bluuebunny/crossref_metadata_2025 huggingface dataset:
Surveillance for substandard and falsified medicines by local faith-based organizations in 13 low- and middle-income countries using the GPHF Minilab
Authors: Gnegel Gesa , Häfele-Abah Christine , Neci Richard ,   Difäm-EPN Minilab Network, Alladjaba Markous , Lächele Micha , Grace Neenodji , Djekadoum Ndilta , Gounouman Julien Basile , Mpawenimana Servilien , Muziganyi Egide , Mukamanzi Anastasie , Zawadi Jean Claude , Cletus Tambo Ajong , Ngah Ndze Edward , Chakraborty Bishnu , Mutombo Georges Munguakonkwa , Chioke Sr Jane Frances , Okpan Esther , Ngene Juliet , Higenyi Emmanuel , Agiro Priscilla , Uggi Titus , Anderson Tumaini Petro , Ndakengurutse Pamella , Ndayikeza Emmanuel , Kigera Stephen , Wanyama Mildred , Sowah Frederick , Kachiponde Fredrick , Malanda Folita , Julienne Dina Pecke , Nyaah Fidelis , Dohnji Manyi Pattinora , Neci Richard , Gnegel Gesa , Häfele-Abah Christine , Heide Lutz
Published: July 2022

This study evaluates the use of the Global Pharma Health Fund (GPHF) Minilab for medicine quality screening by 16 faith-based drug supply organizations located in 13 low- and middle-income countries. The study period included the year before the COVID-19 pandemic (2019) and the first year of the pandemic (2020). In total 1,919 medicine samples were screened using the GPHF Minilab, and samples showing serious quality deficiencies were subjected to compendial analysis in fully equipped laboratories. Thirty-four (1.8%) of the samples were found not to contain the declared active pharmaceutical ingredient (API), or less than 50% of the declared API, or undeclared APIs, and probably represented falsified products. Fifty-four (2.8%) of the samples were reported as substandard, although the true number of substandard medicines may have been higher due to the limited sensitivity of the GPHF Minilab. The number of probably falsified products increased during the COVID-19 pandemic, especially due to falsified preparations of chloroquine; chloroquine had been incorrectly advocated as treatment for COVID-19. The reports from this project resulted in four international WHO Medical Product Alerts and several national alerts. Within this project, the costs for GPHF Minilab analysis resulted as 25.85 € per sample. Medicine quality screening with the GPHF Minilab is a cost-effective way to contribute to the global surveillance for substandard and falsified medical products.
Spatial distribution differences of 25-hydroxyvitamin D in healthy elderly people under the influence of geographical environmental factors
Authors: Yang Wenjie , Ge Miao , Wang Yabo , Pang Xinrui , Wang Congxia
Published: July 2022

The main targets of this were to screen the factors that may influence the distribution of 25-hydroxyvitamin D[25(OH)D] reference value in healthy elderly people in China, and further explored the geographical distribution differences of 25(OH)D reference value in China. In this study, we collected the 25(OH)D of 25,470 healthy elderly from 58 cities in China to analyze the correlation between 25(OH)D and 22 geography secondary indexes through spearman regression analysis. Six indexes with significant correlation were extracted, and a ridge regression model was built, and the country’s urban healthy elderly’25(OH)D reference value was predicted. By using the disjunctive Kriging method, we obtained the geographical distribution of 25(OH)D reference values for healthy elderly people in China. The reference value of 25(OH)D for healthy elderly in China was significantly correlated with the 6 secondary indexes, namely, latitude (°), annual temperature range (°C), annual sunshine hours (h), annual mean temperature (°C), annual mean relative humidity (%), and annual precipitation (mm). The geographical distribution of 25(OH)D values of healthy elderly in China showed a trend of being higher in South China and lower in North China, and higher in coastal areas and lower in inland areas. This study lays a foundation for further research on the mechanism of different influencing factors on the reference value of 25(OH)D index. A ridge regression model composed of significant influencing factors has been established to provide the basis for formulating reference criteria for the treatment factors of the vitamin D deficiency and prognostic factors of the COVID-19 using 25(OH)D reference value in different regions.
Modelling monthly pan evaporation utilising Random Forest and deep learning algorithms
Authors: Abed Mustafa , Imteaz Monzur Alam , Ahmed Ali Najah , Huang Yuk Feng
Published: July 2022

Evaporation is the primary aspect causing water loss in the hydrological cycle; therefore, water loss must be precisely measured. Evaporation is an intricate nonlinear process occurring as a result of several climatic aspects. The purpose of this research is to assess the feasibility of using Random Forest (RF) and two deep learning techniques, namely convolutional neural network (CNN), and deep neural network (DNN) to accurately estimate monthly pan evaporation rates. Month-based weather data gathered from four Malaysian weather stations during the 2000–2019 timeframe was used to train and evaluate the models. Several input attributes (predictor variables) were investigated to select the most suitable variables for machine learning models. Every approach was tested with several models, each with a different set of model aspects and input parameter combinations. The formulated ML approaches were benchmarked against two commonly used empirical methods: Stephens & Stewart and Thornthwaite. Model outcomes were assessed using standard statistical measures to determine their effectiveness in predicting evaporation. The results indicated that the three ML models developed in the study performed better than empirical models and could significantly improve the precision of monthly Ep estimates even with the identical input sets. The performance assessment metrics also show that the formulated CNN approach was acceptable for modelling monthly water loss due to evaporation with a higher degree of accuracy than other ML frameworks explored in this study. In addition, the CNN framework outperformed other AI techniques evaluated for the same areas using identical data inputs. The investigation’s findings in relation to the various performance criteria show that the proposed CNN model is capable of capturing the highly non-linearity of evaporation and could be regarded as an effective tool to predict evaporation.
Human umbilical cord mesenchymal stem cells derived extracellular vesicles regulate acquired immune response of lupus mouse in vitro
Authors: Xie Min , Li Cuifang , She Zhou , Wu Feifeng , Mao Jueyi , Hun Marady , Luo Senlin , Wan Wuqing , Tian Jidong , Wen Chuan
Published: July 2022

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 × 105hUCMSCs, 25 µg/ml hUCMSC-EVs, 50 µg/ml hUCMSC-EVs were co-cultured with 2 × 106activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4+T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4+T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-β1) (P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 (P > 0.05); only hUCMSCs inhibited CD19+B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.
DltC acts as an interaction hub for AcpS, DltA and DltB in the teichoic acid d-alanylation pathway of Lactiplantibacillus plantarum
Authors: Nikolopoulos Nikos , Matos Renata C. , Courtin Pascal , Ayala Isabel , Akherraz Houssam , Simorre Jean-Pierre , Chapot-Chartier Marie-Pierre , Leulier François , Ravaud Stéphanie , Grangeasse Christophe
Published: July 2022

Teichoic acids (TA) are crucial for the homeostasis of the bacterial cell wall as well as their developmental behavior and interplay with the environment. TA can be decorated by different modifications, modulating thus their biochemical properties. One major modification consists in the esterification of TA by d-alanine, a process known as d-alanylation. TA d-alanylation is performed by the Dlt pathway, which starts in the cytoplasm and continues extracellularly after d-Ala transportation through the membrane. In this study, we combined structural biology and in vivo approaches to dissect the cytoplasmic steps of this pathway in Lactiplantibacillus plantarum, a bacterial species conferring health benefits to its animal host. After establishing that AcpS, DltB, DltC1 and DltA are required for the promotion of Drosophila juvenile growth under chronic undernutrition, we solved their crystal structure and/or used NMR and molecular modeling to study their interactions. Our work demonstrates that the suite of interactions between these proteins is ordered with a conserved surface of DltC1 docking sequentially AcpS, DltA and eventually DltB. Altogether, we conclude that DltC1 acts as an interaction hub for all the successive cytoplasmic steps of the TA d-alanylation pathway.
A systematic review of skin ageing genes: gene pleiotropy and genes on the chromosomal band 16q24.3 may drive skin ageing
Authors: Ng Jun Yan , Chew Fook Tim
Published: July 2022

Skin ageing is the result of intrinsic genetic and extrinsic lifestyle factors. However, there is no consensus on skin ageing phenotypes and ways to quantify them. In this systematic review, we first carefully identified 56 skin ageing phenotypes from multiple literature sources and sought the best photo-numeric grading scales to evaluate them. Next, we conducted a systematic review on all 44 Genome-wide Association Studies (GWAS) on skin ageing published to date and identified genetic risk factors (2349 SNPs and 366 genes) associated with skin ageing. We identified 19 promising SNPs found to be significantly (p-Value < 1E−05) associated with skin ageing phenotypes in two or more independent studies. Here we show, using enrichment analyses strategies and gene expression data, that (1) pleiotropy is a recurring theme among skin ageing genes, (2) SNPs associated with skin ageing phenotypes are mostly located in a small handful of 44 pleiotropic and hub genes (mostly on the chromosome band 16q24.3) and 32 skin colour genes. Since numerous genes on the chromosome band 16q24.3 and skin colour genes show pleiotropy, we propose that (1) genes traditionally identified to contribute to skin colour have more than just skin pigmentation roles, and (2) further progress towards understand the development of skin pigmentation requires understanding the contributions of genes on the chromosomal band 16q24.3. We anticipate our systematic review to serve as a hub to locate primary literature sources pertaining to the genetics of skin ageing and to be a starting point for more sophisticated work examining pleiotropic genes, hub genes, and skin ageing phenotypes.
A maternal high-fat diet induces fetal origins of NASH-HCC in mice
Authors: Takiyama Takao , Sera Toshihiro , Nakamura Masanori , Hoshino Masato , Uesugi Kentaro , Horike Shin-ichi , Meguro-Horike Makiko , Bessho Ryoichi , Takiyama Yuri , Kitsunai Hiroya , Takeda Yasutaka , Sawamoto Kazuki , Yagi Naoto , Nishikawa Yuji , Takiyama Yumi
Published: July 2022

Maternal overnutrition affects offspring susceptibility to nonalcoholic steatohepatitis (NASH). Male offspring from high-fat diet (HFD)-fed dams developed a severe form of NASH, leading to highly vascular tumor formation. The cancer/testis antigen HORMA domain containing protein 1 (HORMAD1), one of 146 upregulated differentially expressed genes in fetal livers from HFD-fed dams, was overexpressed with hypoxia-inducible factor 1 alpha (HIF-1alpha) in hepatoblasts and in NASH-based hepatocellular carcinoma (HCC) in offspring from HFD-fed dams at 15 weeks old. Hypoxia substantially increased Hormad1 expression in primary mouse hepatocytes. Despite the presence of three putative hypoxia response elements within the mouse Hormad1 gene, the Hif-1alpha siRNA only slightly decreased hypoxia-induced Hormad1 mRNA expression. In contrast, N-acetylcysteine, but not rotenone, inhibited hypoxia-induced Hormad1 expression, indicating its dependency on nonmitochondrial reactive oxygen species production. Synchrotron-based phase-contrast micro-CT of the fetuses from HFD-fed dams showed significant enlargement of the liver accompanied by a consistent size of the umbilical vein, which may cause hypoxia in the fetal liver. Based on these findings, a maternal HFD induces fetal origins of NASH/HCC via hypoxia, and HORMAD1 is a potential therapeutic target for NASH/HCC.
Examining sex disparity in the association of waist circumference, waist-hip ratio and BMI with hypertension among older adults in India
Authors: Muhammad T. , Paul Ronak , Rashmi Rashmi , Srivastava Shobhit
Published: July 2022

Hypertension is a public health issue touted as a “silent killer” worldwide. The present study aimed to explore the sex differential in the association of anthropometric measures including body mass index, waist circumference, and waist-hip ratio with hypertension among older adults in India. The study used data from the Longitudinal Aging Study in India (LASI) conducted during 2017–18. The sample contains 15,098 males and 16,366 females aged 60 years and above. Descriptive statistics (percentages) along with bivariate analysis were presented. Multivariable binary logistic regression analyses were used to examine the associations between the outcome variable (hypertension) and putative risk or protective factors. About 33.9% of males and 38.2% of females aged 60 years and above suffered from hypertension. After adjusting for the socioeconomic, demographic and health-behavioral factors, the odds of hypertension were 1.37 times (CI: 1.27–1.47), significantly higher among older adults who were obese or overweight than those with no overweight/obese condition. Older adults with high-risk waist circumference and waist-hip ratio had 1.16 times (CI: 1.08–1.25) and 1.42 times (CI: 1.32–1.51) higher odds of suffering from hypertension, respectively compared to their counterparts with no high-risk waist circumference or waist-hip ratio. The interaction effects showed that older females with overweight/obesity [OR: 0.84; CI: 0.61–0.74], high-risk waist circumference [OR: 0.89; CI: 0.78–0.99], and high-risk waist-hip ratio [OR: 0.90; CI: 0.83–0.97] had a lower chance of suffering from hypertension than their male counterparts with the similar anthropometric status. The findings suggested a larger magnitude of the association between obesity, high-risk waist circumference, high-risk waist-hip ratio and prevalent hypertension among older males than females. The study also highlights the importance of measuring obesity and central adiposity in older individuals and using such measures as screening tools for timely identification of hypertension.
Mycobacterium tuberculosis/Mycobacterium bovis triggered different variations in lipid composition of Bovine Alveolar Macrophages
Authors: Chen Yuqi , Ma Huiya , Duan Yangbo , Ma Xueyan , Tan Lihui , Dong Jianjian , Jin Chenkai , Wei Rong
Published: July 2022

The lipid composition performs important functions in interaction between macropha-ge and Mycobacterium tuberculosis (MTB)/Mycobacterium bovis (MB). Current understanding regarding the lipid responses of bovine alveolar macrophage (BAM) to MTB/MB is quite limited. The present study conducted lipidomics and transcriptome to assess alterations in BAM lipid compositions upon MB and MTB infection. We found that both MTB and MB induced glycerophospholipids accumulation in BAM, and MTB induced more alterations in lipid composition. MTB could affect the contents of various lipids, especially ceramide phosphocholines, polystyrene (PS) (17:0/0:0), testolic acid and testosterone acetate. Meanwhile, MB particularly induced accumulation of 1-alkyl,2-acylglycerophosphoinositols. Both MB and MTB suppressed the contents of palmitoleamide, N-ethyl arachidonoyl amine, N-(1,1-dimethyl-2-hydroxy-ethyl) arachidonoyll amine, eicosanoyl-EA, and PS (O-18:0/17:0) in BAM. Additionally, transcriptome analysis revealed that only MTB triggered genes involved in immune signaling and lipid related pathways in BAM. And MTB mainly activated genes CXCL2 and CXCL3 relevant to NOD-like receptor, IL-17 and TNF to further induce lipid accumulation in BAM, which in turn promoted the formation of foam cells. Meanwhile, time course RT-qPCR results showed that MTB was recognized by BAM to triggered dramatic immune responses, whereas MB could effectively escape the recognition system of BAM, leading rearrangement of lipid metabolisms in BAM at early infection stage. Altogether, the results of the present study provided evidence for changes in lipid metabolism of MTB/MB attacked BAM and contributed to the detection and treatment of zoonotic tuberculosis.
See-N-Seq: RNA sequencing of target single cells identified by microscopy via micropatterning of hydrogel porosity
Authors: Lee Jeong Hyun , Park Emily S. , Choi Jane Ru , Matthews Kerryn , Lam Alice V. , Deng Xiaoyan , Duffy Simon P. , Ma Hongshen
Published: July 2022

Single cell RNA sequencing has the potential to elucidate transcriptional programs underlying key cellular phenotypes and behaviors. However, many cell phenotypes are incompatible with indiscriminate single cell sequencing because they are rare, transient, or can only be identified by imaging. Existing methods for isolating cells based on imaging for single cell sequencing are technically challenging, time-consuming, and prone to loss because of the need to physically transport single cells. Here, we developed See-N-Seq, a method to rapidly screen cells in microwell plates in order to isolate RNA from specific single cells without needing to physically extract each cell. Our approach involves encapsulating the cell sample in a micropatterned hydrogel with spatially varying porosity to selectively expose specific cells for targeted RNA extraction. Extracted RNA can then be captured, barcoded, reverse transcribed, amplified, and sequenced at high-depth. We used See-N-Seq to isolate and sequence RNA from cell-cell conjugates forming an immunological synapse between T-cells and antigen presenting cells. In the hours after synapsing, we found time-dependent bifurcation of single cell transcriptomic profiles towards Type 1 and Type 2 helper T-cells lineages. Our results demonstrate how See-N-Seq can be used to associate transcriptomic data with specific functions and behaviors in single cells.
Chiral trabeated metabeam for low-frequency multimode wave mitigation via dual-bandgap mechanism
Authors: Park Jeonghoon , Lee Dongwoo , Jang Yeongtae , Lee Anna , Rho Junsuk
Published: July 2022

An elastic wave in a physical beam naturally possesses many wave modes, such as flexural, longitudinal, and torsional. Therefore, suppression of all possible vibration modes has been rarely achieved in beam-shaped periodic systems, especially at low frequencies. Here we present a low-frequency complete bandgap mechanism by overlapping the flexural bandgap with the longitudinal-torsional bandgap. To strengthen the general framework, we enforce an extra degree of freedom (rotational and torsional-spring) on the spring-mass system for the flexural and coupled (longitudinal-torsional) modes. The low rotational stiffness provides a low flexural bandgap, whereas the torsional stiffness yields a coupled-mode bandgap. To meet these prerequisites in physical modeling, a chiral trabeated metabeam is conceived, which allows all wave modes to be suppressed by a complete bandgap. Apart from single-mode mitigation, our work provides a route to implementing a low-frequency complete bandgap in a periodic fashion, potentially enabling the use of chirality in elastic structures.
Geometric origin of intrinsic spin hall effect in an inhomogeneous electric field
Authors: Zhang Anwei , Rhim Jun-Won
Published: July 2022

In recent years, the spin Hall effect has received great attention because of its potential application in spintronics and quantum information processing and storage. However, this effect is usually studied under the external homogeneous electric field. Understanding how the inhomogeneous electric field affects the spin Hall effect is still lacking. Here, we investigate a two-dimensional two-band time-reversal symmetric system and give an expression for the intrinsic spin Hall conductivity in the presence of the inhomogeneous electric field, which is shown to be expressed through the geometric quantities: quantum metric and interband Berry connection. We show that for Rashba and Dresselhaus systems, the inhomogeneous intrinsic spin Hall conductivity can be tuned with the Fermi energy. On the other hand, when people get physical intuition on transport phenomena from the wave packet, one issue appears. It is shown that the conductivity obtained from the conventional wave packet approach cannot be fully consistent with the one predicted by the Kubo-Greenwood formula. Here, we attempt to solve this problem.
The structure and electronic properties of the MoSe2/PtS2 van der Waals heterostructure
Authors: Zhang Hui , Pei Meng , Liu Boyang , Wang Zongli , Zhao Xu
Published: July 2022

The tunable band alignment of the MoSe2/PtS2 heterostructure from the type-I band alignment to the type-II one can be realized.
Breaking the sodium solubility limit for extraordinary thermoelectric performance in p-type PbTe
Authors: Zhu Yingcai , Hu Lei , Zhan Shaoping , Ina Toshiaki , Gao Xiang , Hong Tao , Zhao Li-Dong
Published: July 2022

Sodium solubility is largely enhanced with the introduction of AgInSe2 in Pb1−yNayTe matrixes, which facilitates band convergence, leading to an exceptional figure-of-merit ZT of ∼2.5 at 773 K in p-type PbTe.
Real-time personalized health status prediction of lithium-ion batteries using deep transfer learning
Authors: Ma Guijun , Xu Songpei , Jiang Benben , Cheng Cheng , Yang Xin , Shen Yue , Yang Tao , Huang Yunhui , Ding Han , Yuan Ye
Published: July 2022

We have developed a high-performance deep transfer learning framework to predict the health status of lithium-ion batteries for each end-user at any charge–discharge cycle.
Reactive halogen radicals in saline water promote photochemically-assisted formation of manganese oxide nanosheets
Authors: Gao Zhenwei , Skurie Charlie , Jun Young-Shin
Published: July 2022

Fast photochemically-assisted abiotic oxidation of Mn2+(aq) by reactive halogen radicals was observed to form δ-MnO2 nanosheets.
AqSO biorefinery: a green and parameter-controlled process for the production of lignin–carbohydrate hybrid materials
Authors: Tarasov Dmitry , Schlee Philipp , Pranovich Andrey , Moreno Adrian , Wang Luyao , Rigo Davide , Sipponen Mika H. , Xu Chunlin , Balakshin Mikhail
Published: July 2022

The current biorefineries are focused on the comprehensive fractionation of biomass components into separate lignin and carbohydrate fractions for the production of materials, platform chemicals and biofuel.
Fabricated fractals as unique fingerprints for data and image encryption
Authors: Shivadas Damini , Kamathe Vishal , Nagar Rupali
Published: July 2022

With advancements in telecommunication technology, data or information transfer has become the backbone of daily transactions.
A sensitive fluorescent sensor based on terpyridine@Zn2+-modified mesoporous silica for the detection of sulfonamide antibiotics
Authors: Zhao Qian , Wang Jing
Published: July 2022

A terpyridine@Zn2+-modified mesoporous silica, denoted ATpy@Zn-SBA-15, was developed and applied as a highly sensitive and quickly responsive fluorescent sensor for the detection of sulfonamide antibiotics in tap water and milk.
Templated synthesis of 2D TiO2 nanoflakes for durable lithium ion batteries
Authors: He Yaxuan , Li Haibo
Published: July 2022

A facile method has been proposed to prepare 2D TiO2 nanoflakes with high cycling performance and stability.
Preventing soft skill decay among early-career women in STEM during COVID-19: Evidence from a longitudinal intervention
Authors: Melin Julia L. , Correll Shelley J.
Published: August 2022

As the workforce shifts to being predominantly hybrid and remote, how can companies help employees—particularly early-career women in science, technology, engineering, and mathematics (STEM) fields—develop greater confidence in their soft skills, shown to improve organizational retention? We evaluate the effects of an online longitudinal intervention to develop soft skills among early-career women employees at a North American biotechnology company during the height of the COVID-19 pandemic. Controlling for baseline levels collected immediately prior to nationwide lockdowns, we find that a 6-month online intervention increased early-career women’s assessments of their soft skills at work by an average of 9% (P< 0.001), compared with a decrease of about 3.5% for a matched control group (P< 0.05), resulting in an average treatment effect of nearly 13% on the treated group. Furthermore, we find evidence that the intervention led to an increase in manager-assessed performance for early-career women relative to employees not in the intervention, and that overall, increased self-assessments of soft skill competencies were associated with greater odds of retention. Results show how employee soft skill development was affected by the pandemic and provide insights for a feasible and cost-effective method to train and engage a hybrid or fully remote workforce.
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

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 (<32, <30, <27 and < 26 kg for men; <21, <20 and < 16 kg for women), the cut-off of <36 kg for men (sensitivity = 58.59%, specificity = 72.96%, area under the curve [AUC] = 0.66) and < 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 <36 kg for men and < 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

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

Background

Empiric 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.

Methods

Patients 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.

Results

Of 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 < .001).

Conclusions

The 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

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 <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

This 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

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 <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 < .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

Background and Aims

Inflammatory 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.

Methods

We 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.

Results

A 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 [<2.6%].

Conclusions

Turner 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

The 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

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

STUDY QUESTION

Does embryo vitrification affect placental histopathology pattern and perinatal outcome in singleton live births?

SUMMARY ANSWER

Embryo vitrification has a significant effect on the placental histopathology pattern and is associated with a higher prevalence of dysfunctional labor.

WHAT IS KNOWN ALREADY

Obstetrical 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, DURATION

Retrospective 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, METHODS

All 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 CHANCE

A 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 CAUTION

Since 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 FINDINGS

The 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 NUMBER

N/A.