , 22. SevIn conclusion, we intend to evaluate the prediction effect of PI on supraclavicular brachial plexus block after the induction of general anesthesia with sevoflurane or propofol in children, which could be used as a clue to evaluating the requirements of postoperative analgesics in children.Protocol version number and date: Ethics Approval No. 2020-S134 on 15 July 2020Date recruitment began: May 2021Approximate date when recruitment will complete: December 2022


Culture can be understood as an explicit social product arising from social interaction as an intentional or unintentional consequence of behavior. Educational Institutions culture differs from other organizational cultures as it impacts teachers' performance and students' learning. In this survey the definition of organizational culture used is given by Schein, “The deeper level of basic assumptions and beliefs that are, learned responses to the group's problems of survival in its external environment and its problems of internal integration; are shared by members of an organization; that operate unconsciously; and that define in a basic ‘taken -for-granted’ fashion in an organization's view of itself and its environment”  We identified sixty-five schools through the convenience sample method. A total of 1158 teachers' responses are considered in this dataset. The questionnaire is self administered by the school teachers. To maintain confidentiality, the identity of the teachers and the school names are not disclosed in the survey. The data were analyzed using SPSS software. Descriptive statistics was computed. A standardized tool measuring organizational culture - OCTAPACE scale The survey tool collected data on ten demographics of the teachers namely; Type of Board(Syllabus), Type of School(Management), Gender, Marital status, Age, Educational qualifications, Years of teaching experience, primary Teaching subject and Level of School. To measure the value and beliefs of organizational culture the OCTPACE scale was used. The OCTAPACE scale is primarily a forty item instrument that gives the profile of institutions ' ethos in eight dimensions, the dataset has data for thirty items more relevant to Indian schools. The eight dimensions of the OCTAPACE scale are: Pro-action, Authenticity, Openness, Collaboration, Experimenting, Trust, Confrontation and Autonomy. The scale contains 2 parts, Part-1, 22 items for the 8 dimensions is stated and the respondent is required to check on a 4-point scale how much each item is valued in their organization. The rating is 1=very low value, 2=rather low value, 3=fairly high value, and 4=highly valued. Part-2 contains 8 items on beliefs for the 8 dimensions stated and the respondent is required to check on a 4-point scale how widely each item is shared in their organization. The rating is 1=only a few or none share this belief, 2=only some share this belief, 3=fairly widely shared belief, and 4=very widely shared belief.The authors: Dr Jacqueline Kareem, Prof Harold Andrew Patrick, Dr Veerta Tantia and Dr Sharon Valarmathi hereby declare that this dataset has not been previously published elsewhere, nor is this dataset considered for publication elsewhere. Before collecting data from the respondents, a clear explanation was provided to the respondent of the research objective. The respondent's consent was duly obtained for publication of the data. We also received approval from the Research Ethics Committee (REC) of CHRIST (Deemed to be University), Bangalore (CU: RCEC/00217/08/21) After reviewing the objective, methodology of the survey, informed consent and the questionnaire, the Committee approved the survey. Respondents were communicated that the survey is used exclusively for academic purposes.Jacqueline Kareem: Conceptualization, Methodology, Investigation, Formal analysis. Harold Andrew Patrick: Conceptualization, Methodology, Investigation, Supervision. Veerta Tantia: Writing – original draft, Investigation. Sharon Valarmathi B: Investigation, Writing – review & editing.We as authors declare that we have no known competing financial interests or personal relationships, which have or could be perceived to have influenced our work reported in this article. The research is a non-funded survey.


Objective To evaluate clinical characteristics, maternal and fetal outcomes in pregnant women who underwent surgery for adnexal torsion (AT).Methods All patients, who underwent surgical operation due to AT during pregnancy at the Department of Obstetrics and Gynecology, School of Medicine, Ege University between 2005 and 2020 were retrospectively investigated. Main clinical and perioperative outcomes were evaluated.Results A total of 21 patients who underwent surgery due to AT during pregnancy were included. Of all patients, 61.9% underwent laparoscopy and the remaining 38.1% underwent laparotomy. The most common surgical procedure was adnexal detorsion in both groups (48%). Mean gestational age at the time of diagnosis, duration of surgery and hospitalization were significantly lower in the laparoscopy group, when compared with the laparotomy group  One of the patients had an infection during the postoperative period. Spontaneous abortion was only observed in one case.Conclusion It can be concluded that the surgical intervention implemented for the exact diagnosis and treatment of AT (laparotomy or laparoscopy) did not have an unfavorable effect on pregnancy outcomes such as abortion, preterm delivery, and fetal anomaly. However, laparoscopy may be superior to laparotomy in terms of advantages. Ovarian torsion is the complete or partial twisting of the pedicle on its vascular axis, which includes the ovarian arterial and venous vessels, interrupting the blood supply. If the ovarian torsion is accompanied by fallopian torsion, it is called adnexal torsion (AT). The adnexal detorsion (AD) surgery constitutes 2.7% of all gynecological emergent surgeries during pregnancy and may affect women of all ages, particularly during the reproductive period.The AT is rather rare during pregnancy and its incidence is between 1 and 5 in every 10,000 patients, among cases with spontaneous pregnancy.Early diagnosis is crucial for the preservation of the ovarian and tubal functions and decrease of the related risks of other morbidities. Since there are no exact diagnostic and imaging criteria for the confirmation of the preoperative diagnosis of AT, immediate surgical intervention is also important to preserve ovarian tissue and fertility, and preventing the adverse pregnancy outcomes. Laparoscopy is an effective and safe surgical method mostly preferred for AT treatment in pregnant and non-pregnant women in experienced centers.All patients, who had undergone surgery due to AT during pregnancy at the Department of Obstetrics and Gynecology, School of Medicine, Ege University  between 2005 and 2020, were retrospectively investigated. The data related to the demographic characteristics, medical, surgical and obstetric history, findings of the preoperative laboratory and ultrasound examinations, surgery reports, anesthesia, and hospitalization were accessed from the patients' antenatal follow-up files. Pregnancy outcomes such as abortion, gestational age at birth, birth weight, and congenital anomalies were investigated in detail. This study was approved by the Local Ethics Committee of the School of Medicine at Ege University . Patients whose medical records related to pregnancy monitoring and delivery were not available were excluded from the study.th–14thgestational weeks; second trimester: 14th–28thgestational weeks; third trimester: 28thgestational week–term). We evaluated the differences for the surgical characteristics, ultrasound findings, and pregnancy outcomes between the two groups.Regarding imaging methods, we used 2-D ultrasonography, with the Voluson-E8 , 3–9 MHz Transducer scanner and, less frequently, the magnetic resonance imaging (MRI) Magnetom Symphony  1.5-Tesla scanner. The ultrasound reports were retrospectively scanned, and the findings were divided into three groups: normal ovaries without the presence of cysts or mass, cystic ovaries, and hyperstimulated ovaries. The evaluation of the ultrasound reports showed that the short and long axis of the ovaries were measured in all patients. Furthermore, the mean ovarian diameter was measured, as the calculation of the ovarian volume was not possible. The preoperative white blood counts (WBC) and C-reactive protein (CRP) values were available for all patients. The participating patients were divided into groups according to the preferred surgical intervention (laparoscopy and laparotomy) and the trimester during which AT emerged , the Veress needle was inserted at the Palmer point to create pneumoperitoneum. After the intraabdominal pressure reached 10 to 12 mm Hg, and the 10 to 12 mm primary trocar was placed, the surgeon decided for the placements of the assistant trocars, taking the gestational week and the size of the adnexal mass into consideration. The supine position was selected for first-trimester patients, and left lateral position for the second-trimester patients to avoid aortocaval compression syndrome. In the laparotomy group, the decision of the abdominal incision was made according to the size of the uterus, and size and location of the adnexal mass. In the cases of patients who had undergone cystectomy and salpingo-oophorectomy, all resected materials were referred to the pathological examination. The fetal heartbeat was checked with an ultrasound before and after the intervention. All operations were performed by experienced, high-volume surgeons.t-test was used in normal distribution, and the Mann-Whitney U test was used in non-normal distribution. The Pearson Chi-square test and the Fisher exact test were used for the categorical variables.The Statistical Package for the Social Sciences  software, version 25.0, was used for the statistical analysis. The normal distribution of the numerical variables was analyzed with the Shapiro-Wilk test (n < 50). The numerical variables were given in mean ± standard deviation (SD), or median (min–max). The categorical variables were given in numbers and percentages. The independent binary sampleA total of 21 patients who had undergone surgery due to the AT during pregnancy were retrospectively investigated throughout the study period. The demographic and obstetric characteristics, as well as laboratory findings, were listed inThe preoperative imaging examination was mainly performed with ultrasonography and, less frequently, with MRI. We observed cystic lesions in the adnexa  in 47.6% of the cases, ovarian enlargement without mass or cyst in 38.1% of the patients, and hyperstimulated ovaries in 14.3% of the patients. The mean ovarian diameter was 77 ± 19 mm (range 52–130). Thirteen patients had their blood flow assessed by Doppler ultrasonography and normal blood flow was observed in 6 patients, who were surgically diagnosed with AT . The laboratory analysis showed that both preoperative WBC (12.368 ± 4.864 cells/µL) and CRP (1.2 ± 0.8 mg/dL) were slightly elevated.p = 0.006), duration of surgery (p = 0.001), and hospitalization (p = 0.001). There was no statistically significant difference between the groups for the gestational week at delivery, birth weight, preterm birth, cesarean section, ultrasound findings, and complications  and 38.1% (n = 8/21) of the patients, respectively. The most common surgical procedures were only adnexal detorsion (48%) . In onecations .thgestational week, and the remaining 18 cases (85.7%) in the 37thgestational week or later. The rate of cesarean section was 52.4% (n = 11/21) and all indications depended on the routine fetal, obstetric, or maternal factors. The majority of the patients (95.2%) gave live birth (n = 20/21) and only in one first-trimester patient, who had undergone laparoscopy and AD, spontaneous abortion happened two weeks after surgery. We observed no fetal anomaly in women who had given live birth. The comparison of patients according to the trimester, during which surgery was performed (first trimester and second trimester), showed that there was a statistically significant difference between the groups for the duration of surgery (p = 0.020) and hospitalization (p = 0.009). There was no statistically significant difference between these groups for the abortion rates, gestational age at delivery, birth weight, preterm birth, and cesarean section  among women with live birth; three of the cases (14.3%) had delivered before the 37section .The AT is one of the most common emergent conditions in obstetrics and gynecology, and it challenges the clinicians because of the maternal and fetal risks.Transabdominal ultrasonography is frequently the preferred imaging method for AT. Enlarged ovary, solid/cystic/complex ovarian mass, pelvic fluid, and edematous ovarian stroma with peripherally located small follicles are the most common findings in ultrasonographic examinations.thgestational week were reported.The decision for surgery during pregnancy, particularly in emergencies, is not always easy depending both on the circumstances related to surgery and possible effects of surgery on pregnancy outcomes. In the current literature, it was reported that laparoscopy did not increase the rate of the maternal and fetal complications, and it can be safely and effectively used in the diagnosis and treatment of AT.Some precautions should be taken to decrease complications during pregnancy related to these procedures, as noted in the literature. These include left lateral recumbent positioning, to minimize compression of vena cava inferior and aorta; initial port placement; and the Veress needle insertion sites should be adjusted according to the gravid's uterine size. Safer alternative sites, such as the Palmer point open technique, can be implemented to prevent devastating complications. Intra-abdominal pressure should not exceed 15 mm Hg during surgery, to minimize pressure-related complications. Moreover, the patient's carbon dioxide levels should be monitored with capnography during surgery.There are some differences between pregnant women and non-pregnant women in the management of the AT. The choice of anesthesia is generally guided by maternal indications, as well as the site and nature of the planned surgical procedure. However, most abdominal surgical procedures, including laparoscopy, require general anesthesia and muscle relaxation. Preservation of maternal hemodynamic stability, uteroplacental blood flow, and avoidance of maternal and fetal hypoxia throughout surgery, as well as avoidance of preterm delivery, are mandatory.There are different studies focused on the obstetric alterations in laparoscopy and laparotomy surgeries implemented due to AT in pregnant women.The small sample size and the retrospective nature were the main limitations of the present study. However, as AT during pregnancy is a rare disorder, to conduct a prospective study would be rather difficult. The absence of postnatal data is another limitation of our study.If AT is suspected during pregnancy, regardless of the trimester, surgery should not be delayed, to preserve the ovarian and tubal functions and prevent the torsion-related complications. The surgical method (laparotomy or laparoscopy) chosen for the diagnosis and treatment does not have any negative effect on pregnancy outcomes like abortion, preterm birth, and fetal anomaly. In cases with small, simple, non-malignant cystic lesions, adnexal detorsion and cyst fenestration seem a suitable treatment to preserve the ovarian reserve. Furthermore, according to the results of the present study, obstetric outcomes of pregnant women who underwent surgery for AT are generally favorable. If the surgery can be done via laparoscopy in pregnant cases within early gestations, postoperative recovery will be better than open surgery.


In the last decade, there have been substantial improvements in the outcome of the management of metastatic hormone-sensitive prostate cancer (mHSPC) following the development of several novel agents as well as by combining several therapeutic strategies. Although the overall survival (OS) of mHSPC is shown to improve with intense androgen deprivation therapy (ADT), combined with docetaxel, as well as other novel hormonal therapy agents, or alongside local intervention to the primary neoplasm. Notably, luteinizing hormone-releasing hormone (LHRH) antagonists are known to cause fewer cardiovascular side effects compared with LHRH agonists. Thus, in this mini review, we explore the different approaches in the management of mHSPC, with the aim that we may provide useful information for both basic scientists and clinicians when managing relevant clinical situations. Prostate cancer (PCa) is one of the most common cancers of the urino-genital system; its associated morbidity has progressively increased in the last decade . The morRecent advances in ADT drug therapy predominantly relate to the manufacturing of luteinizing hormone-releasing hormone (LHRH) antagonists, such as degarelix and relugolix.via a subcutaneous injection. In a randomized, parallel-group, phase III clinical study, Klotz et al. reported that testosterone suppression (≤0.5 ng/ml) was achieved in 97.2%, 98.3%, and 96.4% of the intention-to-treat population in degarelix 240/80 mg, degarelix 240/160 mg, and leuprolide groups, respectively. On Day 3, testosterone suppression was achieved in 96.1% and 95.5% of these patients, with a median testosterone (0.24–0.26) response to the degarelix 240/80 mg and 240/160 mg groups, respectively. Moreover, testosterone suppression was increased by 65% in the leuprolide group (Degarelix is a luteinizing hormone-releasing hormone (LHRH) antagonist for castration and testosterone suppression administered Relugolix is an oral LHRH antagonist. A multinational, randomized, phase III study showed that castration was maintained in 96.7% of the patients in the relugolix group compared with 88.8% in the leuprolide group. This indicated that relugolix was superior to leuprolide in all endpoints . The major cardiovascular adverse effects were reported by 2.9% of the patients in the relugolix group vs 6.2% of those in the leuprolide group, indicating that relugolix was superior to leuprolide in relation to sustained testosterone suppression with lower cardiovascular adverse effects (A phase II study investigated the impact of LHRH antagonists on cardiovascular disorders (CVDs) and reported that major cardiovascular and cerebrovascular events developed in 20% of patients in the LHRH agonist group vs only 3% of those in the LHRH antagonist group (p = 0.013); the absolute risk reduction in cardiovascular-related events in the antagonist group was 18.1% . These rExisting Novel hormonal therapy (NHT) drugs for treating mHSPC include abiraterone, enzalutamide, apalutamide, and darolutamide. ADT, combined with some of the aforementioned NHT drugs, is approved for the treatment of mHSPC as recommended by the National Comprehensive Cancer Network (NCCN), American Urological Association (AUA), and European Association of Urology (EAU) guidelines –13.post-hoc analysis of the LATITUDE trial showed that the median time to prostate-specific antigen (PSA) progression was 33.2 months in the abiraterone group and 7.4 months in the placebo group . Moreover, a significantly higher PSA50/90 was achieved in the abiraterone group than in the placebo group , and the risk of death was significantly reduced in patients who had a PSA50/90 response compared with patients who did not have a PSA response  were significantly prolonged by abiraterone compared with the placebo in the low-risk group . Also, the same conclusion was drawn in the other subgroups. No significant difference was found in the OS or FFS between the high-risk and low-risk groups, but the number of patients retreated in the low-risk group was fourfold higher than that in the high-risk group , which is produced during androgen synthesis. To manage adverse effects related to mineralocorticoid excess, such as hypokalemia, hypertension, and fluid retention, which can occur as a result of CYP17 inhibition, the administration of abiraterone with prednisone or prednisolone at a low dose of 5 mg twice daily is necessary . The LATresponse . A post-sk group . The STAPost-hoc analysis of the ARCHES study further clarified that compared to the placebo, enzalutamide reduced the risks of radiographic progression of bone metastases  and bone metastases with lymphatic metastasis  but did not significantly reduce the risk of lymph node metastases  activity at three levels: 1) AR nuclear translocation, 2) DNA binding, and 3) coactivator recruitment. The ENZAMET study estimated a 3-year OS using the Kaplan–Meier estimator and reported that the 3-year OS was 80% in the enzalutamide+ADT group (based on 94 events) and 72% in the first-generation anti-androgen+ADT group (based on 130 events) in mHSPC patients; enzalutamide also significantly benefitted secondary endpoints, but a high incidence of lassitude, epilepsy, or other adverse effects was observed in the enzalutamide group . The ARCtastases . The anatastases . In brietastases .Apalutamide is an anti-androgen drug similar to enzalutamide, but it has a higher affinity to AR . The TITDarolutamide is another AR inhibitor. In the latest ARASENS study in mHSPC, the results showed that compared to the placebo+ADT+docetaxel group, the risk of death was significantly reduced by 32.5% in the darolutamide+ADT+docetaxel group  and that darolutamide was beneficial for all secondary endpoints and subgroups . The ARAAlthough combination therapy with any of the above four NHT drugs provides a significant OS benefit compared with ADT alone, the best therapeutic sequences are still unclear. Regarding adverse effects on the central nervous system (CNS), the available evidence suggests that CNS-related adverse effects are less prevalent with darolutamide than with enzalutamide and apalutamide due to the moderate blood–brain barrier penetration of apalutamide and enzalutamide compared with the lower blood–brain barrier penetration of darolutamide and abiraterone , 35.post-hoc analysis suggested that no statistically significant OS benefit was achieved in the high-volume disease in the docetaxel group (2 = 0%)  . As trea(2 = 0%) –13.Although systemic therapy is important for mHSPC patients, accumulating evidence suggests that for mHSPC patients with low-volume disease, cytoreductive procedures, combined with systemic therapy, such as radiotherapy (RT) to the primary tumor and cytoreductive prostatectomy, can significantly improve the OS. However, such procedures need to be supported by a large number of randomized controlled trials . The HORAlthough NHT drugs and chemotherapy have significant efficacy in the treatment of mHSPC patients, the optimal drugs for the best therapeutic option should be determined. Sathianathen et al. performed a meta-analysis by focusing on papers published from January 2014 up to June 2019 and reported that the combination of ADT+docetaxel/abiraterone/enzalutamide/apalutamide is superior to ADT alone and that enzalutamide+ADT has the lowest absolute risk among all studied combination therapies  . Wang etMany comparative studies on abiraterone and chemotherapy have been conducted. Kassem et al. performed a network meta-analysis to compare abiraterone and docetaxel in the treatment of mHSPC, and they suggested that abiraterone therapy had a better PFS and lower drug toxicity than docetaxel but that there was a trend for the abiraterone therapy to benefit OS without statistical significance . In a meAs gene mutations are significantly associated with the prognosis of metastatic castration-resistant prostate cancer (mCRPC) –60, prevRevolutionary progress has been made in the development of mHSPC treatment options, notably including LHRH antagonists, NHT drugs, chemotherapy, and local intervention of low-volume disease of mHSPC, as well as in certain combined treatments. This has provided major benefits for mHSPC patients over the last decade. Nonetheless, further research is still needed to determine the optimal combinational therapies of these drugs. Therefore, multicenter prospective studies with larger sample sizes will inevitably be conducted in the future.XP-L, YL, XR-W participated in drafting the manuscript. MZ was responsible for revising the manuscript. HP-L designed the study and was responsible for revising the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by a grant from Gansu Provincial Hospital (17GSSY3-4).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


When parents lived apart, greater difficulties in concentration in children using DL (p = 0.05) and a lower parental capacity to support DL (p = 0.002) were reported. Adequate digital structures appeared related to living in owned compared to rented property, higher levels of parental education, and better familial financial situations. Conclusions: Students from families with financial difficulties and low levels of parental education, or even those living in houses for rent or having separated parents, may be disadvantaged in an educational context since the introduction of DL.Objectives: To investigate the experiences by distance learning (DL) method during the first wave of the SARS-CoV-2 pandemic in Italy, and to search for correlations with purported experiences and respective levels of social determinants of health (SDH). Study design and methods: Cross-sectional online survey, investigating various SDH and parents’ attitude towards DL, proposed 6 months after the beginning of the pandemic to a sample population of parents with school-aged children throughout Italy. Results: A total of 3791 questionnaires were analyzed. Non-Italian parents complained more frequently of difficulties in providing support to their children in DL due to poor digital skills ( Social determinants of health (SDH) are the set of conditions in which people are born, grow, live, work, and age, that affect their state of health . OverallDue to the need to limit the spread of the SARS-CoV-2 infection, distance learning (DL) became the prevailing schooling modality during the first months of the pandemic.   and is sThe aim of the present study was to investigate the experiences encountered by families with children utilizing the DL method during the months of the first wave and nationwide lockdown due to the COVID-19 pandemic in Italy, namely from March to May 2020, and to search for correlations with purported experiences and respective levels of SDH.From 1 September to 15 October 2020, a cross-sectional online survey of 78 questions was proposed to a sample population of parents with children up to the age of 18 years and domiciled throughout the Italian national territory. The survey was developed on the online platform Qualtrics and distributed through dissemination of a link and a QR code in a tertiary care pediatric hospital and in the waiting rooms of the pediatricians’ offices, and through social networks with a snowball sampling technique. It queried the demographic variables of families, various SDH , topics related to children’s behavior during lockdown , and parents’ attitude and opinions towards DL. The methods and the questionnaire have already been described in detail elsewhere . Here weU test and Kruskal–Wallis test, where appropriate. Although the purpose of this analysis is mainly exploratory [p values were corrected using the Simes–Benjamini–Hochberg method for false discovery rate control [Numerical variables were summarized as mean ± standard deviation; categorical variables were summarized as counts (percentages). Comparisons between groups were performed with Fisher’s exact test, Mann–Whitney loratory , all p v control ,16,17, w control . All datThe present study was approved by the Ethics Committee of the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant’Orsola  .Overall, 4031 parents of school-age children filled in the survey. After excluding incomplete answers about SDH and DL responses , 3791 questionnaires (94.0%) were included in the analysis.n = 105) and 37.0% had Italian citizenship (n = 44).One hundred nineteen parents (3.1%) were not of Italian origin: 88 (73.9%) came from other European countries, 13 (10.9%) from Latin America, 6 (5.0%) from Northern America, 6 (5.0%) from Asia, and 5 (4.2%) from Africa, while 1 was of unspecified origins. A total of 88.2% of these subjects had lived in Italy for at least 5 years (p = 0.01). Similarly, non-Italian parents complained more frequently of a lack of good-quality digital equipment  and reported an overall lower number of personal computers (p = 0.04). As compared with Italians, non-Italian parents had more difficulties with the Italian language , and reported an insufficient level of education to support the school commitments of their children .As shown in p = 0.05) and parents referred to a lower capacity for commitment in support of DL   .p < 0.001, 13.7% vs. 4.7%, p < 0.001, and 8.3% vs. 3.8%, p < 0.001, respectively)  .p < 0.001).Parental level of education  exhibited a large number of significant associations with perceived impairment in DL . The numAs reported in The economic status of the family was assessed based on the personal perception of the family’s economic situation  . ParentsAt the beginning of the COVID-19 pandemic, the abrupt schooling transition to DL represented one of the greatest disruptions to youths’ lives , and a gAfter a thorough search on the PubMed database, we identified 12 studies investigating the relationship between SDH and DL at school age (primary to higher secondary grades) in different countries worldwide, although the age of schoolers and the considered parameters are highly variable. Papers evaluating this relationship are reported in Our study highlighted the differences in access to digital devices in relation to SDH in a wide population sample distributed all over the Italian territory. The lack of adequate equipment seems to correlate with parents being of non-Italian origin, parents not having reached a higher level of education, families not living in owned housing, and parents perceiving their economic situation as difficult. In 2018, a survey in American colleges reported that about 20% of students had issues in accessing essential technology for DL (laptops and high-speed Internet) . In the According to a report by the Italian National Institute of Statistics (ISTAT), relating to the period 2018–2019, 33.8% of families in Italy do not have computers or tablets at home; this rate decreases to 14.3% among families with at least a minor. Only 22.2% of families have a PC or tablet available for each family member. In Southern Italy, 41.6% of families have no computer at home (compared to an average of about 30% in other areas of the country), and only 14.1% have at least one computer for each family member . In 2020The economic state of a family is a fundamental SDH, showing that families of better economic standing were able to offer superior global digital support to their children. Although not new, this fact should further emphasize that adequate access to the web has been shown to affect the health of people and communities . On the In our study, several factors  included in common SDH frameworks appeared to influence the ability of parents to support their children in DL during the lockdown period. A multicenter study based on an online self-report questionnaire explored adolescents’ emotional reactions during lockdown in a sample of 2105 secondary school students (aged 14–19) in Italy, Croatia, and Romania. It highlighted how the students who believed that family support was relevant to overcome this period  were less likely to report both boredom/emptiness and anxiety compared to those who had not recognized such an important role of the family .The findings determining DL among children from families not living together coincides with research showing lower scores and measures of academic achievement in children of single-parent households, when compared to children in two-parent households. Moreover, high rates of family fragmentation, worldwide, account for multiple socio-economic consequences, compromising economies, hindering innovation, as well as competition and growth.Although a child’s home environment, stability, and surroundings superseded home ownership in the achievement of improved social child outcomes, it was found that subsidized home ownership led to improved outcomes, in so far as the child maintained a suitable residing environment . The finAccording to our results, in general a more prosperous family economic context seems to favor DL in several respects. This concurs with the studies that highlight strong evidence of associations between income factors and COVID-19 pandemic outcomes ,48,49. Fhttp://dati.istat.it/, last accessed on 24 April 2022), a value much higher than the percentage of people with an immigration background observed in our study sample (3.1%). Moreover, we did not include all parameters of SDH, but we focused on the ones that we believed to be most relevant to this pandemic. Lastly, we only obtained parental point-of-views about DL. Despite its limitations, our work confirms and analyzes the difficulties in DL and its correlation to SDH during the COVID-19 pandemic.The present study has several limitations. This survey was spread predominantly by social media. We, therefore, do not know the true response rate. The study design could limit the ability to reach groups of the population that do not have access to the Internet and who were probably not able to follow DL in a beneficial way; indeed, the foreign-born population in Italy is estimated at around 10% by the National Institute of Statistics , and parental ability to effectively support their children. School closures affected all children, but not all in the same way: students from families with financial difficulties and low levels of parental education, or even those living in houses for rent or having separated parents, may be disadvantaged in a school setting since the introduction of DL. When remote learning cannot be avoided due to public health requirements, institutions should be aware of those groups who may experience augmented impairment of effective learning and take measures to avoid the increase in social inequities. Moreover, obstacles in DL might likely lead to disproportionate learning losses and, finally, to long lasting inequalities with consequences in adult life, reflecting both at an individual and societal level. Thus, all stakeholders, including governmental, national, and local authorities, should take action to minimize these gaps and ensure the right of education for everyone.


Postpartum depression (PPD) is the most common mental illness affecting women during lactation, and good social capital is considered a protective factor. This study aimed to investigate PPD symptoms, and explore the relationships between social capital and PPD symptoms of lactating women in southwest minority areas in China.This cross-sectional study was conducted among 413 lactating women in Guangxi, China. Data were collected using the Edinburgh Postnatal Depression Scale and the Chinese version of the Social Capital Assessment Questionnaire. Hierarchical regression analysis was conducted to explore the factors influencing PPD symptoms, and a structural equation model was used to examine how social participation and cognitive social capital mediated PPD symptoms.The total prevalence of PPD symptoms (score > 12) was 16.46%, and that of mild depression symptoms (9–12 score) was 22.03%. Nine variables predicted PPD symptoms and explained 71.6% of the variance in the regression model: higher age, lack of medical security, fixed occupation, breastfeeding time, self-caregiver, maternity leave, social participation, social trust, and social reciprocity. Furthermore, cognitive social capital mediated the relationship between social participation and PPD symptoms, with a mediation effect rate was 44.00%.The findings of this study highlight that social capital, support from family members, maternity leave, and medical insurance play protective roles in the PPD symptoms of lactating women. It is necessary to improve social capital as a key strategy for interventions for PPD symptoms, and active social participation activities are critical to reducing PPD symptoms among lactating women in minority areas. Lactation is a high-risk period for women to experience postpartum depression (PPD). PPD symptoms usually occur 4–6 weeks after a baby is born and usually manifest as lack of sleep, poor appetite, anxiety, irritability, and sadness, which even increases the risk of suicide in postpartum women . The intPPD symptoms is widely regarded as a cross-cultural, serious public health problem that needs to be solved urgently . AccordiSeveral studies have explored the risk factors for PPD symptoms . These rAccording to Coleman and Putnam, SC is an inherent social resource in social structures and connections . In thesIn the internal structure of social capital, CSC and SSC are two closely related concepts, and there may be a causal relationship with each other. We tend to argue that an individual’s objective behaviors will have an impact on his subjective cognition, and when the external SSC changes, the subjective CSC may change accordingly, thus affecting the individual’s mental health. This view has been confirmed in previous studies . ScholarStudies have shown a strong correlation between SC and mental health . ResidenChinese women also face PPD, the incidence in economically developed regions is as high as 23.2–34.0% . As a reSome evidence suggests that the incidence of depression in low-income minority women is high. A survey of immigrant mothers in Australia showed that 35% of mothers in multi-ethnic areas and with low socioeconomic status suffered from severe depression . China iBased on the literature and social capital theory, we propose two hypotheses: 1. there may have directed effect of four indicators of cognitive and structural social capital  on PPD symptoms, lower social capital would be associated with higher level PPD symptoms; 2. we also further tested the mediating role of cognitive social capital between structural social capital and PPD symptoms. Hence, this study aimed to understand the status of PPD symptoms in lactating women in minority areas in southwestern China and to explore the possible associations between PPD symptoms and SC.This research was conducted in the Guangxi Zhuang Autonomous Region of southwestern China. The geographical features of this area are dominated by mountainous areas bordering many Southeast Asian countries. Guangxi is a typical gathering place for ethnic minorities and has the largest ethnic minority population in China. The proportion of ethnic minorities dominated by Zhuang nationality reached 39.00%. In GuanAccording to the WHO’s breastfeeding guidelines, infants should be breastfed for the first 6 months of life, and breastfeeding continues for up to 2 years of age or beyond. Therefore, the lactation period for postpartum women in this study ranged from the birth of the newborn to 24 months. Two-stage sampling was adopted to conduct a cross-sectional survey; data were collected from December 2018 to May 2019. Three cities in Guangxi were randomly selected, and a maternity hospital pediatric outpatient clinic was selected from each city as a recruitment point. Random sampling was used to recruit lactating women. Before conducting the questionnaire survey, the content of the research project was introduced to each potential participant. To participate in the study, the women must be: (1) Breastfeeding; (2) registered at a Guangxi household and living there for over a year; (3) 18 years or older; (4) voluntary participants; and (5) must have reading comprehension skills. After the respondents signed the informed consent form, the investigators gave them paper questionnaires to complete, which were collected after completion. A total of 500 questionnaires were distributed; incomplete questionnaires were excluded after quality reviews by three researchers, and 413 valid questionnaires were returned, with an effective response rate of 82.60%. The study protocol was conducted in accordance with the Helsinki Declaration and was approved by the Medical Ethics Committee of Guilin Medical University (reference No: GLMC201806301).The Edinburgh Postnatal Depression Scale (EPDS) is widely used to measure the symptoms of depression in postpartum women. The scale consists of ten self-reported items, each with a score of 0–3. The reliability and validity of the Chinese version of the EPDS (C-EPDS) for Chinese maternal measurement have been verified  . To measThe Social Capital scale was revised using the World Bank’s Social Capital Assessment Tool and the social capital scale of perinatal women in eastern China . In a prSSC was measured using the two dimensions of social participation (SP) and social network (SN). SP was assessed using nine items to reflect the frequency of participation in different activities and the degree of the activity. A five-point system (1–5 points) was used to evaluate each item of SP and calculate the total score; the higher the total score, the higher the level of social participation. SN was comprehensively reflected by the number of occupation types and the prestige status of the occupations that the respondents encountered in social interaction. This included the diversity of social networks , the prestige of the occupation , and the prestige range in the social network (the highest prestige score minus the lowest prestige score). Occupational prestige refers to the results of Li Chunling’s hierarchical measurement of contemporary Chinese social prestige, which covers 81 occupations in China. The occupational prestige score ranges from 9.73 to 90.15 . As the Covariate control variables included sociodemographic characteristics , socioeconomic status , and factors during breastfeeding . The variable assignments are listed in t-test and analysis of variance were used to analyze the association between different demographic and social characteristics and PPD symptoms; Pearson correlation analysis was adopted to evaluate the correlation between SC and PPD symptoms; and a hierarchical regression analysis model was used to evaluate the effects of sociodemographic characteristics, factors during breastfeeding, and social capital on PPD symptoms in lactating women.Data analysis was conducted using SPSS 23.0 and Amos24.0. The specific steps were as follows: Descriptive analysis of the basic situation of the research object; n = 5,000), and statistical significance was set at P < 0.05.Based on the relevant experience in the literature and the results of hierarchical regression analysis, we developed a conceptual model, as shown in P < 0.05) (see The 413 respondents were between the ages of 19 and 43 (28.33 ± 4.10), ethnic minorities accounted for 33.66%, and rural household registration accounted for 56.66%. Nearly half of the respondents had a high school education or below, and the distribution of monthly household income was relatively even, Further, 7.26% of participants were not enrolled in basic medical insurance; The lactation period ranged from 1 to 531 days (173.44 ± 109.46), and 51.33% of lactating women did not have maternity leave. The EPDS scores of respondents ranged from 0 to 27 (7.87 ± 4.02), 254 participants (61.50%) did not have PPD symptoms, and the prevalence of PPD symptoms was 16.46%. The distribution of PPD symptoms among the other characteristic variables was statistically significant (P < 0.001); Model 1 significantly explained 39.7% of the variance in PPD symptoms . In Model 2, the individual factors, including breastfeeding time, primary caregiver, number of caregivers, and maternity leave of women during the breastfeeding period were added; Model 2 significantly explained 45.5% of the variance in PPD symptoms .In Model 1, demographic and sociological factors were included. Age, family monthly income, and medical security of lactating women had statistically significant effects on PPD symptoms . This model explained 71.6% of the variance and revealed nine variables that contributed significantly to PPD symptoms. Among SC, ST , SR , and SP  had statistically significant effects on PPD symptoms, whereas SN had no significant effect.In Model 3, SC was added, leading to an improvement with a significant change in By comparing the results of Models 3 and 1/2, after adding the four dimensions of SC, the regression coefficient of age changed from 0.296 to 0.182, the regression coefficient of the breastfeeding period decreased from 0.006 to 0.003, and the regression coefficients of all types of medical insurance increased. This meant that the negative effect of no insurance was relatively reduced. Further, the regression coefficients of parents-in-law care, parental care, and nanny care increased, which meant that the negative impact of self-care was relatively reduced. The length of maternity leave had a significant protective effect on PPD symptoms; however, compared with regular professionals, freelancers were significantly negatively correlated with PPD symptoms. Overall, the results showed that ST, SR, and SP played protective roles in regulating PPD symptoms in lactating women.2/dfχ = 3.563, RMSEA = 0.079, CFI = 0.981, NIF = 0.981, and AGFI = 0.931, the fit of the model is fine.Based on the results of the hierarchical regression analysis, we further examine how social capital acts on PPD symptoms. According to the fitting index requirements of SEM, we excluded the two mediation models in which the SSC dimension is composed of the observation indexes SN and SP, and the SSC dimension is only represented by the observation index SN. An SEM was further adopted to test the mediating effect of the CSC on the relationship between SP and PPD symptoms of lactating women, in which SP is the observation index of SSC. The fit indices for the SEM were: P < 0.001), and the standardized direct effect value of SP on PPD symptoms was -0.453 (P < 0.001). SP significantly predicted CSC, and the standardized direct effect of SP on CSC was 0.865 (P < 0.001). According to the results of the bootstrap mediation effect test, the bias-corrected 95% CI of path 1 was 0.812–0.908, and the bias-corrected 95% CI of path 2 was -0.62 to -0.218. This confirmed that the indirect effect of SP on PPD symptoms through CSC was significant. The standardized indirect effect of SP on PPD symptoms through CSC was -0.356 (bias-corrected 95% CI -0.55 to -0.19). Further, the standardized total effect of SP on PPD symptoms was -0.809, with indirect effects accounting for 44.00% of the total effect.In this study, the continuous EPDS score was used to evaluate PPD symptoms of lactating women in minority areas of southwest China. Our findings show that the mean PPD symptoms score was 7.87, and the prevalence of PPD symptoms was 16.46%, compared with 7.8 and 23.2% reported in other studies on lactating Chinese women based on the same standards . The preHierarchical regression analysis was performed to confirm the correlations of sociodemographic characteristics, breastfeeding factors, and SC with PPD symptoms. The symptoms of depression gradually increased with age in lactating women, consistent with previous studies from Spain, Sweden, and Guangzhou China . One posAmong the factors during the breastfeeding period, the duration of breastfeeding, primary caregiver, and length of maternity leave were important predictors of PPD symptoms. Our research results showed that with an increase in breastfeeding time, the severity of PPD symptoms increased if lactating women did not receive care support from other family members but only takes care of the baby by themselves, consistent with a previous study . HoweverAfter adjusting for the control variables , SP, SR, and ST were negatively correlated with PPD symptoms scores, and the explained variance increased to 71.6% in Model 3. This indicated that SC was associated with PPD symptoms of lactating women in minority areas of Southwest China. Our research found that the impact of SSC is relatively vague; in which SP had a significant impact on PPD symptoms, but SN did not. Our findings are supported by other studies , but alsOur results showed that CSC plays a protective role in postpartum depression; similar findings were reported in previous studies by Kritsotakis, Zhou, and Murray, the higher the level of CSC, the lower level of depression symptoms . One posFurthermore, we found that SR was more important than ST for PPD symptoms among lactating women in minority areas, consistent with other research results on antenatal depression among Chinese primiparas . It mighAn interesting finding was that SEM showed a mediating effect of CSC on the relationship between SP and PPD symptoms. The mediation effect rate was 44.00%, confirming that SP indirectly affected PPD symptoms through CSC. This may be attributed to the gradual development of China’s community service system and the increasing sense of community belonging among residents . A studyFirst, this study was not based on clinical diagnosis to assess PPD, but rather on a self-report scale (EPDS); a continuous score was used to measure levels of PPD symptomatology. However, it cannot be used to confirm PPD in women clinically. Second, the study only conducted a cross-sectional survey design, which could not test the causal relationship between SC and PPD symptoms; therefore, future prospective studies are needed. Finally, the sample was from the Guangxi Zhuang Autonomous Region in southwest China, which may limit the generalizability of the findings. Thus, further research is needed to confirm whether the current research results apply to other regions.To the best of our knowledge, this study is the first to investigate the relationship between SC and PPD symptoms among lactating women in ethnic minority areas in China. Our study showed that elderly lactating women who are primary caregivers with no medical insurance, fixed occupations, and short maternity leave were more likely to experience postpartum depression. Further, higher SC, including SP, ST, and SR was strongly associated with lower PPD symptoms, and CSC composed of ST and SR mediated the relationship between SP and PPD symptoms. These findings provide new evidence for the social capital theory applied to the field of postpartum mental health. It also helps policymakers to formulate preventive interventions to enhance SSC especially SP and CSC, to effectively alleviate PPD symptoms in lactating women. Moreover, favorable conditions should be provided to promote the SP of lactating women. These include extending maternity leave, providing family support, and creating peer support groups. Finally, it is important to cultivate lactating women’s SC via community centers and hospitals. Healthcare professionals and community workers should regularly conduct activities to promote mental health awareness and provide information about postpartum health and baby care. Moreover, timely social support through psychological counseling should also be provided.The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.The study meets the ethical guidelines of the Helsinki Declaration and it was approved by the Medical Ethics Committee of Guilin Medical University. Written informed consent was obtained from participants before participation in this study.QHW and WXS were responsible for the overall design of the research. YHQ analyzed the results and drafted the manuscript. PFG and SCJ substantially contributed to data acquisition. JCL, XZ, and RZW assisted with the literature review. JHW and HL contributed to the interpretation of the results and the writing of the manuscript. FY, JJL, and KXW revised the manuscript. All authors contributed to this manuscript and approved the current version for publication.


Chlorella vulgaris (C. vulgaris) display a recalcitrant cell wall, characterized by a complex matrix of polysaccharides and glycoproteins, which constitutes a major barrier for monogastric species digestibility and extraction of inner valuable nutritional compounds. To overcome this limitation, the development of feed enzymes, in particular Carbohydrate-Active enZymes (CAZymes) with capacity to disrupt C. vulgaris cell wall may contribute to improve the bioavailability of these microalgae compounds in monogastric diets, namely at high levels of incorporation. In order to disclosure novel combination of feed enzymes to disrupt C. vulgaris cell wall, a lab protocol was implemented by our research team containing the following key steps: after microalgae cultivation and having available a repertoire of two hundred pre-selected CAZymes produced by high-throughput technology, the step 1 is the individual screening of the most functional enzymes on disrupting C. vulgaris cell wall  and the determination of reducing sugars released by the 3,5-dinitrosalicylic acid (DNSA) method; step 2 concerns on finding the best CAZymes cocktail, testing the synergistic effect of enzymes, to disrupt C. vulgaris cell wall  along with characterization of each enzyme thermostability and resistance to proteolytic attack, to which feed enzymes are subjected in the animal gastrointestinal tract; step 3 is the assessment of C. vulgaris cell wall degradation degree by measuring the amount of reducing sugars released by the DNSA method, fatty acid analysis by gas chromatography (GC) with flame ionization detector (FID), oligosaccharides quantification by high performance liquid chromatography (HPLC) equipped with an electrochemical detector (ECD), protein content by the Kjeldahl method, and various pigments  in the supernatant. In the correspondent residue, we also assessed cellular counting using a Neubauer chamber by direct observation on a bright-field microscope and fluorescence intensity, after staining with Calcofluor White for both control and CAZymes cocktail treatments, on a fluorescence microscope. Beyond animal feed industry with impact on human nutrition, our lab protocol may increase the yield in obtaining valued constituents from C. vulgaris microalga for other biotechnological industries.Over the last decades, microalgae have gained popularity due to demand for novel environmental green solutions and development of innovative mass-production sources for multiple processes, including animal feed and human diet, turning microalgae into an exquisite candidate for several ecofriendly technologies. Notwithstanding, there is a catch. Most species of microalgae, as the case of common  Microalgae stand now as a proper candidate for various ecofriendly technologies due to their importance, both biologically and economically. The interest in microalgae has increased during the last decades as a result of the need for additional food supplies, among others, contributing to bring back to balance the interplay among environmental, human food and animal feed sustainability . MicroalThe biggest drawback on the use of microalgae is their recalcitrant cell wall. It provides resistance against invaders and/or harsh environmental conditions (such as desiccation during growth), is refractory to breakage and drying, and thus to products removal , being lhttps://dx.doi.org/10.17504/protocols.io.dm6gpb9z5lzp/v1 and is included for printing as The protocol described in this peer-reviewed article is published on protocols.io, C. vulgaris cell wall is to cultivate this species  presents complete and detailed information about the described CAZymes. These enzymes are naturally chosen, according to the composition of the matrix of insoluble carbohydrates of C. vulgaris cell wall, comprising glucosamine, galactose, rhamnose, mannose or alginates [Leinster, Ireland) and Prozomix Limited  in order to be applied in any microalgae cell wall disruption protocol. Afterwards, the individual screening of the aforementioned enzymes to assess possible disruption of C. vulgaris cell wall is the goal. Still in step 1, pre-washed C. vulgaris is incubated, overnight, at 20 mg/mL and each individual enzyme at 20 μg/mL, versus a control, defined as the microalgae suspension incubated with PBS 1×, in triplicate, followed by the measurement of the amount of reducing sugars released using the classical 5-dinitrosalicylic acid (DNSA) protocol [C. vulgaris cell wall, of each one of the 200 CAZymes that compose the large enzyme library, aiming to classify the CAZymes according to its cell wall disruption ability. The microalgae concentration was fixed and defined according to a previous protocol of microalgae cell wall disruption [C. vulgaris cell wall , with enzymatic activities according to C. vulgaris cell wall composition, and with good rates of recombinant production. Then, these enzymes are tested, in triplicate, in combination at 20 μg/mL in a ratio of 1:1:1:1 to obtain the maximum possible yield of cell wall disruption due to an enzymatic synergistic effect . At this stage, it is also important to characterize biochemically each selected enzyme present in the mixture, by testing thermostability and resistance to proteolysis [g for 8 min at 4 °C. The supernatant is recovered and the protein amount is quantified using a NanoDrop 2000/2000c. To validate results, the supernatants are also analysed by 14% SDS-PAGE gels ..C. vulgasruption . The conteolysis , 10. OneAGE gels . In ordeAGE gels .C. vulgaris cell wall. This enzyme mixture is applied from now on. In step 3, the degree of microalga cell wall disruption induced by the enzymatic cocktail is assessed in the residue by optical and fluorescence microscopy, for cell counting using a Neubauer chamber by direct observation on a bright-field microscope for both control and CAZymes cocktail treatments  during the incubation. Chitinase, rhamnohydrolase, and galactanase displayed the best results on the individual screening. The next step was to perform an incubation with C. vulgaris and a mixture of these enzymes, evaluating its ability to degrade the cell wall through the bioaccessibility of lipid and protein, measurement of the particle size of cells, and observation on a light microscope [More recently, several studies on the development of enzymatic strategies to promote the disruption of i et al. , studiedll walls . Finallyll walls  developecroscope .Microalgae can provide a sustainable and environmentally-friendly solution to fight food and energy crisis that our planet is currently facing. The best possible knowledge on the physicochemical characterization of microalgae is paramount, as it allows selecting which microalgae species are the best for different biotechnological applications and scientific purposes . Top resS1 File(PDF)Click here for additional data file.


Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common chronic liver disease. MAFLD is a major risk factor for end-stage liver disease including cirrhosis and primary liver cancer. The pathogenesis of MAFLD is complex and has not yet been clarified. To the best of our knowledge, few studies have conducted quantitative bibliometric analysis to evaluate published MAFLD research. In this study, we conducted a comprehensive analysis of MAFLD publications over the past decade to summarize the current research hotspots and predict future research directions in this field.Articles into MAFLD published from 2012 to 2021 were identified from the Science Citation Index-Expanded of Web of Science Core Collection. CiteSpace software, VOSviewer, the “bibliometrix” R package, and the Online Analysis Platform of Literature Metrology were used to analyze the current publication trends and hotspots.We retrieved 13959 English articles about MAFLD published from 2012 to 2021. Primary sites of publication were dominated by the United States until 2014, when China became the source of most published MAFLD-related research papers. The United States was found to be the most engaged country in international cooperative efforts. Shanghai Jiao Tong University was the most productive institution. Loomba R was the most productive author with 123 articles. The co-cited keyword cluster tag showed ten main clusters: #0 liver fibrosis, #1 hemoglobin, #2 metabolic associated fatty liver disease, #3 egcg, #4 myocardial infarction, #5 heart disease, #6 pnpla3, #7 hepatocellular carcinoma, #8 noninvasive marker, and #9 children. Keyword burst analysis showed that gut microbiota was the highest-intensity research hotspot.In the past decade, the number of publications on MAFLD increased dramatically, especially in the last three years. Gut microbiota became an important research direction for etiological and therapeutic investigations into MAFLD. Insulin resistance was also a key factor in studying the development of MAFLD in recent years. Liver fibrosis was an important focus of disease development. This study provides systematic information, helps guide future research, and helps to identify mechanisms and new treatment methods for MAFLD. Metabolic dysfunction-associated fatty liver disease, formerly named non-alcoholic fatty liver disease (NAFLD), is a public health problem that is the most common chronic liver disease worldwide. The renaming from NAFLD to MAFLD in 2020 stemmed from a need for precise diagnosis and effective treatment . One-quaThe large global prevalence of MAFLD has attracted major pressures on medical systems and imposed economic burdens, resulting in an increased demand for in-depth research in this field. However, in the past decade, few bibliometric articles have summarized the latest progress in this field and predicted research hotspots. The latest bibliometric study only summarized literature related to MAFLD research before 2014 . In thisWe conducted a comprehensive literature search within the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC) database for the period 2012-2021, on September 6, 2022. To reduce the deviation caused by frequent database updates, we completed the search and retrieval of data in one day. We retrieved relevant publications in WoSCC through the following search strategy: TS= from January 1, 2012, to December 31, 2021, and the “Document Type” was limited to “Articles” only. To confirm the accuracy of bibliometric analysis results, we examined all publications retrieved through the above search strategy by title, abstract, and year of publication. Exclusion criteria were as follows: (i) not related to MAFLD, (ii) non-article document types , (iii) repeated publishing, and (iv) non-English language publications. We finally identified 13,959 articles on MAFLD research for econometric analysis. The detailed filtering is shown in http://wcs.webofknowledge.com) was used to analyze retrieval results and extract the histogram showing the publication trends. We converted all data that met the requirements from WOSCC to TXT format and imported the data into CiteSpace analysis software , bibliometric online platform analysis (http://biblimetric.com), VOSviewer 1.6.18 , and used the bibliometrix R package for visual processing.To describe all the literature features related to MAFLD studies, Web of Science , years per slice (1), term source , node type (choose one at a time), pruning (pathfinder), and visualization . CiteSpace was used to perform the bibliometric analysis. Visualization knowledge maps consist of nodes and links. Different nodes in a map represent elements such as a cited reference, institution, author, and country, and links between nodes represent relationships of collaboration/cooccurrence or co-citations. The publication number from the top 10 countries/regions and the top 10 most productive journals were exported from the Online Analysis Platform of Literature Metrology. The bibliometrix R package was used to output the high-frequency keywords as a world cloud map. Collaborations between countries/regions were analyzed by VOSviewer software.3-24979x2+5E+07x-3E+10 (R2 = 0.9988), which predicted that nearly 7000 articles will be published by 2025 , and 145 were excluded because they were not published in English. According to the defined search criteria, 13,959 articles were extracted from WoSCC. As shown in http://bibliometric.com/). The generated histogram shows the number of publications from the top 10 countries/regions over the last 10 years . The top 10 most productive authors are shown in Journal of Hepatology , Gastroenterology , Plos One , World Journal of Gastroenterology , Liver International , Clinical Gastroenterology and Hepatology , Metabolism-Clinical and Experimental , Journal of Gastroenterology and Hepatology , and Gut . Five of these journals are from the United States, while the others are from the Netherlands, China, Denmark, Australia, and England. Articles published in Gastroenterology had the highest average citation per paper (47.37).The 13,959 original articles were published in 1,696 academic journals. A bibliometrics online analysis platform was used to analyze journal influence. The top 10 most-cited journals are shown in Nature in 2012 ranked first in terms of citations  retrieved from WoSCC were analyzed by CiteSpace to identify mutual homogeneity and then to cluster them. Map of co-citation references in CiteSpace on MAFLD research is presented in Hepatology in 2016 . The overall publication numbers maintained a stable growth trend. Since 2018 there has been a booming growth in publications. The United States showed the greatest international cooperative efforts, while China published the largest number of papers. The representative clusters of cited articles are liver fibrosis and hemoglobin. Gut microbiota, atherosclerosis, and cholesterol were the most intensively utilized keywords over the past decade. This study is the first bibliometric analysis article on MAFLD/NAFLD over the past 10 years and demonstrates a systematic overview of this field and guides future studies. With the help of our bibliometric analysis, researchers interested in MAFLD can obtain a general understanding of the field and quickly grasp the latest research hot spots.The annual publications output in this field indicates a continuous and steady upward trend in the last 10 years. The increasing rate accelerated from 2018, indicating that the study of MAFLD has gained greater research attention. Hepatology studied the therapeutic effect of combination therapies including Cilofexor and Firsocostat on the development of MAFLD , mainly studying treatments and the prognosis of MAFLD. His article published in of MAFLD . His recof MAFLD  and the of MAFLD . Nobili of MAFLD . Byrne Cof MAFLD , which iof MAFLD .Hepatology had the most citations . Papers published in Gastroenterology had the most average citations per paper (47.37) and likely contributed to its high impact factor (33.883). The journal PLoS One had the largest publication count (465 papers) while its average citation per paper was 7.77, which implied that the papers published in PLoS One were of less interest and thus resulted in fewer citations. Five of the ten journals were from the USA, showing that the USA provides an important platform for the development of the MAFLD field.Amongst the top 10 most cited journals, the journal In the analysis of the 228,186 references from 13,959 articles, the top 10 most cited authors are shown in Through the timeline view of MAFLD research hotspot shifts, we found that, in addition to clusters such as liver fibrosis and metabolic fatty liver disease, children and hemoglobin, which seemed to have less correlation with MAFLD, were also highlighted. MAFLD is one of the most common chronic liver diseases in children in the developed world. It is estimated that the worldwide prevalence of pediatric NAFLD is up to 7.6% in the general population and is 34% in the obese pediatric population . After 2Keyword burst refers to the keywords that are significantly cited by papers over a specific period; it is considered another important indicator of study hotspots or emerging trends over time. As is shown in Secondly, the “cholesterol” keyword emerged in 2019, with a strength of 48.48, continuing until the end of 2021. It has been pointed out that hepatic cholesterol transport plays an important role in MAFLD and atherosclerosis  and cholThe third keyword burst that lasted until the end of 2021 was “mortality”. The concern about MAFLD mortality indicates that the disease has become a public problem threatening health and life , 63. TheOur study has some limitations. Firstly, the data analyzed were only extracted from the SCI-E database from WoSCC, and records from other important search engines such as PubMed, Embase, and Ovid were excluded, potentially resulting in an incomplete representation of the publications on MAFLD/NAFLD over the past 10 years. However, data retrieved from WoSCC included comprehensive records such as title, author, institute, and reference which are necessary for bibliometric analysis. In addition, only data retrieved from WoSCC contains complete information for co-citation analysis by CiteSpace whereas other databases do not. Secondly, English is still the preferred language for academic journals today, therefore we focused on papers published in English, which resulted in an omission of articles published in other languages.With the help of bibliometric mapping, we analyzed the research on MAFLD in the past 10 years. Since 2018, the number of publications has increased rapidly. The United States and China made the largest contributions to the MAFLD field. The United States was in the leading position in terms of international cooperation, while China has led in the number of publications since 2015. The current research mainly focuses on liver fibrosis and gut microbiota. Gut microbiota may be an important research direction to investigate the transition of fatty liver to liver fibrosis. This study guides future research work, which may help to discover the mechanism of MAFLD and new treatment methods.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.PG and WY put forward the concept of this study and designed this study. YL and LW screened articles and wrote original manuscript. YL, LW, and FL conducted CiteSpace and VOSviewer analysis. PG, WY, YL, LW, FL, LY, YJ, YZ, ZZ, DT, and SX revised and critically edited the manuscript. All authors contributed to the article and approved the submitted version.


Smartphone usage has significantly increased in the last decade among young adults has significantly increased in the last decade. While its benefits are undeniable, its negative implications are increasingly emerging. Studies are needed to investigate the effects of excessive smartphone use on a young person's life. This study aimed to determine the prevalence of excessive smartphone use among medical students and its relations with social anxiety, self-esteem, and quality of life.p-value of < 0.05 from the Pearson correlation coefficient test.A cross-sectional study was conducted among medical students from Universiti Kebangsaan Malaysia (UKM) in UKM Medical Center. A total of 273 students have consented to participate and completed self-reported questionnaires encompassing sociodemographic information, the Short Version Smartphone Addiction Scale (SAS-SV), the Social Interaction Anxiety Scale (SIAS), the World Health Organization Quality of Life (WHOQOL-BREF) and the Rosenberg Self-esteem Scale (RSES). Sociodemographic data, SIAS score, WHOQOL-BREF score and the Rosenberg Self-esteem Scale score were treated as independent variables. Smartphone addiction Scale score was treated as the dependent variable. Bivariate analysis was used to explore the relationship between independent and dependent variables using the Fisher exact test, Pearson Chi-Square and Pearson correlation coefficient. Multiple linear regression analysis was used to analyze the variables with a r = 0.173, p = 0.004) and negative correlations with physical health , psychological wellbeing , social relationships , environment  and self-esteem . In the multiple regression analysis, a better environment predicted a reduced risk for smartphone addiction .The percentage of excessive smarphone use among UKM medical students is 48%. The bivariate analysis showed that excessive smartphone use has a small but significant positive correlation with social anxiety (Almost half of the students were found to have smartphone overdependence. Excessive smartphone use has shown a significant relationship with an increased risk for social anxiety, reduction in self-esteem, and quality of life among medical students. A closer look into the possible intervention is needed in the future to curb the negative effects arising from excessive smartphone use. The usage of smartphones has significantly increased during the last decade, particularly among young adults. In Malaysia, smartphone usage in 2021 was approximately 98.7%, a slight increase from 98.2% in 2020 . In the Nonetheless, with smartphones' growing necessity in our daily activities, social and psychological problems have risen due to their overuse. A clear obstacle to a systematic investigation into this issue is the lack of a clear definition of a “smartphone addiction”, and the unavailability of its diagnosis in the International classification of disease 11 (ICD-11)  or Diagnvia desktop computers, due to the former's ability to be used anywhere and at any time  will be used due to the lack of a clear and established clinical diagnostic definition. ESU is a complex and multifactorial condition. A theory that explains this condition is the “Object Attachment Theory”  which orany time . In addiVarious studies have found that ESU correlates with impaired psychological wellbeing, such as depression, anxiety, and stress , 24. SomSocial anxiety or social phobia is a condition characterized by marked fear of being scrutinized or humiliated by others . Social via their usage, one may construct an extensive social network, build a self-image, and feel connected with the rest of the world , quality of life consists of four domains: physical health; psychological wellbeing; social relationships; and the environment . StudiesMedical students are among those with a high rate of smartphone use . The stuThis study is cross-sectional in design and involves 1st- and 4th-year medical students at UKMMC. Data collection was conducted using convenience sampling, where year 1 and 4 students who are present on campus during the data collection period were approached after classes. The year-1 students represent those undergoing pre-clinical rotations, while the year-4 students represent those undergoing clinical rotations. The sample size of this study was determined using a manual sample size calculation formula for the prevalence study  based onwhere,Z1-α = Z0.95 = 1.96 .P  = 0.17, was taken from the prevalence of smartphone addiction in a study among students in Switzerland (D (Absolute precision required) = 5% = 0.05.n = 1.962 [0.17(1–0.17)/0.052] = 217. The final estimation of the sample size required is estimated to be a minimum of 260 students .Therefore, th June 2018–30th June 2018. Briefing on the purpose and nature of the study, as well as the inclusion and exclusion criteria, were delivered to the sampled students before the interview. The inclusion criteria were twofold: (1) the participant must be a year-1 or year-4 undergraduate medical student at UKM; and (2) the participant must consent to voluntarily take part in this research. The exclusion criterion was a participant who does not give his/her consent. Those who fulfilled the criteria were given a set of self-report questionnaires and written consent. The participants were asked to complete the questionnaires that consist of questions regarding their socio-demography, the short version of the Smartphone Addiction Scale (SAS-SV) (The data collection process was conducted between 15(SAS-SV) , the Soc(SAS-SV) , WHO Qua(SAS-SV) , and RosWritten permission and approval to conduct the study were obtained from the Research and Ethics Committee, Faculty of Medicine, Universiti Kebangsaan Malaysia (Project Code: FF-2018-243).This is a self-reported questionnaire that includes questions on respondents' age, ethnicity, religion, year of study, place of origin , parents' living status, parents' marital status, parents' household income, existing medical condition, and existing psychiatric condition.The first Smartphone Addiction Scale (SAS) questionnaire was developed and validated by Kwon et al. . The oriA shorter version of SAS was created and validated again in the same year by Kwon et al. . The shoThe Social Interaction Anxiety Scale (SIAS) is a self-report scale that measures the anxiety experienced by a person during social interactions with others. This scale was first developed and validated by Mattick and Clarke . The scaIn terms of its discriminant validity, SIAS has been compared to other scales that measure social anxiety, such as the Social Phobia Scale (SPS) and the Social Phobia & Anxiety Inventory (SPAI) by Peters . The SIAThe WHO's definition of Quality of Life (QoL) is “An individual's perceptions of their position in life in the context of the culture and value systems in which they live and about their goals, expectations, standards, and concerns” . WHOQOL The WHOQOL-BREF consists of 26 items . In total 24 of these items are divided into four domains: physical; psychological wellbeing; social relationship; and environmental. The remaining two items represent the person's perception of their overall QoL and general health. A 5-points Likert scale is used for the questionnaire's scoring. The total raw score for each of the four WHOQOL-BREF domains can be obtained by summing the item scores and converting them to a scale ranging from 0 to 100 using the formula below:The original WHOQOL (U.S version) has an acceptable internal consistency with Cronbach's alpha of 0.82–0.95 across its domains . MeanwhiThis is a self-rated scale developed by Rosenberg to measure the level of self-esteem among high school students . It utilp-value of < 0.05 from the Pearson correlation coefficient test to control for confounders. Smartphone addiction was then analyzed as categorical data  for comparison with sociodemographic data (using Fisher's exact test and Pearson chi-square test). On top of that, smartphone addiction's continuous data was used for correlation and regression analysis.The collected data were keyed into the Statistical Package for Social Sciences (SPSS) software version 21. The completed Smartphone Addiction Scale (SAS), Social Interaction Anxiety Scale (SIAS), WHOQOL-BREF, and Rosenberg Self-Esteem Scale (RSES) questionnaires were scored according to their respective manuals or based on reviews of the literature. The calculated scores were then keyed into SPSS. Descriptive analyses were performed on the sociodemographic variables. Sociodemographic data, Social Interaction Anxiety Scale score, WHOQOL-BREF score, and the Rosenberg Self-esteem Scale score were treated as independent variables, while the Smartphone Addiction Scale score was treated as the dependent variable. Bivariate analysis was used to explore the relationship between the independent and dependent variables using the Fisher's exact test, Pearson Chi-Square analysis, and Pearson correlation coefficient. Furthermore, a multiple linear regression analysis was used to analyze the variables with a A total of 367 eligible medical students from year-1 and year-4 groups were approached to be recruited into this study as participants. However, 94 of them did not give their consent, thus excluding them from the final sample . The remn = 48, 17.6%), Chinese , and others . The most predominant religion was Islam, with 184 followers (67.4%) followed sequentially by Buddhism , Hinduism , Christianity , and others . With regards to the place of origin, 214 students came from urban areas (78.4%) while the remaining 59 students (21.6%) came from rural areas. Moreover, regarding the parents' living status, a total of 25 students (9.16%) have lost their fathers, while three students (1.1%) have lost their mothers. In terms of parental marital status, 245 (89.7%) were in marriage, 10 (3.66%) were divorced, and 18 (6.6%) were widowed. Lastly, 31 students (11.4%) had an existing medical condition, and only 7 of them (2.56%) had an existing psychiatric condition or illness.From the sociodemographic data, male students from both batches represent 30.7% (84 students) of the sample, while female students represent 69.2% (189 students). In terms of ethnicity, Malays made up most of the study sample, with 169 students (61.9%), followed by Indians (n = 132) (n = 43) are male and 67.4% (n = 89) are female. These figures were calculated based on the cutoff point of 31 score points for boys and 33 score points for girls  . From thor girls .p = 0.026 (p < 0.05). The other factors do not seem to be different across the two above groups.Additionally, Fisher's exact test and Pearson Chi-Square were conducted to investigate whether there are statistically significant differences in sociodemographic information between the group of smartphone and non-smartphone addicts. The final result showed that there was a statistically significant difference in terms of religious beliefs between the smartphone addicts vis-à-vis the non-addicts with r = 0.173). This correlation was highly statistically significant (p = 0.004)  for physical health and psychological wellbeing and was highly significant (p < 0.01) for social relationships and environment. On top of that, ESU was also found to exhibit a statistically significant negative correlation with self-esteem (r = −0.128).From the analysis, it may be determined that ESU was positively correlated with the domains of social anxiety (= 0.004) . Furtherp = 0.009). Meanwhile, the results from p = 0.027). And again, an increase of 1 point in the WHOQOL-BREF environment domain score is statistically significantly associated with the reduction of ESU score by 0.233 (p = 0.013) in In This study was designed to identify the prevalence of ESU among UKM medical students and its relationship with social anxiety, quality of life, and self-esteem. Studies investigating the relationship between ESU and the above factors are still lacking, and to the best of our knowledge, have yet to be conducted in the local Malaysian context.The rate of ESU in this study for both male and female students – as measured by the Short-version Smartphone Addiction Scale (SAS-SV) – is around 48%. This rate is similar to a local study (40.6%) . Howeverr = 0.173, p = 0.004). This is consistent with findings from previous studies that demonstrated a higher strength of association between ESU and social anxiety (n = 55).In this study, the bivariate analysis yields a significant positive correlation between ESU with risk for social anxiety  and Rios-Risquez et al.   , 76.Another possible explanation for the small association between ESU and social anxiety may be due to the different types of activities available on smartphones. People with social anxiety may prefer to engage in offline to online activities using smartphones. Elhai et al. reported that “non-social” features of smartphones are more related to anxiety as compared to “social” ones . This inThere is a notion that excessive use or being addicted to a smartphone can negatively affect a person's quality of life (QoL). A part of the results of this study seems to support that view. Based on the bivariate (correlation) analysis, it appears that those with a higher risk for ESU will have a small but significant negative implication in several areas, such as physical & psychological health, social relationship, and the environment domains. In this study, excessive usage of smartphones has been shown to affect our physical health in several ways. This finding is similar to a recent study . Besidesvia social media . Therefore, the usage of smartphones in this regard may boost students' self-esteem levels. This is largely similar to the findings made by Valkenburg et al.  albeit the relationship is not statistically significant. This is largely supported by other past studies. An experimental social study revealed that the presence of a smartphone negatively affects the quality of a conversation (n = 768), the outcome demonstrated that the student-student relationship was negatively associated with ESU  has been identified as one of the risk factors for ESU (p < 0.05)  consistently displays a significant negative relationship with ESU across the different analyses conducted. Among the facets incorporated within this domain are financial status and home environment. Brown et al. found that the duration of smartphone usage among undergraduate students from low-income families was higher than those from higher-income families . This di for ESU . Parents for ESU . Another < 0.05) , 91. WHI < 0.05) .Additionally, among the other results of this study is the significant association between an individual's belief system with the risk of ESU. This result needs to be interpreted cautiously as all religions – including Islam – generally promote healthy living. In this study, the sample students are predominantly Muslim, a fact that may influence the findings. In a report released by Pew Research Center, statistics show that the percentage of smartphone ownership has significantly increased in Muslim-majority countries like Lebanon and Jordan by 25–28% between 2015 to 2017 . A localLooking at ESU from a slightly different angle, Parent et al.  suggesteThere are limitations to this study. Firstly, the sample size of 273 might not be enough for a good statistical analysis. Secondly, this study was conducted on a specific population , making the generalizability of the interpretation of its results to other populations to be limited. Furthermore, this study did not look into specific activities during the use of smartphones – like gaming, internet use, or social media. These activities represent another aspect to be explored in future studies. The small sample size and the sample heterogeneity in this study also did not allow Bonferroni corrections to be administered.This study offers insight into excessive smartphone use and its effects on Malaysian medical students. ESU is prevalent among UKM medical students regardless of their gender. Our study suggests that there is a significant positive correlation between ESU and social anxiety. We also discovered negative correlations between ESU and quality of life in various domains. Despite the limitations, we believe that this study may contribute to the development of new knowledge, particularly on the effects of smartphones on people's daily lives. Hopefully, this knowledge will help to guide users to maximize the potential of a smartphone to enrich their lives while averting the pitfalls. Further studies on smartphone use are necessary to explore how and under what conditions would smartphone use – despite being excessive – still be beneficial to users. The studies may also explore what other conditions would smartphone use be considered harmful.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Research and Ethics Committee, Faculty of Medicine, Universiti Kebangsaan Malaysia (Project Code: FF-2018-243). The patients/participants provided their written informed consent to participate in this study.MM, SS, and NN contributed to conception and design of the study. AA, KS, NB, NM, and SK collected and organized the database. MN performed the statistical analysis. HM, AA, KS, NB, NM, SK, MM, NN, and SS wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.