bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of esophagogastric varices in patients with advanced pancreatic cancer
Authors: Chen Yu-Jen , Hou Ming-Chih , Yang Tsung-Chieh , Lee Pei-Chang , Chao Yee , Li Chung-Pin , Huang Yi-Hsiang , Lee Fa-Yauh 
Published: September 2021

Background:
The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients.

Methods:
A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV.

Results:
Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient’s survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001).

Conclusion:
Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.
The Debate Between Two of the Founders of American Psychiatric Genetics, Aaron Rosanoff and Abraham Myerson, on Mendelian Models for Psychiatric Illness
Authors: Kendler Kenneth S. 
Published: September 2021

Abstract
In 1911, Aaron Rosanoff published among the first pedigree studies of psychiatric illness, and the first ever in the United States, claiming that the neuropathic constitution was transmitted in as a Mendelian recessive disorder. In 1917, Abraham Myerson harshly critiqued that study, focusing on the very wide phenotypic definition of neuropathic constitution. Here, I describe Rosanoff and Myerson's backgrounds, the details of Rosanoff's study, and Myerson's critique and put this controversy in the context of the history of psychiatric genetics, emphasizing four themes: a) the close interrelationship between psychiatric diagnosis and models of genetic transmission, b) the strong attraction of Mendelian models to psychiatric geneticists after their 1900 rediscovery, c) the controversy about whether familial transmission of psychiatric illness is largely homogeneous or heterogeneous, and d) the methods taken by researchers to the problems of psychiatric genetics that typically emerged as part of their broader approach to the nature of psychiatric illness.
Inpatient compliance with venous thromboembolism prophylaxis after orthopaedic trauma: results from a randomized controlled trial of aspirin versus low molecular weight heparin
Authors: Haac Bryce E. , O’Hara Nathan N. , Manson Theodore T. , Slobogean Gerard P. , Castillo Renan C. , O’Toole Robert V. , Stein Deborah M. 
Published: September 2021

Abstract

Objectives:
To compare inpatient compliance with venous thromboembolism prophylaxis regimens.

Design:
A secondary analysis of patients enrolled in the ADAPT (A Different Approach to Preventing Thrombosis) randomized controlled trial.

Setting:
Level I trauma center.

Patients/Participants:
Patients with operative extremity or any pelvic or acetabular fracture requiring venous thromboembolism prophylaxis.

Intervention:
We compared patients randomized to receive either low molecular weight heparin (LMWH) 30 mg or aspirin 81 mg BID during their inpatient admission.

Main Outcome Measurements:
The primary outcome measure was the number of doses missed compared with prescribed number of doses.

Results:
A total of 329 patients were randomized to receive either LMWH 30 mg BID (164 patients) or aspirin 81 mg BID (165 patients). No differences observed in percentage of patients who missed a dose (aspirin: 41.2% vs LMWH: 43.3%, P = .7) or mean number of missed doses (0.6 vs 0.7 doses, P = .4). The majority of patients (57.8%, n = 190) did not miss any doses. Missed doses were often associated with an operation.

Conclusions:
These data should reassure clinicians that inpatient compliance is similar for low molecular weight heparin and aspirin regimens.
Role of sleep quality in the acceleration of biological aging and its potential for preventive interaction on air pollution insults: findings from the UK Biobank cohort
Authors: Gao Xu , Huang Ninghao , Huang Tao 
Published: September 2021

AbstractBackgroundSleep has been associated with aging and relevant health outcomes, but their causal relationship remains inconclusive.MethodsIn this study, we investigated the associations of sleep behaviors with biological ages (BAs) among 363,886 middle and elderly-aged adults from UK Biobank. Sleep index (0 [worst]-6 [best]) of each participant was retrieved from six sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, and difficulties in getting up. Two BAs, the KDM-biological age and PhenoAge, were estimated by corresponding algorithms based on clinical traits, and their discrepancies with chronological age were defined as the age accelerations (AAs).ResultsWe first observed negative associations between the sleep index and the two AAs, and demonstrated that the change of AAs could be the consequence of sleep quality using Mendelian randomization with genetic risk scores of sleep index and BAs. Particularly, one unit increase in sleep index was associated with 0.105- and 0.125-year decreases in KDM-biological age acceleration and PhenoAge acceleration, respectively. Furthermore, we observed significant independent and joint effects of sleep and air pollution (i.e. PM2.5 and NO2), another key driver of aging, on BAs. Sleep quality also showed modifying effect on the associations of elevated PM2.5 and NO2 levels with accelerated aging. For instance, an interquartile range increase in PM2.5 level was associated with 0.011-, 0.047-, and 0.078-year increase in PhenoAge acceleration among people with high (5-6), medium (3-4), and low (0-2) sleep index, respectively.ConclusionsOur findings elucidate that better sleep quality could lessen accelerated biological aging resulting from exogenous exposures including air pollution.FundingPeking University Start-up Grant (BMU2021YJ044)
VALIDATION OF A SALIVA-BASED TEST FOR THE MOLECULAR DIAGNOSIS OF SARS-CoV-2 INFECTION
Authors: Bulfoni Michela , Sozio Emanuela , Marcon Barbara , De Martino Maria , Cesselli Daniela , De Carlo Chiara , Martinella Romina , Migotti Angelica , Vania Eleonora , Zanus-Fortes Agnese , De Piero Jessica , Nencioni Emanuele , Tascini Carlo , Isola Miriam , Curcio Francesco 
Published: September 2021

ABSTRACTBackgroundSince the beginning of the pandemic, clinicians and researchers have been searching for alternative tests to improve screening and diagnosis of SARS-CoV-2 infection (Y. Yang et al., medRxiv 2020; W. Wang et al., 2020.3786; A Senok et al., Infect Drug Resist 2020). Currently, the gold standard for virus identification is the nasopharyngeal (NP) swab (N. Sethuraman et al., JAMA 2020; A.J. Jamal et al Clinical Infect Disease 2021). Saliva samples, however, offer clear practical and logistical advantages (K.K.W To et al, Clinical Microb and Infect; A.L. Wylle et al. N Engl J Med 2020; N. Matic et al, Eur J Clin 2021) but due to lack of collection, transport, and storage solutions, high-throughput saliva-based laboratory tests are difficult to scale up as a screening or diagnostic tool (D. Esser et al., Biomark Insights 2008; E. Kaufman et al., Crit Rev Oral Biol Med2002). With this study, we aimed to validate an intra-laboratory molecular detection method for SARS-CoV-2 on saliva samples collected in a new storage saline solution, comparing the results to NP swabs to determine the difference in sensitivity between the two tests.MethodsIn this study, 156 patients (cases) and 1005 asymptomatic subjects (controls) were enrolled and tested simultaneously for the detection of the SARS-CoV-2 viral genome by RT-PCR on both NP swab and saliva samples. Saliva samples were collected in a preservative and inhibiting saline solution (Biofarma Srl). Internal method validation was performed to standardize the entire workflow for saliva samples.ResultsThe identification of SARS-CoV-2 conducted on saliva samples showed a clinical sensitivity of 95.1% and specificity of 97.8% compared to NP swabs. The positive predictive value (PPV) was 81% while the negative predictive value (NPV) was 99.5%. Test concordance was 97.6% (Cohen’s Kappa=0.86; 95% CI 0.81-0.91). The LoD of the test was 5 viral copies for both samples.ConclusionsRT-PCR assays conducted on a stored saliva sample achieved similar performance to those on NP swabs and this may provide a very effective tool for population screening and diagnosis. Collection of saliva in a stabilizing solution makes the test more convenient and widely available; furthermore, the denaturing properties of the solution reduce the infective risks belonging to sample manipulation.
Social-economic drivers overwhelm climate in underlying the COVID-19 early growth rate
Authors: Liu Zhenghua 
Published: September 2021

AbstractIdentifying the drivers underlying the spatial occurrence and spreading rate of COVID-19 can provide valuable information for their preventions and controls. Here, we examine how socio-economic and climate drivers affect the early growth rates of COVID-19 in China and the other countries, the former of which have consistently stricter quarantine during early epidemic and thus are used to enquire the influences of human interventions on trainsimissions. We find that the early growth rates of COVID-19 are higher in China than the other countries, which is consistent with previous reports. The global spread is mainly driven by the socio-economic factors such as GDP per capita, human movement and population density rather than climate. Among socio-economic factors, GDP per capita is most important showing negative relationships in China, while positive in the other countries. However, the predicability of early growth rates by socio-economic and climate variables is at least 1.6 times higher in China’s provinces than the other countries, which is further supported by metapopulation network model. These findings collectively indicate that the stochasticity of transimission processes decrease upon strict quarantine measures such as travel restrictions.Key findingsGDP per capita is most important in driving the spread of COVID-19, which shows negative relationships within China, while positive in the other countries.Socio-economic and climate factors are key in driving the early growth rate of COVID-19, while the former is more important.Socio-economic and climate features explain more variations of early growth rates in China due to the decreased stochasticity of transimission processes upon strict quarantine measures.
Store-Operated Calcium Entry Controls Innate and Adaptive Immune Cell Function in Inflammatory Bowel Disease
Authors: Letizia Marilena , Kaufmann Ulrike , Wang Yin-Hu , Gerbeth Lorenz , Sand Annegret , Brunkhorst Max , Ziegler Jörn Felix , Böttcher Chotima , Schlickeiser Stephan , Fernández-Zapata Camila , Stauderman Kenneth , Kunkel Désirée ,   IBDome researchers, Siegmund Britta , Feske Stefan , Weidinger Carl 
Published: September 2021

AbstractObjectiveInflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses and constitutes a major clinical challenge in need of new treatment modalities to improve patient care. Store-operated Ca2+entry (SOCE) is the predominant Ca2+influx pathway in T cells and other immune cells, regulating many of their functional properties. It is currently unknown whether the pharmacologic blockade of SOCE represents a suitable drug-target for IBD treatment.DesignUsing mass and flow cytometry the effects of SOCE inhibition on lamina propria (LP) immune cells of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were investigated. Primary organoid cultures served to study the impact of SOCE inhibition on the function, differentiation and survival of intestinal epithelial cells (IEC). T cell transfer models of colitis were applied to examine how the genetic or pharmacologic ablation of SOCE affects the clinical course of IBD in mice.ResultsWe observed that the LP of IBD patients is characterized by an enrichment of innate lymphoid cells (ILC), CD4+and CD8+effector- as well as T regulatory cells producing IL-17 and TNFα. The pharmacologic inhibition of SOCE attenuated the production of pathogenic cytokines including IL-2, IL-4, IL-6, IL-17, TNFα and IFNγ by human colonic T cells and ILC, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, without affecting the viability, differentiation and function of primary IEC. T cell-specific genetic deletion of the SOCE signaling componentsOrai1,Stim1orStim2revealed that the magnitude of SOCE correlates with the function of T cells and intestinal inflammation in mice. Moreover, the pharmacologic inhibition of SOCE alleviated the clinical course of colitic mice.ConclusionOur data suggest that SOCE inhibition may serve as a new pharmacologic strategy for treating IBD.
Critical Pressure of Intramural Delamination in Aortic Dissection
Authors: Ban Ehsan , Cavinato Cristina , Humphrey Jay D. 
Published: September 2021

ABSTRACTComputational models of aortic dissection can examine mechanisms by which this potentially lethal condition develops and propagates. We present results from phase-field finite element simulations that are motivated by a classical but seldom repeated experiment. Initial simulations agreed qualitatively and quantitatively with data, yet because of the complexity of the problem it was difficult to discern trends. Simplified analytical models were used to gain further insight. Together, simplified and phase-field models reveal power-law-based relationships between the pressure that initiates an intramural tear and key geometric and mechanical factors – insult surface area, wall stiffness, and tearing energy. The degree of axial stretch and luminal pressure similarly influence the pressure of tearing, which was ∼88 kPa for healthy and diseased human aortas having sub-millimeter-sized initial insults, but lower for larger tear sizes. Finally, simulations show that the direction a tear propagates is influenced by focal regions of weakening or strengthening, which can drive the tear towards the lumen (dissection) or adventitia (rupture). Additional data on human aortas having different predisposing disease conditions will be needed to extend these results further, but the present findings show that physiologic pressures can propagate initial medial defects into delaminations that can serve as precursors to dissection.
The extended second law of thermodynamics suggests a thermodynamic imperative driving the evolution of life systems towards increased complexity
Authors: Menendez Sergio 
Published: September 2021

AbstractFrom a thermodynamic point of view life structures can be viewed as dissipative systems capable of self replication. Energy flowing from the external environment into the system allows growth of its self replicative components increasing the system complexity concomitantly with an increase in the entropy of the universe, thus observing the second law of thermodynamics. However, general thermodynamic models of life systems have been hampered by the lack of precise equations modelling far from equilibrium driven systems operating in non-linear response regimes. Recent theoretical advances, applying time reversal symmetry and coarse grained state transitions, have provided theoretical insights into the thermodynamic constraints that bind the behaviour of such far from equilibrium life systems. Setting additional constraints based on empirical observations allows us to apply this theoretical framework to gain a further semiquantitative insight on the thermodynamic boundaries and evolution of complex self replicative life systems. This interpretation suggests a thermodynamic hierarchical organisation based on increasing accessible levels of usable energy, which in turn drives an exponential punctuated growth of the system’s complexity. For the earth life system this growth has historically not been limited by the total energy available from the external driving field, but by the system’s internal adaptability needed to access higher levels of usable energy. Therefore, in the absence of external perturbations, the emergence of an initial self replicative dissipative structure capable of variation that enables access to higher energy levels is sufficient to drive the system’s growth irreversibly towards increased complexity across time and space in a hierarchical manner. This interpretation is consistent with current empirical observation of life systems across both time and space and explains from a thermodynamic point of view the evolutionary patterns of complex life systems on earth.
Comparative analysis of wild type accessions reveals novel determinants of Arabidopsis seed longevity
Authors: Niñoles Regina , Planes Dolores , Arjona Paloma , Ruiz-Pastor Carmen , Chazarra Rubén , Renard Joan , Bueso Eduardo , Forment Javier , Serrano Ramón , Kranner Ilse , Roach Thomas , Gadea José 
Published: September 2021

AbstractUnderstanding the genetic factors involved in seed longevity is of paramount importance in agricultural and ecological contexts. The polygenic nature of this trait suggests that many of them remain undiscovered. Here, we exploited the contrasting seed longevity found amongst wild type Arabidopsis thaliana accessions to further understand this phenomenon. Concentrations of the antioxidant glutathione were consistently higher in longer-lived than shorter-lived accessions, supporting that redox poise plays a prominent role in seed longevity. However, high seed permeability, normally associated with shorter longevity, is also present in accessions with longer seed longevity. Transcriptome analysis indicated that the detrimental effect on longevity caused by seed coat permeability may be counterbalanced by higher levels of specific mRNAs stored in dry seed, particularly those of heat-shock proteins. Indeed, reverse genetics demonstrated that heat-shock factors HSF1A and 1B contributed to longevity. Furthermore, loss-of-function mutants of RNA-binding proteins, such as the stress-granule zinc-finger protein TZF9, or the spliceosome subunits MOS4 or MAC3A/MAC3B, extended seed longevity, positioning RNA as a novel player in the regulation of seed viability. mRNAs of proteins with putative relevance to longevity were also abundant in shorter-lived accessions, reinforcing the idea that resistance to ageing is determined by multiple factors.
A natural genetic variation screen identifies insulin signaling, neuronal communication, and innate immunity as modifiers of hyperglycemia in the absence of Sirt1
Authors: Owings Katie G. , Palu Rebecca A.S. 
Published: September 2021

ABSTRACTVariation in the onset, progression, and severity of symptoms associated with metabolic disorders such as diabetes impairs the diagnosis and treatment of at-risk patients. Diabetes symptoms, and patient variation in these symptoms, is attributed to a combination of genetic and environmental factors, but identifying the genes and pathways that modify diabetes in humans has proven difficult. A greater understanding of genetic modifiers and the ways in which they interact with metabolic pathways could improve the ability to predict a patient’s risk for severe symptoms, as well as enhance the development of individualized therapeutic approaches. In this study we use the Drosophila Genetic Reference Panel (DGRP) to identify genetic variation influencing hyperglycemia associated with loss of Sirt1 function. Through analysis of individual candidate functions, physical interaction networks, and Gene Set Enrichment Analysis (GSEA) we identify not only modifiers involved in canonical glucose metabolism and insulin signaling, but also genes important for neuronal signaling and the innate immune response. Furthermore, reducing the expression of several of these candidates suppressed hyperglycemia, making them ideal candidate therapeutic targets. These analyses showcase the diverse processes contributing to glucose homeostasis and open up several avenues of future investigation.
Emerging chikungunya virus variants at the E1-E1 inter-glycoprotein spike interface impact virus attachment and Inflammation
Authors: Rangel Margarita V. , McAllister Nicole , Dancel-Manning Kristen , Noval Maria G. , Silva Laurie A. , Stapleford Kenneth A. 
Published: September 2021

ABSTRACTChikungunya virus (CHIKV) is a re-emerging arthropod-borne alphavirus and a serious threat to human health. Therefore, efforts toward elucidating how this virus causes disease and the molecular mechanisms underlying steps of the viral replication cycle are crucial. Using anin vivotransmission system that allows intra-host evolution, we identified an emerging CHIKV variant carrying a mutation in the E1 glycoprotein (V156A) in the serum of mice and saliva of mosquitoes. E1 V156A has since emerged in humans during an outbreak in Brazil, co-occurring with a second mutation, E1 K211T, suggesting an important role for these residues in CHIKV biology. Given the emergence of these variants, we hypothesized that they function to promote CHIKV infectivity and subsequent disease. Here, we show that E1 V156A and E1 K211T modulate virus attachment and fusion and impact binding to heparin, a homolog of heparan sulfate, a key entry factor on host cells. These variants also exhibit differential neutralization by anti-glycoprotein monoclonal antibodies, suggesting structural impacts on the particle that may be responsible for altered interactions at the host membrane. Finally, E1 V156A and E1 K211T exhibit increased titers in an adult arthritic mouse model and induce increased foot-swelling at the site of injection. Taken together, this work has revealed new roles for E1 where discrete regions of the glycoprotein are able to modulate cell attachment and swelling within the host.IMPORTANCEAlphaviruses represent a growing threat to human health worldwide. Chikungunya virus (CHIKV) has rapidly spread to new geographic regions in the last several decades, causing overwhelming outbreaks of disease, yet there are no approved therapeutics. The CHIKV glycoproteins are key determinants of CHIKV adaptation and virulence. In this study, we characterize the naturally emerging E1 glycoprotein variants, V156A and K211T. We demonstrate that E1 V156A and K211T function in virus attachment to cells, a role that until now has been only attributed to the CHIKV E2 glycoprotein. We also demonstrate E1 V156A and K211T to increase foot-swelling in mice. Observing that these variants and other pathogenic variants occur at the E1-E1 inter-spike interface, we highlight this structurally important region as critical for multiple steps during CHIKV infection. Together, these studies further defines the function of E1 in CHIKV infection and can inform the development of therapeutic or preventative strategies.