bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early overnutrition in male mice negates metabolic benefits of a diet high in monounsaturated and omega-3 fats
Authors: Glavas Maria M. , Hui Queenie , Miao Ian , Yang Fan , Erener Suheda , Prentice Kacey J. , Wheeler Michael B. , Kieffer Timothy J. 
Published: July 2021

AbstractOverconsumption of saturated fats promotes obesity and type 2 diabetes. Excess weight gain in early life may be particularly detrimental by promoting earlier diabetes onset and potentially by adversely affecting normal development. In the present study we investigated the effects of dietary fat composition on early overnutrition-induced body weight and glucose regulation in Swiss Webster mice, which show susceptibility to high-fat diet-induced diabetes. We compared glucose homeostasis between a high-fat lard-based (HFL) diet, high in saturated fats, and a high-fat olive oil/fish oil-based (HFO) diet, high in monounsaturated and omega-3 fats. We hypothesized that the healthier fat profile of the latter diet would improve early overnutrition-induced glucose dysregulation. However, early overnutrition HFO pups gained more weight and adiposity and had higher diabetes incidence compared to HFL. In contrast, control pups had less weight gain, adiposity, and lower diabetes incidence. Plasma metabolomics revealed reductions in various phosphatidylcholine species in early overnutrition HFO mice as well as with diabetes. These findings suggest that early overnutrition may negate any beneficial effects of a high-fat diet that favours monounsaturated and omega-3 fats over saturated fats. Thus, quantity, quality, and timing of fat intake throughout life should be considered with respect to metabolic health outcomes.
Health economics modeling of antiretroviral interventions amongst HIV serodiscordant couples
Authors: Wu Haisheng , Yu Qiuyan , Ma Liping , Zhang Lin , Chen Yuliang , Guo Pi , Xu Peng 
Published: July 2021

AbstractAntiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for HIV-serodiscordant couples, effectively reduce mortality, transmission events and influence quality of life at the expense of increased costs. We aimed to evaluate health economics of antiretroviral-based strategies for HIV-serodiscordant couples in the China context. A deterministic model of HIV evolution and transmission within a cohort of serodiscordant couples was parameterized using the real-world database of Zhoukou city and published literature. We evaluated the mid-ART (a historical strategy, initiating ART with CD4 < 500 cells/mm3), early-ART (the current strategy, offering ART regardless of CD4 cell counts) and a hypothetical strategy (early-ART combined short-term daily PrEP) versus the late-ART (the baseline strategy, initiating ART with CD4 < 350 cells/mm3) offered by 2008 national guidelines. We estimated the incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR) from a societal perspective, derived by clinical benefits and HIV-caused life quality respectively, and portrayed their changes over a 0–30 year’s timeframe. The model projections indicated that the antiretroviral-based interventions were more likely to obtain clinical benefits but difficult to improve quality of life, and cumulative ICER and ICUR were generally decreasing without achieving cost-saving. Scale-up access to ART for the HIV-positive among serodiscordant couples was easily fallen within the range of paying for incremental life-years and quality adjusted life years by the societal willingness. The hypothetical strategy had the potential to prevent most seroconversion events within marriages but required enormous upfront costs, thus it took a long time to reach established thresholds. The current strategy of early-ART is the most cost-effective. Clarifying the obstacles of high cost of PrEP and improving life quality for HIV-serodiscordant couples have emerged as an urgent requisition.
SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy
Authors: Ji Xiaolin , Liu Yan , Mei Fang , Li Xinyang , Zhang Mengxue , Yao Buwen , Wu Rui , You Jiangfeng , Pei Fei 
Published: July 2021

AbstractThe screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer.
Detection of unknown ototoxic adverse drug reactions: an electronic healthcare record-based longitudinal nationwide cohort analysis
Authors: Lee Suehyun , Cha Jaehun , Kim Jong-Yeup , Son Gil Myeong , Kim Dong-Kyu 
Published: July 2021

AbstractOtotoxic medications can lead to significant morbidity. Thus, pre-marketing clinical trials have assessed new drugs that have ototoxic potential. Nevertheless, several ototoxic side effects of drugs may remain undetected. Hence, we sought to retrospectively investigate the potential risk of ototoxic adverse drug reactions among commonly used drugs via a longitudinal cohort study. An electronic health records-based data analysis with a propensity-matched comparator group was carried out. This study was conducted using the MetaNurse algorithm for standard nursing statements on electronic healthcare records and the National Sample Cohort obtained from the South Korea National Health Insurance Service. Five target drugs capable of causing ototoxic adverse drug reactions were identified using MetaNurse; two drugs were excluded after database-based analysis because of the absence of bilateral hearing loss events in patients. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio of bilateral hearing loss among patients who were prescribed candidate ototoxic drugs. The adjusted hazard ratio of bilateral hearing loss was 1.31 (1.03–1.68), 2.20 (1.05–4.60), and 2.26 (1.18–4.33) in cimetidine, hydroxyzine, and sucralfate users, respectively. Our results indicated that hydroxyzine and sucralfate may cause ototoxic adverse drug reactions in patients. Thus, clinicians should consider avoiding co-administration of these drugs with other well-confirmed ototoxic drugs should be emphasized.
Labelling experiments in red deer provide a general model for early bone growth dynamics in ruminants
Authors: Calderón Teresa , Arnold Walter , Stalder Gabrielle , Painer Johanna , Köhler Meike 
Published: July 2021

AbstractGrowth rates importantly determine developmental time and are, therefore, a key variable of a species' life history. A widely used method to reconstruct growth rates and to estimate age at death in extant and particularly in fossil vertebrates is the analysis of bone tissue apposition rates. Lines of arrested growth (LAGs) are of special interest here, as they indicate a halt in bone growth. However, although of great importance, the time intervals between, and particularly the reason of growth arrests remains unknown. Therefore, experiments are increasingly called for to calibrate growth rates with tissue types and life history events, and to provide reliable measurements of the time involved in the formation of LAGs. Based on in vivo bone labelling, we calibrated periods of bone tissue apposition, growth arrest, drift and resorption over the period from birth to post-weaning in a large mammal, the red deer. We found that bone growth rates tightly matched the daily weight gain curve, i.e. decreased with age, with two discrete periods of growth rate disruption that coincided with the life history events birth and weaning, that were visually recognisable in bone tissue as either partial LAGs or annuli. Our study identified for the first time in a large mammal a general pattern for juvenile bone growth rates, including periods of growth arrest. The tight correlation between daily weight gain and bone tissue apposition suggests that the red deer bone growth model is valid for ruminants in general where the daily weight gain curve is comparable.
Biomechanical evaluation of the human mandible after temporomandibular joint replacement under different biting conditions
Authors: Pinheiro Manuel , Willaert Robin , Khan Afaq , Krairi Anouar , Van Paepegem Wim 
Published: July 2021

AbstractTemporomandibular joint (TMJ) replacement with an implant is only used when all other conservative treatments fail. Despite the promising short-term results, the long-term implications of TMJ replacement in masticatory function are not fully understood. Previous human and animal studies have shown that perturbations to the normal masticatory function can lead to morphological and functional changes in the craniomaxillofacial system. A clearer understanding of the biomechanical implications of TMJ replacement in masticatory function may help identify design shortcomings that hinder their long-term success. In this study, patient-specific finite element models of the intact and implanted mandible were developed and simulated under four different biting tasks. In addition, the impact of re-attaching of the lateral pterygoid was also evaluated. The biomechanics of both models was compared regarding both mandibular displacements and principal strain patterns. The results show an excessive mediolateral and anteroposterior displacement of the TMJ implant compared to the intact joint in three biting tasks, namely incisor (INC), left moral (LML), and right molar (RML) biting. The main differences in principal strain distributions were found across the entire mandible, most notably from the symphysis to the ramus of the implanted side. Furthermore, the re-attachment of the lateral pterygoid seems to increase joint anteroposterior displacement in both INC, LML and RML biting while reducing it during LGF. Accordingly, any new TMJ implant design must consider stabilising both mediolateral and anteroposterior movement of the condyle during biting activities and promoting a more natural load transmission along the entire mandible.
Conserved residues in the extracellular loop 2 regulate Stachel-mediated activation of ADGRG2
Authors: Gad Abanoub A. , Azimzadeh Pedram , Balenga Nariman 
Published: July 2021

AbstractCleavage and dissociation of a large N-terminal fragment and the consequent unmasking of a short sequence (Stachel) remaining on the N-terminus have been proposed as mechanisms of activation of some members of the adhesion G protein-coupled receptor (aGPCR) family. However, the identity of residues that play a role in the activation of aGPCRs by the cognate Stachel remains largely unknown. Protein sequence alignments revealed a conserved stretch of residues in the extracellular loop 2 (ECL2) of all 33 members of the aGPCR family. ADGRG2, an orphan aGPCR, plays a major role in male fertility, Ewing sarcoma cell proliferation, and parathyroid cell function. We used ADGRG2 as a model aGPCR and generated mutants of the conserved residues in the ECL2 via site-directed mutagenesis. We show that tryptophan and isoleucine in the ECL2 are essential for receptor stability and surface expression in the HEK293 cells. By adjusting the receptor surface expression levels, we show that mutation of these residues of ECL2 ablates the Stachel-mediated activation of multiple signaling pathways of ADGRG2. This study provides a novel understanding of the role of the ECL2 in Stachel-mediated signaling and degradation of ADGRG2, which may lay the foundation for the rational design of therapeutics to target aGPCRs.
Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma
Authors: Schwinn Stefanie , Mokhtari Zeinab , Thusek Sina , Schneider Theresa , Sirén Anna-Leena , Tiemeyer Nicola , Caruana Ignazio , Miele Evelina , Schlegel Paul G. , Beilhack Andreas , Wölfl Matthias 
Published: July 2021

AbstractMedulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.
A recent update about seroprevalence of ovine neosporosis in Northern Egypt and its associated risk factors
Authors: Selim Abdelfattah , Khater Hanem , Almohammed Hamdan I. 
Published: July 2021

AbstractNeospora caninum (Family: Sarcocystidae) is an obligate intracellular protozoan. It is one of the most critical abortifacients in ruminants. The seroprevalence of antibodies against N. caninum and its risk factors was investigated among 430 sheep from four North Egyptian governorates, Alexandria, Gharbia, Menofia, and Qalyubia, during the period from 2017 to 2018. Generally, the overall prevalence rate of N. caninum among sheep was 8.6%. The logistic regression analysis for the obtained data revealed that N. caninum increased significantly with age (OR = 2.4, 95% CI: 8.4–18.7) of the ewe (OR = 3.3, 95% CI: 7.6–14.9), particularly among sheep in contact with dogs (OR = 4.9, 95% CI: 7.5–14.3). Besides, locality, season, and pregnancy status of examined sheep had no significant effect on the appearance of N. caninum infection. the present findings confirm the presence of N. caninum among sheep in Egypt which probably play a role in reproductive failure in sheep. Therefore, sanitary measures and monitoring of the infection should be implemented to reduce the spreading of the infection.
An engineered tetra-valent antibody fully activates the Tie2 receptor with comparable potency to its natural ligand angiopoietin-1
Authors: Koya Yukari , Nara Hiromi , Yagi Shigenori , Ueno Chihoko , Kamohara Masazumi 
Published: July 2021

AbstractActivation of the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor by angiopoietin-1 (Ang1) is critical for vascular stabilization: it promotes survival signal transduction via auto-phosphorylation and reduces vascular permeability by strengthening tight junctions between endothelial cells. Thus, Tie2/Ang1 signaling is a promising therapeutic target for vascular diseases. However, in vivo use of existing Tie2 signaling modulators, such as recombinant Ang1, is restricted by limitations in manufacturability and stability. Here, we present a novel engineered tetra-valent agonistic antibody, ASP4021, which can specifically and fully activate the Tie2 receptor in an equivalent manner to Ang1. ASP4021 induced Tie2 self-phosphorylation and inhibited apoptosis in a human primary endothelial cell line. Additionally, single administration of ASP4021 significantly suppressed mustard-oil-induced vascular permeability in rats. ASP4021 may thus be a potential therapeutic candidate for diseases associated with vascular weakness such as diabetic retinopathy, diabetic macular edema and critical limb ischemia.
Clinicopathological and prognostic significance of LINC00673 in human malignancy: a review and meta-analysis
Authors: Zhu Yurong , Zhang Zhifa , Peng Hui , Li Weiping , Hu Shaowei , Zhao Min , Lin Weifeng 
Published: July 2021

Abstract
Background: We conducted this research to investigate the relationship between long intergenic non-protein coding RNA 673 (linc00673) expression and prognosis and clinicopathological parameters in human malignancies.
Methods: The PubMed, Embase, WOS, and CNKI databases were used to collect eligible research data before 4 January 2021. Meta-analysis was performed using Stata 12.0 software. Pooled odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence interval (CIs) were calculated to evaluate the association of linc00673 expression with survival outcomes and clinical parameters.
Results: We finally included 17 articles and a total of 1539 cases for the meta-analysis. The results indicated that linc00673 was significantly correlated with T stage (P=0.006), tumor stage (P&lt;0.001), lymph node metastasis (P&lt;0.001), and distant metastasis (P&lt;0.001). In addition, the results suggested that elevated linc00673 expression predicted a poor overall survival (OS) time (P=0.013) and acted as an independent prognostic factor (P&lt;0.001) for OS in patients with malignancy. Although potential evidence of publication bias was found in the studies on OS in relation to tumor stage in the multivariate analysis, the trim-and-fill analysis confirmed that the results remained stable.
Conclusions: Overexpression of linc00673 was significantly correlated with shorter OS time in patients with malignant tumors. Moreover, the increased expression level of linc00673 was significantly correlated with T stage, tumor stage, lymph node metastasis, and distant metastasis. The results presented in this article revealed that linc00673 might be involved in the progression and invasion of malignancy and serve as a novel prognostic biomarker and potential therapeutic target for malignancy.
Minimal invasive prothetische Versorgung als wertvolle Alternative
zum kieferorthopädischen Lückenschluss bei
Zahnnichtanlagen
Authors: Kern Matthias 
Published: July 2021

ZusammenfassungUntere, aber auch obere zweite Prämolaren und obere laterale
Schneidezähne sind die am häufigsten nicht angelegten
Zähne; nicht selten sind auch untere Schneidezähne und erste
Prämolaren nicht angelegt. Im Rahmen einer kieferorthopädischen
Gesamttherapie ist der kieferorthopädische Lückenschluss eine
wertvolle Therapieoption, die aber längst nicht für alle
betroffenen Patientenfälle in Frage kommt.In diesen Fällen sollten die Lückenbreiten der nicht angelegten
Zähne zum Abschluss der kieferorthopädischen Therapie auf
adäquate Dimensionen eingestellt sein, um die Lücken
jugendlicher Patienten restaurativ zu versorgen. Minimal invasive
Adhäsivbrücken wurden lange Zeit von vielen nur als
provisorische Versorgung zur Überbrückung der Zeit bis zu einer
geplanten „definitiven“ Versorgung mit dentalen Implantaten
angesehen.Neuere wissenschaftliche Erkenntnisse zeigen jedoch, dass insbesondere
einflügelige Adhäsivbrücken zum Schneidezahnersatz
exzellente Langzeitergebnisse aufweisen, die denen von Einzelzahnimplantaten
nicht nachstehen oder sogar überlegen sind. Aber auch der Ersatz von
nicht angelegten Prämolaren mit einflügeligen
Adhäsivbrücken ist sehr vielversprechend.Dieser Beitrag fasst den wissenschaftlichen Stand der Versorgung von Patienten
mit minimal invasiven Adhäsivbrücken unter besonderer
Berücksichtigung der Versorgung jugendlicher Patienten mit
Zahnnichtanlagen zusammen.
Iridium-Catalyzed Transfer Hydrogenation for Construction of Quinolines from 2-Aminobenzyl Alcohols with Enones in Water
Authors: Luo Renshi , Luo Nanhua , Shui Hongling , Zhong Yuhong , Huang Jiuzhong 
Published: July 2021

AbstractHerein, we describe a method for the synthesis of functionalized quinolines from 2-aminobenzyl alcohols with α,β-unsaturated ketones. This method exhibits tolerance to various functional groups and high efficiency, is environmentally benign, and can be performed on a gram scale. Control experiments suggest that this transformation is accomplished by iridium complex catalyzed transfer hydrogenation, which is then followed by Friedländer cyclization. The results display that alkali is essential for the high selectivities of this catalytic system.
Effect of an Educational Intervention on the Knowledge about Traumatic Brain Injury Guidelines among Clinical Nurses
Authors: Subramaniam Sivakami , Prabhakar Preetham , Kanagaraj Umadevi , Baby Priya 
Published: July 2021

Abstract
Objective Traumatic brain injury (TBI) is a major cause of death and disability throughout the world including developing countries like India. Adherence to guideline based TBI management has proven to decrease death rate and improve neurological outcomes. This study aimed to assess the knowledge of TBI guidelines among clinical nurses caring for TBI patients, and to determine the effect of an educational intervention on their knowledge.
Methods Preexperimental, one group pretest and posttest design was used. A purposive sample of 60 nurses was included in the study. A structured questionnaire was prepared to assess the knowledge of nurses. Educational intervention was given in the form of a planned teaching program that was prepared based on the national TBI guidelines.
Results There was a significant gain in the knowledge scores of the nurses after the educational intervention when compared with the knowledge scores before the intervention (p = 0.001) Nurses who were experienced more than 10 years were found to have significantly higher knowledge score than others with lesser years of experience.
Discussion This study demonstrates important knowledge gap about TBI guidelines among clinical nurses. Educational interventions can be effectively used to improve the knowledge about TBI guidelines among nurses.