Quantitative Label-Free Proteomic Analysis of Mouse Ovarian Antral Follicles Following Oral Exposure to a Human Relevant Mixture of Three Phthalates.

Dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), and benzyl butyl phthalate (BBP) are used in personal and medical care products. In the ovary, antral follicles are essential for steroidogenesis and ovulation. DBP, BBP, and DEHP are known to inhibit mouse antral follicle growth and ovulation in vitro, and associate with decreased antral follicle counts in women. Given that the in vivo effects of a three-phthalate mixture on antral follicles are unknown, we evaluated the effects of a human relevant mixture of DBP, BBP, and DEHP on ovarian follicles through proteome profiling analysis. Adult CD-1 female mice were fed corn oil (vehicle), or two dose levels of a phthalate mixture based on estimated exposures in general (32 µg/kg/day; PHT 32) and occupationally exposed (500 µg/kg/day; PHT 500) populations for 10 days. Antral follicles (>250 µm) were isolated and subjected to proteome profiling via label-free tandem mass spectrometry. A total of 5,417 antral follicle proteins were detected, of which 194 were differentially abundant between vehicle and PHT 32, and 136 between vehicle and PHT 500. Bioinformatic analysis revealed significantly different responses between the two phthalate doses. Protein abundance differences in the PHT 32 exposure mapped to cytoplasm, mitochondria, and lipid metabolism; while those in the PHT 500 exposure mapped to cytoplasm, nucleus, and phosphorylation. When both doses altered proteins mapped to common processes, the associated predicted transcription factors were different. These findings provide novel mechanistic insight into phthalate-associated, ovary-driven reproductive outcomes in women.

Strengthening a culture of research dissemination: A narrative report of research day at King Faisal Hospital Rwanda, a tertiary-level teaching hospital in Rwanda.

BACKGROUND: There are significant gaps in research output and authorship in low- and middle-income countries. Research dissemination events have the potential to help bridge this gap through knowledge transfer, institutional collaboration, and stakeholder engagement. These events may also have an impact on both clinical service delivery and policy development. King Faisal Hospital Rwanda (KFH) is a tertiary-level teaching hospital located in Kigali, Rwanda. To strengthen its research dissemination, KFH conducted an inaugural Research Day (RD) to disseminate its research activities, recognize staff and student researchers at KFH, define a research agenda for the hospital, and promote a culture of research both at KFH and in Rwanda. METHODS: RD was coordinated by an interdisciplinary committee of clinical and non-clinical staff at KFH. Researchers were encouraged to disseminate their research across all disciplines. Abstracts were blind reviewed using a weighted rubric and ranked by overall score. Top researchers were also awarded and recognized for their work, and equity and inclusion was at the forefront of RD programming. RESULTS: RD had over 100 attendees from KFH and other public, private, and academic institutions. Forty-seven abstracts were submitted from the call for abstracts, with the highest proportion studying cancer (17.02%) and sexual and reproductive health (10.64%). Thirty-seven researchers submitted abstracts, and most of the principal investigators were medical doctors (35.14%), allied health professionals (27.03%), and nurses and midwives (16.22%). Furthermore, 30% of principal investigators were female, with the highest proportion of them being nurses and midwives (36.36%). CONCLUSION: RD is an effective way to disseminate research in a hospital setting. RD has the potential to strengthen the institution's research agenda, engage the community in ongoing projects, and provide content-area support to researchers. Equity and inclusion should be at the forefront of research dissemination, including gender equity, authorship representation, and the inclusion of interdisciplinary health professionals. Stakeholder engagement can also be utilized to strengthen institutional research collaboration for greater impact.

Portable X-ray fluorescence spectrometry: a cost-effective method for analysing trace metals in deposited dust.

For projects requiring extensive environmental sampling and rapid decision-making to identify trace metal contamination using dust wipes, the cost and time required for wet chemistry analysis can be prohibitive. Under such circumstances there is a need for a suitable screening method that is cost-effective, efficient, and portable. To address this need, this study investigated the utility of portable X-ray fluorescence (pXRF) for the analysis of trace metals in dust wipes. Here, 316 dust wipe samples from three different geographical settings co-located with mining and smelting operations were investigated for their trace metal loadings (µg m-2) of arsenic (As), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) using pXRF. Results collected using pXRF were compared against inductively coupled plasma mass spectrometry (ICP-MS) concentrations using matched dust wipes (n = 87) to assess reproducibility. A subset of dust wipes (n = 4) were subject to different pXRF analytical scenarios (ranging from 1 to 12 pXRF measurements) using a standardised test duration of 30 seconds to identify the most efficient number of tests for analytical precision. Conducting four pXRF tests on a single wipe (total exposure time of 120 seconds) returned comparable results to ICP-MS and was adopted for analysis of all samples. Results from dust wipes analysed with both ICP-MS and pXRF (n = 87) showed moderate to strong Spearman Rho correlations (rs = 0.489-0.956, p < 0.01) and linear regression coefficients of variation demonstrated good agreement between methods (R2 = 0.432-0.989, p < 0.05). Linear regression equations were used to correct pXRF data to the ICP-MS dust wipe data for samples analysed by both approaches, and applied to pXRF data that were not subject to ICP-MS analysis (n = 229). Application of the correction formula resulted in a substantial improvement of pXRF's accuracy and precision, confirming its effectiveness for assessing trace metals in dust wipes.

CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice.

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.

Biparametric versus multiparametric MRI for the detection of clinically significant prostate cancer in a diverse, multiethnic population.

PURPOSE: There is not yet satisfactory performance data comparing multiparametric MRI (mpMRI) versus biparametric MRI (bpMRI) for detecting prostate cancer (PCa), particularly in high-risk populations. We compared both protocols for detecting overall PCa and clinically significant PCa (CS-PCa; defined as Grade Group ≥ 2) in a multiethnic urban population. METHODS: We retrospectively reviewed electronic medical record data from men who underwent image-guided fusion prostate biopsy (FB) between 2016 and 2021 at our institution. Patient characteristics, Prostate Imaging Reporting and Data System (PI-RADS) scores, and FB outcomes were analyzed based on MRI protocol. Multivariate mixed-effects logistic regression models were used to examine associations of bpMRI versus mpMRI for detecting overall PCa and CS-PCa in targeted lesions, among all patients and stratified by race/ethnicity. RESULTS: Overall, 566 men (44.0% Non-Hispanic Black [NHB]; 27.0% Hispanic) with 975 PI-RADS 3-5 lesions on MRI underwent FB. Of these, 312 (55%) men with 497 lesions underwent mpMRI and 254 (45%) men with 478 lesions underwent bpMRI. On multivariate analyses among all men, the odds of detecting overall PCa (OR = 1.18, 95% CI: 1.05-3.11, p = 0.031) and CS-PCa (OR = 2.15, 95% CI: 1.16-4.00, p = 0.014) on FB were higher for lesions identified on bpMRI than mpMRI. When stratified by race/ethnicity, the odds of detecting overall PCa (OR = 1.86; p = 0.15) and CS-PCa (OR = 2.20; p = 0.06) were not statistically different between lesions detected on bpMRI or mpMRI. CONCLUSION: BpMRI has similar diagnostic performance to mpMRI in detecting overall and CS-PCa within a racially/ethnically diverse population. BpMRI can be utilized for evaluating suspected CS-PCa among NHB and Hispanic men.

Early Life Adversity Predicts Reduced Hippocampal Volume in the Adolescent Brain Cognitive Development Study.

PURPOSE: Cross-sectional studies in adults have demonstrated associations between early life adversity (ELA) and reduced hippocampal volume, but the timing of these effects is not clear. The present study sought to examine whether ELA predicts changes in hippocampal volume over time in a large sample of early adolescents. METHODS: The Adolescent Brain Cognitive Development Study provides a large dataset of tabulated neuroimaging, youth-reported adverse experiences, and parent-reported financial adversity from a sample of children around the United States. Linear mixed effects modeling was used to determine the relationship between ELA and hippocampal volume change within youth (n = 7036) from ages 9-10 to 11-12 years. RESULTS: Results of the models indicated that the number of early adverse events predicted bilateral hippocampal volume change (ß = -0.02, t = -2.02, p < .05). Higher adversity was associated with lower hippocampal volume at Baseline (t = 5.55, p < .01) and at Year 2 (t = 6.14, p < .001). DISCUSSION: These findings suggest that ELA may affect hippocampal development during early adolescence. Prevention and early intervention are needed to alter the course of this trajectory. Future work should examine associations between ELA, hippocampal development, and educational and socioemotional outcomes.

Concurrent RB1 Loss and BRCA-Deficiency Predicts Enhanced Immunological Response and Long-Term Survival in Tubo-Ovarian High-Grade Serous Carcinoma.

PURPOSE: To evaluate RB1 expression and survival across ovarian carcinoma histotypes, and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 primary HGSC to characterize tumors with concurrent BRCA-deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC, but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared to patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA-deficiency correlated with transcriptional markers of enhanced interferon response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA-deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Immature platelet counts in transfused platelet units given to neonates.

BACKGROUND: Immature platelets, young and large platelets recently released from the bone marrow, have gained interest over the last decade as a clinically informative variable during thrombocytopenic presentations. These immature platelets are found in all donated platelet units, however, the role, if any, that these younger platelets play post transfusion is not known. It has also been reported that the immune response can affect responses to platelet transfusions. Thus, we looked at PLT increments in a cohort of neonates receiving platelet transfusions in our neonatal intensive care unit. METHODS: During a twelve-month period, platelet transfusions received by neonates born and not discharged from our institution at time of transfusion were retrospectively analyzed. In the study period a total of 33 patients received either a single or multiple transfusions during their hospitalization, for a total of 100 transfusion events. RESULTS: The cohort was mostly premature neonates with a mean gestational age of 29.6 weeks. The units transfused appeared to have a broad range of absolute immature platelet counts (A-IPC) but overall, it was similar between those receiving single or multiple transfusions. Considering that platelet count was similar among aliquots transfused, it appeared that count increments were influenced by higher A-IPC content of the aliquot especially among 2nd trimester and 3rd trimester premature neonates. Patients with higher baseline platelet count (PLT) tended to receive a single transfusion aliquot while those receiving multiple transfusions had lower baseline PLT (p = 0.0022). Looking at aliquot dose, regardless if receiving a single or multiple transfusions, younger patients received incrementally higher dose (ml/kg) with each transfusion. CONCLUSIONS: A-IPC in platelet aliquots transfused to neonates may influence post-transfusion PLT. Full effect of A-IPC in platelet aliquots may not be seen since irradiation of units may hamper immature platelets viability and function. Further research is needed to determine if A-IPC plays an active role to limit the need for further transfusions of patients receiving transfusions.

The tidyomics ecosystem: Enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis, and integration. Addressing these challenges, Bioconductor1 provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming2 offers a revolutionary standard for data organisation and manipulation. Here, we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning, and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analysing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas3, spanning six data frameworks and ten analysis tools.

The tidyomics ecosystem: enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.

Association of Unmet Social Needs With Missed In-Person Urology Clinic Appointments.

INTRODUCTION: Social determinants of health (SDH) are nonbiologic influencers of disease and health care disparities. This study focused on understanding the association between SDH and urology clinic "no-show" visits within a diverse urban population. METHODS: We retrospectively identified patients scheduled for urology clinic visits from October 2015 to June 2022 who completed a 10-question social needs screener. For each patient, demographic variables, and number of missed clinic appointments were abstracted. Multivariable logistic regression was performed to determine the association of unmet social needs and no-shows. RESULTS: Of 5761 unique patients seen in clinic, 5293 completed a social needs screener. Respondents were most commonly male (62.8%), Hispanic (50.3%), English-speaking (75.5%), and insured by Medicare (46.0%). Overall, 8.2%, 4.6%, and 6.1% reported 1, 2, and 3+ unmet social needs, respectively. Most patients (61.7%) had 0 no-shows; 38.3% had 1+ no-shows. Between the 0 and 1+ no-show groups, we found significant differences with respect to gender (P =.05), race/ethnicity (P = .002), preferred language (P = .006), insurance payer (P < .001), SDH status (P = .003), and total number of unmet social needs (P = .006). On multivariable analysis, patients concerned about housing quality (odds ratio [OR] = 1.50, P = .002), legal help (OR = 1.53, P = .009), and with 3+ unmet social needs (OR = 1.39, P = .006) were more likely to have 1+ no-shows. CONCLUSIONS: Unmet social needs were associated with increased no-show urology clinic visits. Routine social needs screening could identify at-risk patients who would benefit from services. This may be particularly pertinent for patients with urgent diagnoses or those requiring frequent office visits where missing appointments could impact morbidity and mortality.

Piloting a brief assessment to capture consumption of whole plant food and water: version 1.0 of the American College of Lifestyle Medicine Diet Screener (ACLM Diet Screener).

Background: Despite the availability of various dietary assessment tools, there is a need for a tool aligned with the needs of lifestyle medicine (LM) physicians. Such a tool would be brief, aimed at use in a clinical setting, and focused on a "food as medicine" approach consistent with recommendations for a diet based predominately on whole plant foods. The objective of this study is to describe the development and initial pilot testing of a brief, dietary screener to assess the proportion of whole, unrefined plant foods and water relative to total food and beverage intake. Methods: A multidisciplinary study team led the screener development, providing input on the design and food/beverage items included, and existing published dietary assessment tools were reviewed for relevance. Feedback was solicited from LM practitioners in the form of a cross-sectional survey that captured information on medical practice, barriers, and needs in assessing patients' diets, in addition to an opportunity to complete the screener and provide feedback on its utility. The study team assessed feedback and revised the screener accordingly, which included seeking and incorporating feedback on additional food items to be included from subject matter experts in specific cultural and ethnic groups in the United States. The final screener was submitted for professional design, and scoring was developed. Results: Of 539 total participants, the majority reported assessing diet either informally (62%) or formally (26%) during patient encounters, and 73% reported discussing diet with all or most of their patients. Participants also reported facing barriers (80%) to assessing diet. Eighty-eight percent believed the screener was quick enough to use in a clinical setting, and 68% reported they would use it. Conclusion: The ACLM Diet Screener was developed through iterative review and pilot testing. The screener is a brief, 27-item diet assessment tool that can be successfully used in clinical settings to track patient dietary intakes, guide clinical conversations, and support nutrition prescriptions. Pilot testing of the screener found strong alignment with clinician needs for assessing a patient's intake of whole plant food and water relative to the overall diet. Future research will involve pilot testing the screener in clinical interventions and conducting a validation study to establish construct validity.

The Learning Curve From Converting From Fluoroscopic to Robotic-Assisted Direct Anterior Total Hip Arthroplasty.

INTRODUCTION: Robotic-assisted total hip arthroplasty (RA-THA) provides an alternative to fluoroscopic guidance, thus reducing radiation exposure for orthopaedic surgeons. This study was performed to assess the learning curve associated with the adoption of RA-THA using the direct anterior approach (DAA) with regard to surgical time, use of fluoroscopy, and implant placement. In addition, we compared complication rates and patient-reported outcome scores between both cohorts. A case report of an RA-THA is also presented. MATERIALS AND METHODS: This was a retrospective, non-randomized evaluation of the learning curve by assessing surgical time on a consecutive series of 89 DAA cases performed by a single surgeon. There were 53 cases that had manual THA with fluoroscopy and 36 cases with RA-THA. All cases had an acetabular component placement target of 40° inclination and 20° anteversion. An independent reviewer blinded to surgical technique used the Widmer method to measure acetabular inclination and version. Patient demographics were similar for both groups. RESULTS: The mean surgical time for the manual fluoroscopic group was 88 ± 21 minutes and 101 ± 14 minutes for the RA-THA group. After 15 RA-THA cases, surgical time reached time neutral compared to the manual fluoroscopic group. The first 17 RA-THA cases utilized fluoroscopy to verify implant position until the surgeon became comfortable with the accuracy of the RA-THA system. After case 17, fluoroscopy was abandoned in all subsequent RA-THA cases. The mean radiation dose delivered to the surgical field was 5.61 ± 5.71 mGy. Manual THA with fluoroscopy resulted in a mean acetabular inclination of 41.3 ± 4.4° and a mean anteversion of 22.4 ± 3.0°. The RA-THA resulted in a mean acetabular inclination of 42.0 ± 4.2° and a mean anteversion of 22.3 ± 3.9°. There was no noted change in RA-THA placement accuracy after case 17, when fluoroscopy was eliminated from the surgical workflow. There were no statistical differences between the manual fluoroscopic and robotic-assisted groups with respect to complications and clinical PROM outcomes. CONCLUSION: The DAA THA can be performed with RA-THA and achieve comparable acetabular placement without fluoroscopy. Surgical time was higher for the RA-THA group during the learning curve, but then decreased and was consistent with the manual fluoroscopic group after 15 cases.

Evaluation of the Impact of Concentration and Extraction Methods on the Targeted Sequencing of Human Viruses from Wastewater.

Sequencing human viruses in wastewater is challenging due to their low abundance compared to the total microbial background. This study compared the impact of four virus concentration/extraction methods (Innovaprep, Nanotrap, Promega, and Solids extraction) on probe-capture enrichment for human viruses followed by sequencing. Different concentration/extraction methods yielded distinct virus profiles. Innovaprep ultrafiltration (following solids removal) had the highest sequencing sensitivity and richness, resulting in the successful assembly of several near-complete human virus genomes. However, it was less sensitive in detecting SARS-CoV-2 by digital polymerase chain reaction (dPCR) compared to Promega and Nanotrap. Across all preparation methods, astroviruses and polyomaviruses were the most highly abundant human viruses, and SARS-CoV-2 was rare. These findings suggest that sequencing success can be increased using methods that reduce nontarget nucleic acids in the extract, though the absolute concentration of total extracted nucleic acid, as indicated by Qubit, and targeted viruses, as indicated by dPCR, may not be directly related to targeted sequencing performance. Further, using broadly targeted sequencing panels may capture viral diversity but risks losing signals for specific low-abundance viruses. Overall, this study highlights the importance of aligning wet lab and bioinformatic methods with specific goals when employing probe-capture enrichment for human virus sequencing from wastewater.

Transnasal Endoscopy Acquires Esophageal Biopsies Adequate for Comprehensive Pathology Evaluation in Patients With Eosinophilic Esophagitis.

BACKGROUND: Transnasal endoscopy (TNE) does not require general anesthesia, an attractive characteristic for monitoring eosinophilic esophagitis (EoE). We evaluated the adequacy of TNE-obtained esophageal biopsies using the EoE Histology Scoring System (EoEHSS). METHODS: The Cincinnati Center for Eosinophilic Disorders database was searched for esophageal biopsies obtained by the same endoscopist, using either TNE or conventional endoscopy (CE). Whole-slide biopsy images were evaluated. The Mann-Whitney test was used for median (interquartile range) values and Fisher exact test for categorical variables. P ≤ .05 was considered significant. RESULTS: Median age (P = .82) or height (P = .83) did not differ between TNE (n = 17) and CE (n = 17) groups. Although median largest piece size (mm2) differed between the groups (TNE: 0.59 (0.45, 0.86), CE: 2.24 (1.09, 2.82), P < .001), all 8 EoEHSS features were evaluated in each group; only 1 feature (lamina propria fibrosis) was missing in both groups (TNE: 19/34, CE: 11/34, P = .09). The median peak eosinophil count/high-power field differed (TNE: 3 (0, 29), CE: 16 (1, 66), P = .03), but overall grade (TNE: 0.17 (0.10, 0.29), CE: 0.22 (0.14, 0.46), P = .12), stage (TNE: 0.14 (0.10, 0.24), CE: 0.20 (0.10, 0.43), P = .15), and non-eosinophil-related individual EoEHSS scores did not differ. CONCLUSIONS: TNE- and CE-obtained esophageal biopsies are similarly sufficient for evaluation of key pathological features in EoE.

Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science. Additionally, we describe applications of network science to foster, maintain and expand cultural changes related to scientific rigour and opportunities to embed rigourous practices into didactic courses, training experiences and degree programme requirements. We hope this piece provides a primer for the wider research community on current discussions and actions and inspires individuals to build, join or expand collaborative networks within their own institutions that prioritize rigourous research practices.

Shape-Versatile Fixed Cellular Materials for Multiple Target Immunomodulation.

Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell-based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. 3D cellular materials may be useful to prolong the effect of cellular therapies and offer the possibility of creating structural volumetric constructs. Here, the manufacturing of shape-versatile fixed cell-based materials with immunomodulatory properties is reported. Living cell aggregates with different shapes (spheres and centimeter-long fibers) are fixed using a method compatible with maintenance of structural integrity, robustness, and flexibility of 3D constructs. The biological properties of living cells can be modulated before fixation, rendering an in vitro anti-inflammatory effect toward human macrophages, in line with a decreased activation of the nuclear factor kappa B (NF-κB) pathway that preponderantly correlated with the surface area of the materials. These findings are further corroborated in vivo in mouse skin wounds. Contact with fixed materials also reduces the proliferation of activated primary T lymphocytes, while promoting regulatory populations. The fixation of cellular constructs is proposed as a versatile phenotypic stabilization method that can be easily implemented to prepare immunomodulatory materials with therapeutic potential.