Intrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer characterized by rapid progression and poor prognosis. There are few effective tools for evaluating the prognosis of ICCA patients, and the use of liver transplantation (LT) of the treatment for ICCA is still controversial.Cox regression analyses and then used to establish a nomogram. The prediction performance of the nomogram was evaluated with receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA) plots. Propensity score matching (PSM) was used to balance the baseline data of patients undergoing LT and other operations, and then, univariate Cox regression analysis was used to evaluate the therapeutic value of LT for ICCA.We analyzed ICCA incidence data and clinicopathological data from the Surveillance, Epidemiology, and End Results database. Prognostic predictors were identified by univariate and multivariate Cox regression analysis showed that age under 60 years old, female, tumor size ≤ 50 mm, better differentiation, smaller range of tumor invasion, lack of distant metastasis, regional lymph node surgery and treatment were associated with a better prognosis. The ROC curves, calibration plots, and DCA plots showed that the nomogram had good discrimination and calibration power, as well as clinical utility. After PSM, the univariate Cox regression analysis showed no significant difference in OS between patients treated with LT and patients treated with other operations.The incidence of ICCA increased significantly, from 0.6 per 100,000 in 2,000 to 1.3 per 100,000 in 2018. The median overall survival (OS) of the patients was 13 months, and the 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively. The incidence of ICCA increased significantly. A nomogram with good predictive performance was developed to predict the OS of ICCA patients. LT might be considered as a potential option for some ICCA patients. Intrahepatic cholangiocarcinoma (ICCA) is one of the most prevalent types of primary liver cancer, and its prevalence is second only to that of hepatocellular carcinoma (HCC) . ICCA orAlmost all guidelines recommend that surgical resection is the only potentially curative treatment for ICCA, especially for resectable lesions –9. Howev1 has the advantages of including data across a long-time span and from a large population, and this database is beneficial for medical research on rare diseases.In the current era of individualized medicine, more effective tools for predicting disease prognosis are beneficial for decreasing excessive intervention and improving doctor–patient communication. Compared with conventional staging methods, nomograms are more individualized and easy to understand . HoweverIn this study, we analyzed the clinicopathologic variables and incidence data of ICCA based on data from the SEER database, further studied the incidence trend of ICCA, and established a nomogram related to the prognosis of patients with ICCA. We also evaluated the value of LT in the treatment of ICCA after propensity score matching (PSM).2 Patients with a histology code of 8,160/3 and a topography code of C22.1 were enrolled in this study . Because the AJCC staging system (8th edition) was not used in the SEER database at the time of this study, the AJCC staging system (7th edition) was used. Patients with any of the following variables missing were excluded: staging groups (AJCC stage), primary tumor (AJCC-T), regional lymph nodes (AJCC-N), distant metastasis (AJCC-M), tumor size, race, and survival time . Then, patients with survival time of less than 1 month were excluded (n = 186). The included patients were randomly divided into the training dataset and testing dataset at a ratio of 7:3, and patients who underwent surgery were included in the surgery dataset. We used the training dataset to analyze the prognosis of ICCA and establish the nomogram, and then used the testing dataset to verify the effectiveness of the nomogram .nomogram . We usednomogram .The predictive covariates were categorized as demographic, and clinical variables. Demographic variables included age of diagnosis, race, origin, and marital status at diagnosis. Clinical-pathological variables included grade, tumor size, AJCC stage, AJCC-T, AJCC-N, AJCC-M, regional lymph node (LN) surgery, radiotherapy, and chemotherapy. Patients were classified into three age groups: < 60, 60–79, and = 80 years old. The histological grades included I (well differentiated), II (moderately differentiated), III (poorly differentiated) and IV (undifferentiated). Since all cases had been diagnosed and included to SEER database until 2018, it was not possible to subclassify cases as: large duct/small duct/cholangiocarcinoma, as more recently defined by WHO Classification of Tumors—5th Edition, Digestive System Tumors, 2019. Adjuvant therapy included preoperative or postoperative radiotherapy alone, chemotherapy alone or a combination of radiotherapy and chemotherapy. Systemic therapy was defined as surgery combined with adjuvant therapy. The survival status was defined as alive or death due to all causes, and the survival time was the overall survival (OS) in months which was defined as the interval measured between diagnosis and death or last follow-up.weighted least squares method. The APC is significantly different from zero (p < 0.05). We plotted incidence trends and performed linear regression using the ggplot2 package in R software (version 4.0.2).3The age-adjusted incidence trend of ICCA was calculated according to the 2,000 US standard population. The annual percentage change (APC) values were calculated using the chi-square-test or Fisher’s exact test was used for categorical variables. Survival curves were drawn by the Kaplan-Meier method, and these curves were used to calculate the 1-, 3-, and 5-year OS rates. The impact of variables on prognosis was evaluated by univariate and multivariate Cox regression analyses of the training dataset. Candidate variables with two-tailed p < 0.05 in the univariate Cox regression analysis were included in the multivariable Cox regression analysis, and variables with two-tailed p < 0.05 in the multivariate Cox regression analysis were defined as independent factors, which were used to establish a nomogram. We verified the nomogram internally using the testing dataset. We used the area under the curve (AUC) of receiver operating characteristic (ROC) curves to evaluate the discrimination, calibration plots to evaluate the calibration, and DCA plots to evaluate the clinical utility of the nomogram  . AdditioA total of 2,516 patients with ICCA from 2010 to 2015 from the SEER database were enrolled in this study. Most of the patients with ICCA were elderly at the time of diagnosis (71.3%), white (79.2%), Non-Spanish-Hispanic-Latino (86.2%) and married or unmarried with domestic partners (60.7%). The proportions of male and female patients were approximately equal (49.9 vs. 50.1%). Most patients had tumors larger than 50 mm. More patients had moderately differentiated to poorly differentiated tumors (47.4%). More than half of the patients’ tumors were localized . Approximately one-third of patients had regional lymph node metastasis or distant metastasis at the time of diagnosis (30.8 and 32.4%). Most patients did not undergo any surgeries (64.5%), but more patients received adjuvant therapy alone (43.7%). In addition, most patients received chemotherapy (56.2%), while only a few received radiotherapy (16.5%). The details can be found in In this study, 2,144 patients had died (66.5%), and 427 patients survived (33.5%). The median OS of the patients was 13 months, with a 95% CI of 12–14 months. The 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively .Cox regression analysis using the training dataset showed that age of diagnosis, gender, race, tumor size, grade, AJCC-T, AJCC-N, AJCC-M, AJCC-stage, regional LN surgery and therapy were related to the prognosis of patients with ICCA . As expected, we found significant differences in AJCC-T, AJCC-N, AJCC-M and AJCC stage between the two groups in the surgery dataset. After PSM, there was no significant difference in baseline data between the two groups . The medo groups .Evaluating the prognosis of uncommon diseases such ICCA is difficult for both single-center and multicenter cohort studies alike. Large databases, such as the SEER database, provide new and effective tools for such research. ICCA was presented separately for the first time in the AJCC staging manual (7th edition), but some limitations with that edition were identified, so it was revised in the AJCC staging manual (8th edition); this suggests that the prognostic assessment of ICCA is still controversial , 20. In In this study, the median OS of all patients was 13 months, and the 1-, 3-, and 5-year OS rates were only 51.40, 22.14, and 13.79%, respectively. Some cohort studies showed that the 1-year OS was 83.7%, the 3-year OS was 40.8%, and the 5-year OS was 10–37.2% –23. HoweClonorchis sinensis is also an important cause of high prevalence of ICCA in East and Southeast Asia , a tumor size larger than 50 mm is one of the cutoff values for determining stages. Although it is still controversial whether tumor size affects the prognosis of ICCA patients , 26, tumWe found that the prognosis of the treatment group could be better, especially for patients who underwent surgery combined with adjuvant therapy. Surgery is the first choice for the treatment of ICCA, and whether margin-negative (R0) resection with sufficient FLR can be achieved is the focus of preoperative evaluation and the key to tumor-free survival , 11, 14.The AJCC staging manual is the most widely used tool for predicting the prognosis of ICCA patients , 20, butEarly studies revealed that patients with ICCA had an unsatisfactory prognosis after LT, so many medical centers consider ICCA to be a contraindication for LT , 45, 46.Nonetheless, the present study had several weaknesses. First, this was a retrospective study, and most cases were excluded because of a lack of data, so selection bias may be present. Second, liver cirrhosis, PSC and other variables were not included in the SEER database, so there were limitations related to the selection of predictive factors. Third, our model was only validated internally, not externally or prospectively, which may affect its scope of application. Our goal for the future is to evaluate the performance of the nomogram through prospective external verification and further explore the indications for LT in ICCA patients.In summary, the incidence of ICCA increased significantly, and the prognosis of patients with ICCA was poor, so more attention should be paid to the management of ICCA. Furthermore, we established a nomogram with good predictive performance using prognostic factors. In some patients with ICCA for whom routine surgery is not possible, LT seems to be a potential treatment option, but the long-term outcome may be not satisfactory enough.https://seer.cancer.gov/.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by the Institutional Review Board of Children’s Hospital of Chongqing Medical University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.HX was responsible for conceptualization, methodology, formal analysis, and writing and editing. BT and CY were responsible for investigation and review. MZ was responsible for conceptualization, review, and supervision. All authors have read and agreed to the published version of the manuscript.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.


Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses  may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups  by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L). Vitamin D is crucial for musculoskeletal health, as it plays an important role in the regulation of bone and mineral metabolism, and it can prevent and cure nutritional rickets and osteomalacia ,2. In adIn clinical practice, a great variability and controversy is reported regarding vitamin D testing and supplementation, thus requiring an improved guidance for clinicians . Therefo® for voting on various statements on a 9-point scale with the following numeric (and descriptive) anchors: 1 (strongly disagree), 3 (disagree), 5 , 7 (agree), and 9 (strongly agree). It was pre-specified that a consensus will be established, in the case that ≥75% of the participants agree with the statement, by a voting scale of 7 or above. In case of failing to reach a consensus according to this criterion, it was planned to repeat these surveys after group discussions and statement modifications, if necessary, until a consensus is reached.A European expert panel with 10 members and a focus on physicians from Eastern Europe, who are usually underrepresented in such groups, was established by selecting clinicians and key opinion leaders with expertise in vitamin D and related topics from their respective countries. The first and senior authors (P.P. and S.P.) of this article served as the chairs of this expert panel, who selected and invited the other panel members. The consensus-reaching process itself was conducted by using the Delphi method, which is a widely accepted tool for clinical consensus statements ,36. The After the alignment of the scope of this consensus document and recruitment of the 10 members of the expert panel, the detailed process of this work started with drafting various questions on practical issues regarding vitamin D, which were exclusively discussed and fine-tuned by the chairs. These questions were subsequently used in a first survey round in September 2021. All panel members were involved in this survey, and their answers, along with the existing literature on vitamin D, served as the basis to formulate respective statements by the chairs. At a hybrid meeting in Darmstadt, Germany on the 20 November 2021, the results of the first survey round, along with the subsequently formulated statements, were presented by the chairs. At the same meeting, each statement was subject to a group discussion and a Delphi voting round to reach consensus, which was finally successful for all statements. The 10 authors of this paper are the 10 experts who participated in the Delphi voting rounds. Each voting round was performed for the whole content of each Table or Figure, respectively. Group discussions before each voting round, however, were used to fine tune the statements according to the opinions and recommendations of the panel members. The work on this consensus document was funded and organized by Wörwag Pharma . The sponsor provided financial and logistic support but did not actively participate in the scientific discussions and consensus-reaching processes.The final consensus statements with the level of agreement within the expert group are subsequently presented below. The evidence and considerations underpinning each statement are also outlined. It was our aim to base our work on the totality of available evidence by considering the established hierarchy of evidence levels. The expert panel group was encouraged to perform systematic literature reviews on the topics of this consensus document, but we have to acknowledge that this gathering of information did not follow a pre-specified structured process.Epidemiological studies have documented a high prevalence of vitamin D deficiency worldwide . Data frNo published study evaluated the effects of a screening program for vitamin D deficiency in the general population, so the evidence is insufficient to balance the benefits and harms of such a screening ,43. Acco3 and 25(OH)D2, is the accepted marker for the assessment of vitamin D status, as it best reflects vitamin D supply by all different sources, i.e., endogenous vitamin D synthesis in the skin, diet, supplements, and mobilization from tissue stores. Previous reports on a relatively high inter-assay and inter-laboratory variability of 25(OH)D measurements underscore the need for assay standardization and laboratory quality assurance [per se no contraindication) except of rare conditions with an increased sensitivity to vitamin D treatment, such as inherited 24-hydroxylase-deficiency [Total serum 25(OH)D concentration, i.e., the sum of 25(OH)Dssurance ,45. In pssurance . There aficiency . This isficiency . If suchficiency .Classification of vitamin D status and its terminology, according to 25(OH)D concentration, remains a controversial issue in the scientific literature ,16,21. BMost nutritional vitamin D guidelines conclude that vitamin D requirements are met for the vast majority  of the population when achieving a target 25(OH)D concentration of at least 20 ng/mL (50 nmol/L) ,12. RecoIn detail, we recommend a vitamin D supplementation dose of 800 to 2000 IU per day for adults who want to ensure a sufficient vitamin D status, with up to 4000 IU per day for certain groups, particularly for patients with obesity and malabsorption syndromes, as well as for individuals with a dark skin pigmentation see . The relDaily, weekly, or monthly vitamin D supplementation, at equivalent doses, lead to similar increases in 25(OH)D serum concentrations, when measured after 2 to 3 months ,66,67. AIndividuals with a measured 25(OH)D concentration below 20 ng/mL (50 nmol/L) should be treated with vitamin D supplementation, because their vitamin D requirements may not be met ,12. TherIf a rapid correction of vitamin D deficiency is clinically indicated, a regimen with a higher initial vitamin D dose, i.e., 6000 IU per day, and in certain cases, even up to 10,000 IU per day, followed by a maintenance dose with 800 to 2000 IU per day is recommended . Such doRegarding treatment of vitamin D deficiency and its prevention, we want to emphasize that promoting a healthy lifestyle by preventing or reducing obesity, regular physical activity with moderate (cautious) sunlight exposure, and a healthy balanced diet are also effective measures to improve both vitamin D status and overall health. Promoting such lifestyle measures is, of course, also highly recommended, and it should accompany any vitamin D treatment.As for the prevention of vitamin D deficiency, we recommend vitamin D3  over vitamin D2  for its treatment. Although parenteral, particularly intramuscular, vitamin D treatment can be considered in patients with malabsorption, e.g., inflammatory bowel disease, we primarily suggest to increase the oral vitamin D dose in such settings . CliniciSome experts argue that calcifediol (=25(OH)D3, calcidiol) may also be used to correct vitamin D deficiency in certain conditions. The use of calcifediol seems to be more justified in obese people, people with malabsorption syndromes, people with liver disease, patients suffering from chronic kidney disease (stage 3 or 4), and those in all conditions where rapid correction of vitamin D deficiency is required ,83,84. FCalcitriol 2D) and its analogues are used at much lower doses compared to vitamin D3, have a relatively high risk of hypercalcemia and a relatively narrow therapeutic window, and are not recommended for the treatment of common vitamin D deficiency . TherefoWhile older meta-analyses of vitamin D RCTs showed a significant reduction in fractures by vitamin D supplementation at a daily dose of about 800 to 2000 IU per day, these data have recently been challenged by updated meta-analyses, suggesting no significant effect on fractures and falls ,87,88. NThe expression of the VDR and of vitamin D-metabolizing enzymes in almost all human tissues and cells suggests a widespread role of vitamin D for overall human health ,10. In lMeta-analyses of vitamin D RCTs suggest that vitamin D supplementation may reduce the incidence of acute respiratory infections, cancer mortality, as well as asthma and chronic obstructive pulmonary disease (COPD) exacerbations ,107,108.Numerous studies have been published on vitamin D, in the context of the Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,112,113.Based on our consensus statements, we developed an algorithm for the prevention and treatment of vitamin D deficiency that was also subject to a Delphi voting round, with the following point scale results: 9 points (20% of panel members), 8 points (30%), and 7 points (50%) see .As a potential limitation, the financial and logistic support by an industry sponsor (Wörwag Pharma) must be acknowledged. Despite no involvement of the sponsor in the scientific group discussions and consensus reaching processes, we cannot totally exclude some sort of funding bias ,18. MoreThis consensus statement covers various statements with relevance for the clinical practice in the prevention, diagnosis, and treatment of vitamin D deficiency. We highlighted the relevance of vitamin D for public health and provided guidance regarding this issue by considering the totality of the available scientific evidence, including our personal experience and opinions.We consider that our work adds to the existing literature by providing a useful and evidence-based guidance for clinicians and health-care workers regarding several relevant and partially controversial topics for the practical management, with reference to vitamin D. In addition, we also addressed various issues with relevance for public health authorities and individuals from the general population that will, hopefully, help to reduce the global health burden of vitamin D deficiency.


Twisted light beams such as optical angular momentum (OAM) with numerous possible orthogonal states have drawn the prodigious contemplation of researchers. OAM multiplexing is a futuristic multi-access technique that has not been scrutinized for optical satellite communication (OSC) systems thus far, and it opens up a new window for ultra-high-capacity systems. This paper presents the 4.8 Tbps (5 wavelengths × 3 OAM beams × 320 Gbps) ultra-high capacity OSC system by incorporating polarization division multiplexed (PDM) 256-Quadrature amplitude modulation (256-QAM) and OAM beams. To realize OAM multiplexing, Laguerre Gaussian (LG) transverse mode profiles such as LG00, LG140, and LG400 were used in the proposed study. The effects of the receiver’s digital signal processing (DSP) module were also investigated, and performance improvement was observed using DSP for its potential to compensate for the effects of dispersion, phase errors, and nonlinear effects using the blind phase search (BPS), Viterbi phase estimation (VPE), and the constant modulus algorithm (CMA). The results revealed that the proposed OAM-OSC system successfully covered the 22,000 km OSC link distance and, out of three OAM beams, fundamental mode LG00 offered excellent performance. Further, a detailed comparison of the proposed system and reported state-of-the-art schemes was performed. With the proliferation of multimedia services and internet applications such as high definition (HD) live streaming, HD video conferencing, voice over IP (VoIP), 4/8 K video transmission, and recently introduced virtual reality technology, i.e., metaverse, contemporary data transmission techniques are experiencing peer pressure due to explosive demands for wide-bandwidth . Radio-fSatellites can be placed in any of the three available earth orbits depending upon the distance from the earth, such as low satellite orbit (LSO) (≤2000 km), medium satellite orbit (MSO) , and high earth orbit (HSO)  ,12,13. TThe European Space Agency (ESA) demonstrated the first OSC link at 50 Mbps between ARTEMIS and SPOT-4 . In 18]18], an LThe polarization dimension is an important property of light among other dimensions such as frequency, space, and time, but it has yet to be extensively explored to obtain ultra-high data rates. The hybridization of multilevel modulations with different states of polarizations (SOPs) has opened a new window for high-capacity optical systems . In the l), and radial numbers (m) of EM waves in [l and m numbers. HG modes were used in [Ultra-high speeds of several Tbps can be achieved with the deployment of PDM in multilevel modulations. An ultra-long-range 60,000 km OSC link was proposed employing PDM in CO-OFDM at 400 Gbps . Furtherwaves in  for a 40waves in  and cove used in , where t used in . As resel), and the expression for OAM is given as l = +1, +3 was demonstrated using 4 × 4 multi-input multi-output (MIMO) technology [EM waves have four features such as amplitude, wave vector, frequency, and angular momentum (AM), and it is perceived that the AM feature of EM waves has yet to be fully explored, unlike amplitude, frequency, and wave vector. Spin AM (SAM) and OAM are the two prominent types of AM, where SAM is associated with the polarization of light and OAM with electrical field distribution around the propagation axis. OAM is preferred over SAM due to its potential to support high speed, be less prone to atmospheric effects, and offer mathematical encryption of data which in turn provides improved security. Ring-shaped and helical structures are the two types of OAM beams generated from the direction of rotation of phase and intensity patterns. Different OAM beams can be generated by changing the charge value  mode crosstalk in OAM beams due to smaller differences in l between different modes, (2) lower power efficiency of the receiver due to very high order LG modes in OAM, (3) mode leakage due to pointing errors, and (4) phase modulation under atmospheric turbulences. As per the author’s best knowledge, OAM beams are not investigated in OSC systems for ultra-high capacity and long transmission.In this work, an ultra-high capacity OSC system is presented incorporating the OAM multiplexing technique over 22,000 km, and a detailed investigation of the OSC system is performed at different input parameters such as OSC link length, pointing errors, and receiver telescope antenna diameter in terms of log BER, signal to noise ratio (SNR), and EVM%.The rest of the paper is structured as follows: Compared to RFC, large bandwidth and high speed are offered by OSC due to the incorporation of high-frequency optical carriers, and these features make OSC a paramount data transmission candidate for space-based satellite communications. Moreover, high frequency in OSC enables manufacturers to design lightweight satellites due to smaller size antennas.PR) is expressed as:For the long-distance data transmission between two satellites, high-power signals are transmitted (It is depicted in Equation (1) that vely, as :(2)TPL=eFor the realization of an ideal OSC system, as observed from Equations (1)–(3), l. The LG mode profile depends on the focus point, the axis of the beam, the optical frequency, and the radius of the beam. Doughnut, like the shape of LG modes, has a helical phase front and it is expressed as [There are two basic phenomena in light propagation through free space, such as (1) with the propagation of light in OWC, a significant change in the intensity profiles of light has been observed; and (2) modes of light  cannot change with the transmission through free space. The direction of the variation in the electrical field remains constant only; however, other components such as phase, profile, and receiver power of light keep on changing. The generation of LG and HG modes is the outcome of constant electrical field distribution of light in wireless mediums. Both LG and HG modes differ in structure shape such as LG modes have a horizontal circular structure and HG modes have a vertical helical structure. Preferred modes for the communication systems and OAM are LG modes due to their simple multiplexing/de-multiplexing and can have a significant gap in the rings depending upon essed as (4)Ψlmr,l and the boundary around these peaks varies with m. These different LG modes with distant values of l are combined to realize OAM multiplexing for high-speed OWC systems.The number of peaks in the light profile is a function of For OSC systems, single polarization QAM  and dualAs shown in A symbol rate of 20 Gsymbols per second is achieved using 8 bits per symbol in the QAM, making it 256-QAM. The M-ary pulse generator provides m number of different levels to different 8 bits per symbol and for the generation of different polarizations in the system, laser signals are divided into two different SOPs incorporating polarization beam splitter (PBS) such that horizontal and vertical polarizations can be realized. Further, these horizontal and vertical SOP-based laser signals are given to the upper and lower Mach–Zehndar modulators, respectively. Further, data modulated on these two SOPs are combined with the help of a polarization controller (PC) and a particular LG mode is assigned to each channel. To accommodate all the channels, a WDM multiplexer is employed for different wavelengths, and an MDM multiplexer is incorporated to realize OAM multiplexing from different LG modes. WDM-OAM multiplexed signals are communicated over an OSC loop having an OSC channel, and pre and post-erbium-doped fiber amplifier (EDFA). Simulation specifications are listed in Signals after traveling through the OSC channel reached the receiver section placed in the destination satellite. A de-multiplexer 1 × 5 is placed to route all five wavelengths to the specific port and further, each wavelength is divided into three sub-channels. OAM beams are filtered at each sub-wavelength and followed by a PDM-256-QAM receiver as shown in This section covers the detailed performance analysis of the proposed system at different input parameters such as distance between satellites, pointing errors, and receiver antenna diameters, and we further explore the performance of each OAM beam in the system in terms of BER, EVM, and constellations. For the investigation of the proposed OAM-OSC system, a prominently used simulation environment, Optisystem, is considered. Light profiles of different LG modes such as LG0,0, LG14,0, and LG40,0 are represented in We have considered an appropriate  difference in l so that only minimum mode coupling occurs and is restricted to a maximum value of 40 because detection becomes difficult at higher-order modes.The majority of satellite communications take place in space, where there is no atmosphere and only a vacuum exists, resulting in less power loss for the signal. However, the distance between satellites is the major factor that derives the final performance of received signals. Therefore, the OSC link length is increased from 10,000 to 24,000 km in the proposed investigation to find out the maximum supported distance by OAM-OSC. BER is validated for different OAM beams at different OSC links as shown in With the increase in the OSC link length, symbols at the receiver deteriorate and displace from their ideal positions, which in turn increases the BER. Furthermore, phase errors in the 256-QAM symbols, attenuation, scattering, and nonlinear effects at high power also introduce bit errors. It is discerned that all the OAM beams have different output BER such that fundamental mode LG0,0 has the least BER due to narrow beam mode and LG40,0 has the highest BER because of the power losses at the receiver due to higher order mode. In this case, the receiver antenna diameter is 15 cm, and therefore, small-size antennas are sometimes not wide enough to accumulate all the power of higher-order modes. However, all the OAM beams have covered 22,000 km successfully within the acceptable log BER condition i.e., −2.42 [Relay communication in OSC systems plays an important part in covering ultra-long transmission distances between satellites, and LoS is the utmost condition to be satisfied. Slight misalignment in the LoS can cause severe bit errors and performance degradation. Moreover, in the case of OAM beams, the spot size of LG modes increases with the distance, and slight misalignment can cause high mode power loss due to the small diameter of the OSC receiver telescope. Therefore, in The proposed OSC systems have PDM-256-QAM modulation that has 8 bits per symbol and in turn, generates 256 different symbols in the data transmission. These 256 symbols have a fixed phase and amplitude at the transmitter, and due to noise and other performance-limiting effects, their phase and amplitude become distorted as they travel toward the receiver. At the receiver, optical signals are converted into electrical data with balanced detection, and these 256 symbols are represented by a constellation analyzer. A constellation analyzer is a two-dimensional (2D) plot with an I and Q axis for the symbols received at the receiver. EVM can also be calculated from the constellation analyzer as the displacement of symbols from their ideal positions can be seen from the 2D plot. Further, we explored the effects of DSP on the OAM-based OSC system and it was observed that DSP had a significant impact on the performance of the systems due to the compensation of NL, dispersion, phase errors, etc. In this section, the performance of the proposed OAM-OSC system is compared with the different reported OSC systems in terms of data rate, channels, capacity, OSC link length, modulation used, multiplexing employed, and performance, as shown in We investigated a PDM-256-QAM-based OSC system incorporating three different OAM profiles for the first time. A detailed literature review made us understand the shortcomings of OSC systems, such as low capacity, shorter OSC link length, high cost, mode crosstalk, and high BER. The performance of the OSC systems depends on different parameters such as pointing errors, LoS, transmitter power, antenna aperture size, antenna gain, beam divergence, etc. However, the two major performance-affecting entities are modulation and multiplexing. For a high bandwidth efficient carrier spectrum, PDM-256-QAM was considered in the proposed work, and for reducing mode crosstalk, OAM is selected. As explained earlier, the most significant limitation encountered in most of the MDM-OSC systems is the multiple modes placed with shorter gaps ,43,44,56In this research study, an ultra-high capacity OSC system was presented over a 22,000 km link distance between satellites, and we have also manifested the potential of OAM beams by incorporating LG00, LG140, and LG400 transverse mode profiles and PDM-256-QAM. OAM beams were selected at an optimal one number difference to reduce the effects of mode coupling and to avoid generating very higher order modes, which in turn reduce RAP at the receiver. A total of 15 channels were generated from only 5 wavelengths using LG modes, which reduced the cost of the system by one third. Results revealed that all the OAM beams had different output BER at diverse OSC link lengths such that the fundamental mode LG0,0 had the least BER due to the narrow beam mode spot size and LG40,0 had the highest BER because of the power losses at the receiver due to the higher order mode. The EVM% value for LG0,0 was 15.01, for LG14,0 was 16.99, and for LG40,0 was 19 at 0.5 µrad, and for increased pointing errors such as 4 µrad, EVM% increased to 32.98, 35.02, and 37.99 for LG0,0, LG14,0, and LG40,0, respectively. Higher-order modes have very wide spot sizes of light profiles, and it becomes tedious for the receiver antenna to detect the entire mode power. Therefore, it is interesting to observe the effects of different TADs. It is perceived that until the TAD of 20 cm, LG40,0 and LG14,0 OAM beams experienced more log BER as compared to LG00, but at TAD values greater than 20 cm, LG40,0 and LG14,0 OAM beams surpassed the performance of LG0,0 due to higher RAP at the receiver. Moreover, LG40,0 provided the least log BER (−17.23) followed by LG14,0 (−16.47) at 30 cm TAD at the receiver satellite, and the maximum log BER was observed in the case of LG0,0 (−15). Whereas LG0,0 encountered the least BER (−2.4) at 5 cm TAD and LG40,0 had the highest (−1.5) bit errors. It is suggested to use higher TADs for the higher-order OAM beams. We considered LG mode profiles with larger differences such as LG00, LG140, and LG400 to realize OAM multiplexing, and it was observed that mode coupling becomes insignificant in these distant mode profiles as compared to the reported research where LG/HG modes with lesser gaps are considered ,44,58. W


Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments.2 test, Kruskal–Wallis test, and Mann–Whitney U-test.We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies  between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response  among patients with and without CAS using the χP = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups.Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS  than in those without CAS (6, IQR 12 to 3; In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments. Migraine is the second cause of disability worldwide mainly affecting young and middle-aged women . The IntThe trigeminal cervical complex is a relay, where signals run from central to peripheral structures of the nervous system and the other way round. Migraine initiates in the Central nervous system (CNS)—dorsal pons, hypothalamus, and thalamus—from where pain signals reach the trigeminal ganglion activating the trigeminovascular system, then the trigeminal cervical complex and back to the initial CNS areas , 7. The This prospective open-label study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines  and the Until July 2020, manufacturers provided mAbs upon request from the Headache Centers to treat patients with migraine with or without aura according to the ICHD-3 criteria , 14. AftThe presence of CAS was prospectively assessed at the beginning of treatment with mAbs through clinical interview; for the classification of CAS , we referred to a previous prospective study . We consThe study comprised a baseline period  and a 12-week follow-up . We recorded patients' age, sex, migraine type (episodic or chronic), medication overuse, presence of aura, and disease duration at baseline. Patients reported monthly headache days (MHDs) on specific diaries throughout baseline and follow-up. During baseline and follow-up clinical interviews, patients reported the frequency of CAS on a five-level Likert scale . We computed median MHDs as a 4-week mean of the 12-week baseline and the 12-week follow-up. Similarly, we computed the 12-week response rate as 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% median MHDs reduction throughout the follow-up period from baseline. Treatment was recommended to patients for at least 12 weeks; however, before the issue of reimbursement criteria, patients were allowed to stop the treatment before week 12 due to perceived ineffectiveness. Patients reporting severe adverse events before week 12 of also stopped the treatment. Patients stopping the treatment before week 12 were considered in the analyses and 12-week MHDs were estimated from the last available value, following a “last observation carried forward” approach. A “headache day” was defined as a day when patients reported any headache, migraine, or non-migraine in their diaries. Data were entered in an electronic anonymized database created on the Research Electronic Data Capture (REDCap) software for the analyses hosted at the University of L'Aquila , 18.2 test to compare categorical data, and the Mann–Whitney U-test or Kruskal–Wallis test to compare continuous data.We reported descriptive statistics about patients' demographics and disease characteristics . Categorical data were reported as numbers and percentage, while continuous data were reported as the median and interquartile range (IQR). We did not perform a formal sample size calculation as we were based upon a convenience sample; therefore, we used conservative non-parametric tests: the χWe included 136 patients treated with mAbs for 12 weeks in our Headache centers: 116 (85.3%) were female, the median age was 49 (IQR 41–56.7), median disease duration was 26.5 years (IQR 17–38.5), 105 (77.2) suffered from chronic migraine, 80 (58.8%) had medication overuse headache as comorbidity, and 24 (17.6%) reported aura. Baseline characteristics were similar between patients with and without CAS . One-hunP = 0.007): disease characteristics were similar across the two groups  reported at least one CAS: 36 (41%) reported one CAS, 24 (27%) two CAS, and 28 (32%) more than two CAS . The freo groups .P < 0.001); median difference in MHDs from baseline to 12 weeks was higher in patients with CAS than those without, −10 (IQR −15 to −6) and −6 (IQR −12 to −3), respectively (P = 0.009) , 25 (18.4%), 38 (27.9%), 36 (26.5%), and five (3.7%) patients, respectively. The 30 to 49, 50 to 74, 75 to 99, and 100% response rates were numerically higher in patients with CAS than in those without; however, the between-group difference was not significant . MHDs de= 0.009) ,B.Out of 88 patients with CAS, 80 patients (91%) reported the frequency of symptoms throughout the entire study period. MAbs response did not differ according to the frequency and the number of CAS –4.In our cohort, two-thirds of patients suffering from different forms of migraine  reported at least one CAS. The high frequency of CAS was expected because a similar rate was reported in other studies, where those symptoms had been reported by up to 74% of patients with migraine , 19. A hMAbs targeting the CGRP pathway significantly reduced MHDs and more remarkably in patients with CAS. The higher efficacy of treatment in these patients might be due to greater activation of the trigeminovascular system, where the CGRP plays a key role in mechanisms underlying migraine pain—a mediator of nociception, neuroinflammation, and vasodilation . The preSeveral studies have demonstrated how CAS respond to triptans, such as sumatriptan and rizatriptan, and how patients with these symptoms report better responses to triptans . PatientThe advent of highly effective and migraine-specific preventatives such as mAbs imposes a new tailored-made approach to migraine therapy, which should consider patients' responses and needs. Clinical predictors of response to preventatives and acute treatments targeting the CGRP pathway could help to maximize the cost-effectiveness of these drugs. Real-world studies proved that some peculiarities of the attacks predict mAbs response such as unilateral pain, baseline MHDs, acute medication intake, number of prior treatment failures, allodynia, and psychiatric comorbidities , 31–33. To our knowledge, this is the first study evaluating the efficacy of mAbs according to the presence of CAS. We support the idea that the CGRP pathway plays a role in the genesis of these symptoms, which might be useful in phenotyping migraine attacks. Changes in prescription criteria for mAbs affected the presence of CAS but not the other baseline disease characteristics, thus, they did not influence patient selection. We prescribed mAbs to those suffering from the most severe forms of migraine before and after the issue of national reimbursement criteria. The small sample size might have affected the results. Also, we did not distinguish between monthly headache days and migraine days, thus we did not precisely assess changes in CAS frequency according to migraine attacks; the collection of CAS frequency through patients' interviews might have been prone to a recall bias. We did not collect data such as number of triptans or acute medications, concomitant preventive treatments, intensity of the attacks, and localization of pain and CAS ; the short follow-up and the 12-week unique assessment timepoint did not allow to identify early and late responders to the treatment and CAS frequency according to this response. Larger studies might confirm our results and show a possible statistical difference in response rate according to the presence of CAS.In conclusion, our data suggest the clinical relevance of investigating CAS in patients with migraine with and without aura as they might signal a high trigeminal activation and thus be associated with a high response to treatments targeting the CGRP. Our hypothesis stemmed from real-world data that needs confirmation from basic science.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Internal Review Board (IRB), University of L'Aquila, L'Aquila. The patients/participants provided their written informed consent to participate in this study.RO, SS, and ED conceived the study and its design, performed the acquisition, analysis, interpretation of data, and drafted the manuscript. AC, IF, VC, AG, GA, MG, MM, SV, and FP collected data and substantively revised the manuscript. All authors approved the final manuscript.This work was supported by the Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.Author RO has received sponsorship to attend meetings from Novartis and Teva. Author SS had a financial relationship (lecturer or member of advisory board) with Abbott, Allergan, Novartis, Teva, and Eli Lilly. Author GA has received funds for congress participation from Innovet Italia Srl, Epitech Group, and Lusofarmaco. Author MG received funds for congress participation from IBSA. The remaining 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.


Down fiber is one of the most superior materials, with excellent thermal properties, that can be used in bedding, clothing, and so on. Down products are usually encapsulated in fabrics that are more compact and, therefore, impart an anti-drilling performance. In this study, down fibers were encapsulated in polypropylene melt-blown nonwoven fabric, and also in polyester woven cloth, to form two different kinds of composite waddings. The waddings made of down fiber encapsulated in melt-blown nonwoven fabrics have a superior moisture permeability, thermal insulation, and anti-drilling performance, and a slightly inferior air permeability compared to that of waddings made with traditional woven fabrics. The pore fractal dimensions of melt-blown nonwoven fabrics are larger than that of woven fabrics. The relationship between the fractal dimension and performance of waddings explains the difference. Down fiber is recognized as one of the most superior natural materials, and possesses excellent thermal and elastic properties. It often exists in bedding, clothing, and so on. Many researchers have paid attention to the thermal ,2,3,4 anAlthough down fibers possess excellent thermal insulation properties, due to their fineness and light weight, they are difficult to be controlled during fiber processing, easy to drill out during use, and, consequently, the product appearance and consumer experience are poorly affected. Therefore, down fibers are usually encapsulated in fabrics during process and use, such as woven and knitted fabrics.Compared to traditional fabrics, melt-blown nonwoven fabric has become a more popular covering fabric in wadding due to its fine pore structure. There has been a large amount of research on the manufacturing technique ,12,13 anAt the same time, a fractal approach was applied to explain the difference between the two types of waddings. The fractal approach has shown great potential in describing hierarchical systems and also in modeling the heterogeneous structures of fiber assemblies ,17,18. GIn this paper, two different kinds of down fiber composite waddings were investigated, which were made of down fibers encapsulated in polypropylene melt-blown nonwoven fabric and in polyester woven fabrics. The structural parameters and properties of these two kinds of waddings were investigated, such as their air permeability, moisture permeability, thermal performance, and anti-drilling performance. In order to explain the mechanism behind why these two waddings are different, the pore fractal dimensions of melt-blown nonwoven fabrics and polyester woven fabrics were calculated. The relationship between the pore fractal dimension and properties of the two waddings was also analyzed.Down fibers were purchased in Haining Sea Snow Leopard Down Ltd., Jiaxing, China. The average length of down cluster is 20–25 mm, and the average fineness of down branch is 19–21 μm.Polypropylene (PP) slices were purchased from Shandong Dawn Polymer Material Co., Ltd. . The nominal molecular weight is 80,000, the ash content is ≤200 PPM, and the moisture content is ≤0.2%. The polypropylene nonwovens were manufactured by the melt-blown equipment (SH-RBJ), which was produced by Shanghai Sunhoo Automation Equipment Co., Ltd., Shanghai, China. It has a spinning jet, a compressed air heater, and a rotating drum (collector). PP slices were fed to the extruder, where they were melted under inlet/outlet temperature of 120 °C/230 °C, and then fed to the spinning jet with through-put of 0.1 g/min. The velocity of the air at the exit of nozzle was set at a few thousand meters per minute to blow the nonwoven fabric to deposit on the collector, with a collecting distance of 15 cm.Three different series of melt-blown nonwoven fabrics were acquired with different thickness and gram per square meter, which were numbered as N1, N2, and N3. Parameters of nonwoven fabrics are listed in Polyester woven fabric was purchased from Jichuang Textile Ltd., Jiaxing, China. and was numbered as W#. The basic parameters of woven fabric were tested and summarized in Three specifications of polypropylene melt-blown nonwoven fabrics N1, N2, and N3, and a polyester plain cloth W#, were separately cut into two pieces of 30 cm × 30 cm square samples. Then, two pieces were stitched using a slit edge stitching machine to form a bag, filled with down fibers of 5 g, 8 g, and 10 g, and the fourth side was also stitched to seal up the wadding. The flowchart of composite wadding is shown in Several measurements were applied to characterize the properties of composite waddings. Ten samples were tested in each experiment to acquire accurate results.2, experimental pressure was set as 100 Pa, and a suitable nozzle was chosen. Measurements were acquired under standard temperature (20 °C) and relative humidity (65%).Air permeability performance of composite waddings were tested using YG461D digital fabric air permeability tester . According to standard GB/T5453, testing area was chosen as 20 cmWVT (g/m × 24 h) is the moisture mass per square meter per day, Δm (g) is the difference between two weights of the samples, s (m2) is the area of sample, and t (h) is experiment time.Moisture permeability performances of composite waddings were tested using LCK-131 water vapor permeability tester  with a silica gel dryer . According to standards GB/T12704-1991, the moisture mass of fabric can be calculated according toThe experimental instrument adopted was 606D YG (b) plate insulation system , and, according to standards GB/T11048, the test was performed under standard temperature (20 °C) and humidity (65%). The temperatures of the protection plate, test plate, and base plate were all set as 36 °C, preheating time was set as 30 min, and the number of cycles was 5.Down fiber products in daily use undergo two main forces, which are friction and washing force, so the anti-drilling tests were implemented by simulating these two forces.Simulation of friction force The surface of the samples was cleaned before test. Simulation of friction was realized by the ball milling apparatus . After 30 min of rubbing on fabric surface, down fibers drilled out of samples that were longer than 2 mm were counted by magnifier and tweezers.Simulation of washing force The surface of the samples was cleaned before test. Washing machine  was used to simulate the washing force. Washing power was applied on samples for approximately 30 min. Later, down fibers drilled out of samples that were longer than 2 mm were counted by magnifier and tweezers.Samples were characterized by SEM (Hitachi SU-70)  after coating with platinum.Fractal geometry, as a tool for studying irregular geometrical morphology, was first proposed by B. B. Mandelbrot . It is aIn this paper, the pore fractal dimensions of melt-blown nonwoven fabric and woven fabric were calculated by box-counting method. This method is according to image analysis of sample imagesBefore calculation, image pretreatment is needed to obtain clearer images; thus, the calculation results are more accurate. Firstly, grey tonal range of images were extended to cover all, making the contrast between bright and dull more obvious. Then, histograms of images were distributed evenly to achieve a balance. Next, all images were median-filtered to remove noisy points in order to acquire clearer images.Then, the binarization images of a sample were covered using square boxes with a length of side ε, and the number of square boxes that include at least one white pixel point was counted as N(ε). The fractal dimension can be determined by the slope of a linear fit through the values on a logarithmic plot of the cumulative number of boxes N(ε), versus the reciprocal length of side 1/ε, as illustrated in Formula (2). During the process of calculation, several instances of computer software were needed, such as Matlab, and were used to calculate fractal dimensions. Photoshop was applied to process the images.Air permeability is an important attribute of waddings. The results of air permeability for all of the waddings are shown in The thickness of the fabric also affects air permeability; this can be seen from the comparison of waddings with the same down fiber mass but encapsulated in different nonwoven fabrics, such as N1-5, N2-5, and N3-5. The results show that the air permeability of the fabric decreases with an increase in the thickness of nonwoven fabrics.Down fibers with the same mass encapsulated in different fabrics possess a different air permeability, according to the comparison between samples N2- and W-, which have nearly the same fabric thickness. It can be seen that the air permeability of melt-blown nonwoven fabrics–down-fiber composite waddings is lower than that of plain polyester-cloth–down-fiber composite waddings by approximately 10–20%. The reason for this may be due to the more compact fiber assemblies and much finer pore structure in melt-blown nonwoven fabrics.During the use of waddings, especially in clothing and home textiles, a good air permeability is preferred. From this point of view, less down fiber, thinner fabrics, and woven fabrics seem to be more appropriate.As another important parameter of composite waddings, the moisture permeability of all of the waddings in both the positive side and opposite side are measured and shown in The thermal performance is the most valuable property of down waddings. Three parameters of thermal performance were acquired through thermal measurement, which are the CLO value, heat preservation rate, and heat transfer coefficient, where the CLO value is an engineering unit that describes the thermal insulation properties of fabrics. When the room temperature is 20 °C, the relative humidity does not exceed 50%, the air velocity does not exceed 10 cm/s, and the thermal insulation value or CLO of the clothing worn by a person sitting still or engaging in light mental work to maintain a comfortable state is 1, which is measured by legal measures. The unit is defined as l CLO = 4.30 × 10 K·m·h/J = 155 m·K/W. The results are shown in Waddings with a high CLO, high heat preservation rate, and low heat transfer coefficient are preferred. As can be seen from Meanwhile, the CLO value and heat preservation rate of waddings encapsulated in melt-blown nonwoven fabrics are superior to that of woven fabrics. On the contrary, the heat-transfer coefficient of waddings shows an opposite trend and seems to decrease with the increasing down fiber mass in each group c. GeneraThe anti-drilling performance is the most concerned property in this study. After applying a rubbing and washing force on the waddings, the numbers of drilling fibers were counted, and the results are shown in The anti-drilling results after rubbing and washing are very similar. Generally speaking, waddings encapsulated in melt-blown nonwoven fabrics have a more excellent anti-drilling performance than those in woven fabrics, and is nearly triple. This can be explained by the finer pores and more complicated path in melt-blown nonwoven fabrics. In contrast, the fiber mass and fabric thickness have less of an impact on the anti-drilling performance.In summary, waddings encapsulated in melt-blown nonwoven fabrics have a better moisture permeability, thermal insulation property, and anti-drilling performance, while having some shortage in air permeability.According to Formula (2), the pore fractal dimension of nonwoven fabrics and woven fabrics can be calculated.After the calculation of ten images for each sample, the average fractal dimensions of nonwoven fabric N2 and woven W# are listed in From The waddings made of down fiber encapsulated in melt-blown nonwoven fabrics have a superior moisture permeability, thermal insulation performance, and anti-drilling performance. However, the air permeability is slightly inferior to that of waddings that are encapsulated in traditional woven fabrics.The pore fractal dimensions of melt-blown nonwoven fabrics are larger than that of woven fabrics. The relationship between the fractal dimension and performance of waddings reveals the mechanism.Generally speaking, the fundamental performance of the composite waddings made of down fibers encapsulated in melt-blown nonwoven fabrics is satisfied. Furthermore, the industrial process of melt-blown nonwoven fabrics has a high efficiency and low cost.


To investigate the clinical characteristics and the site of pulmonary involvement in Takayasu arteritis (TAK) patients with pulmonary artery involvement (PAI).We retrospectively investigated data of 141 TAK patients. The clinical and image data of the patients with and without PAI were analyzed and compared. The patients were followed up. The major outcome was all-cause mortality. The minor outcome was exacerbation or new occurrence of PAI, which leads to disease progression events.P < 0.001). The frequencies of the following were significantly higher in TAK with PAI than those in TAK without PAI: disease duration , hemoptysis , oppression in the chest , fever , Mycobacterium tuberculosis infection , pulmonary hypertension (PAH) , pulmonary infarction , and hypoxemia . Multivariate logistic regression analysis of data of TAK patients with symptom presentation showed that oppression in the chest  and thoracic aorta involvement  were associated with PAI. The cluster analysis performed for data of TAK patients with PAI revealed that the cluster characterized as the upper lobe of the right lung (Cluster1) had the worst prognosis.For the 141 TAK patients considered, PAI was detected in 65 (46.1%) patients. TAK patients with PAI had a significantly higher cumulative incidence of events than those without PAI (In TAK, PAI is associated with thoracic aorta involvement. In TAK patients with PAI, the involvement of the upper lobe of the right lung is characterized with the worst prognosis. Takayasu arteritis (TAK) is a chronic, large-vessel vasculitis that mostly affects young Asian women –4. VascuIn the present study, we aimed to investigate the clinical characteristics, the inflammatory cytokines, and the site of the pulmonary involvement in TAK patients with PAI by using computer tomography pulmonary angiography (CTPA) and by performing cluster analysis for prognostic evaluation to facilitate early identification of PAI, prolong patient survival, and improve patient’s quality of life.A retrospective study was performed. The study cohort consisted of 193 patients with TAK from January 2013 to June 2021 from inpatient services in Beijing Anzhen Hospital, Capital Medical University, Beijing, China. All TAK patients fulfilled the criteria of the 1990 American College of Rheumatology (ACR) for TAK . TAK vasLaboratory parameters and clinical data were obtained from the medical records. Clinical characteristics, including the disease duration, complications, and medication history, were collected for all patients, and the NIH scores were recorded.The tests were carried out at the diagnosis of Takayasu’s arteritis. Blood samples (6 mL each) were collected from each patient for laboratory measurements. Clinical data, including hepatic and renal function, were collected for all patients by using an automatic biochemical analyzer . Serum immune globulin and complement were measured by using an automatic biochemical analyzer . The serum C-reaction protein concentrations were determined by immunonephelometry, and the ESR was measured by the traditional Westergren method. IL-6 levels were tested by using chemiluminescent immunoassay techniques .All patients had either a vascular computed tomography angiography (CTA) and/or a magnetic resonance angiography (MRA) of the aorta and of all of its primary branches at presentation. Vascular Doppler data were additionally used to evaluate the involvement of the peripheral arteries, such as the axillary and humeral arteries, which could not always be visualized with CTA angiography and MRA. The vascular Doppler specialist performed peripheral vascular Doppler examinations. CTA and MRA were interpreted in consensus by 2 radiologists. The arterials of the patients were evaluated for the presence or absence of any of the following vascular lesions: wall thickening , stenosis [defined as a more than 25% (>25%) decrease in the diameter of the diseased artery when compared with the normal PA], dilatation , aneurysm [defined as a more than 50% (>50%) increase in the diameter of the diseased artery when compared with the normal PA], and occlusion. The presence of any of these lesions in a given vessel during the follow-up period was recorded as the involvement of that vessel.The retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University [No. 2022173X].One hundred forty-one patients were followed up and the major outcome and the minor outcome were recorded. The major outcome was all-cause mortality. The minor outcome was the combined secondary endpoints, which was exacerbation or new occurrence of PAI and disease progression events. For evaluating exacerbation or new occurrence of PAI, the changes in pulmonary arteries that concerned wall thickening, stenosis, occlusion, and dilatation were assessed by CTPA. Exacerbation or new PAI lead to disease progression events including exacerbation or new occurrence of pulmonary hypertension, exacerbation or new onset of hypoxemia, new pulmonary infarction, exacerbation or new onset of chest pain, and death.CTPA data from the 65 TAK patients identified to have PAI were retrospectively recorded. For our statistical analysis, we used R software and Ward’s method of hierarchical clustering for clustering analysis of the following vascular beds: the main PA, left PA, right PA, right upper lobar PA, apical segment, posterior segment, anterior segment, right middle lobar PA, medial segment, lateral segment, right lower lobar PA, superior segment, medial basal segment, anterior basal segment, lateral basal segment, posterior basal segment, left upper lobar PA, apicoposterior segment, anterior segment, superior lingular segment, inferior lingular segment, left lower lobar PA, superior segment, anteromedial segment, lateral basal segment, and posterior basal segment.t-test was used to compare differences between two groups. Medians and interquartile ranges were used to describe abnormally distributed data, and the rank-sum test was used to compare differences between two groups. Discrete variables were described through frequencies and percentages. Depending on the number of events, chi-square or Fisher’s exact test was performed. To identify predictors of TAK-PAI, univariate and multivariate logistic regression analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were calculated. The cumulative incidence of disease progression events was calculated by the Kaplan-Meier method. All statistical analyses were performed using the Statistical Package for Social Sciences version 22.0 . P < 0.05 was considered statistically significant.Continuous data were expressed as mean ± standard deviation , oppression in the chest , fever , and Mycobacterium tuberculosis infection   were significantly more frequent compared with those in patients with TAK without PAI.According to CTPA, PA was involved in 65 patients (patients with PAI) and was not involved in 76 patients (patients without PAI). One hundred forty-one TAK patients were included. Patients’ clinical characteristics, laboratory findings, and the artery involvement are presented in Table P < 0.001], pulmonary infarction , and hypoxemia (18.5% vs. 1.3%: P < 0.001). There were two cases of PAH in TAK patients without PAI. In one case, right heart catheterization proved the presence of PAH of left heart origin. In another case, echocardiography suggested PAH, but the patient refused right heart catheterization. The incidence of Numano type V was higher in TAK patients with PAI. No significant differences were found with respect to gender, age, total white blood cell (WBC), hemoglobin (HGB), platelet (PLT), erythrocyte sedimentation rate (ESR), C-reaction protein (CRP), and NIH score between the patients of TAK with PAI and those without PAI. Echocardiography, arterial ultrasound, and MRA/CTA were performed in all the TAK patients. The incidence of thoracic aorta involvement in patients with PAI was significantly higher than that in patients without PAI (P < 0.001).TAK patients with PAI, compared to those without PAI, had a higher risk of PAH [21.5% vs. 2.6%; P = 0.044) and thoracic aorta involvement  were associated with the occurrence of PAI  instances. Fifty-two of the 65 patients had segmental involvement, 26 patients had more than 3 segments involved, 11 patients had more than 10 segments involved, and the patient with the largest number of involved segments had 18 segments involved. The number of pulmonary segments involved for each case is showed in Fig. P = 0.013), Mycobacterium tuberculosis infection , and hypoxemia  than non-Cluster1. Cluster2 was named as “few arteries type”. It was characterized by fewer involved PAs. In particular, left PA, right PA, and right lobar PA and its segment were rarely involved. Thirteen of the 19 patients had only one PA involved and six had two PAs involved. Cluster2 had a higher frequency of dizziness  than non-Cluster2. Cluster3 was named as “pulmonary trunk type”. It was characterized by the involvement of the main PA and left and right main PAs. Cluster3 had a higher frequency of PAH  than non-Cluster3, but this difference was not statistically significant. Cluster4 was named as “right pulmonary middle lower type”. It was characterized by the involvement of the right middle lobar PA and its segment and the right lower lobar PA and its segment. Cluster4 had a higher frequency of pulmonary infarction  than non-Cluster4, but this difference was not statistically significant. Cluster5 was named as “left pulmonary type”. It is characterized by the involvement of left PA and its lobar and segment.Cluster analysis revealed five clusters of patients Fig. ; Table 4One hundred forty-one TAK patients were followed up for a median of 46 (4–120) months. Sixty-five TAK patients with PAI were followed up for a median of 37 months (4–120), among whom, 42 cases did not experience any events, with a median follow-up duration of 53 (8–120) months. Twenty-seven events (1–3 per person) were observed in 23 (35.4%) patients, with a median follow-up duration of 18 months (4–66). Seventy-six TAK patients without PAI were followed up for a median of 49 months (8–116), among whom, 70 cases did not experience any events, with a medium follow-up duration of 48.5 months (8–116). Seven events (1-2 per person) were observed in 6 (7.9%) patients, with a median follow-up duration of 57.5 months (16–84).CTPA confirmed that PA exacerbation or new PA involvement occurred in 26 patients including 1 patient who died and 25 patients who had disease progression events. Four patients died, which was attributed to all-cause mortality. Three of these were TAK patients with PAI. Among them, one died of exacerbation of PAH, one died of heart failure, and one died of side effect of the drug. The death of the TAK patient without PAI was due to exacerbation of TAK. In TAK patients with PAI, exacerbation of PAH occurred in 5 patients, exacerbation or new onset of hypoxemia occurred in 15 patients, and exacerbation of chest pain occurred in four patients. In TAK patients without PAI, new onset of hypoxemia occurred in four patients, new onset of chest pain occurred in two patients, and there was no occurrence of new pulmonary infarction.P < 0.001) . Cluster1 had the worst prognosis . There was no difference between Cluster2 and Cluster4 (P = 0.900). Also, there was no difference in the cumulative incidence of events among Cluster2 and Cluster4 and TAK without PAI groups (P = 0.521). Patients with Cluster1 suffered from worse cumulative incidence of events in comparison with non-Cluster1 patients (P = 0.001)   Fig. A. Cumulasis Fig. B. There To the best of our knowledge, the present study is the first to identify that the involvement of the thoracic aorta in TAK patients is related to PAI. Also, this is the first time that the cluster analysis of PAI in TAK with PAI has been reported, where it was found that Cluster1 (named as “right upper lobar PA type”) had the worst prognosis.Our results about the relationship between the involvement of the thoracic aorta in TAK patients and PAI suggest that PAI should be considered once thoracic aorta involvement is identified in TAK patients. Sporadic evidence pertaining to the relationship between PAI and the involvement of thoracic aorta can be found in the literature , 14–21. Mycobacterium tuberculosis infection were observed in patients with Cluster1. In our study, Cluster2 and Cluster4 had good prognoses, with no difference in the incidence of the involved disease progression events compared with the non-PAI group. The prognosis of the few arteries type (Cluster2) and the right pulmonary middle lower type (Clsuter4) was good. In a few arteries type (Cluster2), only one or two PAs were involved and in the right pulmonary middle lower type (Clsuter4) right middle lobar PA and its segment, and right lower lobar PA and its segment were involved, which indicate good prognosis. The prognoses of pulmonary trunk type (Cluster3), which involved main PA, and left pulmonary type (Cluster5), which involved left PA and its lobar and segment, were worse than those of Cluster2 and Cluster 4, suggesting that patients with main PA or left PA involvement should be treated actively. Cluster1 had the worst prognosis, where the right upper PA and its branches were mainly involved. The patients of Cluster1 had a high incidence of Mycobacterium tuberculosis infection (TB), and the clinical symptoms of fever and hypoxemia were more frequent. Many studies have found that TB is common in patients with TAK [Mycobacterium tuberculosis infection should be vigilant about the involvement of the right upper PA to guide the clinical treatment and prognosis.In our study, right upper lobar PA type (Cluster1) had the worst prognosis. A higher frequency of fever, worse hypoxemia status, and higher prevalence of with TAK –25. Sevewith TAK –28. PulmMycobacterium tuberculosis infection than TAK without PAI. One study showed that among the TAK patients studied, about 17.7% had a history of tuberculosis, which was higher than that of the general population, which is 5.5–5.8% [Mycobacterium tuberculosis infection remain to be understood. A possible hypothesis is that Mycobacterium tuberculosis infection can promote the differentiation of CD4+ T cells into Th1 and Th17 lymphocytes [Our study demonstrated that oppression in the chest and fever were more frequent in patients with TAK with PAI compared with those with TAK without PAI, which was consistent with a previous report by Kong et al. . Further5.5–5.8% . Another5.5–5.8% . The exaphocytes –33. We sphocytes .Many studies have found that PAH is more common in TAK with PAI. According to previous reports, the prevalence of PAH in TAK patients with PAI widely varied, in the range 15.74–61.7% , 30, 34.In previous studies, the incidence of PAI in patients with TAK who had undergone imaging of the PAI varied in the range 6.9–86% , 35–39. A longer disease duration was found in TAK with PAI, which is in line with the finding of a previous study . AccordiMycobacterium tuberculosis infection than TAK patients without PAI. In TAK, PAI is associated with oppression in the chest and thoracic aorta involvement. In TAK patients with PAI, the involvement of the upper lobe of the right lung is characterized with the worst prognosis.TAK patients with PAI have longer disease duration; have higher cumulative incidence of events; have higher risks of pulmonary hypertension, pulmonary infarction, and hypoxemia; and more frequently have hemoptysis, oppression in the chest, fever, and Our study has some limitations. First, it has a retrospective design. Second, the sample size is small. A prospective cohort study with a larger number of TAK cases is needed to confirm the characteristics of the pulmonary involvement in TAK patients.In conclusion, this study demonstrated that the involvement of the thoracic aorta in TAK patients is related to PAI. Also, this study reports for the first time a cluster analysis of PAI in TAK with PAI, where it was found that the right upper lobar PA type (Cluster1) had the worst prognosis.


E. coli and S. aureus in these biomaterials. Similar to the antibacterial effects, the NaOH coating did not contribute any significant changes in cell proliferation and cell loading, and CrPEEK showed better biocompatibility among the biomaterials. Therefore, this study concluded that the surface modification of biomaterials could potentially improve the functional properties but not the antibacterial and biocompatibility, and CrPEEK could be an alternative material to Ti and Zr with desirable qualities in orthopedic applications.Several metallic and polymer-based implants have been fabricated for orthopedic applications. For instance, titanium (Ti), zirconia (Zr), and polyetheretherketone (PEEK) are employed due to their excellent biocompatibility properties. Hence, the present study aimed to compare the functional and biological properties of these three biomaterials with surface modification. For this purpose, Ti, Zr, and ceramic-reinforced PEEK (CrPEEK) were coated with NaOH and tested for the biological response. Our results showed that the surface modification of these biomaterials significantly improved the water contact, protein adhesion, and bioactivity compared with uncoated samples. Among the NaOH-coated biomaterials, Ti and CrPEEK showed higher protein absorption than Zr. However, the mineral binding ability was higher in CrPEEK than in the other two biomaterials. Although the coating improved the functional properties, NaOH coating did not influence the antibacterial effect against  Alloys-based metallic biomaterials are the most convincing implants that are widely used in orthopedic applications for the replacement of bone and dental tissues. Empirical evidence has already proved the biocompatibility, conductivity, and tissue regenerative properties of alloy-based materials. Among the biomedical alloys, titanium (Ti) and zirconia (Zr) are the best known materials in dental applications .Ti, a well-known metal, is widely used in several practical applications as implants and abutments due to its excellent strength, light weight, and biocompatibility. More specifically, due to the excellent biocompatibility with the periodontal and bone tissues, Ti implants are considered as the most suitable materials in dental and bone regeneration. However, many scientific reports claimed the undesirable effects of Ti implants due to corrosion and poor esthetics, as well as the liberation of titanium ions ,3,4,5,6.3), stiffness, being insolvable in water, thermal stability, chemical stability, resistance to a wide range of chemicals , processing performance, and good tribological properties. Among other biocompatible synthetic polymers, PEEK has the highest level of mechanical strength, chemical stability, and biocompatibility. Interestingly, the elastic modulus (3–4 MPa) of PEEK exactly resembles the human cancellous bone [Recently, several researchers have initiated the improvisation of the features of dental implants using other polymer materials. In this sense, polyetheretherketone (PEEK) has been widely studied as a suitable material ,13,14,15ous bone ,17,18,19However, Caballé-Serrano et al. reported a contradictory finding where they concluded that the PEEK had no better effect than Ti . There aAlthough PEEK has several advantages, the bioinert property limits the use of PEEK in practical applications ,23. To sFor instance, Guo et al. compared the effect of Ti, Zr, and PEEK with or without plasma and UV treatment in human dental pulp stem cells (hDPSCs) and human gingival fibroblasts and concluded that the UV and non-thermal plasma treatment improved the cellular attachment of Ti, Zr, and BioHPP PEEK and also upregulated the osteogenic differentiation of hDPSCs ,27. It wThe circular specimens with a diameter of 10 × 3 mm were prefabricated from Ti, Zr, and ceramic-reinforced polyetheretherketone (CrPEEK) (BIOHPP) by Bredent Group GmbH & Co.KG, Senden, Germany. BioHPP is a ceramic-reinforced high-performance polymer that displays great mechanical properties and biocompatibility . All theThe surface of the specimen was functionalized by using sodium hydroxide (NaOH). To do this, the three specimens were incubated in 10 M NaOH for 24 h at 37 °C . After iThe protein adsorption ability of the specimen was determined by following our previous protocol . BrieflyEvaluation of the apatite-forming ability of coated and uncoated specimens was conducted by using simulated body fluid (SBF) according to ISO/FDIS 23317 recommendations . The SBFThe coated and uncoated samples were subjected to water and glycerol contact angle tests by using drop shape analysis at room temperature. Briefly, 5 µL of deionized water or 10 µL glycerol was dropped on the surface of the specimens, and the contact angle was measured at different time points, 0, 10, and 30 s. The samples were adapted to room temperature (with an RH of 60%) for moisture equilibrium prior to the experiment.The morphology of coated and uncoated specimens was visualized by using scanning electron microscopy in a SEM-Hitachi S-3500N device with energy-dispersive X-ray spectroscopy . The specimens were captured under different magnifications at 500 (100 μm), 1 (50 μm), 2 (20 μm), and 3 k (10 μm), respectively.Staphylococcus aureus (CECT 239), and Gram-negative strain, Escherichia coli (CECT 101), from the Spanish Type Culture Collection (CECT), Valencia, Spain. Freeze-dried bacteria were activated by culturing in Nutrient Broth from the activation kit of CECT and cultured for 24 h at 37 °C, followed by two 10 mL consecutive cultures in Nutrient Broth .The antimicrobial activities of coated and uncoated specimens were tested using the Gram-positive strain, The strains from the second culture were spread using a sterile bent rod on a Standard Methods Agar  culture plate (60 nm). In order to evaluate the effect of specimens on bacterial growth, after spreading, coated and uncoated specimens were placed into an agar plate and incubated for 24 h at 37 °C. The two antibiotics, penicillin and amphotericin-B (10 µL), were used to obtain the positive control. After incubation time, the zone of inhibition of coated and uncoated specimens was measured using an automatic Interscience scan 500 zone reader .® iD3 Multi-Mode Microplate Reader .In order to investigate the bacterial attachment capacity on specimens, coated and uncoated specimens were placed into 24-well plates, and 400 µL from the second bacterial culture was added on top of the specimens and incubated for 24 h at 37 °C. After incubation time, the remaining unattached bacteria were removed gently with a PBS wash. Next, 3--2,5-diphenyltetrazolium bromide (MTT)  reagent (400 µL) was added into wells for 2 h, and then the formazan dye was solubilized with 200 µL of dimethyl sulfoxide (DMSO) . The effect of bacteria attachment on specimens was spectrophotometrically quantified at 570 nm using a SpectraMax2 incubator at 37 °C. When the cells were at confluence around 70–80%, the medium was removed, cells were washed with PBS gently to remove the remaining medium or unbound cells, and trypsinization was performed using 0.25% trypsin-EDTA . The detached cells were centrifuged at 200× g for 5 min, and the cell pellet was redistributed with fresh medium for cell passage. Every time, the cell number was counted by using an automated Invitrogen cell counter .Human bone Mesenchymal stem cells (hMSCs)  were used to evaluate the biocompatibility of the samples. The phenotyping and surface-specific marker expression of MSCs were reported in our earlier work . The cel4 were carefully seeded on top of the specimens and incubated for 6 h. After the incubation period, the medium was removed, cells were trypsinized, and the total cell number was recorded using an automated Invitrogen cell counter . The cells seeded without specimens were considered as control.The coated and uncoated specimens were placed into 24-well plates with 800 µL of fresh medium in order to just cover the surface of the specimen. Then, the hMSC cells at a cell density of 5 × 104 on top of the specimens as mentioned earlier, the culture plates were incubated for 7 days at 37 °C. The culture medium was changed every 2–3 days. After 7 days, the cells were trypsinized as mentioned earlier and counted by using an automated Invitrogen cell counter. The cells seeded without specimens were considered as the control.The proliferation of hMSC cells in coated and uncoated specimens was evaluated. After seeding cells with a density of 5 × 10The structure of the hMSC cells on top of the specimens was confirmed by fluorescence staining. Briefly, the cells were cultured on all specimens and trypsinized as mentioned before. Then, the cells (100 microliters) from each coated and uncoated specimen were collected and stained with fluorescence dye DAPI following standard protocol. In order to visualize the nucleolus of the cells, the images were captured by using fluorescence microscopy coupled with ZEISS Axiocam 305 mono .p-value less than 0.05  was considered statistically significant.All the experiments were conducted in three independent setups, and the results were obtained in triplicate. The data were presented as mean standard deviation. The statistical significance was calculated by ANOVA using GraphPrism 9.0.1 . A The absorption ability of coated and uncoated samples was evaluated using the CBB dye method. In general, all coated and uncoated samples exhibited high adsorption ability to serum protein after FBS treatment. Notably, NaOH coating could potentially increase the ability of protein adsorption of the specimens A. The quThe mineral deposition (apatite layer formation) on the active surface of tested materials was measured using Alizarin red stain after SBF treatment for 30 days. In general, all the samples showed favourable mineralization on the active surface A. As we The hydrophilic and hydrophobic behaviour of the specimens were tested by using contact angle measurement . NaOH trIn order to investigate the pattern of surface coating, the uncoated and coated specimens were subjected to SEM. The results showed that all the uncoated specimens had a uniform homogenous surface; however, a smooth surface for Ti, a striated surface for Zr, and a rough surface for CrPEEK were seen at a higher magnification (10 μm) A. The suS. aureus and E. coli. Positive controls in terms of two antibiotics were also tested. Surprisingly, the results showed that the antimicrobial activity of coated materials decreased drastically compared with uncoated samples, and these changes in antimicrobial activity were specifically noticed in the samples tested with S. aureus strains , the coated and uncoated Zr and CrPEEK samples had a comparable proliferative effect.The biocompatibility of specimens in MSCs proliferation was investigated by culturing cells over the disc surface for 7 days. As shown in The biocompatibility of coated and uncoated specimens in hMSC was further confirmed using a fluorescence microscope using a DAPI stain . The intensity of DAPI (nuclei) staining is a directional proposed for the efficiency of materials in cell proliferation and biocompatibility. The result showed that the fluorescent staining of the uncoated group loaded with MSCs was similar to a coated group . Among tIn the present study, a wet chemical technique by enrichment with functional groups -OH (surface coating) was carried out in order to investigate the functional and antibacterial effects and biocompatibility of Ti, Zr, and CrPEEK specimens. All the specimens were coated with 10 M NaOH for 24 h at 37 °C based on the optimum conditions reported in earlier work . SimilarE. coli) [3N4) against Staphylococcus epidermidis, S. aureus, Pseudomonas aeruginosa, E. coli, and Enterococcus. The authors explained the phenomenon that wettability (hydrophilic and hydrophobic), topography, protein adsorption, and other intrinsic biomaterial properties could potentially affect bacterial affinity, thereby influencing the antibacterial properties [2 on a carbon-fibre-reinforced polyetheretherketone surface could effectively reduce adhesion and growth of S. aureus and also had a partial influence on E. coli [Among the specimens tested against two bacterial strains, the uncoated Zr had poor antibacterial activity. To support this finding, Aktuğ et al. reported that uncoated Zr exhibited greater adhesion to gram strains (E. coli)  and concoperties . On the  E. coli .In general, the specimens did not show any toxic effect in hMSCs and, interestingly, showed a higher proliferative rate of hMSCs cultured on specimens than the control. Similarly, the in vitro biocompatibility of PEEK was previously tested in pre-osteoblast cells via attachment, spreading, and proliferation rate, and it was found that the PEEK specimen could significantly promote the formation of bone-like apatite. The authors also concluded that PEEK was a novel system to enhance bioactivity and thus expanded its possible applications in orthopedic and dental implants . AnotherThe major limitations of this study are that the biocompatibility and the osteogenic stimulatory effect of NaOH-coated specimens need to be verified by in vivo and in vitro models. The efficiency of the NaOH coating in these three samples needs to be compared with other types of coating such as plasma, ozone, and calcium in dental applications.E. coli and S. aureus. In general, all three biomaterials showed biocompatibility, and the cells cultured on CrPEEK had a high proliferative rate compared with the other biomaterials; however, the effect was insignificant between biomaterials. Surprisingly, surface modification of the biomaterials did not contribute to promoting cell proliferation compared with uncoated samples. As expected, the cell loading ability of CrPEEK was more pronounced than Ti and Zr biomaterials. Overall, our study concluded that the CrPEEK could be an excellent alternative to Zr and Ti and a suitable material for the orthopedic applications.In the present study, the functional, antibacterial and biocompatible effects of three different biomaterials  with and without surface modification were investigated. Our results showed that the surface modification improved wettability, protein adhesion, and bioactivity; however, the beneficial effect of surface-modified biomaterials was not observed in the antibacterial activities of