bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies
Authors: Chung Chen-Fang , Papillon Joan , Navarro-Betancourt José R. , Guillemette Julie , Bhope Ameya , Emad Amin , Cybulsky Andrey V. 
Published: March 2023

BackgroundHuman glomerulonephritis (GN)—membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), as well as diabetic nephropathy (DN) are leading causes of chronic kidney disease. In these glomerulopathies, distinct stimuli disrupt metabolic pathways in glomerular cells. Other pathways, including the endoplasmic reticulum (ER) unfolded protein response (UPR) and autophagy, are activated in parallel to attenuate cell injury or promote repair.MethodsWe used publicly available datasets to examine gene transcriptional pathways in glomeruli of human GN and DN and to identify drugs.ResultsWe demonstrate that there are many common genes upregulated in MN, FSGS, IgAN, and DN. Furthermore, these glomerulopathies were associated with increased expression of ER/UPR and autophagy genes, a significant number of which were shared. Several candidate drugs for treatment of glomerulopathies were identified by relating gene expression signatures of distinct drugs in cell culture with the ER/UPR and autophagy genes upregulated in the glomerulopathies (“connectivity mapping”). Using a glomerular cell culture assay that correlates with glomerular damage in vivo, we showed that one candidate drug – neratinib (an epidermal growth factor receptor inhibitor) is cytoprotective.ConclusionThe UPR and autophagy are activated in multiple types of glomerular injury. Connectivity mapping identified candidate drugs that shared common signatures with ER/UPR and autophagy genes upregulated in glomerulopathies, and one of these drugs attenuated injury of glomerular cells. The present study opens the possibility for modulating the UPR or autophagy pharmacologically as therapy for GN.
Environmental factors and host genotype control foliar epiphytic microbial community of wild soybeans across China
Authors: Zhou Rui , Duan Gui-Lan , García-Palacios Pablo , Yang Guang , Cui Hui-Ling , Yan Ming , Yin Yue , Yi Xing-Yun , Li Lv , Delgado-Baquerizo Manuel , Zhu Yong-Guan 
Published: March 2023

IntroductionThe microbiome inhabiting plant leaves is critical for plant health and productivity. Wild soybean (Glycine soja), which originated in China, is the progenitor of cultivated soybean (Glycine max). So far, the community structure and assembly mechanism of phyllosphere microbial community on G. soja were poorly understood.MethodsHere, we combined a national-scale survey with high-throughput sequencing and microsatellite data to evaluate the contribution of host genotype vs. climate in explaining the foliar microbiome of G. soja, and the core foliar microbiota of G. soja were identified.ResultsOur findings revealed that both the host genotype and environmental factors (i.e., geographic location and climatic conditions) were important factors regulating foliar community assembly of G. soja. Host genotypes explained 0.4% and 3.6% variations of the foliar bacterial and fungal community composition, respectively, while environmental factors explained 25.8% and 19.9% variations, respectively. We further identified a core microbiome thriving on the foliage of all G. soja populations, including bacterial (dominated by Methylobacterium-Methylorubrum, Pantoea, Quadrisphaera, Pseudomonas, and Sphingomonas) and fungal (dominated by Cladosporium, Alternaria, and Penicillium) taxa.ConclusionOur study revealed the significant role of host genetic distance as a driver of the foliar microbiome of the wild progenitor of soya, as well as the effects of climatic changes on foliar microbiomes. These findings would increase our knowledge of assembly mechanisms in the phyllosphere of wild soybeans and suggest the potential to manage the phyllosphere of soya plantations by plant breeding and selecting specific genotypes under climate change.
Design of a randomized cross-over study evaluating effects of carbohydrate intake on glycemic control in persons with type 1 diabetes
Authors: Sterner Isaksson Sofia , Ólafsdóttir Arndís F. , Lind Marcus 
Published: March 2023

IntroductionDiet is an important factor in managing glycemic control in type 1 diabetes (T1D). Reducing carbohydrate intake may be important for stabilizing blood glucose levels in certain groups of patients with T1D. There are few studies examining the effects of a low carbohydrate diet in patients with T1D. The aim of this study is to investigate the effects of carbohydrate intake on glucose control in adults with T1D.Materials and methodsAdults with T1D (N = 54) and inadequate glycemic control (HbA1c ≥ 7.5%; 58 mmol/mol) were randomized in a cross-over design to a moderate carbohydrate diet (30 percent of total energy from carbohydrates) versus a traditional diabetes diet (50 percent of total energy from carbohydrates) for 4 weeks with a between wash-out period of 4 weeks. Masked continuous glucose monitoring was used throughout the study to evaluate effects on mean blood glucose levels, time-in-range, hypoglycemia, hyperglycemia, and glycemic variability. Diabetes treatment satisfaction, hypoglycemic confidence, and physical activity were measured using questionnaires during different phases of the trial. HbA1c, blood lipids, blood pressure, and ketone levels were also measured. The primary endpoint is the difference in mean blood glucose level between the diet periods. Study completion is anticipated during winter 2022.DiscussionThe study seeks to increase knowledge about the effects of dietary carbohydrate intake on glycemic control and other health parameters in patients with T1D. If beneficial effects on mean blood glucose level without elevated risk of hypoglycemia or ketoacidosis are shown, a moderate carbohydrate diet may be a treatment option for people with T1D that have unsatisfactory blood glucose levels.Clinical Trials Registration:www.clinicaltrials.gov, ID: NCT03400618.
Indo-cyanine green administration to identify loss of lymph after axillary lymph node dissection
Authors: Roman Mirela Mariana , Delrue Pauline , Karler Clarence , Del Marmol Véronique , Bourgeois Pierre 
Published: March 2023

BackgroundNear infrared fluorescence imaging with Indocyanine Green (ICG) is now used for the imaging of lymph nodes and lymphatic vessels. In this work, we investigated the impact of its pre-operative and peri-operative administration on our ability to detect axillary lymphatic loss after breast cancer surgery.MethodsOne subcutaneous injection of ICG was administered in the ipsilateral hand of 109 women who were scheduled to have either a mastectomy with total axillary lymph node dissection (CALND) or a lumpectomy with selective lymphadenectomy (SLN) the day before (n = 53) or the same day of surgery (n = 56). The lymph leakages were assessed by means of the application of a compress in the operated armpit and by the presence or absence of fluorescence on it, as well as in the post-operative axillary drains.ResultsThe compress was fluorescent in 28% of SLN patients and 71% of CALND patients. The liquids in the axillary drains were also fluorescent in 71% of patients with CALND. No statistical significance was observed between the ICG injection groups. The association between compressive fluorescent and the presence of fluorescence in the axillary drains is significant in the pre-operative subgroup and in the whole group.ConclusionOur research demonstrates that lymphatic leaks aid in the development of seromas and calls into question the effectiveness of the ligatures and/or cauterizations used during surgery. A prospective, multicentric, randomized trial should be conducted to verify the efficacy of this approach.
Adjuvant EGFR-TKI therapy in resected EGFR-mutation positive non-small cell lung cancer: A real-world study
Authors: Liu Jun-Feng , Sun Xu-Sheng , Yin Jin-Huan , Xu Xi-E 
Published: March 2023

BackgroundAlthough several clinical studies have laid the foundation for the adjuvant application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), some questions remain unresolved. This real-world study aimed to address questions such as the effect of adjuvant chemotherapy prior to adjuvant EGFR-TKI therapy on survival outcomes, and the duration of adjuvant EGFR-TKI therapy, etc.MethodsBetween October 2005 and October 2020, 227 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete pulmonary resections were included in this retrospective study. Patients received postoperative adjuvant chemotherapy followed by EGFR-TKI or adjuvant EGFR-TKI monotherapy. The disease-free survival (DFS) and overall survival (OS) were evaluated.ResultsOf the total 227 patients, 55 (24.2%) patients underwent 3-4 cycles of chemotherapy prior to receiving adjuvant EGFR-TKI therapy. The 5-year DFS rate was 67.8%, while the 5-year OS rate was 76.4%. The stages were significantly associated with both DFS (P&lt;0.001) and OS (P&lt;0.001), while no significant differences were observed in the DFS (P=0.093) and OS (P=0.399) between the adjuvant chemotherapy followed by EGFR-TKI and adjuvant EGFR-TKI monotherapy groups. A longer duration of EGFR-TKI therapy was associated with better DFS (P&lt;0.001) and OS (P&lt;0.001) benefit. Additionally, pTNM stage and duration of EGFR-TKI therapy were considered independent prognostic factors for long-term survival (All P&lt;0.05).ConclusionsThis study supports the use of EGFR-TKI as a postoperative adjuvant treatment for patients with stage II-IIIA EGFR-mutation positive NSCLC. Additionally, patients with stage I who had pathological risk factors were also suitable for receiving adjuvant EGFR-TKI therapy. Postoperative EGFR-TKI based, chemotherapy-free adjuvant regimen may be a potential therapeutic option for patients with EGFR-mutation positive NSCLC.
Quantifying changes in respiratory syncytial virus—associated hospitalizations among children in Texas during COVID-19 pandemic using records from 2006 to 2021
Authors: Uwak Inyang , Johnson Natalie , Mustapha Toriq , Rahman Mariya , Tonpay Tanaya , Regan Annette K. , Mendoza-Sanchez Itza 
Published: March 2023

AimTo quantify changes on RSV- associated hospitalizations during COVID-19 pandemic, among children four years of age or younger at the state and county levels of Texas using routinely acquired hospital admission records.MethodsWe used the Texas Public Use Data Files (PUDF) of the Department of State Human Services (DSHS) to obtain hospital admissions and healthcare outcomes from 2006 to 2021. We used the 2006–2019 period to estimate a long-term temporal trend and predict expected values for 2020–2021. Actual and predicted values were used to quantify changes in seasonal trends of the number of hospital admissions and mean length of hospital stay. Additionally, we calculated hospitalization rates and assessed their similarity to rates reported in the RSV Hospitalization Surveillance Network (RSV-NET).ResultsAn unusually low number of hospitalizations in 2020 was followed by an unusual peak in the third quarter of 2021. Hospital admissions in 2021 were approximately twice those in a typical year. The mean length of hospital stay typically followed a seasonal trend before COVID-19, but increased by a factor of ∼6.5 during the pandemic. Spatial distribution of hospitalization rates revealed localized healthcare infrastructure overburdens during COVID-19. RSV associated hospitalization rates were, on average, two times higher than those of RSV-NET.ConclusionHospital admission data can be used to estimate long-term temporal and spatial trends and quantify changes during events that exacerbate healthcare systems, such as pandemics. Using the mean difference between hospital rates calculated with hospital admissions and hospital rates obtained from RSV-NET, we speculate that state-level hospitalization rates for 2022 could be at least twice those observed in the two previous years, and the highest in the last 17 years.
Population pharmacokinetics of tigecycline in critically ill patients
Authors: Luo Xiangru , Wang Shiyi , Li Dong , Wen Jun , Sun Na , Fan Guangjun 
Published: March 2023

Objective: In critically ill patients, the change of pathophysiological status may affect the pharmacokinetic (PK) process of drugs. The purpose of this study was to develop a PK model for tigecycline in critically ill patients, identify the factors influencing the PK and optimiz dosing regimens.Method: The concentration of tigecycline was measured LC-MS/MS. We established population PK model with the non-linear mixed effect model and optimized the dosing regimens by Monte Carlo simulation.Result: A total of 143 blood samples from 54 patients were adequately described by a one-compartment linear model with first-order elimination. In the covariate screening analysis, the APACHEII score and age as significant covariates. The population-typical values of CL and Vd in the final model were 11.30 ± 3.54 L/h and 105.00 ± 4.47 L, respectively. The PTA value of the standard dose regimen (100 mg loading dose followed by a 50 mg maintenance dose at q12 h) was 40.96% with an MIC of 2 mg/L in patients with HAP, the ideal effect can be achieved by increasing the dosage. No dose adjustment was needed for Klebsiella pneumoniae for AUC0–24/MIC targets of 4.5 and 6.96, and the three dose regimens almost all reached 90%. A target AUC0–24/MIC of ≥17.9 reached 100% in patients with cSSSI in the three tigecycline dose regimens, considering MIC ≤ 0.25 mg/L.Conclusion: The final model indicated that APACHEII score and age could affect the Cl and Vd of tigecycline, respectively. The standard dose regimen of tigecycline was often not able to obtain satisfactory therapeutic effects for critically ill patients. For patients with HAP and cIAI caused by one of three pathogens, the efficacy rate can be improved by increasing the dose, but for cSSSI infections caused by Acinetobacter baumannii and K. pneumoniae, it is recommended to change the drug or use a combination of drugs.
Dose adjustment not required for contezolid in patients with moderate hepatic impairment based on pharmacokinetic/pharmacodynamic analysis
Authors: Wu Junzhen , Yang Xinyi , Wu Jufang , Wang Jingjing , Wu Hailan , Wang Yu , Yuan Hong , Yang Huahui , Wang Hailin , Zhang Jing 
Published: March 2023

Objective: Contezolid is an oxazolidinone antimicrobial agent newly approved for treatment of Gram-positive bacterial infections. It is primarily metabolized by the liver. This study aimed to assess whether it is required to adjust the dose of contezolid in patients with moderate hepatic impairment for clinicians to use the drug more rationally.Methods: A single-center, open-label, parallel-group study was conducted to compare the pharmacokinetic (PK) parameters of contezolid and its metabolite M2 between the patients with moderate hepatic impairment and healthy controls with normal liver function after oral administration of 800 mg contezolid tablets. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) of contezolid based on the PK and pharmacodynamic data.Results: Oral treatment with 800 mg contezolid tablets was safe and well tolerated in both the patients with moderate hepatic impairment and healthy controls. Moderate hepatic impairment did not result in substantial difference in the area under the concentration-time curve from 0 to 24 h (AUC0–24h, 106.79 vs. 97.07 h μg/mL) of contezolid even though lower maximum concentration (Cmax, 19.03 vs. 34.49 μg/mL) compared with healthy controls. The mean cumulative amount excreted in urine from 0 to 48 h (Ae0–48h) and renal clearance (CLR) of contezolid did not show significant difference between the two groups. Moderate hepatic impairment was associated with lower Cmax, slightly lower AUC and Ae0–48h of M2 compared to the healthy controls. fAUC/MIC was the best PK/PD index to predict the clinical efficacy of contezolid. Monte Carlo simulation results indicated that at the proposed fAUC/MIC target value of 2.3, the dosing regimen of oral contezolid 800 mg q12h could achieve satisfactory PTA and CFR (both &gt;90%) for the target pathogen (methicillin-resistant S. aureus, MIC ≤4 mg/L) in patients with moderate hepatic impairment.Conclusion: Our preliminary data suggest that dose adjustment is not required for contezolid in patients with moderate hepatic impairment.Clinical Trial Registration:https://chinadrugtrials.org.cn, identifier: CTR20171377.
Nitrogen fluorescence emission pumped by femtosecond optical vortex beams
Authors: Chen You , Man Xiaoman , Liu Binxian , Lin Zhiyang 
Published: March 2023

An experimental investigation on nitrogen fluorescence emissions pumped by a single 800 nm fs optical vortex (OV) beam with different topological charges (TC) is reported. The intensity of the two prototype emission lines from neutral nitrogen molecules (N2) and molecular nitrogen ions (N2+), i.e., 337 nm and 391 nm, respectively, shows different TC dependences: the former slightly decreases as the TC increases, while the latter sharply decreases as the TC changes from zero to a non-zero value. The dependences of the 337-nm and 391-nm emission intensity on pulse energy are also different: the former shows a linear variation for different TCs, while the latter has an abrupt change in the slope when changing the TC. Furthermore, the dependence of the 337-nm emission intensity on gas pressure exhibits a plateau which is universal for different TCs. In contrast, the dependence of the 391-nm emission intensity on gas pressure shows an apparent hump which is respective of the TC. These actual new results will facilitate further theoretical study on the formation dynamics of the nitrogen fluorescence emissions induced by the OV beam, and inspire that such beam can been taken as a unique pure optical tool to manipulate the transitions between different electronic-vibrational states.
A correlation between fractal growth, water contact angle, and SERS intensity of R6G on ion beam nanostructured ultra-thin gold (Au) films
Authors: Jasrotia Priya , Priya Bhanu , Kumar Raj , Bishnoi Priyanka , vij Ankush , Kumar Tanuj 
Published: March 2023

Introduction: This study focuses on the detection of rhodamine-6G using surface-enhanced Raman scattering (SERS) on gold nanostructures (AuNS) of different sizes. Ion beam irradiation has been carried out to tune the size of AuNS and investigate the underlying mechanisms of sputtering and diffusion that govern their growth. Additionally, the study established a correlation between fractal growth parameters, water contact angle, and SERS detection of R6G. The results of this study offer new insights into the mechanisms of SERS detection on roughened metallic surfaces.Methods: Thermal evaporation was used to deposit an Au thin film on a glass substrate. Subsequent 10 keV Ar+ irradiation was done on Au thin film for fluences ranging from 3×1014 to 3×1016 ions/cm2 to tune the size of AuNS. Rutherford backscattering spectroscopy (RBS) was used to confirm that the decrease in Au concentration under ion beam sputtering was responsible for the tuning in size and structure of AuNS. Fractal dimension (Df) and interface width (w) were used as statistical parameters to control the wettable characteristics of the AuNS surfaces.Results and discussion: The researchers found that the growth of AuNS was governed by ion beam induced sputtering and diffusion mechanisms. They established a correlation between fractal growth parameters, water contact angle, and SERS detection of R6G. They found that a higher surface coverage area of Au NPs with lower fractal dimensions and water contact angles favoured the SERS detection of R6G. This study provides new insights into the mechanisms of SERS detection on roughened metallic surfaces. It is found that the growth of AuNS was governed by ion beam-induced sputtering and diffusion mechanisms, and established a correlation between fractal growth parameters, water contact angle, and SERS detection of R6G. The findings of this study may have applications in the development of more sensitive and efficient SERS-based chemical sensors.
The effect of aquatic exercise on bone mineral density in older adults. A systematic review and meta-analysis
Authors: Schinzel Eileen , Kast Stephanie , Kohl Matthias , von Stengel Simon , Jakob Franz , Kerschan-Schindl Katharina , Kladny Bernd , Lange Uwe , Peters Stefan , Thomasius Friederike , Clausen Jürgen , Uder Michael , Kemmler Wolfgang 
Published: March 2023

Introduction: Aquatic or water-based exercise is a very popular type of exercise in particular for people with physical limitations, joint problems and fear of falling. The present systematic review and meta-analysis aimed to provide evidence for the effect of aquatic exercise on Bone Mineral Density (BMD) in adults.Methods: A systematic literature search of five electronic databases (PubMed/MEDLINE, Cochrane Library, Scopus, Web of Science and CINAHL) according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted until 2022/01/30, with an update to 2022/10/07. We included controlled trials with a duration of more than 6 months and at least two study groups, aquatic exercise (EG) versus non-training controls (CG) with no language restrictions. Outcome measures were standardized mean differences (SMD) with 95%-confidence intervals (95%-CI) for BMD changes at the lumbar spine (LS) and femoral neck (FN). We applied a random-effects meta-analysis and used the inverse heterogeneity (IVhet) model to analyze the data.Results: Excluding an outlier study with an exceptionally high effect size for LS-BMD, we observed a statistically significant (p = .002) effect (EG vs. CG) of aquatic exercise for the LS-BMD (n = 10; SMD: 0.30; 95%-CI: 0.11–0.49). In parallel, the effect of aquatic exercise on FN-BMD was statistically significant (p = .034) compared to the CG (n = 10; SMD: 0.76, 95%-CI: 0.06–1.46). Of importance, heterogeneity between the trial results was negligible for LS (I2: 7%) but substantial for FN-BMD (I2: 87%). Evidence for risks of small study/publication bias was low for LS-BMD and considerable for FN-BMD.Discussion: In summary, the present systematic review and meta-analysis provides further evidence for the favorable effect of exercise on bone health in adults. Due to its safety and attractiveness, we particularly recommend water-based exercise for people unable, afraid or unmotivated to conduct intense land-based exercise programs.
Did smartphones enhance or diminish well-being during the COVID-19 pandemic?
Authors: Heyman Jennifer L. , Kushlev Kostadin 
Published: March 2023

IntroductionAs smartphones have become increasingly integrated into people’s lives, researchers have attempted to answer whether they are beneficial or detrimental to well-being. Of particular interest to the current study is the role that smartphones played during the first year of the COVID-19 Pandemic.MethodsIn an intensive longitudinal study, we explore how varying uses of smartphones relate to well-being using the Displacement-Interference-Complementarity framework.ResultsConsistent with pre-pandemic research, we show that people felt better, calmer, and more energetic when they used their phones more for complementary purposes (i.e., to access information, entertainment, and connection not otherwise available). In contrast to most pre-pandemic research, however, we find no evidence that any type of phone use predicted lower well-being during the pandemic.DiscussionOverall, this study lends support to the idea that smartphones can be beneficial for individuals, particularly during times when face-to-face interaction is limited.