bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Clinical Outcomes in Acute Coronary Syndrome Patients Who Undergo Percutaneous Coronary Intervention Using Different P2Y12 Inhibitors: A SMS Hospital Based Observational Study
Authors: Swami Raghuraj , Kumar Sharma Sohan , Meena Pradeep 
Published: December 2023

ABSTRACTBackgroundTo compare the safety, and efficacy of contemporary P2Y12 inhibitors, prescription rates, drug defaulter and switch over rates in acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI).Methodsin this prospective observational study we studied 195 ACS patients who underwent PCI in SMS Hospital, Jaipur. We compared prescription rates, bleeding, and major adverse cardiac events (MACEs: cardiac death, nonfatal myocardial infarction, or stroke) according to ticagrelor, prasugrel, or clopidogrel use.ResultsThe prescription rates of ticagrelor, prasugrel, and clopidogrel were 29.5%, 4.3%, and 66.2% respectively. Bleeding occurred in total 6 patients (2.9%) out of which 3 patients (2.2%) in clopidogrel group, 1 patient (11.1%) in prasugrel group and 2 patients (3.2%) in ticagrelor group (p=0.29)), respectively, with higher incidence in ticagrelor and prasugrel users than in clopidogrel users but statistically not significant. After six month follow up, all-cause mortality was total 5 cases (2.4%) out of which 4 death (2.9%) occurred in clopidogrel group while 1 death (1.6%) occurred in ticagrelor group(p=0.76). no mortality was recorded in prasugrel group. Repeat myocardial infarction (Re MI) occurred in total 4 patients (1.9%) with 2 patients in clopidogrel and ticagrelor group each. A total 5 patients (2.4%) switch over to another p2y12 inhibitor, mostly from ticagrelor group(p=0.045). During this follow up period, a total of 4 patients (1.9%) were drug defaulter (0.622).ConclusionsAs clopidogrel based DAPT was prescribed more in our centre because of free institutional supply and found no significant difference in clinical outcomes, although slight increase in bleeding risk in ticagrelor or prasugrel based DAPT, demonstrate clopidogrel based DAPT regime can be preferably prescribed safely in our population. Drug defaulter rates in first six month following PCI are low in all groups but more switch over from ticagrelor group to other groups significantly shows importance of low cost and free institutional supply in drug adherence.
The Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) oncogene is upregulated in pre-cystic epithelial cells revealing a new target for polycystic kidney disease
Authors: Smith Abigail O. , Frantz William Tyler , Preval Kenley M. , Edwards Yvonne J.K. , Ceol Craig J. , Jonassen Julie A. , Pazour Gregory J. 
Published: December 2023

AbstractPolycystic kidney disease (PKD) is an important cause of end stage renal disease, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of renal tubules into cysts are not understood. To identify factors that promote the initiation of cysts we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed. We identified 74 genes which we term cyst initiation candidates (CICs). To identify conserved changes with relevance to human disease we compared these murine CICs to single cell transcriptomic data derived from patients with PKD and from healthy controls. Tumor-associated calcium signal transducer 2 (Tacstd2) stood out as an epithelial-expressed gene whose levels were elevated prior to cystic transformation and further increased with disease progression. Human tissue biopsies and organoids show that TACSTD2 protein is low in normal kidney cells but is elevated in cyst lining cells. While TACSTD2 has not been studied in PKD, it has been studied in cancer where it is highly expressed in solid tumors while showing minimal expression in normal tissue. This property is being exploited by antibody drug conjugates that target TACSTD2 for the delivery of cytotoxic drugs. Our finding that Tacstd2 is highly expressed in cysts, but not normal tissue, suggests that it should be explored as a candidate for drug development in PKD. More immediately, our work suggests that PKD patients undergoing TACSTD2 treatment for cancer should be monitored for kidney effects.One Sentence SummaryThe oncogene, tumor-associated calcium signal transducer 2 (Tacstd2) mRNA increased in abundance shortly after Pkd2 loss and may be a driver of cyst initiation in polycystic kidney disease.
Interleukin-6 -174 G/C promoter gene polymorphism and polycystic ovary syndrome: A cross sectional investigation in adult women
Authors: Gupta A , Gupta V , Shah K , Gupta V 
Published: December 2023

AbstractPolycystic ovarian syndrome (PCOS), a metabolic disorder, manifests itself in a variety of ways. In this cross-sectional study, we evaluated the IL-6-174 G/C promoter gene polymorphism in adult PCOS women and its relationship to circulating levels and metabolic risk indicators. A total of 298 women between the ages between 15 and 35 years were chosen, 126 of whom had PCOS, and 172 of whom did not (control group). Both groups were further divided into subgroups of obese and lean women. The lipid profile, serum IL-6 level, and Homeostatic Model Assessment (HOMA) index were all examined. By using PCR-RFLP, the genotype of IL-6-174 G/C was identified. Women in the PCOS and non-PCOS groups showed significant variations in genotype frequencies and metabolic risk indicators. In PCOS compared to non-PCOS, there was a stronger correlation between the mutant ‘C’ allele of IL-6-174 G/C (p<0.0001; OR=1.91; 95% CI=1.38-2.66). Women with PCOS (61.2%) were significantly more associated with both the homozygous CC and heterozygous GC genotypes of IL-6-174 G/C in respect of WHR>0.85 than non-PCOS women (59.2%). In PCOS women, the distribution of the mutant genotypes CC and GC of the IL-6-174 G/C gene was likewise significantly different from GG, with higher WHR (p=0.0191), HOMA index (p=0.031), and serum IL-6 level (p=0.0094). These findings imply that the IL-6-174 G/C promoter mutant CC genotype was substantially related with increased circulating IL-6 levels, and that the presence of IR may be a risk indicator for the development of the metabolic syndrome (MetS) in PCOS women.
Clinical application of ISO and CEN/TS standards for liquid biopsies - information everybody wants but nobody wants to pay for
Authors: Bonstingl Lilli , Skofler Christina , Ulz Christine , Zinnegger Margret , Sallinger Katja , Schönberger Julia , Schuch Katharina , Pankratz Karin , Borrás-Cherrier Anatol , Somodi Visnja , Abuja Peter M. , Oberauner-Wappis Lisa , Bauernhofer Thomas , Kroneis Thomas , El-Heliebi Amin 
Published: December 2023

AbstractBackgroundLiquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Despite increasing clinical use, standardization remains a challenge. ISO and CEN/TS standardized workflows exist, but their integration into clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS liquid biopsy standards in a real-world clinical setting.MethodsWe evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and tracked all essential criteria. This included assessing tube filing level, complete timing from blood draw until storage, transport conditions, temperature control, hemolysis score and tube draw order and its effects on hemolysis.ResultsAmong 659 samples, 92.4% (609/659) met the essential criteria for ISO and CEN/TS compliance. In total 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filing level. In our advanced prostate cancer cohort, 12.9% (40/311) of the evaluated plasma samples were hemolytic. Within the draw order of five blood collection tubes, hemolysis did not significantly increase from tube one to five. The complete ccfDNA ISO and CTC CEN/TS workflows were completed within an average of 168 (+/- 71 min) and 248 minutes (+/- 76 min), respectively, from blood draw until storage.ConclusionsOur study demonstrates the feasibility and benefits of adhering to ISO and CEN/T standards in a clinical liquid biopsy study. ISO and CEN/TS standards revealed that hemolysis is a common phenomenon in pre-treated advanced prostate cancer patients, as we eliminated pre-analytical errors as cause.
A computational model for lipid-anchored polysaccharide export by the outer-membrane protein GfcD
Authors: Fruet Cecilia , Martinez-Goikoetxea Mikel , Merino Felipe , Lupas Andrei N. 
Published: December 2023

AbstractMany bacteria are protected by different types of polysaccharide capsules, structures formed of long repetitive glycan chains that are sometimes free and sometimes anchored to the outer membrane via lipid tails. One type, called group 4 capsule, results from expression of thegfcABCDE-etp-etkoperon inEscherichia coli. Of the proteins encoded in this operon, GfcE is thought to provide the export pore for free polysaccharide chains, but none of the proteins has been implicated in the export of chains carrying a lipid anchor. For this function, GfcD has been a focus of attention as the only outer-membrane β-barrel encoded in the operon. AlphaFold predicts two β-barrel domains in GfcD, a canonical N-terminal one of 12 strands and an unusual C-terminal one of 13 strands, which features a large lateral aperture between strands β1 and β13. This immediately suggests a lateral exit gate for hydrophobic molecules into the membrane, analogous to the one proposed for the lipopolysaccharide export pore LptD. Here, we report an unsteered molecular dynamics study of GfcD embedded in the bacterial outer membrane, with the common polysaccharide anchor, lipid A, inserted in the pore of the C-terminal barrel. Our results show that the lateral aperture does not collapse during simulations, that membrane lipids nevertheless do not penetrate the barrel, but that the lipid chains of the lipid A molecule readily exit into the membrane.Statement of SignificanceDespite the essential role polysaccharide capsules play in the resilience of bacteria to hostile environments, many aspects of their biogenesis are still poorly understood. One aspect concerns the export of capsular polysaccharides carrying a lipid anchor, for which even the proteins mediating the process are unknown. Here we propose that one of the largest families of β-barrel proteins in the bacterial outer membrane is a key agent of this process and show by biophysical simulation that it allows the exit of lipid anchors into the membrane through a lateral opening. More generally, our model illuminates the lateral exit mechanisms proposed for the export of hydrophobic macromolecules into the bacterial outer membrane.Graphical abstract
ISWI catalyzes nucleosome sliding in condensed nucleosome arrays
Authors: Vizjak Petra , Kamp Dieter , Hepp Nicola , Scacchetti Alessandro , Gonzalez Pisfil Mariano , Bartho Joseph , Halic Mario , Becker Peter B. , Smolle Michaela , Stigler Johannes , Mueller-Planitz Felix 
Published: December 2023

SummaryHow chromatin enzymes work in condensed chromatin and how they maintain diffusional mobility inside remains unexplored. We investigated these challenges using theDrosophilaISWI remodeling ATPase, which slides nucleosomes along DNA. Folding of chromatin fibers did not affect slidingin vitro. Catalytic rates were also comparable in- and outside of chromatin condensates. ISWI cross-links and thereby stiffens condensates, except when ATP hydrolysis is possible. Active hydrolysis is also required for ISWI’s mobility in condensates. Energy from ATP hydrolysis therefore fuels ISWI’s diffusion through chromatin and prevents ISWI from cross-linking chromatin. Molecular dynamics simulations of a ‘monkey-bar’ model in which ISWI grabs onto neighboring nucleosomes, then withdraws from one before rebinding another in an ATP hydrolysis-dependent manner qualitatively agree with our data. We speculate that ‘monkey-bar’ mechanisms could be shared with other chromatin factors and that changes in chromatin dynamics caused by mutations in remodelers could contribute to pathologies.
Alternative splicing expands the antiviral IFITM repertoire in Chinese horseshoe bats
Authors: Mak Nelly , Zhang Dan , Li Xiaomeng , Rahman Kazi , Datta Siddhartha A.K. , Taylor Jordan , Liu Jingyan , Shi Zhengli , Temperton Nigel , Irving Aaron T. , Compton Alex A. , Sloan Richard D. 
Published: December 2023

AbstractThe interferon response is shaped by the evolutionary arms race between hosts and the pathogens they carry. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviralIFITMgenes that arose by gene duplication, they restrict virus entry and are key players of the interferon response. Yet, little is known about IFITMs in other mammals. Here, we identified anIFITMgene in Chinese horseshoe bat, a natural host of SARS-coronaviruses, that is alternatively spliced to produce two IFITM isoforms. These bat IFITMs have conserved structures in vitro and differential antiviral activities against influenza A virus and coronaviruses including SARS- and MERS-coronavirus. In parallel with human IFITM1-3, the bat IFITM isoforms localize to distinct cellular compartments. Further analysis of IFITM repertoires in 205 mammals reveals that alternative splicing is a ubiquitous strategy for IFITM diversification, albeit less widely adopted than gene duplication. These findings showcase an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.
Neurophysiology of perceptual decision-making and its alterations in attention-deficit hyperactivity disorder (ADHD)
Authors: Biabani Mana , Walsh Kevin , Zhou Shou-Han , Wagner Joseph , Johnstone Alexandra , Paterson Julia , Johnson Beth P. , Loughnane Gerard M. , O’Connell Redmond G. , Bellgrove Mark A. 
Published: December 2023

AbstractDespite the prevalence of ADHD, efforts to develop a detailed understanding of the neuropsychology of this neurodevelopmental condition are complicated by the diversity of interindividual presentations and the inability of current clinical tests to distinguish between its sensory, attentional, arousal or motoric contributions. Identifying objective methods that can decompose the clinical heterogeneity of ADHD is a long-held goal that is hoped to advance our understanding of etiological processes and potentially aid the development of personalized treatment approaches. Here, we examine key neuropsychological components of ADHD within an electrophysiological (EEG) perceptual decision-making paradigm that is capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from attentional selection to motor responses. We show that compared to typically developing children, children with ADHD displayed slower and less accurate performance, which was driven by the atypical dynamics of discrete electrophysiological signatures of attentional selection, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of decision-making in ADHD and establish discrete neural signals that can be used to understand the wide range of neuropsychological performance variations in individuals with ADHD.Significance StatementThe efficacy of diagnostic and therapeutic pathways in ADHD is limited by our incomplete understanding of its neurological basis. One promising avenue of research is the search for basic neural mechanisms that may contribute to the variety of cognitive challenges associated with ADHD. We developed a mechanistic account of differences in a fundamental cognitive process by integrating across neurocognitive, neurophysiological (i.e., EEG), and computational levels of analysis. We detected distinct neural changes in ADHD that explained altered performance (e.g., slowed and less accurate responses). These included changes in neural patterns of attentional selection, sensory information processing, and response preparation. These findings enhance our understanding of the neurophysiological profile of ADHD and may offer potential targets for more effective, personalized interventions.
Performance of neural networks for prediction of asparagine content in wheat grain from imaging data
Authors: Oddy Joseph 
Published: December 2023

ABSTRACTBackgroundThe prediction of desirable traits in wheat from imaging data is an area of growing interest thanks to the increasing accessibility of remote sensing technology. However, as the amount of data generated continues to grow, it is important that the most appropriate models are used to make sense of this information. Here, the performance of neural network models in predicting grain asparagine content is assessed against the performance of other models.ResultsNeural networks had greater accuracies than partial least squares regression models and gaussian naïve Bayes models for prediction of grain asparagine content, yield, genotype, and fertiliser treatment. Genotype was also more accurately predicted from seed data than from canopy data.ConclusionUsing wheat canopy spectral data and combinations of wheat seed morphology and spectral data, neural networks can provide improved accuracies over other models for the prediction of agronomically important traits.
Armillaria korhonenii, the sixteenth biological species ofArmillariafrom China
Authors: Liu Jianwei , Qin Guofu , Chen Jian , Song Jing , Yan Zhuyue , Yang Shimei , Tian Meng-hua , Xu Xin , Zhang Changfei , Luangharn Thatsanee , Bhunjun Chitrabhanu S. , Yu Fuqiang , Yang Zhuliang 
Published: December 2023

ABSTRACTArmillaria korhonenii, designated as Chinese biological species Q (CBSQ) here, is described as a new species based on phylogenetic and morphological evidence as well as the results of mating tests. This species is the sixteenth biological species ofArmillariareported from China following the discovery of 15 previously known biological species. Phylogenetically,A.korhoneniiis the earliest divergent lineage of the genusArmillariaas inferred from the nucleotide sequences of the Elongation Factor 1-Alpha (EF1a). Morphologically, it is characterized by its ellipsoid to elongate basidiospores, yellowish orange to honey yellow pileus with fibrillose squamules. Mating tests indicated thatA.korhoneniiis a tetrapolar heterogeneous species and is inter-sterile with all the tested species except partial compatibility with CBSH.
Exploring natural genetic variation in photosynthesis-related traits of barley in the field
Authors: Gao Yanrong , Stein Merle , Oshana Lilian , Zhao Wenxia , Matsubara Shizue , Stich Benjamin 
Published: December 2023

AbstractOptimizing photosynthesis is considered an important strategy for improving crop yields to ensure food security. To evaluate the potential of using photosynthesis-related parameters in crop breeding programs, we measured chlorophyll fluorescence along with growth-related and morphological traits of 23 barley inbreds across different developmental stages in field conditions. The photosynthesis-related parameters were highly variable, changing with light intensity and developmental progression of plants. Yet, the variations in photosystem II (PSII) quantum yield observed among the inbreds in the field largely reflected the variations in CO2assimilation properties in controlled climate chamber conditions, confirming that the chlorophyll fluorescence-based technique can provide proxy parameters of photosynthesis to explore genetic variations under field conditions. Heritability (H2) of the photosynthesis-related parameters in the field ranged from 0.16 for the quantum yield of non-photochemical quenching to 0.78 for the fraction of open PSII center. Two parameters, the maximum PSII efficiency in light-adapted state (H20.58) and the total non-photochemical quenching (H20.53), showed significant positive and negative correlations, respectively, with yield-related traits (dry weight per plant and net straw weight) in the barley inbreds. These results indicate the possibility of improving crop yield through optimizing photosynthetic light use efficiency by conventional breeding programs.
5’ extended protein-codingINO80Etranscript regulates expression of two head-to-head overlapping genes:INO80EandHIRIP3
Authors: Ryczek Natalia , Łyś Aneta , Wanowska Elżbieta , Kozłowska-Masłoń Joanna , Makałowska Izabela 
Published: December 2023

AbstractTheINO80Egene encodes the protein involved in the chromatin remodeling processes as a part of the multi-subunit INO80-chromatin remodeling complex. TheINO80Egene is located on chromosome 16 and overlaps head-to-head with theHIRIP3gene encoding protein, which binds H2B and H3 core histones and HIRA protein and regulates the chromatin and histone metabolism. Antisense transcription of head-to-head overlapping PC genes may have several consequences and none of them have been comprehensively investigated and explained. Here, we determined that INO80E-201, which overlaps theHIRIP3gene transcripts, forms an R-loop at its 5’ end. We also demonstrated that overlapping transcripts of INO80E andHIRIP3form an RNA:RNA duplex that has the stabilizing effect on the involved mRNAs. Our results confirmed that this stabilization could be mediated by the ELAVL1 protein. We additionally introducedde novomethylation using the CRISPR/Cas system into the promoter sequence ofINO80Egene. As a result of the introduced changes, reduced expression ofHIRIP3andINO80Egene transcripts was observed. It was determined that methylated cytosines were located in the binding sites for four transcription factors including RARG, which was further confirmed to be important in the transcription of both studied genes. Our results strongly suggest that the formation of an RNA:RNA duplex is necessary for stable simultaneous expression of both genes. Lack of this dsRNA structure results in a loss of a wider DNA opening and in consequence transcriptional interference. We also concluded that forming R-loops probably plays only a supplementary role and is not required for proper expression ofHIRIP3andINO80Egene transcripts.
Identification and Characterization of a Novel Nematode Pan Allergen (NPA) fromWuchereria bancroftiand their Potential Role in Human Filarial Tropical Pulmonary Eosinophilia (TPE)
Authors: Katru Samuel Christopher , Munirathinam Gnanasekar , Hadadianpour Azadeh , Balakrishnan Anand Setty , Smith Scott A. , Kalyansundaram Ramaswamy 
Published: December 2023

AbstractTropical pulmonary eosinophilia (TPE) is a chronic respiratory syndrome associated with Lymphatic Filariasis (LF), a tropical parasitic infection of the human, transmitted by mosquitoes. A larval form of LF, the microfilariae trapped in the lungs of TPE subjects have a major role in initiating the TPE syndrome. To date, there are no reports on the potential allergen that is responsible for generating parasite-specific IgE in TPE. In this project, we screened a cDNA expression library of the microfilarial stages ofWuchereria bancroftiwith monoclonal IgE antibodies prepared from subjects with clinical filarial infections. Our studies identified a novel molecule that showed significant sequence similarity to an allergen. A blast analysis showed the presence of similar proteins in a number of nematodes parasites. Thus, we named the molecule as Nematode Pan Allergen (NPA). Subsequent functional analysis showed that NPA is a potent allergen that can cause release of histamine from mast cells, induce secretion of proinflammatory cytokines from alveolar macrophages and promote accumulation of eosinophils, all of which occur in TPE lungs. Therefore, we believe that NPA may have a significant role in the pathology of the TPE syndrome.