bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiopathic Ileal Ulceration After Intestinal Transplantation
Authors: Hussan Elsadig , Kroemer Alexander , Elsabbagh Ahmed M. , Khan Khalid M. , Yazigi Nada A. , Ekong Udeme D. , Subramanian Sukanya , Ghobrial Shahira S. , Guerra Juan-Francisco , Fishbein Thomas M. , Matsumoto Cal S. , Kaufman Stuart S. 
Published: October 2023

Background.
Idiopathic ileal ulceration after intestinal transplantation (ITx) has been discussed infrequently and has an uncertain natural history and relation to graft rejection. Herein, we review our experience with this pathology.

Methods.
We retrospectively reviewed 225 ITx in 217 patients with minimum 1 y graft survival. Routine graft endoscopy was conducted up to twice weekly within the first 90 d after ITx, gradually decreasing to once yearly. Risks for ulceration over time were evaluated using Cox regression.

Results.
Of 93 (41%) patients with ulcers, 50 were found within 90 d after ITx mostly via ileoscopy; delayed healing after biopsy appeared causal in the majority. Of the remaining 43 patients with ulcers found >90 d after ITx, 36 were after ileostomy closure. Multivariable modeling demonstrated within 90-d ulcer associations with increasing patient age (hazard ratio [HR], 1.027; P < 0.001) and loop ileostomy (versus Santulli ileostomy; HR, 0.271; P < 0.001). For ulcers appearing after ileostomy closure, their sole association was with absence of graft colon (HR, 7.232; P < 0.001). For ulcers requiring extended anti-microbial and anti-inflammatory therapy, associations included de novo donor-specific antibodies (HR, 3.222; P < 0.007) and nucleotide oligomerization domain mutations (HR, 2.772; P < 0.016). Whole-cohort post-ITx ulceration was not associated with either graft rejection (P = 0.161) or graft failure (P = 0.410).

Conclusions.
Idiopathic ulceration after ITx is relatively common but has little independent influence on outcome; risks include ileostomy construction, colon-free ITx, immunologic mutation, and donor sensitization.
The role of polycystic ovary syndrome in preclinical left ventricular diastolic dysfunction: an echocardiographic approach: a systematic review and meta-analysis
Authors: Mirzohreh Seyedeh-Tarlan , Panahi Padideh , Zafardoust Hooman , Zavvar Morteza , Fathi Nima , Dehghan Mahshid , Sarbakhsh Parvin 
Published: October 2023

Background
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of childbearing age, causing hormonal imbalances, reproductive issues, and metabolic disturbances. Women with PCOS have an increased risk of cardiovascular disease due to insulin resistance, obesity, and hyperandrogenism. Detecting impaired left ventricular (LV) function is important in managing this condition. Echocardiography, a non-invasive imaging technique, can effectively detect LV dysfunction.

Aim
The goal of this systematic review was to assess whether there are any variations in echocardiographic measures between women with PCOS and those without the condition in order to determine the potential impact of PCOS on LV function.

Methods
This review followed the PRISMA reporting guidelines. A thorough search of databases including PubMed, Scopus, Web of Science, and Cochrane was conducted. The quality of the selected studies was assessed using the Joanna Briggs Institute appraisal instruments. After applying strict eligibility criteria, data were extracted and organized in Microsoft Excel sheets. Review Manager (RevMan) software was used for the analysis.

Results
Analysis of 29 studies revealed significant differences in echocardiographic measures related to diastolic function between women with PCOS and healthy controls. However, there were no significant differences in measures of systolic function.

Conclusion
These findings indicate that PCOS may be linked to impaired LV function, thereby increasing the risk of cardiovascular disease. Further research is necessary to better understand this association and its clinical implications. Early detection and management of PCOS could potentially help prevent cardiovascular complications in affected women.
Systems genetics identifies the association between Enc1 and cognitive function in the hippocampus
Authors: He Hongjie , Tao Ran , Han Zhe , Yin Quanting , Pan Shuijing , Lu Lu , Bajpai Akhilesh Kumar , Mi Jia , Qi Donglai , Li He , Xu Fuyi 
Published: October 2023

AbstractEctodermal-Neural Cortex 1 (ENC1) is expressed in multiple regions of the brain, including the hippocampus. However, knowledge about its function has been well explored only in the context of peroxidative stress and cancer. In this study, we investigated the association of hippocampal Enc1 with cognitive function in BXD mice. We performed Pearson correlation, phenotype-wide association analysis (PheWAS), expression-Based PheWAS, pathway enrichment, and protein interaction networks on Enc1 and BXD phenotypes/transcriptome of the hippocampus, and the results indicated that Enc1 is inextricably linked to cognitive performance. In addition, we found that most of theEnc1co-expressed genes were highly expressed in GABAergic neuronal cells. Expression quantitative trait loci analysis indicated that Enc1 wascis-regulated in the hippocampus of mice as well as human. Genome-wide association analysis revealed ENC1 to be significantly associated with cognitive-related traits, including age-related cognitive changes etc. In conclusion, our findings demonstrated thatEnc1is involved in cognitive functions mainly in hippocampal GABAergic neuronal cells through neurogenesis, synaptic signaling, and CGMP-PKG signaling pathways, and interacts with the neurological function-related genes.
In-vitro digestion models to examine the effects of Plant-Based Meat substitutes on Gut Microbial Metabolites
Authors: Izquierdo-Sandoval David , Duan Xiang , Fryganas Christos , Portolés Tania , Sancho Juan Vicente , Rubert Josep 
Published: October 2023

AbstractThe increasing popularity of plant-based meat alternatives (PBMAs) has triggered a contentious debate about their impact on gut health in comparison to traditional animal-based meats. This study investigates the digestibility and bioavailability of a beef patty, a commercial PBMA, and a homemade pea protein-based ’patty’ by examining their influence on gut microbial metabolism. Fecal samples from five different donors were utilized to replicate colonic fermentation in vitro, with samples collected at various time points (0, 6, 12, 24, 32, and 48 hours). A rapid biochemical profiling, comparing red meat and meat analogs in terms of traditional biomarkers of gut health (ammonia, phenols, indoles, pH, and short-chain fatty acids), was conducted. Additionally, an untargeted metabolomics workflow specially designed for time-series studies, utilizing ultra-high performance liquid chromatography hyphenated to a quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS), was implemented to assess differences in terms of protein-related gut microbial metabolites (GMMs). The findings of this approach revealed notable differences in the production of intestinal inflammation markers, metabolites related to the carnitine pathways, and GMMs with signaling functions in the intestinal tract during the fermentation of animal- and plant-based burgers.
Mycobacterial DnaQ is an Alternative Proofreader Ensuring DNA Replication Fidelity
Authors: Deng Ming-Zhi , Liu Qingyun , Cui Shu-Jun , Fu Han , Gan Mingyu , Xu Yuan-Yuan , Cai Xia , Sha Wei , Zhao Guo-Ping , Fortune Sarah M. , Lyu Liang-Dong 
Published: October 2023

AbstractRemove of mis-incorporated nucleotides ensures replicative fidelity. Although the ε-exonuclease DnaQ is a well-established proofreader in the model organismEscherichia coli, proofreading in mycobacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase despite the presence of an alternative DnaQ homolog. Here, we show that depletion of DnaQ inMycolicibacterium smegmatisresults in increased mutation rate, leading to AT-biased mutagenesis and elevated insertions/deletions in homopolymer tract. We demonstrated that mycobacterial DnaQ binds to the β-clamp and functions synergistically with the PHP domain to correct replication errors. Further, we found that the mycobacterial DnaQ sustains replicative fidelity upon chromosome topological stress. Intriguingly, we showed that a naturally evolved DnaQ variant prevalent in clinicalMycobacterium tuberculosisisolates enables hypermutability and is associated with extensive drug resistance. These results collectively establish that the alternative DnaQ functions in proofreading, and thus reveal that mycobacteria deploy two proofreaders to maintain replicative fidelity.
A Spatiotemporal and Machine-Learning Platform Accelerates the Manufacturing of hPSC-derived Esophageal Mucosa
Authors: Yang Ying , McCullough Carmel Grace , Seninge Lucas , Guo Lihao , Kwon Woo-Joo , Zhang Yongchun , Li Nancy Yanzhe , Gaddam Sadhana , Pan Cory , Zhen Hanson , Torkelson Jessica , Glass Ian A. ,   the Birth Defects Research Laboratory, Charville Greg , Que Jianwen , Stuart Joshua , Ding Hongxu , Oro Anthony 
Published: October 2023

ABSTRACTHuman pluripotent stem cell-derived tissue engineering offers great promise in designer cell-based personalized therapeutics. To harness such potential, a broader approach requires a deeper understanding of tissue-level interactions. We previously developed a manufacturing system for the ectoderm-derived skin epithelium for cell replacement therapy. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium, despite both possessing similar stratified structure. Here we employ single cell and spatial technologies to generate a spatiotemporal multi-omics cell atlas for human esophageal development. We illuminate the cellular diversity, dynamics and signal communications for the developing esophageal epithelium and stroma. Using the machine-learning based Manatee, we prioritize the combinations of candidate human developmental signals forin vitroderivation of esophageal basal cells. Functional validation of the Manatee predictions leads to a clinically-compatible system for manufacturing human esophageal mucosa. Our approach creates a versatile platform to accelerate human tissue manufacturing for future cell replacement therapies to treat human genetic defects and wounds.
Gene expression analyses reveal differences in children’s response to malaria according to their age
Authors: Tebben Kieran , Yirampo Salif , Coulibaly Drissa , Koné Abdoulaye K. , Laurens Matthew B. , Stucke Emily M. , Dembélé Ahmadou , Tolo Youssouf , Traoré Karim , Niangaly Amadou , Berry Andrea A. , Kouriba Bourema , Plowe Christopher V. , Doumbo Ogobara K , Lyke Kirsten E. , Takala-Harrison Shannon , Thera Mahamadou A. , Travassos Mark A. , Serre David 
Published: October 2023

AbstractIn Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484Plasmodiumgenes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child’s age was also strongly correlated with gene expression variations.Plasmodium falciparumgenes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation duringP. falciparumsymptomatic infections and emphasize the importance of considering the children’s age when studying and treating malaria infections.One Sentence SummaryHuman andP. falciparumgene expression differs according to the infection’s parasitemia and the child’s age, highlighting an age-dependent response to malaria and complex cellular and molecular -host/parasite interactions.
Pharmacologically inducing regenerative cardiac cells by small molecule drugs
Authors: Zhou Wei , He Kezhang , Wang Chiyin , Wang Pengqi , Wang Dan , Wang Bowen , Geng Han , Lian Hong , Ma Tianhua , Nie Yu , Ding Sheng 
Published: October 2023

SummaryAdult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, i.e., regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell (hESC)-derived TNNT2+CMsin vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells (ECs), and smooth muscle cells (SMCs). Importantly, similar results were observed in neonatal rat CMs bothin vitroandin vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts.
AI facilitated sperm detection in azoospermic samples for use in ICSI
Authors: Goss DM. , Vasilescu SA. , Vasilescu PA. , Cooke S. , Kim SHK. , Sacks GP. , Gardner DK , Warkiani ME. 
Published: October 2023

AbstractResearch questionCan artificial intelligence (AI) improve efficiency and efficacy of sperm searches in azoospermic samples?DesignThis two-phase proof-of-concept study beginning with a training phase using 8 azoospermic patients (>10000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify sperm. Secondly, side-by-side testing on 2 cohorts, an embryologist versus the AI identifying all sperm in still images (cohort 1, N=4, 2660 sperm) and then a side-by-side test with deployment of the AI model on an ICSI microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, N=4, >1300 sperm). Time taken, accuracy and precision of sperm identification was measured.ResultsIn cohort 1, the AI model showed improvement in time-taken to identify all sperm per field of view (0.019±0.30 x 10-5s versus 36.10±1.18s, P<0.0001) and improved accuracy (91.95±0.81% vs 86.52±1.34%, P<0.001) compared to an embryologist. From a total of 688 sperm in all samples combined, 560 were found by an embryologist and 611 were found by the AI in <1000thof the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90±3.19s vs 168.7±7.84s, P<0.0001) and found 1396 sperm, while 1274 were found without AI, although no significant difference was observed.ConclusionsAI-powered image analysis has the potential for seamless integration into laboratory workflows, and to reduce time to identify and isolate sperm from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.
Artificial intelligence and health equity in primary care: A qualitative study with key stakeholders
Authors: d’Elia Alexander , Gabbay Mark , Frith Lucy , Rodgers Sarah , Kierans Ciara 
Published: October 2023

AbstractArtificial Intelligence (AI)-augmented interventions are currently being rolled out across primary care, but how it affects health equity remains insufficiently understood. This qualitative study addresses this gap through an ethnographical inquiry based on 32 interviews and focus groups with stakeholders including commissioners, decision makers, AI developers, researchers, GPs and patient groups involved in the implementation of AI in English primary care. We took a sociotechnical perspective in order to assess how the stakeholders can improve health equity through the implementation process of AI within the wider system. We found that regulation and policy alone cannot guarantee equitable implementation of AI but can provide a framework to enable other stakeholders to take measures to promote equity: fostering a shared understanding of the causal mechanisms of AI and health equity, how to measure health equity, and how to share data necessary for equity promotion. Further, all stakeholders need to be on board for equitable implementation, and currently innovation leaves clinicians and patients behind. Capacity building is needed to achieve this, in particular at local commissioning and clinician level. Careful implementation and pragmatically focused research are needed to make AI in primary care capable of advancing health equity.
The TARCiS statement: Guidance on terminology, application, and reporting of citation searching
Authors: Hirt Julian , Nordhausen Thomas , Fuerst Thomas , Ewald Hannah ,   TARCiS study group, Appenzeller-Herzog Christian 
Published: October 2023

ABSTRACTEvidence syntheses adhering to systematic literature searching techniques are a cornerstone of evidence-based health care. Beyond term-based searching in electronic databases, citation searching is a prevalent search technique to identify relevant sources of evidence. However, for decades, citation searching methodology and terminology has not been standardized. We performed an evidence-guided four-round Delphi consensus study with 27 international methodological experts in order to develop the Terminology, Application, and Reporting of Citation Searching (TARCiS) statement. TARCiS comprises ten specific recommendations on when and how to conduct and report citation searching in the context of systematic literature searches and four research priorities. We encourage systematic reviewers and information specialists to incorporate TARCiS into their standardized workflows.
Policy impact evaluation: A potential use case for longitudinal monitoring of viruses in wastewater at small geographic scales
Authors: Chan Elana M. G. , Bidwell Amanda , Li Zongxi , Tilmans Sebastien , Boehm Alexandria B. 
Published: October 2023

AbstractWe used wastewater monitoring data to evaluate the impact of public health policies and interventions on the spread of COVID-19 among a university population. We first evaluated the correlation between incident, reported COVID-19 cases and wastewater SARS-CoV-2 RNA concentrations and observed changes to the correlation over time. Using a difference-in-differences approach, we evaluated the association between university COVID-19 policy changes and levels of SARS-CoV-2 RNA concentrations in wastewater. Policy changes associated with a significant change in campus wastewater SARS-CoV-2 RNA concentrations included changes to face covering recommendations, indoor gathering bans, and routine surveillance testing requirements and availability. We did not observe changes in SARS-CoV-2 RNA concentrations associated with other policy changes. The work presented herein demonstrates how longitudinal wastewater monitoring of viruses may be used for causal inference such as policy impact evaluation, especially at small geographic scales.
Plasticity of Human Microglia and Brain Perivascular Macrophages in Aging and Alzheimer’s Disease
Authors: Lee Donghoon , Vicari James M. , Porras Christian , Spencer Collin , Pjanic Milos , Wang Xinyi , Kinrot Seon , Weiler Philipp , Kosoy Roman , Bendl Jaroslav , Prashant N M , Psychogyiou Konstantina , Malakates Periklis , Hennigan Evelyn , Monteiro Fortes Jennifer , Zheng Shiwei , Therrien Karen , Mathur Deepika , Kleopoulos Steven P. , Shao Zhiping , Argyriou Stathis , Alvia Marcela , Casey Clara , Hong Aram , Beaumont Kristin G. , Sebra Robert , Kellner Christopher P. , Bennett David A. , Yuan Guo-Cheng , Voloudakis George , Theis Fabian J. , Haroutunian Vahram , Hoffman Gabriel E. , Fullard John F. , Roussos Panos 
Published: October 2023

AbstractThe complex roles of myeloid cells, including microglia and perivascular macrophages, are central to the neurobiology of Alzheimer’s disease (AD), yet they remain incompletely understood. Here, we profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 unique donors covering the human lifespan and varying degrees of AD neuropathology. We delineated 13 transcriptionally distinct myeloid subtypes organized into 6 subclasses and identified AD-associated adaptive changes in myeloid cells over aging and disease progression. The GPNMB subtype, linked to phagocytosis, increased significantly with AD burden and correlated with polygenic AD risk scores. By organizing AD-risk genes into a regulatory hierarchy, we identified and validatedMITFas an upstream transcriptional activator ofGPNMB, critical for maintaining phagocytosis. Through cell-to-cell interaction networks, we prioritizedAPOE-SORL1andAPOE-TREM2ligand-receptor pairs, associated with AD progression. In both human and mouse models,TREM2deficiency disrupted GPNMB expansion and reduced phagocytic function, suggesting that GPNMB’s role in neuroprotection wasTREM2-dependent. Our findings clarify myeloid subtypes implicated in aging and AD, advancing the mechanistic understanding of their role in AD and aiding therapeutic discovery.