bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Age on Obesity-related Comorbidity After Gastric Bypass
Authors: Gerber Peter , Anderin Claes , Gustafsson Ulf O. , Thorell Anders 
Published: April 2021

Objective:
To evaluate the resolution of obesity-related comorbidities after gastric bypass in relation to age.

Summary Background Data:
Previous studies have shown that age >60 years is associated with a significant, but small, increased risk of complications after gastric bypass. The effect in terms of improvement of obesity-related comorbidities in this group of patients is not studied.

Methods:
Data on 57,215 patients operated with primary gastric bypass between May 2007 and December 2018 was extracted from the Scandinavian Obesity Surgery Registry. Odds ratio and 95% confidence interval for resolution of comorbidities in 5-years age groups at 1, 2, and 5 years postoperatively was calculated by logistic regression with the entire cohort of patients as reference. Resolution was defined as no longer in need for pharmacological (or continuous positive airway pressure) treatment.

Results:
Follow-up rates in all eligible patients were 89%, 69%, and 59% at 1, 2, and 5 years, respectively, and 64% in patients >60 years at 5 years. At baseline, the prevalence of most comorbidities was higher in patients above 60 years. In this group of patients, the preoperative prevalence of diabetes, hypertension, dyslipidemia and obstructive sleep apnea syndrome was reduced at 5years by 45%, 10%, 24%, and 62%, respectively. Compared to all patients, the odds ratio (95% confidence interval) for resolution of these comorbidities in patients above 60 years at five years were 0.70 (0.57–0.86) 0.45 (0.37–0.53), 0.80 (0.63–1.01), and 0.54 (0.40–0.72).

Conclusions:
Although to somewhat lower rates compared to younger patients, marked and sustained improvements in obesity-related comorbidities are seen after gastric bypass in patients >60 years. This, together with the finding that bariatric surgery is safe in this group of patients, suggests that age should not be considered an exclusion criterion by itself.
Pancreatic Enucleation Patients Share the Same Quality of Life as the General Population at Long-Term Follow-Up
Authors: Giuliani Tommaso , De Pastena Matteo , Paiella Salvatore , Marchegiani Giovanni , Landoni Luca , Festini Michele , Ramera Marco , Marinelli Veronica , Casetti Luca , Esposito Alessandro , Bassi Claudio , Salvia Roberto 
Published: April 2021

Objective:
The aim of this study was to assess short- and long-term outcomes including quality of life (QoL) following pancreatic enucleation (PE).

Background:
PE is deemed to preserve both the endocrine and the exocrine function while ensuring radicality. However, to assess whether this reflects an actual benefit perceived by patients, QoL has to be considered.

Methods:
Data from all consecutive patients undergoing PE from January 2010 to December 2019 were retrospectively analyzed. Surgical outcomes were graded according to the Clavien-Dindo classification, and EORTC-C30 and the EORTC-Pan26 were administered as a cross-sectional assessment of QoL. A control group consisting of healthy individuals from the general population was obtained and matched using the propensity score matching method.

Results:
Eighty-one patients underwent PE using the open (59.3%), laparoscopic (27.2%), or robot-assisted (13.5%) approach. Sixty-five (80.2%) patients exhibited functioning/nonfunctioning pancreatic neuroendocrine tumors at final pathology.
Surgical morbidity and complications of a Clavien-Dindo grade ≥3 were 48.1% and 16.0%, respectively. In-hospital mortality was 0%. Postoperative pancreatic fistula, post-pancreatectomy hemorrhage, and delayed gastric emptying rates were 21.0%, 9.9%, and 4.9%, respectively.
Patients returned the questionnaires after a median of 74.2 months from the index surgery. Postoperative new onset of diabetes mellitus (NODM) was observed in 5 subjects (7.1%), with age being an independent predictor. Seven patients (10.0%) developed postoperative exocrine insufficiency. At the analysis of QoL, all function and symptom scales were comparable between the 2 groups, except for 2 of the EORTC-Pan 26 symptom scales, (“worries for the future” and “body image”, P < 0.05).

Conclusions:
Despite being associated with significant postoperative morbidity, PE provides excellent long-term outcomes. The risk of NODM is low and related to patient age, with QoL being comparable to the general population. Such information should drive surgeons to pursue PE whenever properly indicated.
Safety and Reactogenicity of 2 Doses of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients
Authors: Ou Michael T. , Boyarsky Brian J. , Motter Jennifer D. , Greenberg Ross S. , Teles Aura T. , Ruddy Jake A. , Krach Michelle R. , Jain Vedant S. , Werbel William A. , Avery Robin K. , Massie Allan B. , Segev Dorry L. , Garonzik-Wang Jacqueline M. 
Published: April 2021

Background.
We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials.

Methods.
US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression.

Results.
We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44–69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P < 0.001), systemic reactions increased (49% D1 versus 69% D2, P < 0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 y = 0.850.900.94, P < 0.001) and D2 (aIRR per 10 y = 0.910.930.96, P < 0.001). Participants who experienced pain (aIRR = 1.111.662.47, P = 0.01) or redness (aIRR = 1.833.928.41, P < 0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post-D2.

Conclusions.
In solid organ transplant recipients undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients.
Solid Organ Donation From Brain-dead Donors With Cardiorespiratory Arrest After Snow Avalanche Burial: A Retrospective Single-center Study
Authors: Gasteiger Lukas , Putzer Gabriel , Unterpertinger Regina , Cardini Benno , Schneeberger Stefan , Eschertzhuber Stephan , Mair Peter 
Published: April 2021

Background.
Complete snow avalanche burial is associated with high mortality. The aim of this study was to assess the feasibility and incidence of organ retrieval in brain-dead donors following cardiorespiratory arrest due to avalanche burial and to evaluate the function of transplanted organs.

Methods.
The transplant registry of the Medical University of Innsbruck was searched for organ donors with a history of avalanche burial, and the function and survival of transplanted organs were assessed.

Results.
Thirty-three organs were procured from eight donors and 31 organs (13 kidneys, 6 livers, 3 pancreases, 5 hearts, and 4 lungs) were ultimately transplanted. Allograft and recipient 1-y survival were 100% and both initial and long-term graft function were good. Only one-third of all avalanche victims who died in the intensive care unit with signs of irreversible hypoxic brain injury became organ donors.

Conclusions.
Initial experience from this retrospective study suggests that organs from brain-dead avalanche victims can be transplanted with good results. Starting a Donation after Circulatory Determination of Death program might be an option for increasing the number of organ donations from avalanche victims with irreversible hypoxic brain injury.
Drug interactions and risks associated with the use of triptans, ditans and monoclonal antibodies in migraine
Authors: Al-Hassany Linda , MaassenVanDenBrink Antoinette 
Published: April 2021

Purpose of review
The aim of this study was to review current evidence concerning potential risks and interactions associated with concomitant use of drugs indicated for the abortive treatment of migraine, namely triptans and ditans, and more recently developed drugs used for the preventive treatment. The latter drug class encompasses monoclonal antibodies (mAbs), which target either calcitonin gene-related peptide (CGRP) or its receptor.

Recent findings
To date, no pharmacokinetic interactions between these drug classes have been reported. However, patients who suffer from triptan- (or ditan-) induced medication overuse headache or those who are nonresponders to triptans might respond less effectively to mAbs. Caution is warranted when coadministrating these drugs in migraine patients with comorbid cardiovascular disease or with an increased cardiovascular risk profile.

Summary
In this review, the main mechanisms of action of triptans, ditans and mAbs targeting CGRP or its receptor are summarized as well as the current evidence on their individual risks. Studies on risks and interactions in case of concomitant use of triptans, ditans and mAbs in migraine patients are relatively scarce. Therefore, these aspects have been considered from a theoretical and hypothetical point of view by taking both their overlapping target, CGRP, and contraindications into account.
Neuropathogenesis of acute coronavirus disease 2019
Authors: Farhadian Shelli F. , Seilhean Danielle , Spudich Serena 
Published: April 2021

Purpose of review
Over the course of the coronavirus disease (COVID-19) pandemic, it has become increasingly clear that there is a high prevalence of neurological complications in people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Recent findings
Studies of central nervous system (CNS) tissue in brain model systems and from adults with acute SARS-CoV-2 infection have begun to uncover potential mechanisms for neurological damage during COVID-19. These studies suggest that direct viral invasion of the CNS occurs in a subset of cases but does not frequently cause overt viral meningoencephalitis. Vascular abnormalities including microvascular thrombi and endothelial activation, as well as parainfectious processes, including CNS specific immune responses, may contribute to neurological symptoms during acute SARS-CoV-2 infection.

Summary
Neuroimmune perturbations and vascular inflammation observed in people with COVID-19 may warrant investigation of immune-modulating interventions to ameliorate neurological complications associated with acute SARS-CoV-2 infection. These therapies may also impact the trajectory of potential long-term complications of COVID-19.
Evolutionary consequences of environmental effects on gamete performance
Authors: Crean Angela J. , Immler Simone 
Published: April 2021

Variation in pre- and post-release gamete environments can influence evolutionary processes by altering fertilization outcomes and offspring traits. It is now widely accepted that offspring inherit epigenetic information from both their mothers and fathers. Genetic and epigenetic alterations to eggs and sperm-acquired post-release may also persist post-fertilization with consequences for offspring developmental success and later-life fitness. In externally fertilizing species, gametes are directly exposed to anthropogenically induced environmental impacts including pollution, ocean acidification and climate change. When fertilization occurs within the female reproductive tract, although gametes are at least partially protected from external environmental variation, the selective environment is likely to vary among females. In both scenarios, gamete traits and selection on gametes can be influenced by environmental conditions such as temperature and pollution as well as intrinsic factors such as male and female reproductive fluids, which may be altered by changes in male and female health and physiology. Here, we highlight some of the pathways through which changes in gamete environments can affect fertilization dynamics, gamete interactions and ultimately offspring fitness. We hope that by drawing attention to this important yet often overlooked source of variation, we will inspire future research into the evolutionary implications of anthropogenic interference of gamete environments including the use of assisted reproductive technologies.This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
Intergenerational effects of manipulating DNA methylation in the early life of an iconic invader
Authors: Sarma Roshmi R. , Crossland Michael R. , Eyck Harrison J. F. , DeVore Jayna L. , Edwards Richard J. , Cocomazzo Michael , Zhou Jia , Brown Gregory P. , Shine Richard , Rollins Lee A. 
Published: April 2021

In response to novel environments, invasive populations often evolve rapidly. Standing genetic variation is an important predictor of evolutionary response but epigenetic variation may also play a role. Here, we use an iconic invader, the cane toad (Rhinella marina), to investigate how manipulating epigenetic status affects phenotypic traits. We collected wild toads from across Australia, bred them, and experimentally manipulated DNA methylation of the subsequent two generations (G1, G2) through exposure to the DNA methylation inhibitor zebularine and/or conspecific tadpole alarm cues. Direct exposure to alarm cues (an indicator of predation risk) increased the potency of G2 tadpole chemical cues, but this was accompanied by reductions in survival. Exposure to alarm cues during G1 also increased the potency of G2 tadpole cues, indicating intergenerational plasticity in this inducible defence. In addition, the negative effects of alarm cues on tadpole viability (i.e. the costs of producing the inducible defence) were minimized in the second generation. Exposure to zebularine during G1 induced similar intergenerational effects, suggesting a role for alteration in DNA methylation. Accordingly, we identified intergenerational shifts in DNA methylation at some loci in response to alarm cue exposure. Substantial demethylation occurred within thesodium channel epithelial 1 subunit gammagene (SCNN1G) in alarm cue exposed individuals and their offspring. This gene is a key to the regulation of sodium in epithelial cells and may help to maintain the protective epidermal barrier. These data suggest that early life experiences of tadpoles induce intergenerational effects through epigenetic mechanisms, which enhance larval fitness.This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
A Randomized Trial of Otilimab in Severe COVID-19 Pneumonia (OSCAR)
Authors: Patel Jatin , Beishuizen Albertus , Ruiz Xavier Bocca , Boughanmi Hatem , Cahn Anthony , Criner Gerard J , Davy Katherine , de-Miguel-Díez Javier , Fernandes Sofia , François Bruno , Gupta Anubha , Hanrott Kate , Hatlen Timothy , Inman Dave , Isaacs John D , Jarvis Emily , Kostina Natalia , Lacherade Jean-Claude , Martinez-Ayala Pedro , McEvoy Charlene , Muñoz-Bermúdez Rosana , Neisen Jessica , Plantefeve Gaëtan , Schifano Lorrie , Schwab Lee , Shahid Zainab , Shirano Michinori , Smith Julia E. , Sprinz Eduardo , Summers Charlotte , Terzi Nicolas , Tidswell Mark A , Williamson Russell , Wyncoll Duncan , Layton Mark 
Published: April 2021

AbstractBACKGROUNDIncreasing age is a risk factor for COVID-19 severity and mortality; emerging science implicates GM-CSF and dysregulated myeloid cell responses in the pathophysiology of severe COVID-19.METHODSWe conducted a large, global, double-blind, randomized, placebo-controlled study evaluating a single 90 mg infusion of otilimab (human anti-GM-CSF monoclonal) plus standard of care in adults hospitalized with severe COVID-19 respiratory failure and systemic inflammation, stratified by age and clinical status. Primary outcome was the proportion of patients alive and free of respiratory failure at Day 28; secondary endpoints included all-cause mortality at Day 60.RESULTSOverall, 806 patients were randomized (1:1); 71% of patients receiving otilimab were alive and free of respiratory failure at Day 28 versus 67% receiving placebo, although this did not reach statistical significance (model-adjusted difference 5.3% [95% CI −0.8, 11.4]; p=0.09). However, there was a benefit in the pre-defined ≥70-year age group (model-adjusted difference 19.1% [95% CI 5.2, 33.1]; nominal p=0.009); these patients also had a reduction of 14.4% (95% CI 0.9, 27.9%; nominal p=0.04) in model-adjusted all-cause mortality at Day 60. Safety findings were comparable between otilimab and placebo, and consistent with severe COVID-19.CONCLUSIONSAlthough not statistically significant in the overall population, otilimab demonstrated a substantial benefit in patients aged ≥70, possibly reflecting a population that could benefit from therapeutic blocking of GM-CSF in severe COVID-19 where myeloid cell dysregulation is predominant. These findings are being confirmed in a further cohort of patients aged ≥70 in Part 2 of this study. (ClinicalTrials.gov number: NCT04376684).
Signal quality and power spectrum analysis of remote ultra long-term subcutaneous EEG
Authors: Viana Pedro F. , Remvig Line S. , Duun-Henriksen Jonas , Glasstetter Martin , Dümpelmann Matthias , Nurse Ewan S. , Martins Isabel P. , Schulze-Bonhage Andreas , Freestone Dean R. , Brinkmann Benjamin H. , Kjaer Troels W. , Richardson Mark P. 
Published: April 2021

SummaryObjectiveUltra long-term subcutaneous EEG (sqEEG) monitoring is a new modality with great potential for both health and disease, including epileptic seizure detection and forecasting. However, little is known about the long-term quality and consistency of the sqEEG signal, which is the objective of this study.MethodsThe largest multicenter cohort of sqEEG was analyzed, including fourteen patients with epilepsy and twelve healthy subjects, implanted with a sqEEG device (24/7 EEG™ SubQ), and recorded from 23 to 230 days (median 42 days), with a median data capture rate of 75% (17.9 hours/day). Median power spectral density plots of each subject were examined for physiological peaks, including at diurnal and nocturnal periods. Long-term temporal trends in signal impedance and power spectral features were investigated with subject-specific linear regression models and group-level linear mixed effects models.ResultssqEEG spectrograms showed an approximately 1/f power distribution. Diurnal peaks in the alpha range (8-13Hz) and nocturnal peaks in the sigma range (12-16Hz) were seen in the majority of subjects. Signal impedances remained low and frequency band powers were highly stable throughout the recording periods.SignificanceThe spectral characteristics of minimally-invasive, ultra long-term sqEEG are similar to scalp EEG, while the signal is highly stationary. Our findings reinforce the suitability of this system for chronic implantation on diverse clinical applications, from seizure detection and forecasting to brain-computer interfaces.Key PointsSubcutaneous EEG shows similar spectral characteristics to scalp EEGThe subcutaneous EEG signal is highly stable throughout weeks and months of recordingSubcutaneous EEG systems are well suited for chronic implantation, for seizure detection and seizure forecasting
Decoding microbiome and protein family linkage to improve protein structure prediction
Authors: Yang Pengshuo , Zheng Wei , Ning Kang , Zhang Yang 
Published: April 2021

AbstractInformation extracted from microbiome sequences through deep-learning techniques can significantly improve protein structure and function modeling. However, the model training and metagenome search were largely blind with low efficiency. Built on 4.25 billion microbiome sequences from four major biomes (Gut, Lake, Soil and Fermentor), we proposed a MetaSource model to decode the inherent link of microbial niches with protein homologous families. Large-scale protein family folding experiments showed that a targeted approach using predicted biomes significantly outperform combined metagenome datasets in both speed of MSA collection and accuracy of deep-learning structure assembly. These results revealed the important link of biomes with protein families and provided a useful bluebook to guide future microbiome sequence database and modeling development for protein structure and function prediction.
Separation of cohorts on the basis of bacterial type IV conjugation systems identified from metagenomic assemblies
Authors: Joris Benjamin R. , Browne Tyler S. , Hamilton Thomas A. , Edgell David R. , Gloor Gregory B. 
Published: April 2021

AbstractConjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. Here, we outline two distinct methods to identify conjugative systems in the human gut microbiome. We first show that conjugative systems exhibit strong population and age-level stratification. Additionally, we find that the total relative abundance of all conjugative systems present in a sample is not an informative metric to use, regardless of the method of identifying the systems. Finally, we demonstrate that the majority of assembled conjugative systems are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in “high-quality” metagenomic bins. Our findings highlight that conjugative systems differ between general North Americans and a cohort of North American pre-term infants, revealing a potential use as an age-related biomarker. Furthermore, conjugative systems can distinguish between other geographical-based cohorts. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines.ImportanceThe human gut microbiome is increasingly being associated with human health outcomes through shotgun metagenomic sequencing. The usual approach of metagenomic-level analyses is to bin assembled sequences into approximations of bacterial genomes and perform further investigations on the resultant bins. Here, we show that type IV conjugative systems differ between age and geographically-based cohorts and that these systems are systematically excluded by binning algorithms. We suggest that analysis of type IV conjugative systems should be added to the current metagenomic analysis approaches as they contain much information that could explain differences between cohorts beyond those we investigated.