bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter
Authors: Chen Shijian , Sun Junlong , Wen Wen , Chen Zhenfeng , Yu Ziheng 
Published: September 2024

BackgroundAtrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach.MethodsThis study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 &gt; 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) &lt; 0.05 and p_HEIDI &gt; 0.01.ResultsAt the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 &gt; 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 &gt; 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845–0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844–0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF.ConclusionThis study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.
From single-cell to spatial transcriptomics: decoding the glioma stem cell niche and its clinical implications
Authors: Cao Lei , Lu Xu , Wang Xia , Wu Hao , Miao Xiaye 
Published: September 2024

BackgroundGliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.MethodsSingle-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.ResultsA distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.ConclusionThis study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.
Effects of temperature and storage duration on quality of an insect artificial diet
Authors: Ho Khanh-Van , Hibbard Bruce E. , Vella Michael G. , Shelby Kent S. , Huynh Man P. 
Published: September 2024

Artificial diets are widely used to produce insects for research and education programs. Completed diets, in which the diets are fully made from individual ingredients and ready to use, often have high water activity, making them vulnerable to degradation. Proper storage is critical to maintaining diet quality, yet the storage conditions are not well investigated. In this study, we characterized the effects of storage conditions (temperatures and storage duration) on the quality of a diet capable of rearing both specialist and generalist insect species. The completed diet, produced by both private industry and a USDA-Agricultural Research Service laboratory, was exposed to varying temperatures during a 24-hour transit over 1600 km. After transit, it was stored at 4°C for a total storage period of 28 days. In a separate experiment, the completed diet was stored immediately after diet production at five fixed temperatures (-20, 4, 22, 25, and 33°C) for up to 28 days. For both experiments, at 5 intervals after storage (1, 7, 14, 21, and 28 days), diet quality was accessed by life history parameters (survival, molting, and weight) of western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae, the most serious maize pest in the United States. Our results showed that exposure to varying temperatures between -2°C and 27°C for 24 hours had no significant impact on diet quality. However, extended storage (beyond 24 hours) at any of the fixed temperatures negatively affected diet quality. Insects reared on diets stored for over 24 hours at fixed temperatures ranging from -20°C to 33°C had significant declines in performance. Among the tested temperatures, -20°C and 4°C were found to be the most effective for preserving diet quality. At these low temperatures, there were no significant changes in insect weight and survival for diets stored within 21 and 28 days, respectively, though molting was significantly reduced within 7 days of storage. These findings provide the base of information on the storage conditions for completed diets, supporting the production of healthy insects.
Seawater temperature drives the diversity of key cyanobacteria (Synechococcus and Prochlorococcus) in a warming sea
Authors: Coello-Camba Alexandra , Agustí Susana 
Published: September 2024

The picocyanobacteria genera Prochlorococcus and Synechococcus play a significant role globally, dominating the primary production in warm and oligotrophic tropical and subtropical areas, which represent the largest oceanic ecosystem. Genomic studies have revealed high microdiversity within these genera. It is anticipated that ocean warming may cause decreased biodiversity in marine tropical areas, as increasing temperatures may lead to the development of a new thermal niche in these regions. Thus, our study aimed to characterize the microdiversity of picocyanobacteria in the Red Sea, one of the warmest oligotrophic seas on the planet, which is experiencing warming at a rate that exceeds the global average. We identified picocyanobacteria microdiversity in the open waters of the Eastern Red Sea basin, where seawater temperatures ranged from 22.2 to 32.4°C throughout the water column (from surface to 160 m depth). Both Prochlorococcus and Synechococcus populations were characterized to deep taxonomic levels, applying amplicon sequencing targeting the petB gene, revealing up to 15 different (sub)clades. Synechococcus dominated the basin, representing an average of 68.8% of the total reads assigned to both cyanobacteria. The subclade Synechococcus IIa and Prochlorococcus clade HLII were ubiquitous in the water column of the Eastern Red Sea basin, representing 73% and 56% of the Synechococcus and Prochlorococcus assigned reads, respectively. Maximum cyanobacteria richness was observed at approximately 27.5°C, declining at higher and lower temperatures (polynomial fit, R2 = 0.2, p&lt;0.0001). Synechococcus IIa dominated in the warmest surface waters (&gt;30°C) of the Red Sea, displacing other (sub)clades to more saline and nutrient-poor waters, thereby reducing community diversity (polynomial fit, R2 = 0.77, p&lt;0.0001). Our study contributes to identifying changes in picocyanobacterial diversity when exposed to temperatures exceeding current oceanic thermal limits, through the analysis of Red Sea communities already inhabiting such higher-temperature niches.
Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell tropism
Authors: Addison Max , Hapeshi Alexia , Wong Zi Xin , Connolly John E. , Waterfield Nicholas Robin 
Published: September 2024

BackgroundPhotorhabdus asymbiotica is a species of the insect pathogenic Photorhabdus genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells.MethodsIn this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood.ResultsHere, we present the findings from the Australian (Kingscliff) and North American (ATCC43949) clinical isolates, and non-clinical soilborne nematode isolates from Thailand (PB68) and Northern Europe (HIT and JUN) of P. asymbiotica. We also show the first findings from a new clinical isolate of P. luminescens (Texas), the first non-asymbiotica species to cause a human infection, confirming its ability to infect and survive inside human immune cells.ConclusionHere for the first time, we show how P. asymbiotica selectively infects certain immune cells while avoiding others and that infectivity varies depending on growth temperature. We also show that the tropism varies depending on the geographic location a strain is isolated from, with only the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.
Multidrug-resistant tuberculosis clusters and transmission in Taiwan: a population-based cohort study
Authors: Liu Kuang-Hung , Xiao Yu-Xin , Jou Ruwen 
Published: September 2024

IntroductionMultidrug-resistant tuberculosis (MDR-TB) remains a challenge in the TB program of Taiwan, where 0.5% of new cases and 2.1% of previously treated cases were resistant to at least rifampin (RIF) and isoniazid (INH). Since &gt;80% of our MDR-TB are new cases, genotyping of MDR Mycobacterium tuberculosis is implemented to facilitate contact investigation, cluster identification, and outbreak delineation.MethodsThis is a population-based retrospective cohort study analyzing MDR-TB cases from 2019 to 2022. Whole genome sequencing (WGS) was performed using the Illumina MiSeq and analyzed using the TB Profiler. A single nucleotide polymorphism (SNP) threshold of ≤ 12 and phylogenetic methods were used to identify putative transmission clusters. An outbreak was confirmed using genomic data and epidemiologic links.ResultsOf the 297 MDR-TB cases, 246 (82.8%), 45 (15.2%), and 6 (2.0%) were simple MDR, extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), respectively. The sublineage 2.2 modern Beijing was the predominant (48.8%) MDR-TB strain in Taiwan. Phylogenetic analysis identified 25.3% isolates in 20 clusters, with cluster sizes ranging from 2 to 13 isolates. Nevertheless, only 2 clusters, one household and one community, were confirmed as outbreaks. In this study, we found that males had a higher risk of MDR-TB transmission compared to females, and those infected with the sublineage 2.1-proto-Beijing genotype isolates were at a higher risk of transmission. Furthermore, 161 (54.2%) isolates harbored compensatory mutations in the rpoC and non-rifampicin resistant determinant region (non-RRDR) of the rpoB gene. MDR-TB strains containing rpoB S450L and other compensatory mutations concurrently were significantly associated with clusters, especially the proto-Beijing genotype strains with the compensatory mutation rpoC E750D or the modern Beijing genotype strains with rpoC D485Y/rpoC E1140D.DiscussionRoutine and continuous surveillance using WGS-based analysis is recommended to warn of risks and delineate transmission clusters of MDR-TB. We proposed the use of compensatory mutations as epidemiological markers of M. tuberculosis to interrupt putative MDR-TB transmission.
Unlocking the potential of Kluyveromyces marxianus in the definition of aroma composition of cheeses
Authors: Perpetuini Giorgia , Rossetti Alessio Pio , Rapagnetta Arianna , Tofalo Rosanna 
Published: September 2024

IntroductionThe cheese microbiota is very complex and is made up of technologically-relevant, spoilage, opportunistic and pathogenic microorganisms. Among them lactic acid bacteria and yeasts are the main ones. One of the most interesting dairy yeasts is Kluyveromyces marxianus because of its technological properties including the ability to produce aroma compounds.MethodsThis study investigated the contribution of Kluyveromyces marxianus to the gross composition and aroma profile of cow cheeses. Experimental cheeses were prepared by inoculating a co-culture of K. marxianus FM09 and a commercial strain of Lacticaseibacillus casei and compared with cheeses obtained with only L. casei. The gross composition was determined by a FoodScan™ 2 Dairy Analyser, and free amino acids were evaluated at 507 nm after reaction with Cd-ninhydrin. The volatile organic compounds were extracted by head-space solid phase micro-extraction and analyzed by gas chromatography–mass spectrometry coupled with odor activity values. qRT-PCR was applied to determine the expression of genes involved in esters synthesis and degradation.ResultsThe inoculation of K. marxianus induced an increase of pH and a reduction of protein content of cheeses, in agreement with the stronger proteolysis detected in these cheeses. K. marxianus influenced the content of aroma compounds both quantitatively and qualitatively. In particular, an increase of higher alcohols, esters and organic acids was observed. Moreover, 12 compounds were detected only in cheeses obtained with the co-culture. These differences were in agreement with the odor activity values (OAV). In fact, only 11 compounds showed OAV &gt; 1 in cheeses obtained with the commercial strain, and 24 in those obtained with the co-culture. The qPCR analysis revealed an over expression of ATF1, EAT1, and IAH1 genes.ConclusionKluyveromyces marxianus could act as an important auxiliary starter for cheese production through the development and diversification of compounds related to flavor in short-aged cow cheeses.
Combinatorial protection of cochlear hair cells: not too little but not too much
Authors: Kurabi Arwa , Pak Kwang , Lee Eun Jung , Ryan Allen F. 
Published: September 2024

BackgroundA number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in in vivo and/or in vitro animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective.MethodsUsing an in vitro model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 μM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects.ResultsIncreasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection.ConclusionThe results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.
Association between hypertension requiring medication and postoperative 30-day mortality in adult patients with tumor craniotomy: an analysis of data using propensity score matching
Authors: Liu Yufei , Hu Haofei , Zheng Wenjian , Deng Zhong , Yang Jihu , Zhang Xiejun , Li Zongyang , Chen Lei , Chen Fanfan , Ji Nan , Huang Guodong 
Published: September 2024

BackgroundReliable quantification of the association between hypertension requiring medication and postoperative 30-day mortality in adult patients who undergo craniotomy for tumor resection is limited. We aimed to explore the associations between these factors.Materials and methodsThis work was a retrospective cohort study that used propensity score matching (PSM) among 18,642 participants from the American College of Surgeons National Surgical Quality Improvement Program database between 2012 and 2015. Hypertension requiring medication and postoperative 30-day mortality were the independent and dependent target variables, respectively. PSM was conducted via nonparsimonious multivariate logistic regression to balance the confounders. Robust estimation methods were used to investigate the association between hypertension requiring medication and postoperative 30-day mortality.ResultsA total of 18,642 participants (52.6% male and 47.4% female) met our inclusion criteria; 7,116 (38.17%) participants with hypertension required medication and had a 3.74% mortality rate versus an overall mortality rate of 2.46% in the adult cohort of patients who underwent craniotomy for tumor resection. In the PSM cohort, the risk of postoperative 30-day mortality significantly increased by 39.0% among patients with hypertension who required medication (OR = 1.390, 95% confidence interval (CI): 1.071–1.804, p = 0.01324) after adjusting for the full covariates. Compared with participants without hypertension requiring medication, those with hypertension requiring medication had a 34.0% greater risk of postoperative 30-day mortality after adjusting for the propensity score (OR = 1.340, 95% CI: 1.040–1.727, p = 0.02366) and a 37.6% greater risk of postoperative 30-day mortality in the inverse probability of treatment weights (IPTW) cohort (OR = 1.376, 95% CI: 1.202, 1.576, p &lt; 0.00001).ConclusionAmong U.S. adult patients undergoing craniotomy for tumor resection, hypertension requiring medication is a notable contributor to 30-day mortality after surgery, with odds ratios ranging from 1.34 to 1.39.
The examination of detrusor underactivity in multiple system atrophy
Authors: Yamamoto Tatsuya , Sakakibara Ryuji , Uchiyama Tomoyuki , Kuwabara Satoshi 
Published: September 2024

AimsThe urinary dysfunction in multiple system atrophy (MSA) is characterized by large post-void residuals (PVR) due to impaired bladder contractility. However, the evaluations of bladder contractility are not well validated in MSA. Because the bladder contractility index can be generally represented as Pdet Qmax (detrusor pressure at maximum urinary flow rate) + kQmax (maximum urinary flow rate), we aim to examine which “k” value is suitable for representing bladder contractility concerning its correlations to PVR and voided percentage (VOID%).MethodsWe retrospectively reviewed 133 patients with MSA (74 males, 59 females, mean disease duration 3.2 years) who underwent an urodynamic study. We calculated bladder contractility using the formula PIPk = Pdet Qmax + kQmax by increasing the “k” value from 0.1 to 10 by increments of 0.1. We calculated the correlations between each PIPk (k = 0.1–10.0) and PVR and VOID%.ResultsThe correlational coefficients between PIPk and VOID% were larger than those between PIPk and PVR. The correlational coefficients between PIPk and VOID% reached a plateau level at a “k” value &gt;5.0 in male patients, suggesting that currently used formulas such as Pdet Qmax + 5Qmax for males might be appropriate for male MSA patients. However, the correlational coefficients between PIPk and VOID% reached a plateau level in female patients when the “k” values were &gt;6.0, which might overestimate bladder contractility in female patients.ConclusionAlthough currently used formulas such as Pdet Qmax + 5Qmax might be appropriate for male MSA patients, formulas for female patients need further evaluation.