After community transmission of monkeypox virus was identified in Europe, interviews of 45 case-patients from England indicated transmission in international sexual networks of gay and bisexual men since April 2022. Interventions targeting sex-on-premises venues, geospatial dating applications, and sexual health services are likely to be critical for outbreak control. Monkeypox is a zoonotic viral infection endemic to West and Central Africa. Human-to-human transmission of monkeypox virus (MPXV) is thought to be primarily through close skin-to-skin contact; other transmission routes include respiratory secretions and fomites  Regulations 2020 and Section 251 of the National Health Service Act 2006. All data were anonymized during analysis, and records were stored securely.Persons with confirmed MPXV infection were identified by PCR at the Rare and Imported Pathogens Laboratory at UKHSA, according to standard procedure, and reported to local health protection teams, who were responsible for public health management. Case-patients with known or suspected links to transmission in GBMSM sexual networks were invited for follow-up interviews focused on their sexual health; phone interviews were conducted during May 25–30, 2022, and followed a structured questionnaire. Participation in the follow-up interviews was voluntary, and verbal consent was obtained after the context and rationale for the additional interview was explained. The questionnaire information was similar to that captured in previous outbreaks: demographics ; potential exposures in the 21 days before symptom onset ; markers of sexual behavior associated with higher risk of acquiring sexually transmitted infections (STIs) ; and HIV prevention and care  , crystal methamphetamine, or mephedrone during sex. Exposure sites/events included sex-on-premises venues , private sex parties, cruising, and international events/festivals. Cruising was defined as sexual activity with anonymous partners in public outdoor spaces. Private sex parties were defined as group sex in a household, and when not explicitly mentioned, private sex parties were inferred if a person reported group sex and chemsex outside sex-on-premises venues.https://www.snapsurverys.com) and extracted data for analysis on May 30, 2022. We used Stata 17.0 (https://www.stata.com) to clean and summarize the data to provide descriptive statistics. To assess participation bias, we used Mann-Whitney U, χ2, and Fisher exact tests to compare case-patients by age, region of residence, and travel history; data were sourced from the public health case management system . To identify time when community transmission started and potential routes of importation, we plotted onset of first symptoms (prodrome or rash), travel, and venue attendance dates on timelines.We securely recorded data by using the online questionnaire tool Snap 11 Professional . HIV status was reported by 43 case-patients: 74% (32/43) were HIV negative, of which 91% (29/32) were receiving PrEP; 11/43 (26%) reported living with HIV and all were receiving HIV treatment. Although most  case-patients reported attending sex-on-premises venues, festivals, private sex parties, or cruising grounds in the 21 days before symptom onset, 16/45 (36%) did not report such exposures . Of thosOur findings suggest that sustained domestic MPXV transmission in sexual networks of GBMSM in England has been occurring since at least April 2022, with potential importations and exportations from other countries in Europe. MPXV transmission in sexual networks has been suggested for outbreak investigations in Nigeria  as PrEP for MPXV (Persons with a monkeypox diagnosis were in frequent contact with sexual health services and linked to care for HIV medication or PrEP. This link to existing services and programs provides an opportunity for policymakers to implement other interventions to reach those with highest need, including using smallpox Modified Vaccinia Ankara vaccine (Bavarian Nordic, A substantial proportion of case-patients did not report specific exposure settings, stressing the need for wider interventions to reach all GBMSM in these sexual networks. The high use of geospatial dating applications highlights their utility as a platform for health promotion.Limitations of this study include social desirability bias, participation bias, and evolving patterns of transmission, affecting their generalizability. Nonetheless, these analyses may provide information for the initial outbreak response in countries with similar transmission patterns. Because of the high interconnectivity of sexual networks, urgent multilateral action is needed to stop human-to-human transmission and avoid global endemicity.


The association between out-of-hospital cardiac arrest patient survival and advanced life support response time remained controversial. We aimed to test the hypothesis that for adult, non-traumatic, out-of-hospital cardiac arrest patients, a shorter advanced life support response time is associated with a better chance of survival. We analyzed Utstein-based registry data on adult, non-traumatic, out-of-hospital cardiac arrest patients in Taipei from 2011 to 2015.Patients without complete data, witnessed by emergency medical technicians, or with response times of ≥ 15 minutes, were excluded. We used logistic regression with an exposure of advanced life support response time. Primary and secondary outcomes were survival to hospital discharge and favorable neurological outcomes , respectively. Subgroup analyses were based on presenting rhythms of out-of-hospital cardiac arrest, bystander cardiopulmonary resuscitation, and witness status.A total of 4,278 cases were included in the final analysis. The median advanced life support response time was 9 minutes. For every minute delayed in advanced life support response time, the chance of survival to hospital discharge would reduce by 7% and chance of favorable neurological outcome by 9%. Subgroup analysis showed that a longer advanced life support response time was negatively associated with the chance of survival to hospital discharge among out-of-hospital cardiac arrest patients with shockable rhythm and pulse electrical activity groups.In non-traumatic, adult, out-of-hospital cardiac arrest patients in Taipei, a longer advanced life support response time was associated with declining odds of survival to hospital discharge and favorable neurologic outcomes, especially in patients presenting with shockable rhythm and pulse electrical activity. Out-of-hospital cardiac arrest (OHCA) is a major disease worldwide, with a high mortality rate. Taiwan has approximately 9,815 cases of OHCA annually, with a survival rate of approximately 9.8% . SeveralThe effect of advanced life support (ALS) treatments in prehospital settings remains controversial. Several studies reported that earlier ALS intervention is associated with increasing survival rate –16, whilRegarding the EMS system in Taipei, previous studies showed that the intervention of ALS and the number of ALS personnel are associated with better outcomes in OHCA patients , 23–27; We conducted a 5-year retrospective cohort study using prospectively collected Utstein-based registry data from the Taipei EMS to investigate the association between the response time of ALS care and OHCA patient outcomes. All methods were performed in accordance with the study protocol which was approved by the Institutional Review Board (IRB) of the National Taiwan University Hospital (201606007RIND). Informed consent was waived due to the anonymized database and retrospective nature of the study, which was also approved by IRB of the National Taiwan University Hospital. The preliminary version of the abstract had been published at the European Resuscitation Council annual conference 2019 in Slovenia before we develop it into a full-length article.The Utstein-based OHCA registry system from the Taipei EMS was initially developed for OHCA quality control . The reg2, with 2.6 million registered residents. The majority of the population is Taiwanese. Taipei City has an EMS system based on the fire service with a two-tiered response team, including a basic life support (BLS) team and an ALS team. Taipei City has 45 prehospital BLS stations with 1,279 emergency medical technician (EMT) intermediate staff, who have completed at least 320 hours of training; and four ALS stations with 141 EMT paramedics, who have completed at least 1280 hours of training and need to conduct OHCA re-training every year  Q1–Q3). We performed chi-squared or Fisher’s exact tests to assess the associations between the categorical variables and outcomes. For continuous variables, we conducted non-parametric Mann–Whitney rank sum tests for analyses. All variables previously determined to be associated with the outcomes were included in the multivariable logistic regression analysis to prevent overfitting. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and two-tailed p-values < 0.05 were considered statistically significant.We conducted a subgroup analysis using the new Utstein template, with methods suggested by the International Liaison Committee on Resuscitation (ILCOR) in 2014, to explore the effect of ALS response time among different subgroups of patients with OHCA. For this analysis, we stratified the data based on presenting rhythms of OHCA, including shockable rhythm (pVT/Vf), pulseless electrical activity (PEA), and asystole . We alsoOf the 16,062 OHCA cases treated between 2010 and 2015, 7,571 cases were adult, non-trauma OHCA without EMT witness with resuscitation attempted and 4,278 cases with ALS dispatch were included in the final analysis.  The propThe restricted cubic spline curve in In this large observational study in Taipei, we found that every minute of delay in ALS response time was associated with a 7% reduction in survival to hospital discharge and a 9% reduction in favorable neurological outcome in adult, non-traumatic, OHCA patients. A swift response by ALS not only benefited all OHCA patients, but also significantly benefited the subgroups of patients initially presenting shockable rhythms or PEA. An ALS response time of less than 8 minutes was associated with better outcomes in OHCA patients, while over 11 minutes was associated with a diminished chance of survival. We previously announced the preliminary results of this study [Our findings are similar to those of Grunau et al. , with neThere are several reasonable explanations for early ALS team response time improving the rate of survival to hospital discharge and neurological outcome among OHCA patients. ALS treatment includes airway management and drug administration. Network meta-analysis of randomized control trials reveal that ET tube placement and supraglottic airway (SGA) do increase the rate of ROSC compared to BVM ; the sucSome studies have opposed ALS treatment. The OPALS study compared the before and after of implementation of ALS paramedics into EMS in Canada. The results revealed no improvement in the rate of survival to hospital discharge and functional outcome in OHCA patients after ALS intervention . AlthougOur study had several limitations. First, this was a retrospective observational study. While selection bias inherent to our study design cannot be eliminated, we believe it was mitigated by our population-based approach. While we adjusted for common OHCA confounders, additional unmeasured or unmeasurable confounders may have been present, such as in-hospital care, which may have influenced OHCA survival , 57. SecIn non-traumatic, adult, OHCA patients in Taipei, a longer ALS response time was associated with worse odds of survival to hospital discharge and favorable neurological outcomes, especially in patients presenting with shockable rhythm and PEA.Our study further suggests the optimal ALS response time for the EMS system.S1 TableALS: advanced life support. BLS: basic life support. CPR: cardiopulmonary resuscitation. EMS: emergency medical service. EMT: emergency medical technician. OHCA: out-of-hospital cardiac arrest. OR: odds ratio. pVT: pulseless ventricular tachycardia. PEA: pulseless electrical activity. STHD: survival to hospital discharge. VF: ventricular fibrillation.(DOCX)Click here for additional data file.S2 Tablea: cannot performed due to N = 1 in group CPC1-2.ALS: advanced life support. BLS: basic life support. CPC: cerebral performance category. CPR: cardiopulmonary resuscitation. EMS: emergency medical service. EMT: emergency medical technician. OHCA: out-of-hospital cardiac arrest. OR: odds ratio. pVT: pulseless ventricular tachycardia. PEA: pulseless electrical activity. VF: ventricular fibrillation. (DOCX)Click here for additional data file.


Contextualization: Emotional experiences of psychologists related to the care of suicide crises are important since the health professional has been trained to save lives. It makes him apprehend the aggressive side of suicide and symbolize it as an attack. When the patient’s desire to liveceases, the professional may feel confused, since his/her profession/vocation was confronted.AIM: To explore and interpret the meanings of emotional experiences reported by psychologists who care for patients in suicide crises.Strategies: clinical-qualitative design, semi-directed interviews with open-ended questions in-depth. Six clinical psychologists from a Brazilian city participated, with a sample closed by information saturation. Interviews audio recorded, full transcribed and categorized by Qualitative Content Analysis. Results were peer-reviewed in meetings in a Qualitative Research Study Group.Findings: Three emerging categories - (1) Ambivalent emotions as challenges for clinical management, (2) The non-paralyzing experience of emotions, (3) The management that is learned in practice.Considerations: assistance to patients with a suicidal crisis can generate ambivalent emotions, not always paralyzing. When recognized and elaborated can assist in clinical practice. It can be tools that will support qualified approaches, especially in relation to suicide. As a public health problem, it demands a combination collective actions with effective individual clinical approaches.


HIV testing is a primary prevention strategy against the HIV epidemic and an entry point for HIV/AIDS-related care, prevention and treatment. This study aimed to estimate the uptake of HIV testing among Sino-Vietnam female sex workers (FSWs) in Guangxi, China, from 2016 to 2018, and to identify the factors influencing HIV testing uptake.A cross-sectional survey was conducted among FSWs in two Sino-Vietnam border cities of Guangxi, China. The survey was conducted through face-to-face interview, the data were collected by a structured questionnaire, and HIV-1 infection was detected simultaneously. Logistic regression analysis was used to determine the factors associated with uptake of HIV testing.In total, 4565 Chinese local FSWs (CL-FSWs) and 636 cross-border migrant Vietnamese FSWs (CMV-FSWs) were recruited into this study. HIV-1 prevalence in CL-FSWs and CMV-FSWs was 0.70% and 3.14%, respectively. The rate of self-reported uptake of HIV testing in CL-FSWs and CMV-FSWs was 54.56% and 45.44%, respectively. The rates of self-reported uptake of HIV testing declined in both groups from 2016 to 2018. Logistic regression analysis indicated that a number of factors, including socio-demographic characteristics , behaviour factors , psychological factors  were the factors significantly related to uptake of HIV testing.In recent years, the rate of HIV testing uptake among Sino-Vietnam border FSWs in Guangxi, China was low, which may be an important reason for the high HIV-1 prevalence among FSWs in the region. A number of factors were identified to be associated with HIV-1 testing uptake, suggesting that HIV testing prevention strategies in this region could include accelerating AIDS education training, raising personal awareness of HIV testing, and improving accessibility of HIV testing.The online version contains supplementary material available at 10.1186/s12879-022-07459-3. HIV testing, a key policy response to the HIV/AIDS epidemic, has been promoted as a primary prevention strategy and an entry point for assessing HIV/AIDS-related services, such as treatments and the subsequent improvements in life expectancy. Expanding HIV testing not only increases the proportion of HIV-positive people who know their infection status, but also provides an effective method of secondary prevention for those who test positive. China's HIV testing system has been developed over a period of time and has gone through several stages, including three testing models: voluntary counselling and testing (VCT), high-risk group testing, and provider-initiated testing and counselling (PITC) . HoweverGuangxi, a province in the Southwest of China that borders Vietnam and the ‘Golden Triangle’, is a gateway for drug trafficking routes and cross-border migration of sex workers. By the end of 2017, Guangxi had the second highest number of HIV reported cases among provincial-level regions in China, accounting for 12% of the total national HIV reported cases, and heterosexual intercourse had become the primary transmission route in Guangxi . A revieA number of studies have documented many factors associated with uptake of HIV testing among FSWs in China, including older age , less edFrom 2016 to 2018, a cross-sectional survey was conducted among FSWs in two Sino-Vietnam border cities  from May to July every year. The two cities share a 637-km border with northern Vietnam and have eleven land ports .The participants were recruited from a variety of venues where the local Center for Disease Control and Prevention (CDC) provided intervention services for HIV high-risk populations. Random sampling was conducted on venues, and cluster sampling was performed on FSWs of the selected sites. The venues included high- or middle (mid)—tier venues and low-tier venues based on the mean income of FSW per transaction , 20 and After obtaining informed consent from the participants, trained CDC staff conducted face-to-face interviews in a private room, using a structured questionnaire. During the survey, interviewers provided explanations and instructions to help participants understand any questions in the questionnaire. For migrants with limited Chinese language proficiency, a Vietnamese-Chinese interpreter assisted in the survey. After completing the questionnaire, each participant was compensated 50 RMB (about $7 USD) for the participation. This study was approved by the Human Research Ethics Committee of Guangxi Medical University .The survey collected socio-demographic data including nationality, age, ethnicity, marital status, education, and current location. According to nationality information, the participants were divided into two groups: Chinese local FSWs (CL-FSWs) and cross-border migrant Vietnamese FSWs (CMV-FSWs).Behavioural variables were measured by questions regarding condom use, commercial sex transaction, injected illicit drug, their regular commercial or non-commercial sexual partners, STI history, having received HIV-related services, self-reported uptake of HIV testing, etc.HIV/AIDS-related knowledge was assessed with an 8-question evaluation form proposed by the Chinese CDC , which iPsychological variables mainly referred to the perceived risk of HIV infection and the perception of vulnerability to HIV/STIs. The assessment of the perceived risk for HIV infection was scored using four-option questions. The assessment of perception of vulnerability to HIV/STI was scored using Yes/No questions, and the two-item scale had a Cronbach’s alpha value of 0.80. In addition, we investigated the participants’ perceptions of family attitudes toward their work.The behavioural variables, assessment of HIV/AIDS-related knowledge and psychological variables can be seen in Additional file At the time of the survey, participants were asked to provide blood specimens to test for HIV antibodies. Specimens that screened positive by enzyme-linked immunosorbent assay (ELISA)  were confirmed by western blot (WB) assay . The purpose of the HIV testing is to estimate the HIV prevalence among FSW population.In addition, the questionnaire presented the option of self-reported uptake of HIV testing in the preceding year. “HIV Testing” in the questionnaire refers to the history of HIV testing, which is self-reported, using either ELISA or WB.The collected data were double entered with EpiData3.0. For socio-demographic characteristics, the proportions were calculated for the two groups (CL-FSWs and CMV-FSWs). The chi-square trend test was used to test the significance of time trend. Univariate logistic regression analyses were performed for each independent variable of uptake of HIV testing, with crude odds ratio and 95% confidence intervals (CI) indicated. Variables with significant univariate level (p < 0.1) were input into the logistic regression model to calculate the adjusted ORs and 95% CIs against the dependent variable for each group. Finally, a multivariate logistic regression model was established by the stepwise method. Statistical significance was defined as p < 0.05 (two-tailed test). All analyses were performed using SPSS statistical package version 23.As shown in Table 2 = 187.04, p < 0.001). Similarly, the rate of receiving free AIDS education and condom distribution services, peer education services were also significantly decreased. In the CMV-FSWs group, the HIV prevalence increased significantly , but the rates of self-reported uptake of HIV testing in the preceding year, receiving free AIDS education and condom distribution services, and peer education services declined significantly , but the rates of self-reported uptake of HIV testing in the preceding year, receiving free AIDS education and condom distribution services, and peer education services declined significantly , 0.91% (2017), and 1.12% (2018) , especially among CMV-FSWs . These data are higher than the general level of FSWs in Guangxi , 26 and Despite the Chinese government began free testing service in 2003 and expanded the program to over 10,000 sites by the end of 2018 , the actOur study indicates that age < 35 years and higher education were significantly related to uptake of HIV testing. The finding of an association between younger age and HIV testing was consistent with previous studies –31. ReceWe also found that HIV testing was significantly associated with a higher rate of risky sexual behaviours such as inconsistent condom use, more years of FSW experience, and serving more male clients. These findings were consistent with previous studies showing that people who engaged in high–risk sexual behaviours were more likely to take HIV tests , 33, 34.In our study, HIV testing was associated with a history of self-reported STIs, which has also been reported in previous studies . The reaIt is worth mentioning that whether CL-FSWs had received free AIDS education and condoms, and whether they had received peer education from HIV prevention programs were the two most important factors influencing uptake of HIV testing, which is consistent with previous studies , 37, 39.We recognize several limitations of our study. Firstly, due to the cross-sectional design of this study, we were unable to determine whether certain behaviors occurred before or after HIV testing, which limited our ability to establish causal relationship. Secondly, because the participants in our study were anonymous and the time-series samples in the same cities were used for three consecutive years, multiple presenting FSWs might result in sample overlap across years. Thirdly, as our survey involved some stigma-related behaviours, a social desirability bias may have resulted in under-reporting of high-risk behaviours. Despite these limitations, the current study represents one of the few large-scale studies to investigate HIV prevalence, uptake of HIV testing, and related factors among FSWs, including cross-border migrant Vietnamese FSWs, in the Sino-Vietnam border areas in China. In addition, this study has the advantage of examining a wide range of explanatory factors and using a large representative population sample, by which providing insights into HIV testing for FSWs in cross-border areas.Findings from this study have important implications for developing intervention programs targeting Sino-Vietnamese areas in China. First, because the rate of HIV testing uptake among Sino-Vietnam border FSWs in Guangxi, China was low, two aspects can be considered to improve the uptake of HIV testing: the accessibility of HIV testing provided by the government and the improvement of personal awareness. Second, since age, working condition, education level and location were the factors influencing uptake of HIV testing, future interventions should target those working in low-tier venues, older, less educated, and cross-border migrant Vietnamese FSWs. Third, since free AIDS education, free condom programs, peer education were the important factors promoting uptake of HIV testing, these approaches may be more effective in enhancing HIV testing in the future. Last, In addition to traditional intervention sites, STD clinics can also be convenient places to disseminate AIDS education materials.Additional file 1: Key population quantitative questionnaires.


To compare the effectiveness of high-resolution dermal ultrasound (US) guided superficial radiotherapy (SRT) to non-image-guided radiotherapy in the treatment of early-stage Non-Melanoma Skin Cancer (NMSC).A high-resolution dermal ultrasound (US) image guided form of superficial radiation therapy (designated here as US-SRT) was developed in 2013 where the tumor configuration and depth can be visualized prior to, during, and subsequent to treatments, using a 22 megahertz (MHz) dermal ultrasound (US) with a doppler component. We previously published the results using this technology to treat 2917 early-stage epithelial cancers showing a high local control (LC) rate of 99.3%. We compared these results with similar American studies from a comprehensive literature search used in an article/guideline published by American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions from 1988 to 2018. Only U.S. based studies with greater than 100 cases with similar patient/lesion characteristics and stages treated by external beam, electron, or superficial/orthovoltage radiation therapy were included in the criteria for selection. The resultant 4 studies had appropriate comparable cases identified and the data analyzed/calculated with regard to local control. Logistic regression analysis was performed comparing each study to US-SRT individually and collectively with stratification by histology .p-values ranging from p < 0.0001 to p = 0.0438.US-SRT LC was found to be statistically superior to each of the 4 non-image-guided radiation therapy studies individually and collectively (as well as stratified by histology subtype) with Results of US-SRT in local control were statistically significantly superior across the board versus non-image-guided radiation modalities in treatment of epithelial NMSC and should be considered a new gold standard for treatment of early-stage cutaneous BCC, SCC, and SCCIS. Non-melanoma skin cancer (NMSC) is the most common cancer diagnosed in the United States and it is comprised mostly of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in-situ (SCCIS) . In 2012Despite NMSC having a low mortality, high cure rates, rare metastasis, and only accounting for 0·1% of cancer deaths, the standard of treatment is surgical removal . HoweverMultiple radiation modalities exist for the treatment of NMSC, including brachytherapy, electron beam radiotherapy (EBRT), external radiation therapy (XRT), and superficial radiation therapy (SRT). Specifically, superficial radiation therapy, has been used by dermatologists for the past century to treat NMSC . With th1To statistically evaluate the local control (LC) differences, if any, of US-SRT versus non-image-guided radiotherapy modalities for the treatment of early-stage epithelial cancer.US-SRT results have been investigated in two seminal studies referenced hereafter as the 2021 US-SRT study and the 2022 US-SRT study , 9. DataUS-SRT outcomes included in the present analyses are from a subset of the 2021 US-SRT study patients who have a follow-up of greater than 52 weeks; and are from the entire study population of the 2022 US-SRT study.The American Society of Radiation Oncology (ASTRO) published a literature review containing 143 studies on curative radiation treatment for NMSC . A subseOnly studies performed in the USA.Meta-analysis, brachytherapy, pre-operative, post-operative ± chemo/targeted agents used, recurrent or predominately recurrent, prior radiotherapy, T4 only/predominant, metastatic to parotids, involvement of parotids, wound healing only, no local control reported, perineural invasion in These criteria resulted in four high-quality, recent, evidenced-based studies, each with greater than 100 subjects. The four studies provided the XRT/SRT outcome data for this study and are hereafter referenced as the Lovett study, Locke study, Silverman study, and Cognetta study –15.is, T1 and T2 lesions were included. Specifically, the 2 US-SRT studies only had Tis, T1 and T2 lesions in the entire cohort whereas in the other studies, only early stage lesions of stage 0 to stage II were included for analysis. This was done to allow proper comparisons (of “apples to apples”) so that better local control caused by higher proportion of favorable patients as a confounding factor is eliminated.Local Control for this analysis was defined as complete resolution of the treated lesion without evidence of recurrence. Lesion counts for the two US-SRT studies and the four XRT/SRT studies were used to compute LC as “Number of lesions that did not recur / Total number of lesions”. Lesions were analyzed as independent events. Only TData availability in the two US-SRT studies and the four XRT/SRT studies made it possible to compare each US-SRT study  to the following XRT/SRT studies: Lovett, Locke, Silverman, and Cognetta for BCC; Lovett, Locke, and Cognetta for SCC; and Cognetta for SCCIS. For each comparison, a logistic model was implemented that contained the effect of treatment with treatment levels defined as the studies under consideration. Odds ratios were then derived that compared the US-SRT studies to each available XRT/SRT study and to all XRT/SRT studies combined.not involved in the study design, collection, analysis, interpretation of data, or writing of the report. The decision to submit the paper for publication was solely that of Dr. Lio Yu and the co-authors.The sponsor of the study (SkinCure Oncology) was Table p-values ranging from p < 0·0001 to p = 0·0438. Figure Table Our analysis shows US-SRT confers a statistically significant improvement in local control for all histologic subtypes of epithelial NMSC  compared to all four high-quality, recent, large studies using non-image-guided forms of radiotherapy (XRT/SRT). The improvement in local control can be attributed to the image-guided component of superficial radiotherapy, as the high definition integrated dermal ultrasound with doppler features allows for visualization of the early-stage lesions’ depth, breadth, and overall configuration prior to, during, and after treatment. Visualization during treatment allows for the treatment provider to adjust radiotherapy dosages and energies of penetration daily if necessary. Visualization after treatment allows for confirmation of lesion resolution/response.Advantages of US-SRT include high cure-rates as demonstrated in the 2021 and 2022 papers. It is cost effective, due to its low-recurrence rate. It offers cosmetic benefits as it is tissue sparing and the majority of NMSC lesions occur in cosmetically sensitive areas, such as the head and neck. Patients can avoid pain, scarring and risk of infection and/or bleeding since this is a non-surgical treatment modality. As many patients often have more than one lesion diagnosed simultaneously, multiple lesions can also be treated synchronously with US-SRT. Offices that use US-SRT have reported overall excellent (> 95%) patient satisfaction and provider satisfaction . Indeed, a wide variety of patients could benefit from US-SRT, especially those with lesions on the head and neck region such as the ear, nose, or eyelids for functional preservation purposes, on the face where cosmesis is of concern, as well as the scalp where surgical closure is challenging often requiring flap placement for larger or multiple adjacent/confluent lesions. In the below knee locations where poor vascularization can result in protracted non-healing, US-SRT has an advantage over surgery because of its non-invasive nature.Absolute and relative contraindications to US-SRT, as previously described in the 2021 US-SRT studies, include lesion invasion to underlying bone or muscle, thickness > 6 mm, previous radiation to the same lesion site, ataxia telangiectasia, active connective tissue disease, active lupus or rheumatologic disease, concomitant management with radiation sensitizing chemotherapy agent, T4 stage, and node positive status .US-SRT could be considered the preferred standard non-surgical radiotherapeutic treatment modality for appropriate patients with early-stage epithelial skin cancers  with comparable LC to MMS without the drawbacks of surgery. At the minimum, patients should be presented with the option to have their NMSC treated with US-SRT.No randomized controlled trial exists for direct comparison of US-SRT to radiotherapy modalities, including superficial and external radiotherapy. The follow-up periods in this paper, though long enough to reasonably assure meaningful and accurate US-SRT to XRT/SRT comparisons, are unequal among studies.3Image guidance with high resolution dermal ultrasound in the form of US-SRT is shown to confer a statistically significant advantage in lesion local control over non- image guided forms of SRT or XRT in all subtypes of cutaneous epithelial NMSC and should be considered the preferred standard of non-surgical treatment for early stage cutaneous BCC, SCC, and SCCIS.


Necroptosis, is intimately linked to tumor development and prognosis and has been considered as a target for anticancer therapy. However, the role of necroptosis-related genes (NRGs) in colon cancer is unclear.In the present study, we screened 76 NRGs from previous studies and described the landscape of transcriptomic and genetic variation of NRGs in colon cancer (CC) patient samples. Molecular subtypes of necroptosis in colon cancer were identified by clustering analysis, and these molecular subtypes were linked to patient prognosis and TME cell infiltration characteristics. Then, the NRS-score for predicting overall survival (OS) was built based on the TCGA database and validated in the GSE39582 cohort for its predictive power in CC patients. Besides, the ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between NRS-score and tumor immune microenvironment.We identified two molecular subtypes associated with necroptosis in CC, which have diverse prognosis and immune microenvironment characteristics. Based on the differentially expressed genes between the two molecular subtypes, we further developed a necroptosis risk score signature, referred to as NRS-score. High NRS-score was associated with poor prognosis in CC through immunosuppressive microenvironment and immune escape mechanisms. The nomogram based on NRS-score showed excellent ability to predict prognosis. In addition, NRS-score presented a positive correlation with tumor mutational burden (TMB) and immune checkpoint blockade (ICB) expression and was closely correlated with multiple anticancer agent susceptibility.This work revealed a close relationship between necroptosis and the prognosis and immune microenvironment of colon cancer. The NRS-score based on the 8-gene signature may be used to predict the sensitivity of immunotherapy and chemotherapy in colon cancer patients, and provides a foundation for future studies targeting necroptosis and its immune microenvironment. According to global cancer statistics, colon cancer (CC) is the third most common malignancy and the second leading cause of cancer death worldwide . DespiteNecroptosis is a genetically regulated form of programmed necrotic cell death that is mainly activated by receptor-interacting protein kinase 1 (RIPK1), with RIPK3 and mixed lineage kinase domain-like pseudokinase (MLKL) mediated . As a coThis study integrated transcriptomic data from 1,172 CC samples from TCGA and GEO databases and collected 76 necroptosis-related regulators from previous studies. We successfully classified colon cancer patients into two necroptosis-related molecular subtypes with diverse clinical outcomes and tumor microenvironment (TME) infiltration characteristics. In addition, the necroptosis score was established to quantify the level of necroptosis in individual tumors, allowing for more individualized and effective anti-cancer treatment strategies.https://cancergenome.nih.gov/) and the Gene Expression Omnibus . Patients with no survival information were excluded from further analysis. A total of 1,172 patients were enrolled for analysis, which consisted of two GEO cohorts (GSE39582 and GSE17536) and the TCGA-CORD cohort. Baseline information for all colon cancer patient datasets is listed in The RNA sequencing data and corresponding clinical profiles of CC patients were acquired from The Cancer Genome Atlas .Seventy-six necroptosis-related genes (NRGs) were obtained from previous studies  algorithm was used to quantify the relative abundance of each cell infiltrate in TME of CC. The gene sets used to mark each TME-infiltrating immune cell type were obtained from Charoentong's study (We performed consensus clustering using the R package “ConsensusClusterPlus” to identify distinct molecular subtypes associated with necroptosis based on the expression of DENRGs . Kaplan-'s study .P < 0.05 and | Log2(fold change) | > 0.5 . Subsequently, the extracted RNA was reverse transcribed using the PrimeScript RT kit and gDNA Eraser . SYBR Green-based quantitative real-time PCR was used for analysis. Data were calculated by the 2–ΔΔC(T) strategy and standardized with GAPDH. The primers used in the real-time PCR analysis are listed in To investigate the relationship between the NRS-score and TME, the ESTIMATE algorithm was applied to quantify the immune score, stromal score, ESTIMATE score, and tumor purity for each patient in TCGA-CORD . The R pData from the Genomics of Drug Sensitivity in Cancer (GDSC) database were used to predict the sensitivity of CC patients to chemotherapeutic and targeted therapeutic agents. The “pRRophetic” R package was used to estimate the half maximal inhibitory concentration (IC50), which was extensively utilized in medical studies , 31.P < 0.05 if not explicitly mentioned.All data analyses were performed using R software (version 4.0.5). Wilcoxon test was used to compare the differences in gene expression levels between cancer and normal tissues. Correlation tests were used using the Spearman coefficient test. The statistical significance threshold was considered as P < 0.05), of which 31 regulators were upregulated and 31 were downregulated in cancer tissues  of the 399 CC samples showed regulatory mutations associated with necroptosis . Among t tissues . However tissues .k = 2 seemed to be the best choice for classifying the whole cohort into molecular subtypes (n = 631) and C2 (n = 541). Survival analysis revealed a significant survival advantage with the C2 subtype  + (0.0508* LAMP5 expression) + (0.0354 * GRP expression) + (0.0514* FABP4 expression) + (−0.0910* MMP10 expression) + (−0.0081 * MMP1 expression) + (−0.0799* SPINK1 expression) + (−0.0332* CLCA4 expression). CC patients in the TCGA cohort were divided into high NRS-score (n = 216) and low NRS-score groups (n = 217) according to median risk cut-off values. Principal component analysis of the different NRS-score groups showed satisfactory separation  and low scoring group (n = 265)  . The resn = 265) . The ROCn = 265) .For further verifying the significance of the NRS-score in clinical practice, we checked its correlation with the available clinical traits of CC. The results showed that NRS-score was significantly associated with high T-stage, N-stage, and M-stage in patients with colon cancer . In addiTo establish a clinically applicable survival prediction method for CC patients, we combined the above five independent prognostic factors to construct a nomogram to predict the 1-, 3-, and 5-year survival probabilities of CC patients . Then, wIn addition, to assess the predictive strength of the NRS-score for clinical use in the CC patient cohort, we compared our prognostic signature with other recently reported CC signatures. Relevant prognostic genes were obtained from the corresponding literature: the hypoxia-related prognostic signature from He (referred to as HeSig), the xenobiotic metabolism-related prognostic signature from Wen (referred to as WenSig), and the inflammation-related prognostic signature from Qiu (referred to as QiuSig). We found that our model performed slightly better than the other three models in predicting CC prognosis  through the comparative analysis of these models .We examined the mRNA levels of eight signature genes in six pairs of colon cancer tissues and adjacent normal tissue samples collected from our hospital. The results showed that, compared with the corresponding normal tissues, the expression levels of MMP10, GRP, MMP1, FABP4, and SPINK1 were elevated in CC tissues, whereas the expression levels of GPRASP1, CLCA4, and LAMP5 were downregulated . Interesp < 0.001, p = 0.0064, p = 0.0059, Since TME plays a crucial role in cancer development and treatment, we further explored the differences in immune characteristics between the various NRS-score groups. ESTIMATE analysis showed that both the stromal score  and low TMB group (n = 183). The results showed no significant difference in the survival prognosis of patients in the high and low TMB groups . Multivariate Cox regression analysis showed that NRS-score, T-stage, N-stage, and M-stage were identified as independent prognostic factors and were included in the nomogram. The calibration curves indicated that the nomogram was an effective tool for predicting the prognosis of CC. Our results demonstrated that the constructed model could well-differentiate colon cancer patients and predict prognosis, thus helping to develop individualized treatment plans based on the NRS-score of patients.The prognostic signature we constructed contains a total of eight hub genes, which have attracted much attention in the cancer field so far. Gastrin-releasing peptide (GRP) and its receptor (GRPR) have been reported to be aberrantly expressed in the colon after malignant transformation and have been associated with delayed tumor recurrence and improved survival . They maThe regulation of the inflammatory reactions induced by necroptosis is crucial in the tumor microenvironment. The present study showed that different NRS-score groups exhibited different TME infiltration characteristics. NRS-score showed a significant positive correlation with ESTIMATES score and stromal score, but a negative correlation with tumor purity. In other words, tumors in the high NRS-score group were of lower purity and had a worse prognosis, consistent with the findings of several previous studies in colon cancer , 68. We Recently, targeted immune checkpoint blockade (ICB) therapy has been considered as a promising approach for the treatment of CC . HoweverFinally, we determined the drug sensitivity of different anticancer drugs in the treatment of patients with CC in distinct NRS-score groups. Based on IC50 values, vinblastine, axitinib, bleomycin, cisplatin, doxorubicin, imatinib, dasatinib, and elesclomol showed better responses in the high NRS-score group, while paclitaxel, rapamycin, and sorafenib in the low-score group showed better response. Screening chemotherapeutic agents according to the molecular subtypes of patients for individualized treatment is the inevitable way to overcome drug resistance.in vivo and in vitro experiments to investigate. In addition, the clinical application of NRS-score in the individualized treatment of colon cancer needs to be further investigated. These not only raise the challenges but also give us more incentives to keep digging.In summary, our study was designed to identify molecular subtypes of necroptosis in CC patients, construct a prognostic signature based on genes differentially expressed between subtypes, and link necroptosis to patient prognosis and immune microenvironment. The NRS-score based on the prognostic signature can predict not only the long-term survival of patients but also their clinical response to anti-PDL1 immunotherapy, the efficiency of chemotherapy and targeted therapy. However, there are still some limitations of our study. First, our study samples were all based on retrospective data, and large-scale prospective data are needed to validate our findings. Second, the specific molecular mechanisms of the eight prognostic gene signatures in colon cancer require further The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/RH wrote the article. MZ, LH, JH, and CM processed the data analysis. XW and YL conceived of this study. YF revised the final manuscript. All authors read and approved the final manuscript, contributed to the article, and approved the submitted version.This study was supported by Jiangsu Innovative Team Leading Talent Fund (CXTDC2016006 and QNRC2016446), Jiangsu 333 Talent Fund (BRA2020016), Jiangsu Provincial Key Research and Development Special Fund (BE2015666), Jiangsu Six High Peak Talent Fund (WSW-205 and WSW236), Zhenjiang Key Research and Development Fund (SH2021038), and Suqian Science and Technology Support Project Fund (K201907).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.


Motivation. Immunoglobulin proteins (IGP)  are glycoproteins that act as B-cell receptors against external or internal antigens like viruses and bacteria. IGPs play a significant role in diverse cellular processes ranging from adhesion to cell recognition. IGP identifications via the in-silico approach are faster and more cost-effective than wet-lab technological methods. Methods. In this study, we developed an intelligent theoretical deep learning framework, “IGPred-HDnet” for the discrimination of IGPs and non-IGPs. Three types of promising descriptors are feature extraction based on graphical and statistical features (FEGS), amphiphilic pseudo-amino acid composition (Amp-PseAAC), and dipeptide composition (DPC) to extract the graphical, physicochemical, and sequential features. Next, the extracted attributes are evaluated through machine learning, i.e., decision tree (DT), support vector machine (SVM), k-nearest neighbour (KNN), and hierarchical deep network (HDnet) classifiers. The proposed predictor IGPred-HDnet was trained and tested using a 10-fold cross-validation and independent test. Results and Conclusion. The success rates in terms of accuracy (ACC) and Matthew's correlation coefficient (MCC) of IGPred-HDnet on training and independent dataset (Dtrain Dtest) are ACC = 98.00%, 99.10%, and MCC = 0.958, and 0.980 points, respectively. The empirical outcomes demonstrate that the IGPred-HDnet model efficacy on both datasets using the novel FEGS feature and HDnet algorithm achieved superior predictions to other existing computational models. We hope this research will provide great insights into the large-scale identification of IGPs and pharmaceutical companies in new drug design. Immunoglobulins are serum proteins in the human body. These proteins act as an antibody involved in the various cellular processes such as a decision, binding, or recognition of the cell. Immunoglobulin significantly boosts the immune system by discovering the dangerous macromolecules that entered the body . When unImmunoglobulins are linked/related to various disease treatments , such asn-gram features representation, where the occurrence of n-length peptides are utilized as feature matrices 63], SVM Several judgements are made on the reported results of all classifiers in Secondly, among the feature representation approaches, FEGS  produced the best results for overall hypothesis learners (classifiers) than other feature vectors such as DPC and APAAC. The underlyingreason for the high prediction rate of FEGS methods is that FEGS extracts the conserved local and global graphical, physicochemical and statistical attributes from a protein sequence. As in test were unseen, and none of the immunoglobulin samples was used in training the model. In this subsection, we examine the success rates of our model via an independent test to show its generalization power. It was ensured that the samples in the independent test DIn this section, we theoretically compare the efficacy of our proposed model with the three developed approaches such as CC-PSSM , IGPred The underlying reason for achieving high predictions is to extract the graphical-based, physicochemical-based, and sequence-based attributes. Also, the hierarchical type structure of the HDnet classifier enables a better forecast of the IGs samples from the extracted attributes .IGPs are a crucial constituent of the immune system. Understanding deep insight IGPs can provide useful hints in drug discovery for disease treatment. Thus, the objective of this research was to construct a novel sequence-based computational method for predicting and analyzing IGPs. The proposed theoretical model “IGPred-HDnet” is superior to other advance immunoglobulin-based predictors due to several reasons. Firstly, we designed an innovative graphical algorithm FEGS to capture structured information buried in the protein sample. The structure features produced better results than the other feature schemes. Secondly, we implemented a deep learning model called HDnet for the first time as a learning model for recognizing IGPs.Despite enhancing the model's overall performance, further gaps still exist for future, such as several previous publications like Tang et al.  establis


The availability of a simple web-based platform for DMS-MaPseq analysis will dramatically expand studies of RNA structure and aid in the design of structure-based therapeutics.RNA structures play critical roles in regulating gene expression across all domains of life and viruses. Chemical probing methods coupled with massively parallel sequencing have revolutionized the RNA structure field by enabling the assessment of many structures in their native, physiological context. Previously, we developed Dimethyl-Sulfate-based Mutational Profiling and Sequencing (DMS-MaPseq), which uses DMS to label the Watson-Crick face of open and accessible adenine and cytosine bases in the RNA. We used this approach to determine the genome-wide structures of HIV-1 and SARS-CoV-2 in infected cells, which permitted uncovering new biology and identifying therapeutic targets. Due to the simplicity and ease of the experimental procedure, DMS-MaPseq has been adopted by labs worldwide. However, bioinformatic analysis remains a substantial hurdle for labs that often lack the necessary infrastructure and computational expertise. Here we present a modern web-based interface that automates the analysis of chemical probing profiles from raw sequencing files (  RNA is an informational intermediate between DNA and proteins and drives a diverse set of biological processes . RNA’s aA wealth of techniques have been utilized to study RNA structures at different levels of resolution. Biophysical approaches such as NMR and X-ray crystallography have proven useful at resolving RNA structures at an atomic scale and can provide information on tertiary structure; however, these high-resolution approaches are time-intensive, requiring pure samples, making them not ideal for high-throughput data collection. In contrast, when combined with next-generation sequencing, chemical probing has allowed for the elucidation of the secondary structure of RNAs in a high throughput manner both in vivo and in vitro with single-nucleotide precision . One sucDMS-MaPseq has been used to determine the genome structure of both HIV-1  and SARSThe high-throughput nature of DMS-MaPseq produces orders of magnitude more data than previous chemical mapping procedures leading to a new analysis bottleneck. Furthermore, incorporating next-generation sequencing requires a host of new bioinformatics tools that may be unfamiliar to RNA structural biologists. These tools also require new computational infrastructure and know-how to run. These new challenges can lead to a significant barrier to analyzing high-throughput chemical mapping data. We have developed a MaP analysis webserver to alleviate the computational burden for extracting RNA structure information from mutational profiling chemical mapping data. This web-based platform will enable the scientific community to analyze high throughput chemical probing data without dedicated computational knowledge or infrastructure.The DMS-MaPseq protocol is extensively detailed in a dedicated paper (see ref: ). In shohttps://cherrypy.dev) framework based on Python3 (https://www.python.org/) for server web services and data management. The client-side utilizes HTML5 (http://www.w3.org/TR/html5/) styled with Bootstrap (http://getbootstrap.com/) coupled with jQuery (http://jquery.com) for interactive user-interface components. The MaP analysis server supports most web browsers, including Google Chrome, Mozilla Firefox, Apple Safari, and Microsoft Edge. The job submission page has been streamlined to be user-friendly  and support various functions, such as hovering for more information and zooming. Investigating the mutation fraction per nucleotide can reveal structural details for a reference RNA sequence. Generally, As and Cs with low reactivity (mutation fraction < 0.01) are in Watson-crick base pairs (e.g. AU or GC pairs). Conversely, nucleotides with high reactivity are unpaired or in noncanonical interactions. For a more in-depth discussion of DMS reactivity values, please see refs: , and if it's lower, this may be a sign of an incorrect reference sequence or too many similar reference sequences. For each reference sequence, an interactive bar plot displays the mutational fraction of each nucleotide. Coloring is static, with guanosine, cytidine, adenosine, and uridine as orange, blue, red, and green. These interactive plots were generated with Plotly  ,16. ThisIn the past decade, the coupling of next-generation sequencing to chemical mapping has seen the emergence of rapid and high-throughput probing experiments. We expect experiments such as DMS-MaPseq to increase in popularity, with more groups adopting and expanding chemical mapping to supplement their other molecular and structural biology experiments. With the ever-increasing usage of high-throughput chemical mapping techniques, there will be a corresponding demand for new computational resources to analyze the results of these experiments. The webserver presented herein brings the first free and easy-to-use computational tool for analyzing MaP chemical mapping experiments. The MaP analysis webserver will alleviate the existing computational burden allowing to dramatically expand studies of RNA structure and aid in the design of structure-based therapeutics.


Purpose: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. Methods: A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Results: Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA)  compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall  after lutein plus zeaxanthin supplementation. Conclusions: Combinations of lutein and zeaxanthin with n-3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of n-3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients. Age-related macular-degeneration (AMD), a multifactorial neurodegenerative ophthalmic disease, is the most common cause of visual loss in the elderly population in the industrialized countries . NowadayCFH, CFI), complement components C2 and C3, and age-related maculopathy sensitivity 2 (ARMS2) ) as compared to the control group (1.0 logMAR [0.46–1.5]) but no significant change in central macular thickness [Allegrini et al. reported a significantly improved BCVA (hickness . In addin-3 LC-PUFA) which had reported measurements of BCVA and mfERG.Our meta-analysis and SR aimed to analyze if certain dietary supplements could delay the progression of AMD or even exert an improvement in any AMD stages by examining different parameters measuring visual and retinal functions. However, due to the diverse outcome measurements for visual functions and the various supplements used in the trials, only a few studies could be included into the meta-analyses. Therefore, three meta-analyses were conducted with carotenoid supplementations, i.e., lutein and zeaxanthin  function ,24. It hn-3 LC-PUFA revealed a significant improvement in BCVA  and  in BCVA . In addiN et al. ). Thereframeters ,27,31.The effect of carotenoid supplementation on other parameters measuring retinal function and appearance showed an improvement in MPOD depending on the dose and duration of the supplementation ,23,31,37n-3 LC-PUFA. It should be noted that vitamin E was present in these two studies without any significant effect on outcome measurements [n-3 LC-PUFA supplementation would benefit patients in the earlier stages of AMD.Querques et al. and Souied et al. did not detect any statistical significance in any visual parameters and drusen remodeling when AMD patients were supplemented with urements ,40. Howeurements ,35,40. TBoth studies using zinc supplements have observed positive effects in BCVA or AMD progression ,41. FurtCurcumin, another oxidant compound which has been combined with resveratrol, was administered in one of the selected studies and was associated with improvements in BCVA and a decrease in the number of anti-VFGF injections . LaboratThe heterogeneity in all meta-analyses was high. On the one hand, this can be explained by the low number of studies; on the other hand, several factors such as ethnicity, BMI, or education status can bias the study outcomes. For example, our meta-analyses included studies from different ethnic groups, which may have influenced the overall result. Several investigators have demonstrated that the prevalence of early and late AMD varies in different racial/ethnic groups. Thus, one study claimed that the highest AMD prevalence occurs in the Caucasian and Chinese populations . Other fIn addition to the administration of cholesterol-lowering medication i.e., statins, which seem to be protective for early and wet AMD ,60, it hTaking everything together, it does seem that the incidence and progression of AMD are influenced by many factors which could modify the outcomes of nutrient supplementation studies and should be taken into account in upcoming trials, since most of the included studies did not consider these confounding factors in their analyses.According to common clinical principles, the diagnosis of AMD is currently based on BCVA, fundus images, OCT, and fluorescein angiography . Howevern-3 LC-PUFA or lutein and zeaxanthin into the original AREDS formulation which contained beta-carotene did not have any additional benefit on the overall risk for the progression of AMD. These commonly accepted findings support the results of our meta-analysis. However, the benefit of n-3 LC-PUFA supplementation when combined with lutein and zeaxanthin was revealed in our meta-analysis of patients with early, dry and intermediate AMD . Longer interventions are more likely to show positive effects, but further studies are warranted to clarify whether long-term supplementations with carotenoids can modify the course of AMD. Due to a lack of studies with other supplements, no final conclusion can be drawn. Nevertheless, since they represent the whole AMD patient population, the results from this meta-analysis can be used as a basis for future clinical trials e.g., administering promising nutritional supplement combinations to well-specified patient populations.Combinations of carotenoids, namely lutein, and zeaxanthin, with Several of the retrieved studies provided their test subjects with formulations containing many different compounds. This makes it difficult to conclude if any of the effects were attributable to a single compound, whereas if the compounds exerted a synergistic effect, this might lead to improvements in the course of AMD. Finally, we propose that in the future, there should be a consensus reached on appropriate outcome measurements in AMD so that the outcomes of different trials will be truly comparable.


Globally, suicide is the fourth leading cause of adolescent mortality. Although post-primary school-based suicide prevention (PSSP) interventions are an evidence-based strategy for targeting adolescent suicidal thoughts and behaviors (STBs), PSSP effectiveness does not easily translate to school settings. Adolescents’ perspectives on PSSP are particularly important for (1) intervention effectiveness and implementation in both research and practice, (2) addressing PSSP evidence-practice gaps, and (3) enhancing meaningful adolescent involvement in PSSP, yet there is a gap in understanding adolescents’ experiences of engaging with PSSP. As such, this protocol outlines a meta-ethnography which will explore and synthesize adolescents’ perspectives on engaging with PSSP interventions, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers.The meta-ethnography protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. The protocol was guided by the seven-stage process for meta-ethnography proposed by Noblit and Hare. Searches of PsycINFO, MEDLINE, Web of Science, CINAHL, ERIC, Scopus, and study reference lists will identify peer-reviewed studies. Gray literature will be identified by searches in ProQuest, British Library EThOS, and DART-Europe E-theses Portal. The main reviewer will initially assess the eligibility of studies based on title and abstract, with full texts reviewed by at least two reviewers. Findings of the included studies will be synthesized in line with Noblit and Hare’s stages and evaluated using the Critical Appraisal Skills Program (CASP) checklist.To our knowledge, this is the first proposed meta-ethnography to explore and integrate the findings of qualitative studies exploring adolescents’ perspectives on engaging with PSSP interventions. Understanding adolescents’ experiences of engaging with PSSP will impact the field of PSSP in several ways by (1) enhancing research processes and intervention effectiveness and implementation, (2) informing decision-making and policymaking relevant to practice, (3) guiding meaningful adolescent involvement in PSSP, and (4) contributing to knowledge on the safety implications of engaging adolescents in PSSP. Finally, it is expected that the insights from this meta-ethnography will be widely applicable, given the growing demand for meaningful youth involvement in health-related fields.PROSPERO CRD42022319424. Suicide is the fourth leading cause of mortality in 15–19-year-olds globally –4 necessAdolescents’ experiences of engaging with PSSP are largely unexplored but are yet likely paramount to bridging the evidence-practice gap in PSSP. How acceptable and suitable health interventions are perceived by individuals engaged in interventions is critical to both intervention effectiveness  and implA review of school-based mental health interventions supported intervention fidelity components linked to adolescents’ perspectives  as stronger predictors of postvention mental health outcomes, in comparison to intervention fidelity components linked to the intervention itself , indicating that adolescents’ perspectives on school-based mental health interventions are markedly important to intervention success . The parFurthermore, understanding adolescents’ perspectives on PSSP thus far is a fundamental step in progressing meaningful adolescent engagement in PSSP research, which can be understood as adolescents’ active and decisive involvement throughout the research process . One reaMoreover, knowledge of adolescents’ perspectives on PSSP and enhancing meaningful adolescent involvement in PSSP research also responds to moral and socio-political obligations; the United Nation’s Convention on the Rights of the Child mandates that adolescents’ views are forefront to matters concerning them , and theThere is a critical need to address the gap in understanding adolescents’ perspectives on engaging with PSSP. There is no known synthesis of the qualitative research exploring and collating the varied experiences of young people engaging with PSSP, despite the existence of qualitative research exploring adolescents’ perspectives on engaging with PSSP. Meta-ethnography is well-positioned to draw qualitative findings together, generate over-arching understandings of collective experiences, and develop insights to inform decision-making .What are the perspectives of adolescents aged 11–19 years on engaging with PSSP interventions, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers?What are the experiences of adolescents aged 11–19 years in engaging with PSSP interventions, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers?The aim of the current protocol is to outline a meta-ethnography review, which will explore adolescents’ perspectives on and experiences of engaging with PSSP interventions, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers. The research questions guiding the meta-ethnography were developed based on the Population, Exposure and Outcome (PEO) framework  and are The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines  informedQualitative studies will be identified in the review and subject to a meta-ethnographic approach. Meta-ethnography will be used to synthesise and evaluate the outcomes of the included studies, in line with Noblit and Hare’s (1988) seven stage process for conducting meta-ethnography, which includes the following stages (1) getting started, (2) describing what is relevant to the initial interest, (3) reading included studies, (4) determining how the studies are related, (5) translating the studies into one another, (6) synthesising translations, and (7) expressing the synthesis. The meta-ethnography will also be guided by Campbell and colleagues , Lee andConsistent with the PEO framework studies were eligible for inclusion if they sampled adolescents aged 11–19-year-olds who had engaged with PSSP interventions as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers (“Population”); included interventions conducted in post-primary school settings targeting suicide-related outcomes  as both primary intervention outcomes and with other health and well-being outcomes (“Exposure”); and reported adolescents’ experiences with and perspectives on engaging with PSSP (“Outcome”).Inclusion criteria include (1) English language studies, (2) peer-reviewed journal articles and gray literature, and (3) qualitative and mixed-method studies reporting qualitative data collection methods and qualitative analysis. Exclusion criteria include (1) studies which do not include a method of qualitative data collection or analysis, (2) review and synthesis studies, and (3) studies which sample participants engaging with PSSP located in third-level education or university settings. Third-level education refers to education after second-level schooling, which results in a level 4 + qualification .Studies available from database inception will be identified by searches in PsycINFO, MEDLINE, Web of Science, CINAHL, ERIC, and Scopus. Gray literature will be identified by searches in ProQuest, British Library EThOS, and DART-Europe E-theses Portal. Where appropriate, MeSH, subject, and wildcard terms and truncation will be applied to database search strings. Database searches will be supplemented by searches in Google Scholar and reference lists of screened studies. Table Initially, the main reviewer will assess the eligibility of studies based on title and abstract. Any uncertainty of eligibility will be discussed by the reviewers until consensus is met. Then, the main reviewer will assess the eligibility of all full-texts, with full-texts reviewed by at least two reviewers. Any discrepancies in full-text assessment will be discussed with the aim of reaching consensus. If necessary, where consensus cannot be met between the main reviewer and the other reviewer, a third reviewer will be consulted. Inter-rater reliability of full text assessment will be quantified using Cohen’s Kappa Measure of Agreement Coefficient . All excStudy appraisal will be undertaken using CASP checklists , which wThe topic of interest was identified and discussed by the co-authors and explored based on the literature presented in the “The end-goal of this stage is to develop an exhaustive list of studies to be included in the meta-ethnography , which wReading the included studies will be undertaken to achieve several goals, including familiarization, extraction, appraisal, and comparison . The mai. Secondly, coded constructs (and within-study relationships) will be compared across studies. Key themes representing common and reoccurring constructs sharing underlying central concepts will be developed. Study characteristics including research design, intervention characteristics, and participant characteristics will be subject to cross study comparison. Thirdly, how studies relate to one another  will be determined based on the relationships between studies and key themes. Studies will be grouped based on the presence or absence of key themes. The relationships between key themes will also be considered in relation to the research questions and study characteristics [The main reviewer will lead data analysis, and at least one other reviewer will provide critique and guidance on analysis, in line with Lee and colleagues’ recommendations of enriching meta-ethnographic interpretation through collaboration. Stage 4 will involve three key steps : (1) liseristics , 43, 53.Stage 5 will involve the translation of constructs from one study into another to arrive at constructs which embody multiple constructs , 53. TheThe type of synthesis approach undertaken will determine if constructs and their respective translations encompass those in other studies, leading to analysis of competing translations and translation into each other. Stage 6 will result in key meta themes and a line-of argument synthesis will be created from the resulting third-order constructs. Line-of-argument synthesis may lead to a new model or theory beyond the individual interpretations of the included studies, about the experiences of young people engaging with PSSP , 43, 53.The synthesis will follow the eMERGe reporting guidance and will be submitted for peer review publication. It is expected that key findings from the meta-ethnography will be presented to academic and lay audiences.To our knowledge, this is the first proposed meta-ethnography which will explore and synthesize qualitative studies documenting adolescents’ perspectives on engaging with PSSP, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers. Insights from this meta-ethnography will address a key gap in the field of PSSP by enhancing understanding of the experiences of adolescents’ engaging with PSSP, such as how acceptable and suitable (or not) PSSP may be perceived by adolescents and the potential barriers to and facilitators of engaging with PSSP. The generation of a “line-of-argument” will result in a novel and overarching understanding of adolescents’ experiences with PSSP, which may reveal interpretations which were not apparent in the individual studies . These ihow adolescents should be involved in PSSP, as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers, which is necessary to alter the trajectory of adolescents’ lack of meaningful involvement in PSSP research. No known comprehensive guidance of this kind exists.Given that qualitative analysis of experiences is critical for informing intervention research and highlighting important information relating to intervention context and implementation , 57, theTo enhance meaningful youth involvement in youth mental health research in general, research must move away from a focus of young people engaging in research as passive subjects, towards a view of young people as central to research . CollateAlthough evidence does not indicate harmful effects after exposure to suicide research in assessment , screeniThere is increasing momentum for understanding the involvement of young people involved in research in wider-health-related fields . As suchhow adolescents engaged with PSSP is subordinate to the similarities and differences across the studies. Finally, amendments to the protocol will be described in the completed review publication.With respect to operational issues, initially adolescents’ experiences with and perspectives on PSSP will be synthesized with respect to whether adolescents engaged with PSSP as participants/end-users, intervention advisors, facilitators, and co-designers and co-researchers. Data will be fully integrated, similar to the procedure of Evans and Hurrell , provide


N-acyl-homoserine lactones, by bacteria to coordinate their response to population density and biofilm development. However, detailed information on the heterogeneity of QS metabolites in biofilms remains largely unknown. Here, we describe the utilization of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to follow the production of specific metabolites, including QS metabolites, during Pseudomonas putida biofilm development. To do so, a method to grow an agar-based biofilm was first established, and MALDI-MSI was used to detect and visualize the distribution of QS metabolites in biofilms at different cultivation times. This study demonstrated that N-acyl-homoserine lactones are homogeneously produced in the early stages of P. putida biofilm formation. In contrast, the spatial distribution of quinolones and pyochelin correlated with the swarming motility of P. putida in mature biofilms. These two metabolites are involved in the production of extracellular polymeric substances and iron chelators. Our study thus contributes to establishing the specific temporal regulation and spatial distribution of N-acyl-homoserine lactone-related metabolites and quinolone and pyochelin in P. putida biofilms.Quorum sensing (QS) is generally used to describe the process involving the release and recognition of signaling molecules, such as  N-acyl-homoserine lactones (AHLs) have been extensively studied among the various QS molecules identified. AHLs have been shown to control the expression of numerous traits, including bioluminescence, virulence, symbiosis, different forms of motility, biofilm formation, production of antibiotics and toxins, conjugation, and metal chelation +) were similar to the data from previous studies, indicating good validation of our analysis method, as presented in P. putida 6157 biofilms, mainly at the biofilm’s front line. In contrast, the repartitioning of the other quinolones was homogenous in the biofilm. These results indicated a clear relationship between the temporal production and spatial distribution of QS metabolites and biofilm development in P. putida 6157.To elucidate the relationship between the spatial distribution of QS metabolites produced by on times . Two disP. aeruginosa using MALDI-MSI [P. aeruginosa also exist in some P. putida strains, such as KT2440 [P. putida via MALDI-MSI had not been successful, and this may be due to the difficulties associated with sample preparation. Recently, Li et al. [P. putida F1. Using this approach, robust biofilms for MSI analysis were obtained within 72 h of inoculation. The spatial distribution of lipids and oligosaccharides was reported in this study; however, attempts to visualize QS metabolites were unsuccessful. It was reported that the abundance of QS compounds dramatically decreased in 48 h biofilms [P. putida biofilms.The development of the method for agar-based biofilm formation described in this study takes several factors into consideration, including wide application range, ease of operation, reproducible performance, and reduced risk of contamination. The agar-based biofilm approach proposed in this study was used to prepare biofilm samples for MSI because it has a lower risk of contamination. Furthermore, it can be used to study more than one colony per target plate, increasing sample throughput and allowing numerous samples to be processed via a single MALDI-MSI analysis. Previous studies have reported the visualization of QS molecules in ALDI-MSI ,23. Seves KT2440 . Howeveri et al.  demonstrbiofilms . TherefoP. putida, using MALDI-MSI. Our results showed that C4-HSL and 3-oxo-C12-HSL production was only observed in young biofilms. This agrees with previous work on biofilm formation and QS metabolite production using liquid chromatography coupled with mass spectrometry (LC-MS) [P. putida, and our results demonstrated that these metabolites were only observed in mature biofilms. Previous reports have shown that the AHL-QS system is controlled by a transcriptional factor pair, RhlI-RhlR, subordinate to the LasI-LasR pair. LasI is involved in the production of 3-oxoC12-HSL and RhlI in C4-HSL, both of which are produced at the early stage of biofilm formation. These AHLs bind to the transcriptional activators LasR and RhlR and activate target promoters. Both las and rhl have been implicated in the regulation of quinolone-like signaling molecule production in a group of Pseudomonas [P. putida biofilm. AHLs and quinolones have been reported to regulate the expression of genes required for specialized metabolite production, including that of the siderophore, pyochelin [Our modified agar-based biofilm workflow  was the  (LC-MS) . In addiudomonas ,30. As Cyochelin . This isP. putida. These findings expand our knowledge of QS and the mechanisms of AHL-QS-based biofilm formation. Furthermore, the QS metabolites detected in our study could be used as targets to impair the development of pathogen biofilms during infection.Our study demonstrated that QS heterogeneity could be visualized using a modified agar-based biofilm approach, which is convenient for MALDI-MSI analysis. The workflow used in our study was simple and could easily be adapted to various microbial biofilms. This study revealed the relationship between biofilm development and spatial production of specific QS metabolites in


Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc).We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India–Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc.Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies , and technical knowledge  from baseline. Participating ARTc increased TB screening , TB diagnosis , ART initiation  and TB preventive treatment completion .Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice. With 2.35 million people living with HIV (PLHIV)  and 2.59To strengthen collaboration between India’s National AIDS Control Programme (NACP) and National TB Elimination Programme (NTEP), the Government of India (GoI) launched single-window services for prevention and management of TB in PLHIV through Antiretroviral Therapy centres (ARTc) in December 2016 . The oveTherefore, case-based learning initiative for mentoring and capacity building using ECHO  platform, was designed to build communities of practice to strengthen HIV-TB care at ARTc. This initiative is a virtual, case-based learning model designed to build capacity of ART Centres healthcare providers for HIV-TB case management through biweekly sessions using the ECHO platform. Case based e-learning is anchored on the principle of moving knowledge instead of patients by linking less-experienced providers with subject matter experts.Globally, this is the first ever innovation which dealt with two different diseases and trained health care providers on integrated management of HIV-TB through case-based e-learning. The ECHO model has been successfully used in Presidents Emergency Plan for AIDS Relief (PEPFAR) supported countries to scale up HIV treatment , 12 and In May 2018, NACP rolled out this case-based e-learning initiative to strengthen HIV-TB care at 115 ARTc that provided care to 391,264 PLHIV. Here, we describe the feasibility and acceptability of the case-based e-learning for HIV-TB care and its impact on professional satisfaction, self-efficacy , technical knowledge retention (short-and long-term) and change in practice among HIV-TB care providers at ARTc in India.This quasi-experimental study included a cohort of ARTc staff invited to participate in case-based e-learning. NACP continues to provide ART to 1.4 million PLHIV and HIV-TB single-window services for co-infected persons through 540 ARTc that are primarily located in the public health institutions. National Institute of Tuberculosis and Respiratory Diseases (NITRD), moderated sessions as hub and 115 ARTc from four states  participated as spokes. Subject matter experts (referred to as experts) on HIV and TB were drawn both from NACP and NTEP, who provided expert opinion and facilitated case discussion.We purposively selected two states  with a high HIV prevalence  and two states  with low HIV prevalence  to implement the intervention at all ARTc in the above states . GeograpThis intervention was anchored on the conceptual framework of building communities of practice, defined as “groups of people who share a common concern/problems/passion, and deepen their knowledge and expertise by interacting on an ongoing basis” . We deveThe spokes shared difficult-to-manage cases in a standard format that captured clinical and laboratory details and the key queries about the case management. During the one-hour sessions, a predetermined spoke presented the case, followed by case discussion/didactic and proposed recommendations for case management by the invited subject experts.Data was collected to understand– (1) feasibility and acceptability of the case-based e-learning; (2) impact on professional satisfaction, self-efficacy scoring , technical knowledge retention (short-and long-term) and change in practices among providers. We referred to the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines from EQUATOR network which provide framework for reporting quality improvement in healthcare .–quality, clarity, relevance of content, appropriateness of duration; and overall rating of the session which allowed open-ended comments from participating sites. Feedback regarding the appropriate topics, interaction of the participants, internet connectivity, quality of case presentation by spokes, relevance of case study, timeliness and effectiveness of e-learning using a structured questionnaire was collected from the experts and response were classified as Agree, Neutral and Disagree.Feasibility and acceptability was assessed by using in-session information on date/time, participation, topic and expert. Each session concluded with a poll which captured feedback on four variables–self-efficacy , knowledge retention, and change in practices and patient outcomes. To assess self-efficacy , each spoke was subjected to an electronic survey at baseline and completion (at the end of 18 months). The scales used for assessment of self-efficacy were adapted from similar protocols used for evaluation of ECHO projects in other countries , treatment [n = 27(46%)], prevention [n = 8(14%)], pharmacology [n = 8 (14%)] and monitoring [n = 6 (10%)].The mean number of participating spokes per session was 55 and 100% spokes were retained until the completion of the study period. Each session had an average of 152 participants (range: 95–281) of which 16% were medical officers, 13% nurses, 26% treatment counsellors, 17% pharmacist and 38% were others   had facilitated 2 or more e-learning sessions. All the experts (100%) agreed that e-learning was an effective modus of capacity building of staff spread across various geographies; the case studies presented by the ARTc were relevant; pre-session information and assistance was adequate; and opined that the e-learning initiative should be scaled up. Whereas 87% responded that internet connectivity was not a challenge; 73% thought participant interaction to be adequate and case presentation by the ARTc of good quality and; 93% agreed that format and time for the session were appropriate and adequate Fig. .Fig. 4ExFeedback from the session experts included comments such as: “a promising initiative to help field staff across different geographies”; “a good initiative to be scaled”; “it's a pathbreaking in terms of imparting pertinent clinical knowledge”; “helps in building communities of practice” and “overall a good initiative”; “need to expand the scope to non-communicable diseases”.72/115 (63%) of spokes responded both for the baseline as well as the completion survey for assessment of self-efficacy  and long-term knowledge assessment.Perceived ease of access to experts and perceived ability to share clinical expertise with colleagues from other ARTc increased by 13% and 6% respectively. An increase of 8.6% p = 0.025) was reported in self-efficacy  on self-assessment, particularly with reference to ability to identify symptoms of TB in PLHIV , ability to diagnose and treat complicated cases of HIV-TB  and ability to assess and manage other co-morbidities in patients with HIV-TB   improvement in technical knowledge score across the domains. Spokes who responded to both baseline and completion survey on long-term technical knowledge retention (n = 72/115), reflected an overall improvement in correct responses to technical questions by 18.3% (p = 0.04) from baseline.There was an increase in four-symptom screening by 4.2% ; referrals for TB diagnosis by 2.0% ; TB diagnosis by 2.7% ; ART initiation by 4.3% , TPT completion by 5.2% . There was no significant difference in practices and patient outcomes between high and mid patient load ARTc.To address gaps in HIV-TB management, innovative means of service delivery, complemented by continuous capacity building of staff are critical. The study evaluated the feasibility, acceptability, and effectiveness of case-based e-learning for HIV-TB care among providers at ARTc. The findings indicate substantial improvement in knowledge of participating spokes across all curriculum domains and a significant increase in self-efficacy, satisfaction, acquisition of knowledge and new skills.All categories of staff were interested in sessions, corroborating that the case-based e-learning sessions as an acceptable means of team learning for ART centres’ staff and for building communities of practice. Participation of non-clinical healthcare providers in the e-learning initiative suggests increase in ownership and accountability by engaging them in development of session topics and presenting didactic lectures and cases. Participants reported most of the sessions to be clear with appropriate content, suitable timing and seamlessly broadcast without technical issues. The improvement in knowledge was translated into clinical management of TB as indicated by increase in symptom screening, diagnostic referral, TB treatment initiation and TPT completion rates.Like other ECHO projects, our study demonstrated the ability of the HIV-TB e-learning initiative to improve healthcare worker knowledge and satisfaction and decrease professional isolation –18. E-leExperts engaged in this intervention found e-learning as an effective and interactive means for capacity building of staff distributed across remote geographies and suggested expansion to other geographies and disease programmes , 26.The e-learning initiative facilitated both short-and long-term retention of participant knowledge, which was comparable to other similar interventions , 28, thoARTC were selected on a convenience and not on the basis of population, as this is considered a programmatic activity by NACO. Improvement in knowledge, practices and patient outcomes was measured by participating sites and not at individual level count, in accordance with the study objectives. The scales used for assessment of self-efficacy were adapted from similar protocols used for evaluation of ECHO projects in other countries, with no specific validation for this project. Implementation coincided with COVID surge, leading to competing priorities for health care providers which influenced their participation and therefore impact may have been more than what we were able to measure.The communities of practice developed through this intervention have decreased provider isolation and increased provider satisfaction, especially in light of current high staff turnover. This initiative garnered combined expertise from TB/HIV programmes to seek timely guidance by ARTc staff on complex queries related to prevention and management of HIV-TB. Findings recommend expansion of this initiative across the country to augment the existing capacity building interventions and engage other cadres who could potentially benefit from routine mentorship and continued professional development. Resonating well with lessons learnt during COVID-19 pandemic regarding use of technology, this initiative not only promoted health equity by timely provision of expert opinion but also kept the peripheral sites motivated by reducing professional isolation, even during pandemic times. Scale-up of this e-learning initiative by national programmes could help address the demand for accessible, cost-efficient and sustainable continuing professional education for management of other communicable and non-communicable diseases and offer an opportunity for preparedness to provide continued learning through communities of practice, even during unprecedented restrictive scenarios in future.Reshu Agarwal, Upasna Agarwal, Chinmoyee Das, Ramesh Allam Reddy et al.: Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV–India.The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC or other affiliated organisations.