bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma and vacuolar membrane sphingolipidomes: composition and insights on the role of main molecular species
Authors: Carmona-Salazar Laura , Cahoon Rebecca E , Gasca-Pineda Jaime , González-Solís Ariadna , Vera-Estrella Rosario , Treviño Victor , Cahoon Edgar B , Gavilanes-Ruiz Marina 
Published: February 2021

Abstract
Lipid structures affect membrane biophysical properties such as thickness, stability, permeability, curvature, fluidity, asymmetry, and interdigitation, contributing to membrane function. Sphingolipids are abundant in plant endomembranes and plasma membranes (PMs) and comprise four classes: ceramides, hydroxyceramides, glucosylceramides, and glycosylinositolphosphoceramides (GIPCs). They constitute an array of chemical structures whose distribution in plant membranes is unknown. With the aim of describing the hydrophobic portion of sphingolipids, 18 preparations from microsomal (MIC), vacuolar (VM), PM, and detergent-resistant membranes (DRM) were isolated from Arabidopsis (Arabidopsis thaliana) leaves. Sphingolipid species, encompassing pairing of long-chain bases and fatty acids, were identified and quantified in these membranes. Sphingolipid concentrations were compared using univariate and multivariate analysis to assess sphingolipid diversity, abundance, and predominance across membranes. The four sphingolipid classes were present at different levels in each membrane: VM was enriched in glucosylceramides, hydroxyceramides, and GIPCs; PM in GIPCs, in agreement with their key role in signal recognition and sensing; and DRM in GIPCs, as reported by their function in nanodomain formation. While a total of 84 sphingolipid species was identified in MIC, VM, PM, and DRM, only 34 were selectively distributed in the four membrane types. Conversely, every membrane contained a different number of predominant species (11 in VM, 6 in PM, and 17 in DRM). This study reveals that MIC, VM, PM, and DRM contain the same set of sphingolipid species but every membrane source contains its own specific assortment based on the proportion of sphingolipid classes and on the predominance of individual species.
Regressive Mortgage Credit Redistribution in the Post-Crisis Era
Authors: D’Acunto Francesco , Rossi Alberto G 
Published: February 2021

Abstract
We document four secular trends about U.S. mortgage origination by traditional and FinTech lenders after the 2008-2009 financial crisis. First, since 2011, the overall number, size, and approval rate of small and medium-sized loans have been decreasing over time, relative to large loans. Second, the largest lenders redistribute their lending the most. Third, this loan-size redistribution of credit increases in the size of the lender. Fourth, the effects are stronger for mortgages further away from the conforming loan limit(s) in both directions. We argue that the supply of credit drives these secular trends, and we assess several potential economic mechanisms.
Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients
Authors: Ruscio Mirko Di , Tinazzi Ilaria , Variola Angela , Geccherle Andrea , Marchetta Antonio , McGonagle Dennis 
Published: February 2021

Abstract

Background
Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases.

Methods
In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described.

Results
A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6–119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications

Conclusions
A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.
Home confinement during the COVID-19: day-to-day associations of sleep quality with rumination, psychotic-like experiences, and somatic symptoms
Authors: Simor Péter , Polner Bertalan , Báthori Noémi , Sifuentes-Ortega Rebeca , Van Roy Anke , Albajara Sáenz Ariadna , Luque González Alba , Benkirane Oumaima , Nagy Tamás , Peigneux Philippe 
Published: February 2021

AbstractDue to the coronavirus disease 2019 (COVID-19) pandemic, populations from many countries have been confined at home for extended periods of time in stressful environmental and media conditions. Cross-sectional studies already evidence deleterious psychological consequences, with poor sleep as a risk factor for impaired mental health. However, limitations of cross-sectional assessments are response bias tendencies and the inability to track daily fluctuations in specific subjective experiences in extended confinement conditions. In a prospective study conducted across three European countries, we queried participants (N = 166) twice a day through an online interface about their sleep quality and their negative psychological experiences for two consecutive weeks. The focus was set on between- and within-person associations of subjective sleep quality with daytime experiences, such as rumination, psychotic-like experiences, and somatic complaints about the typical symptoms of the coronavirus. The results show that daily reports of country-specific COVID-19 deaths predicted increased negative mood, psychotic-like experiences, and somatic complaints during the same day and decreased subjective sleep quality the following night. Disrupted sleep was globally associated with negative psychological outcomes during the study period, and a relatively poorer night of sleep predicted increased rumination, psychotic-like experiences, and somatic complaints the following day. This temporal association was not paralleled by daytime mental complaints predicting relatively poorer sleep quality on the following night. Our findings show that night-to-night changes in sleep quality predict how individuals cope the next day with daily challenges induced by home confinement.
Self-Report and Biological Indexes of Work-Related Stress in Neonatal Healthcare Professionals
Authors: Fumagalli Monica , Provenzi Livio , Sorrentino Gabriele , Ciceri Francesca , Fontana Camilla , Passera Sofia , Moncecchi Michela , Plevani Laura , Laquintana Dario , Borgatti Renato , Mosca Fabio , Montirosso Rosario 
Published: February 2021

Background:
Healthcare providers working in neonatal intensive care units (NICUs) are considered at high risk for psychological work-related stress.

Purpose:
To evaluate both perceived and biological measures of work-related stress in neonatal healthcare professionals and to compare professionals working in the NICU with their colleagues working in less critical environments (ie, neonatal wards [NWs]).

Methods:
The salivary cortisol level at the beginning (CORT-B) and at the end (CORT-E) of a daily work shift was collected once a week for 6 weeks and a psychological questionnaire was submitted to NW and NICU workers of a tertiary university center.

Results:
No differences emerged in the overall cortisol secretion between professionals (NW 45 vs NICU 28), but the decrease in the mean cortisol values between CORT-B and CORT-E was less pronounced in NICU professionals (P < .001) who had greater psychological stress (P < .001). Lack of correlation between perceived and biological indexes was observed.

Implications for Practice:
NICU professionals reported greater levels of self-perceived psychological stress, especially in terms of professional self-doubt and the complexity of interactions with infants and their parents.
The disconnection between psychological and biological indexes raises the issue that work-related stress might be covert to the professionals themselves. Dedicated resources should be developed to address quality of life and the work environment of NICU professionals.

Implications for Research:
The absence of a correlation between perceived and biological indexes highlights the need to incorporate multidimensional physiological and biological measurements in evaluating burnout levels in neonatal healthcare providers.
Interleukin-6 Trajectory and Secondary Infections in Mechanically Ventilated Patients With Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Treated With Interleukin-6 Receptor Blocker
Authors: Vazquez Guillamet M. Cristina , Kulkarni Hrishikesh S. , Montes Kevin , Samant Maanasi , Shaikh Preet A. , Betthauser Kevin , Mudd Philip A. , Reynolds Daniel , O’Halloran Jane , Lyons Patrick , McEvoy Colleen , Vazquez Guillamet Rodrigo 
Published: February 2021

Objectives:
To describe the infectious complications and interleukin-6 trajectories in mechanically ventilated patients with coronavirus disease 2019.

Design:
Retrospective cohort study.

Setting:
ICUs at Washington University-Barnes Jewish Hospital in St. Louis, MO.

Participants:
All consecutive patients admitted to the medical ICU and requiring mechanical ventilation from March 12, 2020, to April 21, 2020, were included.

Interventions:
Tocilizumab, an interleukin-6 receptor blocker, was prescribed at the discretion of the treating physicians to patients with a clinical picture compatible with cytokine release syndrome.

Measurements:
All the patients were followed to death or hospital discharge. Demographic and laboratory data were collected retrospectively from the electronic medical record. Interleukin-6 levels were measured at days 0, 3, 7, 14, and 21. Infections were divided into culture positive and culture negative (clinically suspected and treated). The main outcomes were infectious complications and interleukin-6 levels at different points in time.

Results:
Forty-three patients with respiratory failure secondary to coronavirus disease 2019 were on mechanical ventilation during the study period. Twenty-seven (68%) were male, and 31 (72.1%) were African-American. Median Charlson score was 2 (interquartile range, 0–4). Median Pao2/Fio2 was 171.5 (122–221) on the day of mechanical ventilation initiation, and 13 patients (30.2%) required vasopressors. C-reactive protein was 142.7 (97.7–213.7), d-dimer 1,621 (559–13,434), and Acute Physiology and Chronic Health Evaluation-II 11 (9–15). Interleukin-6 levels at admission were 61 pg/mL (interquartile range, 28.6–439 pg/mL). Patients treated with tocilizumab had higher levels of interleukin-6 at each measurement (days 0, 3, 7, 14, and 21) compared with patients receiving standard of care. Both groups reached peak interleukin-6 levels at day 7. Administration of tocilizumab was associated with a trend toward increased risk of infection.

Conclusions:
Interleukin-6 levels peak at day 7 in patients with severe coronavirus disease 2019 pneumonia requiring mechanical ventilation and follows a similar trajectory in patients with coronavirus disease 2019 pneumonia requiring mechanical ventilation irrespective of treatment with interleukin-6R blockers. Interleukin-6 levels continued to rise in nonsurvivors, in comparison with survivors, where the rise in interleukin-6 levels was followed by a decline.
Co-Occurrence of Neurodevelopmental Disorders in Pediatric Sickle Cell Disease
Authors: Lance Eboni I. , Cannon Alicia D. , Shapiro Bruce K. , Lee Li-Ching , Johnston Michael V. , Casella James F. 
Published: February 2021

ABSTRACT:

Objective:
The objective of this study is to retrospectively determine the co-occurrence, associated characteristics, and risk factors for neurodevelopmental disorders (NDD) in a pediatric sickle cell disease (SCD) clinic population.

Method:
We investigated the co-occurrence and features of NDD in pediatric SCD through a retrospective cohort study conducted between July 2017 and January 2019. The participants were patients with SCD younger than 18 years of age identified from our institutions' clinic rosters and medical records databases.

Results:
A total of 276 participants were eligible for study inclusion, and 65 participants were found to have various NDD. Children with SCD and NDD were more likely to have a history of multiple SCD-related complications in comparison to children with SCD without NDD. Children with SCD and NDD were more likely to use disease-modifying therapies in comparison to children with SCD without NDD (χ2 27.2, p < 0.001).

Conclusion:
Children with SCD and NDD have higher odds of having certain disease-related complications and higher use of disease-modifying treatments than children with SCD who do not have NDD. Screening and diagnoses of NDD may be relevant to clinical management of pediatric SCD.
Sociodemographic and Clinical Characteristics of 1350 Patients With Young Onset Dementia
Authors: Ryan Brigid , Martinez Ruiz Adrian , Rivera-Rodriguez Claudia , Curtis Maurice , Cheung Gary 
Published: February 2021

Objective:
To determine the sociodemographic and clinical characteristics of a large cohort of patients with young onset dementia (YOD) (aged below 65), and whether they differ from older (age 65+) adults with dementia.

Methods:
Retrospective cross-sectional study. Participants were New Zealanders who were assessed with International Residential Assessment Instrument (interRAI) assessments (including community-dwelling adults and those in long-term care) from 2016 to 2019 and had a diagnosis of dementia. Outcomes were sociodemographic and clinical characteristics captured in the interRAI assessment.

Results:
People with YOD were more likely to be male, of non-European ethnicity, and live in a dwelling other than a private home or be homeless. They were more likely to exhibit problematic behaviors and neuropsychiatric symptoms but were less frail and less dependent for activities of daily living. Financial strain and loneliness were more common in people with YOD. Carers of people with YOD were more likely to feel distress, anger, or depression, and families of people with YOD were more likely to feel overwhelmed.

Conclusions:
YOD patients have different needs than older adults with dementia. These differences must be considered by clinicians and organizations that provide care and support to people living with dementia.
Subtle Changes in Medication-taking Are Associated With Incident Mild Cognitive Impairment
Authors: Dorociak Katherine E. , Mattek Nora , Ferguson John E. , Beattie Zachary T. , Sharma Nicole , Kaye Jeffrey A. , Leese Mira I. , Doane Bridget M. , Hughes Adriana M. 
Published: February 2021

Introduction:
Medication-taking is a routine instrumental activity of daily living affected by mild cognitive impairment (MCI) but difficult to measure with clinical tools. This prospective longitudinal study examined in-home medication-taking and transition from normative aging to MCI.

Methods:
Daily, weekly, and monthly medication-taking metrics derived from an instrumented pillbox were examined in 64 healthy cognitively intact older adults (Mage=85.5 y) followed for a mean of 2.3 years; 9 transitioned to MCI during study follow-up.

Results:
In the time up to and after MCI diagnosis, incident MCI participants opened their pillbox later in the day (by 19 min/mo; β=0.46, P<0.001) and had increased day-to-day variability in the first pillbox opening over time (by 4 min/mo) as compared with stable cognitively intact participants (β=4.0, P=0.003).

Discussion:
Individuals who transitioned to MCI opened their pillboxes later in the day and were more variable in their medication-taking habits. These differences increased in the time up to and after diagnosis of MCI. Unobtrusive medication-taking monitoring is an ecologically valid approach for identifying early activity of daily living changes that signal transition to MCI.
Soil Microbial Composition and Structure Allow Assessment of Biological Product Effectiveness and Crop Yield Prediction
Authors: Imam Nabeel , Belda Ignacio , Duehl Adrian J. , Doroghazi James R. , Almonacid Daniel E. , Thomas Varghese P. , Acedo Alberto 
Published: February 2021

ABSTRACTUnderstanding the effectiveness and potential mechanism of action of agricultural biological products under different soil profiles and crops will allow more precise product recommendations based on local conditions and will ultimately result in increased crop yield. This study aimed to use bulk and rhizosphere soil’s microbial composition and structure to evaluate the effect of aBacillus amyloliquefaciensstrain QST713 inoculant on potatoes, and to explore its relationship with crop yield. We implemented NGS and bioinformatics approaches to assess the bacterial and fungal biodiversity in 185 soil samples, distributed over four different time points -from planting to harvest -from three different geographical regions in the United States.In addition to variety, phenological stage of the potato plant and geography being important factors defining the microbiome composition and structure, the microbial inoculant applied as a treatment also had a significant effect. However, treatment preserved the native communities without causing a detectable long-lasting effect on the alpha- and beta-diversity patterns after harvest. Specific taxonomic groups, and most interestingly the structure of the fungal and bacterial communities (measured using co-occurrence and co-exclusion networks), changed after inoculation. Additionally, using information about the application of the microbial inoculant and considering microbiome composition and structure data we were able to train a Random Forest model to estimate if a bulk or rhizosphere soil sample came from a low or high yield block with relatively high accuracy, concluding that the structure of fungal communities is a better estimator of potato yield than the structure of bacterial communities.IMPORTANCEThe manuscript’s results reinforce the notion that each crop variety on each location recruits a unique microbial community and that these communities are modulated by the vegetative growth stage of the plant. Moreover, inoculation of aBacillus amyloliquefaciensstrain QST713-based product on potatoes also changed specific taxonomic groups and, most interestingly, the structure of local fungal and bacterial networks in bulk and rhizosphere soil. The data obtained, coming from in-field assays performed in three different geographical locations, allowed training a predictive model to estimate the yield of a certain block, identifying microbiome variables -especially those related to microbial community structure- with a higher predictive power than the variety and geography of the block. The methods described here can be replicated to fit new models predicting yield in any other crop, and to evaluate the effect of any Ag-input product in the composition and structure of the soil microbiome.
Structural variants in Chinese population and their impact on phenotypes, diseases and population adaptation
Authors: Wu Zhikun , Jiang Zehang , Li Tong , Xie Chuanbo , Zhao Liansheng , Yang Jiaqi , Ouyang Shuai , Liu Yizhi , Li Tao , Xie Zhi 
Published: February 2021

SummaryA complete characterization of genetic variation is a fundamental goal of human genome research. Long-read sequencing (LRS) improves the sensitivity for structural variant (SV) discovery and facilitates a better understanding of the SV spectrum in human genomes. Here, we conduct the first LRS-based SV analysis in Chinese population. We perform whole-genome LRS for 405 unrelated Chinese, with 68 phenotypic and clinical measurements. We discover a complex landscape of 132,312 non-redundant SVs, of which 53.3% are novel. The identified SVs are of high-quality validated by the PacBio high-fidelity sequencing and PCR experiments. The total length of SVs represents approximately 13.2% of the human reference genome. We annotate 1,929 loss-of-function SVs affecting the coding sequences of 1,681 genes. We discover new associations of SVs with phenotypes and diseases, such as rare deletions inHBA1/HBA2/HBBassociated with anemia and common deletions inGHRassociated with body height. Furthermore, we identify SV candidates related to human immunity that differentiate sub-populations of Chinese. Our study reveals the complex landscape of human SVs in unprecedented detail and provides new insights into their roles contributing to phenotypes, diseases and evolution. The genotypic and phenotypic resource is freely available to the scientific community.
T cell derived HB-EGF prevents Th17 cell differentiation in an autocrine way
Authors: Macdonald Felicity , van Loosdregt Jorg , Zaiss Dietmar M W 
Published: February 2021

ABSTRACTCD4 T cells critically contribute to host immunity against infections, but can also contribute to the development of autoimmune diseases. The underlying mechanisms that govern differentiation of naïve CD4 T cells into different effector populations remain poorly understood. Here, we show that the expression of the Epidermal Growth Factor (EGF)-like growth factor HB-EGF by CD4 T cells sustained their expression of Interleukin (IL)-2 and reduced their capacity to differentiate into T Helper 17 (Th17) cells. Concordantly, mice with a T cell specific deficiency of HB-EGF showed an enhanced differentiation of naïve CD4 T cells into Th17 cells and a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Furthermore, transfer of naïve HB-EGF-deficient CD4 T cells intoRag1-/-mice led to the rapid induction of multi-organ inflammation in recipient mice. Together, our data reveal a novel mechanism by which an HB-EGF-mediated constrain on Th17 differentiation prevents the development of autoimmune diseases.SUMMARYCD4 T cell activation induces the expression of the EGFR and its high-affinity ligand HB-EGF. HB-EGF sustains IL-2 expression in an autocrine manner, preventing the differentiation of Th17 cells and the subsequent induction of Th17 cell-mediated autoimmune diseases.