bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propensity scores as a novel method to guide sample allocation and minimize batch effects during the design of high throughput experiments
Authors: Carry Patrick M. , Vigers Tim , Vanderlinden Lauren A. , Keeter Carson , Dong Fran , Buckner Teresa , Litkowski Elizabeth , Yang Ivana , Norris Jill M. , Kechris Katerina 
Published: March 2023

AbstractBackgroundWe developed a novel approach to minimize batch effects when assigning samples to batches. Our algorithm selects a batch allocation, among all possible ways of assigning samples to batches, that minimizes differences in average propensity score between batches. This strategy was compared to randomization and stratified randomization in a case–control study (30 per group) with a covariate (case vs control, represented as β1, set to be null) and two biologically relevant confounding variables (age, represented as β2, and hemoglobin A1c (HbA1c), represented as β3). Gene expression values were obtained from a publicly available dataset of expression data obtained from pancreas islet cells. Batch effects were simulated as twice the median biological variation across the gene expression dataset and were added to the publicly available dataset to simulate a batch effect condition. Bias was calculated as the absolute difference between observed betas under the batch allocation strategies and the true beta (no batch effects). Bias was also evaluated after adjustment for batch effects using ComBat as well as a linear regression model. In order to understand performance of our optimal allocation strategy under the alternative hypothesis, we also evaluated bias at a single gene associated with both age and HbA1c levels in the ‘true’ dataset (CAPN13 gene).ResultsPre-batch correction, under the null hypothesis (β1), maximum absolute bias and root mean square (RMS) of maximum absolute bias, were minimized using the optimal allocation strategy. Under the alternative hypothesis (β2 and β3 for the CAPN13 gene), maximum absolute bias and RMS of maximum absolute bias were also consistently lower using the optimal allocation strategy. ComBat and the regression batch adjustment methods performed well as the bias estimates moved towards the true values in all conditions under both the null and alternative hypotheses. Although the differences between methods were less pronounced following batch correction, estimates of bias (average and RMS) were consistently lower using the optimal allocation strategy under both the null and alternative hypotheses.ConclusionsOur algorithm provides an extremely flexible and effective method for assigning samples to batches by exploiting knowledge of covariates prior to sample allocation.
Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells
Authors: Dan Qi-Qin , Chen Li , shi Lan-Lan , Zhou Xiu , Wang Ting-Hua , Liu Hua 
Published: March 2023

Abstract
Objectives
This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms.

Methods
Primary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by β-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs).

Results
The number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function.

Conclusions
Collectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.
Factors affecting the microbiological quality and contamination of farm bulk milk by Staphylococcus aureus in dairy farms in Asella, Ethiopia
Authors: Deddefo Abiot , Mamo Gezahegne , Asfaw Minda , Amenu Kebede 
Published: March 2023

AbstractBackgroundThe determination of the microbiological quality and safety of raw milk and the associated influencing factors at the farm level is very critical given that the quality or safety of subsequent products that are further produced depends on this. Therefore, this study aimed to determine the microbiological quality and safety of bulk milk and identify associated risk factors, and assess the presence/absence ofS. aureusin bulk milk with potential contaminating sources in dairy farms in Asella, Ethiopia.ResultsThe geometric means of bacterial counts in farm bulk milk were 5.25 log cfu/ml, 3.1 log cfu/ml and 2.97 log cfu/ml for total bacterial count (TBC), coliform count (CC) and coagulase-positive staphylococci count (CPS), respectively. Of the 50 dairy farms, 66, 88, and 32% had TBC, CC and CPS counts, respectively, that exceeded the standard international limits for raw cow’s milk intended for direct human consumption. TBC tended to increase as CC increased in bulk milk (r = 0.5). In the final regression model, increased TBC, CC and the contamination of farm bulk milk byS. aureuswere significantly associated with dirty barns, dirty cows and soiled udder and teats. TBC was higher during the rainy season than during the dry season. The reported practice of washing teats with warm water significantly decreased CC and CPS. The occurrence ofS. aureuswas significantly (p < 0.05) higher in bulk farm milk (42%) than in pooled udder milk (37.3%), teat swabs (22.5%), milkers’ hand swabs (18%), bulking bucket swabs (16.7%), milking container swabs (14%), and water for cleaning of udder and milkers’ hands (10%). The questionnaire survey result showed widespred raw milk consumption habits, low level of training and poor hygienic milking practices.ConclusionsThis study revealed low-quality bulk farm milk with high bacterial counts and a high occurrence ofS. aureus. This indicates the potential food safety risks due to consumption of raw milk or its products. This study suggests awareness creation to dairy farmers and the public on hygienic milk production and heat treatment of milk before consumption.
Controlling taxa abundance improves metatranscriptomics differential analysis
Authors: Ji Zhicheng , Ma Li 
Published: March 2023

AbstractBackgroundA common task in analyzing metatranscriptomics data is to identify microbial metabolic pathways with differential RNA abundances across multiple sample groups. With information from paired metagenomics data, some differential methods control for either DNA or taxa abundances to address their strong correlation with RNA abundance. However, it remains unknown if both factors need to be controlled for simultaneously.ResultsWe discovered that when either DNA or taxa abundance is controlled for, RNA abundance still has a strong partial correlation with the other factor. In both simulation studies and a real data analysis, we demonstrated that controlling for both DNA and taxa abundances leads to superior performance compared to only controlling for one factor.ConclusionsTo fully address the confounding effects in analyzing metatranscriptomics data, both DNA and taxa abundances need to be controlled for in the differential analysis.
Clonal transmission of polymyxin B-resistant hypervirulent Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaKPC-2 in a tertiary hospital in China
Authors: Tang Mengli , Li Jun , Liu Zhaojun , Xia Fengjun , Min Changhang , Hu Yongmei , Wang Haichen , Zou Mingxiang 
Published: March 2023

Abstract
Background
The prevalence of multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKP) has gradually increased. It poses a severe threat to human health. However, polymyxin-resistant hvKP is rare. Here, we collected eight polymyxin B-resistant K. pneumoniae isolates from a Chinese teaching hospital as a suspected outbreak.

Results
The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. HvKP was identified by detecting virulence-related genes and using a Galleria mellonella infection model. Their resistance to serum, growth, biofilm formation, and plasmid conjugation were analyzed in this study. Molecular characteristics were analyzed using whole-genome sequencing (WGS) and mutations of chromosome-mediated two-component systems pmrAB and phoPQ, and the negative phoPQ regulator mgrB to cause polymyxin B (PB) resistance were screened. All isolates were resistant to polymyxin B and sensitive to tigecycline; four were resistant to ceftazidime/avibactam. Except for KP16 (a newly discovered ST5254), all were of the K64 capsular serotype and belonged to ST11. Four strains co-harbored blaKPC-2, blaNDM-1, and the virulence-related genes prmpA, prmpA2, iucA, and peg344, and were confirmed to be hypervirulent by the G. mellonella infection model. According to WGS analysis, three hvKP strains showed evidence of clonal transmission (8–20 single nucleotide polymorphisms) and had a highly transferable pKOX_NDM1-like plasmid. KP25 had multiple plasmids carrying blaKPC-2, blaNDM-1, blaSHV-12, blaLAP-2, tet(A), fosA5, and a pLVPK-like virulence plasmid. Tn1722 and multiple additional insert sequence-mediated transpositions were observed. Mutations in chromosomal genes phoQ and pmrB, and insertion mutations in mgrB were major causes of PB resistance.

Conclusions
Polymyxin-resistant hvKP has become an essential new superbug prevalent in China, posing a serious challenge to public health. Its epidemic transmission characteristics and mechanisms of resistance and virulence deserve attention.
Tree peony transcription factor PrWRI1 enhances seed oil accumulation
Authors: Xie Lihang , Hu Jiayuan , Yan Zhenguo , Li Xinyao , Wei Sailong , Xu Ruilin , Yang Weizong , Gu Huihui , Zhang Qingyu 
Published: March 2023

Abstract
Background
WRINKLED1 (WRI1) encodes a transcription factor, belonging to the APETALA2 (AP2) family, and plays a key role in regulating plant oil biosynthesis. As a newly woody oil crop, tree peony (Paeonia rockii) was notable for the abundant unsaturated fatty acids in its seed oil. However, the role of WRI1 during the accumulation of P. rockii seeds oil remains largely unknown.

Results
In this study, a new member of the WRI1 family was isolated from P. rockii and was named PrWRI1. The ORF of PrWRI1 consisted of 1269 nucleotides, encoding a putative protein of 422 amino acids, and was highly expressed in immature seeds. Subcellular localization analysis in onion inner epidermal cells showed that PrWRI1 was located at the nucleolus. Ectopic overexpression of PrWRI1 could significantly increase the total fatty acid content in Nicotiana benthamiana leaf tissue and even PUFAs in transgenic Arabidopsis thaliana seeds. Furthermore, the transcript levels of most genes related to fatty acids (FA) synthesis and triacylglycerol (TAG) assembly were also up-regulated in transgenic Arabidopsis seeds.

Conclusions
Together, PrWRI1 could push carbon flow to FA biosynthesis and further enhance the TAG amount in seeds with a high proportion of PUFAs.
Comprehensive analysis of the laccase gene family in tea plant highlights its roles in development and stress responses
Authors: Zhu Jiaxin , Zhang Hongxiu , Huang Kelin , Guo Rui , Zhao Jingjuan , Xie Hui , Zhu Junyan , Gu Honglian , Chen Hongrong , Li Guoqiang , Wei Chaoling , Liu Shengrui 
Published: March 2023

Abstract
Background
Laccase (LAC) is the pivotal enzyme responsible for the polymerization of monolignols and stress responses in plants. However, the roles of LAC genes in plant development and tolerance to diverse stresses are still largely unknown, especially in tea plant (Camellia sinensis), one of the most economically important crops worldwide.

Results
In total, 51 CsLAC genes were identified, they were unevenly distributed on different chromosomes and classified into six groups based on phylogenetic analysis. The CsLAC gene family had diverse intron–exon patterns and a highly conserved motif distribution. Cis-acting elements in the promoter demonstrated that promoter regions of CsLACs encode various elements associated with light, phytohormones, development and stresses. Collinearity analysis identified some orthologous gene pairs in C. sinensis and many paralogous gene pairs among C. sinensis, Arabidopsis and Populus. Tissue-specific expression profiles revealed that the majority of CsLACs had high expression in roots and stems and some members had specific expression patterns in other tissues, and the expression patterns of six genes by qRT‒PCR were highly consistent with the transcriptome data. Most CsLACs showed significant variation in their expression level under abiotic (cold and drought) and biotic (insect and fungus) stresses via transcriptome data. Among them, CsLAC3 was localized in the plasma membrane and its expression level increased significantly at 13 d under gray blight treatment. We found that 12 CsLACs were predicted to be targets of cs-miR397a, and most CsLACs showed opposite expression patterns compared to cs-miR397a under gray blight infection. Additionally, 18 highly polymorphic SSR markers were developed, these markers can be widely used for diverse genetic studies of tea plants.

Conclusions
This study provides a comprehensive understanding of the classification, evolution, structure, tissue-specific profiles, and (a)biotic stress responses of CsLAC genes. It also provides valuable genetic resources for functional characterization towards enhancing tea plant tolerance to multiple (a)biotic stresses.
Effect of isotemporal substitution of sedentary behavior with different intensities of physical activity on the muscle function of older adults in the context of a medical center
Authors: Lai Ting-Fu , Liao Yung , Hsueh Ming-Chun , Lin Kun-Pei , Chan Ding-Cheng , Chen Yung-Ming , Wen Chiung-Jung 
Published: March 2023

Abstract
Background
Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on the muscle function of older adults at a medical center in Taiwan.

Methods
We recruited 141 older adults (51.1% men; 81.1 ± 6.9 years old) and asked them to wear a triaxial accelerometer on the waist to measure their sedentary behavior and physical activity. Functional performance was assessed based on handgrip strength, Timed Up and Go (TUG) test, gait speed, and five-times-sit-to-stand test (5XSST). Isotemporal substitution analysis was performed to examine the effect of substituting 60 min of sedentary time with 60 min of LPA, MVPA, and combined LPA and MVPA in different proportions.

Results
Reallocating 60 min of sedentary behavior per day to LPA was associated with better handgrip strength (Beta [B] = 1.587, 95% confidence interval [CI] = 0.706, 2.468), TUG test findings (B = -1.415, 95% CI = -2.186, -0.643), and gait speed (B = 0.042, 95% CI = 0.007, 0.078). Reallocating 60 min of sedentary behavior per day to MVPA was associated with better gait speed (B = 0.105, 95% CI = 0.018, 0.193) and 5XSST findings (B = -0.060, 95% CI = -0.117, -0.003). In addition, each 5-min increment in MVPA in the total physical activity replacing 60 min of sedentary behavior per day resulted in greater gait speed. Replacing 60 min of sedentary behavior with 30-min of LPA and 30-min of MVPA per day significantly decreased the 5XSST test time.

Conclusion
Our study indicates that introducing LPA and a combination of LPA and MVPA to specifically replace sedentary behavior may help maintain muscle function in older adults.
Re-examination of successful agers with lower biological than chronological age still after a 20-year follow-up period
Authors: Viljanen Anna , Salminen Marika , Irjala Kerttu , Korhonen Päivi , Vahlberg Tero , Viitanen Matti , Löppönen Minna , Viikari Laura 
Published: March 2023

Abstract
Background
Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing.

Methods
Successful ageing was defined as the ability to live at home without daily care. Data on the participants’ functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted.

Results
The participants’ mean age was 87.6 years (Standard deviation 2.5, range 84–96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years.

Discussion
Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers.

Conclusions
Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality.
Implementation of an antimicrobial stewardship program in the Vascular Surgery ward of a university tertiary care hospital in Pavia, Northern Italy
Authors: Vecchia Marco , Colaneri Marta , Sacchi Paolo , Marvulli Lea Nadia , Salvaderi Andrea , Lanza Jessica , Boschini Stefano , Ragni Franco , Marone Piero , Cutti Sara , Muzzi Alba , Marena Carlo , Calvi Monica , Scudeller Luigia , Marone Enrico Maria , Bruno Raffaele 
Published: March 2023

Abstract
Purpose
The commitment of multidisciplinary teams in antimicrobial stewardship programs (ASPs) is often inadequately considered, especially in surgical wards. We wanted to evaluate clinical, microbiological, and pharmacological outcomes before and after the implementation of an ASP in the Vascular Surgery ward of Fondazione IRCCS Policlinico San Matteo, a tertiary care hospital in Pavia, Italy.

Methods
This was a quasi-experimental quality-improvement study. The antimicrobial stewardship activity was conducted twice a week for 12 months and consisted of both prospective audit and feedback of all the ongoing antimicrobial prescriptions by the infectious diseases’ consultants and educational meetings for the healthcare workers of the Vascular Surgery ward. For comparison between the study periods, Student t test (Mann–Whitney test for skewed distributions) was used for quantitative variables (ANOVA or Kruskall-Wallis for > 2 groups respectively), and Pearson’s chi-squared test (Fisher exact test where appropriate) for categorical variables. 2-tailed tests were used. P-value significance cut-off was 0.05.

Results
During the 12-month intervention period, among a total number of 698 patients, 186 prescriptions were revised, mostly leading to de-escalating an ongoing antimicrobial therapy (39, 20.97%). A statistically significant reduction in isolates of carbapenem-resistant Pseudomonas aeruginosa (p-value 0.003) and the absence of Clostridioides difficile infections were reported. No statistically significant changes were observed in terms of length of stay and all-cause in-hospital mortality. A significant decrease in the administration of carbapenems (p-value 0.01), daptomycin (p-value < 0.01) and linezolid (p-value 0.43) was registered. A significant reduction in antimicrobial costs was also observed.

Conclusions
The implementation of a 12-month ASP brought significant clinical and economic results, highlighting the benefits of a multidisciplinary teamwork.
Ocular Mycobacterium haemophilum infection originating in the cornea: a case report
Authors: Zhang Yu-Qiang , Xu Ting-Ting , Wang Fu-Yan , Wang Shuang , Cheng Jun 
Published: March 2023

Abstract
Background
Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature.

Case presentation
A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured.

Conclusion
M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.