bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of newly introduced endoscopic submucosal dissection in a Western center: a real-life study
Authors: Sferrazza Sandro , Maida Marcello , Calabrese Giulio , Fiorentino Andrea , Vieceli Filippo , Facciorusso Antonio , Fuccio Lorenzo , Maselli Roberta , Repici Alessandro , Di Mitri Roberto 
Published: July 2024

Objectives
Endoscopic submucosal dissection (ESD) is a minimally invasive technique for the resection of superficial gastrointestinal lesions, providing high rates of ‘en bloc’ and R0 resection. East-West differences in ESD quality indicators have been reported. This study aims to assess feasibility, effectiveness, and safety of ESD for the treatment of superficial gastrointestinal (GI) lesions in a Western cohort.

Methods
Consecutive patients undergoing ESD at one Italian endoscopic referral center from September 2018 to March 2020 were included in this prospective study. Primary outcomes were technical success, R0 resection rate, curative resection rate, and adverse events (AEs).

Results
In total 111 patients (111 lesions) undergoing ESD were included. Anatomic site of the lesions was rectum in 56.8%, colon in 13.5%, stomach in 24.3%, and esophagus in 5.4% of cases, respectively. For upper GI procedures, technical success was 100%, and R0 and curative resection rates were 84.8% and 78.8%, respectively. For colorectal procedures, technical success was 98.7%, R0 and curative resection rates were 88.5% and 84.6%, respectively. Major AEs were reported in 12 cases (10.8%).

Conclusion
The introduction of ESD in a Tertiary Center is feasible, effective, and safe, and should be taken into consideration for the treatment of superficial GI lesions requiring ‘en bloc’ resection.
Key factors for sustainable working conditions in emergency departments: an EUSEM-initiated, Europe-wide consensus survey
Authors: Weigl Matthias , Lifschitz Michael , Dodt Christoph 
Published: July 2024

Background and importance
Modern emergency medicine (EM) is a complex, demanding, and occasionally stressful field of work. Working conditions, provider well-being, and associated health and performance outcomes are key factors influencing the establishment of a sustainable emergency department (ED) working environment.

Objectives
This multinational European Delphi survey aimed to identify unequivocal major factors for good and poor ED working conditions and their possible effects on health care provider well-being.

Design/setting and participants
A total of 18 experts from six European countries (Belgium, Finland, Germany, Italy, Romania, and the UK) covering three different hospital sizes (small, medium, and large) in their respective countries participated in the two-round Delphi survey. All panelists held leadership roles in EM.

Outcome measures and analysis
The first step involved conducting an extensive literature search on ED working conditions. The second step involved the first Delphi round, which consisted of structured interviews with the panelists. The survey was designed to obtain information concerning important working conditions, comments regarding work-life factors identified from the literature, and ratings of their importance. Interviews were transcribed and analyzed following a standardized protocol. In the second Delphi round, experts rated the relevance of items consolidated from the first Delphi round (classified into ED work system factors, provider health outcomes, and ED work-life intervention approaches).

Results
A nearly unequivocal consensus was obtained in four ED work condition categories, including positive (e.g. job challenges, personal motivation, and case complexities) and negative (e.g. overcrowding, workflow interruptions/multitasking, medical errors) ED work conditions. The highly relevant adverse personal health events identified included physical fatigue, exhaustion, and burnout. Concerning intervention practices, the panelists offered a wide spectrum of opportunities with less consensus.

Conclusion
Work system conditions exert positive and negative effects on the work life of ED providers across Europe. Although most European countries have varying health care systems, the expert-based survey results presented herein strongly suggest that improvement strategies should focus on system-related external stressors common in various countries. Our findings lay the scientific groundwork for future intervention studies at the local and systemic levels to improve ED provider work life.
Concept Analysis of Woman-Centered Care
Authors: Sposato Margaret F. , Miller Wendy R. 
Published: July 2024

Abstract
Approximately two-thirds of pregnancy-related deaths in the United States occur during the postpartum period, yet there is minimal research focusing on the postpartum hospital stay, a critical point of contact between women and the health care system and an important opportunity for intervention. A new approach to postpartum care is needed. “Woman-centered” postpartum care is recommended to improve maternal outcomes, but the concept of woman-centered care is not well-defined. Using Walker & Avant's method of concept analysis, we identified four defining attributes of woman-centered care in the literature: 1) choice, control, and involvement in decision-making; 2) communication and collaboration in the caregiver–woman relationship; 3) individualized and holistic care; and 4) continuity of care. Using these findings, we offer a conceptual definition of woman-centered care and apply the attributes to the postpartum hospitalization in the model and contrary cases. We discuss the potential of the concept to improve maternal health care during this critical period.
HETEROGENEOUS EXPANSION OF POLYMORPHONUCLEAR MYELOID-DERIVED SUPPRESSOR CELLS DISTINGUISHES HIGH-RISK SEPSIS IMMUNOPHENOTYPES IN UGANDA
Authors: Cummings Matthew J. , Guichard Vincent , Owor Nicholas , Ochar Thomas , Kiwubeyi Moses , Nankwanga Rittah , Kibisi Richard , Kassaja Charles , Ross Jesse E. , Postler Thomas S. , Kayiwa John , Reynolds Steven J. , Nakibuuka Martina Cathy , Nakaseegu Joweria , Lutwama Julius J. , Lipkin W. Ian , Ghosh Sankar , Bakamutumaho Barnabas , O’Donnell Max R. 
Published: July 2024

ABSTRACT

Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36–59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. Results: Patients who died showed heterogeneous expansion of polymorphonuclear myeloid-derived suppressor cells, with increased and decreased abundance of CD16−PD-L1dim and CD16brightPD-L1bright subsets, respectively, significantly associated with mortality. While differences between CD16−PD-L1dim cell abundance and mortality risk appeared consistent throughout the course of illness, those for the CD16brightPD-L1bright subset were more pronounced early after illness onset. Independent of HIV co-infection, depletion of CD4+ T cells, dendritic cells, and CD56−CD16bright NK cells were significantly associated with mortality risk, as was expansion of immature, CD56+CD16−CD11c+ NK cells. Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG-3) was similar between patients who died versus those who survived. Conclusions: This is the first study to define high-risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of myeloid derived suppressor cell expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.
Bridging the gap: a prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia
Authors: Rafehi Haloom , Fearnley Liam G. , Read Justin , Snell Penny , Davies Kayli C. , Scott Liam , Gillies Greta , Thompson Genevieve C. , Field Tess A. , Eldo Aleena , Bodek Simon , Butler Ernest , Chen Luke , Drago John , Goel Himanshu , Hackett Anna , Halmagyi G. Michael , Hannaford Andrew , Kotschet Katya , Kumar Kishore R. , Kumble Smitha , Lee-Archer Matthew , Malhotra Abhishek , Paine Mark , Poon Michael , Pope Kate , Reardon Katrina , Ring Steven , Ronan Anne , Silsby Matthew , Smyth Renee , Stutterd Chloe , Wallis Mathew , Waterston John , Wellings Thomas , West Kirsty , Wools Christine , Wu Kathy H. C. , Szmulewicz David J. , Delatycki Martin B. , Bahlo Melanie , Lockhart Paul J. 
Published: July 2024

ABSTRACTThe cerebellar ataxias (CA) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% of genetic diagnoses. Despite this, diagnostic testing is limited and inefficient, often utilizing single gene assays. This study evaluated the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Independently, long-read sequencing with adaptive sampling (LR-AS) and performed to identify pathogenic RE. SR-GS identified pathogenic variants in 38% of the cohort (40/110). RE caused disease in 33 individuals, with the most common condition being SCA27B (n=24). In comparison, LR-AS identified pathogenic RE in 29 individuals. RE identification for the two methods was concordant apart from four SCA27B cases not detected by LR-AS due to low read depth. For both technologies manual review of the RE alignment enhanced diagnostic outcomes. Orthogonal testing for SCA27B revealed a 16% and 0% false positive rate for SR-GS and LR-AS respectively. In conclusion, both technologies are powerful screening tools for CA. SR-GS is a mature technology currently utilized by diagnostic providers, requiring only minor changes in bioinformatic workflows to enable CA diagnostics. LR-AS offers considerable advantages in the context of RE detection and characterization but requires optimization prior to clinical implementation.
CT-Perfusion absolute Ghost Infarct Core is a rare phenomenon associated with poor collateral status in acute ischemic stroke patients
Authors: Busto Giorgio , Morotti Andrea , Casetta Ilaria , Poggesi Anna , Gadda Davide , Ginestroni Andrea , Arcara Giorgio , Rustici Arianna , Zini Andrea , Padovani Alessandro , Fainardi Enrico 
Published: July 2024

ABSTRACTBackgroundCT-Perfusion (CTP) overestimation of core volume >10 mL compared to the final infarct volume (FIV) size is the current definition of the ghost infarct core (GIC) phenomenon. However, subsequent infarct growth might influence FIV. We aimed to report a more reliable assessment of GIC occurrence, defined as the lack of FIV at 24 hours follow-up imaging, compared to CTP core volume at admission. This phenomenon was named absolute GIC (aGIC) and we investigated its prevalence and predictors.MethodsA total of 652 consecutive stroke patients with large vessel occlusion who achieved successful recanalization (mTICI 2b-3) after Endovascular Treatment (EVT) and non-contrast CT (NCCT) follow-up imaging at 24 hours were retrospectively analyzed. Ischemic core volume was automatically generated from CTP, and FIV was manually determined on follow-up NCCT. Multivariable logistic regression was used to explore aGIC predictors.ResultsWe included 652 patients (53.3% female, median age 75 years), of whom 35 (5.3%) had an aGIC. The aGIC group showed higher ASPECTS (p<0.001), shorter (<3 hours) onset-to-imaging time (p<0.001), poorer collaterals (p<0.001), higher hypoperfusion intensity ratio (p=0.001) compared to the non-aGIC group. In multivariate analysis, ASPECTS (odds ratio [OR], 1.87; p<0.001), onset-to-imaging time (OR, 0.99; p=0.013), collateral score (OR, 0.45; p<0.004) and hypoperfusion intensity ratio (OR, 23.2; p<0.001) were independently associated with aGIC.ConclusionaGIC is a more reliable evaluation of infarct core volume overestimation assessed on admission CTP and represents a rare phenomenon, associated with ultra-early presentation and poor collaterals.
Serum Glial Fibrillary Acidic Protein: Potential to Determine Stroke-Type, Time-Line and Tissue-Impact in Acute Stroke
Authors: Paul Julien F. , Ducroux Célina , Correia Pamela , Daigneault Audrey , Larochelle Catherine , Stapf Christian , Gioia Laura C. 
Published: July 2024

ABSTRACTBackgroundInterest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management.MethodsIn 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging. Serum levels (pg/mL) of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were analyzed according to time of symptom onset, neuroimaging, and final diagnosis.ResultsAcute ischemic stroke (AIS) was diagnosed in 35 patients, 10 with large-vessel occlusion (LVO). The remaining were diagnosed with intracerebral hemorrhage (ICH) (n = 12), transient ischemic attack (n=4), and stroke mimics (n=11). Median(IQR) GFAP levels were significantly higher in ICH (2,877.8 [1,002.1-10,402.5] pg/mL) compared to others diagnoses. In AIS, GFAP levels appear to increase over time from symptom onset, and were higher in patients with more extensive ischemic changes on baseline CT (ASPECTS ≤ 7) than those without, particularly in LVO stroke. NfL values were similar across groups.ConclusionsIn acute stroke, serum GFAP shows potential as an adjunct tool for the distinction between ICH and AIS. Specific to AIS, GFAP may also offer insight into time from onset, and extent of ischemic tissue injury on neuroimaging, particularly in LVO stroke. These preliminary findings merit further study.
Measuring the Immune Memory Response of In Vitro Polarized Th1, Th2, and Th17 Cells in the Face of OVA TransgenicLeishmania major inMouse Model
Authors: Tedla Mebrahtu G. , Nahar Musammat F. , Every Alison L. , Scheerlinck Jean-Pierre Y. 
Published: July 2024

AbstractTh1 and Th2 cytokines determine the outcome ofLeishmania majorinfection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenicLeishmania majorexpressing membrane associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) are used as a model to study whether fully differentiated Th1/ Th2 &Th17 cells can recall immune memory and tolerate pathogen manipulation. Naïve OT-II T cells werein vitropolarised into Th1/Th2, and these cells were transferred adoptively into recipient mice. Following transferring the memory cells, recipient mice were challenged with OVA transgenicLeishmania majorand wild type parasite was used a control. Thein vitropolarised T helper cells continued to produce the same cytokine signatures after challenged by both forms of OVA-expressingLeishmania majorparasitesin vivo. This suggests antigen-experienced cells cells remain the same or unaltered in the face of OVA transgenicLeishmania major. Such ability of the antigen-experienced cells to remain resilient to manipulation by the parasite signifies that vaccines might be able to produce immune memory responses and withstand against the parasite immune manipulation and protect the host from infection.
Restoring data balance via generative models of T-cell receptors for antigen-binding prediction
Authors: Loffredo Emanuele , Pastore Mauro , Cocco Simona , Monasson Rémi 
Published: July 2024

Unveiling the specificity in T-cell-receptor and antigen recognition represents a major step to understand the immune system response. Many supervised machine learning approaches have been designed to build sequence-based predictive models of such specificity using binding and non-binding examples of data. Due to the presence of few specific and many non-specific T-cell receptors for each antigen, available datasets are heavily imbalanced and make the goal of achieving solid predictive performances very challenging. Here, we propose to restore data balance through data augmentation using generative unsupervised models. We then use these augmented data to train supervised models for prediction of peptide-specific T-cell receptors and binding pairs of peptide and T-cell receptors sequences. We show that our pipeline yields increased performance in terms of T-cell receptors specificity prediction tasks. More broadly, our work provides a general framework to restore balance in computational problems involving biological sequence data.Significance StatementThe adaptive immune system carries a diverse set of T-cell receptors capable of recognizing pathogens and protect the host from diseases. Predicting whether a receptor binds a pathogenic peptide is a fundamental computational problem, made difficult by the imbalance in available data: relatively few binding pairs are known compared to all possible pairs of receptors and peptides. Here, we propose to mitigate this imbalance problem by generating putative binding pairs through data augmentation machine-learning methods. We show that these extra data helps training binding prediction models and improves their performances. Our framework for sequence data augmentation is generic and could be applied to other biological computational problems.
Physical activity modulates early visual response and improves target detection in humans
Authors: Weischner Tom , Che Xinyun , Schmid Paul , Reichert Christoph , Scholz Annemarie , Knight Robert T. , Dürschmid Stefan 
Published: July 2024

AbstractBrain state changes affect visual perception by altering spatial resolution. Attention enhances the spatial resolution decorrelating neuronal activity in early nonhuman primate (NHP) visual cortex. Physical activity (PA) amplifies these attentional effects in rodents but impact of PA on visual perception in humans remains uncertain. We investigated the relationship between broadband high-frequency activity (BHA: 80-150 Hz) recorded with magnetoencephalography (MEG) and visual detection performance. We found that PA enhanced visual target detection predicted by a reduction of early BHA responses (<90 msec). This effect may be due to reduced interneuronal correlation to improve spatial resolution. Moreover, PA improved spatial integration time, as indicated by a linear relationship between reaction times and BHA variation with target eccentricity. These findings provide evidence that PA influences neuronal activity critical for early visual perception, optimizing visual processing at the initial stages of the visual hierarchy.
Uneven Walking is Challenging: step-ups or extended steps that is the question
Authors: Hosseini-Yazdi Seyed-Saleh 
Published: July 2024

AbstractUneven terrain presents significant challenges for walkers, resulting in increased energy expenditures. Given that Center of Mass (COM) work reflects this energy demand, it's reasonable to assume that individuals also seek strategies to minimize mechanical work. One such strategy involves deciding between extending step length to avoid terrain irregularities or simply traversing over them. Each approach carries its own mechanical cost, leading to the adoption of the less costly option. To investigate this, we conducted a simulation focusing on COM mechanical work under the assumption that gait energy is entirely provided through pre-emptive push-off. We examined the COM work required for step length extension, ranging from nominal to twice its magnitude, and compared it with the mechanical work needed for step-ups from zero to 0.05 m. The simulation revealed a critical threshold for a given walking velocity and perturbation amplitude: below it, extending step length was more favorable, while beyond it, landing atop perturbations became the preferred choice. As perturbation amplitude rose, the magnitude of the threshold also increased.
Determining potential immunomodulatory drug efficacy in sepsis using ELISpot
Authors: Walton AH , Mazer MB , Remy KE , Davitt EB , Griffith TS , Gould RW , Badovinac VP , Brakenridge SC , Drewry AM , Loftus TJ , Efron PA , Moldawer LL , Caldwell CC , Hotchkiss RS 
Published: July 2024

ABSTRACTPurposeThis study evaluated the ability of ELISpot to identify immuno-modulatory drug therapies for their potential efficacy in patients with sepsis.MethodsELISpot was performed using diluted whole blood from 61 septic patients and 48 healthy matched controls. Innate and adaptive immunity were evaluated byex vivostimulated production of TNF-α and IFN-γ respectively. Potential drug efficacy was determined by the drugs’ effects to increase or decrease the number of cytokine-producing cells and amount of cytokine produced per cell as determined by spot size and intensity. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T-cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance immune responses in sepsis.ResultsSpontaneous production of TNF-α and IFN-γ varied among healthy subjects and septic patients. LPS or resiquimod stimulation increased total TNF-α production in septic patients by 1,648% and 1,929% respectively. Conversely, dexamethasone diminished the responses to LPS or resiquimod by 71% and 61% respectively. IL-7, but not anti-PD-1 mAb markedly increased IFN-γ production in both healthy subjects (127%) and septic patients (79%). Dexamethasone also reduced anti-CD3/CD28 mAb stimulated IFN-γ production by 54%; while IL-7 ameliorated dexamethasone-induced suppression. IL-7 significantly enhanced lymphocyte function in over 90% of septic patients.ConclusionELISpot can reveal host immune response patterns and the effects of drugs to selectively down– or up-regulate patient immunity. Furthermore, the ability of ELISpot to detect the effect of specific immuno-modulatory drugs to independently regulate the innate and adaptive host response could enable precision-based immune drug therapies in sepsis.