bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVIDENCE FROM FATAL COVID-19 FOR TARGETING THE BRADYKININ METABOLISM—A SINGLE-CENTER COHORT STUDY
Authors: Zinn Sebastian , Talbot Steven R. , Rajapakse Dammith , Ruskowski Katharina , Neb Holger , Adam Elisabeth H. , von Knethen Andreas , Zacharowski Kai , Heinicke Ulrike 
Published: October 2023

ABSTRACT

Background: Severe progression of COVID-19 to critical illness, with pulmonary failure, multiple organ failure, and death, is driven by systemic inflammatory responses with overproduction of inflammatory cytokines. In the past years, the potential role of bradykinin, leading to inappropriate immune responses in the pathogenesis of COVID-19, has been raised in a so-called bradykinin storm. However, clinical investigations of bradykinin, its metabolite des-Arg9-bradykinin, or substance P, are rare or completely lacking during intensive care of COVID-19 patients. A prospective prolonged cohort study was conducted, including 44 COVID-19 patients (09/2020–02/2021, prevalent wildtype SARS-CoV-2) from the intensive care unit. Plasma levels of bradykinin, des-Arg9-bradykinin, and substance P were measured daily by ELISA in survivors (n = 21) and nonsurvivors (n = 23) of COVID-19 from admission until discharge or death. Results: We found significantly higher plasma levels of des-Arg9-bradykinin in survivors and nonsurvivors of COVID-19 compared with healthy controls. In addition, plasma des-Arg9-bradykinin levels were higher (P < 0.001, effect size = 0.79) in nonsurvivors compared with survivors of COVID-19 and correlated significantly with disease worsening, and clinical parameters of inflammation, like leukocyte count, IL-6 or lactate dehydrogenase, and outcome. Consequently, compared with healthy controls, bradykinin and substance P plasma levels were significantly reduced in survivors and nonsurvivors of COVID-19. Furthermore, plasma substance P levels were significantly reduced (P < 0.001, effect size = 0.7) in nonsurvivors compared with survivors of COVID-19, whereas plasma bradykinin levels did not significantly differ between survivors and nonsurvivors of COVID-19. Conclusion: Our data demonstrates that des-Arg9-bradykinin is significantly elevated in COVID-19 intensive care unit patients and is associated with disease severity, clinical inflammatory parameters, and survival. These results indicate that des-Arg9-bradykinin, not bradykinin, is one of the pivotal peptides of concern for the lethal COVID-19 aggravation and outcome. Further investigations are necessary to evaluate whether des-Arg9-bradykinin exhibits potent blood biomarker properties in COVID-19 and offer new treatment approaches.
GENIPOSIDE IMPROVES CLP-INDUCED SEPSIS MODEL PROGNOSIS BY UPREGULATING PPARγ TO MODULATE MONOCYTE PHENOTYPE AND CYTOKINE NETWORK
Authors: Zhang Dewen , He Jian , Ding Xian , Wang Rui , Chen Wei 
Published: October 2023

ABSTRACT

Background: We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods: A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. The survival rate of different groups was observed. In addition, the expression levels of CD16 and major histocompatibility complex class II in monocytes were assessed using flow cytometry. The concentrations of TNF-α, IL-1β, IL-6, and IL-10 in the serum were measured by ELISA. We also observed the biological effects of geniposide on CD16 and MHC-II expression levels in RAW264.7 cells, as well as the secretion of TNF-α, IL-1β, IL-6, and IL-10 in the LPS-induced RAW264.7 cell model. The PPARγ levels were determined using western blot analysis. Results: Intravenous administration of 40 mg/kg of geniposide at 0 h after CLP significantly improved the survival outcomes in the septic mouse model, with no significant benefits from low dosing (20 mg/kg) or delayed administration (24 h). The effective dose of geniposide significantly decreased the serum cytokine TNF-α, IL-1β, IL-6, and IL-10 concentrations in septic mice (P < 0.05). Notably, in vitro assays showed that geniposide specifically increased the IL-10 level. Geniposide significantly reduced the CD16 expression (P < 0.05) and increased MHC-II expression in monocytes (P < 0.05). In addition, geniposide elevated the PPARγ level in monocytes (P < 0.05). Conclusions: High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.
Pulmonary Ventilation Analysis Using1H Ultra-Short Echo Time (UTE) Lung MRI: A Reproducibility Study
Authors: Tan Fei , Zhu Xucheng , Chan Marilynn , Deveshwar Nikhil , Willmering Matthew M. , Lustig Michael , Larson Peder E. Z. 
Published: October 2023

AbstractPurposeTo evaluate methods for quantification of pulmonary ventilation with ultrashort echo time (UTE) MRI.MethodsWe performed a reproducibility study, acquiring two free-breathing1H UTE lung MRIs on the same day for six healthy volunteers. The 1) 3D + t cyclic b-spline and 2) symmetric image normalization (SyN) methods for image registration were applied after respiratory phase-resolved image reconstruction. Ventilation maps were calculated using 1) Jacobian determinant of the deformation fields minus one, termed regional ventilation, and 2) intensity percentage difference between the registered and fixed image, termed specific ventilation. We compared the reproducibility of all four method combinations via statistical analysis.ResultsSplit violin plots and Bland-Altman plots are shown for whole lungs and lung sections. The cyclic b-spline registration and Jacobian determinant regional ventilation quantification provide total ventilation volumes that match the segmentation tidal volume, smooth and uniform ventilation maps. The cyclic b-spline registration and specific ventilation combination yields the smallest standard deviation in the Bland-Altman plot.ConclusionCyclic registration performs better than SyN for respiratory phase-resolved1H UTE MRI ventilation quantification. Regional ventilation correlates better with segmentation lung volume, while specific ventilation is more reproducible.
The history of chromosomal instability in genome doubled tumors
Authors: Baker Toby M. , Lai Siqi , Lesluyes Tom , Yan Haixi , Verfaillie Annelien , Dentro Stefan , Lynch Andrew R. , Bowes Amy L. , Pillay Nischalan , Flanagan Adrienne M. , Swanton Charles , Tarabichi Maxime , Loo Peter Van 
Published: October 2023

AbstractTumors frequently display high chromosomal instability (CIN) and contain multiple copies of genomic regions. Here, we describe GRITIC, a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 5,656 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-duplicated tumors. We measured CIN before and after genome duplication in human tumors and found that late genome doubling was followed by an increase in the rate of copy number gain. Copy number gains often accumulate as punctuated bursts, commonly after genome duplication. We infer that genome duplications typically affect the selection landscape of copy number losses, while only minimally impacting copy number gains. In summary, GRITIC is a novel copy number gain timing framework that permits the analysis of copy number evolution in chromosomally unstable tumors.Statement of significanceComplex genomic gains are associated with whole-genome duplications, which are frequent across tumors, span a large fraction of their genomes, and are linked to poorer outcomes. GRITIC infers when these gains occur during tumor development, which will help to identify the genetic events that drive tumor evolution.
β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice
Authors: Franklin Michael K. , Sawada Hisashi , Ito Sohei , Howatt Deborah A. , Amioka Naofumi , Liang Ching-Ling , Zhang Nancy , Graf David B. , Moorleghen Jessica J. , Katsumata Yuriko , Lu Hong S. , Daugherty Alan 
Published: October 2023

ABSTRACTBACKGROUNDβ-aminopropionitrile (BAPN) is a pharmacological inhibitor of lysyl oxidase and lysyl oxidase-like proteins. Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice.METHODSBAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to dose, strain, age, and sex. BAPN-induced aortic pathological characterization was conducted using histology and immunostaining. To investigate the mechanistic basis of regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration before the appearance of overt pathology.RESULTSBAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta in young C57BL/6J or N mice. No apparent differences were found between male and female mice. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. One week of BAPN administration compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the two aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components.CONCLUSIONSBAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in mice.
Age at menopause and risk of ischemic stroke: a systematic review and meta-analysis
Authors: Wang Jie , Chen Ying 
Published: October 2023

AbstractBackgroundDespite its importance in being among the top 10 causes of old women death, there is limited data on age at menopause and ischemic stroke.AimsWe performed a systematic review and meta-analysis to estimate the effect of age at onset of menopause on ischemic stroke.MethodsWe screened four databases (PubMed, Cochrane, Web of Science, and EMBASE databases) up to July 17, 2023. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42023444245). Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Revman5.4 to calculate the risk ratio of the incidence of ischemic stroke. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed.ResultsOut of 725 records identified, 10 studies were included in the qualitative synthesis and the quantitative meta-analysis. The pooled incidence rate for ischemic strokes which age at onset of menopause before 43 years old was 1.22 (95% confidence interval (CI): 1.02-1.46). The pooled incidence rate of early menopause was 1.26 (95% CI: 1.07-1.48) for ischemic stroke. The incidence rate of ischemic stroke for women with early menopause may be in an environment with a high incidence for a long time.ConclusionEvidence from this meta-analysis suggests that early menopause is associated with an increased risk of ischemic stroke. Age at onset of menopause before 43 years old may be the cut-off value of increased risk of ischemic stroke.
Growth couples temporal and spatial fluctuations of tissue properties during morphogenesis
Authors: Fruleux Antoine , Hong Lilan , Roeder Adrienne H. K. , Li Chun-Biu , Boudaoud Arezki 
Published: October 2023

Living tissues display fluctuations – random spatial and temporal variations of tissue properties around their reference values – at multiple scales. It is believed that such fluctuations may enable tissues to sense their state or their size. Recent theoretical studies developed specific models of fluctuations in growing tissues and predicted that fluctuations of growth show long-range correlations. Here we elaborated upon these predictions and we tested them using experimental data. We first introduced a minimal model for the fluctuations of any quantity that has some level of temporal persistence or memory, such as concentration of a molecule, local growth rate, or mechanical property. We found that long-range correlations are generic, applying to any such quantity, and that growth couples temporal and spatial fluctuations, through a mechanism that we call ‘fluctuation stretching’ — growth enlarges the lengthscale of variation of this quantity. We then analysed growth data from sepals of the model plant Arabidopsis and we quantified spatial and temporal fluctuations of cell growth using the previously developed Cellular Fourier Transform. Growth appears to have long-range correlations. We compared different genotypes and growth conditions: mutants with lower or higher response to mechanical stress have lower temporal correlations and longer-range spatial correlations than wild-type plants. Finally, we used theoretical predictions to merge experimental data from all conditions and developmental stages into an unifying curve, validating the notion that temporal and spatial fluctuations are coupled by growth. Altogether, our work reveals kinematic constraints on spatiotemporal fluctuations that have an impact on the robustness of morphogenesis.Significance StatementHow do organs and organisms grow and achieve robust shapes in the face of subcellular and cellular variability? In order to address this outstanding mystery, we investigated the variability of growth at multiple scales and we analysed experimental data from growing plant tissues. Our results support the prediction that tissue expansion couples temporal memory of growth with spatial variability of growth. Our work reveals a constraint on the spatial and temporal variability of growth that may impact the robustness of morphogenesis.
INTRAVENOUS VITAMIN C SUPPLEMENTATION IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS: SALUTARY IMPACT ON CLINICAL OUTCOMES
Authors: Simmons Gary , Sabo Roy , Aziz May , Martin Erika , Bernard Robyn J. , Sriparna Manjari , McIntire Cody , Krieger Elizabeth , Brophy Donald F. , Natarajan Ramesh , Fowler Alpha , Roberts Catherine H. , Toor Amir 
Published: October 2023

AbstractIntravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (SCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic hematopoietic stem cell transplant (HSCT) were evaluated in a phase I/II trial and clinical outcomes compared with a propensity score - matched historical control.MethodsPatients with advanced hematologic malignancies were enrolled in a phase 2 clinical trial, receiving IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HSCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT.Results55 patients received IV vitamin C: these include 10/10 HLA-MRD and MUD (n=48) and 9/10 HLA MUD recipients (n=7). All patients enrolled were deficient in vitamin C at day 0 and had restoration to normal levels for the remainder of the course. Vitamin C recipients had lower non-relapse mortality (11% vs. 25%, p-value = 0.07) and consequently, improved survival compared to historical controls (82% vs 62% p=0.06), with no attributable grade 3 and 4 toxicities to vitamin C. Patients with myeloid malignancies had improved survival (83% vs. 54%, p=0.02) and non-relapse mortality (NRM) (10% vs. 37%, p=0.009), as well as chronic GVHD, with similar relapse rates compared to controls.ConclusionsIn patients undergoing allogeneic HSCT the administration of IV vitamin C is safe and reduces non-relapse mortality improving overall survival. Randomized trials are needed to confirm the utility of this easily available and inexpensive therapy.
Machine Learning Enables Single-Score Assessment of MASLD Presence and Severity
Authors: Chen Robert , Petrazzini Ben Omega , Nadkarni Girish , Rocheleau Ghislain , Bansal Meena , Do Ron 
Published: October 2023

AbstractMetabolic dysfunction-associated steatotic liver disease (MASLD) affects 30% of the global population but is often underdiagnosed. To fill this diagnostic gap, we developed a digital score reflecting presence and severity of MASLD. We fitted a machine learning model to electronic health records from 37,212 UK Biobank participants with proton density fat fraction measurements and/or a MASLD diagnosis to generate a “MASLD score”. In holdout testing, our model achieved areas under the receiver-operating curve of 0.83-0.84 for MASLD diagnosis and 0.90-0.91 for identifying MASLD-associated advanced fibrosis. MASLD score was significantly associated with MASLD risk factors, progression to cirrhosis, and mortality. External testing in 252,725 diverse American participants demonstrated consistent results, and hepatologist chart review showed MASLD score identified probable MASLD underdiagnosis. The MASLD score could improve early diagnosis and intervention of chronic liver disease by providing a non-invasive, low-cost method for population-wide screening of MASLD.
Inferring community transmission of SARS-CoV-2 in the United Kingdom using the ONS COVID-19 Infection Survey
Authors: McCabe Ruth , Danelian Gabriel , Panovska-Griffiths Jasmina , Donnelly Christl A. 
Published: October 2023

AbstractKey epidemiological parameters, including the effective reproduction number,R(t), and the instantaneous growth rate,r(t), generated from an ensemble of models, have been informing public health policy throughout the COVID-19 pandemic in the four nations of the United Kingdom of Great Britain and Northern Ireland (UK). However, estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the “emergency” to “endemic” phase of the pandemic.The Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) provided an opportunity to continue estimating these parameters in the absence of other data streams. We used a penalised spline model fitted to the ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over time. The resulting fitted curve was used to estimate the “ONS-based”R(t) andr(t) across the four nations of the UK. Estimates produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these parameters.Depending on the nation and parameter, we found that up to 77% of the variance in the government-published estimates can be explained by the ONS-based estimates, demonstrating the value of this singular data stream to track the epidemic in each of the four nations. We additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published estimates.Our work shows that the ONS CIS can be used to generate the key COVID-19 epidemics across the four UK nations. This is not intended as an alternative to ensemble modelling, rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.
Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 Vaccine
Authors: Kohli M , Maschio M , Lee A , Igarashi A 
Published: October 2023

AbstractBackgroundThe study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a Fall 2023 COVID-19 vaccine for adults ≥18 years on these outcomes.MethodsA previously developed Susceptible-Exposed-Infected-Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19– related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed.ResultsThe base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial vaccine effectiveness (VE) against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning.ConclusionsResults suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19 related infections, hospitalizations, and deaths.
A Comparative Analysis of Global Adult Tobacco Survey (GATS): Prevalence and Predictors of Tobacco Smoking in Seven Regions of India
Authors: Tikhute Vishal 
Published: October 2023

AimThis article aims to assess the prevalence of tobacco smoking among the adult study population and also explore the association between socio-demographic factors and tobacco use in the six geographical regions of India.MethodsThis is a cross-sectional comparative research design that used nationally representative population-based household GATS-1 data on tobacco use in India. Six states representing the respective six geographic regions (one state per region) of India were selected using systematic random sampling. The prevalence of tobacco smoking among the study population was calculated and used for comparison between the six regions. Logistic regression was used to assess the association between socio-demographic factors and tobacco smoking in each zone.ResultsThe North-eastern, Central, and Eastern regions had a high prevalence of tobacco smoking. Further, factors such as sex, place of residence, literacy, and working status had a significant association with current use of tobacco (smoking).ConclusionDespite there are policies and legal frameworks to control the use and sell of tobacco in India, the prevalence of tobacco smoking is high, particularly in the North-eastern, Central, and Eastern regions of India. Policies and community-based approaches to provide health education to reduce tobacco smoking are recommended.