bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Prevalence of Pulmonary Tuberculosis Patients at Nakfa Hospital from 2014-2019, Eritrea
Authors: Kesete Yafet 
Published: February 2020

AbstractBackgroundTuberculosis, an infectious disease, is one of the top 10 causes of death, and the leading cause from a single infectious agent M. tuberculosis. According to recent WHO estimate report, at least 3100 new TB cases occur every year in Eritrea. However, very little information is available in Eritrea related to area specific prevalence of tuberculosis and risk factors attributed to it. This is a retrospective study aimed to assess the prevalence of tuberculosis disease among patients attending at Nakfa Hospital, Eritrea.MethodsA retrospective study was conducted on patients visiting Nakfa Hospital, 221km north of Asmara, Eritrea from April 2014 to March 2019. Data was extracted from secondary data sources like patient admission records and laboratory registers at Nakfa Hospital.ResultsA total of 1100 patients were examined for tuberculosis using acid fast staining test. The overall prevalence of smear positive pulmonary TB cases was 7.8% (86 cases out of 1100). Females (8.2%) were more prone to have a positive Tuberculosis smear than males (7.4%). According to severity of infection, 38(3.5%) of subjects were +1 positive, whereas 23(2.1%) and 24(2.2%) of patients were +2 and +3 positives respectively. The highest prevalence of pulmonary TB was observed in the adult age group of 41-60 years (11%) and a comparatively higher number of cases was recorded in age group 21-40 years (8.3%). Adults aged between 41 to 60 had a two times more likelihood to be infected with Tuberculosis than those aged below 20 years old. Moreover, pulmonary tuberculosis was highly prevalent among middle age (20-60) than any other age class in all study years (2014-2019). The pulmonary TB cases were highly predominant during the year 2014 which was 16.8% (19 of 113 subjects) whereas the almost a quarter of it (4.5%) was recorded in following year. Based on locality, the highest rate of infection was observed in Adobha (25%), a town at border of Sudan and Eritrea, in which patients who came from Adobha had 4 times more likelihood to be infected than those from Nakfa town.ConclusionThis study showed Nakfa subzone has relatively increased prevalence of smear positive pulmonary tuberculosis than the average WHO estimate for the country. Therefore, appropriate policies and strategies for prevention, targeted detection of cases and treatment are required to reinforce Tuberculosis control programs.
Predicting loss of independence and mortality in frontotemporal lobar degeneration syndromes
Authors: Murley Alexander G. , Rouse Matthew A. , Coyle-Gilchrist Ian , Jones P Simon , Li Win , Wiggins Julie , Lansdall Claire , Rodriguez Patricia Vazquez , Wilcox Alicia , Patterson Karalyn , Rowe James B. 
Published: February 2020

AbstractObjectiveTo test the hypothesis that in syndromes associated with frontotemporal lobar degeneration, behavioural impairment predicts loss of functional independence and motor clinical features predict mortality, irrespective of syndrome subtype.MethodWe used a transdiagnostic approach to survival in an epidemiological cohort, testing the association between clinical features, independence and survival in patients with clinical diagnoses of behavioural variant frontotemporal dementia (n=64), non-fluent variant primary progressive aphasia (n=36), semantic variant primary progressive aphasia (n=25), progressive supranuclear palsy (n=101) and corticobasal syndrome (n=68). A principal components analysis identified six dimensions of clinical features. Using Cox proportional hazards and logistic regression we identified the association between each of these dimensions and functionally independent survival (time from clinical assessment to care home admission), and absolute survival (time to death). Analyses adjusted for the covariates of age, gender and diagnostic group. Secondary analysis excluded specific diagnostic groups.ResultsBehavioural disturbance, including impulsivity and apathy, was associated with reduced functionally independent survival (OR 2.46, p<0.001), even if patients with bvFTD were removed from the analysis. Motor impairments were associated with reduced absolute survival, even if patients with PSP and CBS were removed from the analysis.ConclusionOur results may help individualised prognostication and planning of disease-modifying trials and support a transdiagnostic approach to symptomatic treatment trials in patients with clinical syndromes associated with frontotemporal lobar degeneration.
Optimal timing for cancer screening and adaptive surveillance using mathematical modeling
Authors: Curtius Kit , Dewanji Anup , Hazelton William D. , Rubenstein Joel H. , Luebeck E. Georg 
Published: February 2020

AbstractCancer screening and early detection efforts have been partially successful in reducing incidence and mortality but many improvements are needed. Although current medical practice is mostly informed by epidemiological studies, the decisions for guidelines are ultimately madead hoc. We propose that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and to optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain “window of opportunity” for intervention when early cancer development may be observable. Alternative to a strictly empirical approach, or microsimulations of a multitude of possible scenarios, biologically-based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett’s esophagus (BE), we applied our methods for a model of esophageal adenocarcinoma (EAC) that was previously calibrated to US cancer registry data. We found optimal screening ages for patients with symptomatic gastroesophageal reflux disease to be older (58 for men, 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Our framework captures critical aspects of cancer evolution within BE patients for a more personalized screening design.SignificanceOur study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes. Surveillance regimes could also be improved if they were based on these models.Graphical Abstract
A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer
Authors: López de Maturana E , Rodríguez JA , Alonso L , Lao O , Molina-Montes E , Martín-Antoniano I , Gómez-Rubio P , Lawlor RT , Carrato A , Hidalgo M , Iglesias M , Molero X , Löhr M , Michalski CW , Perea J , O’Rorke M , Barberà VM , Tardón A , Farré A , Muñoz-Bellvís L , Crnogorac-Jurcevic T , Domínguez-Muñoz E , Gress T , Greenhalf W , Sharp L , Arnes L , Cecchini Ll , Balsells J , Costello E , Ilzarbe L , Kleeff J , Kong B , Márquez M , Mora J , O’Driscoll D , Scarpa A , Ye W , Yu J ,   PanGenEU Investigators, García-Closas M , Kogevinas M , Rothman N , Silverman D ,   SBC/EPICURO Investigators, Albanes D , Arslan AA , Beane-Freeman L , Bracci PM , Brennan P , Bueno-de-Mesquita B , Buring J , Canzian F , Du M , Gallinger S , Gaziano JM , Goodman PJ , Gunter M , LeMarchand L , Li D , Neale RE , Peters U , Petersen GM , Risch HA , Sánchez MJ , Shu XO , Thornquist MD , Visvanathan K , Zheng W , Chanock S , Easton D , Wolpin BM , Stolzenberg-Solomon RZ , Klein AP , Amundadottir LT , Marti-Renom MA , Real FX , Malats N 
Published: February 2020

ABSTRACTPancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To-date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. Here, we complemented a classical new PC GWAS (1D) with spatial autocorrelation analysis (2D) and Hi-C maps (3D) to gain additional insight into the inherited basis of PC.In-silicofunctional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. We replicated 17/40 previous PC-GWAS hits and identified novel variants with potential biological functions. The spatial autocorrelation approach prioritized low MAF variants not detected by GWAS. These were further expanded via 3D interactions to 54 target regions with high functional relevance. This multi-step strategy, combined with an in-depthin-silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.
read_haps: using read haplotypes to detect same species contamination in DNA sequences
Authors: Eggertsson Hannes P. , Halldorsson Bjarni V. 
Published: February 2020

AbstractMotivationData analysis is requisite on reliable data. In genetics this includes verifying that the sample is not contaminated with another, a problem ubiquitous in biology.ResultsIn human, and other diploid species, DNA contamination from the same species can be found by the presence of three haplotypes between polymorphic SNPs. read_haps is a tool that detects sample contamination from short read whole genome sequencing data.Availabilitygithub.com/DecodeGenetics/read_hapsContactbjarni.halldorsson@decode.is
Design and fabrication of recombinant reflectin-based Bragg reflectors: bio-design engineering and photoisomerism induced wavelength modulation
Authors: Wolde-Michael Emmanuel , Roberts Aled D , Heyes Derren J , Dumanli Ahu G , Blaker Jonny J , Takano Eriko , Scrutton Nigel S 
Published: February 2020

ABSTRACTThe remarkable camouflage capabilities of cephalopods have inspired many to develop dynamic optical materials which exploit certain design principles and/or material properties from cephalopod dermal cells. Here, the angle-dependent optical properties of various single-layer reflectin thin-films are characterized within the UV-Vis-NIR regions. Following this, the design and fabrication of the first bio-inspired reflectin-based Bragg reflector is described, which was found to conserve the optical properties of single layer films but exhibit a unique characteristic; reduced angle-dependent reflectivity. Finally, a novel method of controlling reflectin thin-film optical properties is introduced; visible light-induced photoisomerism, representing a new class of reflectin-based optical materials.
Selective LXR agonist, DMHCA, corrects the retina-bone marrow axis in type 2 diabetes
Authors: Vieira Cristiano P. , Fortmann Seth D. , Hossain Masroor , Longhini Ana Leda , Hammer Sandra S. , Asare-Bediako Bright , Crossman David K. , Sielski Micheli S. , Adu-Agyeiwaah Yvonne , Dupont Mariana , Floyd Jason L. , Calzi Sergio Li , Lydic Todd , Welner Robert S , Blanchard Gary J. , Busik Julia V. , Grant Maria B. 
Published: February 2020

ABSTRACTIn diabetic dyslipidemia, cholesterol accumulates in the plasma membrane, decreasing fluidity and thereby suppressing the ability of cells to transduce ligand-activated signaling pathways. Liver X receptors (LXRs) are the main cellular mechanism by which intracellular cholesterol is regulated and play important roles in inflammation and disease pathogenesis. N,N-dimethyl-3β-hydroxy-cholenamide (DMHCA), a selective LXR agonist, specifically activates the cholesterol efflux arm of the LXR pathway without stimulating triglyceride synthesis. Thus, DMHCA possesses superior clinical potential as a cholesterol lowering agent than current LXR pan-agonist. In this study, we use a multi-systems approach to understand the effects and molecular mechanisms of DMHCA treatment in type 2 diabetic db/db mice and human -derived circulating angiogenic cells (CACs), which are vascular reparative cells. We find that DMHCA is sufficient to correct the retina-bone marrow (BM) axis in diabetes, thereby restoring retinal structure, function, and cholesterol homeostasis, rejuvenating membrane fluidity in circulating vascular reparative cells, hampering systemic inflammation, and correcting BM dysfunction. Using single-cell RNA-seq on lineage-sca1+cKit+(LSK) hematopoietic stem cells (HSCs) from untreated and DMHCA-treated diabetic mice, we provide novel insights into hematopoiesis and reveal DMHCA’s mechanism of action in correcting diabetic HSCs by reducing myeloidosis and increasing CACs and erythrocyte progenitors. Taken together, these findings demonstrate the broad and pleiotropic effects of DMHCA treatment, which has exciting potential to correct the retina-BM axis in diabetic subjects.
IGF-I Governs Cortical Inhibitory Synaptic Plasticity By Astrocyte Activation
Authors: Noriega-Prieto José Antonio , Maglio Laura Eva , Zegarra-Valdivia Jonathan A. , Pignatelli Jaime , Fernandez Ana M. , Martinez-Rachadell Laura , Fernandes Jansen , Núñez Ángel , Araque Alfonso , Alemán Ignacio Torres , de Sevilla David Fernández 
Published: February 2020

ABSTRACTInsulin-like growth factor-I (IGF-I) signaling plays key regulatory roles in multiple processes of brain physiology and pathology. While the direct effects of IGF-I in neurons have been extensively studied, the astrocyte involvement in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. Here we show that IGF-I induces the long-term depression (LTD) of inhibitory synaptic transmission in the mouse barrel cortex. This LTD requires the activation of the IGF-I receptor (IGF-IR) in astrocytes, which stimulates astrocyte Ca2+signaling and the release of ATP/adenosine that in turn activates A2Aadenosine receptors at presynaptic inhibitory terminals. Specific deletion of IGF-IR in cortical astrocytes (IGF-IR-/-) impaired the behavioral performance in a whisker discrimination task. These results show novel mechanisms and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing astrocytes as key elements in these processes.
Multimodal finger-printing of the human precentral cortex forming the motor hand knob
Authors: Dubbioso Raffaele , Madsen Kristoffer Hougaard , Thielscher Axel , Siebner Hartwig Roman 
Published: February 2020

AbstractTranscranial magnetic stimulation (TMS) of the precentral hand knob can evoke motor evoked potentials (MEP) in contralateral hand muscles. Biophysical modelling points to the dorsal premotor cortex (PMd) in the superficial crown-lip region as primary site of TMS-induced neuronal excitation. Here, we used a sulcus-aligned MRI-informed TMS mapping approach to determine the optimal site (hotspot) for evoking MEPs in the precentral hand knob. Individual precentral hotspot location varied along the rostro-caudal axis. Individuals with a more rostral location had longer MEP latencies. Spatiotemporal “hotspot rostrality” was associated with higher precentral myelin-related signals, stronger movement-related activation of PMd in the precentral crown, and higher temporal precision during paced finger tapping. Together, our multimodal mapping approach provides first-time evidence for behaviourally relevant, structural and functional phenotypic variation in the crown of human precentral motor hand knob. The results have important implications for physiological and interventional TMS studies targeting the precentral hand knob.
Recognition of A Highly Conserved DSRCPTQ Epitope in Envelope Protein of Zika Virus Throughin silicoApproaches
Authors: Rahman Anisur , Hossain Md. Iqbal , Tamanna Saheda , Ullah Md Neamat 
Published: February 2020

AbstractThe recurrent and recent outbreak of Zika Virus (ZIKV) has turned into global concern as yet there is no appropriate preventive measure been found. Situation getting worse as this virus also associates with several birth defects in neonatal such as primary microcephaly as well as many other neurological disorders. ZIKV adopts a wide host range which has hastened its expansion more recklessly. Hence, now there is an acute demand for developing a preventive vaccine against ZIKV. Immunoinformatic techniques have been employed in this study to pick out a highly conserved versatile antigenic B-cell linear epitope for all strains of ZIKV. Capsid protein (C), Membrane Glycoprotein Precursor (PrM), envelope protein (E) and RNA-dependent RNA Polymerase (NS5) have investigated by the implementation of sequence analysis and different epitope prediction methods. Some potential linear peptides have been recognized and tested for hydrophilicity and conservancy. Peptide with best antigenic properties was selected as ultimate final epitope and further structural exploration revealed its compatible position in protein 3D structure. Being fully conserved in all strains of ZIKV and its position in Envelope protein suggested epitope DSRCPTQ can be a quantum leap in the advancement of ZIKV prevention. However, extensivein vitroplusin vivoexperimentations are needed to be clarified about the real potency of the selected epitope.
A genome-wide screen for genes affecting spontaneous direct-repeat recombination inSaccharomyces cerevisiae
Authors: Novarina Daniele , Desai Ridhdhi , Vaisica Jessica A. , Ou Jiongwen , Bellaoui Mohammed , Brown Grant W. , Chang Michael 
Published: February 2020

ABSTRACTHomologous recombination is an important mechanism for genome integrity maintenance, and several homologous recombination genes are mutated in various cancers and cancer-prone syndromes. However, since in some cases homologous recombination can lead to mutagenic outcomes, this pathway must be tightly regulated, and mitotic hyper-recombination is a hallmark of genomic instability. We performed two screens inSaccharomyces cerevisiaefor genes that, when deleted, cause hyper-recombination between direct repeats. One was performed with the classical patch and replica-plating method. The other was performed with a high-throughput replica-pinning technique that was designed to detect low-frequency events. This approach allowed us to validate the high-throughput replica-pinning methodology independently of the replicative aging context in which it was developed. Furthermore, by combining the two approaches, we were able to identify and validate 35 genes whose deletion causes elevated spontaneous direct-repeat recombination. Among these are mismatch repair genes, the Sgs1-Top3-Rmi1 complex, the RNase H2 complex, genes involved in the oxidative stress response, and a number of other DNA replication, repair and recombination genes. Since several of our hits are evolutionary conserved, and repeated elements constitute a significant fraction of mammalian genomes, our work might be relevant for understanding genome integrity maintenance in humans.
Platelet TSP-1 Controls Prostate Cancer-Induced Osteoclast Differentiation and Bone Marrow-Derived Cell Mobilization through TGFβ-1
Authors: Kerr Bethany A. , Harris Koran S. , Shi Lihong , Willey Jeffrey S. , Soto-Pantoja David R. , Byzova Tatiana V. 
Published: February 2020

ABSTRACTThe development of distant metastasis is the main cause of prostate cancer (CaP)-related death with the skeleton being the primary site of metastasis. While the progression of primary tumors and the growth of bone metastatic tumors are well described, the mechanisms controlling pre-metastatic niche formation and homing of CaP to bone remain unclear. Through prior studies, we demonstrated that platelet secretion was required for ongoing tumor growth and pre-metastatic tumor-induce bone formation and bone marrow-derived cell mobilization to cancers supporting angiogenesis. We hypothesized that proteins released by the platelet α granules were responsible for inducing changes in the pre-metastatic bone niche. We found that the classically anti-angiogenic protein thrombospondin (TSP)-1 was significantly increased in the platelets of mice bearing tumors. To determine the role of increased TSP-1, we implanted tumors in TSP-1 null animals and assessed changes in tumor growth and pre-metastatic niche formation. TSP-1 loss resulted in increased tumor size and enhanced angiogenesis but reduced bone marrow-derived cell mobilization and tumor-induced bone formation with enhanced osteoclast formation. We hypothesized that these changes in the pre-metastatic niche were due to the retention of TGF-β1 in the platelets of mice with TSP-1 deleted. To assess the importance of platelet-derived TGF-β1, we implanted CaP tumors in mice with platelet-specific deletion of TGF-β1. Similar to TSP-1 deletion, loss of platelet TGF-β1 resulted in increased angiogenesis with a milder effect on tumor size and BMDC release. Within the bone microenvironment, platelet TGF-β1 deletion prevented tumor-induced bone formation due to increased osteoclastogenesis. Thus, we demonstrate that the TSP-1/TGF-β1 axis regulates pre-metastatic niche formation and tumor-induced bone turnover. Targeting the platelet release of TSP-1 or TGF-β1 represents a potential method to interfere with the process of CaP metastasis to bone.
Replication protein A binds RNA and promotes R-loop formation
Authors: Mazina Olga M. , Somarowthu Srinivas , Kadyrova Lyudmila Y. , Baranovskiy Andrey G. , Tahirov Tahir H. , Kadyrov Farid A. , Mazin Alexander V. 
Published: February 2020

SUMMARYReplication protein A (RPA), a major eukaryotic ssDNA-binding protein, is essential for all metabolic processes that involve ssDNA including DNA replication, repair, and damage signaling. Surprisingly, we found here that RPA binds RNAin vitrowith high affinity. Using native RIP method, we isolated RNA-RPA complexes from human cells. Furthermore, RPA promotes R-loop formation between RNA and homologous dsDNA. R-loops, the three-stranded nucleic acid structure consisting of an RNA-DNA hybrid and the displaced ssDNA strand, are common in human genome. R-loops may play an important role in transcription-coupled homologous recombination and DNA replication restart. We reconstituted the process of replication restartin vitrousing RPA-generated R-loops and human DNA polymerases. These findings indicate that RPA may play a role in RNA metabolism and suggest a mechanism of genome maintenance that depends on RPA and RNA.
Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation
Authors: Huebner Robert J. , Malmi-Kakkada Abdul Naseer , Sarikaya Sena , Weng Shinuo , Thirumalai D. , Wallingford John B. 
Published: February 2020

AbstractMorphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at sub-cellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of a vertebrate embryo, we combine tools from cell biology and physics to demonstrate that individual cell-cell junctions display finely-patterned local mechanical heterogeneity along their length. We show that such local mechanical patterning is essential for the cell movements of convergent extension and is imparted by locally patterned clustering of a classical cadherin. Finally, the patterning of cadherins and thus local mechanics along cell-cell junctions are controlled by Planar Cell Polarity signaling, a key genetic module for CE that is mutated in diverse human birth defects.