bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Apoptosis and PAI-1 are Involved in the Pro-Coagulant State of Immune Thrombocytopaenia Patients Treated with Thrombopoietin Receptor Agonists
Authors: Justo Sanz Raul , Monzón Manzano Elena , Fernández Bello Ihosvany , Teresa Álvarez Román Maria , Martín Salces Mónica , Rivas Pollmar Maria , Jiménez Yuste Víctor , Butta Nora 
Published: February 2019

AbstractThe treatment goal for patients with immune thrombocytopaenia (ITP) is to raise platelet counts to levels that minimize or stop bleeding. Thrombopoietin receptor agonists (TPO-RAs) have been successfully and extensively employed as second-line therapy for ITP. However, TPO-RAs have a small but significant increase in the risk of thrombosis. The aim of this study was to elucidate the mechanisms involved in the pro-coagulant effect of TPO-RAs to take them into account when considering their use in ITP patients with concomitant diseases/conditions that might increase risk of suffering thrombotic events. Eighty-two patients with chronic primary ITP (40 untreated and 42 undergoing TPO-RA therapy) and 112 healthy individuals were recruited. The patients with ITP undergoing TPO-RA therapy presented a pro-coagulant profile due to the formation of a more fibrinolysis-resistant clot because of increased plasminogen activator inhibitor-1 (PAI-1) levels. Increase in platelet content of PAI-1 might be the result of the effect of TPO-RA during megakaryopoiesis, as suggested by experiments performed in MEG-01 cells. Moreover, patients under TPO-RA treatment presented an enhanced pro-coagulant activity associated with microparticles and an increased platelet apoptosis that causes a higher exposure of phosphatidylserine and, consequently, a larger surface for the binding of the prothrombinase complex.
Sex‐related differences in joint‐angle‐specific hamstring‐to‐quadriceps function following fatigue
Authors: El‐Ashker Said , Allardyce Joanna M. , Carson Brian P. 
Published: February 2019

AbstractThe purpose of this study was to examine the effect of fatiguing exercise on sex‐related differences in the function of hamstring and quadriceps muscles at several angular velocities and joint angles. Physically active participants (50 male: 28.7 ± 4.5y, 1.82 ± 0.07 m, 82.3 ± 6.87 kg; 50 female: 27.0 ± 5.8y, 1.61 ± 0.08 m, 68.75 ± 9.24 kg) carried out an isokinetic assessment to determine concentric and eccentric torques during knee extension and flexion actions at three different angular velocities (60/180/300°/s). The H/QFUNCT was calculated using peak torque (PT) values at 3 different joint‐angle‐specific (15°, 30° and 45° of knee flexion). A repeated measures analysis of variance (ANOVA) was used to compare within group results. Between group comparisons of sex‐related differences were assessed by independent T‐tests. Fatiguing exercise in males resulted in a decrease in H/QFUNCT ratios for each angle of knee flexion at both 60°/s and 300°/s angular velocities (p < 0.05). In females, significant decreases in H/QFUNCT ratios were observed following fatiguing exercise for each angle of knee flexion and angular velocity (p < 0.01). Significant differences in H/QFUNCT ratios following fatiguing exercise were evident between males and females at each joint angle and angular velocity (p < 0.01). These findings indicate sex related differences in H/QFUNCT ratios following fatiguing exercise. Females have greater reductions in torque and H/QFUNCT ratios following fatigue than their male counterparts. This potentially exposes females to higher risks of injury, particularly when fatigued. Practitioners should attend to the imbalance in fatigue resistance of hamstring and quadriceps function, particularly in female athletes.
New simulation and analysis fiber Bragg grating: narrow bandwidth without side lobes
Authors: Toba Mofreh , Mustafa Fathy M , Barakat Tamer M 
Published: February 2019

Abstract
The purpose of this paper is to simulate and analyze the spectral characteristics of the fiber Bragg grating (FBG) to obtain narrow bandwidth and minimization side lobes in reflectivity. Fiber Bragg grating has made a big revolution in telecommunication systems. The existence of fiber Bragg grating is needed when an optical fiber amplifier and filter are used. They can be used as band reject filter or band pass filter for optical devices. The model equations of the cascaded uniform fiber Bragg grating and different cascaded apodization functions such as, Hamming apodized fiber Bragg grating, Barthan apodized fiber Bragg grating, Nuttal apodized fiber Bragg grating, Sinc apodized fiber Bragg grating and Proposed apodized fiber Bragg grating are numerically handled and processed via specially cast software to achieve maximum Reflectivity, narrow bandwidth without side lobes.
Trends of renal diseases in Germany: review of a regional renal biopsy database from 1990 to 2013
Authors: Zink Corinna M , Ernst Sabine , Riehl Jochen , Helmchen Udo , Gröne Hermann-Josef , Floege Jürgen , Schlieper Georg 
Published: February 2019

Abstract

Background
Several renal biopsy registries in Europe have shown geographical and temporal variations in the patterns of renal diseases. However, there is a lack of current data on trends of renal disease in Central Europe.

Methods
After exclusion of transplant and re-biopsies, the renal biopsy registry of the German RWTH Aachen University Hospital included data of 1208 biopsies over a period of 24 years (1990–2013). Trends in the biopsy rate and diagnosis of glomerular diseases were analysed.

Results
The average annual biopsy incidence was 6.1 biopsies per 100 000 population. The frequency of kidney biopsies increased significantly over the years (P &lt; 0.001). Primary glomerulonephritis (GN) accounted for nearly two-thirds (58.4%) of all native kidney biopsies, and immunoglobulin A-nephropathy (IgAN) was the leading histological diagnosis (34.7%) followed by necrotizing GN (RPGN) at 18.7%. IgAN increased 2-fold over the study periods (+195%, P &lt; 0.001). Focal segmental glomerulosclerosis accounted for 6.1% of all diagnoses, and its frequency rose to 3.9-fold (+388%, P &lt; 0.001). Lupus nephritis showed a doubling in incidence (P = 0.0499), while acute tubular necrosis decreased to 3.5-fold (P = 0.0008). All other disease entities failed to exhibit linear trends over time. In children, the most common pathologies were IgAN (26.1%) and minimal change disease (21.7%), whereas RPGN (19.4%) dominated in the group of patients &gt;60 years.

Conclusion
IgAN was the most common primary glomerular disease in our centre and its prevalence increased over 24 years.
Glucocorticoid receptor–IRS-1 axis controls EMT and the metastasis of breast cancers
Authors: Shi Weiwei , Wang Dongmei , Yuan Xinwang , Liu Yi , Guo Xiaojie , Li Jingsong , Song Jianguo 
Published: February 2019

Abstract
Glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes that are important for various biological functions, including tumor growth and metastatic progression. However, the cellular and biological effects of GR remain poorly understood. Here, we investigated the role of GR and its underlying mechanism in mediating breast cancer cell survival and metastasis. We observed that the GR levels were increased in drug-resistant breast cancer cells and in metastatic breast cancer samples. GR promoted tumor cell invasion and lung metastasis in vivo. The GR expression levels were negatively correlated with the survival rates of breast cancer patients. Both ectopic expression and knockdown of GR revealed that GR is a strong inducer of epithelial-to-mesenchymal transition (EMT), which is consistent with its effects on cell survival and metastasis. GR suppressed the expression of insulin receptor substrate 1 (IRS-1) by acting as an IRS-1 transcriptional repressor. In addition, GR has an opposite effect on the expression levels of IRS-2, indicating that GR is able to differentially regulate the IRS-1 and IRS-2 expression. The cellular and biological effects elicited by GR were consistent with the reduced levels of IRS-1 observed in cancer cells, and GR-mediated IRS-1 suppression activated the ERK2 MAP kinase pathway, which is required for GR-mediated EMT. Taken together, our results indicate that GR–IRS-1 signaling axis plays an essential role in regulating the survival, invasion, and metastasis of breast cancer cells.
MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis
Authors: Zhu Yunxia , Sun Yi , Zhou Yuncai , Zhang Yan , Zhang Tao , Li Yating , You Weiyan , Chang Xiaoai , Yuan Li , Han Xiao 
Published: February 2019

AbstractCurrent research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis; however, the mechanisms by which this occurs remain poorly understood. Our previous study demonstrated that elevation of microRNA-24 (miR-24) in a diabetic setting caused beta cell dysfunction and replicative deficiency. In this study, we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum (ER) stress conditions. We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucose-stimulated insulin secretion (GSIS) and enhancing the presence of dedifferentiation markers. Ingenuity® Pathway Analysis (IPA) revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4, which are downstream effectors of two key branches of ER stress, by inhibiting its direct target, Ire1α. Notably, elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells, thus guiding their dedifferentiation under ER stress conditions. Our results demonstrated that the elevated miR-24, to the utmost extent, preserves beta cell mass by inhibiting apoptosis and inducing dedifferentiation. This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation.
Impact of Antibiotic Therapy in the Microbiological Yield of Healthcare–Associated Ventriculitis and Meningitis
Authors: Rogers Thomas , Sok Kevin , Erickson Timothy , Aguilera Elizabeth , Wootton Susan H , Murray Kristy O , Hasbun Rodrigo 
Published: February 2019

Abstract
The impact of antibiotic therapy on the diagnosis of healthcare–associated ventriculitis and meningitis (HCAVM) is unknown. Antibiotics were administered before obtaining cerebrospinal fluid (CSF) in 217 out of 326 (66%) patients with HCAVM, and they impacted the sensitivity of the cerebrospinal fluid Gram stain and culture (P ≤ .004).
Outcomes of a Career Development Program for Underrepresented Minority Investigators in the AIDS Clinical Trials Group
Authors: Velásquez Gustavo E , Huaman Moises A , Powell Kimberly R , Cohn Susan E , Swaminathan Shobha , Outlaw Martine , Schulte Gail , McNeil Quinteka , Currier Judith S , Del Rio Carlos , Castillo-Mancilla Jose 
Published: February 2019

Abstract
We surveyed awardees of the Minority HIV Investigator Mentoring Program (MHIMP) of the AIDS Clinical Trials Group. Most reported clinical specialization in infectious diseases or HIV medicine (86%), and all but 1 (95%) are engaged in medical/health sciences research. The MHIMP helped retain early-career minority investigators in HIV/AIDS-related research.
Heat Pain and Cold Pain
Authors: Viana Félix , Voets Thomas 
Published: February 2019

Abstract
Noxious cold and noxious heat have detrimental effects on key biological macromolecules and thus on the integrity of cells, tissues, and organisms. Thanks to the action of a subset of somatosensory neurons, mammals can swiftly detect noxiously cold or hot objects or environments. These temperature-sensitive nociceptor neurons become activated when the temperature at their free endings in the skin or mucosae reaches noxious levels, provoking acute pain and rapid avoidance reflexes. Whereas acute temperature-induced pain is essential to prevent or limit burn injury, pathological conditions such as inflammation or tissue injury can deregulate the thermal sensitivity of the somatosensory system, resulting in painful dysesthesias such as heat and cold hypersensitivity. In recent years, important advances have been made in our understanding of the cellular and molecular mechanisms that underlie the detection of painful heat or cold. These research efforts not only provided key insights into an evolutionary conserved biological alarm system, but also revealed new avenues for the development of novel therapies to treat various forms of persistent pain.
Diversity of Ocular Surface Bacterial Microbiome Adherent to Worn Contact Lenses and Bacterial Communities Associated With Care Solution Use
Authors: Retuerto Mauricio A. , Szczotka-Flynn Loretta , Mukherjee Pranab K. , Debanne Sara , Iyengar Sudha K. , Richardson Brian , Cameron Mark , Ghannoum Mahmoud A. 
Published: February 2019

Purpose:
This study assessed microbiome adherent to contact lenses and defined the bacterial communities associated with use of lens care solutions.

Methods:
Among 84 lenses screened for adherent ocular surface bacterial microbiome using 16S rRNA molecular amplification, 63 (75%) generated bacterial-specific amplicons processed using the Ion Torrent Personal Genome Machine workflow. Data were stratified by solution use (peroxide vs. polyhexamethylene biguanide [PHMB]–preserved multipurpose solution [MPS]). Diversity of lens-adherent microbiome was characterized using Shannon diversity index and richness index. Data were analyzed using principal components analysis and Kruskal–Wallis tests.

Results:
We identified 19 phyla and 167 genera of bacteria adherent to the lenses. Proteobacteria was the most abundant phyla, followed by Firmicutes and Actinobacteria. The most abundant bacterial genera (>1% abundance) were Ralstonia, Enterococcus, Streptococcus, Halomonas, Corynebacterium, Staphylococcus, Acinetobacter, Shewanella, Rhodococcus, and Cobetia. Sixteen of 20 lenses (80%) negative for bacterial DNA were worn by participants using peroxide solutions while only 4 (20%) were MPS-treated lenses (P=0.004). Genera diversity of lens-adherent microbiome showed a significant increase in MPS-treated lenses compared with peroxide (P=0.038). Abundance of Corynebacterium, Haemophilus, and Streptococcus were increased 4.3-, 12.3-, and 2.7-fold, respectively, in the MPS group compared with peroxide (P=0.014, 0.006, 0.047, respectively).

Conclusions:
Commensal, environmental, and pathogenic bacteria known to be present in the conjunctival microbiome can be detected on worn contact lenses. Although most contact lenses worn by asymptomatic wearers harbor bacterial DNA, compared with peroxide, lenses stored in a PHMB–preserved MPS have more quantifiable, abundant, and diverse bacterial communities adherent to them.
Medial femoral condyle free flap for head and neck reconstruction
Authors: Banaszewski Jacek , Gaggl Alexander , Andruszko Agata 
Published: February 2019

Purpose of review
The aim of this article is to review the literature on medial femoral condyle (MFC) free flap in head and neck reconstruction.

Recent findings
The MFC flap is a superb material for head and neck reconstruction, especially in smaller bony defects. As an alternative to fibular free flap, it presents many advantages. Combining the periosteal bone with skin and/or muscle paddle, the MFC flap is suitable for complex reconstructions with favorable healing process. Even though this flap has a longer history of orthopedic and traumatologic reconstructions, a number of cases in head and neck surgery have been recently reported.

Summary
The MFC flap has been successfully used to reconstruct various head and neck sites, from the orbit, maxilla, and mandible, to the laryngeal and tracheal scaffolds.
Anti–interferon-α receptor 1 antibodies attenuate inflammation and organ injury following hemorrhagic shock
Authors: Cagliani Joaquin , Yang Weng-Lang , McGinn Joseph T. , Wang Zhimin , Wang Ping 
Published: February 2019

BACKGROUND
Hemorrhagic shock (HS) is a life-threatening condition resulting from rapid and significant loss of intravascular volume, leading to hemodynamic instability and death. Inflammation contributes to the multiple organ injury in HS. Type I interferons (IFNs), such as IFN-α and IFN-β, are a family of cytokines that regulate the inflammatory response through binding to IFN-α receptor (IFNAR) which consists of IFNAR1 and IFNAR2 chains. We hypothesized that type I IFNs provoke inflammation and worsen organ injury in HS.

METHODS
Male C57BL/6 mice (20–25 g) underwent hemorrhage by controlled bleeding via the femoral artery to maintain a mean arterial pressure of 27 ± 2.5 mm Hg for 90 minutes, followed by resuscitation for 30 minutes with two times shed blood volume of Ringer's lactate solution containing 1 mg/kg body weight of anti-IFNAR1 antibody (Ab) or control isotype-matched IgG (IgG). Blood and tissue samples were collected at 20 hours after the resuscitation for various analyses.

RESULTS
The expression of IFN-α and IFN-β mRNAs was significantly elevated in lungs and liver of the mice after HS. The IFNAR1-Ab treatment significantly decreased serum levels of organ injury markers lactate dehydrogenase and aspartate aminotransferase, as well as improved the integrity of lung and liver morphology, compared to the IgG control. The protein levels of proinflammatory cytokines TNF-α and IL-6, and mRNA expression of proinflammatory chemokines monocyte chemoattractant protein (MCP)-1, MCP-2, macrophage inflammatory protein 2 (MIP-2), and keratinocyte cytokine (KC) in the lungs of the HS mice were significantly decreased after treated with IFNAR1-Ab. Moreover, the myeloperoxidase activity and number of apoptotic cells in the lungs of HS mice treated with IFNAR1-Ab were decreased in comparison to the IgG control.

CONCLUSION
Administration of IFNAR1-Ab reduces inflammation and tissue injury. Thus, type I IFN signaling may be a potential therapeutic target for mitigating organ dysfunction in patients suffering from HS.

STUDY TYPE
Translational animal model.
Serum leptin in male hypothyroid prediabetic patients: Association with cardiovascular risk
Authors: El-Zawawy Hanaa T. 
Published: February 2019

Introduction
Hyperliptenemia is a risk factor for coronary heart disease (CHD). Hypothyroidism and prediabetes confer an increased cardiovascular risk. Few studies have addressed the role of leptin in hypothyroid prediabetic patients and its effect on CHD risk factors.

Objective
The aim of this study was to detect serum levels of leptin in hypothyroid prediabetic patients and their relationship with risk factors for CHD.

Patients and methods
The study included three groups; group A included 120 hypothyroid male patients with normal glucose tolerance, group B included 120 hypothyroid male patients with prediabetes, and group C included 120 healthy individuals matched for age and sex as a control group. All groups were subjected to assessment of history, clinical examination, and laboratory investigations including fasting and 2 h postprandial blood glucose, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), free T3, free T4, thyroid-stimulating hormone, and fasting serum leptin.

Results
Serum leptin was significantly higher in groups A and B compared with group C (P=0.0001), whereas there was no significant difference in serum leptin between groups A and B. In comparison with group A, the patients in group B had significantly higher serum TC (P=0.02), LDL (P=0.04), and lower serum HDL (P=0.02). In group B, serum leptin correlated positively with serum TC (P=0.0001), TG (P=0.041), and LDL (P=0.036), and negatively with serum HDL (P=0.039).

Conclusion
Hypothyroidism is associated with high serum leptin independent of prediabetic state. Serum leptin in hypothyroid prediabetic patients showed a direct relationship with some primary markers of metabolic syndrome; thus, leptin may predict the development of CHD in those patients.
Host density predicts the probability of parasitism by avian brood parasites
Authors: Medina Iliana , Langmore Naomi E. 
Published: February 2019

The spatial distribution of hosts can be a determining factor in the reproductive success of parasites. Highly aggregated hosts may offer more opportunities for reproduction but can have better defences than isolated hosts. Here we connect macro- and micro-evolutionary processes to understand the link between host density and parasitism, using avian brood parasites as a model system. We analyse data across more than 200 host species using phylogenetic comparative analyses and quantify parasitism rate and host reproductive success in relation to spatial distribution using field data collected on one host species over 6 years. Our comparative analysis reveals that hosts occurring at intermediate densities are more likely to be parasitized than colonial or widely dispersed hosts. Correspondingly, our intraspecific field data show that individuals living at moderate densities experience higher parasitism rates than individuals at either low or high densities. Moreover, we show for the first time that the effect of host density on host reproductive success varies according to the intensity of parasitism; hosts have greater reproductive success when living at high densities if parasitism rates are high, but fare better at low densities when parasitism rates are low. We provide the first evidence of the trade-off between host density and parasitism at both macro- and micro-evolutionary scales in brood parasites.This article is part of the theme issue ‘The coevolutionary biology of brood parasitism: from mechanism to pattern’.
Reconstruction and Simulation of a Scaffold Model of the Cerebellar Network
Authors: Casali Stefano , Marenzi Elisa , Medini Chaitanya , Casellato Claudia , D’Angelo Egidio 
Published: February 2019

AbstractReconstructing neuronal microcircuits through computational models is fundamental to simulate local neuronal dynamics. Here a scaffold model of the cerebellum has been developed in order to flexibly place neurons in space, connect them synaptically and endow neurons and synapses with biologically-grounded mechanisms. The scaffold model can keep neuronal morphology separated from network connectivity, which can in turn be obtained from convergence/divergence ratios and axonal/dendritic field 3D geometries. We first tested the scaffold on the cerebellar microcircuit, which presents a challenging 3D organization, at the same time providing appropriate datasets to validate emerging network behaviors. The scaffold was designed to integrate the cerebellar cortex with deep cerebellar nuclei (DCN), including different neuronal types: Golgi cells, granule cells, Purkinje cells, stellate cells, basket cells and DCN principal cells. Mossy fiber (mf) inputs were conveyed through the glomeruli. An anisotropic volume (0.077 mm3) of mouse cerebellum was reconstructed, in which point-neuron models were tuned toward the specific discharge properties of neurons and were connected by exponentially decaying excitatory and inhibitory synapses. Simulations using pyNEST and pyNEURON showed the emergence of organized spatio-temporal patterns of neuronal activity similar to those revealed experimentally in response to background noise and burst stimulation of mossy fiber bundles. Different configurations of granular and molecular layer connectivity consistently modified neuronal activation patterns, revealing the importance of structural constraints for cerebellar network functioning. The scaffold provided thus an effective workflow accounting for the complex architecture of the cerebellar network. In principle, the scaffold can incorporate cellular mechanisms at multiple levels of detail and be tuned to test different structural and functional hypotheses. A future implementation using detailed 3D multi-compartment neuron models and dynamic synapses will be needed to investigate the impact of single neuron properties on network computation.