bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clopidogrel resistance is common in patients undergoing vascular and coronary interventions
Authors: Berenson Adam M , Hawken Thomas N , Fort Daniel G , Money Samuel R , Ramee Stephen R , Sternbergh Waldemar Charles , Bazan Hernan A 
Published: January 2022

Objectives “Clopidogrel resistance,” also defined as heightened platelet reactivity (HPR) while on clopidogrel therapy, may lead to a sub-optimal antiplatelet effect and a potential thrombotic event. There is limited literature addressing the prevalence of HPR in a large cohort of patients receiving either coronary or endovascular interventions. Methods In a large integrated healthcare system, patients with a P2Y12 reaction units (PRU) test were identified. HPR was defined as a PRU ≥ 200 during clopidogrel therapy. Vascular and coronary interventions were identified utilizing CPT codes, HPR prevalence was calculated, and Fischer’s exact test was used to determine significance. Results From an initial cohort of 2,405,957 patients (October 2014 to January 2020), we identified 3301 patients with PRU tests administered. Of these, 1789 tests had a PRU ≥ 200 (HPR overall prevalence, 54%). We then identified 1195 patients who underwent either an endovascular or coronary procedure and had a PRU measurement. This corresponded to 935 coronary and 260 endovascular interventions. In the coronary cohort, the HPR prevalence was 54% (503/935). In the vascular cohort, the HPR prevalence was 53% (137/260); there was no difference between cohorts in HPR prevalence ( p = 0.78). Conclusion “Clopidogrel resistance” or HPR was found to be present in nearly half of patients with cardiovascular disease undergoing intervention. Our data suggest HPR is more common in the cardiovascular patient population than previously appreciated. Evaluating patients for HPR is both inexpensive ($25) and rapid (< 10 min). Future randomized studies are warranted to determine whether HPR has a clinically detectable effect on revascularization outcomes.
Epidemiology of Traumatic Posterior Hip Instability in the National Football League
Authors: Ackermann Jakob , Saxena Vishal , Whalen Jim , Mack Christina D. , Herzog Mackenzie , Probst Jessica R. , Price Mark D. 
Published: January 2022

Background: There is a paucity of literature regarding injury incidence, mechanism, and return to play in National Football League (NFL) players who have sustained traumatic posterior hip instability. Purpose: To describe the incidence of traumatic posterior hip instability and the rate of return to play in NFL players across 18 seasons. Study Design: Descriptive epidemiology study. Methods: We retrospectively assessed all traumatic posterior hip dislocations/subluxations that occurred during football-related activities in the NFL seasons from 2000 through 2017. Player demographics and injury data (injury mechanism, season of injury, treatment, days missed, and return to play time) were collected from all 32 NFL teams prospectively through a leaguewide electronic health record system. Descriptive statistics are presented. Results: Across the 18 NFL seasons, 16 posterior hip instability injuries in 14 players were reported, with a maximum incidence of 4 (25%) in 2013. Posterior hip instability was predominantly sustained by offensive players (64.3%), with tight ends being the most affected (31.3%). Half of the injuries occurred during the regular season, 43.8% in the preseason, and 6.2% in the offseason. Of all injuries, 37.5% were noncontact, while 56.3% involved contact (direct or indirect), and 6.2% were of unknown mechanism. Among noncontact injuries, 66.7% occurred during cutting and change of direction while sprinting. The time of return to full participation was documented for 11 of the 16 reported injuries (68.8%); among them, the mean time loss was 136.7 ± 83.8 days—143.3 ± 99.6 days if the player underwent surgery (n = 4) and 116.7 ± 76.2 days missed by players without surgery (n = 6)—the treatment modality was unknown in 1 player. Conclusion: Although the incidence of traumatic posterior hip instability during the study period was low, all injured athletes missed time from football activities and competitions. Injuries that required surgery led to more missed time than those that did not. Ongoing research to understand risk factors and mechanisms of this injury, in conjunction with improvements to prevention and rehabilitation protocols, is necessary to ensure the safety of professional American football players.
A new murine model of Barth syndrome neutropenia links TAFAZZIN deficiency to increased ER stress-induced apoptosis
Authors: Sohn Jihee , Milosevic Jelena , Brouse Thomas , Aziz Najihah , Elkhoury Jenna , Wang Suya , Hauschild Alexander , van Gastel Nick , Cetinbas Murat , Tufa Sara F. , Keene Douglas R. , Sadreyev Ruslan I. , Pu William T. , Sykes David B. 
Published: January 2022

Abstract
Barth syndrome is an inherited X-linked disorder that leads to cardiomyopathy, skeletal myopathy, and neutropenia. These symptoms result from the loss of function of the enzyme TAFAZZIN, a transacylase located in the inner mitochondrial membrane that is responsible for the final steps of cardiolipin production. The link between defective cardiolipin maturation and neutropenia remains unclear. To address potential mechanisms of neutropenia, we examined myeloid progenitor development within the fetal liver of TAFAZZIN knockout (KO) animals as well as within the adult bone marrow of wild-type recipients transplanted with TAFAZZIN-KO hematopoietic stem cells. We also used the ER-Hoxb8 system (estrogen receptor fused to Hoxb8) of conditional immortalization to establish a new murine model system for the ex vivo study of TAFAZZIN-deficient neutrophils. The TAFAZZIN-KO cells demonstrated the expected dramatic differences in cardiolipin maturation that result from a lack of TAFAZZIN enzyme activity. Contrary to our hypothesis, we did not identify any significant differences in neutrophil development or neutrophil function across a variety of assays including phagocytosis and the production of cytokines or reactive oxygen species. However, transcriptomic analysis of the TAFAZZIN-deficient neutrophil progenitors demonstrated an upregulation of markers of endoplasmic reticulum stress and confirmatory testing demonstrated that the TAFAZZIN-deficient cells had increased sensitivity to certain ER stress-mediated and non-ER stress-mediated triggers of apoptosis. Although the link between increased sensitivity to apoptosis and the variably penetrant neutropenia phenotype seen in some patients with Barth syndrome remains to be clarified, our studies and new model system set a foundation for further investigation.
Compression enhances invasive phenotype and matrix degradation of breast cancer cells via Piezo1 activation
Authors: Luo Mingzhi , Cai Grace , Ho Kenneth K. Y. , Wen Kang , Tong Zhaowen , Deng Linhong , Liu Allen P. 
Published: January 2022

Abstract
Background
Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation.

Results
Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content.

Conclusions
Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.
Determine independent gut microbiota-diseases association by eliminating the effects of human lifestyle factors
Authors: Zhu Congmin , Wang Xin , Li Jianchu , Jiang Rui , Chen Hui , Chen Ting , Yang Yuqing 
Published: January 2022

AbstractLifestyle and physiological variables on human disease risk have been revealed to be mediated by gut microbiota. Low concordance between case-control studies for detecting disease-associated microbe existed due to limited sample size and population-wide bias in lifestyle and physiological variables. To infer gut microbiota-disease associations accurately, we propose to build machine learning models by including both human variables and gut microbiota. When the model’s performance with both gut microbiota and human variables is better than the model with just human variables, the independent gut microbiota -disease associations will be confirmed. By building models on the American Gut Project dataset, we found that gut microbiota showed distinct association strengths with different diseases. Adding gut microbiota into human variables enhanced the classification performance of IBD significantly; independent associations between occurrence information of gut microbiota and irritable bowel syndrome, C. difficile infection, and unhealthy status were found; adding gut microbiota showed no improvement on models’ performance for diabetes, small intestinal bacterial overgrowth, lactose intolerance, cardiovascular disease. Our results suggested that although gut microbiota was reported to be associated with many diseases, a considerable proportion of these associations may be very weak. We proposed a list of microbes as biomarkers to classify IBD and unhealthy status. Further functional investigations of these microbes will improve understanding of the molecular mechanism of human diseases.
An antimicrobial peptide specifically active against Listeria monocytogenes is secreted by Bacillus pumilus SF214
Authors: Saggese Anella , De Luca Ylenia , Baccigalupi Loredana , Ricca Ezio 
Published: January 2022

Abstract
Background
Members of the Bacillus genus produce a large variety of antimicrobial peptides including linear or cyclic lipopeptides and thiopeptides, that often have a broad spectrum of action against Gram-positive and Gram-negative bacteria. We have recently reported that SF214, a marine isolated strain of Bacillus pumilus, produces two different antimicrobials specifically active against either Staphylococcus aureus or Listeria monocytogenes. The anti-Staphylococcus molecule has been previously characterized as a pumilacidin, a nonribosomally synthesized lipopetide composed of a mixture of cyclic heptapeptides linked to fatty acids of variable length.

Results
Our analysis on the anti-Listeria molecule of B. pumilus SF214 indicated that it is a peptide slightly smaller than 10 kDa, produced during the exponential phase of growth, stable at a wide range of pH conditions and resistant to various chemical treatments. The peptide showed a lytic activity against growing but not resting cells of Listeria monocytogenes and appeared extremely specific being inactive also against L. innocua, a close relative of L. monocytogenes.

Conclusions
These findings indicate that the B. pumilus peptide is unusual with respect to other antimicrobials both for its time of synthesis and secretion and for its strict specificity against L. monocytogenes. Such specificity, together with its stability, propose this new antimicrobial as a tool for potential biotechnological applications in the fight against the dangerous food-borne pathogen L. monocytogenes.
MYB transcription factor family in sweet cherry (Prunus avium L.): genome-wide investigation, evolution, structure, characterization and expression patterns
Authors: Sabir Irfan Ali , Manzoor Muhammad Aamir , Shah Iftikhar Hussain , Liu Xunju , Zahid Muhmmad Salman , Jiu Songtao , Wang Jiyuan , Abdullah Muhammad , Zhang Caixi 
Published: January 2022

Abstract
Back ground
MYB Transcription factors (TFs) are most imperative and largest gene family in plants, which participate in development, metabolism, defense, differentiation and stress response. The MYB TFs has been studied in various plant species. However, comprehensive studies of MYB gene family in the sweet cherry (Prunus avium L.) are still unknown.

Results
In the current study, a total of 69 MYB genes were investigated from sweet cherry genome and classified into 28 subfamilies (C1-C28 based on phylogenetic and structural analysis). Microcollinearity analysis revealed that dispersed duplication (DSD) events might play an important role in the MYB genes family expansion. Chromosomal localization, the synonymous (Ks) and nonsynonymous (Ka) analysis, molecular characteristics (pI, weight and length of amino acids) and subcellular localization were accomplished using several bioinformatics tools. Furthermore, the members of distinct subfamilies have diverse cis-acting regions, conserved motifs, and intron-exon architectures, indicating functional heterogeneity in the MYB family. Moreover, the transcriptomic data exposed that MYB genes might play vital role in bud dormancy. The quantitative real-time qRT-PCR was carried out and the expression pattern indicated that MYB genes significantly expressed in floral bud as compared to flower and fruit.

Conclusion
Our comprehensive findings provide supportive insights into the evolutions, expansion complexity and functionality of PavMYB genes. These PavMYB genes should be further investigated as they seem to be brilliant candidates for dormancy manipulation in sweet cherry.
Novel insights into water-deficit-responsive mRNAs and lncRNAs during fiber development in Gossypium hirsutum
Authors: Wu Nan , Yang Jun , Wang Guoning , Ke Huifeng , Zhang Yan , Liu Zhengwen , Ma Zhiying , Wang Xingfen 
Published: January 2022

AbstractBackgroundThe fiber yield and quality of cotton are greatly and periodically affected by water deficit. However, the molecular mechanism of the water deficit response in cotton fiber cells has not been fully elucidated.ResultsIn this study, water deficit caused a significant reduction in fiber length, strength, and elongation rate but a dramatic increase in micronaire value. To explore genome-wide transcriptional changes, fibers from cotton plants subjected to water deficit (WD) and normal irrigation (NI) during fiber development were analyzed by transcriptome sequencing. Analysis showed that 3427 mRNAs and 1021 long noncoding RNAs (lncRNAs) from fibers were differentially expressed between WD and NI plants. The maximum number of differentially expressed genes (DEGs) and lncRNAs (DERs) was identified in fibers at the secondary cell wall biosynthesis stage, suggesting that this is a critical period in response to water deficit. Twelve genes in cotton fiber were differentially and persistently expressed at ≥ five time points, suggesting that these genes are involved in both fiber development and the water-deficit response and could potentially be used in breeding to improve cotton resistance to drought stress. A total of 540 DEGs were predicted to be potentially regulated by DERs by analysis of coexpression and genomic colocation, accounting for approximately 15.76% of all DEGs. Four DERs, potentially acting as target mimics for microRNAs (miRNAs), indirectly regulated their corresponding DEGs in response to water deficit.ConclusionsThis work provides a comprehensive transcriptome analysis of fiber cells and a set of protein-coding genes and lncRNAs implicated in the cotton response to water deficit, significantly affecting fiber quality during the fiber development stage.
Identification of Pueraria spp. through DNA barcoding and comparative transcriptomics
Authors: Adolfo Laci M. , Rao Xiaolan , Dixon Richard A. 
Published: January 2022

Abstract
Background
Kudzu is a term used generically to describe members of the genus Pueraria. Kudzu roots have been used for centuries in traditional Chinese medicine in view of their high levels of beneficial isoflavones including the unique 8-C-glycoside of daidzein, puerarin. In the US, kudzu is seen as a noxious weed causing ecological and economic damage. However, not all kudzu species make puerarin or are equally invasive. Kudzu remains difficult to identify due to its diverse morphology and inconsistent nomenclature.

Results
We have generated sequences for the internal transcribed spacer 2 (ITS2) and maturase K (matK) regions of Pueraria montana lobata, P. montana montana, and P. phaseoloides, and identified two accessions previously used for differential analysis of puerarin biosynthesis as P. lobata and P. phaseoloides. Additionally, we have generated root transcriptomes for the puerarin-producing P. m. lobata and the non-puerarin producing P. phaseoloides. Within the transcriptomes, microsatellites were identified to aid in species identification as well as population diversity.

Conclusions
The barcode sequences generated will aid in fast and efficient identification of the three kudzu species. Additionally, the microsatellites identified from the transcriptomes will aid in genetic analysis. The root transcriptomes also provide a molecular toolkit for comparative gene expression analysis towards elucidation of the biosynthesis of kudzu phytochemicals.
Asynapsis and unreduced gamete formation in a Trifolium interspecific hybrid
Authors: Ansari Helal A. , Ellison Nicholas W. , Verry Isabelle M. , Williams Warren M. 
Published: January 2022

AbstractBackgroundUnreduced gametes, a driving force in the widespread polyploidization and speciation of flowering plants, occur relatively frequently in interspecific or intergeneric hybrids. Studies of the mechanisms leading to 2ngamete formation, mainly in the wheat tribeTriticeaehave shown that unreductional meiosis is often associated with chromosome asynapsis during the first meiotic division. The present study explored the mechanisms of meiotic nonreduction leading to functional unreduced gametes in an interspecificTrifolium(clover) hybrid with three sub-genomes fromT. ambiguumand one sub-genome fromT. occidentale.ResultsUnreductional meiosis leading to 2ngametes occurred when there was a high frequency of asynapsis during the first meiotic division. In this hybrid, approximately 39% of chromosomes were unpaired at metaphase I. Within the same cell at anaphase I, sister chromatids of univalents underwent precocious separation and formed laggard chromatids whereas paired chromosomes segregated without separation of sister chromatids as in normal meiosis. This asynchrony was frequently accompanied by incomplete or no movement of chromosomes toward the poles and restitution leading to unreduced chromosome constitutions. Reductional meiosis was restored in progeny where asynapsis frequencies were low. Two progeny plants with approximately 5 and 7% of unpaired chromosomes at metaphase I showed full restoration of reductional meiosis.ConclusionsThe study revealed that formation of 2ngametes occurred when asynapsis (univalent) frequency at meiosis I was high, and that normal gamete production was restored in the next generation when asynapsis frequencies were low. Asynapsis-dependent 2ngamete formation, previously supported by evidence largely from wheat and its relatives and grasshopper, is also applicable to hybrids from the dicotyledonous plant genusTrifolium. The present results align well with those from these widely divergent organisms and strongly suggest common molecular mechanisms involved in unreduced gamete formation.
Slope analysis for the prediction of fluid responsiveness by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients
Authors: Vallier Sylvain , Bouchet Jean-Baptiste , Desebbe Olivier , Francou Camille , Raphael Darren , Tardy Bernard , Gergele Laurent , Morel Jérôme 
Published: January 2022

Abstract
Objective
Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients by analyzing the variations in central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device.

Design
Prospective observational cohort study.

Setting
Intensive Care Unit, Saint-Etienne University Central Hospital.

Patients
Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCO™), requiring volume expansion, with no right ventricular dysfunction.
Interventions.
None.

Measurements and main results
CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL fluid expansion to asses fluid responsiveness. 25 patients were screened and 18 patients analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamic parameters suggested the use of a linear regression model. Slopes for systolic arterial pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during the pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p = 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, prediction of fluid responsiveness can be achieved with 100% sensitivity and 100% specificity (AUC = 0.96; 95% CI, 0.90 to 1.00). One patient showed inconclusive values using the grey zone approach (5.5%).

Conclusions
In patients under mechanical ventilation with no right heart dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath LRM seems to offer a very promising method for prediction of fluid responsiveness without the use and associated cost of a cardiac output measurement device.

Trial registration
NCT04304521, IRBN902018/CHUSTE. Registered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP)