bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving cardiovascular risk prediction beyond pooled cohort equations: a prospective cohort of 304,356 participants
Authors: Elliott Joshua , Bodinier Barbara , Whitaker Matthew , Tzoulaki Ioanna , Elliott Paul , Chadeau-Hyam Marc 
Published: January 2023

AbstractBackgroundPooled Cohort Equations (PCE) are used to predict cardiovascular disease (CVD) risk. Inclusion of other variables may improve risk prediction.ObjectiveIdentify variables improving CVD risk prediction beyond recalibrated PCE.DesignProspective cohort study; sex-stratified Cox survival models with LASSO stability selection to predict CVD in non-overlapping subsets: variable selection (40%), model training (30%) and testing (30%).SettingUK population.ParticipantsUK Biobank: 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline.MeasurementsPersonal/family medical history; lifestyle factors; genetic, biochemical, hematological, and metabolomic blood markers. Outcomes were incident hospitalization or mortality from CVD.ResultsThere were 11,899 (men) and 9,110 (women) incident CVD cases with median 12.1 years follow-up. Variables selected for both men and women were: age, albumin, antihypertensive medication, apolipoprotein B, atrial fibrillation, C-reactive protein, current smoker, cystatin C, family history of coronary artery disease, glycated hemoglobin, polygenic risk score (PRS) for CVD and systolic blood pressure. Also selected: apolipoprotein A1, lipoprotein(a), white blood cell count, deprivation index (men); triglycerides (women). C-statistics for recalibrated PCE were 0.67 [0.66-0.68] and 0.69 [0.68-0.70] in men and women, respectively, improving to 0.71 [0.70-0.72] and 0.72 [0.71-0.73] with LASSO stably selected variables. Categorical net reclassification improvement (7.5% risk threshold) versus PCE was 0.054 [0.038-0.070] (men) and 0.081 [0.063-0.099] (women). Addition of targeted metabolomic data to LASSO stability selection did not improve predictive accuracy.LimitationsAnalyses were done in a single population study and require external replication.ConclusionAdditional personal/family medical history, blood-based markers and genetic information improve CVD risk prediction beyond PCE.Funding sourceNational Institute for Health Research Academic Clinical Fellowship (JE); Medical Research Council studentship (BB); European Union H2020 (MC-H).
Neck pain service utilization and costs: association with timing of non-pharmaceutical services for individuals initially contacting a primary care provider. A retrospective cohort study
Authors: Elton David , Zhang Meng 
Published: January 2023

AbstractBackgroundNeck pain (NP) is prevalent and costly. NP clinical practice guidelines are similar to those for low back pain (LBP), emphasizing non-pharmaceutical and non-interventional first-line approaches. Primary care providers (PCP) are frequently consulted by individuals with NP.ObjectiveExamine the association between guideline concordant incorporation of non-pharmaceutical therapies, use of imaging, pharmaceutical, and interventional services, and total episode cost for individuals with NP initially contacting a PCP.DesignRetrospective cohort study using identical methods to a previous LBP studySetting/PatientsNational sample of individuals with non-surgical NP occurring in 2017-2019.MeasurementsIndependent variables were initial contact with a PCP, and the timing of incorporation of 5 types of non-pharmaceutical therapies. Dependent measures included use of 13 types of health care services and total episode cost.Results70,252 PCPs were initially contacted by 124,780 individuals with 137,274 episodes of non-surgical NP. 30.9% of PCPs and 22.1% of episodes included at least one of five non-pharmaceutical services at any time during an episode. Active care (13.7% of episodes), manual therapy (10.8%), and chiropractic manipulative therapy (9.4%) were the most common non-pharmaceutical services. 7.4% of episodes included a non-pharmaceutical service during the first 7 days with these episodes associated with a modest reduction (risk ratio 0.28 to 0.78) in the use of prescription pharmaceuticals. Younger individuals from ZIP codes with higher adjusted gross income were more likely to receive a non-pharmaceutical service in the first 7 days of an episode. When included during an episode, non-pharmaceutical services were associated with an increase in total episode cost with the smallest increase associated with chiropractic and osteopathic manipulation.LimitationsAs a retrospective observational analysis of associations there are numerous potential confounders and limitations.ConclusionsNon-pharmaceutical services are infrequently provided to individuals with non-surgical NP initially contacting a PCP. For these individuals, non-pharmaceutical services, if provided, are most commonly introduced later in an episode after receiving pharmaceutical, imaging, and interventional services. For individuals with NP initially contacting a PCP there is an opportunity to increase the guideline concordant incorporation of non-pharmaceutical services early in an episode.
Non-invasive thoracoabdominal mapping of post-oesophagectomy conduit function
Authors: Wang Tim Hsu-Han , Tokhi Ashraf , Gharibans Armen , Evennett Nicholas , Beban Grant , Schamberg Gabriel , Varghese Chris , Calder Stefan , Duong Cuong , O’Grady Greg 
Published: January 2023

AbstractIntroductionOesophagectomy is a complex procedure performed for malignant and benign conditions. Post-oesophagectomy conduit dysfunction is common, which can occur for several reasons including conduit dysmotility. However, reliable tools for evaluating conduit motility are lacking. A non-invasive device for gastric electrical mapping was recently developed to evaluate gastric electrical activity and function. This study aimed to assess the feasibility of BSGM in the post-oesophagectomy stomach.MethodsOesophagectomy patients from Auckland, New Zealand, were recruited. The Gastric Alimetry System® (New Zealand) was employed, comprising a stretchable array (8×8 electrodes), a wearable Reader, and validated iOS app for symptom logging. The protocol comprised a 30-minute baseline, a meal challenge, then 4 hours of post-prandial recordings. Analysis encompassed Principal Gastric Frequency, BMI-adjusted amplitude, Gastric Alimetry Rhythm Index (indicating rhythm stability), meal response, and symptoms. Adverse events were recorded.Results6 patients were recruited and gastric activity was successfully captured in all except one with the colonic interposition (negative control). Four patients showed abnormalities indicating post-operative gastric hypofunction: four with low or abnormal frequency (<2.65 cycles/min), three with low amplitude (<22μV), two with low GA-RI (<0.25) and one with a reduced meal response. One patient had significant symptoms (nausea, early satiation) who demonstrated marked hypomotility in all four of these domains. No adverse events occurred.ConclusionGastric Alimetry is a safe and feasible technique to non-invasively assess gastric conduit motility following oesophagectomy. Parameters may need adjustment for post-surgical anatomy. Clinical studies assessing the role in diagnosis and therapy can be advanced.
A human stomach cell type transcriptome atlas
Authors: Öling S , Struck E , Thorsen MN , Zwahlen M , Feilitzen K von , Odeberg J , Pontén F , Lindskog C , Uhlén M , Dusart P , Butler LM 
Published: January 2023

SUMMARYThe identification of cell type-specific genes and their modification under different conditions is central to our understanding of human health and disease. The stomach, a hollow organ in the upper gastrointestinal tract, provides an acidic environment that contributes to microbial defence and facilitates the activity of secreted digestive enzymes to process food and nutrients into chyme. In contrast to other sections of the gastrointestinal tract, detailed descriptions of cell type gene enrichment profiles in the stomach are absent from the major single cell sequencing-based atlases. Here, we use an integrative correlation analysis method to predict human stomach cell type transcriptome signatures using unfractionated stomach RNAseq data from 359 individuals. We profile parietal, chief, gastric mucous, gastric enteroendocrine, mitotic, endothelial, fibroblast, macrophage, neutrophil, T-cell and plasma cells, identifying over 1600 cell type-enriched genes. We uncover the cell type expression profile of several non-coding genes strongly associated with the progression of gastric cancer and, using a sex-based subset analysis, uncover a panel of male-only chief cell-enriched genes. This study provides a roadmap to further understand human stomach biology.
Simple, low-cost, and well-performing method, the outgrowth technique, for the isolation of epithelial cells from nasal polyps
Authors: Kim Jonghui , Hegener Karla , Hagedorn Claudia , Jameel Kaschin Jamal , Weidinger Daniel , Seuthe Inga Marte Charlott , Eichhorn Sabine , Kreppel Florian , Park Jonas Jae-Hyun , Knobloch Jürgen 
Published: January 2023

ABSTRACTObjectivesEpithelial cells are an important part of the pathomechanism in chronic rhinosinusitis with nasal polyps. It is therefore essential to establish a robust method for the isolation and culture of epithelial cells from nasal polyps to enable further research. In this study, the feasibility of the outgrowth technique for the isolation of the epithelial cells from the nasal polyps was evaluated.MethodsThe outgrowth technique was performed to isolate the epithelial cells. Proliferation was evaluated up to the 3rd passage. Epithelial cells were identified and differentiation and proliferation were evaluated using flow cytometry with anti-cytokeratin, anti-p63, and anti-Ki-67. A functionality test was assessed by determining type 2–relevant proteins using ELISA, representatively, interleukin-33 and periostin.ResultsUsing the outgrowth technique, epithelial cells could be isolated from all tissue samples. Isolated epithelial cells showed a proliferation rate of approximately 7- to 23-fold every 6 days up to the 3rd passage. Over 97% of isolated cells were shown to be cytokeratin- and p63-positive, and over 86% of them were Ki-67–positive in flow cytometry. Interleukin-33 and periostin were detectable in the supernatant.ConclusionsWe introduce a simple, low-cost, and well-performing method for isolating epithelial cells from nasal polyps with the outgrowth technique.
Modelling drug responses and evolutionary dynamics using triple negative breast cancer patient-derived xenografts
Authors: Shea Abigail , Eyal-Lubling Yaniv , Guerrero-Romero Daniel , Garcia Raquel Manzano , Greenwood Wendy , O’Reilly Martin , Georgopoulou Dimitra , Callari Maurizio , Lerda Giulia , Wix Sophia , Giovannetti Agnese , Masina Riccardo , Esmaeilishirazifard Elham , Martin Alistair G. , Nagano Ai , Young Lisa , Kupczak Steven , Cheng Yi , Bardwell Helen , Provenzano Elena , Kane Justine , Lay Jonny , Grybowicz Louise , McAdam Karen , Caldas Carlos , Abraham Jean , Rueda Oscar M , Bruna Alejandra 
Published: January 2023

ABSTRACTTriple negative breast cancers (TNBC) exhibit inter- and intra-tumour heterogeneity, which is reflected in diverse drug responses and interplays with tumour evolution. Here, we use TNBC patient-derived tumour xenografts (PDTX) as a platform for co-clinical trials to test their predictive value and explore the molecular features of drug response and resistance. Patients and their matched PDTX exhibited mirrored drug responses to neoadjuvant therapy in a clinical trial. In parallel, additional clinically-relevant treatments were tested in PDTXsin vivoto identify alternative effective therapies for each PDTX model. This framework establishes the foundation for anticipatory personalised therapies for those patients with resistant or relapsed tumours. The PDTXs were further explored to model PDTX- and treatment-specific behaviours. The dynamics of drug response were characterised at single-cell resolution revealing a novel mechanism of response to olaparib. Upon olaparib treatment PDTXs showed phenotypic plasticity, including transient activation of the immediate-early response and irreversible sequential phenotypic switches: from epithelial to epithelial-mesenchymal-hybrid states, and then to mesenchymal states. This molecular mechanism was exploitedex vivoby combining olaparib and salinomycin (an inhibitor of mesenchymal-transduced cells) to reveal synergistic effects. In summary, TNBC PDTXs have the potential to help design individualised treatment strategies derived from model-specific evolutionary insights.
Adult stem cell characterization from theMedial GastrocnemiusandSemitendinosusmuscles in early development of cerebral palsy pathology
Authors: Corvelyn M , Meirlevede J , Deschrevel J , Huyghe E , De Wachter E , Gayan-Ramirez G , Sampaolesi M , Van Campenhout A , Desloovere K , Costamagna D 
Published: January 2023

AbstractCerebral palsy (CP) is one of the most common lifelong conditions leading to childhood physical disability. Literature reported previously altered muscle properties such as lower number of satellite cells (SCs), with altered fusion capacity. However, these observations highly vary among studies, possibly due to heterogeneity in patient population, lack of appropriate control data, methodology and different assessed muscle.In this study we aimed to strengthen previous observations and to understand the heterogeneity of CP muscle pathology. Myogenic differentiation of SCs from theMedial Gastrocnemius(MG) muscle of patients with CP (n=16, 3-9 years old) showed higher fusion capacity compared to age-matched typically developing children (TD, n=13). Furthermore, we uniquely assessed cells of two different lower limb muscles and showed a decreased myogenic potency in cells from theSemitendinosus(ST) compared to the MG. Longitudinal assessments, one year after the first botulinum toxin treatment, showed slightly reduced SC representations and lower fusion capacity. Finally, we proved the robustness of our data, by assessing in parallel the myogenic capacity of two samples from the same TD muscle.In conclusion, these data confirmed previous findings of increased SC fusion capacity from MG muscle of young patients with CP compared to age-matched TD. Further elaboration is reported on potential factors contributing to heterogeneity, such as assessed muscle, CP progression and reliability of primary outcome parameters.
Isogenic lines of rainbow trout (Oncorhynchus mykiss)as a tool to assess how growth and feeding behaviour are correlated to feed efficiency in fish
Authors: Pouil Simon , Kernéis Thierry , Quillet Edwige , Lallias Delphine , Labbé Laurent , Phocas Florence , Dupont-Nivet Mathilde 
Published: January 2023

AbstractAccurately measuring individual feed intake is required to include feed efficiency (FE) as an objective in commercial breeding programs. Phenotyping individual feed intake through direct measurements remains complex in fish reared in groups. One way to overcome this challenge is to find proxies for estimating FE. This study aimed to investigate the correlations between fish FE and potential predictive criteria in rainbow troutOncorhynchus mykiss. As predictive criteria, we considered the variations of body weight assessed as thermal growth coefficients (TGC) and the feeding behaviour assessed as the number of feed demands over a period and the proportion of the demands made before noon. Feed intake was assessed over three different periods in ten isogenic lines allowing a recording for each of the ten genotypes while keeping fish in groups. The protocol consisted of two successive feed deprivation and refeeding phases after initial basal growth periods. Correlations were then calculated between FE, measured either as feed conversion ratio (FCR) or residual feed intake (RFI), and the different indirect criteria. We found positive phenotypic correlations between FCR and RFI over the feed intake measurement periods (r ⩾ 0.79,P< 0.001). Assessment of the relationship between FE traits (FCR and RFI) calculated over the three measurement periods and TGC revealed no significant association. We found significant positive correlations between RFI calculated from the first feed intake measurement period and feeding behaviour, assessed as the number of feed demands (r = 0.42-0.49,P⩽ 0.022). Nevertheless, such correlations were not established for the two other measurement periods following feed deprivation. While we demonstrated that the weight variations during feed deprivation are not a good proxy for FE (FCR or RFI) in rainbow trout, we also highlighted the interest in exploring more the relationships between FE and feeding behaviour in fish.
The great acceleration of island saturation by species introductions in the Anthropocene has altered species-area relationships
Authors: Gleditsch Jason M. , Behm Jocelyn E. , Helmus Matthew R. 
Published: January 2023

AbstractThe species-area relationship (SAR) is a fundamental pattern of island biogeography which is often curvilinear due to reduced accumulation of species on mid-sized island caused by island isolation and the lack of speciation present on larger islands. The curvature of SARs represents lower saturation of species on mid-sized islands and therefore accelerated species accumulation should linearize island SARs. In the Anthropocene, island species accumulation has accelerated from introduced species. We hypothesize three new patterns. First, the saturation of species for the most unsaturated islands should increase more from introduced species than other islands. Second, SARs should become more linear as islands accumulate more species. Third, introduced species should greatly accelerate the island saturation process. We assessed these patterns for the reptile and amphibian of the Caribbean, a global hotspot of biodiversity. Mid-sized Caribbean islands are now more saturated causing a linearization of contemporary herpetofauna SARs resulting from a ca. 30 myr and 40 myr acceleration of island saturation for reptiles and amphibians, respectively. Thus, humans within the last few hundreds of years—starting with European colonization of the Americas—have greatly accelerated the natural process of island saturation by 30 million years within the Caribbean global biodiversity hotspot.
Open Biomedical Network Benchmark A Python Toolkit for Benchmarking Datasets with Biomedical Networks
Authors: Liu Renming , Krishnan Arjun 
Published: January 2023

AbstractOver the past decades, network biology has been a major driver of computational methods developed to better understand the functional roles of each gene in the human genome in their cellular context. Following the application of traditional semi-supervised and supervised machine learning (ML) techniques, the next wave of advances in network biology will come from leveraging graph neural networks (GNN). However, to test new GNN-based approaches, a systematic and comprehensive benchmarking resource that spans a diverse selection of biomedical networks and gene classification tasks is lacking. Here, we present the Open Biomedical Network Benchmark (OBNB), a collection of benchmarking datasets derived using networks from 15 sources and tasks that include predicting genes associated with a wide range of functions, traits, and diseases. The accompanying Python package,obnb, contains reusable modules that enable researchers to download source data from public databases or archived versions and set up ML-ready datasets that are compatible with popular GNN frameworks such as PyG and DGL. Our work lays the foundation for novel GNN applications in network biology.obobwill also help network biologists easily set-up custom benchmarking datasets for answering new questions of interest and collaboratively engage with graph ML practitioners to enhance our understanding of the human genome. OBNB is released under the MIT license and is freely available on GitHub:https://github.com/krishnanlab/obnb
BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians
Authors: Clark Eleanor G. , Petersen Christian P. 
Published: January 2023

AbstractAdult regeneration restores patterning of orthogonal body axes after damage in a post-embryonic context. Planarians regenerate using distinct body-wide signals primarily regulating each axis dimension: anteroposterior Wnts, dorsoventral BMP, and mediolateral Wnt5 and Slit determinants. How regeneration can consistently form perpendicular tissue axes without symmetry-breaking embryonic events is unknown, and could either occur using fully independent, or alternatively, integrated signals defining each dimension. Here, we report that the planarian dorsoventral regulatorbmp4suppresses the posterior determinantwnt1to pattern the anteroposterior axis. Double-FISH identified distinct anteroposterior domains within dorsal midline muscle that express eitherbmp4orwnt1. Homeostatic inhibitionbmp4andsmad1expanded thewnt1expression anteriorly, while elevation of BMP signaling throughnog1;nog2RNAi reduced thewnt1expression domain. BMP signal perturbation broadly affected anteroposterior identity as measured by expression of posterior Wnt pathway factors, without affecting head regionalization. Therefore, dorsal BMP signals broadly limit posterior identity. Furthermore,bmp4RNAi caused medial expansion of the lateral determinantwnt5and reduced expression of the medial regulatorslit. Double RNAi ofbmp4andwnt5resulted in lateral ectopic eye phenotypes, suggestingbmp4acts upstream ofwnt5to pattern the mediolateral axis. Therefore,bmp4acts at the top of a patterning hierarchy both to control dorsoventral information and also, through suppression of Wnt signals, to regulate anteroposterior and mediolateral identity. These results reveal that adult pattern formation involves integration of signals controlling individual orthogonal axes.Author SummarySystems that coordinate long-range communication across axes are likely critical for enabling tissue restoration in regenerative animals. While individual axis pathways have been identified, there is not yet an understanding of how signal integration allows repatterning across 3-dimensions. Here, we report an unanticipated linkage between anteroposterior, dorsoventral, and mediolateral systems in planarians through BMP signaling. We find that dorsally expressed BMP restricts posterior and lateral identity by suppressing distinct Wnt signals in adult planarians. These results demonstrate that orthogonal axis information is not fully independent and suggest a potentially ancient role of integrated axis patterning in generating stable 3-dimensional adult forms.