bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of Na/H exchanger stimulates glioma tumor immunogenicity and enhances combinatorial TMZ and anti-PD-1 therapy
Authors: Guan Xiudong , Hasan Md Nabiul , Begum Gulnaz , Kohanbash Gary , Carney Karen E. , Pigott Victoria M. , Persson Anders I. , Castro Maria G. , Jia Wang , Sun Dandan 
Published: September 2018

AbstractThe weak immunogenicity of gliomas presents a barrier for effective immunotherapy. Na/H exchanger isoform 1 (NHE1) maintains alkaline intracellular pH (pHi) of glioma cells and acidic microenvironment. In addition, NHE1 is expressed in tumor-associated microglia and tumor-associated macrophages (TAMs) and involved in protumoral communications between glioma and TAMs. Therefore, we hypothesize that NHE1 plays a role in developing tumor resistance and immunosuppressive tumor microenvironment. In this study, we investigated the efficacy of pharmacological inhibition of NHE1 on combinatorial therapies. Here we show that temozolomide (TMZ) treatment stimulates NHE1 protein expression in two intracranial syngeneic mouse glioma models (SB28, GL26). Pharmacological inhibition of NHE1 potentiated the cytotoxic effects of TMZ, leading to reduced tumor growth and increased median survival of mice. Blockade of NHE1 stimulated proinflammatory activation of TAM and increased cytotoxic T cell infiltration into tumors. Combining TMZ, anti-PD-1 antibody treatment with NHE1 blockade significantly prolonged the median survival in the mouse glioma model. These results demonstrate that pharmacological inhibition of NHE1 protein presents a new strategy for potentiating TMZ-induced cytotoxicity and increasing tumor immunogenicity for immunotherapy to improve glioma therapy.
Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans
Authors: Harders Rikke Hindsgaul , Morthorst Tine Hørning , Lande Anna Dippel , Hesselager Marianne Overgaard , Mandrup Ole Aalund , Bendixen Emøke , Stensballe Allan , Olsen Anders 
Published: September 2018

AbstractApoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis.
Exome and copy number variation analyses of Mayer–Rokitansky–Küster– Hauser syndrome
Authors: Takahashi Kazumi , Hayano Takahide , Sugimoto Ryota , Kashiwagi Hirofumi , Shinoda Mari , Nishijima Yoshihiro , Suzuki Takahiro , Suzuki Shingo , Ohnuki Yuko , Kondo Akane , Shiina Takashi , Nakaoka Hirofumi , Inoue Ituro , Izumi Shun-ichiro 
Published: September 2018

AbstractMayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by congenital absence of the vagina and uterus. We conducted genome-wide SNP analyses and exome sequencing to detect the causes of MRKH syndrome. We identified de novo variants ofMYCBP2,NAV3, andPTPN3in three families and a variant ofMYCBP2in a sporadic case. Here, we demonstrated the partial genetic makeup of Japanese MRKH syndrome.
Reprogramming of regulatory network using expression uncovers sex-specific gene regulation in Drosophila
Authors: Wang Yijie , Cho Dong-Yeon , Lee Hangnoh , Fear Justin , Oliver Brian , Przytycka Teresa M. 
Published: September 2018

AbstractGene regulatory networks (GRNs) describe regulatory relationships between transcription factors (TFs) and their target genes. Computational methods to infer GRNs typically combine evidence across different conditions to infer context-agnostic networks. We develop a method, Network Reprogramming using EXpression (NetREX), that constructs a context-specific GRN given context-specific expression data and a context-agnostic prior network. NetREX remodels the prior network to obtain the topology that provides the best explanation for expression data. Because NetREX utilizes prior network topology, we also develop PriorBoost, a method that evaluates a prior network in terms of its consistency with the expression data. We validate NetREX and PriorBoost using the “gold standard” E. coli GRN from the DREAM5 network inference challenge and apply them to construct sex-specific Drosophila GRNs. NetREX constructed sex-specific Drosophila GRNs that, on all applied measures, outperform networks obtained from other methods indicating that NetREX is an important milestone toward building more accurate GRNs.
High-content ductile coherent nanoprecipitates achieve ultrastrong high-entropy alloys
Authors: Liang Yao-Jian , Wang Linjing , Wen Yuren , Cheng Baoyuan , Wu Qinli , Cao Tangqing , Xiao Qian , Xue Yunfei , Sha Gang , Wang Yandong , Ren Yang , Li Xiaoyan , Wang Lu , Wang Fuchi , Cai Hongnian 
Published: September 2018

AbstractPrecipitation-hardening high-entropy alloys (PH-HEAs) with good strength−ductility balances are a promising candidate for advanced structural applications. However, current HEAs emphasize near-equiatomic initial compositions, which limit the increase of intermetallic precipitates that are closely related to the alloy strength. Here we present a strategy to design ultrastrong HEAs with high-content nanoprecipitates by phase separation, which can generate a near-equiatomic matrix in situ while forming strengthening phases, producing a PH-HEA regardless of the initial atomic ratio. Accordingly, we develop a non-equiatomic alloy that utilizes spinodal decomposition to create a low-misfit coherent nanostructure combining a near-equiatomic disordered face-centered-cubic (FCC) matrix with high-content ductile Ni3Al-type ordered nanoprecipitates. We find that this spinodal order–disorder nanostructure contributes to a strength increase of ~1.5 GPa (>560%) relative to the HEA without precipitation, achieving one of the highest tensile strength (1.9 GPa) among all bulk HEAs reported previously while retaining good ductility (>9%).
Critical deposition height for sustainable restoration via laser additive manufacturing
Authors: Paul Santanu , Singh Ramesh , Yan Wenyi , Samajdar Indradev , Paradowska Anna , Thool Khushahal , Reid Mark 
Published: September 2018

AbstractLaser material deposition based restoration of high-value components can be a revolutionary technology in remanufacturing. The deposition process induces residual stresses due to thermomechanical behavior and metallurgical transformations. The presence of tensile residual stresses in the deposited layer will compromise the fatigue life of the restored component. We have developed a novel fully coupled metallurgical, thermal and mechanical (metallo-thermomechanical) model to predict residual stresses and identified a critical deposition height, which ensures compressive residual stresses in the deposited layer. Any lower deposition height will result in tensile residual stresses and higher deposition height will result in excessive dilution (substrate melting). We have validated the model using neutron and micro-focus X-ray diffraction measurements. This study highlights that the critical deposition height corresponds to the minimum cooling rate during solidification. It addresses one of the major outstanding problems of additive manufacturing and paves a way for “science-enabled-technology” solutions for sustainable restoration/remanufacturing.
Protein-protein interactions reveal key canonical pathways, upstream regulators, interactome domains, and novel targets in ALS
Authors: Dervishi Ina , Gozutok Oge , Murnan Kevin , Gautam Mukesh , Heller Daniel , Bigio Eileen , Ozdinler P. Hande 
Published: September 2018

AbstractDeveloping effective treatment strategies for neurodegenerative diseases require an understanding of the underlying cellular pathways that lead to neuronal vulnerability and progressive degeneration. To date, numerous mutations in 147 distinct genes are identified to be “associated” with, “modifier” or “causative” of amyotrophic lateral sclerosis (ALS). Protein products of these genes and their interactions helped determine the protein landscape of ALS, and revealed upstream modulators, key canonical pathways, interactome domains and novel therapeutic targets. Our analysis originates from known human mutations and circles back to human, revealing increased PPARG and PPARGC1A expression in the Betz cells of sALS patients and patients with TDP43 pathology, and emphasizes the importance of lipid homeostasis. Downregulation of YWHAZ, a 14-3-3 protein, and cytoplasmic accumulation of ZFYVE27 especially in diseased Betz cells of ALS patients reinforce the idea that perturbed protein communications, interactome defects, and altered converging pathways will reveal novel therapeutic targets in ALS.
Closing water productivity gaps to achieve food and water security for a global maize supply
Authors: Zheng Huifang , Bian Qianqian , Yin Yulong , Ying Hao , Yang Qinghua , Cui Zhenling 
Published: September 2018

AbstractTo achieve food and water security, it is as important to close the water productivity (WP) gap (which was defined as the difference between the maximum attainable WP and the currently achieved WP at the field scale) as it is to close yield gaps. However, few studies have provided quantitative estimates of existing WP gaps and constraining factors for global maize production. Using a meta-analysis of 473 published studies covering 31 countries and 5,553 observations (932 site-years), we found the global average WP value for irrigated maize was 18.6 kg ha−1 mm−1. These WPs varied by factors such as seasonal precipitation, irrigation regimes, soil organic matter and soil pH. In current production systems, there exists a huge scope for improvement in maize WP, but the reported field experiments achieved only 20–46% of potential WP across all countries. Considering the future, raising WP to 85% of potential WP by 2050, a 100% increase in maize production could be achieved with 20% less planted area and 21% less water consumption than in 2005. Closing the WP gap may be critical to ensuring food security and achieving sustainable global agriculture.
Monitoring of microbial dynamics in a drinking water distribution system using the culture-free, user-friendly, MYcrobiota platform
Authors: Boers Stefan A. , Prest Emmanuelle I. , Taučer-Kapteijn Maja , Knezev Aleksandra , Schaap Peter G. , Hays John P. , Jansen Ruud 
Published: September 2018

AbstractDrinking water utilities currently rely on a range of microbiological detection techniques to evaluate the quality of their drinking water (DW). However, microbiota profiling using culture-free 16S rRNA gene next-generation sequencing (NGS) provides an opportunity for improved monitoring of the microbial ecology and quality of DW. Here, we evaluated the utility of a previously validated microbiota profiling platform (MYcrobiota) to investigate the microbial dynamics of a full-scale, non-chlorinated DW distribution system (DWDS). In contrast to conventional methods, we observed spatial and temporal bacterial genus changes (expressed as operational taxonomic units - OTUs) within the DWDS. Further, a small subset of bacterial OTUs dominated with abundances that shifted across the length of the DWDS, and were particularly affected by a post-disinfection step. We also found seasonal variation in OTUs within the DWDS and that many OTUs could not be identified, even though MYcrobiota is specifically designed to reduce potential PCR sequencing artefacts. This suggests that our current knowledge about the microbial ecology of DW communities is limited. Our findings demonstrate that the user-friendly MYcrobiota platform facilitates culture-free, standardized microbial dynamics monitoring and has the capacity to facilitate the introduction of microbiota profiling into the management of drinking water quality.
Rapid in situ synthesis of polymer-metal nanocomposite films in several seconds using a CO2 laser
Authors: Kashihara Kazuhiko , Uto Yuki , Nakajima Takashi 
Published: September 2018

AbstractWe demonstrate the rapid in situ synthesis of polymer-metal nanocomposite films using a CO2 laser at 10.6 μm. The mechanism of our method is that the precursor of the metal nanoparticles, i.e., the metallic ions, is very rapidly reduced in the laser-heated polymer matrix without any reducing agent. Unlike other known laser-induced reduction methods using UV lasers, which produce radicals to promote reduction, the CO2 laser energy is mainly absorbed by the glass substrate, and the laser-heated substrate heats the polymer matrix through heat diffusion to promote reduction. The superiority of the use of CO2 lasers over nanosecond visible~UV lasers is also demonstrated in terms of the damage to the film. The developed method can be a new alternative to quickly synthesize a variety of polymer-metal nanocomposite films.
Spatial and temporal characteristics of temperature effects on cardiovascular disease in Southern China using the Empirical Mode Decomposition method
Authors: Huang Jixia , Wang Li , Wang Shibo , Lu Yaling , Zhang Weiwei , Wang Jinfeng 
Published: September 2018

AbstractUntil now, few studies have analyzed the effects of temperature on cardiovascular disease (CVD) death at different time points. In this study, we chose 9 different cities in the subtropical and tropical areas of China and analyzed the correlation between temperature at different time points and CVD mortality. We completed this study in two steps. First, we analyzed different time trend decomposition data related to CVD mortality in different populations within the 9 selected cities using empirical mode decomposition (EMD). Second, we created a regression fitting analysis of CVD mortality and temperatures at different time periods. The results showed that the CVD mortality of subtropical and tropical areas in southern Chinese cities represented spatial heterogeneity. The CVD mortality rates in Beihai, Hefei and Nanning showed rising trends, whereas the CVD mortality rates in Haikou, Guilin and Changde appeared to be decreasing. At the daily, seasonal and year time scales, low temperatures were negatively correlated with CVD mortality. Other than at the daily time scale, high temperatures did not significantly influence CVD mortality. This article will help to develop appropriate measures to reduce temperature-related mortality risk in different populations within the subtropical and tropical regions of China.
In‐flight RCS measurements of drones and birds at K‐band and W‐band
Authors: Rahman Samiur , Robertson Duncan Alexander 
Published: September 2018

This study presents the in‐flight radar cross‐section (RCS) data of drones and birds at K‐band and W‐band obtained from extensive experimental trials. The focus of this study is to demonstrate the RCS characteristics of these targets in practical scenarios, hence experimental results are used exclusively. Owing to variations in orientation, aspect angle and target motion, the measured RCS values of these targets fluctuate significantly during their flight. Three very well‐calibrated frequency modulated continuous wave radar systems, one operating at the K‐band (24 GHz) and two at W‐band (94 GHz), have been used to collect data for RCS analysis. Three drones of different sizes (DJI Phantom 3 Standard, DJI Inspire 1 and DJI S900 Hexacopter) and four birds of prey of different sizes (Northern Hawk Owl, Harris Hawk, Indian Eagle Owl and Tawny Eagle) have been used for data collection. The results demonstrate that the RCS scales broadly with the size of the target, consistent with the optical scattering regime and that the RCS values for each target are comparable at the K‐band and the W‐band. The statistical distribution of RCS for each target falls within a certain range which is useful for predicting the performance of a drone detection radar.
Pulsierende Schröpftherapie bei Kniegelenkarthrose und Rückenschmerzen
Authors: Teut Michael , Ullmann Alexander , Kaiser Stefan , Binting Sylvia , Cree Margit , Brinkhaus Benno 
Published: September 2018

SummaryBeim pulsierenden Schröpfen werden Schröpfköpfe lokal angesetzt und die Saugeffekte pulsierend durch eine verbundene Pumpe erzeugt. In 2 randomisierten Studien wurdediese Methode auf ihre Wirksamkeit bei Kniegelenksarthrose und chronischen Rückenschmerzen der Lendenwirbelsäule hin überprüft. In Vergleichen zu einer Kontrollgruppe, die nur Bedarfsmedikation erhielt, konnte2-mal Schröpfen pro Woche über einen Monat nach 4 und 12 Wochen Schmerzen lindern, Funktionen verbessern und die körperliche Lebensqualität bei Patienten mit chronischen Schmerzen steigern. Weitere, bestätigende Studien an größeren Patientenkollektiven und mit hochwertigen Methoden müssen folgen, um die Ergebnisse dieser Studien zu bestätigen.
The effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy
Authors: Liu Zu-Qiang , Li Quan-Lin , Chen Wei-Feng , Zhang Xiao-Cen , Wu Qiu-Ning , Cai Ming-Yan , Qin Wen-Zheng , Hu Jian-Wei , Zhang Yi-Qun , Xu Mei-Dong , Yao Li-Qing , Zhou Ping-Hong 
Published: September 2018

Abstract
Background Peroral endoscopic myotomy (POEM) is a treatment option for patients with previous surgical or endoscopic treatment. We aimed to evaluate the influence of prior treatment on perioperative and follow-up outcomes in patients undergoing POEM.
Methods From August 2010 to December 2014, a total of 1384 patients with achalasia underwent POEM at our center. We retrospectively reviewed 849 patients who completed follow-up. Patients with an Eckardt score ≥ 4 after POEM were considered to have a clinical failure. We compared variables between patients with and without prior treatment. We analyzed risk factors for perioperative major adverse events, and clinical reﬂux and failure during follow-up.
Results 245 patients (28.9 %) had undergone prior treatment, and 34 patients (4.0 %) experienced a major adverse event associated with the POEM procedure. During a median follow-up of 23 months (range 1 – 71), clinical reflux occurred in 203 patients (23.9 %) and clinical failure was recorded for 94 patients (11.1 %). Patients with prior treatment had a longer procedure duration (P = 0.001) and longer hospital stay after POEM (P = 0.001). Prior treatment was not an independent risk factor for major adverse events or clinical reflux (odds ratio [OR] 1.19, P = 0.65; OR 1.26, P = 0.19; logistic regression), but it did increase the rate of clinical failure during follow-up (hazard ratio 1.90, P = 0.002; Cox regression).
Conclusions POEM was performed safely with a low rate of major adverse events in patients with achalasia who had undergone prior surgical or endoscopic treatment. However, prior treatment increased the risk of clinical failure after POEM.
SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials
Authors: Wang Keke , Zhang Yansong , Zhao Chunyang , Jiang Mingyan 
Published: September 2018

AbstractSodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD –0.22; 95% CI: –0.30, –0.14; p=0.000) and fasting plasma glucose (SMD –0.48; 95% CI: –0.56, –0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD −0.72; 95% CI: –0.81, –0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.
Allograft Reconstruction of the Knee—Methods and Outcomes
Authors: Temple H. 
Published: September 2018

AbstractAlthough allograft usage has decreased over the past three decades in favor of segmental metal implants, they still have an important role in the reconstruction of large osteochondral defects following tumor resection. The decline of allografts in limb salvage is multifactorial and includes limited availability, technical difficulty, increased rates of infection and fracture, and unpredictable results. There are circumstances where allograft transplantation is useful around the knee resulting in improved function, bone and joint preservation, and acceptable long-term outcomes.
Total Knee Arthroplasty Wrong Side Implant
Authors: Alanazi Hassan , Alahmari Mousa , Hashem Musaab , Alqahtani Muath , Alanazi Abdulaziz , Alenazi Bashir 
Published: September 2018

AbstractWe report a unique wrong implant error during bilateral total knee replacement procedure in 72-year-old woman with bilateral knee osteoarthritis that failed conservative treatment. Patient has severe bilateral knee pain. Examination showed full range of motion. X-ray showed severe bilateral tricompartmental osteoarthritis. Patient underwent surgery in 2013; postoperative radiographs showed well-fixed femoral, tibial, and patellar components but right femoral implant was placed in the left knee. Postoperative examination showed painless full range of motion. One similar case report found describing wrong-site femoral component that ended with symptomatic. In our case, no complications were observed.