bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between COVID-19 Vaccination and Mortality after Major Operations
Authors: Sharath Sherene E. , Kougias Panos , Daviú-Molinari Tomás , Faridmoayer Erfan , Berger David H. 
Published: July 2023

Background and Objectives:
Societal guidelines recommend postponing elective operations for at least 7 weeks in unvaccinated patients with preoperative COVID-19 infection. The role of vaccination on this infection-operation time risk is unclear. The objective was to compare postoperative, 90-day mortality between (1) fully vaccinated COVID-19 positive and negative patients, and (2) vaccinated and unvaccinated COVID-19 positive patients.

Methods:
We conducted a national US multicenter retrospective, matched-cohort study spanning July 2021 to October 2022. Participants were included if they underwent a high-risk general, vascular, orthopedic, neurosurgery, or genitourinary surgery. All-cause mortality occurring within 90 days of the index operation. Inverse probability treatment weighted (IPTW) propensity scores were used to adjust logistic regression models examining the independent and interactive associations between mortality, exposure status, and infection proximity.

Results:
Of 3,401 fully vaccinated patients in the 8-week preoperative period, 437 (12.9%) were COVID-19 positive. Unadjusted mortality rates were not significantly different between vaccinated COVID-19 patients (22, 5.0%) and vaccinated non-COVID-19 patients (99, 3.3%; P=0.07). After IPTW adjustment, independent mortality risk was not significantly different among vaccinated COVID-19 positive relative to vaccinated COVID-19 negative patients (adjusted Odds Ratio [aOR] = 1.38, 95% CI – 0.70, 2.72). Proximity of COVID-19 diagnosis to the index operation did not confer any added mortality risk in either comparison cohort.

Conclusions and relevance:
Contrary to risks observed among unvaccinated patients, postoperative mortality does not differ between COVID-19 positive and negative patients vaccinated against the SARS-CoV-2 virus and receiving a high-risk operation within 8 weeks of the diagnosis, regardless of operation timing relative to diagnosis.
Quality of Life and Gastrointestinal Symptoms in Long-term Survivors of Pancreatic Cancer Following Pancreatoduodenectomy
Authors: Zhang Chi , Zironda Andrea , Vierkant Robert A. , Starlinger Patrick , Warner Susanne , Smoot Rory , Kendrick Michael , Cleary Sean , Truty Mark , Thiels Cornelius 
Published: July 2023

Objective:
To describe long-term quality of life (QOL) and gastrointestinal (GI) symptoms in patients who underwent pancreatoduodenectomy for pancreatic cancer in the modern era.

Summary and Background Data:
As advances in pancreatic cancer management improve outcomes, it is essential to assess long-term patient reported outcomes after surgery.

Methods:
Patients who underwent curative intent pancreatoduodenectomy for pancreatic cancer between 1/2011-6/2019 from a single-center were identified. Patients alive ≥3 years after surgery were considered long-term survivors (LTS). LTS who were alive in 6/2022 received a 55-question survey to assess their QOL (EORTC-QLQ-C30) and GI symptoms (EORTC-PAN26 and Problem Areas in Diabetes Questionnaire). Responses were compared against population norms. Clinicodemographic characteristics in LTS vs non-LTS and survey completion were compared.

Results:
Six-hundred and seventy-two patients underwent pancreatoduodenectomy for pancreatic cancer; 340 were long-term survivors. One-hundred and thirty-seven patients of the 238 eligible to complete the survey responded (response rate: 58%). Compared to the US general population, long-term survivors reported significantly higher QOL (75 vs 64; P<0.001), less nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and constipation, but more diarrhea (all P<0.001). Most patients (n=136/137, 99%) reported experiencing postoperative GI symptoms related to pancreatic insufficiency (n=71/135, 53%), reflux (n=61/135, 45%), delayed gastric emptying (n=31/136, 23%). Most patients (n=113/136, 83%) reported that digestive symptoms overall had little to no impact on QOL, and 91% (n=124/136) would undergo surgery again.

Conclusions:
Despite known long-term complications following pancreatoduodenectomy, cancer survivors appear to have excellent QOL. Specific long-term gastrointestinal symptoms data should be utilized for preoperative education and follow-up planning.
Asymmetry in the peak in Covid-19 daily cases and the pandemic R-parameter
Authors: Bhatkar Sayali , Ma Mingyang , Zsolway Mary , Tarafder Ayush , Doniach Sebastian , Bhanot Gyan 
Published: July 2023

ABSTRACTWithin the context of the standard SIR model of pandemics, we show that the asymmetry in the peak in recorded daily cases during a pandemic can be used to infer the pandemic R-parameter. Using only daily data for symptomatic, confirmed cases, we derive a universal scaling curve that yields: (i) reff, the pandemic R-parameter; (ii) Leff,the effective latency, the average number of days an infected individual is able to infect others and (iii) α, the probability of infection per contact between infected and susceptible individuals. We validate our method using an example and then apply it to estimate these parameters for the first phase of the SARS-Cov-2/Covid-19 pandemic for several countries where there was a well separated peak in identified infected daily cases. The extension of the SIR model developed in this paper differentiates itself from earlier studies in that it provides a simple method to make an a-posteriori estimate of several useful epidemiological parameters, using only data on confirmed, identified cases. Our results are general and can be applied to any pandemic.
Calibrated prediction intervals for polygenic scores across diverse contexts
Authors: Hou Kangcheng , Xu Ziqi , Ding Yi , Harpak Arbel , Pasaniuc Bogdan 
Published: July 2023

AbstractPolygenic scores (PGS) have emerged as the tool of choice for genomic prediction in a wide range of fields from agriculture to personalized medicine. We analyze data from two large biobanks in the US (All of Us) and the UK (UK Biobank) to find widespread variability in PGS performance across contexts. Many contexts, including age, sex, and income, impact PGS accuracies with similar magnitudes as genetic ancestry. PGSs trained in single versus multi-ancestry cohorts show similar context-specificity in their accuracies. We introduce trait prediction intervals that are allowed to vary across contexts as a principled approach to account for context-specific PGS accuracy in genomic prediction. We model the impact of all contexts in a joint framework to enable PGS-based trait predictions that are well-calibrated (contain the trait value with 90% probability in all contexts), whereas methods that ignore context are mis-calibrated. We show that prediction intervals need to be adjusted for all considered traits ranging from 10% for diastolic blood pressure to 80% for waist circumference. Adjustment of prediction intervals depends on the dataset; for example, prediction intervals for education years need to be adjusted by 90% in All of Us versus 8% in UK Biobank. Our results provide a path forward towards utilization of PGS as a prediction tool across all individuals regardless of their contexts while highlighting the importance of comprehensive profile of context information in study design and data collection.
Comparisons of Heart Rate Variability Responses to Head-up Tilt With and Without Abdominal and Lower-Extremity Compression in Healthy Young Individuals: A Randomized Crossover Study
Authors: Oyake Kazuaki , Katai Miyuki , Yoneyama Anzu , Ikegawa Hazuki , Kani Shigeru , Momose Kimito 
Published: July 2023

ABSTRACTIntroductionAbdominal and lower-extremity compression techniques can help reduce orthostatic heart rate increase. However, the effects of body compression on the cardiac autonomic systems, which control heart rate, remain unclear. This study aimed to compare heart rate variability, a reflection of cardiac autonomic regulation, during a head-up tilt test with and without abdominal and lower-extremity compression in healthy young individuals.MethodsIn a randomized crossover design, 39 healthy volunteers (20 females, aged 20.9 ± 1.2 years) underwent two head-up tilt tests with and without abdominal and lower-extremity compression. Heart rate and heart rate variability parameters were measured during the head-up tilt tests, including Stress Index, root mean square of successive differences between adjacent R-R intervals, low- and high-frequency components, and low-to-high frequency ratio.ResultsAbdominal and lower-extremity compression reduced the orthostatic increase in heart rate (p < 0.001). The tilt-induced changes in heart rate variability parameters, except for the low-frequency component, were smaller in the compression condition than in the no-compression condition (p < 0.001). Additionally, multiple regression analysis with potentially confounding variables revealed that the compression-induced decrease in Stress Index during the head-up tilt position was a significant independent variable for the compression-induced reduction in heart rate in the head-up tilt position (coefficient = 0.411, p = 0.025). Comparative analyses revealed that abdominal and lower-extremity compression has a notable impact on the compensatory sympathetic activation and vagal withdrawal typically observed during orthostasis, resulting in a reduction of the increase in heart rate. Furthermore, this decrease in heart rate was primarily attributed to the attenuation of cardiac sympathetic activity associated with compression.ConclusionOur findings could contribute to the appropriate application of compression therapy for preventing orthostatic tachycardia. This study is registered with UMIN000045179.
The Effects of Virtual Reality Neuroscience-based Therapy on Clinical and Neuroimaging Outcomes in Patients with Chronic Back Pain: A Randomized Clinical Trial
Authors: Čeko Marta , Baeuerle Tassilo , Webster Lynn , Wager Tor D. , Lumley Mark A. 
Published: July 2023

AbstractChronic pain remains poorly managed. The integration of innovative immersive technologies (i.e., virtual reality (VR)) with recent neuroscience-based principles that position the brain as the key organ of chronic pain may provide a more effective pain treatment than traditional behavioral therapies. By targeting cognitive and affective processes that maintain pain and potentially directly changing neurobiological circuits associated with pain chronification and amplification, VR-based pain treatment has the potential for significant and long-lasting pain relief.We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (n = 30) in a 2-arm randomized clinical trial (NCT04468074). We also conducted pre- and post-treatment MRI to test whether VRNT affects brain networks previously linked to chronic pain and treatment effects. Compared to the control condition, VRNT led to significantly reduced pain intensity (g = 0.63) and pain interference (g = 0.84) at post-treatment vs. pre-treatment, with effects persisting at 2-week follow-up. The improvements were partially mediated by reduced kinesiophobia and pain catastrophizing. Several secondary clinical outcomes were also improved, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with modest increases in functional connectivity of the somatomotor and default mode networks and decreased white matter fractional anisotropy in the corpus callosum adjacent to anterior cingula, relative to the control condition. This, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly via changes in somatosensory and prefrontal brain networks.
Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements
Authors: Trauernicht Max , Rastogi Chaitanya , Manzo Stefano G. , Bussemaker Harmen J. , van Steensel Bas 
Published: July 2023

ABSTRACTTP53 is a transcription factor that controls multiple cellular processes, including cell cycle arrest, DNA repair, and apoptosis. The relation between TP53 binding site architecture and transcriptional output is still not fully understood. Here, we systematically examined in three different cell lines the effects of binding site affinity and copy number on TP53-dependent transcriptional output, and also probed the impact of spacer length and sequence between adjacent binding sites, and of core promoter identity. Paradoxically, we found that high-affinity TP53 binding sites are less potent than medium-affinity sites. TP53 achieves supra-additive transcriptional activation through optimally spaced adjacent binding sites, suggesting a cooperative mechanism. Optimally spaced adjacent binding sites have a ∼10-bp periodicity, suggesting a role for spatial orientation along the DNA double helix. We leveraged these insights to construct a log-linear model that explains activity from sequence features, and to identify new highly active and sensitive TP53 reporters.
Fecal Dysbiosis and Inflammation in Intestinal-Specific Cftr Knockout Mice on Regimens Preventing Intestinal Obstruction
Authors: Young Sarah M. , Woode Rowena A. , Williams Estela , Ericsson Aaron , Clarke Lane L. 
Published: July 2023

AbstractChronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with CF exhibit intestinal dysbiosis which has potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia and in the leukocyte population. Here, we investigate the contribution of intestinal epithelial-specific loss of Cftr (iCftr KO) to dysbiosis and inflammation in mice treated with either of two anti-obstructive dietary regimens necessary to maintain CF mouse models (PEG laxative or a liquid diet, LiqD). Feces collected from iCftr KO mice and their wildtype (WT) sex-matched littermates were used to measure fecal calprotectin and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT samples of mice consuming either PEG or LiqD. PEG iCftr KO mice did not show a change in α-diversity versus WT but demonstrated a significant difference in microbial composition (β-diversity) with increases in phylumProteobacteria, familyPeptostreptococcaceae, four genera ofClostridiaincludingC. innocuum, and mucolytic genusAkkermansia. Fecal microbiome analysis of LiqD iCftr KO mice showed both decreased α-diversity and differences in microbial composition with increases inProteobacteriafamilyEnterobacteriaceae,FirmicutesfamiliesClostridiaceaeandPeptostreptococcaceae, and enrichment ofClostridium perfringens,C. innocuum,C. difficile, mucolyticRuminococcus gnavus, and reduction ofAkkermansia. It was concluded that epithelial-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of global Cftr KO mice.New and noteworthyChronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CFTR that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR (iCftr KO) in mice is sufficient to induce intestinal dysbiosis and inflammation. Studies were performed on mice consuming either dietary regimen (PEG laxative or liquid diet) routinely used to prevent obstruction in CF mice.
The influence of HLA genetic variation on plasma protein expression
Authors: Krishna Chirag , Chiou Joshua , Lee Isac , Kim Hye In , Aksit Melis Atalar , Sakaue Saori , Schack David Von , Raychaudhuri Soumya , Ziemek Daniel , Hu Xinli 
Published: July 2023

AbstractPolymorphism in the human leukocyte antigen class I (HLA-I) and class II (HLA-II) genes is strongly implicated in susceptibility to immune-mediated diseases. However, the molecular effects of HLA genetic variation, including and beyond antigen presentation, remain unclear. Here we examined the effect of HLA genetic variation on the expression of 2940 plasma proteins using imputed HLA variants in 45,330 Europeans in the UK Biobank. We detected 504 proteins (17.1% of all proteins tested) affected by HLA genetic variation (HLA-pQTL), including widespreadtransregulation of protein expression by autoimmune disease risk alleles. HLA-pQTL were enriched in gene families related to antigen presentation (e.g. B2M), T cell fate (CD8A; CD4), chemokines (CCL19; CCL21), and NK and macrophage receptors (KIR; LILRA/B), suggesting that HLA polymorphism affects both adaptive and innate immunity. HLA-pQTL also affected expression of diverse proteins with unclear roles in the immune response (e.g. SFTPD, LRPAP1, ENPP6, NPTX1), as well as drug targets for immune-mediated diseases, suggesting complex regulatory roles of the HLA loci. AmongtransHLA-pQTL, HLA variants explained 0.1-42.9% of the protein expression variance. Fine-mapping revealed that most HLA-pQTL implicated amino acid positions within the peptide binding groove, suggesting thattransregulation of plasma protein expression by the HLA loci is primarily a consequence of antigen presentation. We also show that HLA-I and II uniquely affect different proteins and biological mechanisms. Altogether, our data reveal the effects of HLA genetic variation on protein expression and aid the interpretation of associations between HLA alleles and immune-mediated diseases.
Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer’s disease and progressive supranuclear palsy
Authors: Batra Richa , Krumsiek Jan , Wang Xue , Allen Mariet , Blach Colette , Kastenmüller Gabi , Arnold Matthias , Ertekin-Taner Nilüfer , Kaddurah-Daouk Rima F. ,   Alzheimer’s Disease Metabolomics Consortium (ADMC)
Published: July 2023

AbstractMetabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP). While metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed. We analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies. Our findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau-induced polyamine stress response. However, specific to AD, we detected glutathione-related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B. Taken together, our findings underscore vast alterations in the brain’s metabolome, illuminating shared neurodegenerative pathways and disease-specific traits in AD and PSP.
Fight or Flight: Emergency Healthcare Workers’ Willingness to Work during Crises and Disasters: A cross-sectional multicentre study in the Netherlands
Authors: Engels Lindsy M.J. , Barten Dennis G. , Boumans Thimo J.T. , Gaakeer Menno I. , Latten Gideon H.P. , Mehagnoul Jannet , Tapirdamaz Özlem , van Osch Frits , Mortelmans Luc 
Published: July 2023

ObjectiveExpanding staff levels is a strategy for hospitals to increase surge capacity. This study aimed to evaluate whether emergency healthcare workers (HCWs) are willing to work (WTW) during a crises or disaster and which working conditions would influence their decision.MethodsHCWs of emergency departments (ED) and intensive care units (ICU) of five Dutch hospitals were surveyed about elevens disaster scenarios. For each scenario, HCWs were asked about their WTW and which conditions would influence their decision. Knowledge and perceived risk and danger was assessed per scenario.Results306/630 HCWs completed the survey. An influenza epidemic, SARS-CoV-2 pandemic and natural disaster were associated with highest WTW rates (69.0%, 63.7% and 53.3% respectively). WTW was lowest in nuclear incident (4.6%) and dirty bomb (3.3%) scenarios. WTW was higher in physicians than in nurses. Male ED HCWS, single HCWs and childless HCWs were more often WTW. Personal protective equipment (PPE) and safety of HCWs’ family were the most important working conditions. Perceived knowledge scored lowest in dirty bomb, biological and nuclear incident scenarios. These scenarios rated highest with regards to perceived danger.ConclusionsWTW depended on disaster type, profession and working department. Provision of PPE and safety of HCWs’ family were found to be predominant working conditions.
The Cost of Keeping Patients Waiting: Retrospective Treatment-Control Study of Additional Healthcare Utilisation for UK Patients Awaiting Elective Treatment Following COVID-19
Authors: James Charlotte , Denholm Rachel , Wood Richard 
Published: July 2023

AbstractObjectiveThe COVID-19 pandemic has led to increased waiting times for elective treatments in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.MethodsWe carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment (‘Treatments’) and people not on a waiting list (‘Controls’). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited treatment, with healthcare usage assessed over various healthcare settings. T-tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.ResultsA total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. Evidence suggests increases (p < 0.05) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, requiring 17.9 [4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.ConclusionPeople waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible ‘false economy’ in failing to promptly resolve long elective waits.HighlightsLong waits for elective care can result in additional healthcare needs to manage symptoms up to the point of definitive treatment. While previous studies indicate some association, these mainly consider only a single elective specialty and are limited in the range of healthcare settings covered.The large number of long-wait pathways produced as a consequence of COVID-19 disruption allows for a more holistic analysis, covering the full range of elective treatment specialties and wider healthcare impacts across primary, secondary, mental health, and community care, as well as emergency service calls and prescriptions.Analysis of 44,616 elective care pathways reveals evidence of increases in wider healthcare consumption additional to that expected for similar patients not awaiting elective treatment. This suggests a ‘false economy’ in failing to promptly resolve elective pathways, which should be reflected by healthcare providers in long-term resource allocation decisions.