bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug repurposing of pyrazolotriazine derivatives as potential anti-SARS-CoV-2 agents: in vitro and in silico studies
Authors: Oudah Khulood H. , Najm Mazin A. A. , Barghash Reham F. , Kutkat Omnia , GabAllah Mohamed , Albohy Amgad , Abouzid Khaled A. M. 
Published: July 2024

AbstractThe search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.
Engineering cyanobacteria as a new platform for producing taxol precursors directly from carbon dioxide
Authors: Zhong Jialing , Wang Yushu , Chen Zhuoyang , Yalikun Yaliqin , He Lin , Liu Tiangang , Ma Gang 
Published: July 2024

AbstractTaxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as ﻿bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.
CREdb: A comprehensive database of Cis-Regulatory Elements and their activity in human cells and tissues
Authors: Hartl Chris , Zhuang Jiali , Tyler Aaron , Zhou Bing , Wong Emily , Merberg David , Farrell Brad , DeBoever Chris , Bryant Julie , Diogo Dorothée 
Published: July 2024

Abstract
Background
Cis-regulatory elements (CREs) play a pivotal role in gene expression regulation, allowing cells to serve diverse functions and respond to external stimuli. Understanding CREs is essential for personalized medicine and disease research, as an increasing number of genetic variants associated with phenotypes and diseases overlap with CREs. However, existing databases often focus on subsets of regulatory elements and present each identified instance of element individually, confounding the effort to obtain a comprehensive view. To address this gap, we have created CREdb, a comprehensive database with over 10 million human regulatory elements across 1,058 cell types and 315 tissues harmonized from different data sources. We curated and aligned the cell types and tissues to standard ontologies for efficient data query.

Results
Data from 11 sources were curated and mapped to standard ontological terms. 11,223,434 combined elements are present in the final database, and these were merged into 5,666,240 consensus elements representing the combined ranges of the individual elements informed by their overlap. Each consensus element contains curated metadata including the number of elements supporting it and a hash linking to the source databases. The inferred activity of each consensus element in various cell-type and tissue context is also provided. Examples presented here show the potential utility of CREdb in annotating non-coding genetic variants and informing chromatin accessibility profiling analysis.

Conclusions
We developed CREdb, a comprehensive database of CREs, to simplify the analysis of CREs by providing a unified framework for researchers. CREdb compiles consensus ranges for each element by integrating the information from all instances identified across various source databases. This unified database facilitates the functional annotation of non-coding genetic variants and complements chromatin accessibility profiling analysis. CREdb will serve as an important resource in expanding our knowledge of the epigenome and its role in human diseases.
Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis
Authors: Nikolaou Evdokia , Tziastoudi Maria , Gougoura Sofia G. , Filippidis Georgios , Dousdampanis Periklis , Bargiota Alexandra , Mertens Peter Rene , Eleftheriadis Theodoros , Hadjigeorgiou Georgios M. , Koukoulis Georgios N. , Stefanidis Ioannis 
Published: July 2024

Abstract
Background
In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.

Methods
In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.

Results
27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.

Conclusions
Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.
Assessment of biofilm-forming capacity and multidrug resistance in Staphylococcus aureus isolates from animal-source foods: implications for lactic acid bacteria intervention
Authors: Sharan Manjeet , Dhaka Pankaj , Bedi Jasbir Singh , Mehta Nitin , Singh Randhir 
Published: July 2024

Abstract
Background
Staphylococcus aureus, a Gram-positive bacterium, poses a significant threat to public health and food safety due to its virulence and its ability to develop antimicrobial resistance (AMR). Moreover, S. aureus can form biofilms in food environments, making it difficult to eradicate and pose a major challenge in foodborne illness prevention.

Methods
The study aimed to investigate the biofilm-forming capabilities and AMR profiles of 107 S. aureus isolates derived from milk, chicken meat, and chicken eggs. Further, the study compared the biofilm formation tendencies between multi-drug resistant (MDR) and non-MDR S. aureus isolates. Additionally, the research explored the antibacterial and anti-biofilm properties of Lactobacillus rhamnosus and Lactobacillus casei, focusing on their aggregation and co-aggregation effects with S. aureus.

Results
Around 70.10% of S. aureus isolates were found to be resistant to at least three antibiotic classes. The biofilm assay revealed that 16.82% isolates were strong biofilm formers. The MDR isolates displayed a strong biofilm-forming ability (i.e., 18.67%) and a higher prevalence of biofilm-associated genes [i.e., icaA (53.33%) and icaD (44.0%)] compared to non-MDR isolates. The LAB strain, L. rhamnosus exhibited a 29.06 mm mean antibacterial inhibition zone, an average reduction of 48.19% in biofilm growth, 55.46% auto-aggregation, and 40.61% co-aggregation with S. aureus. Similarly, L. casei demonstrated a 21.80 mm mean antibacterial inhibition zone, an average reduction of 31.56% in biofilm growth, 45.23% auto-aggregation, and 36.81% co-aggregation with S. aureus isolates.

Conclusion
This study provides valuable insights into the biofilm formation of MDR S. aureus and underscores the potential of L. rhamnosus and L. casei as bio-control agents. These findings highlight the necessity for additional research into the mechanisms through which LAB strains inhibit pathogenic biofilms and their potential applications in enhancing food safety.
Mate selection and current trends in the prevalence of autism
Authors: Forsen Elizabeth , Marrus Natasha , Joyce Jacqueline , Zhang Yi , Constantino John N. 
Published: July 2024

Abstract
Background
According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children.

Methods
Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2).

Results
We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30).

Limitations
The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report.

Conclusion
Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations.
Summer scour syndrome in weaned dairy calves: case series
Authors: Male Here Rischi Robinson , McAloon Catherine , Donlon John , McGee Mark , Duane Mary , Kenny David , Earley Bernadette 
Published: July 2024

Abstract
Background
Summer scour syndrome (SSS) is a recently identified pathological condition affecting weaned dairy and dairy-beef calves during their first grazing season in Ireland. The syndrome is characterised by diarrhoea, weight loss, weakness, and can ultimately lead to death in some calves. Oral and oesophageal ulcerations are present in some cases. This study aimed to characterise a series of SSS cases in weaned dairy-bred calves on Irish commercial farms.

Results
Five farms with calves having unexplained diarrhoea at grass were referred by private veterinary practitioners (PVP) following preliminary testing to exclude coccidiosis and parasitic gastroenteritis. Farms were visited within 2 to 5 days following PVP’s referrals, or 2 days to 3 weeks relative to the onset of clinical signs. Farm management data, grass and concentrate samples, and biological samples from 46 calves (8 to 10 calves/farm) displaying clinical signs were collected. Two farms were subsequently found positive for coccidiosis and/or had chronic pneumonia problems after a thorough herd investigation and were designated as non-case farms (NCF). The remaining three farms were deemed typical SSS outbreaks (case farms; CF). Mean rumen fluid pH per farm ranged from 6.67 to 7.09 on CF, and 6.43–6.88 on NCF. Mean rumen fluid ammonia concentrations ranged from 17.6 to 29.6 mg/L and 17.2–45.0 mg/L on CF and NCF, respectively. Corresponding blood ammonia concentrations ranged from 129 to 223 µmol/L and 22–25 µmol/L. Mean blood copper and molybdenum concentrations were within normal range on all farms. Grass crude protein concentrations on the paddocks where the calves had grazed, and were currently grazing on the day of visit ranged from 137 to 148 g/kg DM and 106–177 g/kg DM, respectively on CF, and 160–200 g/kg DM and 151–186 g/kg DM, respectively on NCF. On CF, inorganic nitrogen fertiliser was applied 1 to 3 weeks pre-grazing, whereas on the two NCF, inorganic nitrogen fertiliser was applied 2 to 3 weeks pre-grazing on one farm and no fertiliser was applied on the other.

Conclusion
These findings suggest that copper or molybdenum toxicity, and ruminal acidosis are not the primary causes of SSS. High blood ammonia concentrations and the timing and level of inorganic nitrogen fertiliser application to paddocks pre-grazing, warrant further investigation.
A framework for co-existence of radar and communication with joint design
Authors: Mao Hao , Zhu Haiyun , He Yinghui , Yu Guanding , Yin Rui 
Published: July 2024

AbstractThe integration of both sensing and communication functions is a crucial feature for future communication systems. This paper considers a novel scenario where a radar covers multiple small-cell base stations which operate in different spectra. Due to the limited spectra resource, the radar needs to reuse the spectra of one BS for tracking. To suppress interference and improve performance, we propose a framework including two stages and the corresponding communication and sensing algorithms. Specifically, at the detection stage, we aim to minimize the system transmit power while maintaining the performance of both radar and communication. At the tracking stage, our goal is to maximize the radar sensing performance under a given power budget, while ensuring communication quality. Due to the complexity of the original problem, we address it by introducing auxiliary variables and proposing a penalty dual decomposition-based algorithm, enabling us to solve a more tractable form of the problem. In the inner loop, we propose a concave–convex procedure-based algorithm to handle the optimization problem, while adopting the block coordinate descent algorithm to iteratively update the variables. In the outer loop, we update the penalty term or Lagrange multipliers. Furthermore, we propose a radar target parameter estimation algorithm based on successive interference cancellation, which aims to mitigate communication interference. Finally, numerical simulations demonstrate the effectiveness of the proposed system, and the superior performance of our proposed algorithms over benchmark algorithms.
Determining the push factors to involve in street vending activities and their challenges: in the case of Ethiopia
Authors: Engidaw Abriham Ebabu , Ning Jing , Kebad Mulugeta Abera , Mulaw Sisay Genanu , Alamirew Mandefro Tagele , Wonda Temesgen Abebaw , Abebe Dagmawi Mandefro , Berihun Zemene 
Published: July 2024

AbstractThe study’s primary goal was to analyse the driving forces behind street vending operations and the difficulties they face in the targeted area. The research was conducted using both quantitative and qualitative methods, utilizing explanatory and descriptive designs in the technique. There was use of both primary and secondary data sources. Four government officials and 222 street businesses were chosen for the study using purposive sampling procedures. Structured questionnaires were used to collect the data. The study findings clearly display that economic and social factors have a significant influence on street vending in the study area. The study went on to look into the difficulties that street sellers in the study area deal with, including things like a lack of funding, a space to work, and credit availability. In conclusion, the study recommends that governments should develop a policy for street vending, fortify stakeholder interactions, and expand the capacity of street sellers when contemplating legalizing the practice and selecting a suitable place in urban centres.
AcornHRD: an HRD algorithm highly associated with anthracycline-based neoadjuvant chemotherapy in breast cancer in China
Authors: Pan Jia-Ni , Li Pu-Chun , Wang Meng , Li Ming-Wei , Ding Xiao-Wen , Zhou Tao , Wang Hui-Na , Wang Yun-Kai , Chen Li-Bin , Wang Rong , Ye Wei-Wu , Wu Wei-Zhu , Lou Feng , Wang Xiao-Jia , Cao Wen-Ming 
Published: July 2024

Abstract
Purpose
Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population.

Methods and materials
Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes.

Results
A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11–81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02–52.36, p = 0.005]).

Conclusion
Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.
Analysis of complication risk factors in preoperative computed tomography-guided hookwire location of pulmonary nodules
Authors: Yin Chuntong , Chen Yu , Zhang Renquan , Chen Anguo , Fang Hanlin , Liu Wenjian , Cui Kai , Wang Zhengqiao , Pan Huaguang 
Published: July 2024

Abstract
Background
This study aimed to explore the efficacy of hookwire for computed tomography (CT)-guided pulmonary nodule (PN) localization before video-assisted thoracoscopic surgery (VATS) resection and determine the risk factors for localization-related complications.

Methods
We enrolled 193 patients who underwent preoperative CT-guided PN hookwire localization. The patients were categorized into groups A (103 patients had no complications) and B (90 patients had complications) according to CT and VATS. Uni- and multivariate logistic regression analyses were used to identify risk factors for localization-related complications. A numerical rating scale was used to evaluate hookwire localization-induced pain.

Results
We successfully performed localization in 173 (89.6%) patients. Pneumothorax was the main complication in 82 patients (42.5%). Patient gender, age, body mass index, tumor diameter, consolidation tumor ratio, pathologic diagnosis, position adjustment during location, lesion location, waiting time for surgery, and pleural adhesions were not significantly different between the two groups. The number of nodules, number of punctures, scapular rest position, and depth of insertion within the lung parenchyma were significant factors for successful localization. Multivariate regression analysis further validated the number of nodules, scapular rest position, and depth of insertion within the lung parenchyma as risk factors for hookwire-localization-related complications. Hookwire localization-induced pain is mainly mild or moderate pre- and postoperatively, and some patients still experience pain 7 days postoperatively.

Conclusions
Hookwire preoperative PN localization has a high success rate, but some complications remain. Thus, clinicians should be vigilant and look forward to further improvement.