bluuebunny/crossref_metadata_2025_split huggingface dataset:
European Working Group on Sarcopenia in Older People 2010 (EWGSOP1) and 2019 (EWGSOP2) criteria or slowness: which is the best predictor of mortality risk in older adults?
Authors: Spexoto Maria Claudia Bernardes , Ramírez Paula Camila , de Oliveira Máximo Roberta , Steptoe Andrew , de Oliveira Cesar , Alexandre Tiago da Silva 
Published: July 2022

Abstract

Objectives
to analyse the accuracy of grip strength and gait speed in identifying mortality; to compare the association between mortality and sarcopenia defined by the EWGSOP1 and EWGSOP2 using the best cut-off found in the present study and those recommended in the literature and to test whether slowness is better than these two definitions to identify the risk of death in older adults.

Methods
a longitudinal study was conducted involving 6,182 individuals aged 60 or older who participated in the English Longitudinal Study of Ageing. Sarcopenia was defined based on the EWGSOP1 and EWGSOP2 using different cut-off for low muscle strength (LMS). Mortality was analysed in a 14-year follow-up.

Results
compared with the LMS definitions in the literature (&lt;32, &lt;30, &lt;27 and &lt; 26 kg for men; &lt;21, &lt;20 and &lt; 16 kg for women), the cut-off of &lt;36 kg for men (sensitivity = 58.59%, specificity = 72.96%, area under the curve [AUC] = 0.66) and &lt; 23 kg for women (sensitivity = 68.90%, specificity = 59.03%, AUC = 0.64) as well as a low gait speed (LGS) ≤0.8 m/s (sensitivity = 53.72%, specificity = 74.02%, AUC = 0.64) demonstrated the best accuracy for mortality. Using the cut-off found in the present study, probable sarcopenia [HR = 1.30 (95%CI: 1.16–1.46)], sarcopenia [HR = 1.48 (95%CI: 1.24–1.78)] and severe sarcopenia [HR = 1.78 (95%CI: 1.49–2.12)] according to EWGSOP2 were better predictors of mortality risk than EWGSOP1. LGS ≤0.8 m/s was a better mortality risk predictor only when LMS was defined by low cut-off.

Conclusions
using LMS &lt;36 kg for men and &lt; 23 kg for women and LGS ≤ 0.8 m/s, EWGSOP2 was the best predictor for mortality risk in older adults.
Antimicrobial Prescribing in the Telehealth Setting: Framework for Stewardship During a Period of Rapid Acceleration Within Primary Care
Authors: Sine Kathryn , Appaneal Haley , Dosa David , LaPlante Kerry L 
Published: July 2022

Abstract
Antibiotic resistance is a global public health threat. The use of telehealth in primary care presents unique barriers to antimicrobial stewardship, including limited physical examination and changes to the patient-provider relationship. Since the coronavirus disease 2019 (COVID-19) pandemic, there is a need to identify novel antimicrobial stewardship strategies with an explosion in the use of telehealth within primary care. Our review proposes a tailored, sustainable approach to antimicrobial prescribing in the telehealth setting based on the Centers for Disease Control and Prevention’s Core Elements of Outpatient Antibiotic Stewardship: commitment, action for policy and practice; tracking and reporting; and education and expertise. The rapid growth of telehealth for all types of primary care visits (not just antibiotic use) is outpacing knowledge associated with strategies for antimicrobial stewardship. Improving antibiotic use within primary care settings is critical as telehealth will remain a priority whether the COVID-19 pandemic recedes, particularly within patient populations with limited access to healthcare.
Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer
Authors: Maertens Johan , Lodewyck Tom , Donnelly J Peter , Chantepie Sylvain , Robin Christine , Blijlevens Nicole , Turlure Pascal , Selleslag Dominik , Baron Frédéric , Aoun Mickael , Heinz Werner J , Bertz Hartmut , Ráčil Zdeněk , Vandercam Bernard , Drgona Lubos , Coiteux Valerie , Llorente Cristina Castilla , Schaefer-Prokop Cornelia , Paesmans Marianne , Ameye Lieveke , Meert Liv , Cheung Kin Jip , Hepler Deborah A , Loeffler Jürgen , Barnes Rosemary , Marchetti Oscar , Verweij Paul , Lamoth Frederic , Bochud Pierre-Yves , Schwarzinger Michael , Cordonnier Catherine ,   for the Infectious Diseases Group and the Acute Leukemia Group of the European Organization for Research and Treatment of Cancer
Published: July 2022

AbstractBackgroundEmpiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown.MethodsPatients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization.ResultsOf 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%–98.3%) when compared with arm A (93.1%; 95% CI, 89.3%–95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%–10.8%) in arm B vs 6.6% (95% CI, 3.6%–9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P &lt; .001).ConclusionsThe preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.
Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial
Authors: Montejano Rocío , de la Calle-Prieto Fernando , Velasco María , Guijarro Carlos , Queiruga-Parada Javier , Jiménez-González María , González-Ruano Patricia , Martínez Patricia , Goikoetxea Ane Josune , Ibarrola Marta , Ciudad Marianela , Gutiérrez Ángela , Torralba Miguel , Díaz-Brasero Ana , Ryan Pablo , Marcelo Cristina , Díez Cristina , Ibarra Sofía , Merino Esperanza , Estrada Vicente , Marcos Javier , Novella María , Rivera María A , Ruiz-Muñoz Manuel , de Miguel Marta , Soler Llanos , del Álamo Mikel , Moreno Santiago , Carcas Antonio J , Borobia Alberto M , Arribas José R ,   for the PANCOVID Study Group
Published: July 2022

Abstract

Background
This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation.

Methods
PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation &lt;95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected.

Results
Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52–5.91; P = .379); it was 0.42 (95% CI, .11–1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66–1.40; P = .774); it was 0.90 (95% CI, .61–1.33; P = .687) for those treated with baricitinib.

Conclusions
Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.

Clinical Trials Registration
EudraCT: 2020-001156-18.
Furloughing and COVID-19: assessing regulatory reform of the state
Authors: Spencer David A , Stuart Mark , Forde Chris , McLachlan Christopher J 
Published: July 2022

AbstractThis article assesses regulatory reform of the state in the context of the move to furloughing in the UK. It establishes that furloughing was a successful response to the COVID-19 crisis, partly because it challenged the traditional UK crisis response of non-state intervention in the labour market. Furloughing prevented higher unemployment and enabled a swifter recovery. The article also identifies the limits of furloughing (not least its temporary nature) but argues that key lessons from furloughing (including the direct support for job retention) should be used to devise new state policies aimed at promoting a more sustainable and equal economy.
Infectious consequences of the AKI-to-CKD transition
Authors: Sánchez Horrillo Ana , Salanova Villanueva Laura , Cabrera Cárdenas Alicia , Muñoz Ramos Patricia , Ortiz Alberto , Quiroga Borja 
Published: July 2022

ABSTRACT

Background
Acute kidney injury (AKI) is associated with short- and long-term complications but the consequences of the AKI-to-CKD transition are still poorly understood. We aimed to evaluate the association between the AKI-to-CKD transition and the long-term risk of infection.

Methods
This retrospective study included patients admitted in a tertiary hospital with community-acquired AKI in 2013 and 2014 who had their estimated glomerular filtration rate (eGFR) assessed at 3 months (±2 weeks) after serum creatinine peaked in the AKI episode. Key exclusion criteria were baseline CKD or confounding factors (active neoplasia, primary immunodeficiency, human immunodeficiency virus, immunosuppressive drugs). The association between the AKI-to-CKD transition (defined as an eGFR &lt;60 ml/min/1.73 m2 at 3 months) and long-term infections (defined using clinical features, blood/urine analysis, cultures and imaging) was assessed during a follow-up of 9 months (range 2–56).

Results
Among the 1731 patients admitted with AKI, 367 (21%) were included in the present analysis (64% male, 71 ± 15 years). Three months after AKI, 159 (43%) developed AKI-to-CKD transition. Baseline and post-AKI eGFR were independent predictors of AKI-to-CKD transition [hazard ratio (HR) 0.97, P = .044 and HR 0.96, P &lt; .001, respectively].
During follow-up, 153 (42%) patients developed an infection. Factors associated with infection were older age, cognitive impairment, lower post-AKI eGFR, eGFR loss from baseline to 3 months and AKI-to-CKD transition. Adjusted Cox regression showed that baseline eGFR, 3-month eGFR, eGFR loss and AKI-to-CKD transition were independent predictors of the long-term risk of infection.

Conclusions
The AKI-to-CKD transition independently predicts the long-term risk of infection following an episode of AKI.
Chromosomal Numerical Aberrations and Rare Copy Number Variation in Patients with Inflammatory Bowel Disease
Authors: Dirvanskyte Paulina , Gurram Bhaskar , Bolton Chrissy , Warner Neil , Jones Kelsey D J , Griffin Helen R ,   Genomics England Research Consortium, Park Jason Y , Keller Klaus-Michael , Gilmour Kimberly C , Hambleton Sophie , Muise Aleixo M , Wysocki Christian , Uhlig Holm H 
Published: July 2022

AbstractBackground and AimsInflammatory bowel diseases [IBD] have a complex polygenic aetiology. Rare genetic variants can cause monogenic intestinal inflammation. The impact of chromosomal aberrations and large structural abnormalities on IBD susceptibility is not clear. We aimed to comprehensively characterise the phenotype and prevalence of patients with IBD who possess rare numerical and structural chromosomal abnormalities.MethodsWe performed a systematic literature search of databases PubMed and Embase; and analysed gnomAD, Clinvar, the 100 000 Genomes Project, and DECIPHER databases. Further, we analysed international paediatric IBD cohorts to investigate the role of IL2RA duplications in IBD susceptibility.ResultsA meta-analysis suggests that monosomy X [Turner syndrome] is associated with increased expressivity of IBD that exceeds the population baseline (1.86%, 95% confidence interval [CI] 1.48 to 2.34%) and causes a younger age of IBD onset. There is little evidence that Klinefelter syndrome, Trisomy 21, Trisomy 18, mosaic Trisomy 9 and 16, or partial trisomies contribute to IBD susceptibility. Copy number analysis studies suggest inconsistent results. Monoallelic loss of X-linked or haploinsufficient genes is associated with IBD by hemizygous or heterozygous deletions, respectively. However, haploinsufficient gene deletions are detected in healthy reference populations, suggesting that the expressivity of IBD might be overestimated. One duplication that has previously been identified as potentially contributing to IBD risk involves the IL2RA/IL15R loci. Here we provide additional evidence that a microduplication of this locus may predispose to very-early-onset IBD by identifying a second case in a distinct kindred. However, the penetrance of intestinal inflammation in this genetic aberration is low [&lt;2.6%].ConclusionsTurner syndrome is associated with increased susceptibility to intestinal inflammation. Duplication of the IL2RA/IL15R loci may contribute to disease risk.
Bacterial battle against acidity
Authors: Schwarz Julia , Schumacher Kilian , Brameyer Sophie , Jung Kirsten 
Published: July 2022

AbstractThe Earth is home to environments characterized by low pH, including the gastrointestinal tract of vertebrates and large areas of acidic soil. Most bacteria are neutralophiles, but can survive fluctuations in pH. Herein, we review how Escherichia, Salmonella, Helicobacter, Brucella, and other acid-resistant Gram-negative bacteria adapt to acidic environments. We discuss the constitutive and inducible defense mechanisms that promote survival, including proton-consuming or ammonia-producing processes, cellular remodeling affecting membranes and chaperones, and chemotaxis. We provide insights into how Gram-negative bacteria sense environmental acidity using membrane-integrated and cytosolic pH sensors. Finally, we address in more detail the powerful proton-consuming decarboxylase systems by examining the phylogeny of their regulatory components and their collective functionality in a population.
Effects of fruit bagging on the physiochemical changes of grapefruit (Citrus paradisi)
Authors: Jiang Anze , Zheng Lizhen , Wang Dengliang , Kang Chen , Wu Jue , Fang Peilin , Cao Jinping , Sun Chongde 
Published: July 2022

Abstract
Fruit bagging is a commonly used cultivation measure to protect citrus fruit from insects and adverse environments. The present study aimed to comprehensively investigate the effects of bagging on the physiochemical characteristics of grapefruit. The grapefruit were bagged at approximately 110–120 d after anthesis with a one-layer kraft paper bag with black coating inside (SL), a double-layer kraft paper bag with one black paper as the inner layer (DL), and a three-layer kraft paper bag with two black papers as inner layers (TL), respectively. Ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) technique was used to identify a total of 19 flavonoids, 2 phenylpropanoids, 9 coumarins, and 5 limonoids. By using UPLC, 50 carotenoids were identified. Gas chromatography–mass spectrometry was used to identify 3 soluble sugars, 3 organic acids, and 11 amino acids. In the quantitated components in the peel (albedo and flavedo), the chlorophylls and the carotenoids components (such as luteoxanthin, violaxanthin, 9-cis-violaxanthin, xanthophyll, zeaxanthin and β-carotene) were significantly downregulated by bagging, causing the surface color of bagged fruit to turn yellow earlier but paler than that of the unbagged control, particularly in the three-layer kraft bag treatment. Unlike the peel, the color and the carotenoid content of the juice sacs were less affected. The physiochemical compounds other than pigments, including soluble sugars, organic acids, amino acids, flavonoids, coumarins and limonoids, were minimally affected by bagging treatments. Our results indicated that bagging at approximately 110–120 d after anthesis exerted influence mainly on peel color, but less on sugars, acids, amino acids, flavonoids, limonoids and coumarins of grapefruit.
The impact of embryo vitrification on placental histopathology features and perinatal outcome in singleton live births
Authors: Volodarsky-Perel A , Ton Nu T N , Orvieto R , Mashiach R , Machado-Gedeon A , Cui Y , Shaul J , Dahan M H 
Published: July 2022

AbstractSTUDY QUESTIONDoes embryo vitrification affect placental histopathology pattern and perinatal outcome in singleton live births?SUMMARY ANSWEREmbryo vitrification has a significant effect on the placental histopathology pattern and is associated with a higher prevalence of dysfunctional labor.WHAT IS KNOWN ALREADYObstetrical and perinatal outcomes differ between live births resulting from fresh and frozen embryo transfers. The effect of embryo vitrification on the placental histopathology features associated with the development of perinatal complications remains unclear.STUDY DESIGN, SIZE, DURATIONRetrospective cohort study evaluating data of all live births from one academic tertiary hospital resulting from IVF treatment with autologous oocytes during the period from 2009 to 2017.PARTICIPANTS/MATERIALS, SETTING, METHODSAll patients had placentas sent for pathological evaluation irrelevant of maternal or fetal complications status. Placental, obstetric and perinatal outcomes of pregnancies resulting from hormone replacement vitrified embryo transfers were compared with those after fresh embryo transfers. A multivariate analysis was conducted to adjust the results for determinants potentially associated with the development of placental histopathology abnormalities.MAIN RESULTS AND THE ROLE OF CHANCEA total of 1014 singleton live births were included in the final analysis and were allocated to the group of pregnancies resulting from fresh (n = 660) and hormone replacement frozen (n = 354) embryo transfers. After the adjustment for confounding factors the frozen embryo transfers were found to be significantly associated with chorioamnionitis with maternal (odds ratio (OR) 2.0; 95% CI 1.2–3.3) and fetal response (OR 2.6; 95% CI 1.2–5.7), fetal vascular malperfusion (OR 3.9; 95% CI 1.4–9.2), furcate cord insertion (OR 2.3 95% CI 1.2–5.3), villitis of unknown etiology (OR 2.1; 95% CI 1.1–4.2), intervillous thrombi (OR 2.1; 95% CI 1.3–3.7), subchorionic thrombi (OR 3.4; 95% CI 1.6–7.0), as well as with failure of labor progress (OR 2.5; 95% CI 1.5–4.2).LIMITATIONS, REASONS FOR CAUTIONSince the live births resulted from frozen-thawed embryos included treatment cycles with previously failed embryo transfers, the factors over embryo vitrification may affect implantation and placental histopathology.WIDER IMPLICATIONS OF THE FINDINGSThe study results contribute to the understanding of the perinatal future of fresh and vitrified embryos. Our findings may have an implication for the clinical decision to perform fresh or frozen-thawed embryo transfer.STUDY FUNDING/COMPETING INTEREST(s)Authors have not received any funding to support this study. There are no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.
The Mechanosensitive Ion Channel PIEZO1 in Intestinal Epithelial Cells Mediates Inflammation through the NOD-Like Receptor 3 Pathway in Crohn’s Disease
Authors: Liu Qiuyuan , Wang Didi , Yang Xiaodong , Ma Fang , Han Wei , Hu Jing , Mei Qiao 
Published: July 2022

Abstract

Background
Crohn’s disease (CD) is an incurable chronic intestinal inflammatory disease with no recognized cause. It has been reported that the mechanosensitive ion channel PIEZO1 initiates proinflammatory responses. However, little is known about the role of PIEZO1 in CD.

Methods
Ileum biopsies were obtained from 30 patients with CD and 15 healthy volunteers. Clinical data were collected to determine the relationship between CD and PIEZO1. First, HT29 cells were incubated with Yoda1 and GsMTx4 (Grammostola spatulata mechanotoxin 4) to activate and inhibit PIEZO1, respectively. Second, PIEZO1 knockdown was performed using small interfering RNA. Third, calcium imaging, flow cytometry, and immunofluorescence were used to detect intracellular calcium and mitochondrial function. Last, real-time quantitative polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to quantify PIEZO1, proinflammatory cytokines, and NLRP3 (NOD-like receptor 3)–related compounds.

Results
PIEZO1 was highly expressed in the ileum of patients with CD and correlated positively with the Crohn’s Disease Activity Index, platelet count, and hematocrit and fecal calprotectin levels. In HT29 cells, Yoda1 triggered calcium influx, which was inhibited by GsMTx4 treatment and small interfering RNA–mediated PIEZO1 knockdown. Increased calcium concentrations resulted in increased reactive oxygen species accumulation and decreased mitochondrial membrane potential, whereas decreased calcium concentrations caused by GsMTx4 and PIEZO1 knockdown had the opposite effect. Mechanistically, molecules in the NLRP3 pathway were activated in patients with CD and HT29 cells were stimulated by lipopolysaccharide; these effects were reversed by the knockdown of PIEZO1. Finally, PIEZO1 and NLRP3 knockdown decreased proinflammatory cytokine levels in HT29 cells.

Conclusions
PIEZO1 in intestinal epithelial cells caused calcium influx, which resulted in mitochondrial dysfunction and activated the NLRP3 inflammasome, mediating intestinal inflammation.