bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation latency and dormancy signatures define fetal liver HSCs at single cell resolution
Authors: Ishida Takashi , Heck Adam M. , Varnum-Finney Barbara , Dozono Stacey , Nourigat-McKay Cynthia , Kraskouskas Katie , Wellington Rachel , Waltner Olivia , Root  , Jackson Dana L , Delaney Colleen , Rafii Shahin , Bernstein Irwin D. , Trapnell  , Hadland Brandon 
Published: June 2023

AbstractDecoding the gene regulatory mechanisms mediating self-renewal of hematopoietic stem cells (HSCs) during their amplification in the fetal liver (FL) is relevant for advancing therapeutic applications aiming to expand transplantable HSCs, a long-standing challenge. Here, to explore intrinsic and extrinsic regulation of self-renewal in FL-HSCs at the single cell level, we engineered a culture platform designed to recapitulate the FL endothelial niche, which supports the amplification of serially engraftable HSCs ex vivo. Leveraging this platform in combination with single cell index flow cytometry, serial transplantation assays, and single cell RNA-sequencing, we elucidated previously unrecognized heterogeneity in immunophenotypically defined FL-HSCs and demonstrated that differentiation latency and transcriptional signatures of biosynthetic dormancy are distinguishing properties of self-renewing FL-HSCs with capacity for serial, long-term multilineage hematopoietic reconstitution. Altogether, our findings provide key insights into HSC expansion and generate a novel resource for future exploration of the intrinsic and niche-derived signaling pathways that support FL-HSC self-renewal.
The impact of respiratory infections and probiotic use on the nasal microbiota of frail residents in long-term care homes
Authors: Bowdish DME , Rossi L , Loeb MB , Johnstone J , Schenck LP , Fontes M , Surette MG , Whelan FJ 
Published: June 2023

AbstractBackgroundResidents in long-term care (LTC) homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrollment in a placebo-controlled trial testing the feasibility of administering aLactobacillus rhamnosusGG probiotic to prevent respiratory infection (2014 - 2017). The microbiome of the nasal (mid-turbinate) of 150 residents of LTC homes was interrogated using 16S rRNA gene sequencing.ResultsWe identified a diverse and individualized microbiota which could be separated into 9 distinct clusters based on Bray Curtis distances. Samples collected during symptoms of influenza-like illness (ILI) differed statistically from those collected pre- and post-cold and influenza season, and we observed decreased temporal stability – as measured by movement between clusters – in individuals who experienced ILI compared to those who did not.ConclusionsThe use of probiotics decreased ILI-induced changes to the microbiota; however, it is not clear whether this decrease is sufficient to prevent respiratory illness.
Translating metagenomics into clinical practice of complex paediatric neurological presentations
Authors: Penner Justin , Hassell Jane , Brown Julianne R , Mankad Kshitij , Storey Nathaniel , Atkinson Laura , Ranganathan Nisha , Lennon Alexander , Lee Jack C D , Champsas Dimitrios , Kopec Angelika , Shah Divya , Venturini Cristina , Dixon Garth , De Surjo , Hatcher James , Harris Kathryn , Aquilina Kristian , Kusters Maaike A. , Moshal Karyn , Shingadia Delane , Worth Austen JJ , Lucchini Giovanna , Merve Ashirwad , Jacques Thomas S , Bamford Alasdair , Kaliakatsos Marios , Breuer Judith , Morfopoulou Sofia 
Published: June 2023

ABSTRACTBackgroundAtypical or complex paediatric neurological presentations are common clinical conundrums and often remain undiagnosed despite extensive investigations. This is particularly pronounced in immunocompromised patients. Here we show that clinical metagenomics (CMg) is a valuable adjunct diagnostic tool to be used by neuro-infection multidisciplinary teams (MDTs).MethodsWe included patients referred to the Great Ormond Street Hospital neuro-infection MDT in whom diagnostic uncertainty remained, despite a standardised comprehensive set of investigations, and who were referred for untargeted CMg on brain tissue and/or cerebrospinal fluid (CSF). In a retrospective review, two clinicians independently assessed whether CMg in conjunction with the MDT resulted in a change of management.Findings60 undiagnosed patients met the inclusion criteria. We detected the causative pathogen by CMg in 14/60 (23%), with 12/36 patients known to be immunocompromised. CMg results, even when negative, informed patient care, resulting in changes in clinical management in 42/57 (74%). Six patients had unexpected findings of pathogens not identified on prior samples. In four patients, the pathogen was found solely in the brain biopsy and was absent from all other specimens, including CSF.InterpretationCMg is particularly useful when conventional diagnostic techniques for meningoencephalitis are exhausted and proved to be an important diagnostic tool for immunocompromised patients. CMg provided increased reassurance against an infective aetiology prior to recommending immunosuppressive or immunomodulatory treatment. Specialised MDTs should advocate for early brain biopsies and routine CMg in an experienced laboratory for undiagnosed complex neurological cases affecting immunocompromised patients.
Trans-ancestral genetic study of diabetes mellitus risk in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort and the Childhood Cancer Survivor Study
Authors: Im Cindy , Neupane Achal , Baedke Jessica L. , Delaney Angela , Dixon Stephanie B. , Chow Eric J. , Mostoufi-Moab Sogol , Richard Melissa A. , Gramatges M. Monica , Lupo Philip J. , Sharafeldin Noha , Bhatia Smita , Armstrong Gregory T. , Hudson Melissa M. , Ness Kirsten K. , Robison Leslie L. , Yasui Yutaka , Wilson Carmen L. , Sapkota Yadav 
Published: June 2023

ABSTRACTType 2 diabetes mellitus (T2D) is an established late effect of treatment for childhood cancer. Leveraging detailed cancer treatment and whole-genome sequencing data among survivors of childhood cancer of European (EUR) and African (AFR) genetic ancestry in the St. Jude Lifetime Cohort (N=3,676; 304 cases), five novel diabetes mellitus (DM) risk loci were identified with independent trans-/within-ancestry replication, including in 5,965 survivors of the Childhood Cancer Survivor Study. Among these, common risk variants at 5p15.2 (LINC02112), 2p25.3 (MYT1L), and 19p12 (ZNF492) modified alkylating agent-related risks across ancestry groups, but AFR survivors with risk alleles experienced disproportionately greater risk of DM (AFR, variant ORs: 3.95-17.81; EUR, variant ORs: 2.37-3.32). Novel risk locusXNDC1Nwas identified in the first genome-wide DM rare variant burden association analysis in survivors (OR=8.65, 95% CI: 3.02-24.74, P=8.1×10-6). Lastly, a general-population 338-variant multi-ancestry T2D polygenic risk score was informative for DM risk in AFR survivors, and showed elevated DM odds after alkylating agent exposures (quintiles: combined OREUR=8.43, P=1.1×10-8; ORAFR=13.85, P=0.033). This study supports future precision diabetes surveillance/survivorship care for all childhood cancer survivors, including those with AFR ancestry.
Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke
Authors: van der Sluijs P. Matthijs , Su R. , Cornelissen S.A.P. , van Es A.C.G.M. , Lycklama a Nijeholt G. , Roozenbeek B. , van Doormaal P.J. , Hofmeijer J. , van der Lugt A. , van Walsum T. ,   MR CLEAN Registry investigators
Published: June 2023

AbstractBackgroundEndovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on DSA and functional outcome, using a large EVT registry.MethodsWe included all patients in the MR CLEAN Registry who underwent EVT. We used digital subtraction angiography (DSA) to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale (mRS) at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR).ResultsVessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 1.9 [95%CI 1.2-3.1]) and distal occlusion locations (aOR 2.2 [95%CI 1.4-3.7]) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.41, 95%CI 0.25-0.68) compared to patients without a vessel perforation. No significant association was found between location of perforation or successful reperfusion and functional outcome.ConclusionThe incidence of vessel perforation during EVT is low, but it has severe clinical consequences. Females and patients with a distal occlusion locations are at higher risk. The location of vessel perforation or successful reperfusion did not affect functional outcome.
Effect of Endovascular therapy in large anterior circulation ischemic strokes -a systematic review and meta-analysis
Authors: Panigrahi Baikuntha , Thakur Hameer Subhangi , Bhatia Rohit , Haldar Partha , Sharma Agrata , Srivastava M.V.Padma 
Published: June 2023

ABSTRACTBackground and purposeThe benefit of endovascular treatment in large anterior circulation ischemic strokes with low ASPECTS score(<6) is uncertain. Recent studies have demonstrated the benefit of endovascular treatment (EVT) in large ischemic strokes. The present meta-analysis aims to assess the combined effect of these studies on efficacy and safety of endovascular treatment in this group of patients.Materials and MethodsWe conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases MEDLINE, PubMed, EMBASE, SCOPUS, Google Scholar, Tripdatabase were searched for randomised controlled trials with at least 50 participants. The primary efficacy outcome analysed was the relative risk of functional independence defined as mRS-0-2 at 90 days. Secondary efficacy outcomes included early neurological improvement, death due to any cause at 90 days and proportion of patients requiring decompressive hemicraniectomy. The primary safety outcome was the risk of developing symptomatic intracerebral haemorrhage.ResultsA total of 3 studies(RESCUE Japan-LIMIT,SELECT 2 and ANGEL ASPECTS) involving 1011 patients ; 510 in the EVT arm and 501 in the medical management (MM) arm met the defined criteria (ASPECTS-3-5). The combined RR for the primary outcome of mRS 0-2 was 2.53 [1.84-3.47] (p=<0.0001) favouring EVT over MM. The primary safety outcome of symptomatic intracerebral haemorrhage was not significant in the EVT arm with a combined RR of 1.84 [0.94-3.60] (p=0.5157). Mortality rates were similar in both arms (26.67% in EVT arm vs 27.94% in MM arm) with a combined RR of 0.95 [0.78; 1.16] (p=1.000).ConclusionIn patients with LVO and low ASPECTS (3-5), EVT was associated with higher likelihood of achieving functional independence and early neurologic improvement but did not provide any mortality benefit. The rates of symptomatic ICH were similar in both the groups whereas the risk of any ICH was significantly higher in the EVT arm.Funding-NilThe protocol for the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database(CRD42023400675)
The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in theDrosophilaCNS
Authors: Sukumar Sanjay Kumar , Antonydhason Vimala , Molander Linnea , Sandakly Jawdat , Kleit Malak , Umapathy Ganesh , Mendoza-Garcia Patricia , Masudi Tafheem , Schlossser Andreas , Nässel Dick R. , Wegener Christian , Shirinian Margret , Palmer Ruth H. 
Published: June 2023

AbstractNumerous roles for the Alk receptor tyrosine kinase have been described inDrosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analysed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk/scRNA-seq and protein datasets from larval brains in which Alk signaling was manipulated, identified a previously uncharacterizedDrosophilaneuropeptide precursor encoded byCG4577as an Alk signaling transcriptional target.CG4577, which we namedSparkly (Spar),is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of theDrosophilaAlk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (Clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in theDrosophilaCNS.
Wearable sensor and machine learning accurately estimate tendon load and walking speed during immobilizing boot ambulation
Authors: Kwon Michelle P. , Hullfish Todd J. , Humbyrd Casey J. , Boakye Lorraine A.T. , Baxter Josh R. 
Published: June 2023

AbstractAchilles tendon injuries are treated with progressive weight bearing to promote tendon healing and restore function. Patient rehabilitation progression are typically studied in controlled, lab settings and do not represent the long-term loading experienced during daily living. The purpose of this study is to develop a wearable paradigm to accurately monitor Achilles tendon loading and walking speed using low-cost sensors that reduce subject burden. Ten healthy adults walked in an immobilizing boot under various heel wedge conditions (30°, 5°, 0°) and walking speeds. Three-dimensional motion capture, ground reaction force, and 6-axis inertial measurement unit (IMU) signals were collected per trial. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to predict peak Achilles tendon load and walking speed. The effects of using only accelerometer data, different sampling frequency, and multiple sensors to train the model were also explored. Walking speed models outperformed (mean absolute percentage error (MAPE): 8.41 ± 4.08%) tendon load models (MAPE: 33.93 ± 23.9%). Models trained with subject-specific data performed significantly better than generalized models. For example, our personalized model that was trained with only subject-specific data predicted tendon load with a 11.5 ± 4.41% MAPE and walking speed with a 4.50 ± 0.91% MAPE. Removing gyroscope channels, decreasing sampling frequency, and using combinations of sensors had inconsequential effects on models performance (changes in MAPE < 6.09%). We developed a simple monitoring paradigm that uses LASSO regression and wearable sensors to accurately predict Achilles tendon loading and walking speed while ambulating in an immobilizing boot. This paradigm provides a clinically implementable strategy to longitudinally monitor patient loading and activity while recovering from Achilles tendon injuries.
Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease: an analysis of survival and disability milestones
Authors: Barbosa Raquel , Guedes Leonor Correia , Begoña Cattoni Maria , Pita Lobo Patricia , Castro Caldas Ana , Fabbri Margherita , Bastos Paulo , Valadas Anabela , Carvalho Herculano , Albuquerque Luisa , Reimão Sofia , Gonçalves Ferreira A , Ferreira Joaquim J , Rosa Mário Miguel , Coelho Miguel 
Published: June 2023

AbstractBackgroundData on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) is limited.ObjectivesTo estimate mortality among PD patients 8 years after STN-DBS and to quantify the frequency /time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization).MethodsA longitudinal retrospective study of patients submitted to STN-DBS between 2006-2012 was carried-out. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions calculated. Multivariable regression analysis in the presence of competing risks was performed based on the Gray’s test of sub-distribution hazards of cumulative incidence functions.ResultsAn overall mortality rate of 16% (mean 62.1 ± 21.3 months after surgery) was observed. Falls (73%) and freezing (47%) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequently observed milestones. Dementia (34%) and hallucinations (32%) soon follow (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Institutionalization occurred in 6% after 62.3 ± 22.0 months. Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization.ConclusionsLong-term mortality rate is low after STN-DBS, with STN-DBS patients developing the same disability milestones as non-DBS patients. Motor milestones occur first and at a higher frequency than cognitive ones. Milestones cluster together before death.
Identification of hepatocyte immune response in Autoimmune Hepatitis from human plasma cfChIP-seq
Authors: Fialkoff Gavriel , Ya’akov Ami Ben , Sharkia Israa , Sadeh Ronen , Gutin Jenia , Goldstein Chen , Khalaileh Abed , Imam Ashraf , Safadi Rifaat , Milgrom Yael , Galun Eithan , Shteyer Eyal , Friedman Nir 
Published: June 2023

AbstractAutoimmune hepatitis (AIH) is a self-perpetuating inflammatory liver disease with significant morbidity and mortality risks. Patients undergo liver biopsy to confirm diagnosis and affirm subsequent remission. Advances in liquid biopsies show promise to replace tissue biopsy in cancer, however little research has been done in liver disease. Here, we use plasma chromatin immunoprecipitation and sequencing (cfChIP-seq) to analyze cell-free nucleosomes carrying an active histone modification which reports on gene transcription in the dying cells. Comparing plasma samples from pediatric AIH patients to a control group we identify immune-related transcriptional processes activated in hepatocytes of AIH patients. We devise a classifier that based on cfChIP-seq profiles distinguishes AIH from other conditions involving increased liver damage. Our work demonstrates the potential of plasma cfChIP-seq as a non-invasive diagnostic tool for AIH, which could replace the need for liver biopsy, aid accurate diagnoses, and enable further scientific exploration of AIH pathogenesis.
Evaluation of the performance of GPT-3.5 and GPT-4 on the Medical Final Examination
Authors: Rosoł Maciej , Gąsior Jakub S. , Łaba Jonasz , Korzeniewski Kacper , Młyńczak Marcel 
Published: June 2023

AbstractIntroductionThe rapid progress in artificial intelligence, machine learning, and natural language processing has led to the emergence of increasingly sophisticated large language models (LLMs) enabling their use in various applications, including medicine and healthcare.ObjectivesThe study aimed to evaluate the performance of two LLMs: ChatGPT (based on GPT-3.5) and GPT-4, on the Medical Final Examination (MFE).MethodsThe models were tested on three editions of the MFE from: Spring 2022, Autumn 2022, and Spring 2023 in two language versions – English and Polish. The accuracies of both models were compared and the relationships between the correctness of answers with the index of difficulty and discrimination power index were investigated.ResultsThe study demonstrated that GPT-4 outperformed GPT-3.5 in all three examinations regardless of the language used. GPT-4 achieved mean accuracies of 80.7% for Polish and 79.6% for English, passing all MFE versions. GPT-3.5 had mean accuracies of 56.6% for Polish and 58.3% for English, passing 2 of 3 Polish versions and all 3 English versions of the test. GPT-4 score was lower than the average score of a medical student. There was a significant positive and negative correlation between the correctness of the answers and the index of difficulty and discrimination power index, respectively, for both models in all three exams.ConclusionsThese findings contribute to the growing body of literature on the utility of LLMs in medicine. They also suggest an increasing potential for the usage of LLMs in terms of medical education and decision-making support.What’s new?Recent advancements in artificial intelligence and natural language processing have resulted in the development of sophisticated large language models (LLMs). This study focused on the evaluation of the performance of two LLMs, ChatGPT (based on GPT-3.5) and GPT-4, on the Medical Final Examination across English and Polish versions from three editions. This study, to the best of our knowledge, presents the first validation of those models on the European-based medical final examinations. The GPT-4 outperformed GPT-3.5 in all exams, achieving mean accuracy of 80.7% (Polish) and 79.6% (English), while GPT-3.5 attained 56.6% (Polish) and 58.3% (English) respectively. However, GPT-4’s scores fell short of typical medical student performance. These findings contribute to understanding LLM’s utility in medicine and hint at their potential in medical education and decision-making support.
The microstructure and corrosion behavior of Cr-containing ferrite-pearlite steels in an acidic environment
Authors: Hao Xuehui , Wang Changzheng , Guo Shuai , Ma Jie , Chen Hui , Zhao Xingchuan 
Published: June 2023

Purpose
The poor corrosion resistance of the ferrite-pearlite steel limits its application in marine engineering because of the enhanced galvanic effect caused by continuously accumulated cementite. Cr as one principal alloying element is commonly used to improve the corrosion resistance of steels. This paper aims to study the effect of Cr on corrosion behaviors of ferrite-pearlite steels in an acidic environment.

Design/methodology/approach
The tested steels were immersed in a simulated solution of 10 Wt.% NaCl with pH 0.85 for 72 h to evaluate the corrosion rate. After the immersion test, the corrosion morphologies and products were tested by scanning electron microscopy, energy dispersive X-ray analysis and X-ray diffraction. Meanwhile, an electrochemical workstation was used to study the electrochemical behaviors of samples.

Findings
At the initial corrosion stage, the corrosion rate increased in the sequence of Cr0, Cr0.5 and Cr1 steels, which was because of the competitive effect between the area ratio and the driving force caused by alloyed Cr. However, Cr1 steel exhibited the best corrosion resistance after a 72-h immersion test. This was because the alloyed Cr promoted the formation of protective Fe2O3 and FeCr2O4, which suppressed the preferential dissolution of ferrite and, thus, reduced the accumulation rate of carbides, resulting in the weakened galvanic corrosion.

Originality/value
This paper reports the role that Cr plays in the galvanic corrosion of ferrite-pearlite steels, which is important for the engineering application of ferrite-pearlite steels in marine environment.