PLoS ONE Research Articles

Female manikin for the evaluation of breast support provided by sports bras

Introduction
 The effect of breast support on running biomechanics (Milligan, 2013) and breast pain on upper-extremity kinematics during running (White et al., 2015) is investigated by different research groups. They mostly found a higher implication for females with large breasts and showed that the use of sports bras is generally beneficial compared to regular bras. A well-fitted supportive sports bra can increase an athlete's performance (Fong & Powell, 2022) and reduce the risk of injuries.
 The support properties of bras are conventionally evaluated by human trials. This is expensive and challenging when comparing the results of different studies.
 Methods
 Empa developed a manikin to investigate the load impact on the body (Wettenschwiler et al., 2017). This manikin was reshaped to a female upper body model equipped with breast prostheses for the realistic simulation of defined running conditions. A Polhemus motion tracking system was used to assess the relative movement of the manikin shell and the nipples during two simulated running conditions (8 km/h). A set of 16 sports bras was tested on the manikin regarding the reduction of relative movement of the nipples during running. In a first validation study, 6 of them were tested by human subjects during jogging (8 km/h) in 3 participants. The subjective support assessment was compared to the manikin data.
 Results
 A comparison of manikin measurement data (reduction in relative movement at 8 km/h) and subject data showed an excellent correlation (R2 > 0.95) for the subjective support assessment.
 The sports bra developed in this project reached high marks regarding support, thermal comfort, and fit.
 Discussion/Conclusion
 Preliminary data indicates that the female manikin is able to provide objective data about breast movement in line with the perceived support of sports bras. In combination with additional methods such as sensory and thermal comfort assessment, this new methodology provides a scientific basis for developing improved sports bras meeting specific requirements for various sports.
 References
 Fong, H. B., & Powell, D. W. (2022). Greater breast support is associated with reduced oxygen consumption and greater running economy during a rreadmill running task. Frontiers in Sports and Active Living, 4, Article 902276. https://doi.org/10.3389/fspor.2022.902276
 Milligan, A. K. (2013). The effect of breast support on running biomechanics [Doctoral Dissertation, University of Portsmouth].
 Wettenschwiler, P. D., Annaheim, S., Lorenzetti, S., Ferguson, S. J., Stämpfli, R., Psikuta, A., & Rossi, R. M. (2017). Validation of an instrumented dummy to assess mechanical aspects of discomfort during load carriage. PLOS ONE, 12(6), Article e0180069. https://doi.org/10.1371/journal.pone.0180069
 White, J., Mills, C., Ball, N., & Scurr, J. (2015). The effect of breast support and breast pain on upper-extremity kinematics during running: Implications for females with large breasts. Journal of Sports Sciences, 33(19), 2043-2050. https://doi.org/10.1080/02640414.2015.1026378

Bibliometric and visual analysis of intestinal flora and immunity.

The gut microbiota and its stability have important relationships with immunity. However, bibliometric analysis in this field is underdeveloped. This study aims to visualize publications related to the gut microbiota and immunity to identify research frontiers and hotspots, providing references and guidance for further research. Gut microbiota and immunity data were retrieved from the Web of Science Core Collection database, and Microsoft Excel, Scimago Graphica and VOSviewer software were used to analyze publication output trends, the most productive countries/regions, journals, authors, co-cited references, and keywords. This study analyzed 16,611 publications, including 10,865 articles and 5746 reviews, and found a continuous increase in publications related to gut microbiota and immunity since 2013. We identified 62,872 authors contributing to this field from 2144 journals and 9965 organizations/institutions in 145 countries/regions. The top publisher with the highest output is University of California System with 525 papers. Among these journals, the top 3 most prolific journals are Frontiers in Immunology, Frontiers in Microbiology, and PLOS ONE. The literature with the highest citation frequency is published in Science and has been cited 3006 times by Patrick M. Smith and others.Gut microbiota research hotspots include gut microbiota inflammation, immune response, inflammatory bowel diseases (IBDs), and microbiota tumors. The gut microbiota and its microbial homeostasis play critical roles in immune reactions, inflammation, and even tumors and IBDs.Current research on gut microbiota and immunity is a popular field. Previous studies have shown that the gut microbiota and its microbial species have important effects on maintaining human health, immune function, inflammation, tumorigenesis, and IBDs. Understanding the roles of microbial communities and specific bacterial species as well as their interactions with humans has led to numerous discoveries that provide unique opportunities for exploring human health and future research. This study used bibliometric and visualization analysis to identify the development trends and hotspots of publications related to the gut microbiota and immunity. The findings of this study provide valuable insights into the emerging trends and future directions in this field.

Global research trends in prediabetes over the past decade: Bibliometric and visualized analysis.

This study aimed to investigate global research advances and hot trends in prediabetes in the last decade based on a bibliometric analysis of publications. Publications from 2013 to 2022 were retrieved from the Web of Science Core Collection database through a topic search. With the use of CiteSpace, VOS viewer, and Bibliometrix R software packages, the number of publications, production categories, countries/regions, institutions, authors, journals, references, and keywords were comprehensively analyzed to sort out the hot spots and directions of prediabetes and predict the future research directions. A total of 13,223 papers were recruited for this study by the end of March 3, 2023. A generally increasing trend was observed in the number of annual publications. PLOS ONE (journal), USA (national), and the University of Copenhagen (institutional) published the most papers in this research area. The top 3 contributor authors were Tuomilehto Jaakko, Rathmann Wolfgang, and Peters Annette. "Intestinal microbiota" (2020-2022) was the most populated keyword in terms of intensity, and "biomarkers," "gut microbiota," and "metabolomics" were the most populated keywords in the last 3 years. "Prediabetes: a high-risk state for diabetes development-2012" was the strongest burst reference. This study summarized the research hotspots and trends in prediabetes research in the last decade. Frontier research can be found in the journal Diabetes Care and Journal of Clinical Endocrinology Metabolism. Prediabetes research focuses on preventing risk factors to reduce the prevalence of prediabetes, and current research hotspots focus on gut microbes and metabolism-related biomarkers.

Publication trends and hot spots in the Journal of Cachexia, Sarcopenia and Muscle: A bibliometric analysis (2010–2022)

AbstractBackgroundThe Journal of Cachexia, Sarcopenia and Muscle is a quarterly peer‐reviewed medical journal published by WILEY since 2010 and has been dedicated to advancing research on chronic diseases, especially cachexia and sarcopenia. Over the past 12 years, sarcopenia research worldwide has significantly changed. This study aimed to investigate different aspects of studies published in this journal.MethodsUsing the term ‘Journal of Cachexia, Sarcopenia and Muscle’, we retrieved related publications from the Web of Science and PubMed databases. Studies published in this journal were classified and analysed from different perspectives, such as the number of studies, total citations, times cited per item, H‐index, research area, article types, institutions, country and funding agency. The VOS viewer software was used for co‐occurrence, bibliographic coupling, co‐citation and co‐authorship analyses.ResultsFrom 2010 to 2022, 1194 studies were published in the Journal of Cachexia, Sarcopenia and Muscle. The United States was the highest contributor, with the most publications and citations and the highest H‐index. Italy ranked first for the times cited per item. The main research area was geriatrics and gerontology. von Haehling S was the author with the highest impact. The National Institutes of Health, USA, and the United States Department of Health Human Services funded the maximum number of studies. The top 5 most frequently used keywords in all publications over 12 years were sarcopenia, cachexia, skeletal muscle, body composition and muscle mass. The Journal of Cachexia, Sarcopenia and Muscle was cited the most by Nutrients, and PLOS ONE was cited the most by the Journal of Cachexia, Sarcopenia and Muscle.ConclusionsPublications in the Journal of Cachexia, Sarcopenia and Muscle have significantly increased from 2010 to 2022, especially in recent years. The United States is still the leader in sarcopenia research. Future submissions to this journal will continue to focus on sarcopenia, cachexia, skeletal muscle, body‐composition and muscle mass. The aetiology, molecular mechanisms and outcomes of sarcopenia and cachexia are current research hotspots.

Automated quality control of structural brain MRI scans from aging and dementia datasets

AbstractBackgroundDementias platform UK (DPUK) currently hosts over 40 dementia cohorts and provides a remote analysis environment for multimodal cross‐cohort data analysis. Nineteen cohorts include brain MRI data, hence automated quality control (QC) becomes crucial for the reliability of image analyses. This work aims to provide a framework for quality prediction of T1‐weighted (T1w) scans from aging and dementia datasets: we compared manual quality ratings with the output of two existing automated QC pipelines and propose a new QC classifier.MethodWe used 2438 T1w scans (including patients and controls, 1.5T and 3T scanners, 3 manufacturers, 11 sites) from 4 different aging and dementia datasets (ADNI, Whitehall II, Oxford Parkinson’s Disease Centre, Oxford Brain Health Clinic). Manual quality ratings for all images were performed by the dataset owners. Each image was processed in MRIQC (Esteban et al. 2017, PLoS ONE) and CAT12 (Computational Anatomy Toolbox, Gaser et al. 2022, bioRxiv). We compared the quality agreement for MRIQC predictions and CAT12’s weighted image quality ratings (IQR) with manual QC using inter‐rater reliability. Further, we explored the effect of changing the accept‐reject threshold from automated QC tools on the reliability measure. Finally, we designed a custom QC classifier (manual QC as target) by combining MRIQC and CAT12’s quality metrics as features and training linear support vector machines in a nested cross‐validation framework.ResultWe found overall agreement between automated QC methods and manual QC when applied to dementia datasets (MRIQC: Kappa = 0.30, p = 0.001; CAT12: Kappa = 0.28, p = 0.001). Adjusting the acceptance thresholds of the automated tools within dataset improved the agreement. On the combined data (training N = 1951; test N = 487), the proposed classifier showed 94.2% accuracy (sensitivity 94.3%, specificity 85.7%) on the test data. Leaving one site out (training with 10 sites, N = 2055), we found 86.4% accuracy (sensitivity 86.2%, specificity 100%) on the test site (N = 383).ConclusionThe performance of the proposed classifier appears promising on these heterogeneous datasets from different scanners. In the future, we aim to utilise this framework for improving generalisability of prediction and release the classifier on the DPUK data portal to robustly QC T1w scans for other aging and dementia cohorts.

Worldwide scientific efforts on nursing in the field of SARS-CoV-2: a cross-sectional survey analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a global public health issue. This study aimed to characterize global nursing research on SARS-CoV-2. Nursing-related publications through December 31, 2022, were identified using Scopus. The number of studies, study types, countries, institutions, journals, authors, h-index, total confirmed cases, total deaths, and the highest-cited studies were investigated. In total, 12,427 studies were identified. The number of studies increased rapidly, particularly between 2020 and 2021, with a 2.36-fold increase. The United States published the most studies (3,289, 26.47%), followed by the United Kingdom (1,059, 8.52%) and China (877, 7.06%). Scientific productivity significantly correlated with the total confirmed cases (r = 0.701, p = 0.024) and total deaths (r = 0.804, p = 0.005). The United States had the highest h-index (80), followed by China (59), and the United Kingdom (57). The University of Toronto published the most studies (181), followed by Harvard Medical School (165), and the University of São Paulo (107). Gravenstein S (23) was the most prolific author, followed by Mor V (22), and Rosa WE (19). The International Journal of Environmental Research and Public Health published the most papers (436), followed by PLOS ONE (219), and BMJ Open (185). Several countries, institutions, journals, and authors contributed greatly to SARS-CoV-2-related nursing studies. Countries with larger numbers of confirmed cases and deaths tended to publish more nursing studies. The United States, United Kingdom, and China had the highest quantity and quality of studies.

Menstrual health and hygiene (MHH): a bibliometric analysis

Purpose Menstruation poses psycho-physiological challenges globally due to a lack of awareness, unhygienic practices and social stigma. This paper aims to assess the existing body of research on menstrual health and hygiene (MHH) worldwide. Design/methodology/approach This study focuses on seminal works published in the Scopus Database from 1946 to 2023 for extensive bibliometric analysis, involving 756 bibliographic records analyzed through Biblioshiny and VOSviewer software. The authors use thematic analysis to identify core research themes and sub-themes, coupled with a critical review of the most highly cited articles within each thematic category. Findings The research into MHH has consistently grown since 2010, with a notable surge in the past five years. Among all countries, the USA emerges as the most active contributor, boasting the highest number of publications and citations. In terms of organizations, The London School of Hygiene and Tropical Medicine takes the lead with 54 articles. Further, PLOS ONE and Waterlines were the most productive and influential journals, respectively. The thematic analysis identifies key research foci, including tampons, menstrual health, sanitation, hygiene and bleeding. Research limitations/implications Further research could be initiated in areas of menstrual education and awareness, menstrual product safety and effectiveness and menstrual disorders and treatments to address the concerns especially encountered by women from developing countries. Originality/value This research provides a comprehensive analysis of 77 years of MHH research, offering valuable insights into key areas of concern and guiding future research directions, ultimately addressing critical global health challenges.

Checkpoint Inhibitor PD-1H/VISTA Affects Myeloma Bone Disease By Osteoclast Cytoskeleton Remodeling

Introduction We have recently described the critical role of checkpoint inhibitor PD-1H/VISTA in osteoclast activation and multiple myeloma bone disease. Highly expressed in osteoclast precursors and mature osteoclasts, PD-1H functions as the receptor for osteoclastogenic factor MMP-13 and mediates MMP-13 induced osteoclast activation and myeloma bone disease ( Nat Commun14, 4271 (2023)). Despite the extensive functional study of PD-1H in immune disease models, the PD-1H interacting cellular complex is yet to be defined. Here we report how PD-1H interacts with cytoskeleton proteins contributing to osteoclast remodeling in multiple myeloma bone disease. Methods and Results To identify interacting proteins of PD-1H, PD-1H-His 6 recombinant protein was overexpressed in mouse mononuclear BMCs, and PD-1H-His 6 binding protein complex was pulled down by Ni-NTA agarose beads followed by mass spectrum analysis (Figure A). LIM and SH3 domain protein 1 (LASP1) was one of the most abundant cytoskeleton proteins identified in the PD-1H complex. We therefore first confirmed its binding to PD-1H by two-way co-IP assays (Figure B and C). Co-localization of LASP1 and PD-1H were further confirmed by immunofluorescence assay when co-expressed in HEK293 cells (Figure D). LASP1 is an F-actin-binding protein that stabilizes F-actin bundles and is involved in podosome regulation in macrophages (PLoS ONE 7(4): e35340). It has four domains: LIM, two nebulin-like repeats (N1 and N2) and SH3 domains. While nebulin-like repeats mediate binding to F-actin, SH3 domain is the major protein-protein binding site (PLoS ONE 7(4): e35340). In co-IP assay using PD-1H and domain deleted LASP1, deletion of LIM (△LIM) or either one or both nebulin-like repeats (△N1, △N2 and △N1/2) did not affect the binding to PD-1H. Instead, deletion of SH3 (△SH3) in LASP1 lead to loss of PD-1H binding, demonstrating that PD-1H binds to LASP1 at the SH3 domain (Figure E). Next, the association of LASP1 and PD-1H in the osteoclast cytoskeleton was demonstrated by confocal immunofluorescence microscopy. LASP1 co-localized with F-actin (Figure F) and PD-1H (Figure G) at the sealing ring in mature osteoclasts. Interestingly, although MMP-13 stimulation increased the size of osteoclasts and the sealing ring, MMP-13 did not change the co-localization pattern of LASP1 with PD-1H or F-actin. Conclusions Taken together, this study reveals the novel mechanism of PD-1H regulation of osteoclasts cytoskeleton reorganization, which is critical for osteoclast bone resorption activity. PD-1H directly associates with LASP1 at its C-terminal SH3 domain. Although LASP1 was reported to regulates podosomes function in macrophages, its role in osteoclast cytoskeletons remain largely obscure. The future study will be focused on delineating the role of LASP1 in osteoclast function, and its role in MMP-13/PD-1H signaling regulated myeloma bone disease.

Covert and overt automatic imitation are correlated.

Most theoretical accounts of imitation assume that covert and overt measures of automatic imitation tap into the same underlying construct. Despite this widespread assumption, it is not well supported by empirical evidence. In fact, the only study investigating the relation between covert and overt automatic imitation failed to find a correlation between them (Genschow et al., 2017, PLOS ONE, 12[9], Article e0183784). However, because overt and covert imitation were measured using two very different tasks, and because the measure of overt imitation was found to be unreliable, it is still not clear whether a correlation between both measures exists. Here, we address this question by reanalyzing the results of a previous virtual reality study in which automatic imitation was indexed with an overt and covert measure of gaze following, both obtained within one and the same task (Cracco et al., 2022, IScience, Article 104891). The results show that, in this situation, both types of imitation do correlate. As such, our results provide support for the idea that overt and covert measures of automatic imitation measure the same underlying construct.

Risk factors and prevention of liver cancer: A bibliometric and visual analysis.

Liver cancer has become an important public health problem. In this study, bibliometrics and visual analysis were performed on the literature related to the risk factors and prevention of liver cancer, in order to understand the latest research progress of the risk factors and prevention of liver cancer. The Web of Science database was used as a retrieval platform to retrieve the published research results from 2012 to 2023. CiteSpace and VOSviewer were utilized for bibliometrics and visual analysis. A total of 2388 articles were screened according to exclusion criteria. Between 2012 and 2018, the number of articles published fluctuated. From 2018 to 2023, the number of published documents showed a steady upward trend. The 3 journals with the most publications are World Journal of Gastroenterology, PLOS ONE, and Hepatology. The United States and China are the countries with the most publications, while Harvard University, the National Institutes of Health and the University of Texas System are the 3 institutions with the most publications. Keywords such as hepatitis B virus, hepatitis C virus, alcohol, obesity, recrudescence rate, global burden are hot words in the field of liver cancer risk factors and prevention. The current research mainly focuses on the influence of environmental factors, behavioral lifestyle and biological factors on liver cancer, as well as the primary and secondary prevention of liver cancer, but there are still many undetermined factors to be explored.

The Impact of Environmental and Behavioral Factors on the Incidence of Dengue Hemorrhagic Fever in Indonesia: Meta-analysis

Cases of dengue fever in Indonesia will increase to 143,000 by the end of 2022. The aim of the research is to examine the impact of environmental and behavioral factors on the incidence of dengue hemorrhagic fever in Indonesia. This research uses the Meta-Analysis Method with PICOS technology. Some sources of information used include Google Scholar, Research Gate, and Plos ONE, with the help of keywords such as "Environmental factors" and "Behavior." 193 articles were obtained, 151 articles came from Google Scholar, 37 articles from Research Gate, and 5 articles from Plos ONE. The articles obtained were filtered using inclusion criteria such as articles that had a 2x2 table, and discussed dengue fever and behavior with the number of selected articles being 21. At the screening stage, researchers used a cross-sectional research design. JASP application version 0.16.3.0 was used to process meta-analysis data. The key findings show that the habit of hanging clothes has a 2.386 higher risk as a cause of dengue hemorrhagic fever, with the pooled OR value as follows e0.87 = 2.386 (CI 95% 0.17-1.57). The presence of larvae has a risk of 2.075 for dengue fever with the following pooled value e0.73 = 2.075 (CI 95% 0.12-1.33). Meanwhile, the 3 M movement has a risk of 0.406 for the incidence of dengue fever with the following pooled value e-0.90 = 0.406 (CI 95% -1.66-0.15). the conclusion is There is an influence of the habit of hanging clothes, the presence of larvae and the 3M movement on the incidence of dengue hemorrhagic fever.

An Intracranial Hemorrhage Complication: Terson Syndrome

Abstract Vitreous hemorrhage associated with subarachnoid hemorrhage is known as Terson's Syndrome (TS). However, it is also seen in the literature in cases of traumatic brain injury or intracranial hemorrhage. Management of visual manifestations is necessary in patients with intracranial hemorrhage. A vitreous hemorrhage was found in the evaluation made due to visual symptoms in a patient who presented to the emergency department with intracranial hemorrhage. In addition to clinical findings, imaging techniques have an important place in the diagnosis of TS. Vitreous hemorrhage findings can be detected with imaging studies such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). In this case, the diagnostic findings and the importance of diagnosis in CT and MRI examinations in a patient with TS will be discussed. The purpose of this case report is to share the imaging findings of TS.

Judging Importance before Checking Correctness: Quick Opinions in Mathematical Peer Review

Peer review has never been a uniform practice but is now more diverse than ever. Despite a vast literature, little is known of how different disciplines organize peer review. This paper draws on ninety-five qualitative interviews with editors and publishers and several hundred written reports to analyze the organization of peer review in pure mathematics. This article focuses on the practice of “quick opinions” at top journals in mathematics: asking (senior) experts about a paper’s importance, and only after positive evaluation sending the paper for a full review (which most importantly means checking the paper’s correctness). Quick opinions constitute a form of “importance only” peer review and are thus the opposite of the “soundness only” approach at mega-journals such as PLOS ONE. Quick opinions emerged in response to increasing submissions and the fact that checking correctness in mathematics is particularly time-consuming. Quick opinions are informal and are often only addressed to editors. They trade on, indeed reinforce, a journal hierarchy, where journal names are often used as a “members’ measurement system” to characterize importance. Finally, quick opinions highlight that a key function of the peer-reviewed journal today, apart from validation and filtration, is “designation”—giving authors items on their CV.

Using Next Generation Sequencing to Identify Trackable Clonotypic Sequences for Minimal Residual Disease Testing in AL Amyloidosis

Introduction: Recent studies have shown that deeper free light chain responses are associated with improved outcomes in patients with systemic light chain (AL) amyloidosis, yet the optimal long-term goal remains unclear.(N Engl J Med 2018; 378:518-528) Unlike multiple myeloma, where the role of minimal residual disease (MRD) testing is well established, in AL amyloidosis the methods to best identify MRD, and whether achieving MRD would benefit disease outcomes, warrant further investigation. (Blood Cancer J. 2021 Jun 21;11(6):117; PLoS ONE 15(7): e0235713. https://doi.org/10.1371/journal.pone. 0235713) In AL amyloidosis, the toxic misfolded oligomers and amyloid deposits are both due to clonal immunoglobulin light chains and cause organ damage and death. Hence, the tracking of clonotypic light chain sequences could present a promising approach for detecting the maintenance of profound therapeutic responses. Our study aimed to assess the frequency with which next generation sequencing (NGS) detects light-chain clones consistent with the patient's clonal light-chain isotype and to determine whether the light-chain sequences identified were encoded by light-chain variable region genes considered AL-related.(Journal of Clinical Oncology 2019 37:15_suppl, 8010; Blood (2017) 129 (3): 299-306; PLoS One 2022 Feb 25;17(2):e0264407) Methods: Ninety patients diagnosed with AL amyloidosis between September 2016 and July 2023 at Tufts Medical Center and University of California San Francisco were included. Bone marrow samples from the 90 patients were sent to Adaptive Biotechnologies Inc. (Seattle, WA) for initial clone identification using the clonoSEQ Assay. IMGT/BlastSearch database (Version 1.2.1) was used to identify the clonotypic immunoglobulin light chain variable domains detected by the clonoSEQ assay. Samples were then divided in to two groups based on the consistency of paraprotein isotype with the trackable sequences, and Mann-Whitney U test was used to compare the difference of the numbers of clonotypic sequences. Results: Of the 90 patients with bone marrow samples sent for clone identification, 85 (94.4%) had at least one trackable clonotypic sequence, with a median number of 3 and a maximum of 11. Of the 85 patients with trackable sequences, 67 (78.8%) had an AL paraprotein isotype consistent with the detected clonotypic sequence isotype, 48 with light chain and 19 with heavy chain isotypes. Compared to the inconsistent ones, patients who had consistency in paraprotein and trackable sequences exhibited higher numbers of clonotypic sequences ( P = 0.001). With respect to marrow plasma cell infiltrations, both consistent and inconsistent groups had a median of 15% marrow plasma cells with no statistically significant difference between them by two-tailed Mann-Whitney. Of note, consistent with the restricted pattern of germline gene use in AL, the 48 patients also used AL-related variable region Ig light chain genes; the variable region light chain genes identified were AL-related and included IGKV1-33 (8 identified sequences), IGKV4-1 (4), IGKV1-16 (3), IGKV1-5 (1), GKV1-13 (1), IGLV6-57 (8), IGLV3-21 (6), IGLV1-44 (5), IGLV3-1 (4), IGLV1-40 (3), IGLV2-14 (3), IGLV1-51 (2). Conclusion: In patients with AL amyloidosis, the ClonoSEQ assay can identify a sequence consistent with the patient's light or heavy chain isotype almost 80% of the time. Of those cases in which a clonal light chain sequence was consistent with the patient's isotype, the genes identified were from the well described AL-related light chain variable region gene repertoire. These findings indicate that the size of the AL clone does not affect this outcome and suggest that other factors related to the adaptive immune dysregulation of AL or to the multiplex PCR process may be involved. ClonoSEQ can identify trackable clonotypic light chain sequences that are AL-related 56% of the time in patients with AL, a finding that may be relevant to patients with myeloma.

Native American Ancestry Is Associated with Successful Immune Tolerance Induction in Admixed Brazilians with Hemophilia a

Immune tolerance induction (ITI) is the treatment of choice for eradicating neutralizing antibodies (inhibitors) against factor VIII (FVIII) in patients with hemophilia A (PwHA). Previous studies have investigated the association of ethnicity with inhibitor development with conflicting results. However, to our concern, studies targeting the role of ethnicity on ITI outcomes are still missing. Since unfavorable ITI response occurs in 30%-40% of these patients, establishing predictors of ITI response is needed. To evaluate genetic determinants of ITI outcome beyond FVIII genotype, we investigated the association of genomic ancestry and ITI response by analyzing the exomes of PwHA from the Brazilian Immune Tolerance Study (Camelo et al. 2021). PwHA were enrolled in 15 hemophilia treatment centers from all Brazilian regions. We collected clinical data and blood samples for DNA extraction. ITI was carried out using a single protocol, regardless of selection based on “good” or “bad” risk of ITI outcome. Inclusion criteria comprised patients with severe and moderately-severe (FVIII<2%) HA with high-responding inhibitors who completed a first course of ITI. Since the characteristics of PwHA who responded with partial and complete success yielded similar results, these groups were analyzed together. Exomes were obtained with high quality using the xGen Exome Research Panel v2 (Illumina). Quality control filters evaluated average coverage and deep coverage, phred score, genomic position, sex, heterozygosity, and duplicated SNPs. In a multiple regression analysis, we used geographic location, inhibitor levels, presence or absence of null mutations (i.e., frameshift, deletions, nonsense, and inversions; Oldenburg et al., 2002), and kinship coefficients as explanatory variables. Inhibitor levels were evaluated as historical inhibitor peak, titer immediately before the start of ITI, and inhibitor peak during ITI. We included 150 PwHA, of whom 136 (91%) had severe (FVIII<1%) HA, median age 0.9 years [IQR, 0.5,1.4] at diagnosis of HA. A total of 44 (29%) PwHA had ITI failure, 60 (40%) had partial success, and 46 (31%) had complete ITI success. Functional annotation showed that most SNPs were intronic (48%) and exonic (29%). We identified 808,706 variants, of which 90,075 were not reported in the dbSNP. Average ancestries of European, African, and Native American were 79.4% [IQR:75.4,83.4], 17.3% [IQR:17.0,17.6), and 3.3% [IQR:2.6,4.0], respectively (Table 1). There was an association between a higher Native American ancestry in patients with successful ITI (2% [IQR:1.95,2.05] ancestry mean) when compared with patients who failed ITI (1% [IQR:0.97,1.03] ancestry mean). A 1% increase in the Native American ancestry proportion was associated with a rise of ~10% in the probability of successful ITI ( odds ratio [OR], 10.43 [95% CI,7.45,13.41], p = 0.040 (Table 2). Neither European nor African ancestry was associated with ITI outcome. In conclusion, Native American ancestry was associated with successful ITI. To our concern, this is the first study to evaluate genomic ancestry as a predictor of ITI response and the first to enroll an admixed population of HA. Identifying ancestry as a predictor of ITI outcome may elicit different therapeutic approaches for inhibitor eradication. However, our findings may not apply to other populations due to a particular characteristic of admixture of the Brazilian population. REFERENCES Camelo, R.M. et al. (2021) ‘Predictors of the outcome of immune tolerance induction in patients with haemophilia A and inhibitors: The Brazilian Immune Tolerance (BRAZIT) study protocol’, PLOS ONE, 16(8). doi:10.1371/journal.pone.0256265. Oldenburg, J., El-Maarri, O. and Schwaab, R. (2002) ‘Inhibitor development in correlation to factor VIII genotypes’, Haemophilia, 8(s2), pp. 23-29. doi:10.1046/j.1351-8216.2001.00134.x.

Expression of Concern. Eduardo R. Ropelle, José R. Pauli, Dennys E. Cintra, Adelino S. da Silva, Cláudio T. De Souza, Dioze Guadagnini, Bruno M. Carvalho, Andrea M. Caricilli, Carlos K. Katashima, Marco A. Carvalho-Filho, Sandro Hirabara, Rui Curi, Lício A. Velloso, Mario J.A. Saad, and José B.C. Carvalheira. Targeted Disruption of Inducible Nitric Oxide Synthase Protects Against Aging, S-Nitrosation, and

On the basisofthe recommendationofthe American Diabetes Association's Panel on Ethical Scientific Programs (ESP), the American Diabetes Association, the publisher of Diabetes,is issuing thisexpressionof concernto alert readers about the authenticity of the data in the above-cited article. Multiple panels in this article are unexpectedly similar to those appearing in articles in PLOS ONE and PLOS Biology authored by the same laboratory.In Fig. 2A, the αtubulin panel appears to be similar to the β-actin panels in Fig. 7J and K of the following 2012 article in PLOS ONE: Cintra DE, Ropelle ER, Moraes JC, etal. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLoS One 2012;7:e30571 (DOI: 10.1371/journal.pone.0030571)In Fig. 2B, the pIKKβ panel appears to be similar to the mirror image of the pPERKThr981 panel in Fig. 7G of the following now-retracted 2010 article in PLOS Biology: Ropelle ER, Flores MB, Cintra DE, etal. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKβ and ER stress inhibition [retracted in: PLoS Biol 2023;21:e3002079]. PLoS Biol 2010;8:e1000465 (DOI: 10.1371/journal.pbio.1000465) Diabetesis a member journal of the Committee on Publication Ethics (COPE) (publicationethics.org). As such, the editors of the journal and the ESP refer to COPE's guidelines and recommendations when reviewing such matters.

Expression of Concern. Marciane Milanski, Ana P. Arruda, Andressa Coope, Letícia M. Ignacio-Souza, Carla E. Nunez, Erika A. Roman, Talita Romanatto, Livia B. Pascoal, Andrea M. Caricilli, Marcio A. Torsoni, Patricia O. Prada, Mario J. Saad, and Licio A. Velloso. Inhibition of Hypothalamic Inflammation Reverses Diet-Induced Insulin Resistance in the Liver. Diabetes 2012;61:1455-1462. DOI: 10.2337/db11-0390. PMID: 22522614. PMCID:PMC3357298.

On the basisofthe recommendationofthe American Diabetes Association's Panel on Ethical Scientific Programs (ESP), the American Diabetes Association, the publisherofDiabetes,is issuing thisexpressionof concernto alert readers about the authenticity of the data in the above-cited article. A within-article panel duplication has been identified, and a panel in this article is unexpectedly similar to a panel appearing in a PLOS ONE article authored by the same laboratory.The βactin panel under pAKt in Fig. 1H appears to be a possible duplicate, with horizontal rotation, of the βactin panel under pAKt in Fig. 3B.The Actin blot in Fig. 2E appears to be a possible duplicate, with size adjustments, of the Actin panel in Fig. 2G in the following 2012 article in PLOS ONE: Lima MHM, Caricilli AM, de Abreu LL, etal. Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial. PLoS One 2012;7:e36974 (DOI: 10.1371/journal.pone.0036974) Diabetesis a member journal of the Committee on Publication Ethics (COPE) (publicationethics.org). As such, the editors of the journal and the ESP refer to COPE's guidelines and recommendations when reviewing such matters.

THU572 Structure, Organisation And Mechanistic Insight Of Cytochrome P450 17A1

Abstract Disclosure: L.L. Martin: None. P. O'Leary: None. S. Arumugam: None. S. Bell: None. R.J. Rodgers: None. Introduction: Cytochrome P45017A1 (CYP17) is a heme-containing, membrane bound enzyme situated at a key branch within steroidogenic pathways. CYP17 is a dual function enzyme that initially catalyses 17α-hydroxylation of pregnenolone and progesterone to 17α-hydroxypregnenolone and 17α-hydroxyprogesterone. CYP17 can further metabolize these steroids via 17,20-lyase reactions to produce androgen/estrogen precursors. Activity of CYP17 requires electrons delivered by cytochrome P450 oxido-reductase (CPR) and and accessory protein cytochrome b5 (cyt b5) for the 17,20-lyase reaction. Previously, we showed that (i) CYP17 could homodimerise and heterodimerise with CPR and cyt b5 in cells using FRET [1] and computer models [2] and (ii) protein-protein interaction of cyt b5 with CYP17 slowed the rate of electron transfer to CYP17 [3] by electrochemistry. The current study focuses on sub-cellular organisation of CYP17 and mechanistic insight gained via analysis of the structural and molecular interactions of CYP17 with its partner proteins associated with 17α-hydroxylase and 17,20-lyase reactions. Methods: Single molecule fluorescence microscopy (SMFM) was used to observe fluorescently tagged CYP17 in live HEK 293 cells. Molecular Dynamics (MD) simulations were done for CYP17 in membranes, in the presence and absence of substrates, while interacting with CPR and cyt b5. Results: Halo-tagged CYP17 was imaged in real-time within the endoplasmic reticulum, providing kinetic data and sub-cellular localisation dynamics of individual molecules.MD simulations, within a membrane environment, allowed the dynamics of full-length models of CYP17 to be simulated: (i) in the absence of substrate, (ii) with a hydroxylase substrate (pregnenolone), and (iii) with a lyase substrate (17α-OH pregnenolone). Intriguingly, the protein-protein interaction of cyt b5 decreased the movement and flexibility within the active site of CYP17, however, regions not necessarily obvious for haem-substrate rearrangement were also altered. Single molecule fluorescence revealed CYP17 molecules moved dynamically along the endoplasmic reticulum. Conclusions: MD analyses provided structural insight on the mechanism underlying the allosteric coupling between the cyt b5 to the CYP17 interface and specifically to the active site. Single molecule fluorescence tracking indicated that CYP17 actively moves dynamically in the endoplasmic reticulum. 1. Praporski, S., et al., Organization of Cyt P450 Enzymes Involved in Sex Steroid Synthesis. J. Biol. Chem., 2009. 284 33224-33232. 2. Holien, J.K., et al., A Homodimer Model Can Resolve the Conundrum as to How CPR and Cyt b5 Compete for the Same Binding Site on Cyt P450c17. Curr Protein Pept Sci, 2017. 18 515-521. 3. Simonov, A.N., et al., Mechanistic Scrutiny Identifies a Kinetic Role for Cyte b5 Regulation of Human Cyt P450c17. PLoS ONE, 2015. 10 e0141252. Presentation Date: Thursday, June 15, 2023

Lexical Demands of Academic Written English: From Students’ Assignments to Scholarly Publications

The article presents a lexical study that investigates the lexical demands of academic written texts at different levels of writing. By employing the British National Corpus/ Corpus of Contemporary American English (BNC/COCA) word list and the Academic Word List (AWL), the present study analyzed data from the British Academic Written English (BAWE) corpus, which contained 2,761 student assignments, and the Public Library of Science One (PLOS ONE) corpus which included 4,000 scholarly articles. Results from the analyses demonstrated significant differences in lexical difficulty between students’ assignments and scholarly publications. The proportion of academic vocabulary in written texts was also found to increase as the writers’ levels went up. Cross-discipline comparisons highlighted the difference in lexical difficulties between scientific disciplines.

Effectiveness of the Inquiry Based Learning Model Based on Mobile Learning on Students' Creative Thinking Skills: A Meta-Analysis

This study aims to determine the effect of the inquiry-based learning model based on Mobile Learning on Students' Creative Thinking Skills. This type of research is quantitative research with meta-analysis methods. The data source comes from analysis of national and international journals. The process of searching for data sources through the Google Scholar, ERIC, DOAJ, Wiley, Taylor of Francis and Plos ONE databases. Inclusion criteria are data sources from national and international journals indexed by SINTA; Scopus, WOS, DOAJ and EBSCO, Research must be related to inquiry models, mobile learning and critical thinking skills, Journals must be published in 2017-2023 and have a value (r), (t), or F N ≥ 25. Research results of 18 studies explains that the inquiry-based learning model based on mobile learning has a significant effect on students' creative thinking skills (z = 6.713; p < 0.001; CI 95% (0.784; 1.206). The effect size in this study is high criteria (rRE = 0.885). These findings show the application of mobile learning-based inquiry learning models has a major effect on students' creative thinking skills.