bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flummoxed by flux: the indeterminate principles of haemodialysis
Authors: Bowry Sudhir K , Kircelli Fatih , Misra Madhukar 
Published: September 2021

ABSTRACTIn haemodialysis (HD), unwanted substances (uraemic retention solutes or ‘uraemic toxins’) that accumulate in uraemia are removed from blood by transport across the semipermeable membrane. Like all membrane separation processes, the transport requires driving forces to facilitate the transfer of molecules across the membrane. The magnitude of the transport is quantified by the phenomenon of ‘flux’, a finite parameter defined as the volume of fluid (or permeate) transferred per unit area of membrane surface per unit time. In HD, as transmembrane pressure is applied to facilitate fluid flow or flux across the membrane to enhance solute removal, flux is defined by the ultrafiltration coefficient (KUF; mL/h/mmHg) reflecting the hydraulic permeability of the membrane. However, in HD, the designation of flux has come to be used in a much broader sense and the term is commonly used interchangeably and erroneously with other measures of membrane separation processes, resulting in considerable confusion. Increased flux is perceived to reflect more ‘porous’ membranes having ‘larger’ pores, even though other membrane and therapy attributes determine the magnitude of flux achieved during HD. Adjectival designations of flux (low-, mid-, high-, super-, ultra-) have found indiscriminate usage in the scientific literature to qualify a parameter that influences clinical decision making and prescription of therapy modalities (low-flux or high-flux HD). Over the years the concept and definition of flux has undergone arbitrary and periodic adjustment and redefinition by authors in publications, regulatory bodies (US Food and Drug Administration) and professional association guidelines (European Renal Association, Kidney Disease Outcomes Quality Initiative), with little consensus. Industry has stretched the boundaries of flux to derive marketing advantages, justify increased reimbursement or contrive new classes of therapy modalities when in fact flux is just one of several specifications that determine membrane or dialyser performance. Membranes considered as high-flux previously are today at the lower end of the flux spectrum. Further, additional parameters unrelated to the rate of diffusive or convective transport (flux) are used in conjunction with or in place of KUF to allude to flux: clearance (mL/min, e.g. of β2-microglobulin) or sieving coefficients (dimensionless). Considering that clinical trials in nephrology, designed to make therapy recommendations and guide policy with economic repercussions, are based on the parameter flux they merit clarification—by regulatory authorities and scientists alike—to avoid further misappropriation.
Blood-incompatibility in haemodialysis: alleviating inflammation and effects of coagulation
Authors: Bowry Sudhir K , Kircelli Fatih , Himmele Rainer , Nigwekar Sagar U 
Published: September 2021

ABSTRACT
Blood-incompatibility is an inevitability of all blood-contacting device applications and therapies, including haemodialysis (HD). Blood leaving the environment of blood vessels and the protection of the endothelium is confronted with several stimuli of the extracorporeal circuit (ECC), triggering the activation of blood cells and various biochemical pathways of plasma. Prevention of blood coagulation, a major obstacle that needed to be overcome to make HD possible, remains an issue to contend with. While anticoagulation (mainly with heparin) successfully prevents clotting within the ECC to allow removal of uraemic toxins across the dialysis membrane wall, it is far from ideal, triggering heparin-induced thrombocytopenia in some instances. Soluble fibrin can form even in the presence of heparin and depending on the constitution of the patient and activation of platelets, could result in physical clots within the ECC (e.g. bubble trap chamber) and, together with other plasma and coagulation proteins, result in increased adsorption of proteins on the membrane surface. The buildup of this secondary membrane layer impairs the transport properties of the membrane to reduce the clearance of uraemic toxins. Activation of complement system-dependent immune response pathways leads to leukopenia, formation of platelet–neutrophil complexes and expression of tissue factor contributing to thrombotic processes and a procoagulant state, respectively. Complement activation also promotes recruitment and activation of leukocytes resulting in oxidative burst and release of pro-inflammatory cytokines and chemokines, thereby worsening the elevated underlying inflammation and oxidative stress condition of chronic kidney disease patients. Restricting all forms of blood-incompatibility, including potential contamination of dialysis fluid with endotoxins leading to inflammation, during HD therapies is thus still a major target towards more blood-compatible and safer dialysis to improve patient outcomes. We describe the mechanisms of various activation pathways during the interaction between blood and components of the ECC and describe approaches to mitigate the effects of these adverse interactions. The opportunities to develop improved dialysis membranes as well as implementation strategies with less potential for undesired biological reactions are discussed.
Subtyping hospitalized patients with hypokalemia by machine learning consensus clustering and associated mortality risks
Authors: Thongprayoon Charat , Mao Michael A , Kattah Andrea G , Keddis Mira T , Pattharanitima Pattharawin , Erickson Stephen B , Dillon John J , Garovic Vesna D , Cheungpasitporn Wisit 
Published: September 2021

ABSTRACT

Background
Hospitalized patients with hypokalemia are heterogeneous and cluster analysis, an unsupervised machine learning methodology, may discover more precise and specific homogeneous groups within this population of interest. Our study aimed to cluster patients with hypokalemia at hospital admission using an unsupervised machine learning approach and assess the mortality risk among these distinct clusters.

Methods
We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities and laboratory data among 4763 hospitalized adult patients with admission serum potassium ≤3.5 mEq/L. We calculated the standardized mean difference of each variable and used the cutoff of ±0.3 to identify each cluster's key features. We assessed the association of the hypokalemia cluster with hospital and 1-year mortality.

Results
Consensus cluster analysis identified three distinct clusters that best represented patients’ baseline characteristics. Cluster 1 had 1150 (32%) patients, cluster 2 had 1344 (28%) patients and cluster 3 had 1909 (40%) patients. Based on the standardized difference, patients in cluster 1 were younger, had less comorbidity burden but higher estimated glomerular filtration rate (eGFR) and higher hemoglobin; patients in cluster 2 were older, more likely to be admitted for cardiovascular disease and had higher serum sodium and chloride levels but lower eGFR, serum bicarbonate, strong ion difference (SID) and hemoglobin, while patients in cluster 3 were older, had a greater comorbidity burden, higher serum bicarbonate and SID but lower serum sodium, chloride and eGFR. Compared with cluster 1, cluster 2 had both higher hospital and 1-year mortality, whereas cluster 3 had higher 1-year mortality but comparable hospital mortality.

Conclusion
Our study demonstrated the use of consensus clustering analysis in the heterogeneous cohort of hospitalized hypokalemic patients to characterize their patterns of baseline clinical and laboratory data into three clinically distinct clusters with different mortality risks.
Emerging Fungal Infections: New Species, New Names, and Antifungal Resistance
Authors: Wiederhold Nathan P 
Published: September 2021

Abstract

Background
Infections caused by fungi can be important causes of morbidity and mortality in certain patient populations, including those who are highly immunocompromised or critically ill. Invasive mycoses can be caused by well-known species, as well as emerging pathogens, including those that are resistant to clinically available antifungals.

Content
This review highlights emerging fungal infections, including newly described species, such as Candida auris, and those that having undergone taxonomic classification and were previously known by other names, including Blastomyces and Emergomyces species, members of the Rasamsonia argillacea species complex, Sporothrix brasiliensis, and Trichophyton indotinae. Antifungal resistance also is highlighted in several of these emerging species, as well as in the well-known opportunistic pathogen Aspergillus fumigatus. Finally, the increased recognition and importance of fungal co-infections with respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is discussed.

Summary
Both clinicians and clinical microbiology laboratories should remain vigilant regarding emerging fungal infections. These may be difficult both to diagnose and treat due to the lack of experience of clinicians and laboratory personnel with these organisms and the infections they may cause. Many of these fungal infections have been associated with poor clinical outcomes, either due to inappropriate therapy or the development of antifungal resistance.
Seasonal drivers of faecal glucocorticoid metabolite concentrations in an African strepsirrhine primate, the thick-tailed greater galago (Otolemur crassicaudatus)
Authors: Long Channen , Tordiffe Adrian , Sauther Michelle , Cuozzo Frank , Millette James , Ganswindt Andre , Scheun Juan 
Published: September 2021

Abstract
As global non-human primate populations show dramatic declines due to climate change, land transformation and other anthropogenic stressors, it has become imperative to study physiological responses to environmental change in order to understand primate adaptability and enhance species conservation strategies. We examined the effects of seasonality on faecal glucocorticoid metabolite (fGCM) concentrations of free-ranging male and female thick-tailed greater galagos (Otolemur crassicaudatus) in an Afromontane habitat. To do so, we established an enzyme immunoassay (EIA) for monitoring fGCM concentrations in the species using a biological validation. Following this, faecal samples were collected each month over the course of a year from free-ranging males and females situated in the Soutpansberg Mountains, Limpopo, South Africa. Multivariate analyses revealed lactation period was a driver of fGCM levels, whereas sex and food availability mostly influenced seasonal fGCM concentrations in the total population. Thus far, the results of this study show that drivers of fGCM levels, an indication of increased adrenocortical activity, in O. crassicaudatus are numerous and complex within the natural environment. The species may be adapted to such conditions and an extreme change to any one component may result in elevated fGCM levels. This increases our understanding of strepsirrhine primate physiology and offers initial insights into species adaptability to a challenging environment.
Combined assessment of stress cardiovascular magnetic resonance and angiography to predict the effect of revascularization in chronic coronary syndrome patients
Authors: Gavara Jose , Perez Nerea , Marcos-Garces Victor , Monmeneu Jose V , Lopez-Lereu Maria P , Rios-Navarro Cesar , De Dios Elena , Bonanad Clara , Cánoves Joaquim , Moratal David , Palau Patricia , Miñana Gema , Nunez Julio , Chorro Francisco Javier , Bodi Vicente 
Published: September 2021

Abstract

Aims
The role of revascularization in chronic coronary syndrome (CCS) and the value of ischaemia vs. anatomy to guide decision-making are in constant debate. We explored the potential of a combined assessment of ischaemic burden by vasodilator stress cardiovascular magnetic resonance (CMR) and presence of multivessel disease by angiography to predict the effect of revascularization on all-cause mortality in CCS.

Methods and results
The study group comprised 1066 CCS patients submitted to vasodilator stress CMR pre-cardiac catheterization (mean age 66 ± 11 years, 69% male). Stress CMR-derived ischaemic burden (extensive if &gt;5 ischaemic segments) and presence of multivessel disease in angiography (two- or three-vessel or left main stem disease) were computed. The influence of revascularization on all-cause mortality was explored and adjusted hazard ratios (HRs) with the corresponding 95% confidence intervals were obtained. During a median 7.51-year follow-up, 557 (52%) CMR-related revascularizations and 308 (29%) deaths were documented. Revascularization exerted a neutral effect on all-cause mortality in the whole study group [HR 0.94 (0.74–1.19), P = 0.6], in patients without multivessel disease [n = 598, 56%, HR 1.12 (0.77–1.62), P = 0.6], and in those with multivessel disease without extensive ischaemic burden [n = 181, 17%, HR 1.66 (0.91–3.04), P = 0.1]. However, compared to non-revascularized patients, revascularization significantly reduced all-cause mortality in patients with simultaneous multivessel disease and extensive ischaemic burden (n = 287, 27%): 3.77 vs. 7.37 deaths per 100 person-years, HR 0.60 (0.40–0.90), P = 0.01.

Conclusions
In patients with CCS submitted to catheterization, evidence of simultaneous extensive CMR-related ischaemic burden and multivessel disease identifies the subset in whom revascularization can reduce all-cause mortality.
Adverse employment histories, work stress and self-reported depression in the French CONSTANCES study
Authors: Hoven Hanno , Wahrendorf Morten , Goldberg Marcel , Zins Marie , Siegrist Johannes 
Published: September 2021

AbstractBackgroundJob instability and disadvantaged work were shown to be associated with poor mental health, but few studies analyzed these conditions in a life course perspective. In this study, adverse employment histories are retrospectively assessed and linked to self-reported depression. Furthermore, indirect effects of later stressful psychosocial work in terms of effort-reward imbalance are investigated.MethodsWith data from the French CONSTANCES cohort study of 13 716 male and 12 767 female employees aged 45 and older, we identify adverse employment histories between age 25 and 45, focussing on job discontinuity, job instability and cumulative disadvantage. Direct effects of these conditions on self-reported depression over a period of up to 5 years are analyzed, using discrete-time logistic regression. Indirect effects of stressful work at baseline are examined.ResultsModerately elevated odds ratios of self-reported depression are observed among participants with discontinued employment histories (number of unemployment periods; years out of work for men). Effort-reward imbalance at work is consistently related to elevated risk of self-reported depression and explains parts of the association between discontinuous employment and depression.ConclusionsApplying a life course perspective to occupational health research extends current knowledge. Specifically, adverse employment histories in terms of recurrent job discontinuity are related to the risk of self-reported depression. This association is partly explained by exposure to a stressful psychosocial work environment. These results can instruct labour market policies and the development of targeted worksite interventions that address disadvantage throughout entire employment trajectories.
Met and unmet need for mental health care before and during the COVID-19 pandemic
Authors: Knudsen Ann Kristin Skrindo , Skogen Jens Christoffer , Stene-Larsen Kim , Gustavson Kristin , Reneflot Anne 
Published: September 2021

Abstract
There is a concern that the coronavirus disease 2019 (COVID-19) pandemic will generate large unmet needs for mental health care. Using data from an epidemiological psychiatric diagnostic interview survey (n = 2159) conducted on a probability sample from the general population, the proportions of met and unmet need for mental health care among individuals with and without mental disorders were compared before and during the COVID-19 pandemic. The results showed no statistical difference in met and unmet need for mental health care, but point estimates were suggestive of a higher unmet need for care among those with a current mental disorder after the lock-down period.
Patient experiences with general practitioners: psychometric performance of the generic PEQ-GP instrument among patients with chronic conditions
Authors: Bjertnæs Øyvind A , Iversen Hilde H , Valderas Jose M 
Published: September 2021

Abstract

Background
Most generic patient experience instruments have not been validated specifically for persons with chronic health problems, even though they are the dominant user of GPs/family physicians.

Objectives
To assess the psychometric properties of the generic Patient Experiences with GP Questionnaire (PEQ-GP) instrument (five scales: assessment of GP, coordination, patient enablement, accessibility, and practice) in persons with chronic conditions, and to develop a short version to maximize response rates and minimize respondent fatigue in future applications.

Methods
Secondary analysis of data from a national survey of patient experiences with general practitioners in 2018–2019 (response rate: 42.6%). The psychometric properties of PEQ-GP were assessed with exploratory factor analysis and Cronbach’s alpha, supplemented with confirmatory factor analysis (CFA) and item response theory (IRT). A short version was constructed and evaluated based on item performance.

Results
Nine hundred and seventy persons reported a chronic condition(s), the most frequent being “musculoskeletal, arthritis, other back and joints” (n = 473, 48.8%). Factor analysis identified three scales with adequate psychometric results: GP (15 items; Cronbach’s alpha: 0.96), practice (3 items; Cronbach’s alpha: 0.87), and accessibility (2 items; Cronbach’s alpha: 0.77). Evaluation of item performance identified a 7-item short version, including a 5-item GP scale with scores with strong concordance with the 15-item scale (Intraclass Correlation Coefficient: 0.97, P &lt; 0.001).

Conclusions
The generic PEQ-GP exhibits adequate psychometric performance for persons with chronic conditions. Three empirically derived PEQ-GP scales cover evaluation of the GP, accessibility, and practice. The 7-item short form minimize respondent burden, but further validation work is warranted before large-scale use.
Apple endophyte community in relation to location, scion and rootstock genotypes and susceptibility to European canker
Authors: Olivieri Leone , Saville Robert J , Gange Alan C , Xu Xiangming 
Published: September 2021

ABSTRACTEuropean apple canker, caused by Neonectria ditissima, is a severe disease of apple. Achieving effective control is difficult with the currently available pesticides. Specific apple endophytes associated with cultivars may partially contribute to the cultivar response to the pathogen and thus could be used for disease management. We sought to determine whether the overall endophyte community differed among cultivars differing in their susceptibility to N. ditissima and to identify specific microbial groups associated with the susceptibility. Using Illumina MiSeq meta-barcoding, we profiled apple tree endophytes in 16 scion–rootstock combinations at two locations and quantified the relative contribution of scion, rootstock and location to the observed variability in the endophyte communities. Endophyte diversity was primarily affected by the orchard location (accounting for 29.4% and 85.9% of the total variation in the PC1 for bacteria and fungi, respectively), followed by the scion genotype (24.3% and 19.5% of PC2), whereas rootstock effects were small (&lt;3% of PC1 and PC2). There were significant differences in the endophyte community between canker-resistant and -susceptible cultivars. Several bacterial and fungal endophyte groups had different relative abundance between susceptible and resistant cultivars. These endophyte groups included putative pathogen antagonists as well as plant pathogens. Their possible ecological roles in the N. ditissima pathosystem are discussed.
Coordinated Gene Expression and Chromatin Regulation during Hydra Head Regeneration
Authors: Murad Rabi , Macias-Muñoz Aide , Wong Ashley , Ma Xinyi , Mortazavi Ali 
Published: September 2021

Abstract
The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-h head regeneration and 72-h budding time courses. In order to understand the regulatory elements controlling Hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of the organism body or regenerating tissue. We used histone modification ChIP-seq to identify 9,998 candidate proximal promoter and 3,018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Gene Duplications Are At Least 50 Times Less Frequent than Gene Transfers in Prokaryotic Genomes
Authors: Tria Fernando D K , Martin William F 
Published: September 2021

AbstractThe contribution of gene duplications to the evolution of eukaryotic genomes is well studied. By contrast, studies of gene duplications in prokaryotes are scarce and generally limited to a handful of genes or careful analysis of a few prokaryotic lineages. Systematic broad-scale studies of prokaryotic genomes that sample available data are lacking, leaving gaps in our understanding of the contribution of gene duplications as a source of genetic novelty in the prokaryotic world. Here, we report conservative and robust estimates for the frequency of recent gene duplications within prokaryotic genomes relative to recent lateral gene transfer (LGT), as mechanisms to generate multiple copies of related sequences in the same genome. We obtain our estimates by focusing on evolutionarily recent events among 5,655 prokaryotic genomes, thereby avoiding vagaries of deep phylogenetic inference and confounding effects of ancient events and differential loss. We find that recent, genome-specific gene duplications are at least 50 times less frequent and probably 100 times less frequent than recent, genome-specific, gene acquisitions via LGT. The frequency of gene duplications varies across lineages and functional categories. The findings improve our understanding of genome evolution in prokaryotes and have far-reaching implications for evolutionary models that entail LGT to gene duplications ratio as a parameter.