bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimethyl sulfoxide as a novel therapy in a murine model of acute lung injury
Authors: Taghavi Sharven , Engelhardt David , Campbell Alexandra , Goldvarg-Abud Inna , Duchesne Juan , Shaheen Farhana , Pociask Derek , Kolls Jay , Jackson-Weaver Olan 
Published: March 2024

INTRODUCTIONThe endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS).METHODSC57BL/6 mice were given ARDS via intratracheally administered lipopolysaccharide (LPS). Dimethyl sulfoxide (220 mg/kg) was administered intravenously for 4 days. Animals were sacrificed postinjury day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts and protein content were quantified. Lung sections were stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify the endothelial glycocalyx. Human umbilical vein endothelial cells (HUVECs) were exposed to LPS. Endothelial glycocalyx was measured using fluorescein isothiocyanate-labeled wheat germ agglutinin, and co-immunoprecipitation was performed to measure interaction between sheddases and syndecan-1.RESULTSDimethyl sulfoxide treatment resulted in greater endothelial glycocalyx staining intensity in the lung when compared with sham (9,641 vs. 36,659 arbitrary units,p< 0.001). Total BAL cell counts were less for animals receiving DMSO (6.93 × 106vs. 2.49 × 106cells,p= 0.04). The treated group had less BAL macrophages (189.2 vs. 76.9 cells,p= 0.02) and lymphocytes (527.7 vs. 200.0 cells,p= 0.02). Interleukin-6 levels were lower in DMSO treated. Animals that received DMSO had less protein leak in BAL (1.48 vs. 1.08 μg/μL,p= 0.02). Dimethyl sulfoxide prevented LPS-induced endothelial glycocalyx loss in HUVECs and reduced the interaction between matrix metalloproteinase 16 and syndecan-1.CONCLUSIONSystemically administered DMSO protects the endothelial glycocalyx in the pulmonary vasculature, mitigating pulmonary capillary leak after acute lung injury. Dimethyl sulfoxide also results in decreased inflammatory response. Dimethyl sulfoxide reduced the interaction between matrix metalloproteinase 16 and syndecan-1 and prevented LPS-induced glycocalyx damage in HUVECs. Dimethyl sulfoxide may be a novel therapeutic for ARDS.
Understanding the impact of numerical solvers on inference for differential equation models
Authors: Creswell Richard , Shepherd Katherine M. , Lambert Ben , Mirams Gary R. , Lei Chon Lok , Tavener Simon , Robinson Martin , Gavaghan David J. 
Published: March 2024

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the
forward problem
, i.e. for obtaining an accurate simulation, might not be sufficiently accurate for the
inverse problem
, i.e. for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which might become jagged, causing inference algorithms to get stuck in local ‘phantom’ optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyse an ODE change point model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall run-off model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that, when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.
How suitable is freshwater sponge Ephydatia fluviatilis (Linnaeus, 1759) for time-integrated biomonitoring of microbial water quality?
Authors: Cartwright Allison , Dooley James S.G. , McGonigle Chris D. , Arnscheidt Joerg 
Published: March 2024

Faecal pollution of water by bacteria has a negative effect on water quality and can pose a potential health hazard. Conventional surveillance of microbial water quality relies on the analysis of low frequency spot samples and is thus likely to miss episodic or periodic pollution. This study aimed to investigate the potential of filter feeding sponges for time-integrated biomonitoring of microbial water quality. Laboratory trials tested the effects of different ratios of bacterial abundance and the sequence of exposure on bacterial retention by the freshwater sponge Ephydatia fluviatilis (Linnaeus, 1759) to establish its potential to indicate bacterial exposure.
Gemmule grown sponges were simultaneously exposed to Escherichia coli and Enterococcus faecalis but at different ratios (Trial 1) or individually exposed to each bacterial species but in different sequential order (Trial 2). The E. coli and E. faecalis retained in each sponge was quantified by culture on selective agars. Data analysis was conducted using the Kruskal- Wallis test and/ or the Mann Whitney U test to compare between the numbers of bacteria retained in each treatment. Additionally, the Wilcoxon Matched-Paired Signed-Rank test was used for comparison of the different bacterial abundances retained within each individual sponge.
Sponges from all trials retained E. coli and E. faecalis in small numbers relative to the exposure (<0.05% Trial 1 and <0.07% Trial 2) but exhibited higher retention of E. coli. Higher abundance of either bacterial species resulted in significantly lower (p<0.005) retention of the same species within sponges (Trial 1). An initial exposure to E. coli resulted in significantly higher (p=0.040) retention of both bacterial species than when sponges were exposed to E. faecalis first (Trial 2).

Bacterial retention by sponges was neither quantitatively representative of bacterial abundance in the ambient water nor the sequence of exposure. This implies either selective filtration or an attempt by sponges to prevent infection. However, freshwater sponges may still be useful in biomonitoring as qualitative time-integrated samplers of faecal indicator bacteria as they detect different bacteria present in the water even if their quantities cannot be estimated.
Misspellings or “miscellings”-non-verifiable cell lines in cancer research publications
Authors: Oste Danielle J. , Pathmendra Pranujan , Richardson Reese A. K. , Johnson Gracen , Ao Yida , Arya Maya D. , Enochs Naomi R. , Hussein Muhammed , Kang Jinghan , Lee Aaron , Danon Jonathan J. , Cabanac Guillaume , Labbé Cyril , Davis Amanda Capes , Stoeger Thomas , Byrne Jennifer A. 
Published: March 2024

AbstractReproducible laboratory research relies on correctly identified reagents. We have previously described human gene research papers with wrongly identified nucleotide sequence reagent(s), including papers studyingmiR-145. Manually verifying reagent identities in more recentmiR-145papers found 20/36 (56%) and 6/36 (17%)miR-145papers with misidentified nucleotide sequence reagent(s) and human cell line(s), respectively. We also found 5 cell line identifiers in twomiR-145papers with wrongly identified nucleotide sequences and cell lines, and 18 identifiers published elsewhere that did not correspond to indexed cell lines. These cell line identifiers were described as non-verifiable, as their identities appeared uncertain. Studying 420 papers that mentioned 8 different non-verifiable cell line identifier(s) found 235 papers (56%) that appeared to refer to BGC-803, BSG-803, BSG-823, GSE-1, HGC-7901, HGC-803 and/or MGC-823 as independent cell lines. We could not find publications describing how these cell lines were established, and they were not indexed in claimed externally accessible cell line repositories. While some papers stated that STR profiles had been generated for BGC-803, GSE-1 and/or MGC-823 cells, no STR profiles were identified. In summary, non-verifiable human cell lines represent new challenges to research reproducibility and require further investigation to clarify their identities.Novelty and Impact StatementThrough verifying reagent identities in research publications, our team found 23 non-verifiable human cell line identifiers, most of which could represent misspellings of contaminated cancer cell lines. Of 8 identifiers studied in detail, 7 non-verifiable identifiers were unexpectedly referred to as independent cell lines across 235 publications. We therefore describe a process “miscelling”, where published cell lines lack descriptions of how they were established, cannot be found in claimed external repositories and lack STR profiles.
HER2 Prognostic Significance and Therapeutic Implications in Gastric Cardia Adenocarcinoma: Insights from Multi-Omics Profiling
Authors: Wang Li-Dong , Xing Pengwei , Zhao Xue-Ke , Song Xin , Wei Meng-Xia , Lei Ling-Ling , Xu Rui-Hua , Wang Ran , Ma Lei , You Duo , Chen Pei-Nan , Xie Minglu , Zhao Miao , Zhang He , Lv Hui-Fang , Li Ai-Li , Wang Xian-Zeng , Zhou Fu-You , Gao She-Gan , Chen Xingqi 
Published: March 2024

AbstractTherapeutic targets for Gastric Cardia Adenocarcinoma (GCA), particularly for HER2-negative patients, are lacking. Here, we conducted multi-omics profiling on 128 GCA patients using mass spectrometry, whole-exome sequencing, RNA-Seq, and metabolomics. We found HER2 to be a favorable prognostic marker for GCA. Employing molecular counting, we categorized patients into HER2-high, -low, and -negative groups. We uncovered an enrichment of DNA repair features in the HER2-high group, while HER2-low and -negative groups exhibited strong inflammation. We found that tumor mutation burden may not be the distinguishing factor among these three groups. We revealed that the HER2-negative and -low groups have a tumor-suppressive immune microenvironment, and HER2 expression is associated with fatty acid metabolic profiles and inflammation in the blood of patients. Our study revealed anti-inflammatory and immune checkpoint inhibition, targeting PD-L2 and the CD47/SIRPA pair, as therapeutic strategies for HER2-negative GCA patients. These findings highlight promising avenues for personalized treatment for GCA.
Meta-analysis of livestock effects on tree regeneration in oak agroforestry systems
Authors: Wadud Abdullah Ibne , Bugalho Miguel N. , Vaz Pedro Gonçalves 
Published: March 2024

ABSTRACTLivestock grazing occupies over a quarter of terrestrial land and is prevalent to agroforestry ecosystems, potentially affecting the survival, growth, and density of trees’ early developmental stages, such as seeds, seedlings, and saplings. To address the effects of livestock on tree recruitment in the face of ongoing debates about their impacts, we conducted a 33-year meta-analysis inQuercus-dominated agroforestry systems. Our analysis revealed a consistently negative effect of livestock on oak acorns, seedlings, and saplings. Significantly, livestock body size influenced oak regeneration, with small-sized livestock, notably sheep and goats, having a more pronounced negative impact compared to mixed-size systems, mainly involving cattle and sheep. The effects of small-sized livestock were markedly detrimental on acorn survival and seedling/sapling density, although no studies eligible for meta-analysis examined large livestock impacts on acorns. Overall, mixed-size livestock systems, often involving cattle and sheep, lessen the negative effects. Our findings indicate that the body size and foraging behaviors of livestock should be considered for the ecological sustainability of the tree component in agroforestry systems. While protective measures have long been integral to well-managed agroforestry systems, our results underscore the importance of integrating diverse livestock sizes and applying specific protective strategies, particularly for acorns and saplings, to further refine these practices. Future research should expand to underrepresented regions and livestock types to refine global agroforestry management practices.HighlightsLivestock reduces oak tree regeneration at acorn, seedling, and sapling stages.Small livestock effect more negative, especially acorn survival and young oak density.Mixed-size livestock agroforestry systems reduce harm more than small single-size ones.We challenge perceptions that replacing cattle with sheep is necessarily less harmful.We advocate for diverse livestock sizes inQuercus-dominated agroforestry systems.
Haplotype-resolved reconstruction and functional interrogation of cancer karyotypes
Authors: Brunette Gregory J. , Tourdot Richard W. , Wangsa Darawalee , Pellman David , Zhang Cheng-Zhong 
Published: March 2024

AbstractGenomic characterization has revealed widespread structural complexity in cancer karyotypes, however shotgun sequencing cannot resolve genomic rearrangements with chromosome-length continuity. Here, we describe a two-tiered approach to determine the segmental composition of rearranged chromosomes with haplotype resolution. First, we presentrefLinker, a new method for robust determination of chromosomal haplotypes using cancer Hi-C data. Second, we use haplotype-specific Hi-C contacts to determine the segmental structure of rearranged chromosomes. By contrast with existing methods for diploid haplotype inference, our approach is robust to the confounding effects of large-scale DNA deletions, duplications, and high-level amplification in cancer sequencing. Using this approach, we examine haplotype-specific expression changes on rearranged homologs and provide direct evidence for long-range transcriptional activation and repression associated with rearrangements of the inactive X chromosome (Xi). Together, these results reveal the significant transcriptional consequences of somatic Xi rearrangements, highlightingrefLinker’s broad utility for studying the functional consequences of chromosomal rearrangements.
Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness
Authors: Jang Kyung Ku , Ercelen Defne , Cen Feng Jing Yu Carolina , Gurunathan Sakteesh , Zhou Chaoting , Korman Aryeh , Newell Luke , Hudesman David , Jones Drew R. , Loke P’ng , Axelrad Jordan E. , Cadwell Ken 
Published: March 2024

ABSTRACTBackground & AimsDespite increasing therapeutic options in the treatment of ulcerative colitis (UC), achieving disease remission remains a major clinical challenge. Nonresponse to therapy is common and clinicians have little guidance in selecting the optimal therapy for an individual patient. This study examined whether patient-derived materials could predict individual clinical responsiveness to the Janus kinase (JAK) inhibitor, tofacitinib, prior to treatment initiation.MethodIn 48 patients with UC initiating tofacitinib, we longitudinally collected clinical covariates, stool, and colonic biopsies to analyze the microbiota, transcriptome, and exome variations associated with clinical responsiveness at week 24. We established patient-derived organoids (n = 23) to determine how their viability upon stimulation with proinflammatory cytokines in the presence of tofacitinib related to drug responsiveness in patients. We performed additional biochemical analyses of organoids and primary tissues to identify the mechanism underlying differential tofacitinib sensitivity.ResultsThe composition of the gut microbiota, rectal transcriptome, inflammatory biomarkers, and exome variations were indistinguishable among UC patients prior to tofacitinib treatment. However, a subset of patient-derived organoids displayed reduced sensitivity to tofacitinib as determined by the ability of the drug to inhibit STAT1 phosphorylation and loss of viability upon cytokine stimulation. Remarkably, sensitivity of organoids to tofacitinib predicted individual clinical patient responsiveness. Reduced responsiveness to tofacitinib was associated with decreased levels of the cationic transporter MATE1, which mediates tofacitinib uptake.ConclusionsPatient-derived intestinal organoids predict and identify mechanisms of individual tofacitinib responsiveness in UC. Specifically, MATE1 expression predicted clinical response to tofacitinib.
Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+T cells to suppress anti-tumor immunity
Authors: Tejero Joanne D. , Hesterberg Rebecca S. , Drapela Stanislav , Ilter Didem , Raizada Devesh , Lazure Felicia , Kashfi Hossein , Liu Min , Fernández-García Juan , Asara John M. , Fendt Sarah-Maria , Cleveland John L. , Gomes Ana P. 
Published: March 2024

AbstractSystemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the tumorigenic role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8+T cells, key anti-tumor immune cells, declines with age and in conditions of vitamin B12 deficiency, the two most well-established conditions that lead to increased systemic levels of MMA. Thus, we hypothesized that increased circulatory levels of MMA leads to suppression of CD8+T cell immunity. Treatment of primary CD8+T cells with MMA induced a dysfunctional phenotype characterized by a robust immunosuppressive transcriptional reprogramming and marked increases in the expression of the exhaustion regulator, TOX. Accordingly, MMA treatment upregulated exhaustion markers in CD8+T cells and decreased their effector functions, which drove the suppression of anti-tumor immunityin vitroandin vivo. Mechanistically, MMA-induced CD8+T cell exhaustion was associated with a suppression of NADH-regenerating reactions in the TCA cycle and concomitant defects in mitochondrial function. Thus, MMA has immunomodulatory roles, thereby highlighting MMA as an important link between aging, immune dysfunction, and cancer.
PCSK9 deficiency promotes the development of peripheral neuropathy
Authors: Jaafar Ali K. , Paulo-Ramos Aurélie , Rastoldo Guillaume , Veeren Bryan , Planesse Cynthia , Bringart Matthieu , Rondeau Philippe , Meilhac Olivier , Lambert Gilles , Bourane Steeve 
Published: March 2024

AbstractPCSK9 best-known and studied function is to induce the hepatic degradation of the low-density lipoprotein receptor (LDLR), thereby increasing the concentration of LDL-cholesterol (LDL-C) in the blood. Beyond its effects on LDL, recent studies have reported pleiotropic effects of PCSK9 notably in septic shock, vascular inflammation, viral infection, and cancer. While the functional and structural integrity of peripheral nerves are critically influenced by circulating lipids, the impact of PCSK9 in the peripheral nervous system is unknown. In this study, we investigated the consequences of PCSK9 deficiency on peripheral nerves. We found that PCSK9 deletion in mice leads to peripheral neuropathy characterized by a reduction of thermal and mechanical pain sensations. PCSK9 deficient mice also presented skin structural changes with a reduction of number of terminal nociceptive Schwann cells, Remak fiber axonal swelling, as well as hypomyelination of small nerve fibers. Interestingly, peripheral nerves of PCSK9 deficient mice presented an upregulation of the fatty acid transporter CD36 expression which correlated with an increase in nerve lipid contents and structural mitochondrial abnormalities. Our findings demonstrate that PCSK9 plays a critical role in the peripheral nerves by regulating lipid homeostasis, and its deficiency could lead to the development of symptoms related to peripheral neuropathy.Graphical abstractPCSK9 modulates nerve energy metabolism and health. Created with BioRender.com.
The immune map of human body
Authors: Gan Rui , Jin Xiangxing , Ren Xianwen 
Published: March 2024

AbstractThe immune system serves as a vital defense mechanism against diseases and infections for human bodies, comprised of a complex network of diverse cells, organs, and tissues. Here, we conduct single-cell deconvolution of 17382 RNA-seq samples from 30 tissues and construct a comprehensive map of the distributions of >1000 different cell states across all the major immune cell types throughout human bodies. This high-resolution immune map covers both sexes and a wide range of ages, enabling interrogation of the immune responses to sex differences and age-related changes. Similarity analysis among the different tissue types depicts the tissue-specific immunity of testis, liver, lung, brain, and kidney besides blood and spleen, and the high immune similarity between breast and adipose tissues for example. This comprehensive immune map may deepen our understanding of human immune system from a holistic perspective.
Assessing Patient Satisfaction in Ibadan South-west Region of Oyo State, Nigeria
Authors: Chukwuemeka Abel Nnandi , Akinsolu Folahanmi Tomiwa , Adekola Marylyn Bukola , Olagunju Mobolaji Timothy , Abodunrin Olunike Rebecca , Adewole Ifeoluwa Eunice , Ola Oluwabukola Mary , Ezechi Oliver Chukwujekwu 
Published: March 2024

AbstractIntroductionPatient satisfaction plays a critical role in healthcare service delivery. Despite growing studies, patient satisfaction levels are still widely under-reported in Nigeria. This study assessed patient satisfaction among patients in primary and secondary healthcare facilities in Ibadan Southwest local government area of Oyo State, Nigeria.Method and MaterialsIn this cross-sectional study, investigators collected data using the Short-form Patient Satisfaction Questionnaire (PSQ-18). The data was analyzed using the Statistical Package for the Social Sciences (SPSS) software with descriptive statistics and One-way analysis of variance (ANOVA).ResultsA total of 387 patients participated in the study, and results showed that overall satisfaction among patients was 67.9%, where Communication (84.5%) and Financial Aspect (54.9%) recorded the highest and lowest percentage of positive responses respectively.ConclusionPatient satisfaction is a growing subject in Nigeria. It has a significant influence on healthcare service delivery. Stakeholders, policymakers, and managers should employ policies, strategies, and programs to improve the quality of healthcare service delivery across Nigeria.