bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-infections of human herpesviruses (CMV, HHV-6, HHV-7 and EBV) in non-transplant acute leukemia patients undergoing chemotherapy
Authors: Handous Imene , Achour Bechir , Marzouk Manel , Rouis Sana , Hazgui Olfa , Brini Ines , Khelif Abderrahim , Hannachi Naila , Boukadida Jalel 
Published: March 2020

Abstract
Background
Human herpesviruses (HHVs) remain latent after primary infection and can be reactivated in response to immunosuppression and chemotherapy. Little is known about their incidence, potential relationships, risk factors and clinical impact in non-transplant leukemia patients.
This study investigated prospectively incidence, risk factors, clinical impact and possible association of HHVs-(1–7) infections in patients with newly diagnosed acute leukemia.

Methods
Study design involved longitudinal sampling before chemotherapy and in different phases of chemotherapy: post-induction, post-remission, and post-salvage during 2016–2018. A total of 734 plasma samples from 95 patients were analyzed by a qualitative, multiplex PCR for HHVs detection and a quantitative real-time PCR was used for cytomegalovirus (CMV) quantification. HHVs-(1–6) IgG and IgM antibodies were tested using immunoassays. Risk factors were analyzed by binary logistic regression and relationships between viruses were analyzed using the Chi-square or Fisher’s exact test as appropriate.

Results
The overall seroprevalences of HHV-(1–6) IgG were high (> 80%). At least one herpes viral agent was detected in 60 patients (63.3%). CMV was the most commonly detected virus in the different phases of chemotherapy (19.4%), followed by HHV-6 (9.7%), HHV-7 (5.2%) and EBV (2.7%). HSV-1/2 and VZV DNA were not detected. Twenty-seven patients (28.4%) had more than one virus detected in the follow-up, with 23 who were co-infected. CMV/HHV-6 was the most frequent co-infection (69.5%, 16/23). HHV-6 infection (p = 0.008) was identified as a risk factor for CMV infection while salvage treatment (p = 0.04) and CMV infection (p = 0.007) were found to be independent risk factors for HHV-6 infection. CMV co-infection was associated with severe lymphopenia with an absolute lymphocyte count (ALC) (< 500/μL) (p = 0.009), rash (p = 0.011), pneumonia (p = 0.016) and opportunistic infections [bacteremia, p < 0.001 and invasive fungal infection, (p = 0.024)] more frequently than CMV mono-viral infections.

Conclusions
Our data suggest that co-infection with HHVs, especially CMV and HHV-6, may contribute to the development of serious clinical manifestations with profound lymphopenia, pneumonia rash and increased risk for bacterial and fungal co-infections. These findings may suggest the synergistic effect of HHVs associated infection.
Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders
Authors:   EuroEPINOMICS-RES Consortium, Lal Dennis , May Patrick , Perez-Palma Eduardo , Samocha Kaitlin E. , Kosmicki Jack A. , Robinson Elise B. , Møller Rikke S. , Krause Roland , Nürnberg Peter , Weckhuysen Sarah , De Jonghe Peter , Guerrini Renzo , Niestroj Lisa M. , Du Juliana , Marini Carla , Ware James S. , Kurki Mitja , Gormley Padhraig , Tang Sha , Wu Sitao , Biskup Saskia , Poduri Annapurna , Neubauer Bernd A. , Koeleman Bobby P. C. , Helbig Katherine L. , Weber Yvonne G. , Helbig Ingo , Majithia Amit R. , Palotie Aarno , Daly Mark J. 
Published: March 2020

Abstract
Background
Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs.

Methods
Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families.

Results
We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint.

Conclusion
This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes.
Mesenchymal stem cells ameliorate myocardial fibrosis in diabetic cardiomyopathy via the secretion of prostaglandin E2
Authors: Jin Liyuan , Zhang Jinying , Deng Zihui , Liu Jiejie , Han Weidong , Chen Guanghui , Si Yiling , Ye Ping 
Published: March 2020

Abstract
Background
Diabetic cardiomyopathy (DCM) is a cardiac complication of long-term uncontrolled diabetes and is characterized by myocardial fibrosis and abnormal cardiac function. Mesenchymal stem cells (MSCs) are multipotent cells with immunoregulatory and secretory functions in diabetes and heart diseases. However, very few studies have focused on the effect and the underlying mechanism of MSCs on myocardial fibrosis in DCM. Therefore, we aimed to explore the therapeutic potential of MSCs in myocardial fibrosis and its underlying mechanism in vivo and in vitro.

Methods
A DCM rat model was induced using a high-fat diet (HFD) combined with a low-dose streptozotocin (STZ) injection. After four infusions of MSCs, rat serum and heart tissues were collected, and the levels of blood glucose and lipid, cardiac structure, and function, and the degree of myocardial fibrosis including the expression levels of pro-fibrotic factor and collagen were analyzed using biochemical methods, echocardiography, histopathology, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). We infused prostaglandin E2 (PGE2)-deficient MSCs to DCM rats in vivo and established a system mimicking diabetic myocardial fibrosis in vitro by inducing cardiac fibroblasts with high glucose (HG) and coculturing them with MSCs or PGE2-deficient MSCs to further explore the underlying mechanism of amelioration of myocardial fibrosis by MSCs.

Results
Metabolic abnormalities, myocardial fibrosis, and cardiac dysfunction in DCM rats were significantly ameliorated after treatment with MSCs. Moreover, the levels of TGF-β, collagen I, collagen III, and collagen accumulation were markedly decreased after MSC infusion compared to those in DCM hearts. However, PGE2-deficient MSCs had decreased ability to alleviate cardiac fibrosis and dysfunction. In addition, in vitro study revealed that the concentration of PGE2 in the MSC group was enhanced, while the proliferation and collagen secretion of cardiac fibroblasts were reduced after MSC treatment. However, MSCs had little effect on alleviating fibrosis when the fibroblasts were pretreated with cyclooxygenase-2 (COX-2) inhibitors, which also inhibited PGE2 secretion. This phenomenon could be reversed by adding PGE2.

Conclusions
Our results indicated that MSC infusion could ameliorate cardiac fibrosis and dysfunction in DCM rats. The underlying mechanisms might involve the function of PGE2 secreted by MSCs.
Dynorphin activation of kappa opioid receptor promotes microglial polarization toward M2 phenotype via TLR4/NF-κB pathway
Authors: Liu Lin , Xu Yingtong , Dai Hongmei , Tan Shan , Mao Xiao , Chen Zhiheng 
Published: March 2020

AbstractBackgroundMicroglia-mediated neuroinflammation is associated with epilepsy. Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for mitigating epileptogenesis. We previously found that dynorphins protected against epilepsy via activation of kappa opioid receptor (KOR). Here, this study aims to investigate the role and the mechanism of dynorphin in regulating microglial polarization.MethodsA pilocarpine-induced rat model of epilepsy was established and lipopolysaccharide (LPS)-activated BV-2 microglial cells were used as an inflammatory model to explore the mechanism of dynorphin regulating microglial polarization.ResultsOverexpression of the dynorphin precursor protein prodynorphin (PDYN) alleviated the pilocarpine-induced neuronal apoptosis, promoted microglial polarization to the M2 phenotype, and inhibited pilocarpine-induced Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in the hippocampi of epileptic rats. Dynorphin activation of KOR promoted microglial M2 polarization via inhibiting TLR4/NF-κB pathway in LPS-stimulated BV-2 microglial cells. Moreover, dynorphin/KOR regulated microglial M2 polarization inhibited apoptosis of the primary mouse hippocampal neurons.ConclusionIn conclusion, dynorphin activation of KOR promotes microglia polarization toward M2 phenotype via inhibiting TLR4/NF-κB pathway.
Adverse drug reactions associated with amitriptyline — protocol for a systematic multiple-indication review and meta-analysis
Authors: Brueckle Maria-Sophie , Thomas Elizabeth T. , Seide Svenja E. , Pilz Maximilian , Gonzalez-Gonzalez Ana Isabel , Nguyen Truc Sophia , Harder Sebastian , Glasziou Paul P. , Gerlach Ferdinand M. , Muth Christiane 
Published: March 2020

Abstract
Background
Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals.

Methods
A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment.

Discussion
We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.

Systematic review registration
Submitted to PROSPERO; assignment is in progress.
A blockchain-based smart home gateway architecture for preventing data forgery
Authors: Lee Younghun , Rathore Shailendra , Park Jin Ho , Park Jong Hyuk 
Published: March 2020

AbstractWith the advancement of Information and Communication Technology (ICT) and the proliferation of sensor technologies, the Internet of Things (IoT) is now being widely used in smart home for the purposes of efficient resource management and pervasive sensing. In smart homes, various IoT devices are connected to each other, and these connections are centered on gateways. The role of gateways in the smart homes is significant, however, its centralized structure presents multiple security vulnerabilities such as integrity, certification, and availability. To address these security vulnerabilities, in this paper, we propose a blockchain-based smart home gateway network that counters possible attacks on the gateway of smart homes. The network consists of three layers including device, gateway, and cloud layers. The blockchain technology is employed at the gateway layer wherein data is stored and exchanged in the form blocks of blockchain to support decentralization and overcome the problem from traditional centralized architecture. The blockchain ensures the integrity of the data inside and outside of the smart home and provides availability through authentication and efficient communication between network members. We implemented the proposed network on the Ethereum blockchain technology and evaluated in terms of standard security measures including security response time and accuracy. The evaluation results demonstrate that the proposed security solutions outperforms over the existing solutions.
Effects of respiratory rate on venous-to-arterial CO2 tension difference in septic shock patients undergoing volume mechanical ventilation
Authors: Guo Zhixiang , Wang Yapeng , Xie Chao , Hua Guofang , Ge Shenglin , Li Yuedong 
Published: March 2020

Abstract
Background
To explore the effects of the respiratory rate (RR) on the venous-to-arterial CO2 tension difference (gapCO2) in septic shock patients undergoing volume mechanical ventilation.

Methods
Adult patients with septic shock underwent volume mechanical ventilation between October 2015 and October 2016. RR was started at 10 breaths/min, and 2 breaths/min were added every 60 min until 16 breaths/min was reached. At every point, central venous and arterial blood gas measurements were obtained simultaneously.

Results
In this study, gapCO2 induced by hyperventilation significantly increased, while the central venous carbon dioxide pressure (PvCO2) and the partial pressure of CO2 (PaCO2) in arteries decreased. The decreasing trend of the PaCO2 was more obvious than that of the PvCO2. HCO3− and ctCO2 were markedly decreased, when the RR was increased (P < 0.05). Central venous oxygen saturation (ScvO2) had a decreasing trend between 14 (77.1 ± 8.3%) and 16 (75.2 ± 8.7%) breaths/min; however, the difference was not significant.

Conclusions
In septic patients undergoing ventilation, respiratory alkalosis induced by hyperventilation caused an increase in the gapCO2. Clinicians should cautiously interpret the gapCO2 in hemodynamically stable ventilated septic shock patients and its relationship with low cardiac output and inadequate perfusion.
Clinical study on the status of transient thyrotoxicosis after surgery for secondary hyperparathyroidism patients with end-stage renal disease and normal thyroid function
Authors: Zou Bao-shan , Liu Jia-shuo , Li Hong , Xu Zhou , Li Hao , Li Hong-yuan , Wu Kai-nan , Kong Ling-quan 
Published: March 2020

Abstract
Objective
Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease (ESRD), and part of SHPT patients need receive parathyroidectomy (PTX). However, as an important postoperative complication of SHPT, thyrotoxicosis has received little attention. Therefore, in this article, we aimed to study the status of transient thyrotoxicosis after PTX for SHPT patients with ESRD and normal thyroid function.

Methods
A total of 24 SHPT patients with preoperative normal thyroid function, normal thyroglobulin (Tg) and normal thyroid antibodies receiving PTX were enrolled from the Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, from January 2017 to January 2019. Tg, high sensitivity thyrotropin stimulating hormone (sTSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4) and free thyroxine (fT4) were evaluated the day before PTX and on day 1, 3 and 5 after PTX. Besides, all enrolled patients were evaluated whether there are symptoms associated with thyrotoxicosis.

Results
Among the 24 SHPT patients, 1 case (4.2%), 8 cases (33.3%) and 13 cases (54.2%) had suffered thyrotoxicosis at the first, third and fifth day after surgery, respectively. Serum FT4 level increased significantly from pre-operation (0.68 ± 0.15 ng/dl, normal range 0.59–1.25 ng/dl) to the third day after operation (1.91 ± 0.97 ng/dl, p<0.001) and then gradually decline. The frequencies of serum sTSH lower than the normal level gradually increased from the first day (8.3%) to fifth day (66.7%) after surgery.

Conclusion
Transient thyrotoxicosis is a common postoperative complication of parathyroidectomy for SHPT patients with ESRD and normal thyroid function, and it is necessary for clinicians to evaluate the perioperative thyroid function to make early diagnosis and appropriate prevention and treatment of thyrotoxicosis.
Best implant choice for coracoid graft fixation during the Latarjet procedure depends on patients’ morphometric considerations
Authors: Boutsiadis Achilleas , Bampis Ioannis , Swan John , Barth Johannes 
Published: March 2020

Abstract
Purpose
To assess the anthropometric dimensions of the coracoid process and the glenoid articular surface and to determine possible implications with the different commercially available Latarjet fixation techniques.

Methods
In a total of 101 skeletal scapulae the glenoid length (GL), the glenoid width (GW), the coracoid length (CL), the coracoid width (CW) and the coracoid thickness (CTh) were measured. In order to assess the ability of the transferred coracoid to restore the glenoid anatomy we created a hypothetical model of 10%, 15%, 20%, 25% and 30% glenoid bone loss. We analyzed four common surgical fixation techniques for the Latarjet procedure (4.5 mm screws, 3.75 mm screws, 3.5 mm screws, and 2.8 mm button). The distances from the superior-inferior and medio-lateral limits of the coracoid using the four different fixation methods were calculated. We hypothesized that the “safe distance” between the implant and the coracoid osteotomy should be at least equal to the diameter of the implant.

Results
The intra and inter-observer reliability tests were almost perfect for all measurements. The mean GH was 36.8 ± 2.5 mm, the GW 26.4 ± 2.2 mm, the CL 23.9 ± 3 mm, the CW 13.6 ± 2.mm, and the mean CTh was 8.7 ± 1.3 mm. The CL was < 25 mm in 46% of the cases. In cases with 25% and 30% bone loss, the coracoid graft restored the glenoid anatomy in 96% and 79.2% of the cases. With the use of the 4.5 mm screws the “safe distance” was present in 56% of the cases, with the 3.75 mm screws in 85%, with the 3.5 mm screws in 87%, and with the 2.8 mm button in 98% of the cases. The distance from the medio-lateral limit of the coracoid could be significantly increased (up to 9 mm) when smaller-button implants are used.

Conclusions
The coracoid graft could not always restore glenoid defects of 30%. Larger implants could be positioned too close to the osteotomy and the “medio-lateral offset” of the coracoid could be increased with smaller implants.
Whole genome phylogeny of Gallus: introgression and data-type effects
Authors: Tiley George P. , Pandey Akanksha , Kimball Rebecca T. , Braun Edward L. , Burleigh J. Gordon 
Published: March 2020

AbstractBackgroundPrevious phylogenetic studies that include the four recognized species ofGallushave resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to converge on a consistent topology, including introgression, incomplete lineage sorting, different data types, or insufficient data.MethodsWe generated three novel whole genome assemblies forGallusspecies, which we combined with data from the published genomes ofGallus gallusandBambusicola thoracicus(a member of the sister genus toGallus). To determine why previous studies have failed to converge on a single topology, we extracted large numbers of orthologous exons, introns, ultra-conserved elements, and conserved non-exonic elements from the genome assemblies. This provided more than 32 million base pairs of data that we used for concatenated maximum likelihood and multispecies coalescent analyses ofGallus.ResultsAll of our analyses, regardless of data type, yielded a single, well-supported topology. We found some evidence for ancient introgression involving specificGalluslineages as well as modest data type effects that had an impact on support and branch length estimates in specific analyses. However, the estimated gene tree spectra for all data types had a relatively good fit to their expectation given the multispecies coalescent.ConclusionsOverall, our data suggest that conflicts among previous studies probably reflect the use of smaller datasets (both in terms of number of sites and of loci) in those analyses. Our results demonstrate the importance of sampling large numbers of loci, each of which has a sufficient number of sites to provide robust estimates of gene trees. Low-coverage whole genome sequencing, as we did here, represents a cost-effective means to generate the very large data sets that include multiple data types that enabled us to obtain a robust estimate ofGallusphylogeny.
Why most patients do not exhibit obstructive sleep apnea after mandibular setback surgery?
Authors: Kim Jin-Wook , Kwon Tae-Geon 
Published: March 2020

AbstractMaxillomandibular advancement (MMA) is effective for the treatment of obstructive sleep apnea (OSA). In previous studies, the airway was increased in the anteroposterior and transverse dimensions after MMA. However, the effect of the opposite of mandibular movement (mandibular setback) on the airway is still controversial. Mandibular setback surgery has been suggested to be one of the risk factors in the development of sleep apnea. Previous studies have found that mandibular setback surgery could reduce the total airway volume and posterior airway space significantly in both the one-jaw and two-jaw surgery groups. However, a direct cause-and-effect relationship between the mandibular setback and development of sleep apnea has not been clearly established. Moreover, there are only a few reported cases of postoperative OSA development after mandibular setback surgery.These findings may be attributed to a fundamental difference in demographic variables such as age, sex, and body mass index (BMI) between patients with mandibular prognathism and patients with OSA. Another possibility is that the site of obstruction or pattern of obstruction may be different between the awake and sleep status in patients with OSA and mandibular prognathism. In a case-controlled study, information including the BMI and other presurgical conditions potentially related to OSA should be considered when evaluating the airway. In conclusion, the preoperative evaluation and management of co-morbid conditions would be essential for the prevention of OSA after mandibular setback surgery despite its low incidence.