bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-sensitivity C-reactive protein modifies the prognostic value of platelet count for clinical outcomes after ischemic stroke
Authors: Liu Fanghua , Yang Pinni , Wang Yinan , Shi Mengyao , Wang Ruirui , Xu Qingyun , Peng Yanbo , Chen Jing , Zhang Jintao , Wang Aili , Xu Tan , Zhang Yong-hong , He Jiang 
Published: March 2023

AbstractBackgroundPlatelets play a critical role in the formation of thrombosis and embolism, and high-sensitivity C-reactive protein (HS-CRP) is an important indicator of inflammation, which contribute to the development of ischemic stroke development. This study aimed to examine whether the relationship between baseline platelet count and adverse clinical outcomes is modulated by HS-CRP in patients with ischemic stroke.MethodsA total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability (modified Rankin Scale [mRS] score ≥3) at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the mRS at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate, odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) were calculated for the highest quartiles of platelet counts compared with the lowest quartile.ResultsThe elevated platelet count was associated with the primary outcome (OR, 3.14;95% CI, 1.77-5.58), major disability (OR, 2.07;95%CI, 1.15-3.71), death (HR, 2.75;95%CI, 1.31-5.79), composite outcome of vascular events or death (HR, 2.57;95%CI, 1.38-4.87), and the ordered 7-level categorical score of the mRS at 1 year (OR, 2.01 [95%CI, 1.33-3.04]) among patients with high HS-CRP levels (allPtrend<0.05). However, platelet count was not associated with the primary outcome (OR, 1.13; 95%CI, 0.75-1.71), major disability (OR, 1.34; 95%CI, 0.87-2.08), death (HR, 0.48; 95%CI, 0.19-1.24), composite outcome of vascular events or death (HR, 0.79; 95%CI, 0.45-1.37), and the ordered 7-level categorical score of the mRS at 1 year (OR, 1.17; 95%CI, 0.91-1.49) (allPtrend>0.05) in those with low HS-CRP levels. There was an interaction effect of platelet count and HS-CRP on the primary outcome, death, composite outcome of vascular events or death, and the ordered 7-level categorical score of the mRS at 1 year after ischemic stroke (allPinteraction<0.05).ConclusionsAn elevated platelet count was associated with adverse clinical outcomes in ischemic stroke patients with high HS-CRP levels but not in those with low HS-CRP levels, the HS-CRP level had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke, suggesting that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.
Prevalence and Factors Associated with Cryptosporidiosis Among Livestock and Dogs in Kasese District, Uganda: A Cross-Sectional Study
Authors: Kankya Clovice , Okello Justine , Natweta Baguma James , Wambi Rogers , Rose Ninsiima Lesley , Tubihemukama Methodius , Tricia Kulabako Christine , Munyeme Musso , Hartnack Sonja , Okello Walter , Bugeza James , Muleme James 
Published: March 2023

AbstractBackgroundCryptosporidiosis is a common cause of diarrheal disease in livestock and dogs, and it can result in significant economic losses due to decreased productivity and higher treatment costs. The cryptosporidiosis burden in livestock and dogs is largely unknown and underexploited. We designed a cross-sectional research study to determine the prevalence and factors associated with cryptosporidiosis in livestock and dogs.MethodsThe questionnaire data was downloaded from the Kobotoolbox server in excel format for cleaning and analysis. Laboratory results were matched with the questionnaire data and statistical analysis was performed using STATA version 14 and R version 4.2.2. Descriptive statistics were conducted to determine the frequencies, percentages, and proportions of the different study variables. For the categorical variables, 95% binomial and multinomial confidence intervals were obtained using the commands BinomCI(), with Jeffreys approach, and MultinomCI() available in the DescTools package. To adjust for potential clustering within household, a logistic mixed model approach with household as random effect was chosen and performed using the package glmmTMB. The outcome was a positive or negative test result of each dog. A likelihood ratio test using the lmtest package was used to determine if a predictor was significantly associated with the outcome. To adjust for multiple comparisons, the multcomp package with Tukeys approach was used. First all variables were included in a univariable approach. Second all variables with p-values <0.2 were included in a multivariable model..ResultsDogs were over 50times more likely to have the cryptosporidium infection compared to goat. With aOR 56.07, 95%CI= [10.2569,306.5307] and p-value <0.001. Furthermore, being of Mukonjo tribe was over 20times more likely to have cryptosporidiosis compared to being Musongora. At aOR 24.92, 95%CI= [3.6971,168.0655], p-value 0.0010. Additionally, persons who drunk water from the river ponds were 76.93 times more likely to have cryptosporidium infection compared to the counterparts whose source of drinking water were from protected sources with aOR 76.93, 95% CI= [3.71,1595.324] p-value= 0.0050.ConclusionCryptosporidiosis still remains a big public health problem in Kasese District. Dogs are more at risk of having cryptosporidiosis whereas drinking from river ponds was highly attributed to acquiring cryptosporidiosis.
Manipulation in grazing, viral pressure and resource availability leads to success in the isolation of abundant marine bacteria
Authors: Rey-Velasco Xavier , Deulofeu Ona , Sanz-Sáez Isabel , Cardelús Clara , Ferrera Isabel , Gasol Josep M. , Sánchez Olga 
Published: March 2023

ABSTRACTIsolation of microorganisms is a useful approach to gather knowledge about their genomic properties, physiology, and ecology, in addition to allowing characterization of novel taxa. We performed an extensive isolation effort on samples from seawater manipulation experiments that were carried out during the four astronomical seasons in a coastal site in the NW Mediterranean to evaluate the impact of grazing, viral mortality, resource competition and light on bacterioplankton growth. Isolates were retrieved using two growth media and their full 16S rRNA gene was sequenced to assess their identity and compute their culturability across seasons and experimental conditions. A total of 1643 isolates were obtained, which mainly affiliated to classesGammaproteobacteria(44%),Alphaproteobacteria(26%) andBacteroidia(17%). The most commonly isolated genera wereAlteromonasandLimimaricola. While isolates varied across culture media, seasons and treatments, those pertaining to classGammaproteobacteriawere the most abundant in all experiments, whileBacteroidiawas preferentially enriched in the treatments with reduced grazing. Sixty-one isolates had a similarity below 97% to cultured taxa and are thus putatively novel. Comparison of isolate sequences with 16S rRNA gene amplicon sequences from the same samples showed that the percentage of reads corresponding to isolates was 21.4% within the whole dataset, with dramatical increases in summer virus-reduced (71%) and diluted (47%) treatments. In fact, we were able to isolate the top-10 abundant taxa in several experiments and from the whole dataset.IMPORTANCEThe traditional observation that we can only culture 1% of bacteria for a given environment has recently been questioned on several grounds, among other reasons because it is importantly influenced by environmental conditions. We cultured a high amount of heterotrophic bacterial strains from experiments where seawater environmental conditions had been manipulated and found that decreasing grazing and viral pressure as well as rising nutrient availability are key factors increasing the success in isolating marine bacteria. Our data clearly suggests that the “1% culturability paradigm” needs to be revised and reinforces bacterial cultures as a powerful way to discover new taxa.
Systematic Identification of Post-Transcriptional Regulatory Modules
Authors: Khoroshkin Matvei , Buyan Andrey , Dodel Martin , Navickas Albertas , Yu Johnny , Trejo Fathima , Doty Anthony , Baratam Rithvik , Zhou Shaopu , Joshi Tanvi , Garcia Kristle , Choi Benedict , Miglani Sohit , Subramanyam Vishvak , Modi Hailey , Markett Daniel , Corces M. Ryan , Kulakovskiy Ivan V. , Mardakheh Faraz , Goodarzi Hani 
Published: March 2023

ABSTRACTIn our cells, a limited number of RNA binding proteins (RBPs) are responsible for all aspects of RNA metabolism across the entire transcriptome. To accomplish this, RBPs form regulatory units that act on specific target regulons. However, the landscape of RBP combinatorial interactions remains poorly explored. Here, we performed a systematic annotation of RBP combinatorial interactions via multimodal data integration. We built a large-scale map of RBP protein neighborhoods by generatingin vivoproximity-dependent biotinylation datasets of 50 human RBPs. In parallel, we used CRISPR interference with single-cell readout to capture transcriptomic changes upon RBP knockdowns. By combining these physical and functional interaction readouts, along with the atlas of RBP mRNA targets from eCLIP assays, we generated an integrated map of functional RBP interactions. We then used this map to match RBPs to their context-specific functions and validated the predicted functions biochemically for four RBPs. This study highlights the previously underappreciated scale of the inter-RBP interactions, be it genetic or physical, and is a first step towards a more comprehensive understanding of post-transcriptional regulatory processes and their underlying molecular grammar.
Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
Authors: Cousins Henry C. , Altman Russ B. 
Published: March 2023

ABSTRACTBackgroundSpironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization.MethodsWe performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map. We identified all patients with a hospital admission for COVID-19 in the study window, defining treatment status based on spironolactone prescription orders. The primary outcomes were progression to respiratory ventilation or mortality during the hospitalization. Odds ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or multivariable regression. Subgroup analysis was performed based on age, gender, body mass index (BMI), and dominant SARS-CoV-2 variant.FindingsAmong 898,303 eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: 0.75-0.88; p < 0.001) and mortality (OR 0.88; 95% CI: 0.78-0.99; p = 0.033) in the PSM analysis, supported by the regression analysis. Spironolactone use was associated with significantly reduced odds of ventilation for all age groups, men, women, and non-obese patients, with the greatest protective effects in younger patients, men, and non-obese patients.InterpretationSpironolactone use was associated with a protective effect against ventilation and mortality following COVID-19 infection, amounting to up to 64% of the protective effect of vaccination against ventilation and consistent with an androgen-dependent mechanism. The findings warrant initiation of large-scale randomized controlled trials to establish a potential therapeutic role for spironolactone in COVID-19 patients.
The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: a multicenter, randomized clinical trial
Authors: Wei Ai , Ma Shijin , Dou Yuzhe , Wang Xiaojun , Wu Jianxiong , Zhou Shuzhi , Deng Yanfang , Liu Xinquan , Li Dongming , Yang Mengchang 
Published: March 2023

AbstractIntroductionHypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol.AimThe aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol.Methods304 patients were divided into the remimazolam tosylate group, the propofol group, and the remimazolam tosylate plus propofol group. The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery.ResultsThe incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, withP< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%),P=0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%).ConclusionCo-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy.Clinical trial registration numberNCT05429086
Atypical cell death in the growth plate chondrocytes ofTric-b-knockout mice
Authors: Ichimura Atsuhiko , Miyazaki Yuu , Nagatomo Hiroki , Tomizawa Masato , Kawabe Takaaki , Nakajima Nobuhisa , Okamoto Naoki , Komazaki Shinji , Kakizawa Sho , Nishi Miyuki , Takeshima Hiroshi 
Published: March 2023

AbstractTRIC-A and TRIC-B proteins form homotrimeric cation-permeable channels in the sarco/endoplasmic reticulum (SR/ER) and nuclear membranes and are thought to contribute to counterionic flux coupled with store Ca2+release in various cell types. Serious mutations in theTRIC-Blocus cause autosomal recessive osteogenesis imperfecta (OI), which is characterized by insufficient bone mineralization. We have reported thatTric-b-knockout mice can be used as an OI model. Here we report irregular cell death in proliferating growth plate chondrocytes in developingTric-b-knockout bones. In the knockout chondrocytes, excess pro-collagen fibers were occasionally accumulated in severely dilated ER elements. Of the major ER stress pathways, the PERK pathway was preferentially hyperactivated in the knockout chondrocytes, and most likely altered gene expression to induce apoptosis-related proteins including CHOP and caspase 12. In Ca2+imaging experiments, the knockout chondrocytes exhibited aberrant Ca2+handling; ER Ca2+release was impaired, and intracellular Ca2+concentration was elevated. Our data suggest thatTric-bdeficiency directs growth plate chondrocytes to pro-apoptotic stages by compromising cellular Ca2+-handling and exacerbating ER stress, leading to atypical apoptotic cell death.
Scalable Solar-Driven Chemical Production by Semiconductor Biohybrids Synthesized from Wastewater Pollutants
Authors: Pi Shanshan , Yang Wenjun , Feng Wei , Yang Ruijie , Chao Weixiang , Cheng Wenbo , Cui Lei , Li Zhida , Lin Yiliang , Yang Chen , Lu Lu , Gao Xiang 
Published: March 2023

AbstractSemiconductors biohybrids integrate the best of biological catalysts and semiconductor nanomaterials for solar-to-chemical conversion. To realize the potential of hybrid systems at the commercial level, it remains an urgent need for cost-competitive and environmentally friendly approaches to scaling up. Here, we successfully tackle this challenge through developing biohybrid route that co-utilize multi-pollutants in wastewater to produce semiconductor biohybridsin-situfor solar-to-chemical production. To achieve cost-effective biohybrid production, we introduced an aerobic sulfate reduction pathway intoVibrio natriegensto enable the direct utilization of the heavy metal ions (i.e., Cd2+), sulfate, and organics in the wastewater to biosynthesize functional semiconductor nanoparticles in livingV. natriegens. Furthermore, 2,3-butanediol biosynthetic pathway was introduced into theV. natriegenshybrid to couple the solar energy for enhanced bioproduction. We demonstrated the scalability of this system in a 5-L illuminated fermenter using wastewater as the feedstock, which resulted in production of 13 g/L of 2,3-butanediol. Life cycle analysis showed this specific biohybrid route had a significantly lower cost and reduced CO2emission compared to both pure sugars fermentation and fossil-based routes. In addition to providing a promising step toward sustainable commercializing semiconductor biohybrids for biomanufacturing, our work may lead to hybrid living matter toward future waste to wealth conversion.
Genetic Predisposition to Neuroblastoma Results from a Regulatory Polymorphism that Promotes the Adrenergic Cell State
Authors: Weichert-Leahey Nina , Shi Hui , Tao Ting , Oldridge Derek A , Durbin Adam D , Abraham Brian J. , Zimmerman Mark W , Zhu Shizhen , Wood Andrew C , Reyon Deepak , Joung J Keith , Young Richard A , Diskin Sharon J , Maris John M. , Look A Thomas 
Published: March 2023

AbstractChildhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like “mesenchymal” cell state and a more differentiated sympathetic “adrenergic” cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional co-factor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism G/T that affects aGATA motif in the first intron of LMO1. Here we show that wild-type zebrafish with theGATA genotype develop adrenergic neuroblastoma, while knock-in of the protectiveTATA allele at this locus reduces the penetrance of MYCN-driven tumors, which are restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrates thatTATA/TATA tumors also exhibit a mesenchymal cell state and are low risk at diagnosis. Thus, conversion of the regulatoryGATA to aTATA allele in the first intron ofLMO1reduces the neuroblastoma initiation rate by preventing formation of the adrenergic cell state, a mechanism that is conserved over 400 million years of evolution separating zebrafish and humans.
Multimodal fusion of multiple rest fMRI networks and MRI gray matter via multilink joint ICA reveals highly significant function/structure coupling in Alzheimer’s disease
Authors: Khalilullah K M Ibrahim , Agcaoglu Oktay , Sui Jing , Adali Tülay , Duda Marlena , Calhoun Vince D. 
Published: March 2023

AbstractIn this paper we focus on estimating the joint relationship between structural MRI (sMRI) gray matter (GM) and multiple functional MRI (fMRI) intrinsic connectivity networks (ICN) using a novel approach called multi-link joint independent component analysis (ml-jICA). The proposed model offers several improvements over the existing joint independent component analysis (jICA) model. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer’s disease (AD) versus controls. The results yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for Alzheimer’s disease versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to gray matter components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.
GIPC3 couples to MYO6 and PDZ domain proteins and shapes the hair cell apical region
Authors: Chatterjee Paroma , Morgan Clive P. , Krey Jocelyn F. , Benson Connor , Goldsmith Jennifer , Bateschell Michael , Ricci Anthony J. , Barr-Gillespie Peter G. 
Published: March 2023

AbstractGIPC3 has been implicated in auditory function. Initially localized to the cytoplasm of inner and outer hair cells of the cochlea, GIPC3 increasingly concentrated in cuticular plates and at cell junctions during postnatal development. Early postnatalGipc3KO/KOmice had mostly normal mechanotransduction currents, but had no auditory brainstem response at one month of age. Cuticular plates ofGipc3KO/KOhair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted inGipc3KO/KOcochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks, and the cuticular plate. Several of immunoprecipitated proteins contained GIPC-family consensus PDZ binding motifs (PBMs), including MYO18A, which binds directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell-junction proteins to shape the cuticular plate.Summary statementThe PDZ-domain protein GIPC3 couples the molecular motors MYO6 and MYO18A to actin cytoskeleton structures in hair cells. GIPC3 is necessary for shaping the hair cell’s cuticular plate and hence the arrangement of the stereocilia in the hair bundle.