bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Specific Symptoms As A Prodrome Of Immune-Related Adverse Events In Patients With Non-Small Cell Lung Cancer Receiving Nivolumab: A Consecutive Analysis Of 200 Patients
Authors: Higashiyama Ryoko Inaba , Horinouchi Hidehito , Kuchiba Aya , Matsumoto Yuji , Murakami Shuji , Goto Yasushi , Kanda Shintaro , Fujiwara Yutaka , Yamamoto Noboru , Ohe Yuichiro 
Published: February 2022

Abstract
Introduction: Immune checkpoint blockade therapy is the standard treatment for metastatic or refractory non-small cell lung cancer (NSCLC). however, it is associated with immune-related adverse events (irAEs). irAEs are sometimes fatal, however, an efficient method for early irAEs detection has not been developed because their onset timing varies. We examined the significance of non-specific symptoms as a prodrome of irAEs in patients with NSCLC.Methods: We reviewed consecutive patients who received nivolumab at a dosage of 3 mg/kg every 2 weeks for metastatic NSCLC between December 2015 and August 2017. Patient demographics, irAEs and signal symptoms were recorded. Non-specific symptoms (fever and fatigue) occurred 7 days or earlier before the onset of irAEs were considered signal symptoms. For statistical analyses, the association between irAEs and clinical information, including signal symptoms, was evaluated using Fisher’s exact test and logistic regression.Results: A total of 200 patients received nivolumab; 131 (65.5%) were male, their median age was 63 years (range, 30-83), 174 (87.0%) had performance status of 0-1. Signal symptoms occurred in 38 (19.0%) of the 77 patients (38.5%) who experienced irAEs, and were positively associated with the occurrence of irAEs (P<0.01). Multivariate analysis showed that the occurrence of irAEs was significantly higher in patients with PS 0-1 (odds ratio [OR] 7.01; 95% confidence intervals [CI], 1.69–29.13) and patients experienced signal symptoms (OR 17.30; 95%CI, 6.51–45.99).Conclusions: The occurrence of signal symptoms could be used in the early detection and management of irAEs in patients during immune checkpoint blockade therapy.
Powder Flow Simulation of a Ring Type Coaxial Nozzle and Cladding Experiment in Laser Metal Deposition
Authors: Zhou Heng , Yang Yongqiang , Wang Di , Li Yang , Zhang Shiqin , Tai Zhiheng 
Published: February 2022

Abstract
A 3D whole size numerical model of a ring type coaxial nozzle was established to obtain particle space trajectory and convergence character. The realizable k-ε model was applied in the gas flow phase; the powder flow was coupled to the gas flow by Euler-Lagrange approach as a discrete phase model. Different powder material and particle size range were chosen to calculate the powder concentration distribution. The simulated powder stream morphology was in good agreement with the experimental results of high-speed camera observations. Simulating results show that the using of mean diameter \(\stackrel{-}{\text{d}}\) to replace Rossin–Rammler distribution of particle size could also get an accurate flowing characteristic results based on this model, this replacement could save a lot computational resource and shrinkage the computing time. The existing of coaxial shielding gas can impact the powder mass concentration spatial distribution, maximum value convergence height and spot size of the powder flow directly. For 316L with small particle size and Ni60A with large particle size, we found different change regularity and no linear relationship was found. So it was not suggest change the input volume of coaxial shielding gas without special needs. Combining with the laser cladding experiments of Ni60A, results show that the developed ring type coaxial nozzle could transport powder well and prepare excellent deposited layers, the conditional powder utilization ratio can up to 75.9%.
A Low-profile Broadband Crossed-dipole Antenna with Fractal Structure and Inverted-L Plates
Authors: Feng Guirong , Qi Tian-yi , Li Jiachen , Wang Xinwei , Li Mingming , Yang Hailong 
Published: February 2022

Abstract
A low-profile broadband circularly polarized (CP) crossed-dipole antenna is proposed. In this antenna, the dipole uses a fractal-based structure with multiple similar patches for obtaining broadband CP radiation and impedance matching. The incorporation of the crossed-dipole antenna with four triangular parasitic patches improves both the impedance and axial ratio (AR) bandwidths. Four parasitic inverted-L metal plates are loaded on the ground plane to significantly enhance the AR bandwidth and reduce the antenna profile. The measured results are in agreement with the simulations, which demonstrates that the proposed antenna has a low profile of 0.18 λ0, a -10 dB impedance bandwidth of 91% (2.78~7.42 GHz), a 3 dB AR bandwidth of 81.5% (2.99~7.1 GHz), and a good right hand circular polarization (RHCP) radiation pattern with an average gain of 7.9 dBi over the whole operating band.
Dinutuximab Beta-Targeted Immunotherapy Kills Pancreatic Beta Cell Tumors
Authors: Kacar Ayse Karatug , Adıguzel Zelal 
Published: February 2022

Abstract
Dinutuximab beta is the first monoclonal antibody that used for the treatment of neuroblastoma. The aim of this study is to investigate the effects of Dinutuximab beta, whose effect is unknown in pancreatic beta cell tumor, based on the similarity between pancreatic beta cells and neurons. We have used insulinoma INS-1 cells. Dinutuximab beta (Qarziba®) which presented by EUSA Pharma was used for the experiments. The cell cytotoxicity was induced by STZ. Dinutuximab beta was administered to the cells following STZ administration and before STZ administration. The cell viability with WST-1 assay, reactive oxygen species by using dichlorofluorescein diacetate were measured. The cells were marked with DAPI to indicate apoptotic markers with confocal microscope. GLUT2, IR, Ins1 and Ins2 expression levels were analyzed with q-RT-PCR. The INS-1 cells proliferated with administration of Dinutuximab beta alone. The result of Dinutuximab beta administered following STZ administration, resulted in more cell death, increased ROS levels, GLUT2, Ins1, Ins2 gene expression levels and decreased IR gene expression levels than Dinutuximab beta administered before STZ administration. After Dinutuximab beta was administered to the cells following STZ administration, the cells predominantly died via apoptosis showing cytoplasmic condensation and DNA fragmentation after 24 and 48 hours. As a result, Dinutuximab beta can show its effect after occurring toxicity. Time-dependent cell death increases as a result of administration of Dinutuximab beta after toxicity induced by STZ in insulinoma cells. Its use as a chemotherapeutic agent in tumor treatment should be supported by in vivo studies.
A Rifampicin-resistant (rpoB) Mutation in Pseudomonas Stutzeri Leads to Enhance the Biosynthesis of Secondary Metabolites and Nitrogen Fixation to Adapt Against Harsh Environments
Authors: Alam Khandakar Mohiul , Yan Yongliang , Lin Min , Islam Md. Ariful , Gaber Ahmed , Hossain Akbar 
Published: February 2022

Abstract
The rpoB gene encoding for β subunit of RNA polymerase has been targeted as a mutation for importance to Rifampicin Resistant (Rifr) phenotype of the bacteria. The study aimed to learn the mutational processes, location of the mutation and metabolic capabilities among the strains and nitrogen fixation capacity of the bacteria for acclimatization in the environment. In this study, wild type and 5 rpoBRifr mutants of Pseudomonas stutzeri such Q518R, D521Y, D521V, H531R and I614T were characterized and used as a test system. The robust Rifr phenotype of P. Stutzeri was associated only with base replacements of the amino deposits. Considering these facts, the current study was conducted to investigate the effect of rpoB mutants on metabolism, a wild-type and five distinct Rifr mutants of P. stutzeri for utilization of 95 substrates through Biolog GN2 MicroPlates. Several oxidized substrate usage patterns occurred in the Rifrmutants, use of carboxylic and amino acids significantly increased in various rifr mutants than that of wild type. The assimilation of carbon and nitrogen sources of rifr mutants reveals that the organism maintains the adaptation in nutritionally complex environments. Acetylene reduction assay carried out at different times it revealed that considerable variability was found in the nitrogen fixation ability among the studied strains. The highest nitrogenase activity was determined rifr mutant D521V that was of 2176.6 nmole ethylene/h/mg protein. Base substitution at different sites of rifrmutatnts caused nucliec acid transition, is responsible for codon change into the amino acids which differ carbon and nitrogen utilization. The assimilation of carbon and nitrogen sources of Pseudomonas stutzeri and its rifr mutants ensures that the organism maintains the adaptation in nutritionally complex environments and can fix nitrogen.
Cardiac Dysfunction in Medulloblastoma Survivors Treated with Photon Irradiation
Authors: Cacciotti Chantel , Chordas Christine , Valentino Katie , Allen Rudy , Lenzen Alicia , Burns Karen , Nagarajan Rajaram , Manley Peter , Pillay-Smiley Natasha 
Published: February 2022

Abstract
Introduction. Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment often includes a combination of surgical resection, craniospinal irradiation (CSI) and chemotherapy. Children who receive standard photon CSI are at risk for cardiac toxicities including coronary artery disease, left ventricular scarring and dysfunction, valvular damage, and atherosclerosis. Current survivorship guidelines recommend routine echocardiogram (ECHO) surveillance. In this multi-institution study, we describe markers of cardiac dysfunction in medulloblastoma survivors. Methods. A retrospective chart review of medulloblastoma patients who had photon beam CSI followed by ECHO between 1980 and 2010 at Lurie Children’s Hospital and Dana-Farber/Boston Children’s Hospital.Results. During the 30-year study period, 168 medulloblastoma patient records were identified. Included in this study were the 75 patients who received CSI or spinal radiation and ECHO follow up. The mean age at CSI was 8.6 years (range, 2.9-20), and the mean number of years between radiation (RT) completion and first ECHO was 7.4 (range, 2-16). Mean ejection fraction (EF) was 60.0% and shortening fraction (SF) was 33.8%. Five patients (7%) had abnormal ECHO results: three with EF <50% and two with SF <28%.Conclusion. Majority of medulloblastoma patients who received CSI have relatively normal ECHOs post treatment, however 7% of patients had abnormal ECHOs. The implication of our study for medulloblastoma survivors is that further investigations are needed in this populations with a more systematic, longitudinal assessment to determine predictors and screenings.
Propensity Score Weighting With Survey Weighted Data When Outcomes Are Binary
Authors: Yang Chen , Cuerden Meaghan S. , Ji Jiayi , Aldridge Melissa , Li Lihua 
Published: February 2022

Abstract
Background Despite that propensity score methods have been widely adopted in observational studies, few studies have focused on how to properly estimate and incorporate propensity scores in complex survey data settings. Particularly, it is lacking that the research on propensity score-based weighting methods when estimating the treatment effect using complex survey data with binary outcomes. The objective of this study is therefore to compare three propensity score weighting methods for complex survey data when outcomes are binary. MethodsA simulation study was used to compare three propensity score weighting approaches for estimating treatment effects using survey data: 1) no survey weights in the propensity score model or the outcome model; 2) survey weights in the outcome model only; 3) survey weights in both models. Each of the three methods is applied in the context of four measures of the treatment effect: the sample average treatment effect (SATE), the population average treatment effect (PATE), the sample average treatment effect on the treated (SATT), and the population average treatment effect on the treated (PATT). The methods are compared in terms of mean relative bias and coverage probability under different scenarios by varying combinations of sample size and treatment effect, degrees of model misspecification and levels of overlap in propensity score. In addition, using the 2015 National Health Interview Survey (NHIS) data as a real data example, each method is employed to estimate the effect of provider-patient discussion about smoking on smoking cessation. ResultsThe methods which account for the survey weight outperform the unweighted method as the degree of misspecification increases, regardless of the sample size, treatment effect and level of overlap in propensity score. The performance of the two weighted methods, where the survey weight is incorporated in the outcome model or both the propensity score model and the outcome model, are similar. Conclusions The propensity score weighting methods accounting for the survey weight are necessary for estimating the population-level treatment effects. This paper provides guidance for selecting an appropriate propensity score weighting method based on the estimand of interest when using complex survey data with binary outcomes.
Inertial Effects Due to Eruption-induced Atmospheric Disturbances Identified by Superconducting Gravimeter Observations at Matsushiro, Japan
Authors: Imanishi Yuichi 
Published: February 2022

Abstract
The violent eruption of Hunga Tonga-Hunga Ha'apai volcano on January 15, 2022 induced strong atmospheric disturbances, which traveled around the world as atmospheric Lamb waves. When this wave passed through the superconducting gravimeter station at Matsushiro, Japan, a large signal of gravity changes was recorded. Also, barometers installed around Matsushiro recorded wave trains of pressure changes. Analysis of the barometer data revealed that the atmospheric disturbances traveled as plane waves. Applying the theory of atmospheric loading for traveling plane waves, the observed gravity changes were well reproduced by a sum of three components of atmospheric loading, namely, Newtonian, free-air and inertial effects. In particular, the inertial effect of atmospheric loading, which is rarely observed, is clearly identified in the gravity data. From the theoretical modeling, an estimate of rigidity in the shallow region of the Earth was also obtained.
In Silico and Experimental Analyses of Long Non-Coding RNA TMPO-AS1 Expression in Gastric Cancer Tissues
Authors: Mohammadali Elaheh , Safaralizadeh Reza , Poursheikhani Arash , Asvadi Tooraj , Baradaran Behzad 
Published: February 2022

Abstract
Background
A large body of evidence has illustrated the prominent roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in cancer progression and diagnosis. In this study, we considered in silico and experimental analyses of long non-coding TMPO-AS1 expression in adjacent nonmalignant tissues and cancerous tissues of the patients with gastric cancer.
Methods
In order to conduct the present study, 40 gastric tumor samples and 40 marginal noncancerous counterparts were collected. The TMPO-AS1 expression levels in patients’ samples were evaluated by qRT-PCR analysis. The Cancer Genome Atlas (TCGA) data were retrieved for TMPO-AS1 and analyzed via Gepia and TANRIC online tools. Student t-test, one-way ANOVA, and chi-square test were accomplished via SPSS software.
Results
The data demonstrated that TMPO-AS1 was overexpressed in cancerous tissues compared to nonmalignant adjacent ones (p: 0.0076). The TCGA data demonstrated that TMPO-AS1 was upregulated in GC tissues in comparison to nonmalignant adjacent ones (p = 0.001).
Conclusion
Altogether, in our study, we demonstrated lncRNA TMPO-AS1 could be considered as a biomarker in GC.However, further investigations are required to indicate the potential application of this lncRNA in diagnosis, prognosis and therapeutic target of GC.
Expression and Structural Characterization of Recombinant Mercuric Reductase Protein Isolated from Streptomyces
Authors: Khasanah Anis Uswatun , Putri Wahyu Aristyaning , Rahayu Hanum Mukti , Sembiring Langkah , Purwestri Yekti Asih 
Published: February 2022

Abstract

Efforts to control mercury pollution have been made for the last twenty years using various biological, physical, and chemical approaches. Streptomyces is able to degrade mercury because it possesses the mercuric reductase enzyme encoded by merA. The merA from Streptomyces isolate AS2 (Accession numbers LC026157) has been cloned into the expression vector pEt-28c(+). Therefore, it is critical to study recombinant mercuric reductase protein's expression and to analyse the protein structure. Expression of merA from an AS2 isolate was successfully performed in the host Escherichia coli BL21. Detection of mercuric reductase using SDS-PAGE showed a dominant band at 55–70 kDa. E. coli BL21 induction by IPTG was optimal at concentrations of 1 and 1.2 mM, and the optimal incubation times were 18 hours. The highest specific activity of mercuric reductase was 294.07 U/mg. Mercuric reductase protein in Streptomyces AS2 shares high homology with Lysinibacillus sphaericus (Swiss-Model), and similar folding to that of c5c1Yc refers to mercuric reductase from L. sphaericus using Phyre2. Based on amino acid sequences, the result revealed that Streptomyces AS2 strains were a group of Streptomyces lividans. These results give new insight to study further into a potential of MerA for bioremediation in the environment.
External Concurrent Occipital and Trigeminal Neurostimulation Relieves Migraine Headache: A Prospective, Randomized, Double-Blind, Sham-Controlled Trial
Authors: Daniel Oved , Tepper Stewart J. , Deutsch Lisa , Sharon Roni 
Published: February 2022

Abstract
Background: Combined peripheral occipital and trigeminal neurostimulation is clinically proven to alleviate migraine symptoms, however, it was previously possible only via high-risk surgical procedures. Neuromodulation using currently available peripheral nerve stimulation devices stimulates only one nerve. The objective of this prospective, randomized, double-blind, sham-controlled trial was to evaluate the efficacy, safety and tolerability of a novel external concurrent occipital and trigeminal neurostimulation (eCOT-NS) device designed as a self-administered home treatment for migraine (Relivion® MG, Neurolief, Ltd; Netanya, Israel).Methods: Episodic and chronic migraine subjects (N=55) were randomized to receive active (n=27) or sham (n=28) treatment. Each subject received an eCOT-NS device and performed a 60 ±20-minute treatment at home within 45 minutes of migraine episode onset. The primary endpoint was the change in mean baseline pain intensity based on VAS pain scores 1 hour after treatment initiation, defined as relative (percent) change. Treatment outcomes assessed at 1, 2 and 24 hours post-treatment initiation were pain-reduction, and proportion of pain-free subjects and treatment responders, defined as ≥50% pain reduction. Categorical pain ratings (none, mild, moderate, and severe pain) were also analyzed.Results: Active stimulation was significantly more effective than sham stimulation for decreasing pain intensity at 1 hour (53% vs.10%), 2 hours (52% vs. 17%) and 24-hours (71% vs. 34%). Pain-free ratings were greater for the active treatment arm at 1 hour (29.2% vs. 16%), 2 hours (41.7% vs. 20%) and 24 hours (65.2% vs. 40%). Subjects with moderate or severe migraine baseline pain who were pain-free at 2 hours was significantly greater among subjects receiving active treatment (43% vs. 10.5%). The responder rate was significantly higher among the active treatment group at 1 hour (67% vs. 20%), 2 hours (66.7% vs. 32%,) and 24 hours (78.3% vs. 48%). Overall headache-relief was significantly higher in the active treatment group at 1 hour (67% vs. 26%) and 2 hours (76% vs. 31.6%). Mild adverse events, reported by a minority of subjects, resolved spontaneously. Conclusions: eCOT-NS provides superior clinically meaningful relief and freedom of migraine pain compared to sham, offering a highly effective and safe non-pharmacological treatment for acute migraine.Trial registration: ClinicalTrials.gov Identiﬁer NCT03398668.
Neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2
Authors: Xiong Hua-Long , Sun Hui , Wang Si-Ling , Yuan Lunzhi , Liu Liqin , Zhu Yuhe , Zhang Jinlei , Huang Yang , Qi Ruoyao , Jiang Yao , Ma Jian , Zhou Min , Ma Yue , Fu Rao , Yan Siping , Yue Mingxi , Wu Yangtao , Wei Min , Wang Yi-Zhen , Li Tingting , Wang Yingbin , Zheng Zi-Zheng , Yu Hai , Cheng Tong , Li Shaowei , Yuan Quan , Zhang Jun , Guan Yi , Zheng Qingbing , Zhang Tianying , Xia Ningshao 
Published: February 2022

Abstract
Antibody therapeutics for the treatment of COVID-19 has been highly successful while faces a challenge of the recent emergence of the Omicron variant which escapes the majority of existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of which, nAbs X01, X10 and X17 showed broadly neutralizing breadths against most variants of concern (VOCs) and X17 was further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-EM structures of three-antibody in complex with the spike proteins of prototyped SARS-CoV-2, Delta, Omicron and SARS-CoV defined three non-overlapping conserved epitopes on the receptor-binding domain (RBD). The triple antibody cocktail exhibited enhanced resistance to viral escape and effective protection against the infection of Beta variant in hamsters. Our finding will aid the development of both antibody therapeutics and broad vaccines against SARS-CoV-2 and emerging variants.
Popular approval of Covid-19 restrictions is strongly correlated with vaccination rate
Authors: Jucker Jean-Luc 
Published: February 2022

Abstract
Most governments in the world have implemented restrictive measures to fight against the Covid-19 pandemic. Little is known, however, on people’s approval or disapproval of these restrictions, and importantly, on the factors that might contribute to approval. Switzerland might be the only country where citizens voted on Covid-19 restrictive measures by referendum, thereby providing a rare opportunity to assess the extent to which people approve Covid-19 restrictions. Using data from the Swiss authorities, we find that the percentage of people who approved Covid-19 restrictions by vote strongly positively correlates with the percentage of people vaccinated in the population (r = 0.929, p < 0.0001). This suggests that vaccinated people are more likely to approve Covid-19 restrictions, which raises interesting questions for further research.