bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic Risk Scores for Subtyping of Schizophrenia
Authors: Chen Jingchun , Mize Travis , Wu Jain-Shing , Hong Elliot , Nimgaonkar Vishwajit , Kendler Kenneth S. , Allen Daniel , Oh Edwin , Netski Alison , Chen Xiangning
Published: July 2020

Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p=0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE,p=0.0099; PROCESSING SPEED,p=0.0006; WORKING MEMORY,p=0.0023; and REASONING,p=0.0015). Class II had modest reduction of positive symptoms (p=0.0492) and better PROCESSING SPEED (p=0.0071). Class IV had a specific reduction of negative symptoms (p=0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction.
The Effects of Titanium Surfaces Modified with an Antimicrobial Peptide GL13K by Silanization on Polarization, Anti‐Inflammatory, and Proinflammatory Properties of Macrophages
Authors: Chen Xuxi , Zhou Lin , Wu Dong , Huang Wenxiu , Lin Yanjun , Zhou Bowei , Chen Jiang
Published: July 2020

The polarization of macrophages and its anti‐inflammatory and proinflammatory properties play a significant role in host response after implant placement to determine the outcome of osseointegration and long‐term survival. In the previous study, we immobilized an antimicrobial peptide, GL13K, onto titanium surfaces to provide immune regulation property. In the herein presented study, we aimed at investigating whether GL13K immobilized titanium surface could improve osteogenesis and reduce the inflammatory reaction around the biomaterials by altering macrophage response. We evaluated the cell proliferation of the different phenotypes of macrophages seeded in GL13K‐coated titanium surface, which indicated an inhibition of M1 macrophages and a good cytocompatibility to M2 macrophages. Then, we measured the inflammatory and anti‐inflammatory activity of the M1 and M2 macrophages seeded on the GL13K‐coated titanium surfaces. The results of the enzyme‐linked immunosorbent assay and quantitative reverse transcription‐polymerase chain reaction showed that the group with the GL13K modified surface had a downregulation in the expression level of the tumor necrosis factor‐α and interleukin‐1β in M1 macrophages and an upregulation of IL‐10 and transforming growth factor‐β3 (TGF‐β3) levels in M2 macrophages. This study demonstrated that the GL13K modified titanium surfaces can regulate macrophages’ polarization and the expression of inflammatory and anti‐inflammatory effects, reducing the effects of the inflammatory process, which may promote the process of bone regeneration and osseointegration.
Mantle-Derived Helium Emission near the Pohang EGS Site, South Korea: Implications for Active Fault Distribution
Authors: Kim Heejun , Lee Hyunwoo , Lee Jaemin , Lee Hyun A. , Woo Nam Chil , Lee Youn-Soo , Kagoshima Takanori , Takahata Naoto , Sano Yuji
Published: July 2020

An Mw 5.5 earthquake occurred in Pohang, South Korea on November 15, 2017, resulting in a great impact on society. Despite a lot of controversy about the cause of the earthquake in relation to the enhanced geothermal system (EGS), the location of earthquake-related active faults is poorly known. Here, we first report the results of the geochemical and isotopic analyses of dissolved gases in groundwater in the Heunghae, Yeonil, and Sinkwang areas. According to the N2-Ar-He relationship, samples from the Heunghae and Yeonil areas are contributed to the mantle, except for the Sinkwang area, where all samples are atmospheric. The Pohang samples consist mainly of N2 and CO2, and some samples of the Heunghae and Yeonil areas contain substantial CH4. Stable isotope compositions of N2 (δ15N=0.2 to 3.6‰), CO2 (δ13C=−27.3 to−16.0‰), and CH4 (δ13C=−76.1 to−70.0‰) indicate that these components are derived from organic substances in sedimentary layer of Pohang Basin. On the other hand, helium isotope ratios (3He/4He, up to 3.83 Ra) represent the significant mantle contribution in the Heunghae and Yeonil areas. Through the distribution of high 3He/4He ratios, we propose that the Heunghae, Namsong, and Jamyeong faults are the passage of mantle-derived fluids. Computed 3He fluxes of the Heunghae (120 to 3,000 atoms cm-2 sec-1), Namsong (52 to 1,300 atoms cm-2 sec-1), and Jamyeong (83 to 2,100 atoms cm-2 sec-1) faults are comparable to other major active faults around the world, reflecting either high porosity or high helium flow rates. Therefore, our results demonstrate that there are active faults near the EGS facilities, which can provide the basis for future studies.
High Isolation and Ideal Correlation Using Spatial Diversity in a Compact MIMO Antenna for Fifth-Generation Applications
Authors: El Hadri Doae , Zakriti Alia , Zugari Asmaa , El Ouahabi Mohssine , El Aoufi Jamal
Published: July 2020

This paper presents a compact Multiple Input Multiple Output antenna with high isolation and low envelope correlation (ECC) for fifth-generation applications using spatial diversity technique. The proposed MIMO antenna consists of two single antennas, each having size of 13 × 12.8 mm2, symmetrically arranged next to each other. The single and MIMO antennas are simulated and analyzed. To verify the simulated results, the prototype antennas were fabricated and measured. A good agreement between measurements and simulations is obtained. The proposed antenna covers the 28 GHz band (27.5–28.35 GHz) allocated by the FCC for 5G applications. Moreover, the isolation is more than 35 dB and the ECC is less than 0.0004 at the operating band, which means that the mutual coupling between the two elements is negligible. The MIMO parameters, such as diversity gain (DG), total active reflection coefficient (TARC), realized gain, and efficiency, are also studied. Thus, the results demonstrate that our antenna is suitable for 5G MIMO applications.
The Effects of Calcium-β-Hydroxy-β-Methylbutyrate on Aging-Associated Apoptotic Signaling and Muscle Mass and Function in Unloaded but Nonatrophied Extensor Digitorum Longus Muscles of Aged Rats
Authors: Bennett Brian T. , Mohamed Junaith S. , Alway Stephen E.
Published: July 2020

Beta-hydroxy-beta-methylbutyrate (HMB), a naturally occurring leucine metabolite, has been shown to attenuate plantar flexor muscle loss and increase myogenic stem cell activation during reloading after a period of significant muscle wasting by disuse in old rodents. However, it was less clear if HMB would alter dorsiflexor muscle response to unloading or reloading when there was no significant atrophy that was induced by unloading. In this study, we tested if calcium HMB (Ca-HMB) would improve muscle function and alter apoptotic signaling in the extensor digitorum longus (EDL) of aged animals that were unloaded but did not undergo atrophy. The EDL muscle was unloaded for 14 days by hindlimb suspension (HS) in aged (34-36 mo.) male Fisher 344×Brown Norway rats. The rats were removed from HS and allowed normal cage ambulation for 14 days of reloading (R). Throughout the study, the rats were gavaged daily with 170 mg of Ca-HMB or water 7 days prior to HS, then throughout 14 days of HS and 14 days of recovery after removing HS. The animals’ body weights were significantly reduced by ~18% after 14 days of HS and continued to decline by ~22% during R as compared to control conditions; however, despite unloading, EDL did not atrophy by HS, nor did it increase in mass after R. No changes were observed in EDL twitch contraction time, force production, fatigue resistance, fiber cross-sectional area, or markers of nuclear apoptosis (myonuclei + satellite cells) after HS or R. While HS and R increased the proapoptotic Bax protein abundance, BCL-2 abundance was also increased as was the frequency of TUNEL-positive myonuclei and satellite cells, yet muscle mass and fiber cross-sectional area did not change and Ca-HMB treatment had no effect reducing apoptotic signaling. These data indicate that (i) increased apoptotic signaling preceded muscle atrophy or occurred without significant EDL atrophy and (ii) that Ca-HMB treatment did not improve EDL signaling, muscle mass, or muscle function in aged rats, when HS and R did not impact mass or function.
Influence of the Inner and Outer Secondary Air Ratios on the Combustion Characteristic and Flame Shape of a Swirl Burner with a Prechamber
Authors: Liu Pengzhong , Niu Fang , Wang Xuewen , Guo Fei , Luo Wei , Wang Naiji
Published: July 2020

The swirl burner with a prechamber was used in a 14 MW pulverized-coal combustion experiment to investigate the influence of inner and secondary air ratios (ISA/OSA) on the combustion characteristic and flame shape in this work. The temperatures and species concentrations in the prechamber were measured via the flue gas analyzer and thermocouples. The flame shape beyond the prechamber outlet was captured by using a high-speed camera. The results showed that the combustion efficiency was increased and low nitrogen combustion was achieved by adopting the swirl burner with a prechamber. The high temperature corrosion and slagging phenomenon did not occur in the prechamber. The influence of ISA/OSA on temperature and species concentration profiles at different areas in the prechamber was different. The flame shape size exhibited an inflection point with increasing ISA/OSA. Considering, comprehensively, the temperature peak, near wall temperature, oxygen-free zone, CO concentration, flame length, flame diameter, and divergence angle, the case of ISA/OSA =1 : 2 had great processing on combustion efficiency and NOx emission. Thus, ISA/OSA = 1 : 2 was selected as the optimized case under experiment conditions.
Increased Serum Level and High Tissue Immunoexpression of Interleukin 17 in Cutaneous Lichen Planus: A Novel Therapeutic Target for Recalcitrant Cases?
Authors: Żychowska Magdalena , Batycka-Baran Aleksandra , Baran Wojciech
Published: July 2020

Background. Interleukin-17 is supposed to play an important role in the pathogenesis of oral lichen planus (OLP). However, there is scarce data in the literature on its significance in the cutaneous variant of the disease. Objectives. To determine the serum level and tissue immunoexpression of IL-17 in cutaneous lichen planus (CLP). Methods. Fifty-two adult patients with CLP, without any significant autoimmune or inflammatory conditions, were included in the first part of the study. The control group consisted of 27 age- and sex-matched healthy volunteers. Serum concentration of IL-17 was quantified using enzyme-linked immunosorbent assay (ELISA) kit. In the second part of the study, the tissue expression of IL-17 was assessed in archival paraffin-embedded biopsy specimens from CLP (n=14) against normal control tissues (n=11) using immunohistochemical assays. The expression was evaluated using Zeiss Axio Imager A2 light microscope. Positively stained cells were counted in 10 fields of view for biopsy specimen at 200x magnification, and the mean value was calculated. Results. The serum level of IL-17 was significantly elevated in patients with CLP, compared with healthy volunteers (0.218±0.221 ng/ml versus 0.126±0.058 ng/ml, respectively; p=0.025). No correlation was found between the serum concentration of IL-17 and patient age, gender, disease duration, extent of skin involvement, the presence or intensity of pruritus, and coexistence of mucosal lesions. In tissue samples from CLP lesions, significantly higher numbers of cells expressing IL-17 were found when compared to a healthy skin (p<0.001). Conclusion. Elevated serum concentration of IL-17 and high expression in a lesional skin support the hypothesis that IL-17 is implicated in the immunopathogenesis of CLP. These findings may constitute a premise for the future use of anti-IL-17 monoclonal antibodies in the treatment of severe and recalcitrant forms of CLP.
An Anisotropic Hyperelastic Constitutive Model with Bending Stiffness Interaction for Cord-Rubber Composites: Comparison of Simulation Results with Experimental Data
Authors: Sun Shulei , Chen Wenguo
Published: July 2020

Based on the invariant theory of continuum mechanics by Spencer, the strain energy depends on deformation, fiber direction, and the gradients of the fiber direction in the deformed configuration. The resulting extended theory is very complicated and brings a nonsymmetric stress and couple stress. By introducing the gradient of fiber vector in the current configuration, the strain energy function can be decomposed into volumetric, isochoric, anisotropic, and bending deformation energy. Due to the particularity of bending deformation, the reinforced material has tensile deformation and compression deformation. The bending stiffness should be taken into consideration, and it is further verified by the bending simulation.
Adaptive Cultural Algorithm-Based Cuckoo Search for Time-Dependent Vehicle Routing Problem with Stochastic Customers Using Adaptive Fractional Kalman Speed Prediction
Authors: Xue H.
Published: July 2020

For the Time-Dependent Vehicle Routing Problem with Stochastic Customers (TDVRPSC), an adaptive Cultural Algorithm-Based Cuckoo Search (CACS) has been proposed in this paper. The convergence of the new algorithm is proved. An adaptive fractional Kalman filter (AFKF) for traffic speed prediction is proposed. An adaptive mechanism for choosing the covariance of state noise is designed. Its mathematical process is proved. Several benchmark instances with different scales are tested, and new solutions are discovered, which are better than the published solutions. The effects of the parameters on the convergence and the results are studied. According to cargo weight of customers to be delivered, the customers can be divided into large, small, and retail customers. The algorithm is tested with fixed demand probability and also different customer types with stochastic demand. The traffic speeds in different business districts in Xiamen at different times are predicted by AFKF. The results show that AFKF has smaller prediction error and better prediction accuracy than fractional Kalman filter and Kalman filter. The effect of different fractional orders on prediction error is compared. The performance of the new algorithm is compared with that of the cultural algorithm and the Cuckoo Search. The result shows that the new algorithm can efficiently and effectively solve DTVRPSC and improve the accuracy of vehicle routing planning of time-varying actual urban traffic road.
Initial Value Determination of Chua System with Hidden Attractors and Its DSP Implementation
Authors: Wu Xianming , Tan Weijie , Wang Huihai
Published: July 2020

In this paper, a method for determining the initial value of the hidden attractors in the Chua system is studied. The initial value of the hidden attractors can be calculated quickly and accurately by the proposed method, and the hidden attractors can be found by numerical simulation. Then, the initial values of the hidden attractors are set accurately by digital signal processor (DSP), so as to the circuit realization of the chaotic system with hidden attractors is performed. The results show that the numerical simulation results of Matlab are consistent with the experimental results of DSP.
The Role of Gastric Mucosal Immunity in Gastric Diseases
Authors: Nie Siru , Yuan Yuan
Published: July 2020

Gastric mucosa plays its immune function through innate and adaptive immunity by recruiting immune cells and releasing corresponding cytokines, which have an inseparable relationship with gastric diseases. Whether infective gastric diseases caused by Helicobacter pylori, Epstein-Barr virus or other microbe, noninfective gastric diseases, or gastric cancer, gastric mucosal immunity plays an important role in the occurrence and development of the disease. Understanding the unique immune-related tissue structure of the gastric mucosa and its role in immune responses can help prevent gastric diseases or treat them through immunotherapy. In this review, we summarize the basic feature of gastric mucosal immunity and its relationship with gastric diseases to track the latest progress of gastric mucosal immunity, update relevant knowledge and provide theoretical reference for the prevention and treatment of gastric diseases based on the gastric mucosal immunity.
A General Model of Population Dynamics Accounting for Multiple Kinds of Interaction
Authors: Stucchi Luciano , Pastor Juan Manuel , García-Algarra Javier , Galeano Javier
Published: July 2020

Population dynamics has been modelled using differential equations almost since Malthus times, more than two centuries ago. Basic ingredients of population dynamics models are typically a growth rate, a saturation term in the form of Verhulst’s logistic brake, and a functional response accounting for interspecific interactions. However, intraspecific interactions are not usually included in the equations. The simplest models use linear terms to represent a simple picture of the nature; meanwhile, to represent more complex landscapes, it is necessary to include more terms with a higher order or that are analytically more complex. The problem to use a simpler or more complex model depends on many factors: mathematical, ecological, or computational. To address it, here we discuss a new model based on a previous logistic-mutualistic model. We have generalized the interspecific terms (for antagonistic and competitive relationships), and we have also included new polynomial terms to explain any intraspecific interaction. We show that, by adding simple intraspecific terms, new free-equilibrium solutions appear driving a much richer dynamics. These new solutions could represent more realistic ecological landscapes by including a new higher order term.
Experimental Study on Freeze‐Thaw Cycle Duration of Saturated Tuff
Authors: Huang Man , Tang Bin , Jiang Jianliang , Guan Renqiu , Wang Huajun
Published: July 2020

The freeze‐thaw duration is one of the important factors affecting the change of rock properties. However, this factor has not formed a unified standard in the freeze‐thaw cycle test. This study uses saturated tuff samples taken from eastern Zhejiang, China, as research objects to explore the change law of the time required for the rock to reach a full freeze‐thaw cycle. Measured results show that the total duration of the freeze‐thaw cycle presents an increasing power function with the increase in the number of freeze‐thaw cycles. The freezing process is divided into three phases: initial freezing, water‐ice phase transition, and deep freezing. The melting process is also divided into three phases: initial melting, ice‐water phase transition, and deep melting. The time required for the ice‐water phase change stage of the melting process does not change with the increase in the number of freeze‐thaw cycles, while the other stages increase as a power function. The proportion of duration of each stage in the freezing process does not change with the increase in the number of cycles. By contrast, the duration proportion of the initial melting phase in the melting process decreases, and the deep melting phase increases. Experimental results of the freeze‐thaw cycles of tuff demonstrate that the freeze‐thaw duration of the freeze‐thaw cycles within 40 times can be set to 9 h. The freezing and melting processes are 6 and 3 h, respectively.
Rehabilitation of Edentulous Jaws with Full-Arch Fixed Implant-Supported Prostheses: An Approach with Short and Ultrashort Implants and Metal-Free Materials
Authors: Aiuto Riccardo , Barbieri Christian , Garcovich Daniele , Dioguardi Mario , Redaelli Mattia , De Micheli Luca
Published: July 2020

Introduction. Short implants represent a valid alternative to bone regeneration techniques. In addition, metal-free prosthetic materials have several advantages for predictable rehabilitation. This case report is aimed at illustrating the advantages of fixed implant-prosthetic rehabilitation on short and ultrashort implants and metal-free prosthetic materials. Case report. A 66-year-old male patient with bone atrophy was treated with temporary denture placement performed based on a rapid protocol. Once the tissues after extractions matured and aesthetic/function was studied, short implants were prosthetically placed, and a fiber-reinforced composite (FRC) bar was digitally designed for a double full-arch fixed rehabilitation. The 2-year follow-up showed the absence of peri-implantitis signs and a stable occlusal relationship of prostheses. Discussion and conclusions. The FRC material has excellent aesthetic properties and is low cost with a simplified and fast workflow owing to digital dentistry methods. Further studies are still needed to confirm the effectiveness of long-term therapy; however, the combination of new minimally invasive surgery and prosthetic advances seems to be very promising.
Quadruple Therapy Offers High SVR Rates in Patients with HCV Genotype 4 with Previous Treatment Failure
Authors: Abo-amer Yousry Esam-Eldin , Badawi Rehab , El-Abgeegy Mohamed , Elsergany Heba Fadl , Mohamed Ahmed Abdelhaleem , Mostafa Sahar Mohamed , Alegaily Hatem Samir , Soliman Shaimaa , Elnawasany Sally , Abd-Elsalam Sherief
Published: July 2020

Background and Aims. Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5–15% of patients treated with DAA‐based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients. Methods. This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000–1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded. Results. SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded. Conclusions. Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.
Vibration Characteristic Analysis of Pressure Fluctuating Attenuator with Circular Elastic Sheets for Linear-Driving Pump
Authors: Nie Songlin , Li Lianwei , Ji Hui , Yin Fanglong , Dai Zhaoyi
Published: July 2020

Aiming at the problem of pipeline vibration caused by fluids in linear-driving pump pipeline system, this paper proposed a vibration reduction method based on a pressure-fluctuating attenuator with circular elastic sheets. Firstly, a new type of pressure-fluctuating attenuator was proposed, and its working principle and frequency characteristics were analyzed. Secondly, the mathematical model of the developed attenuator was established in combination with the dynamic characteristic equations of the pipeline. Besides, the effect of relevant parameters on attenuation performance was investigated through simulation. The size and material of the circular elastic sheet were screened according to the pressure fluctuating frequency of the linear-driving pump under the rated conditions. The prototype of the pressure-fluctuating attenuator was fabricated, and the performance of the prototype in the pipeline was tested. The experimental results show that the pressure-fluctuating attenuator with circular elastic sheets has a good suppression effect on the pulsating pressure of the linear-driving pump under the rated conditions.
Secukinumab-Induced Inflammatory Bowel Disease in a Patient Treated for Chronic Plaque Psoriasis and Psoriatic Arthritis: A Case Report and Review of the Role of Novel Biologic Agents Targeting the p19 Subunit of IL-23
Authors: Darch K. M. , Holland T. L. , Spelman L. J.
Published: July 2020

Chronic plaque psoriasis and psoriatic arthritis are common autoimmune inflammatory conditions, often existing as comorbidities that have a significant impact on a patient’s quality of life. The availability of a range of novel, targeted therapies for their treatment, most notably the availability of biologic agents, has revolutionised management of these conditions and allowed for significant improvements in patient outcomes. Secukinumab (Cosentyx), a fully-human monoclonal antibody that acts by selectively binding to and neutralising the proinflammatory cytokine IL-17A, is used widely for the treatment of both chronic plaque psoriasis and psoriatic arthritis. In this report, we discuss the case of a 54-year-old female with chronic plaque psoriasis and psoriatic arthritis, who experienced the onset of symptoms and was subsequently diagnosed with Crohn’s disease during treatment with secukinumab. It was determined by the gastroenterologist that this may represent secukinumab-induced inflammatory bowel disease. We will review the current understanding of the role of IL-17 in inflammatory bowel disease and the important role of novel agents that target the p19 subunit of IL-23 which have shown significant promise in the management of not only chronic plaque psoriasis and psoriatic arthritis, but also inflammatory bowel disease itself.
Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank
Authors: Knuppel Anika , Fensom Georgina K. , Watts Eleanor L. , Gunter Marc J. , Murphy Neil , Papier Keren , Perez-Cornago Aurora , Schmidt Julie A. , Smith Byrne Karl , Travis Ruth C. , Key Timothy J.
Published: July 2020

Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias. Higher IGF-I concentration was associated with increased risks of thyroid cancer [HR per 5 nmol/L higher concentration 1.18; 95% confidence interval (CI), 1.01–1.37] in addition to colorectal (HR, 1.08; 95% CI, 1.03–1.13), breast (HR, 1.11; 95% CI, 1.07–1.15), and prostate cancer (HR, 1.08; 95% CI, 1.05–1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and the possibility that the observed associations may be influenced by reverse causality bias cannot be excluded. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development.

Significance:

The results from this outcome-wide analysis are consistent with a positive association of IGF-I with cancers at several sites.
Intradialytic Calcium Kinetics and Cardiovascular Disease in Chronic Hemodialysis Patients
Authors: Pirklbauer Markus , Fuchs Lisa , Heiss Ramona , Ratschiller Thomas , Mayer Gert
Published: July 2020

Background/Objective: Calcium loading has been associated with cardiovascular risk in hemodialysis (HD) patients. However, it remains to be elucidated whether alterations of intradialytic calcium buffering add to the increased cardiovascular disease burden in this high-risk population. Methods: Intradialytic calcium kinetics was evaluated in a cross-sectional observational study by measuring dialysate-sided ionized calcium mass balance (iCaMB), calcium buffer capacity, and change in serum calcium levels in 40 chronic HD patients during a routine HD session. A dialysate calcium of 3.5 mEq/L was used to adequately challenge calcium buffer mechanisms. Aortic pulse wave velocity and serum osteocalcin levels were measured prior to the HD session. Presence of cardiovascular disease and diabetes was assessed. Results: The mean dialysate-sided iCaMB, extracellular fluid ionized calcium mass gain, and buffered ionized calcium mass were 469 (±154), 111 (±49), and 358 (±145) mg/HD, respectively. The mean ionized serum calcium increase (∆iCa) was 0.42 (±0.14) mEq/L per HD. The mean intradialytic calcium buffer capacity was 73 (±18)%. Multivariate regression analysis revealed significant independent association of (1) iCaMB with the dialysate-to-blood calcium gradient at HD start and (2) intradialytic calcium buffer capacity with undercarboxylated osteocalcin. The presence of coronary heart disease was associated with higher ∆iCa but not iCaMB in the multivariate model. Conclusions: In line with our proof-of-concept study, we provide clinical evidence for a rapidly accessible and exchangeable calcium pool involved in intradialytic calcium regulation and for the role of osteocalcin as a potential biomarker. Our findings argue for evaluating the prognostic potential of intradialytic calcium kinetics in prospective clinical trials.
Global Response of Phaeobacter inhibens DSM 17395 to Deletion of Its 262-kb Chromid Encoding Antibiotic Synthesis
Authors: Wünsch Daniel , Strijkstra Annemieke , Wöhlbrand Lars , Freese Heike M. , Scheve Sabine , Hinrichs Christina , Trautwein Kathleen , Maczka Michael , Petersen Jörn , Schulz Stefan , Overmann Jörg , Rabus Ralf
Published: July 2020

The marine alphaproteobacterium Phaeobacter inhibens DSM 17395, a member of the Roseobacter group, was recently shown to markedly enhance growth upon deletion of its 262-kb chromid encoding biosynthesis of tropodithietic acid (TDA). To scrutinize the metabolic/regulatory adaptations that underlie enhanced growth of the Δ262 mutant, its transcriptome and proteome compared to the wild type were investigated in process-controlled bioreactors with Casamino Acids as growth substrate. Genome resequencing revealed only few additional genetic changes (a heterogenic insertion, prophage activation, and several point mutations) between wild type and Δ262 mutant, albeit with no conceivable effect on the studied growth physiology. The abundances of the vast majority of transcripts and proteins involved in the catabolic network for complete substrate oxidation to CO2 were found to be unchanged, suggesting that the enhanced amino acid utilization of the Δ262 mutant did not require elevated synthesis of most enzymes of the catabolic network. Similarly, constituents of genetic information processing and cellular processes remained mostly unchanged. In contrast, 426 genes displayed differential expression, of which 410 were localized on the 3.2-Mb chromosome, 5 on the 65-kb chromid, and 11 on the 78-kb chromid. Notably, the branched-chain amino transferase IlvE acting on rapidly utilized Val, Ile, and Leu was upregulated. Moreover, the transportome was reconfigured, as evidenced from increased abundances of transcripts and proteins of several uptake systems for amino acids and inorganic nutrients (e.g., phosphate). Some components of the respiratory chain were also upregulated, which correlates with the higher respiration rates of the Δ262 mutant. Furthermore, chromosomally encoded transcripts and proteins that are peripherally related to TDA biosynthesis (e.g., the serine acyl transferase CysE) were strongly downregulated in the Δ262 mutant. Taken together, these observations reflect adaptations to enhanced growth as well as the functional interconnectivity of the replicons of P. inhibens DSM 17395.
Hepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Authors: Ueshima Kazuomi , Ogasawara Sadahisa , Ikeda Masafumi , Yasui Yutaka , Terashima Takeshi , Yamashita Tatsuya , Obi Shuntaro , Sato Shinpei , Aikata Hiroshi , Ohmura Takumi , Kuroda Hidekatsu , Ohki Takamasa , Nagashima Kengo , Ooka Yoshihiko , Takita Masahiro , Kurosaki Masayuki , Chayama Kazuaki , Kaneko Shuichi , Izumi Namiki , Kato Naoya , Kudo Masatoshi , Omata Masao
Published: July 2020

Background: Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM). Methods: The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM. Results: Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475–0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699–2.155; p = 0.475). Conclusion: HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.
Clinical Significance of Serum Kallistatin and ENOX1 Levels in Patients with Coronary Heart Disease
Authors: Zhang Rui , Ji Zhenjun , Cai Junyan , Li Yongjun , Ma Genshan
Published: July 2020

Background: Kallistatin and ENOX1 are regulators of inflammation and oxidative stress which are typical pathological reactions in atherosclerosis. However, there is limited information of kallistatin and ENOX1 in coronary heart disease (CHD). Methods: Fifty healthy controls, 56 stable angina pectoris (SAP) patients, and 47 acute coronary syndrome (ACS) patients were included in this study. Levels of kallistatin and ENOX1 in serum were measured by ELISA. χ2 test was performed to analyze categorical data. ANOVA, Pearson correlation analysis, and multiple linear regression were performed to analyze the numerical data. Finally, receiver operating characteristic (ROC) curve was applied to assess the diagnostic value of kallistatin in CHD. Results: Among the 153 participants, 59.5% were male and the average age was 63.8 ± 11.39 years. Compared with the control group, kallistatin expression was decreased in the SAP and ACS groups while expression of ENOX1 was increased in the ACS group (p < 0.05). Pearson correlation analysis showed that the kallistatin level was negatively correlated with the Gensini score (r = −0.210, p < 0.01), white blood cell (WBC) count (r = −0.283, p < 0.001), and triglyceride levels (r = −0.242, p < 0.01) and positively correlated with age (r = 0.353, p < 0.001) and high-density lipoprotein cholesterol (r = 0.310, p < 0.001). ENOX1 expression was positively correlated with WBC count (r = 0.244, p < 0.01), international normalized ratio (r = 0.177, p < 0.05), and Gensini score (r = 0.201, p < 0.05). Multiple linear regression showed that Cr, alanine transaminase, glucose, and kallistatin are independent predictors for Gensini score. The ROC curve showed that kallistatin had the highest diagnostic significance (p = 0.007) when the area under curve was 0.636, with a sensitivity of 0.735 and a specificity of 0.495. Conclusion: Expression of kallistatin was decreased in CHD patients and that of ENOX1 was increased in ACS patients. Kallistatin and ENOX1 were closely connected with the severity of CHD, and kallistatin may be helpful in the diagnosis of CHD.
rap da Felicidade e o rap do Silva: Música de protesto?
Authors: Souza Vitor Israel Trindade de
Published: July 2020

Este texto se configura como um ensaio onde abordo elementos da música de protesto negra, especialmente, o gênero conhecido como funk carioca, procurando estabelecer relações com outras abordagens históricas da música de protesto negra no Brasil, principalmente, as produzidas durante os anos de chumbo da ditadura militar brasileira. A metodologia utilizada para a construção deste texto foi a revisão bibliográfica e a análise de diferentes músicas, consideradas enquanto música de protesto, em especial, Rap da Felicidade (CIDINHO; DOCA, 2007) e Rap do Silva (MC Marcinho, 2007), que se estruturaram como ponto de partida para os processos reflexivos.
Resenha da nova edição digital, revisada e modernizada do Livro Educação Musical Através do Teclado volume 1 -Musicalização, de Maria de Lourdes Junqueira Gonçalves e Cacilda Borges Barbosa. Revisores: Tiago Batistone e Ingrid Barancoski.
Authors: Corvisier Fátima Monteiro
Published: July 2020

Resenha sobre nova edição em formato digital, revisada e modernizada, do primeiro volume da série de livros didáticos Educação Musical através do Teclado de Maria de Lourdes Junqueira Gonçalves e Cacilda Borges Barbosa  (livro do aluno - 9a. edição e manual do professor- 3a. edição). Essa edição digital é resultado do trabalho de pesquisa de Tiago Batistone com bolsa de Iniciação Científica PIBIC sob a supervisão e coordenação da Profa. Dra. Ingrid Barancoski, professora titular da Universidade Federal do Estado do Rio de Janeiro (UNIRIO).
Multiple Vulnerabilities to Health Disparities and Incident Heart Failure Hospitalization in the REGARDS Study
Authors: Pinheiro Laura C. , Reshetnyak Evgeniya , Sterling Madeline R. , Levitan Emily B. , Safford Monika M. , Goyal Parag
Published: July 2020

Background:

Socially determined vulnerabilities (SDVs) to health disparities often cluster within the same individual. SDVs are separately associated with increased risk of heart failure (HF). The objective of this study was to determine the cumulative effect of SDVs to health disparities on incident HF hospitalization.

Methods and Results:

Using the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study, we studied 25 790 participants without known HF and followed them for 10+ years. Our primary outcome was an incident HF hospitalization through December 31, 2016. Guided by the Healthy People 2020 framework for social determinants of health, we examined 10 potential SDVs. We retained SDVs associated with incident HF hospitalization (
P
<0.10) and created an SDV count (0, 1, 2, 3+). Using the count, we estimated Cox proportional hazard models to examine associations with incident HF hospitalization, adjusting for potential confounders. Models were stratified by age (45–64, 65–74, and 75+ years) because past reports suggest greater disparities in HF incidence at younger ages. Participants were followed for a median of 10.1 years (interquartile range, 6.5–11.9). Black race, low educational attainment, low annual household income, zip code poverty, poor public health infrastructure, and lack of health insurance were associated with incident HF hospitalization. In adjusted models, among those 45 to 64 years, compared with having no SDV, having 1 SDV (hazard ratio, 1.85 [95% CI, 1.12–3.05]), 2 SDVs (hazard ratio, 2.12 [95% CI, 1.28–3.50]), and 3+ SDVs (hazard ratio, 2.45 [95% CI, 1.48–4.04]) were significantly associated with incident HF hospitalization (
P
for trend, 0.001). We observed no significant associations for older individuals.

Conclusions:

A greater number of SDVs significantly increased risk of incident HF hospitalization among adults <65 years, which persisted after adjustment for cardiovascular risk factors. Using a simple SDV count that could be obtained from a social history during clinical assessment may identify younger individuals at increased risk.
Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B
100
–Reactive CD4
+
T-Regulatory Cells
Authors: Wolf Dennis , Gerhardt Teresa , Winkels Holger , Michel Nathaly Anto , Pramod Akula Bala , Ghosheh Yanal , Brunel Simon , Buscher Konrad , Miller Jacqueline , McArdle Sara , Baas Livia , Kobiyama Kouji , Vassallo Melanie , Ehinger Erik , Dileepan Thamotharampillai , Ali Amal , Schell Maximilian , Mikulski Zbigniew , Sidler Daniel , Kimura Takayuki , Sheng Xia , Horstmann Hauke , Hansen Sophie , Mitre Lucia Sol , Stachon Peter , Hilgendorf Ingo , Gaddis Dalia E. , Hedrick Catherine , Benedict Chris A. , Peters Bjoern , Zirlik Andreas , Sette Alessandro , Ley Klaus
Published: July 2020

Background:

Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4
+
T-helper cells accumulate in the atherosclerotic plaque. Apolipoprotein B
100
(apoB), the core protein of low-density lipoprotein, is an autoantigen that drives the generation of pathogenic T-helper type 1 (T
H
1) cells with proinflammatory cytokine secretion. Clinical data suggest the existence of apoB-specific CD4
+
T cells with an atheroprotective, regulatory T cell (T
reg
) phenotype in healthy individuals. Yet, the function of apoB-reactive T
regs
and their relationship with pathogenic T
H
1 cells remain unknown.

Methods:

To interrogate the function of autoreactive CD4
+
T cells in atherosclerosis, we used a novel tetramer of major histocompatibility complex II to track T cells reactive to the mouse self-peptide apo B
978-993
(apoB
+
) at the single-cell level.

Results:

We found that apoB
+
T cells build an oligoclonal population in lymph nodes of healthy mice that exhibit a T
reg
-like transcriptome, although only 21% of all apoB
+
T cells expressed the T
reg
transcription factor FoxP3 (Forkhead Box P3) protein as detected by flow cytometry. In single-cell RNA sequencing, apoB
+
T cells formed several clusters with mixed T
H
signatures that suggested overlapping multilineage phenotypes with pro- and anti-inflammatory transcripts of T
H
1, T helper cell type 2 (T
H
2), and T helper cell type 17 (T
H
17), and of follicular-helper T cells. ApoB
+
T cells were increased in mice and humans with atherosclerosis and progressively converted into pathogenic T
H
1/T
H
17-like cells with proinflammatory properties and only a residual T
reg
transcriptome. Plaque T cells that expanded during progression of atherosclerosis consistently showed a mixed T
H
1/T
H
17 phenotype in single-cell RNA sequencing. In addition, we observed a loss of FoxP3 in a fraction of apoB
+
T
regs
in lineage tracing of hyperlipidemic
Apoe
–/–
mice. In adoptive transfer experiments, converting apoB
+
T
regs
failed to protect from atherosclerosis.

Conclusions:

Our results demonstrate an unexpected mixed phenotype of apoB-reactive autoimmune T cells in atherosclerosis and suggest an initially protective autoimmune response against apoB with a progressive derangement in clinical disease. These findings identify apoB autoreactive T
regs
as a novel cellular target in atherosclerosis.
Same Root, Different Categories: Encoding Direction in Chinese
Authors: Hu Xuhui
Published: July 2020

The complexity of the directional construction in Chinese involves the following factors: (a) it can take a single directional item as the predicate; (b) two directional items can cooccur to serve as the predicate; (c) one or two directional items can be attached to a matrix verb in a single clause; (d) if more than one directional item is involved, their linear order can differ. I propose that the leading factor behind this complexity is that in Chinese a single Root can take different categories when merged in different syntactic positions. Therefore, the same directional item may in fact have the phonological form of a verb, a preposition, a part of a single preposition, or even a spatial aspectual marker in different directional constructions. I then place this account within the context of parametric studies of motion event constructions, showing that two new dimensions can be added: the special property of Roots in a language and the existence of Spatial Aspect in at least some languages.
Feeding competition inferred from patch depletion in a supergroup of Rwenzori black-and-white colobus monkeys (Colobus angolensis ruwenzorii) in Rwanda
Authors: Miller Alex , Judge Debra S. , Uwingeneye Grace , Ndayishimiye Dieudonne , Kaplin Beth A. , Grueter Cyril C.
Published: July 2020

Competition for food is often a cost associated with living in a group, and can occur in an indirect (scramble) or direct (contest) form. We investigated feeding competition in a supergroup of Rwenzori black-and-white colobus monkeys (Colobus angolensis ruwenzorii) in Rwanda, with the aim of establishing whether freedom from scramble competition allows these monkeys to form supergroups. We used the patch depletion method, measuring intake rate coupled with movement rate, to assess if food patches become depleted over the occupancy period. Resource depletion was evident when the colobus fed on young leaves, but not when feeding on mature leaves. Scramble competition was inferred from a negative correlation between group size and change in intake rate over patch occupancy. Between-group contest competition was inferred from displacement from patches. Although feeding competition exists for select resources, limited competition for mature leaves may enable Rwenzori colobus to live in a supergroup of hundreds of individuals in this montane forest.
A comparative evaluation of the nutritional quality of Eriocheir sinensis and Eriocheir japonica (Brachyura, Varunidae)
Authors: Wang Zhiyan , Zu Lu , Li Qingqing , Jiang Xiaodong , Xu Wengang , Soyano Kiyoshi , Cheng Yongxu , Wu Xugan
Published: July 2020

The Japanese mitten crab Eriocheir japonica is an economically important species widely distributed throughout the East Asia region, but information on the compositional characteristics and nutritional quality of E. japonica is still scarce. Thus, this study was conducted to compare the edible tissue indices, proximate composition, fatty acid profiles and amino acid contents between wild E. sinensis and E. japonica. It showed that: (1) both E. sinensis and E. japonica have a high total edible yield (approximately 40%); (2) E. sinensis and E. japonica have a similar proximate composition, except for total lipids; (3) female E. japonica have higher percentages of C18:3n3, C20:5n3 and C22:6n3; (4) E. sinensis have higher levels of essential amino acids than E. japonica in muscle. In conclusion, these results demonstrated that wild E. japonica is rich in omega-3 fatty acids, and both E. sinensis and E. japonica are aquatic food of high nutritional value, with a high edible yield.