bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for some antimicrobial properties of English churchyard lichens.
Authors: Taylor J A , Fourie T , Powell M , Chianella I 
Published: March 2023

The emergence of multidrug resistant bacteria has driven the need for novel antibiotics. Our investigations have focussed on lichens as they naturally produce a wide range of unique and very effective defence chemicals. The aim of this study was to evaluate some of the antimicrobial properties of ten common British churchyard lichens. The lichen material was sampled from 10 species, namely Caloplaca flavescens, Diploicia canescens, Cladonia fimbriata, Psilolechia lucida, Lecanora campestris subsp. Campestris, Lecanora sulphurea, Pertusaria amara f.amara, Lepraria incana, Porpidia tuberculosa and
Xanthoria calcicola. Crude acetone extracts of these lichens were tested against 6 bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonela typhimurium, Listeria monocytogenes and Lactobacillus acidophilus) and two fungi (Trichophyton interdigitale and Aspergillus flavus) by using the disc diffusion susceptibility test method. Extracts of Diploicia canescens, Psilolechia lucida, Lecanora sulphurea,Pertusaria amara and Lepraria incana showed clear inhibition of the Gram positive bacteria tested (S. aureus, L. monocytogenes, L. Plantarum). Diploicia canescens, Pertusaria amara and Lepraria incana extracts also inhibited the dermatophyte fungi tested. Lepraria incana’s extract was the only sample tested here that showed activity against any of the Gram negative bacteria tested and that was inhibition of Pseudomnas aeruginosa. Overall, our results showed that crude extracts of Diploicia canescens and Pertusaria amara had the most potent antimicrobial activity of all the extracts tested against the organisms in these studies. This finding is in agreement with published findings elsewhere. The activity of the Porpidia tuberculosa margin material being different from that of the main colony material was an interesting and new finding
Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder
Authors: Clancy KJ , Devignes Q , Kumar P , May V , Hammack SE , Akman E , Casteen EJ , Pernia CD , Jobson SA , Lewis MW , Daskalakis NP , Carlezon WA , Ressler KJ , Rauch SL , Rosso IM 
Published: March 2023

AbstractThe pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.
Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease
Authors: Jujo Kentaro , Ueshima Daisuke , Abe Takuro , Shimazaki Kensuke , Fujimoto Yo , Tanaka Tomofumi , Murata Teppei , Miyazaki Toru , Matsumoto Michiaki , Tokuyama Hideo , Shimura Tsukasa , Funada Ryuichi , Murata Naotaka , Higashitani Michiaki 
Published: March 2023

ABSTRACTBackgroundStatins bring favorable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD.MethodsThis study was a sub-analysis of a multicenter prospective cohort of 2,321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1,974 patients (1,021 statin users and 953 non-users) were ultimately analyzed. Enrolled patients were classified into four groups depending on CRP levels: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category.ResultsOverall, statin users showed a significantly lower event rate than non-users (log-rank, p<0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories (p=0.02 and p=0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95% confidence interval: 0.41–0.98]).ConclusionStatins may exert favorable prognostic effects in patients with PAD and highly elevated CRP levels but not in those with low to moderate CRP levels.Condensed abstractThis multicenter retrospective study compared the prognostic effects of statins among patients with peripheral arterial disease (PAD) presenting diverse baseline C-reactive protein (CRP) levels [low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL)]. Multivariable analysis showed that statin use was independently associated with a lower rate of death, stroke, myocardial infarction, and major amputation only in the high-CRP category. This suggests that statins may have favorable prognostic effects in patients with PAD and active inflammation.
Impact of Anemia on Outcomes and Resource Utilization in Patients with Myocardial Infarction: A National Database Analysis
Authors: Jhand Aravdeep S. , Abusnina Waiel , Tak Hyo Jung , Ahmed Arslan , Ismayl Mahmoud , Altin S. Elissa , Sherwood Matthew W. , Alexander John H. , Rao Sunil V. , Abbott J. Dawn , Carson Jeffrey L. , Goldsweig Andrew M. 
Published: March 2023

AbstractBackgroundAlthough anemia is common in patients with myocardial infarction (MI), management remains controversial. We quantified the association of anemia with in-hospital outcomes and resource utilization in patients admitted with MI using a large national database.MethodsAll hospitalizations with a primary diagnosis code for acute MI in the National Inpatient Sample (NIS) between 2014 and 2018 were identified. Among these hospitalizations, patients with anemia were identified using a secondary diagnosis code. Data on demographic and clinical variables were collected. Outcomes of interest included in-hospital adverse events, length of stay (LOS), and total cost. Multivariable logistic regression and generalized linear models were used to evaluate the relationship between anemia and outcomes.ResultsAmong 1,113,181 MI hospitalizations, 254,816 (22.8%) included concomitant anemia. Anemic patients were older and more likely to be women. After adjustment for demographics and comorbidities, anemia was associated with higher mortality (7.1 vs. 4.3%; odds ratio 1.09; 95% confidence interval [CI] 1.07-1.12, p<0.001). Anemia was also associated with a mean of 2.71 days longer LOS (average marginal effects [AME] 2.71; 95% CI 2.68-2.73, p<0.05), and higher total costs (mean cost $9,703 higher; AME $9703, 95% CI $9,577-$9,829, p<0.05). Anemic patients who received blood transfusions had higher mortality as compared with those who did not (8.2% vs. 7.0, p<0.001).ConclusionIn MI patients, anemia was associated with higher in-hospital mortality, adverse events, total cost, and length of stay. Transfusion was associated with increased mortality, and its role in MI requires further research.
Balanced nitrogen-iron nutrition boosts grain yield and nitrogen use efficiency in rice and wheat
Authors: Wu Jie , Song Ying , Wang Jing-Xian , Wan Guang-Yu , Zhang Zi-Sheng , Xia Jin-Qiu , Sun Liang-Qi , Lu Jie , Ma Chuan-Xi , Yu Lin-Hui , Xiang Cheng-Bin 
Published: March 2023

AbstractNutrients must be balanced for optimal plant growth. However, the potential significance of balanced nitrogen-iron (N-Fe) for improving crop yield and nitrogen use efficiency (NUE) has never been addressed. Here, we show that balanced N-Fe substantially increases tiller number and boosts yield and NUE in rice and wheat. NIN-like protein 4 plays a pivotal role in maintaining the N-Fe balance by coordinately regulating the expression of multiple genes in N and Fe metabolism and signaling. Moreover, we show that foliar spraying of balanced N-Fe at the tillering stage can effectively increase rice tillers, yield and NUE in the field, which can be reproduced with wheat. Our findings provide guidelines for innovative fertilization to reduce N fertilizer input and promote yield, thus benefitting environment-friendly and sustainable agriculture worldwide.
Lorazepam stimulates IL-6 production and is associated with poor survival outcomes in pancreatic cancer
Authors: Cornwell Abigail C. , Tisdale Arwen A. , Venkat Swati , Maraszek Kathryn E. , Alahmari Abdulrahman A. , George Anthony , Attwood Kristopher , George Madison , Rempinski Donald , Franco-Barraza Janusz , Parker Mark D. , Gomez Eduardo Cortes , Fountzilas Christos , Cukierman Edna , Steele Nina G. , Feigin Michael E. 
Published: March 2023

AbstractPurposeThis research investigates the association between benzodiazepines (BZDs) and cancer patient survival outcomes. Due to the high prevalence of BZD use in pancreatic cancer patients, we evaluated the effect of commonly prescribed BZDs on the pancreatic cancer tumor microenvironment and cancer-associated fibroblast (CAF) signaling.Experimental DesignMultivariate Cox regression modeling was used to retrospectively measure associations between Roswell Park cancer patient survival outcomes and BZD prescription records. Immunohistochemistry, H&E, Masson’s trichrome,in situhybridization, and RNA sequencing were used to evaluate the impact of lorazepam (LOR) on the PDAC tumor microenvironment, using murine pancreatic cancer models. ELISA and qPCR were used to determine the impact of BZDs on IL-6 expression/secretion by human immortalized pancreatic CAFs. PRESTO-Tango assays, reanalysis of PDAC single cell sequencing/TCGA datasets, and GPR68 CRISPRi knockdown CAF cells were used to mechanistically determine the impact of BZDs on CAF-specific GPR68 signaling.ResultsLOR is associated with worse progression-free survival (PFS) while alprazolam (ALP) is associated with improved PFS, in pancreatic cancer patients receiving chemotherapy. LOR promotes desmoplasia (fibrosis and extracellular matrix protein deposition), inflammatory signaling, IL-6 expression/secretion in CAFs, and ischemic necrosis. LOR promotes inflammatory signaling and IL-6 secretion by CAFs through activation of GPR68. GPR68 is preferentially expressed on human PDAC CAFs, and n-unsubstituted BZDs significantly increase GPR68 activation under acidic conditions. LOR increases IL-6 expression and secretion in CAFs in a pH and GPR68-dependent manner. Conversely, ALP, and other GPR68 non-activator BZDs decrease IL-6 in human CAFs in a pH and GPR68-independent manner. Across many cancer types, LOR is associated with worse survival outcomes relative to ALP and patients not receiving BZDs.ConclusionWe demonstrate that LOR stimulates fibrosis and inflammatory signaling, promotes ischemic necrosis, and is associated with decreased pancreatic cancer patient survival.
Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia
Authors: Guardiola-Ripoll Maria , Almodóvar-Payá Carmen , Arias-Magnasco Angelo , Latorre-Guardia Mariona , Papiol Sergi , Canales-Rodríguez Erick J , García-León María Ángeles , Fuentes-Claramonte Paola , Salavert Josep , Tristany Josep , Torres Llanos , Rodríguez-Cano Elena , Salvador Raymond , Pomarol-Clotet Edith , Fatjó-Vilas Mar 
Published: March 2023

ABSTRACTSchizophrenia (SZ) is hypothesised to represent a costly trade-off in the evolution of the neurodevelopmental ontogenetic mechanisms associated with human-specific cognitive capacities. Human Accelerated Regions (HARs) are evolutionary conserved genomic regions that have accumulated human-specific sequence changes. These evolutionary markers function as neurodevelopmental transcription enhancers and have been associated with the brain’s cortical expansion and connectivity, the processing of neural information, and the risk for SZ. We sought to investigate whether HARs’ polygenic load influenced neuroanatomical measures.Our sample consisted of 128 patients with SZ and 115 healthy controls with high-resolution structural T1 MRI and genome-wide genotyping data. We extracted the cortical thickness (CT) and surface area (SA) for the 34 Desikan-Killiany regions per hemisphere. We calculated four polygenic risk scores (PRS): SZ genetic load (Global PRSSZ), HARs’ specific variability (HARs PRSSZ), HARs’ variability associated with transcriptional regulatory elements uniquely active in the foetal brain (FB-HARs PRSSZ) and in the adult brain (AB-HARs PRSSZ). Through linear regression analyses, we explored whether these four PRSs modulated CT and SA within diagnostic groups and the PRSs and diagnostic interaction on the cortical measures.Results indicate that FB-HARs PRSSZinfluenced patients’ right SA on the lateral orbitofrontal cortex, the superior temporal cortex, the pars triangularis and the paracentral lobule and that a higher SZ risk load in FB-HARs is associated with lower SA values.These findings evidence the involvement of the HARs-foetal gene regulatory activity in SA architecture and the evolutionary component of this regulation in SZ. These data emphasise the importance of HARs in the transcriptional regulatory machinery from early neurodevelopment and their role as the bridging point between the neurodevelopmental and evolutionary hypotheses in SZ.
Rare Comorbidity between Inflammatory Bowel Disease and Primary Biliary Cholangitis: Evidence from Causality, Shared Genetic Architecture and Transcriptomics
Authors: Huang Wentao , Jiang Rui , Zeng Ruijie , Ma Yuying , Zhang Lijun , Tong Shuangshuang , Lyu Yanlin , Wang Jiaxuan , Leung Felix W , Sha Weihong , Chen Hao 
Published: March 2023

AbstractBackgroundClinical studies have found comorbidity between Inflammatory Bowel Disease (IBD) and primary sclerosing cholangitis (PSC). Primary biliary cholangitis (PBC) is another autoimmune liver disease but the coexistence of IBD and PBC is rare. Whether there exists comorbidity between IBD and PBC and potential mechanism remains unclear.MethodsWe assessed the casual effect between PBC and IBD, i.e., Crohn Disease (CD) and Ulcerative Colitis (UC) independently based on genome-wide association studies (GWAS) summary statistics. By leveraging data from GWAS data, Bulk tissue RNA sequencing (bulk RNA-seq) data, and Single-cell RNA sequencing (scRNA-seq) dataset, we investigated the shared genetic architecture between IBDs and PBC. The transcriptomic expressions of shared genes were explored in patients with IBD (intestinal biopsies) and PBC (peripheral CD4+T cells).ResultWe found a bidirectional causal relationship for PBC and IBDs using Mendelian randomization. The IBDs had been considered as the protective factors on PBC (0.87[95% confidence interval (CI): 0.81-0.93],P= 8.72e-5, vice versa (0.91[95% CI: 0.81-0.93],P= 2.65e-09). We find a consistent negative genetic correlation between PBC and IBD (LDSC:rg= -0.2245,P= 2.89e-5). Cross-trait analysis yielded 9 shared risk SNPs and 7 nearest genes. In transcriptome analysis, we observed significant (P< 0.05) differences expression in intestinal biopsies (PGAP3andDENND1B) and in peripheral CD4+T cells (PTPN11andPNMT). We identified shared tissue-specific heritability enrichment for PBC and IBD (including CD not UC) in lung, spleen and cells EBV-transformed lymphocytes and identified shared cell type-level enrichment for IBD, CD and PBC in type 1 dendritic cells, natural killer cells, CD8+cytotoxic T lymphocytes in lung and activated CD8+T cell in spleen.ConclusionOur study indicates that IBD and PBC are protective factors for each other and shared genetic architecture may contribute to the negative genetic correlation. These findings may explain the rare comorbidity between IBD and PBC.
A Novel Collaborative Learning Model for Teeth and Fillings in Radiographs
Authors: Bumann Erin Ealba , Al-Qarni Saeed , Chandrashekar Geetha , Sabzian Roya , Bohaty Brenda , Lee Yugyung 
Published: March 2023

AbstractIt is critical for dentists to identify and differentiate primary and permanent teeth, fillings, dental restorations and areas with pathological findings when reviewing dental radiographs to ensure that an accurate diagnosis is made and the optimal treatment can be planned. Unfortunately, dental radiographs are sometimes read incorrectly due to human error or low-quality images. While secondary or group review can help catch errors, many dentists work in practice alone and/or do not have time to review all of their patients’ radiographs with another dentist. Artificial intelligence may facilitate the accurate interpretation of radiographs. To help support the review of panoramic radiographs, we developed a novel collaborative learning model that simultaneously identifies and differentiates primary and permanent teeth and detects fillings. We used publicly accessible dental panoramic radiographic images and images obtained from the University of Missouri-Kansas City School of Dentistry to develop and optimize two high-performance classifiers: (1) a system for tooth segmentation that can differentiate primary and permanent teeth and (2) a system to detect dental fillings. By utilizing these high-performance classifiers, we created models that can identify primary and permanent teeth, as well as their associated dental fillings. We also designed a novel method for collaborative learning that utilizes these two classifiers to enhance recognition performance. Our model improves upon the existing machine learning models to simultaneously identify and differentiate primary and permanent teeth, and to identify any associated fillings.
Functional host-specific adaptation of the intestinal microbiome in hominids
Authors: Rühlemann MC , Bang C , Gogarten JF , Hermes BM , Groussin M , Waschina S , Poyet M , Ulrich M , Akoua-Koffi C , Deschner T , Muyembe-Tamfum JJ , Robbins MM , Surbeck M , Wittig RM , Zuberbühler K , Baines JF , Leendertz FH , Franke A 
Published: March 2023

SummaryFine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we performed high-resolution metagenomic-based analyses of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in humans populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer new and exciting insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids, demonstrating that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.
Fast and accurate DNASeq Variant Calling workflow composed of LUSH toolkit
Authors: Wang Taifu , Zhang Youjin , Wang Haoling , Zheng Qiwen , Yang Jiaobo , Zhang Tiefeng , Sun Geng , Liu Weicong , Yin Longhui , He Xinqiu , You Rui , Wang Chu , Liu Zhencheng , Liu Zhijian , Wang Jin’an , Jin Xiangqian , He Zengquan 
Published: March 2023

AbstractBackgroundWhole genome sequencing (WGS) is becoming increasingly prevalent for molecular diagnosis, staging and prognosis because of its declining costs and the ability to detect nearly all genes associated with a patient’s disease. The currently widely accepted variant calling pipeline, GATK, is limited in terms of its computational speed and efficiency, which cannot meet the growing analysis needs.MethodsIn this study, we propose a fast and accurate DNASeq variant calling workflow that is purely composed of tools from LUSH toolkit. The LUSH pipeline is highly optimized for the WGS pipeline based on SOAPnuke, BWA and GATK which can be deployed on any general-purpose CPU-based computing system. We validated the accuracy, speed and scalability of the LUSH pipeline on several standard WGS datasets.ResultsOur test results show that the LUSH pipeline and the GATK pipeline are highly consistent in terms of accuracy, achieving over 99% precision and recall on NA12878. For speed, the LUSH pipeline completes 30x WGS data in 1.6 hours, which is about 17x faster than the GATK pipeline. From BAM to VCF, LUSH_HC even takes only 12 minutes, about 76x faster than GATK. Moreover, the LUSH pipeline shows favorable scalability in terms of thread and sequencing depth.ConclusionThe LUSH pipeline provides far superior computational speed to GATK while maintaining a high level of accuracy comparable to that of GATK, which greatly facilitates bedside analysis of acute patients, large-scale cohort data analysis, and variant calling in crop breeding programs.