bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with appendicitis during COVID-19 pandemic: a retrospective cohort study
Authors: Ricard Elizabeth , Marceau Alexandre , Larouche Gabrielle , Dorval Heidi , Malo François-Charles 
Published: April 2023

Background:The Coronavirus Disease 19 (COVID-19) pandemic greatly affected the Quebec healthcare system from spring 2020 onward; the consultation delays that were generated may have delayed the management of urgent intra-abdominal pathologies. Our objective was to evaluate the impact of the pandemic on the length of stay and complications within 30 days of treatment of patients consulting for acute appendicitis (AA) at theCentres intégrés universitaires de santé et de services sociaux(CIUSSS)de l’Estrie-Centre hospitalier universitaire de Sherbrooke(Estrie-CHUS), Quebec, Canada.Methods:The authors conducted a single-center retrospective cohort study on the charts of all patients diagnosed with AA at the CIUSSS de l’Estrie-CHUS between March 13 and June 22, 2019 (control group) and between March 13 and June 22, 2020 (pandemic group). This corresponds to the first wave of COVID-19 in Quebec. Patients included were those with a radiologically confirmed diagnosis of AA. There was no exclusion criteria. Outcomes assessed were length of hospital stay and 30-day complications.Results:The authors analyzed the charts of 209 patients with AA (117 patients in the control group and 92 patients in the pandemic group). No statistically significant difference was observed for the length of stay or the complications between the groups. The only significant difference was the presence of hemodynamic instability on admission (22.2 vs. 41.3%,P=0.004) as well as a trend that did not reach statistical significance regarding the proportions of reoperation before 30 days (0.9 vs. 5.4%,P=0.060).Conclusion:In conclusion, the pandemic did not affect the length of stay of AA managed at the CIUSSS de l’Estrie-CHUS. It is not possible to conclude whether the first wave of the pandemic influenced complications related to AA.
A Random Forest Model Using Flow Cytometry Data Identifies Pulmonary Infection after Thoracic Injury
Authors: Gelbard Rondi B. , Hensman Hannah , Schobel Seth , Stempora Linda , Gann Eric , Moris Dimitrios , Dente Christopher J. , Buchman Timothy , Kirk Allan , Elster Eric 
Published: April 2023

Abstract

Background
Thoracic injury can cause impairment of lung function leading to respiratory complications such as pneumonia. There is increasing evidence that central memory T cells of the adaptive immune system play a key role in pulmonary immunity. We sought to explore whether assessment of cell phenotypes using flow cytometry (FCM) could be used to identify pulmonary infection after thoracic trauma.

Methods
We prospectively studied trauma patients with thoracic injuries who survived >48 h at a Level 1 trauma center from 2014-2020. Clinical and FCM data from serum samples collected within 24 h of admission were considered as potential variables. Random forest (RF) and logistic regression (LR) models were developed to estimate the risk of hospital-acquired and ventilator-associated pneumonia (PNA). Variables were selected using backwards elimination and models were internally validated with leave-one-out.

Results
Seventy patients with thoracic injuries were included (median age 35y (IQR: 25.25 - 51) 62.9% (44/70) male, 61.4% (42/70) blunt trauma). The most common injuries included rib fractures (52/70, 74.3%) and pulmonary contusions (26/70, 37%). The incidence of PNA was 14/70 (20%). Median ISS was similar for patients with and without PNA (30.5 (IQR 22.6 - 39.3) vs 26.5 (IQR 21.6 - 33.3). The final RF model selected three variables (APACHE score, highest pulse rate in first 24 h, and frequency of CD4+ central memory (CM) cells) that identified PNA with an AUC of 0.93, sensitivity of 0.91, and specificity of 0.88. A logistic regression with the same features had an AUC of 0.86, sensitivity of 0.76, and specificity of 0.85.

Conclusion
Clinical and FCM data have diagnostic utility in the early identification of patients at risk of nosocomial pneumonia following thoracic injury. Signs of physiologic stress and lower frequency of CM cells appear to be associated with higher rates of pneumonia after thoracic trauma.

Level of Evidence
Diagnostic test/criteria, IV
The Impact Of COVID-19 on Health Financing in Kenya
Authors: Kairu Angela , Orangi Stacey , Mbuthia Boniface , Arwah Brian , Guleid Fatuma , Keru Janet , Vilcu Ileana , Musuva Anne , Ravishankar Nirmala , Barasa Edwine 
Published: April 2023

ABSTRACTBackgroundSudden shocks to health systems, such as the COVID-19 pandemic may disrupt health system functions. Health system functions may also influence the health system’s ability to deliver in the face of sudden shocks such as the COVID-19 pandemic. We examined the impact of COVID-19 on the health financing function in Kenya, and how specific health financing arrangements influenced the health systems capacity to deliver services during the COVID-19 pandemic.MethodsWe conducted a cross-sectional study in three purposively selected counties in Kenya using a qualitative approach. We collected data using in-depth interviews (n = 56) and relevant document reviews. We interviewed national level health financing stakeholders, county department of health managers, health facility managers and COVID-19 healthcare workers. We analysed data using a framework approach.ResultsPurchasing arrangements: COVID-19 services were partially subsidized by the national government, exposing individuals to out-of-pocket costs given the high costs of these services. The National Health Insurance Fund (NHIF) adapted its enhanced scheme’s benefit package targeting formal sector groups to include COVID-19 services but did not make any adaptations to its general scheme targeting the less well-off in society. This had potential equity implications. Public Finance Management (PFM) systems: Nationally, PFM processes were adaptable and partly flexible allowing shorter timelines for budget and procurement processes. At county level, PFM systems were partially flexible with some resource reallocation but maintained centralized purchasing arrangements. The flow of funds to counties and health facilities was delayed and the procurement processes were lengthy. Reproductive and child health services: Domestic and donor funds were reallocated towards the pandemic response resulting in postponement of program activities and affected family planning service delivery. Universal Health Coverage (UHC) plans: Prioritization of UHC related activities was negatively impacted due the shift of focus to the pandemic response. Contrarily the strategic investments in the health sector were found to be a beneficial approach in strengthening the health system.ConclusionsStrengthening health systems to improve their resilience to cope with public health emergencies requires substantial investment of financial and non-financial resources. Health financing arrangements are integral in determining the extent of adaptability, flexibility, and responsiveness of health system to COVID-19 and future pandemics.
Personalized digital behavior interventions increase short term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health study
Authors: Javed Ali , Kim Daniel Seung , Hershman Steven G , Shcherbina Anna , Johnson Anders , Tolas Alexander , O’Sullivan Jack W , McConnell Michael V , Lazzeroni Laura , King Abby C , Christle Jeffrey W , Oppezzo Marily , Mattsson C. Mikael , Harrington Robert A , Wheeler Matthew T , Ashley Euan A 
Published: April 2023

ABSTRACTBackgroundPhysical activity is strongly protective against the development of chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity. Our randomized crossover trial has continued to digitally enroll participants, allowing increasing statistical power for greater precision in subsequent analyses.MethodsWe offered enrollment to adults aged ≥18 years with access to an iPhone and the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomly allocated to four 7-day interventions. Interventions consisted of: 1) daily personalized e-coaching based on the individual’s baseline activity patterns, 2) daily prompts to complete 10,000 steps, 3) hourly prompts to stand following inactivity, and 4) daily instructions to read guidelines from the American Heart Association website. The trial was completed in a free-living setting, where neither the participants or investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis. This trial is registered withClinicalTrials.gov,NCT03090321.FindingsBetween January 1, 2017 and April 1, 2022, 4500 participants consented to enroll in the trial, of whom 2458 completed 7-days of baseline monitoring (mean daily steps 4232±73) and at least one day of one of the four interventions. The greater statistical power afforded by continued passive enrollment revealed that e-coaching prompts, tailored to an individual, increased step count significantly more than other interventions (402±71 steps,P=7.1×10−8).InterpretationDigital studies can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we show that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized.FundingStanford Data Science Initiative and Catalyst Program, Apple, Google
Direct Estimate of the Specificity Constant: A Possibility or a Fluke? Pre-steady-state Substrate Concentrations and Enabling Mathematical Equations
Authors: Udema Ikechukwu Iloh 
Published: April 2023

ABSTRACTBackgroundA high-ranking scientist has recently proposed the need for direct estimation of the specificity constant rather than by calculation after a separate determination of maximum velocity and the Michaelis-Menten constant (KM).ObjectivesThe objectives of this study are to derive novel equations for the zero-arbitrary determination of pre-steady-state (PSS) concentration of the substrate suitable for PSS assays, direct estimation of specificity constant (SC) under a PSS scenario, saturating concentration [ST] of the substrate, and instantaneous initial rate (otherwise called the “burst phase-like” rate), including its corresponding [ST]0, and to quantitatively evaluate the derived equations so as to give credence to their robustness and applicability.MethodsThe study was experimental and theoretical. It is supported by the Bernfeld method of enzyme assay.ResultThe SC values from the two newest methods for the three different concentrations of the enzyme range between 2,197.546 and 11,101.74 L/g min in one of the methods and 2,185.649 and 13,860.014 L/g min in the other method. The sub-KMvalues of the SC for the three different concentrations of the enzyme range between 1304.368 and 7943 L/g min. The burst phase-like initial rate,v0, and corresponding [ST]0, respectively, range between 14.26 and 55.448 micro-mol./min and 0.171 and 3.752 g/L.ConclusionThe derivation of the equations for the direct calculations of SC in conditions that validate the reverse and standard quasi-steady-state approximations was a possibility; the SC values are higher at lower concentrations of the enzyme. The concept of SC is very different from catalytic efficiency. The total absence of any calculation is impossible.Abstract FigureGraphical abstract figure for the direct estimate of the specificity constantFor the purpose of this study, the legends, SUB (S), ENZ (E), and PRD represents substrate, enzyme and product respectively. Lower number density (red) of the enzyme molecules in Figure 1 showing > number density of the product (light green) for the same concentration of the substrate (darker blue) than in Figure 2 implies that the catalytic efficiency in Figure 1 is > the illustration in Figure 2.
Optimizing rabies vaccination of dogs in India
Authors: Cuddington Kim , McAuliffe William H.B. 
Published: April 2023

SummaryDog vaccination is the key to controlling rabies in human populations. However, in countries like India, with large free-roaming dog populations, vaccination strategies that rely only on parenteral vaccines are unlikely to be either feasible or successful. Oral rabies vaccines could be used to reach these dogs. We use costs estimates for an Indian city and linear optimization to find the most cost-effective vaccination strategies. We show that an oral bait handout method for dogs that are never confined can reduce the per dog costs costs of vaccination, and increase vaccine coverage. This finding holds even when baits cost up to 10x the price of parenteral vaccines, if there is a large dog population or proportion of dogs that are never confined. We suggest that oral rabies vaccine baits will be part of the most cost-effective strategies to eradicate human deaths from dog-mediated rabies by 2030.
Sex Differences in BNST Signaling and BNST CRF in Fear Processing: Implications for Unpredictable Threat in Sustained Fear
Authors: Hon Olivia J. , Neira Sofia , Flanigan Meghan E. , Roland Alison V. , Caira Christina M. , Sides Tori , D’Ambrosio Shannon , Lee Sophia , Simpson Yolanda , Buccini Michelle , Machinski Samantha , Yu Waylin , Boyt Kristen M. , Kash Thomas L. 
Published: April 2023

ABSTRACTFear responses to perceived danger are critical for survival, as they prompt the individual to respond to threats and avoid harm. However, excessive fear can impede normal biological processes and become harmful. This study investigates the neural mechanisms underlying two distinct forms of fear—phasic and sustained—in male and female mice, with a focus on the bed nucleus of the stria terminalis (BNST) and corticotropin-releasing factor (CRF) signaling. Phasic fear is characterized by immediate responses to clear threats, while sustained fear is driven by ambiguous or uncertain cues and persists longer. Using rodent models, we found that sustained fear, modeled by partial fear conditioning, induced greater arousal and BNST activity in males, especially during ambiguous threat cues. In contrast, females exhibited reduced BNST and BNSTCRFactivity, highlighting significant sex differences in fear learning and expression. Additionally, CRF is crucial for appropriate fear response in females, as CRF knockdown led to increased fear responses, but had no effect in males. These sex-specific differences could help inform the development of targeted treatments for anxiety and trauma-related disorders, which disproportionately affect women.
Synaptic dysfunction and dysregulation of extracellular matrix-related genes in dopaminergic neurons derived from Parkinson’s disease sporadic patients and withGBA1mutations
Authors: Rosh Idan , Tripathi Utkarsh , Hussein Yara , Rike Wote Amelo , Manole Andreea , Cordeiro Diogo , Houlden Henry , Winkler Jurgen , Gage Fred , Stern Shani 
Published: April 2023

AbstractParkinson’s disease (PD) is a neurodegenerative disease with both genetic and sporadic origins. In this study, we investigated the electrophysiological properties, synaptic activity, and gene expression differences in dopaminergic (DA) neurons derived from induced pluripotent stem cells (iPSCs) of healthy controls, sporadic PD (sPD) patients, and PD patients with GBA1 mutations. Our results demonstrate reduced sodium currents and synaptic activity in DA neurons derived from PD patients with GBA1 mutations, suggesting a potential contribution to PD pathophysiology. We also observed distinct electrophysiological alterations in sPD DA neurons that were dependent on the age of disease onset. RNA sequencing analysis revealed unique dysregulated pathways in early and late-onset sPD neurons, further supporting the notion that molecular mechanisms driving PD may be different between PD patients. In agreement with our previous reports, ECM and focal adhesion genes were the top dysregulated pathways in DA neurons from sPD patients and from patients with GBA1 mutations. Overall, this study gives further confirmation that the convergent functional phenotypes of DA neurons derived from PD patients are synaptic abnormalities and at the transcriptome level, ECM and focal adhesion pathways are highly involved in PD pathology across multiple PD-associated mutations as well as sPD.
MORE IS DIFFERENT: DRUG PROPERTY ANALYSIS ON CELLULAR HIGH-CONTENT IMAGES USING DEEP LEARNING
Authors: Gao Xiangrui , Guo Xueyu , Zhang Fan , Yao Mengcheng , Wang Xiaoxiao , Chen Dong , Wang Xiaodong , Lai Lipeng 
Published: April 2023

ABSTRACTHigh-content analysis (HCA) holds enormous potential for drug discovery and research, but widely used methods can be cumbersome and yield inaccurate results. Noise and high similarity in cell images impede the accuracy of deep learning-based image analysis. To address these issues, we introduce More Is Different (MID), a novel HCA method that combines cellular experiments, image processing, and deep learning modeling. MID effectively combines the convolutional neural network and Transformer to encode high-content images, effectively filtering out noisy signals and characterizing cell phenotypes with high precision. In comparative tests on drug-induced cardiotoxicity and mitochondrial toxicity classification, as well as compound classification, MID outperformed both DeepProfiler and CellProfiler, which are two highly recognized methods in HCA. We believe that our results demonstrate the utility and versatility of MID and anticipate its widespread adoption in HCA for advancing drug development and disease research.
Single-Copy Orthologs (SCOs) improve species discrimination: A case study in subgusJensoa(Cymbidium)
Authors: He Zheng-Shan , Li De-Zhu , Yang Jun-Bo 
Published: April 2023

AbstractStandard barcodes and ultra-barcodes face challenges in delimitation and discrimination of closely related species with deep coalescence, hybrid speciation, gene flow or low sequence-variation. Single copy orthologs (SCOs) have been recommended as standardized nuclear markers in metazoan DNA taxonomy. Here, we assessed the performance of SCOs in identifying recently diverged species in subgenusJensoa(Cymbidium) which has been poorly settled by ultra-barcode. More than 90% of target 9094 reference SCOs inferred from three genomes ofCymbidiumwere successfully retrieved for all 11 representative species in subg.Jensoaby ALiBaSeq from as low as 5× depth whole genome shotgun sequences. Species tree reconstructed from multiple refined SCO matrices under multispecies coalescent model successfully discriminated all species and discerned wrongly identified or labeled species. Plentiful and refined SCOs matrices obtained by implementing our pipeline facilitate not only phylogenetic study, but also high-resolution species diagnosing. Biparentally inherited SCOs as multi-locus marker not only advances the force of DNA barcoding, but also facilitates an eventual transition to species-tree-based barcoding strategies.
3D environment promotes persistent changes in lamin B1 distribution, the biomechanical signature of the nucleus, and adaptative survival and migratory functions
Authors: González-Novo Raquel , Zamora-Carreras Héctor , Lope-Planelles Ana de , López-Menéndez Horacio , Roda-Navarro Pedro , Monroy Francisco , Wang Lin , Toseland Christopher P. , Redondo Muñoz Javier 
Published: April 2023

ABSTRACTThe interplay between cells and their surrounding microenvironment drives multiple cellular functions, including migration, proliferation, and cell fate transitions. The nucleus is a mechanosensitive organelle that adapts external mechanical and biochemical signals provided by the environment into nuclear changes with functional consequences for cell biology. However, the morphological and functional changes of the nucleus induced by 3D extracellular signals remain unclear. Here, we demonstrated that cells derived from 3D conditions conserve changes from cell confinement and show an aberrant nuclear morphology and localization of lamin B1, even in the absence of cellular confinement. We found that actin polymerization and protein kinase C (PKC) activity mediate the abnormal distribution of lamin B1 in 3D conditions-derived cells. These cells present altered chromatin compaction, gene transcription and cellular functions such as cell viability and migration. By combining biomechanical techniques and single-nucleus analysis, we have determined that the nucleus from 3D conditions-derived cells shows a different mechanical behavior and biophysical signature than the nucleus from control cells. Together, our work substantiates novel insights into how the extracellular environment alters the cell biology by promoting permanent changes in the chromatin, morphology, lamin B1 distribution, and the mechanical response of the nucleus.
The soil-borne white root rot pathogenRosellinia necatrixexpresses antimicrobial proteins during host colonization
Authors: Chavarro-Carrero Edgar A. , Snelders Nick C. , Torres David E. , Kraege Anton , López-Moral Ana , Petti Gabriella C. , Punt Wilko , Wieneke Jan , García-Velasco Rómulo , López-Herrera Carlos J. , Seidl Michael F. , Thomma Bart P.H.J. 
Published: April 2023

ABSTRACTRosellinia necatrixis a prevalent soil-borne plant-pathogenic fungus that is the causal agent of white root rot disease in a broad range of host plants. The limited availability of genomic resources forR. necatrixhas complicated a thorough understanding of its infection biology. Here, we sequenced nineR. necatrixstrains with Oxford Nanopore sequencing technology, and with DNA proximity ligation we generated a gapless assembly of one of the genomes into ten chromosomes. Whereas many filamentous pathogens display a so-called two-speed genome with more dynamic and more conserved compartments, theR. necatrixgenome does not display such genome compartmentalization. It has recently been proposed that fungal plant pathogens may employ effectors with antimicrobial activity to manipulate the host microbiota to promote infection. In the predicted secretome ofR. necatrix, 26 putative antimicrobial effector proteins were identified, nine of which are expressed during plant colonization. Two of the candidates were tested, both of which were found to possess selective antimicrobial activity. Intriguingly, some of the inhibited bacteria are antagonists ofR. necatrixgrowthin vitroand can alleviateR. necatrixinfection on cotton plants. Collectively, our data show thatR. necatrixencodes antimicrobials that are expressed during host colonization and that may contribute to modulation of host-associated microbiota to stimulate disease development.