bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin-Induced Alterations In Gills Of The Freshwater Fish Astyanax Lacustris (Lütken, 1875) Detected By Histological And Scanning Electron Microscopy
Authors: Barbieri Pablo , Mari-Ribeiro Isabelle Pereira , Lupepsa Luara , Gigliolli Adriana Aparecida Sinópolis , Paupitz Brennda Ribeiro , de Melo Rafael Fernando , Mello Eneri Vieira de Souza Leite , Portela-Castro Ana Luiza de Brito , Borin-Carvalho Luciana Andreia
Published: February 2022

The antidiabetic drug metformin is widely prescribed and found in high concentrations in the environment around the world, raising concern about potential impacts on aquatic life. Fish have a fundamental ecological role and are considered excellent experimental models in ecotoxicology studies. Gills of fish are extremely sensitive to even minor chemical or physical changes in the surroundings, mainly because of the large surface of the respiratory epithelium and the high perfusion rate, which both facilitate the entry of pollutants into this tissue. This study aimed to evaluate the occurrence of morphological changes in the gills of Astyanax lacustris exposed to metformin. The animals were subjected to different concentrations of the drug (50 ug/L, 100 ug/L, 1 mg/L and 10 mg/L) for a period of 90 days. Histopathological analyses were performed using light and Scanning Electron Microscopy. The main changes were lamellar fusion, telangiectasia hyperplasia and disappearance of microridges. The observed effects occurred at environmentally relevant concentrations, pointing to a concern that metformin may pose a risk to Astyanax lacustris and likely to other fish species.
Spatiotemporal Variation of Irrigation Water Requirement in the China–Pakistan Economic Corridor
Authors: Li Yaqi , Chen Yaning , Duan Weili , Cao Mengzhu , Qin Jingxiu
Published: February 2022

Agricultural irrigation consumes most of the fresh water in the China–Pakistan Economic Corridor (CPEC), directly affecting water resource management and allocation. Irrigation water demand is an important part of regional water resources management. Herein, we analyzed the spatiotemporal variation of irrigation water requirement, irrigation demand index (IDI), and proposed regional optimization of irrigation water use based on the Bayesian probability network. The results showed that: (1) The IDI in the study area increased slightly (trend slope = 0.028a− 1) as the effective precipitation increased by 63% during this period, and total irrigation water requirement (IR) decreased from 277.61 km3 in 2000 to 240 km3 in 2015 (2) The highest crop IDI was exhibited by cotton, followed by maize and wheat. (3) According to the comprehensive scenario analysis, improving the crop planting structure (by moderately increasing the planting proportion of maize in the CPEC) is conducive to improving regional water and food security by enhancing grain yield (+ 9%), reducing the malnourished population (low state + 7.2%), and bolstering water-saving irrigation technology as well as water conveyance systems in Pakistan. Our results pave the way toward sustainable water resource utilization management in the CPEC.
Quercetin mediated TET1 expression through miR-17 induced cell apoptosis in melanoma cells
Authors: Gao Yongjian , Li Chengshun , Lin Chao , Hou Ruizhi , Xia Qianyun , Ding Dayong , Wang Dongxu , Feng Ye
Published: February 2022

Previous report suggested that the expression of ten-eleven translocation (TET) proteins was abnormal in different cancers. Quercetin, has been demonstrated as anti-caner role in cancer development. To analyze the expression of TETs, quercetin treated with uveal melanoma cells in the present study. Our results suggested that the expression of TET1 was increased following treated with quercetin in OCM-1, SK-MEL-1 and B16 cells. In addition, quercetin treatment induced apoptosis and inhibited invasion. To further investigate if the expression of TET1 was associate with cell growth, apoptosis, migration and invasion, knocked down and overexpressing of TET1 was constructed. The results showed that the increased expression of TET1 induced cell apoptosis, increased 5-hydroxymethylcytosine (5hmC) and inhibited cell invasion. TET1 was a target gene of miR-17. Our results showed that inhibited expression of miR-17 increased TET1 expression in OCM-1 cells. To further confirm the effect of TET1 on melanoma tumors, nude mice was used. The results indicated that quercetin treatment increased TET1 expression and inhibited tumor growth. Taken together, these results suggested that quercetin can regulate cell proliferation and apoptosis through TET1 via miR-17 in melanoma cells.
On Variation of I–V-Characteristics of p-n-Heterojunctions Under Influence of Mismatch-Induced Stress
Authors: Pankratov Evgeny L.
Published: February 2022

In this paper, we consider p-n-junctions, manufactured by diffusion or ion implantation in a heterostructures. We analyzed influence of existing in heterostructure missmatch induced stresses on the current-voltage characteristics of the p-n-junctions. We also introduce an analytical approach for analysis of mass and heat transfer in heterostructures with account changes of their parameters on time, as well as their nonlinearity and missmatch induced stresses. In this paper we introduce an analytical approach for prognosis of the considered processes.
Gut Microbiome of Century-Old Snail Specimens Stable Across Time in Preservation
Authors: Chalifour Bridget , Li Jingchun , Elder Leanne
Published: February 2022

Background
Oreohelix strigosa (Rocky Mountainsnail) is a land snail found in the talus slopes of the Rocky Mountains. The University of Colorado’s Museum of Natural History has densely sampled Oreohelix for the past century; many are preserved in ethanol and available for molecular research. While microbiome compositions in other systems are not affected by short-term field season preservation, the effects of decades-long preservation have yet to be assessed.
Results
We used 16S rRNA (ribosomal ribonucleic acid) gene amplicon sequencing to examine Oreohelix strigosa gut microbiomes from museum specimens across a 98-year range, as well as within short term preservation treatments collected in 2018. Treatment groups included samples extracted fresh, without preservation; samples starved prior to extraction; and samples preserved for 1 month, 6 months, and 9 months. General microbiome composition was similar across all years. Sample groups belonging to specific years, or specific short-term treatments, showed unique associations with select bacterial taxa. Collection year was not a significant predictor of microbial richness, though unpreserved short-term treatments showed significantly higher richness than preserved treatments. While year was a significant factor in microbiome composition, it did not explain much of the variation across samples. Other factors like location collected and drought index were also significant drivers of community composition and explained as much or more of the variability.
Conclusions
This study is the first to examine animal host associated microbiome change across a period of nearly one century. Generally, geographic location was a greater factor in shaping gut microbiome composition, rather than year collected. Consistent patterns across this temporal range indicate that historic specimens can answer many ecological questions surrounding the host associated microbiome.
Correlation Between National Surveillance and Search Engine Query Data on Respiratory Syncytial Virus Infections in Japan
Authors: Uda Kazuhiro , Hagiya Hideharu , Yorifuji Takashi , Koyama Toshihiro , Tsuge Mitsuru , Yashiro Masato , Tsukahara Hirokazu
Published: February 2022

BackgroundThe respiratory syncytial virus (RSV) disease burden is significant, especially in infants and patients with an underlying disease, and prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan.MethodsThe retrospective survey was performed between January 1, 2018, and November 14, 2021, and evaluated the correlation of national surveillance and Google Trends data. Joinpoint regression was used to analyze the data to evaluate the points at which changes in trends occurred. ResultsAs a result, a strong correlation was observed every study year (2018 [r=0.87, p<0.01], 2019 [r=0.83, p<0.01], 2020 [r=0.83, p<0.01], and 2021 [r=0.96, p<0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic in 2018 and 2021 were observed earlier than by sentinel surveillance and in 2019 and 2020 simultaneously with sentinel surveillance.ConclusionsOur data suggested that Google Trends has the potential to enable early identification of the RSV epidemic. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.
Lung muscarinic receptor occupancy by tiotropium: translational PET studies in non-human primates and humans
Authors: Cselényi Zsolt , Jucaite Aurelija , Ewing Pär , Stenkrona Per , Kristensson Cecilia , Johnström Peter , Schou Magnus , Bolin Martin , Halldin Christer , Larsson Bengt , Grime Ken , Eriksson Ulf G , Farde Lars
Published: February 2022

BackgroundThe aim of the present translational PET study was to estimate occupancy of tiotropium at muscarinic acetylcholine receptors (mAChR) in the lungs in vivo. The relationship between the tiotropium exposure and receptor occupancy (RO) in the lung was assessed in non-human primates (NHPs) after intravenous injection of tiotropium doses at a broad dose interval (0.1-1mg/kg). The feasibility of measuring mAChR occupancy in the human lung was then confirmed in seven healthy human subjects after inhalation of a single therapeutic dose of tiotropium (18mg). PET examinations were performed using radioligand [11C]VC-002. Occupancy in lungs was estimated using Lassen plot analysis of parametric images showing total radioligand binding (total distribution volume, VT).ResultsThere was an evident effect of tiotropium on [11C]VC-002 binding to mAChRs in lungs in both NHPs and humans. In NHPs, the occupancy was 11 to 78%, increasing in a dose dependent manner. The Lassen-plot based estimate of non-displaceable binding in NHPs was about 10% of the VT. In humans, occupancy was 6-65%, and non-displaceable binding (VND) was about 20% of total binding, VT at baseline. ConclusionsThe results demonstrated that [11C]VC-002 binds specifically to mAChRs in the lungs such that it allows for the detection and quantification of lung muscarinic receptor occupancy following administration of an intravenously administered or inhaled muscarinic antagonist drugs. The methodology has potential for dose finding and comparison of drug formulations in future applied studies. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03097380, registered: 31 March 2017, url: https://clinicaltrials.gov/ct2/show/NCT03097380
QTL associated with Gummy Stem Blight (GSB) resistance in watermelon
Authors: Nou Ill-Sup , Hong Jeong-Eui , Hossain Mohammad Rashed , Jung Hee-Jeong
Published: February 2022

The authors have requested that this preprint be removed from Research Square.
Assessment of drought tolerance in indica rice: A new method
Authors: Singh Sandeep Kumar , Katara Jawahar Lal , Parameswaran C , Jagadev Prem Narayan , Bastia Debendra Nath , Jeughale Kishor , Samantaray Sanghamitra
Published: February 2022

Background: Most of the rice-growing areas are exposed to the threat of drought stress due to the effects of climate change. In order to meet this challenge and support an increasing population, it is desirable to breed rice varieties with improved drought tolerance. Breeders' success in developing improved drought resistance lines depends entirely on a simple and accurate screening process. All available drought assessment methods are time consuming, labour oriented and indirect indicators of drought. Result: We explain a method which efficiently evaluates the drought tolerance degree (DTD) of lowland indica rice varieties. DTD is defined as the average of the ratio of green leaf length to the total length of the top three leaves of each rice seedling after drought treatment, and therefore takes a value from 0 to 1. To test the potentiality of the DTD method, 118 doubled haploids with two parents showing different degrees of drought tolerance were assessed, from which the DTD value has been determined. Of the 118 doubled haploids identified by the drought tolerance assessment system under severe drought stress, DH102 showed the strongest drought resistance, with the highest DTD value, and DH22 was found to be the weakest drought resistance with the lowest DTD value. Further correlation analysis revealed a high association of DTD values with RWC, leaf tip drying scores, and leaf rolling scores. Based on these characteristics, the entire population under study was divided into two main groups. PCA analysis suggested three principal components with its first principal component possessing the DTD value, RWC, leaf rolling score, leaf tip drying score, and chlorophyll content index with maximum loading score. Conclusion: This new method will help in assessing the drought tolerance of indica rice varieties. This study indicates the DTD method is simple, cost-effective, direct and relatively accurate for drought-tolerant screening of rice varieties.
A Nomogram Predictive Model Of Ileus After Radical Cystectomy
Authors: Zhang Heng , Tian Ye , An Ling-Yue , Shan Gang , Ban Yong , Luo Guang-Heng
Published: February 2022

BACKGROUND: The golden standard for the treatment of muscle-invasive or high-grade bladder cancer is radical cystectomy combined with various forms of urinary diversion, but postoperative paralytic ileus is an troublesome postoperative complication.The purpose of this research is to build and verify the nomogram prediction model of postoperative ileus.METHODS: From January 2015 to December 2020, the clinical data of patients who underwent radical cystectomy in the urology department of Guizhou Provincial People's Hospital for bladder cancer were collected. The risk factors related to postoperative ileus were obtained by logitic single factor and multiple factor regression analysis. Then, the prediction model of postoperative ileus was constructed based on the risk factors and its identification ability and accuracy were verified.RESULT: 252 patients were included, 51 of whom had ileus. Statistical analysis showed that preoperative creatinine level, postoperative creatinine level, and postoperative serum albumin concentration were correlated with postoperative ileus. The area under ROC curve of nomogram predictive model constructed based on the risk factors was 0.748 (95%CI 0.672-0.824). The bootstrap correction curve of the prediction model shows that the prediction accuracy of the model is close to that of the ideal model.CONCLUSION: Preoperative creatinine level, postoperative creatinine level, and postoperative serum albumin concentration were correlated with postoperative ileus and were risk factors for ileus after radical cystectomy, which could be used as predictors of clinical prediction models. The prediction model of nomogram based on these predictors can predict the probability of postoperative intestinal obstruction.
Optimal Self-assembly of Lipid Nanoparticles (LNP) in a Ring Micromixer
Authors: RIPOLL Manon , Martin Elian , Enot Mathilde , Robbe Oscar , Rapisarda Chiara , Nicolai Marie-Claire , Deliot Aurelie , tabeling patrick , Authelin Jean-René , Nakach Mostafa , Wils Pierre
Published: February 2022

Lipid nanoparticles (LNPs) for RNA and DNA delivery have gained considerable attention to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality under low stress conditions added to fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow-rates, a degradation of performances in terms of size, size monodispersivity and encapsulation efficiency. In this study we focus on the ring micromixer, well adapted to high throughputs. We reveal three regimes - side-by-side, transitionnal and highly mixed – which control the mixing performance of the device. Further, on using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We underline the important role of the flow-rate ratio and propose a physical criterion, based on the onset of temporal instabilities, coupled to a stochiometric one, for producing LNPs with optimal characteristics, in term of geometry, monodispersivity and encapsulation yield. These criteria are general.
Revisiting mechanisms of the Mesoamerican Midsummer drought
Authors: García-Franco Jorge Luis , Chadwick Robin , Gray Lesley , Osprey Scott , Adams David K
Published: February 2022

Observations show that the seasonal cycle of precipitation in parts of southern Mexico and Central America exhibits a bimodal signal, known as the Midsummer drought (MSD), but there is no consensus on which processes are most relevant for the two-peak structure of the rainy season. This paper evaluates three hypotheses that could explain the MSD: the SST cloud-radiative feedback, the solar declination angle and the Caribbean LowLevel Jet (CLLJ) moisture transport hypotheses. Model experiments produced by the Met Office Hadley Centre (MOHC) for CMIP6 as well as ERA5 reanalysis data are used to critically assess the predictions of each hypothesis. The simulations capture the double peak signal of precipitation well and reasonably simulate the spatial and temporal variations of the MSD and other relevant climate features such as the CLLJ. Evidence from our analysis suggests that the Eastern Pacific SSTs do not increase in late summer in ERA5 data and only slightly increase in the simulations. More importantly, the Eastern Pacific SST variability in ERA5 and in the model experiments cannot explain the differences in the seasonality of precipitation. The net shortwave radiation at the surface shows a two-peak seasonal cycle; however, this behaviour appears to result from a strong anti-correlation of the incoming shortwave and convective activity due to cloud radiative-effects. There was no evidence found by this study of a causal link in which absorption of shortwave energy forces precipitation variations, as suggested by the solar declination angle hypothesis. The moisture convergence, CLLJ and the precipitable water vapor variations best explain the characteristics of the observed and simulated MSD, particularly for the onset of the MSD. The diagnosed variations of moisture convergence, which are synchronous with the timing of the MSD, point to a dynamic mechanism in which the low-level inflow from the Caribbean is more important for the MSD than other radiative mechanisms.
Morphological and Hemodynamic Differences Between Ruptured and Unruptured Vertebral Artery Dissecting Aneurysms: A Two-Center Retrospective Study
Authors: Wei Heng , Yao Kun , Tian Qi , Han Shoumeng , Gao Wenhong , Han Wenrui , Liu Sheng , Wang Guijun , Chen Qianxue , Li Mingchang
Published: February 2022

Purpose
The morphological and hemodynamic features of patients with vertebral artery dissecting aneurysms (VADAs) are yet unknown. This study sought to elucidate morphological and hemodynamical features of patients with ruptured and unruptured VADAs.
Methods
This study recruited 31 patients with unruptured VADAs and 21 patients with ruptured VADAs who were treated at two hospitals. We collected data on their clinical, morphological, and hemodynamic characteristics. After reconstructing a patient-specific model, computational fluid dynamics (CFD) was performed. Binary logistic regression was used to analyze significant parameters and identify independent risk factors. Receiver operating characteristic (ROC) analysis identified cut-off values separating ruptured from unruptured aneurysms for each parameter.
Results
Three hemodynamic parameters were observed to be significantly different between ruptured and unruptured VADAs: intra-aneurysmal pressure (IAP), wall shear stress (WSS), and normalized pressure (NP). However, no morphological parameters had a significant difference between ruptured and unruptured VADAs. Binary logistic regression analysis revealed that IAP (AUC = 0.9662, 95% CI 1.014–1.068) and WSS (AUC = 0.7873, 95% CI 1.124–16.859) were independently significant variables in the hemodynamics model.
Conclusion
This study indicated significant hemodynamic differences but no significant morphological difference between ruptured and unruptured VADAs. Hemodynamic parameters of IAP and WSS are important in discriminating VADAs rupture status. These results should be confirmed through future larger studies.
Outcomes of Endoscopic Mucosal Resection for Large Superficial Non-Ampullary Duodenal Adenomas
Authors: Amoyel Maxime , Belle Arthur , Dhooge Marion , Ali Einas Abou , Pellat Anna , Hallit Rachel , Terris Benoit , Prat Fréderic , Chaussade Stanislas , Coriat Romain , Barret Maximilien
Published: February 2022

Background
Endoscopic mucosal resection (EMR) is the recommended treatment for superficial non-ampullary duodenal epithelial tumors larger than 6 mm. This endoscopic technique carries a high risk of adverse events. Our aim was to identify the risk factors for adverse events following EMR for non-ampullary duodenal adenomas.
Methods
We retrospectively analyzed a prospectively collected database of consecutive endoscopic resections for duodenal lesions at a tertiary referral center for therapeutic endoscopy. We analyzed patients with non-ampullary duodenal adenomas ≥ 10mm resected by EMR, and searched for factors associated with adverse events after EMR.
Results
167 duodenal adenomas, with a median (range) size of 25 (10–90) mm, were resected by EMR between January 2015 and December 2020. Adverse events occurred in 37/167 (22.2%) after endoscopic resection, with 26/167 (15.6%) delayed bleeding, 4/167 (2.4%) immediate perforation and 4/167 (2.4%) delayed perforation. In logistic regression, the size of the lesion was the only associated risk factor of adverse events (OR = 2.81, 95%CI [1.27; 6.47], p = 0.012). Adverse events increased mean hospitalization time (7.7 ± 9 vs. 1.9 ± 1 days, p < 0.01). None of the currently recommended preventive methods, particularly clips, affected the adverse event rate.
Conclusions
EMR of centimetric and supracentimetric duodenal adenomas carries a high risk of adverse events, increasing with the size of the lesion and with no benefit from any preventive method. These results suggest that these procedures should be performed in expert centers, and underline the need for novel endoscopic tools to limit the rate of adverse events.
Comparison of Efficacy of SolyxTM Single Incision Sling and TO-TVT for Female Stress Urinary Incontinence
Authors: Li Shuaishuai , Ashok Raj , Xue Ning , Zhao Fangzheng , Chen Rui , Zhu Haitao
Published: February 2022

Introduction To compare the efficacy, safety, and complications of the trans-obturator mid-urethral sling (TO-TVT) and SolyxTM single-incision sling for treatment of female SUIMethods The clinical data of 92 patients who underwent urinary incontinence surgery in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The groups were divided on surgical techniques such as TO-TVT and the Solyx single-incision sling groups. Preoperative evaluation included patient's history, urodynamic evaluation, clinical examination results, I-QOL, and UDI-6 scores. The operative time, intraoperative blood loss, complications, and hospital stay were recorded. At six months follow-up, the patient was re-evaluated for I-QOL, UDI-6 scores, and urodynamics and clinical examinations. The PGI-I questionnaire assessed subjective cure rates at six months postoperatively. Results Patients in the TO-TVT and Solyx single-incision sling groups had similar subject cure rates six months after surgery. There was no statistical significance in intraoperative blood loss, length of hospital stay, I-QOL and UDI-6 scores between the two groups except for operation time .There was no significant difference in the incidence of intraoperative and postoperative complications between the two groups.Conclusion In terms of the effect and complications, the TO-TVT is similar to SolyxTM single incision sling. Nevertheless, SolyxTM single incision sling is shorter in operation time, more minimally invasive, and has a definite curative effect worthy of clinical promotion.
Vaccination Hesitancy On Introduction Of COVID 19 Vaccine In Pakistan: A Web-Based Cross Sectional Study April 2021
Authors: Sawani Sobiya , Siddiqui Rehana , Usmani Bilal Ahmed , Azam Syed Iqbal , Siddiqui Durr E Amna , Khwaja Hajra , Karim Sehrish
Published: February 2022

Background: Vaccination against COVID-19 is one of the control measures for an ongoing COVID-19 pandemic. Vaccine acceptance is known to be low in Pakistani population, we identified the factors associated with vaccine hesitancy (VH) for COVID-19 at the time of first introduction of this vaccine for elderly and health care workers. Methods: An online survey was launched using a google form during March to April 2021 to assess VH in adult (> 18 years) Pakistani population. The survey form determined VH individuals who declined to questions on getting vaccinated and maintained a perspective of reluctance to vaccinate. In addition to sociodemographic characteristics, observation of standard precautions, and sources of information on COVID-19 vaccine were inquired. Results: Of the 278 responses 80% of the study population was less than 45 years of age, 68% were males, 91% had 16 or more years of education, 39% were in health care profession, 81% reported consistent use of face masks in public places, 68% sanitized hands each time, 35% always avoided social gatherings, 24% had received vaccination, 20% had suffered from COVID-19, and 45.7% were vaccine hesitant. At multivariable level, being health care worker, increasing mean precautionary score, not being vaccinated against COVID-19 and those with concerns for vaccine safety were the contributing factors for VH. Participants who presumed COVID-19 vaccine was safe were 90% less hesitant to get COVID-19 vaccine (Adjusted Prevalence Ratio: 0.1; 95% CI 0.09, 0.29) than who were uncertain on vaccine safety.Conclusion: Reliable safety information on COVID-19 vaccine and trust building influenced VH, to mass vaccinate Pakistani population to control the pandemic.
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

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

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

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

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

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

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

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

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

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

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

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.