bluuebunny/crossref_metadata_2025_split huggingface dataset:
ScRNA-seq and scATAC-seq reveal that sertoli cell mediate spermatogenesis disorders through stage-specific communications in non-obstructive azoospermia
Authors: Wang Shimin , Wang Hongxian , Jin Bicheng , Yan Hongli , Zheng Qingliang , Zhao Dong 
Published: April 2024

AbstractNon-obstructive azoospermia (NOA) belongs to male infertility due to spermatogenesis failure. However, evidence for cell type-specific abnormalities of spermatogenesis disorders in NOA remains lacking. We performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on testicular tissues from patients with obstructive azoospermia(OA) and NOA. HE staining confirmed the structural abnormalities of the seminiferous tubules in NOA patients. We identified 12 germ cell subtypes (spermatogonial stem cell-0 (SSC0), SSC1, SSC2, diffing-spermatogonia (Diffing-SPG), diffed-spermatogonia (Diffed-SPG), pre-leptotene (Pre-Lep), leptotene-zygotene (L-Z), pachytene (Pa), diplotene (Di), spermatids-1 (SPT1), SPT2, and SPT3) and 8 Sertoli cell subtypes (SC1-SC8). Among them, three novel Sertoli cell subtypes phenotypes were identified, namely SC4/immature, SC7/mature, and SC8/further mature Sertoli cells. For each germ or Sertoli cell subtype, we identified unique new markers, among which immunofluorescence confirmed co-localization of ST3GAL4, A2M, ASB9, and TEX19 and DDX4 (classical marker of germ cell). PRAP1, BST2, and CCDC62 were co-expressed with SOX9 (classical marker of Sertoli cell) in testes tissues also confirmed by immunofluorescence. The interaction between germ cell subtypes and Sertoli cell subtypes exhibits stage-specific-matching pattern, as evidenced by SC1/2/5/7 involving in SSC0-2 development, SC3 participating in the whole process of spermiogenesis, SC4/6 participating in Diffing and Diffed-SPG development, and SC8 involving in the final stage of SPT3. This pattern of specific interactions between subtypes of germ cell and Sertoli cell was confirmed by immunofluorescence of novel markers in testes tissues. The interaction was mainly contributed by Notch1/2/3 signaling. Our study profiled the single-cell transcriptome of human spermatogenesis and provided many potentials molecular markers for developing testicular puncture specific marker kits for NOA patients.Impact statementThe specific interactions between Sertoli cell subtypes and different stages of germ subgroups maintain normal development of germ cells. SC3 subtype absence may be the key factor leading to NOA.
Consensus Guideline for the Management of Peritoneal Metastases in Patients with Neuroendocrine Neoplasms
Authors: Turaga Kiran 
Published: April 2024

ABSTRACTBackgroundNeuroendocrine neoplasms (NEN) with peritoneal metastases (PM) represent a complex clinical challenge due to low incidence and heterogeneous phenotypes. This manuscript describes the results of a national consensus aimed at addressing clinical management of patients with NEN-PMs.MethodsAn update of the 2018 Chicago consensus guidelines was conducted using a modified Delphi technique, encompassing two rounds of voting. The levels of agreement for various pathway blocks were rigorously assessed. Key systemic therapy concepts were summarized by content experts. Supporting evidence was evaluated via a rapid literature review.ResultsOverall, the level of evidence for the management of PM in this disease was universally low. In total, 107 participants responded in the first round, with 88/107 (82%) participating in the second round. Strong consensus (> 90%) was achieved in 5/7 (71%) and 7/7 (100%) blocks in rounds I and II respectively. A multidisciplinary approach including psychosocial and wellness assessments received a strong positive recommendation. Management of NENs with PMs was organized according to disease grade and symptom profiles. In grade 1 and 2 well-differentiated NENs, cytoreductive surgery (CRS) received strong support (>95%) following the management of functional syndromes (if present). For grade 3 well-differentiated NENs, systemic therapy is the primary recommendation, with surgical resection considered in select cases. Poorly differentiated NENs (i.e. neuroendocrine carcinomas) are predominantly treated with chemotherapy.ConclusionGiven limited evidence, the consensus-driven clinical pathway offers vital clinical guidance for the management on NENs with PM. The need for high-quality evidence remains critical to the field.
Consensus Guideline for the Management of Patients with Peritoneal Mesothelioma
Authors:   PSM Writing Group,   PSM Consortium Group, Turaga Kiran K 
Published: April 2024

ABSTRACTBackgroundTreatment of peritoneal mesothelioma (PeM) poses significant challenges owing to its rare incidence, heterogeneity and limited clinical evidence. This manuscript describes results from a national consensus aimed at addressing management of PeM.MethodsAn update of the 2018 Chicago Consensus Guidelines was conducted using a Modified Delphi technique, encompassing two rounds of voting. The levels of agreement for various pathway blocks were assessed.ResultsOf 101 participants responding in the first round of Modified Delphi voting, 95 (94%) responded in the second round. Over 90% consensus was achieved in 5/6 and 6/6 pathway blocks in rounds I and II, respectively. Observation was recommended for benign neoplasms, with guidance for interventions in the presence of symptoms or concerning clinicopathologic features. For malignant pathology, management was outlined based on a multidisciplinary assessment of patient characteristics, disease histology, and predictive success of medical and surgical interventions. Additional emphasis was placed on multimodal therapy for Intermediate-Risk and appropriate High-Risk patients. A rapid review demonstrated limited availability of data and inconclusive findings regarding optimal systemic therapy timing. There was unanimous support for considering clinical trial enrollment.ConclusionsGiven limited evidence, the consensus-driven pathway provides essential guidance regarding the management of PeM. To further direct clinical care, additional dedicated research to generate higher-quality evidence is needed.
Analyzing wav2vec embedding in Parkinson’s disease speech: A study on cross-database classification and regression tasks
Authors: Klempir Ondrej , Krupicka Radim 
Published: April 2024

AbstractAdvancements in deep learning speech representations have facilitated the effective use of extensive datasets comprised of unlabeled speech signals, and have achieved success in modeling tasks associated with Parkinson’s disease (PD) with minimal annotated data. This study focuses on PD non-fine-tuned wav2vec 1.0 architecture. Utilizing features derived from wav2vec embedding, we develop machine learning models tailored for clinically relevant PD speech diagnosis tasks, such as cross-database classification and regression to predict demographic and articulation characteristics, for instance, modeling the subjects’ age and number of characters per second. The primary aim is to conduct feature importance analysis on both classification and regression tasks, investigating whether latent discrete speech representations in PD are shared across models, particularly for related tasks. The proposed wav2vec-based models were evaluated on PD versus healthy controls using three multi-language-task PD datasets. Results indicated that wav2vec accurately detected PD based on speech, outperforming feature extraction using mel-frequency cepstral coefficients in the proposed cross-database scenarios. Furthermore, wav2vec proved effective in regression, modeling various quantitative speech characteristics related to intelligibility and aging. Subsequent analysis of important features, obtained using scikit-learn feature importance built-in tools and the Shapley additive explanations method, examined the presence of significant overlaps between classification and regression models. The feature importance experiments discovered shared features across trained models, with increased sharing for related tasks, further suggesting that wav2vec contributes to improved generalizability. In conclusion, the study proposes wav2vec embedding as a promising step toward a speech-based universal model to assist in the evaluation of PD.
Gastric digestion and changes in serum amino acid concentrations after consumption of casein from cow and goat milk: a randomized crossover trial in healthy men
Authors: van Eijnatten Elise J.M. , Camps Guido , Rombouts Wolf , Pellis Linette , Smeets Paul A.M. 
Published: April 2024

ABSTRACTBackgroundIn vitrostudies show that goat milk proteins form less compact coagulates in the stomach compared to cow milk proteins, which may facilitate gastric digestion and amino acid (AA) absorption. However, this has not been confirmedin vivoin humans.ObjectiveTo examine gastric digestion and changes in AA concentrations after cow milk-derived (cow MC) and goat milk-derived casein (goat MC) ingestion.MethodsIn this single-blind randomized cross-over study 18 men (age 23 ± 1.6 years, BMI 23 ± 1.6 kg/m2) consumed 300 ml of a drink containing 30 g of cow MC or goat MC. Participants underwent gastric MRI scans at baseline and every 10 minutes up to 60 minutes postprandially. Blood was drawn at baseline and up to 4 hours postprandially. In addition, participants verbally rated their appetite after each MRI measurement. Primary outcomes were gastric emptying and AA concentrations. Secondary outcome was gastric coagulation as inferred by image texture metrics.ResultsGastric emptying half-time was 80 ± 25 minutes for goat and 85 ± 24 minutes for cow MC (p = 0.395). In line with this, gastric emptying of the drinks over time was similar (MD 0.77 ml, 95% CI [-6.9, 8.5], p=0.845). Serum essential AA (MD -110 µmol/L, 95% CI [-162, -58]) was higher over time for cow MC (p<0.001). The image texture metric contrast was lower for cow MC (MD 0.010, 95% CI [0.001, 0.020], p=0.036).ConclusionCow MC and goat MC have different coagulating properties, as inferred by AA concentrations and supported by image texture analysis. This did not influence overall gastric emptying or the emptying of the liquid and coagulated fractions, which were similar. This warrants furtherin vivoresearch on casein coagulation in the food matrix to help determine the optimal use for cow and goat milk and their protein fractions.Financial support: the study was funded by Ausnutria Dairy Corporation Ltd.Clinical trial registry number: NL8137 (Netherlands Trial Registry), accessible throughhttps://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON28580
Pregnancy episodes in All of Us: Harnessing multi-source data for pregnancy-related research
Authors: Smith Louisa H. , Wang Wanjiang , Keefe-Oates Brianna 
Published: April 2024

ABSTRACTObjectiveThe National Institutes of Health’s All of Us Research Program addresses gaps in biomedical research by collecting health data from diverse populations. Pregnant individuals have historically been underrepresented in biomedical research, and pregnancy-related research is often limited by data availability, sample size, and inadequate representation of the diversity of pregnant people. We aimed to identify pregnancy episodes with high-quality electronic health record (EHR) data in All of Us Research Program data and evaluate the program’s utility for pregnancy-related research.Materials and MethodsWe used an algorithm to identify pregnancy episodes in All of Us EHR data. We described these pregnancies, validated them with additional data, and compared them to national statistics.ResultsOur study identified 18,970 pregnancy episodes from 14,234 participants; other possible pregnancy episodes had low-quality or insufficient data. Validation against people who reported a current pregnancy on an All of Us survey found low false positive and negative rates. Demographics were similar in some respects to national data; however, Asian-Americans were underrepresented, and older, highly educated pregnant people were overrepresented.DiscussionOur approach demonstrates the capacity of All of Us to support pregnancy research and reveals the diversity of the pregnancy cohort. However, we noted an underrepresentation among some demographics. Other limitations include measurement error in gestational age and limited data on non-live births.ConclusionThe wide variety of data in the All of Us program, encompassing EHR, survey, genomic, and Fitbit data, offers a valuable resource for studying pregnancy, yet care must be taken to avoid biases.
allofus: An R package to facilitate use of the All of Us Researcher Workbench
Authors: Smith Louisa H. , Cavanaugh Robert 
Published: April 2024

ABSTRACTObjectiveWe aimed to increase research and training capacity for the All of Us community through an R package designed to reduce barriers to entry to the Researcher Workbench.Materials and MethodsWe developed the open-source R packageallofus, available on the R package repository CRAN. The package provides functions that address common challenges we encountered while working with All of Us Research Program data. We tested the package with standard R unit tests and in real research projects.ResultsWe describe how the package functions allow for an efficient workflow. We demonstrate the package’s utility by creating a cohort of All of Us participants with one year of electronic health record data prior to survey completion and no previous diagnosis of Type 2 diabetes.DiscussionDespite the program’s easy-to-use tools like the Cohort Builder, using All of Us data for complex research questions requires a relatively high level of technical expertise. We developed an initial set of functions that solve problems we experienced with our own research and in mentoring student projects. In conjunction with the tutorials provided with the package, these tools can reduce the barrier for entry into the All of Us research community. The package will continue to grow and develop with the All of Us Research Program.ConclusionTheallofusR package can help build community research capacity by increasing access to the All of Us Research Program data, the efficiency of its use, and the rigor and reproducibility of the resulting research.
Advancing Bloodstream Infection Prediction Using Explanable Artificial Intelligence Framework
Authors: Bopche Rajeev , Gustad Lise Tuset , Afset Jan Egil , Ehrnström Birgitta , Damås Jan Kristian , Nytrø Øystein 
Published: April 2024

AbstractBloodstream infections (BSIs) represent a critical public health concern, primarily due to their rapid progression and severe implications such as sepsis and septic shock. This study introduces an innovative Explanable Artificial Intelligence (XAI) framework, leveraging historical electronic health records (EHRs) to enhance BSI prediction. Unlike traditional models that rely heavily on real-time clinical data, our XAI-based approach utilizes a comprehensive dataset incorporating demographic data, laboratory results, and full medical histories from St. Olavs Hospital, Trondheim, Norway, covering 35,591 patients between 2015 and 2020. We developed models to differentiate between high-risk and low-risk BSI cases effectively, optimizing healthcare resource allocation and potentially reducing healthcare costs. Our results demonstrate superior predictive accuracy, particularly the tree-based models, which significantly outperformed contemporary models in both specificity and sensitivity metrics.Author SummaryIn this research, we have developed a new tool that uses artificial intelligence to better predict bloodstream infections, which can lead to serious conditions like sepsis if not quickly identified and treated. It is the first of its kind framework that analyzes past health records and helps identify patients who are at high risk of infection more accurately than existing tools. Unlike existing tools our framework can be implemented at any stage of the patient trajectory and is the only framework to achieve good accuracy without the use of intimate patient features such as vital signs. This ability could enable doctors to prioritize care more pre-emptively, effectively, potentially saving lives and reducing unnecessary medical tests. Our approach is designed to be easily understood and used by both medical professionals and those with little technical expertise, making it a valuable addition to hospital systems.
Facilitators and barriers to contraception access and use for Hispanic American adolescent women: An integrative literature review
Authors: Batek Lindsay M. , Leblanc Natalie M. , Alio Amina P. , Stein Karen F. , McMahon James M. 
Published: April 2024

AbstractStatement of the ProblemHispanic American adolescents experience high rates of pregnancy with profound consequences. Compared with White teens, Hispanic teens use contraception less frequently and often choose less effective forms of contraception. Access to contraception is a primary barrier to use which contributes to relatively high and disparate rates of pregnancy in Hispanic teens. This integrative review identifies facilitators and barriers of contraception access and use for Hispanic women, 13-17 years of age, living in the U.S.MethodologyFollowing the Whittemore and Knafl (2005) methodology and PRISMA guidelines, peer reviewed studies were retrieved from PUBMED, CINAHL and EMBASE. TheMixed Methods Appraisal Toolwas used to assess the study quality and thematic analysis was used to categorize barriers and facilitators.FindingsOf 131 studies retrieved, 16 met inclusion criteria. Individual, interpersonal and healthcare provider factors were identified as primary categories of barriers and facilitators with contextual issues comprising an additional barrier category. Individual level barriers were disproportionately represented and further categorized into themes: beliefs/misconceptions, dislike of contraception, pregnancy risk perception, lack of knowledge, and lack of control. The most frequently reported facilitators were perceived parent comfort discussing sexual health and past experience of pregnancy.DiscussionLimitations in this review may stem from heterogeneity in the acculturation and geography of participants and analysis by a single reviewer. Implications include considering the range of information sources and the influence they have on risk perception and risk mitigation for this population.Conclusion & SignificanceAdolescents describe many modifiable influences on contraception access and use. Misperceptions related to contraception, stemming from beliefs and perceptions, can be corrected through increased access to reliable sources of sex education, parental support, and direct access to nurses and healthcare providers. Awareness of these influences can inform further research and intervention development to address these health disparities.
Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer’s Disease Cohorts of Diverse Genetic Ancestries
Authors: Griswold Anthony J. , Rajabli Farid , Gu Tianjie , Arvizu Jamie , Golightly Charles G. , Whitehead Patrice L. , Hamilton-Nelson Kara L. , Adams Larry D. , Sanchez Jose Javier , Mena Pedro R. , Starks Takiyah D. , Illanes-Manrique Maryenela , Silva Concepcion , Bush William S. , Cuccaro Michael L. , Vance Jeffery M. , Cornejo-Olivas Mario R , Feliciano-Astacio Briseida E. , Byrd Goldie S. , Beecham Gary W. , Haines Jonathan L. , Pericak-Vance Margaret A. 
Published: April 2024

AbstractIntroductionPlasma phosphorylated threonine-181 of Tau and amyloid beta are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, generalizability of existing biomarker data is not assured.MethodsIn 2,086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvians) we measured plasma pTau-181 and Aβ42/Aβ40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed.ResultspTau-181 and Aβ42/Aβ40 were consistent across cohorts. Higher levels of pTau181 were associated with AD while Aβ42/Aβ40 had minimal differences. Correspondingly, pTau-181 had greater predictive value than Aβ42/Aβ40, however, the area under the curve differed between cohorts.DiscussionpTau-181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but predictive value may differ. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.
Immune-developmental processes contribute to schizophrenia risk: insights from a genetic overlap study with height
Authors: Romero Cato , de Leeuw Christiaan , Schipper Marijn , Maciel Bernardo de A.P.C. , van den Heuvel Martijn P. , Brouwer Rachel M. , Smit August B. , Koopmans Frank , Posthuma Danielle , van der Sluis Sophie 
Published: April 2024

BackgroundShorter stature has been phenotypically linked to increased prevalence of schizophrenia (SCZ), but the nature of this association is unknown.MethodsUsing genome-wide genetic data, we studied the SCZ-height relationship on a genetic level. Applying novel genetic methods and tools, we analyzed gene-sets, tissue-types, cell-types, local genetic correlation, conditional genetic analyses, and fine-mapping of effector-genes to scrutinize the SCZ-height relationship.ResultsWe identified 142 genes statistically associated with both SCZ and height and found enrichment in immune response gene-sets. Genetic annotations implicated the pituitary and specifically mesenchymal stem cells for height and thyrotropic cells for SCZ. While the global SCZ-height genetic correlation was nonsignificant, 9 genomic regions showed robust local genetic correlations (7 negative, 6 in the MHC-region). The shared genetic signal for SCZ and height within the 6 MHC-regions was partially explained by mutual genetic overlap with white blood cell count, particularly lymphocytes. Fine-mapping prioritized 3 shared effector-genes (GIGYF2,HLA-C, andLIN28B) involved in immune response sensitivity and development of immune and pituitary cell-types.ConclusionsOverall, our findings suggest an involvement during height-development of thyrotropic cells and immune response sensitivity contributing towards risk of SCZ.