bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of metabolic syndrome among patients with type 2 diabetes mellitus: A cross-sectional study in a tertiary care center of western Nepal
Authors: Karki Manoj , Shrestha Rejma , Dhungana Milan , Rayamajhi Bidhata 
Published: June 2024

INTRODUCTIONThe coexistence of Metabolic Syndrome in Type 2 diabetic patients significantly increases the risk of stroke and cardiovascular disease. Due to its remarkably high prevalence, metabolic syndrome has gained significant interest over the last decade. Limited information exists regarding the occurrence of Metabolic Syndrome in Type 2 diabetic patients in developing nations like Nepal. Our study aims to determine the prevalence of Metabolic Syndrome among patients with Type 2 Diabetes Mellitus in Western Nepal.METHODSThis prospective cross-sectional study was conducted at the Universal College of Medical Sciences (UCMS) among patients with Type 2 Diabetes Mellitus. Patients with gestational diabetes mellitus, Type I Diabetes Mellitus, and those aged less than 20 were excluded. Metabolic syndrome has been diagnosed based on the definition given by the International Diabetes Federation.RESULTSThe study involved 123 patients with a mean age of 61.44 ± 12.88 years, predominantly female (55.3%). Of these patients, 42.3% were classified as Obese. The overall prevalence of Metabolic Syndrome in Type 2 Diabetes Mellitus patients was 61%, comprising 75 cases. The most common component in our study was hypertension, with 82 cases (66.7%), followed by central obesity with 81 cases (65.9%). Among patients with Metabolic Syndrome, 66.7% had an estimated glomerular filtration rate (eGFR) in the 60-89 ml/min range. In females, central obesity was the most common component, while in males, hypertension was the most common component of Metabolic Syndrome.CONCLUSIONThe prevalence of Metabolic Syndrome in patients with Type 2 Diabetes Mellitus was high. Therefore, timely detection and management of Metabolic Syndrome is crucial in preventing consequences and premature mortality in individuals with Type 2 Diabetes Mellitus.
SalmonellaTyphi Haplotype 58 (H58) Biofilm Formation and Genetic Variation in Typhoid Fever Patients with Gallstones in an Endemic Setting in Kenya
Authors: Muturi Peter , Wachira Peter , Wagacha Maina , Mbae Cecilia , Kavai Susan , Mugo Michael , Muhammed Musa , González Juan F. , Kariuki Samuel , Gunn John S. 
Published: June 2024

AbstractThe causative agent of typhoid fever,Salmonella entericaserovar Typhi, is a human restricted pathogen. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, butS. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify biofilm forming ability and the genetic differences in longitudinal clinicalS. Typhi isolates from asymptomatic carriers with gallstones in Nairobi, Kenya. Whole genome sequences were analyzed from 22S. Typhi isolates, 20 from stool and 2 from blood samples, all genotype 4.3.1 (H58). Nineteen strains were from four patients also diagnosed with gallstones, of whom, three had typhoid symptoms and continued to shedS. Typhi after treatment. All isolates had point mutations in the quinolone resistance determining region (QRDR) and only sub-lineage 4.3.1.2EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR), isolates formed significantly stronger biofilmsin vitrothan the MDR isolates, p<0.001. A point mutation within thetreBgene (treBA383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. Missense mutations in Vi capsular polysaccharide genes,tviEP263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes and genetic variations inS.Typhi from asymptomatic carriers.ImportanceAlthough typhoid fever has largely been eliminated in high income countries, it remains a major global public health concern especially among low- and middle-income countries. The bacteria responsible for this infectious disease,SalmonellaTyphi, has limited ability to replicate outside the human host and human carriers serve as a reservoir of infection. Typhoid is a common infection in parts of sub-Saharan Africa and Asia, and is endemic in our study setting. Our research findings on differences inS.Typhi strains causing typhoid fever and carriage will influence public health approaches aimed at reducing carriage and transmission ofS. Typhi.
Inequalities in Compliance with the Two-Dose Measles Vaccination in Peruvian Children Aged 12 to 59 Months in 2023
Authors: Intimayta-Escalante Claudio , Tapia-Sequeiros Gustavo , Cueva-Cañola Luis E. 
Published: June 2024

AbstractIntroductionInadequate measles vaccination coverage leads to outbreaks that affect the pediatric population in Peru. The aim of this study was to evaluate sociodemographic inequalities related to the coverage and compliance in the two-dose measles vaccination schedule among Peruvian children in 2023.MethodsAn analytical cross-sectional study was conducted using data from a national Peruvian survey. Mothers aged 15 to 49 with children aged 12 to 59 months were included. Sociodemographic and health characteristics of the mother and child were considered sources of inequality. Prevalence ratios (PR) were calculated to measure the characteristics associated with adherence to the measles vaccination schedule. Inequality analysis was assessed using the Erreygers Concentration Index (ECI).ResultsA total of 8,148 households were evaluated. Vaccination coverage was identified as 85.9% (95%CI: 94.7 – 87.1) for the first dose and 53.9% (95%CI: 52.1 – 55.7) for the second dose. In the inequality analysis, mothers with no education (CI: -0.57), aged 15 to 17 years (CI: -0.38), residing in the jungle (CI: -0.41) or highlands (CI: -0.26), and without health insurance (CI: -0.01) showed greater inequality in adherence to the vaccination schedule. Additionally, adherence to growth and development check-ups in infants was a source of inequality (CI: -0.09).ConclussionMeasles vaccination coverage did not reach the minimum values required to prevent outbreaks in Peru. The factors contributing to inequality in vaccination coverage included education level, age, region of residence, area of residence, health insurance status, and adherence to growth and development check-ups.
Sitetack: A Deep Learning Model that Improves PTM Prediction by Using Known PTMs
Authors: Gutierrez Clair S. , Kassim Alia A. , Gutierrez Benjamin D. , Raines Ronald T. 
Published: June 2024

AbstractPost-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success. Here we evaluate the use of known PTM sites in prediction via sequence-based deep learning algorithms. Specifically, PTM locations were encoded as a separate amino acid before sequences were encoded via word embedding and passed into a convolutional neural network that predicts the probability of a modification at a given site. Without labeling known PTMs, our model is on par with others. With labeling, however, we improved significantly upon extant models. Moreover, knowing PTM locations can increase the predictability of a different PTM. Our findings highlight the importance of PTMs for the installation of additional PTMs. We anticipate that including known PTM locations will enhance the performance of other proteomic machine learning algorithms.
Plant interaction traits determine the biomass of arbuscular mycorrhizal fungi and bacteria in soil
Authors: Lewe Natascha , Keyzers Robert A. , Tylianakis Jason M. , Deslippe Julie R. 
Published: June 2024

AbstractPlant-arbuscular mycorrhizal fungal (AMF) mutualisms play key roles in the biodiversity and productivity of ecosystems. Yet we have limited understanding of the functional roles of plants as AMF generalists or specialists, and the consequences of these plant interaction traits for soil ecosystems are virtually unknown. We grew eight pasture plant species under two experimental conditions and determined their root AMF communities by sequencing. We determined plant species interaction traits with AMF using a set of numeric and phylogenetic α-, β– and γ-diversities and characterized plant species’ relative interaction generalism for AMF. We used lipid analysis of rhizosphere soils and Bayesian modelling to explore how host interaction traits affected carbon allocation to AMF and bacteria. Plant interaction traits for AMF appear to be stable despite large variation in edaphic conditions and AMF pools. We show that host interaction generalism was associated with opposite patterns of bacterial and AMF biomass; the phylogenetic diversity of host interactions was positively associated with AMF biomass whereas the richness of host interactions was negatively associated with bacterial biomass in rhizosphere soils. Explicit consideration of plant interaction niches may enhance understanding of how changes in biodiversity affect ecosystem carbon cycling.Open research statementThis publication does not use novel code, and the bioinformatic and statistic pipelines for this manuscript will be made available athttps://github.com/NLewe/Bayes-interaction-niche.Raw data will be made available at NCBI as BioProject: PRJNA997080
APOE4 increases energy metabolism in APOE-isogenic iPSC-derived neurons
Authors: Budny Vanessa , Knöpfli Yannic , Meier Debora , Zürcher Kathrin , Bodenmann Chantal , Peter Siri L. , Müller Terry , Tardy Marie , Cortijo Cedric , Tackenberg Christian 
Published: June 2024

AbstractThe apolipoprotein E4 (APOE4) allele represents the major genetic risk factor for Alzheimer’s disease (AD). In contrast, APOE2 is known to lower the AD risk while APOE3 is defined as risk neutral. APOE plays a prominent role in the bioenergetic homeostasis of the brain, and early-stage metabolic changes have been detected in brains of AD patients. Although APOE is primarily expressed by astrocytes in the brain, neurons also have been shown as source for APOE. However, little is known about the differential role of the three APOE isoforms for neuronal energy homeostasis. In this study, we generated pure human neurons (iN cells) from APOE-isogenic induced pluripotent stem cells (iPSCs), expressing either APOE2, APOE3, APOE4 or carrying an APOE-knockout (KO) to investigate APOE isoform-specific effects on neuronal energy metabolism. We showed that endogenously produced APOE4 enhanced mitochondrial ATP production in APOE-isogenic iN cells but not in the corresponding iPS cell line. This effect neither correlated with the expression levels of mitochondrial fission or fusion proteins, nor with the intracellular or secreted levels of APOE, which were similar for APOE2, APOE3 and APOE4 iN cells. ATP production and basal respiration in APOE-KO iN cells strongly differed from APOE4 and more closely resembled APOE2 and APOE3 iN cells indicating a gain-of-function mechanism of APOE4 rather than a loss-of-function. Taken together, our findings in APOE isogenic iN cells reveal an APOE genotype-dependent and neuron-specific regulation of oxidative energy metabolism.
PT-seq: A method for metagenomic analysis of phosphorothioate epigenetics in complex microbial communities
Authors: Yuan Yifeng , DeMott Michael S. , Byrne Shane R. ,   the Global Microbiome Conservancy, Dedon Peter C. 
Published: June 2024

ABSTRACTAmong dozens of known epigenetic marks, naturally occurring phosphorothioate (PT) DNA modifications are unique in replacing a non-bridging phosphate oxygen with redox-active sulfur and function in prokaryotic restriction-modification and transcriptional regulation. Interest in PTs has grown due to the widespread distribution of thednd, ssp, andbrxgenes among bacteria and archaea, as well as the discovery of PTs in 5-10% of gut microbes. Efforts to map PTs in complex microbiomes using existing next-generation and direct sequencing technologies have failed due to poor sensitivity. Here we developed PT-seq as a high-sensitivity method to quantitatively map PTs across genomes and metagenomically identify PT-containing microbes in complex genomic mixtures. Like other methods for mapping PTs in individual genomes, PT-seq exploits targeted DNA strand cleavage at PTs by iodine, followed by sequencing library construction using ligation or template switching approaches. However, PT-specific sequencing reads are dramatically increased by adding steps to heat denature the DNA, block pre-existing 3’-ends, fragment DNA after T-tailing, and enrich iodine-induced breaks using biotin-labeling and streptavidin beads capture. Iterative optimization of the sensitivity and specificity of PT-seq is demonstrated with individual bacteria and human fecal DNA.
Disruption of recombination machinery alters the mutational landscape in plant organellar genomes
Authors: Waneka Gus , Broz Amanda K. , Wold-McGimsey Forrest , Zou Yi , Wu Zhiqiang , Sloan Daniel B. 
Published: June 2024

ABSTRACTLand plant organellar genomes have extremely low rates of point mutation yet also experience high rates of recombination and genome instability. Characterizing the molecular machinery responsible for these patterns is critical for understanding the evolution of these genomes. While much progress has been made towards understanding recombination activity in land plant organellar genomes, the relationship between recombination pathways and point mutation rates remains uncertain. The organellar targetedmutShomolog MSH1 has previously been shown to suppress point mutations as well as non-allelic recombination between short repeats inArabidopsis thaliana. We therefore implemented high-fidelity Duplex Sequencing to test if other genes that function in recombination and maintenance of genome stability also affect point mutation rates. We found small to moderate increases in the frequency of single nucleotide variants (SNVs) and indels in mitochondrial and/or plastid genomes ofA. thalianamutant lines lackingradA,recA1, orrecA3. In contrast,osb2andwhy2mutants did not exhibit an increase in point mutations compared to wild type (WT) controls. In addition, we analyzed the distribution of SNVs in previously generated Duplex Sequencing data fromA. thalianaorganellar genomes and found unexpected strand asymmetries and large effects of flanking nucleotides on mutation rates in WT plants andmsh1mutants. Finally, using long- read Oxford Nanopore sequencing, we characterized structural variants in organellar genomes of the mutant lines and show that different short repeat sequences become recombinationally active in different mutant backgrounds. Together, these complementary sequencing approaches shed light on how recombination may impact the extraordinarily low point mutation rates in plant organellar genomes.
Hallmarks of tumor-experienced T cells are absent in multiple myeloma patients from diagnosis through maintenance therapy
Authors: Shasha Carolyn , Glass David R. , Moelhman Ernest , Islas Laura , Tian Yuan , Szeto Gregory L. , Peng Tao , Song Xiaoling , Wurscher Michelle , Bumol Thomas F. , Torgerson Troy R. , Greenberg Philip D. , Green Damian J. , Newell Evan W. 
Published: June 2024

ABSTRACTDysregulation of the bone marrow (BM) niche in multiple myeloma (MM) alters the composition and state of resident immune cells, potentially impeding anti-tumor immunity. One common mechanism of immune inhibition in solid tumors is the induction of exhaustion in tumor-specific T cells. However, the extent of T cell tumor recognition and exhaustion is not well-characterized in MM. As the specific mechanisms of immune evasion are critical for devising effective therapeutic strategies, we deeply profiled the CD8+T cell compartment of newly-diagnosed MM (NDMM) patients for evidence of tumor reactivity and T cell exhaustion. We applied single-cell multi-omic sequencing and antigen-specific mass cytometry to longitudinal BM and peripheral blood (PB) samples taken from timepoints spanning from diagnosis through induction therapy, autologous stem cell transplant (ASCT), and maintenance therapy. We identified an exhausted-like population that lacked several canonical exhaustion markers, was not significantly enriched in NDMM patients, and consisted of small, nonpersistent clones. We also observed an activated population with increased frequency in the PB of NDMM patients exhibiting phenotypic and clonal features consistent with homeostatic, antigen-nonspecific activation. However, there was no evidence of “tumor-experienced” T cells displaying hallmarks of terminal exhaustion and/or tumor-specific activation/expansion in NDMM patients at any timepoint.
No Miracle, Just a Mineral: The Not-So-Magical Antimicrobial World of Chlorine Dioxide
Authors: Dudek-Wicher R. , Brożyna M. , Paleczny J. , Mączyńska B. , Dudek B. , Migdał P. , Dołowacka-Jóźwiak A. , Fischer J. , Junka A. 
Published: June 2024

AbstractThis study evaluates thein vitroantimicrobial efficacy and cytotoxicity of acidified sodium chlorite (ASC), a source of chlorine dioxide. Despite its controversial promotion in alternative medicine as a cure-all solution, known as “Miracle Mineral Solution” (MMS), the data on its factual medicinal activity is very limited. Therefore, we aimed to elucidate the activity of ASC against biofilms ofStaphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus mutans, Pseudomonas aeruginosa, Escherichia coli, andLactobacillus sp. The study also investigated the in vitrocytotoxic effects of ASC towards eukaryotic fibroblasts and inin vivomodel ofGalleria mellonellalarvae. Our findings demonstrate that these concentrations of ASC which can effectively eradicate biofilms, also pose potential health risks due to theirin vitroandin vivocytotoxicity. It implies that ASC applied in human can lead to damage to the mucous membrane of the gastrointestinal tract. This research contributes to the ongoing debate on the safety and efficacy of chlorine dioxide in clinical applications, highlighting the need for precise dosing to avoid mucosal damage in therapeutic contexts.
Genomic analysis revealed hotspots of genetic adaptation and risk of disappearance in the Brazilian goat populations
Authors: Sobrinho Francisco de A. Diniz , Coelho Ronaldo Cunha , de Oliveira Moura Jeane , do Nascimento Igor Ferreira , Bajay Miklos Maximiliano , Branco Carvalho Leonardo Castelo , Britto Fábio Barros , Rocha Sarmento José Lindenberg , M. Ribeiro Azevedo Danielle Maria , Mastrangelo Salvatore , de Araújo Adriana Mello 
Published: June 2024

AbstractWe accessed a 50K Illumina SNP genotype dataset from two important goat breeds of the Brazilian semi- arid region to analyze the abundance and length of runs of homozygosity (ROH). This analysis aims to elucidate the importance of adaptation history in the genome of the Brazilian goat populations and to measure genomic inbreeding. Heterozygosity-rich regions (HRR) or genome regions of high genetic variability provide clues about how diversity might be associated with increased fitness, avoiding deleterious homozygous alleles. Overall, 22,872 ROH were identified. The average number of ROH per individual ranged from 74.73 (Anglo-Nubian commercial breed) to 173.85 (Marota landrace). Analysis of the distribution of runs of homozygosity according to their size showed that, for both breeds, the majority of ROH were in the short (<2.0 Mb) category (65.6%). ROH-based inbreeding (FROH) revealed low levels in Anglo-Nubian (0.0627) and high levels in Marota (0.1419), likely due to a reduction in effective population size over generations in the Marota landrace. We defined islands of ROH and HRR and identified common regions in the Marota goat, where genes related to various traits such as embryonic development, body growth, lipid homeostasis, and brain functions are located. These results indicate that such regions are associated with many traits and have therefore been under selective pressure in these goat breeds reared for different purposes.
The FGFR inhibitor Rogaratinib reduces microglia reactivity and synaptic loss in TBI
Authors: Rehman Rida , Froehlich Albrecht , olde Heuvel Florian , Elsayed Lobna , Boeckers Tobias , Huber-Lang Markus , Morganti-Kossmann Cristina , Roselli Francesco 
Published: June 2024

AbstractBackgroundTraumatic brain injury (TBI) induces an acute reactive state of microglia, which contribute to secondary injury processes through phagocytic activity and release of cytokines. Several receptor tyrosine kinases (RTK) are activated in microglia upon TBI, and their blockade may reduce the acute inflammation and decrease the secondary loss of neurons; thus RTKs are potential therapeutic targets. We have previously demonstrated that several members of the FGFR family are transiently phosporylated upon TBI; the availability for drug repurposing of FGFR inhibitors makes worthwhile the elucidation of the role of FGFR in the acute phases of the response to TBI and the effect of FGFR inhibition.MethodsA closed, blunt, weight-drop mild TBI protocol was employed. The pan-FGFR inhibitor Rogaratinib was administered to mice 30min after the TBI and daily up to 7 days post injury. Phosphor-RTK Arrays and proteomic antibody arrays were used to determine target engagement and large-scale impact of the FGFR inhibitor. pFGFR1 and pFGFR3 immunostaining were employed for validation. As outcome parameters of the TBI injury immunostainings for NeuN, VGLUT1, VGAT at 7dpi were considered.ResultsInhibition of FGFR during TBI restricted phosphorylation of FGFR1, FGFR3, FGFR4 and ErbB4. Phosphorylation of FGFR1 and FGFR3 during TBI was traced back to Iba1+ microglia. Rogaratinib substantially dowregulated the proteomic signature of the neuroimmunological response to trauma, including the expression of CD40L, CXCR3, CCL4, CCR4, ILR6, MMP3 and OPG. Protracted Rogaratinib treatment exhibited a neuroprotective effect on neuronal density at 7dpi and limited the loss of excitatory (vGLUT+) synapses.ConclusionThe FGFR family is involved in the early induction of reactive microglia in TBI. FGFR inhibition selectively prevented FGFR phosphorylation in the microglia, dampened the overall neuroimmunological response and enhanced the preservation of neuronal and synaptic integrity. Thus, FGFR inhibitors display potential as microglial modulators in TBI.