bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of Renewable Energy Use and Mitigation of Carbon Footprint for Selected Developing and Developed Nations
Authors: Rai Pratibha , Gupta Priya , Saini Neha
Published: October 2021

The focus of this paper is to investigate whether carbon footprints are reduced due to renewable energy use in fuelling the business and commercial interests of the nation’s right from trade, production, consumption in the presence of foreign direct investment (FDI). The quantification of the relationship is carried out for three developed nations and five developing nations. Error Correction Model (ECM) using Autoregressive distributed lag (ARDL) methodology is used to assess short-term and long-term country-wise parameters for the chosen variables in sample countries from 1990 to 2017. The findings demonstrate the persuasive evidence that green energy use is the sustainable path of development. The cointegrated relationship amongst the variables for the long run is validated for all eight individual countries included in the study. High-economic growth and non-renewable energy use are recognized as the major sources of environmental degradation across the country analysis. However, the panel data series of eight countries did not support the analysis in the ARDL framework, hence the Random effect model and Granger Causality technique is used to quantify the magnitude and direction of association that exists between carbon emissions, renewable energy in the presence of other macroeconomic variables including square of GDP per capita (included to test EKC behaviour) respectively. In the presence of renewable energy resource as an influencer of carbon emissions, the overemphasized EKC hypothesis, however, is not supported in the panel data analysis and in country wise analysis.
Correlation Analyses between Downward Longwave Radiation Particulate Matters, Aerosol Optical Depth, and Metrological Variables Under Non-Dusty and Cloudless Conditions
Authors: maghrabi abdullrahman , Alharbi Badr , Alharbi Hamoud , Aldosari Abdulah
Published: October 2021

This study used downward (LW) radiation measurements, air temperature (T), particulate matter (PM) concentrations of fine (PM 2.5) and coarse (PM10) particles, aerosol optical depth (AOD), wind speed, and precipitable water vapor (PWV) data from Riyadh, an arid site in central Saudi Arabia, between 2014–2019 to characterize their variations and investigate the influence of these variables on the measured downward LW radiation under non-dusty, clear sky conditions. The LW radiation and air temperature, it was found, attain their maximum in summer and minimum in winter. Conversely, the PM mean concentrations and AOD showed their maximum in spring and minimum in winter. PWV features an increasing trend during spring, summer, and fall, whereas it features a decreasing trend during the winter. The monthly variation of WS shows low monthly values during fall and winter and considerably higher monthly mean variation during spring and summer. Apart from wind speed, which doesn’t affect the LW radiation, correlation analyses demonstrated that the LW correlates positively with the remainder of the considered variables. The strength and degree of association between the LW radiation and these variables differ from one variable to another, with air temperature having the strongest correlation (correlation coefficient = 0.98) with the LW radiation, followed by the AOD (correlation coefficient = 0.69), with a correlation coefficient of 0.36 with the PWV. Similarly, the relationships between the LW radiation and both PM10 and PM2.5 had the same correlation coefficient of 0.32. The effect of the meteorological variables (mainly air temperature, relative humidity, and wind speed) on the PM concentrations were investigated using the regression analyses. The results showed a significant positive relationship with air temperature and wind speed and a negative relationship with RH.
Acacia Jacquemontii Ethyl Acetate Extract Downregulated the Hyperglycemia Through Its Modulatory Effects On Endogenous Antioxidant, Anti-Inflammatory And Pancreatic β- Cell Regenerative Status in Alloxan Induced Diabetic Rats.
Authors: Awan Ambreen Mehmood , Majeed Wafa , Muhammad Faqir , Faisal Muhammad Naeem
Published: October 2021

Diabetes mellitus is among the world’s greatest health hazards. Acacia jacquemontii possess numerous traditional therapeutic uses. This study investigated the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in alloxan induced diabetes in rat model. Current study was performed in two parts, in-vitro, through characterization (HPLC), estimation of TFC, TPC, antioxidant (DPPH assay) and α-amylase inhibitory activities of the studied extract, and in vivo on wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250mg/kg and AJEAE 500mg/kg. The effects of AJEAE on FBG, serum glucose, insulin, HBA1c, lipid profile, inflammatory cytokines (IL-6, TNF-alpha) and oxidative stress markers (LPO, NO, SOD, CAT, GPx) were evaluated. Our findings confirmed the presence of quercitin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinamic acid and ferulic acid in AJEAE. TFC and TPC in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g respectively. Significant inhibition of DPPH and α-amylase activities was exhibited by AJEAE. Alloxan injected rats showed marked hyperglycemia, hypoinsulinemia and increased inflammatory markers levels as compared to normal control. Additionally raised levels of TG, TC, VLDL, LDL, LPO, NO and decreased levels of SOD, CAT and GPx were observed in diabetic rats. AJEAE significantly (p< 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic β cells. Conclusively our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory and pancreatic beta cells regenerative properties of AJEAE against alloxan induced diabetes.
Controllable Kerr Nonlinearity in a Degenerate V-Type Inhomogeneously Broadening Atomic Medium Aided By a Magnetic Field
Authors: Minh Dong Hoang , Doan Thanh Thai , Tuan Anh Nguyen
Published: October 2021

We propose a degenerate V-type inhomogeneously broadening atomic model for Kerr nonlinear control under the support of an external magnetic field. The magnetic field is used as a control knob to convert the medium from transparency to absorption at the resonance center. It is shown that the magnitude and sign of the Kerr nonlinearity index are manipulated by the magnetic field. Especially, we can easily convert the Kerr nonlinearity index from the positive peak into a negative peak, and from zero value can be transferred to enhanced positive or negative peaks simply only by changing the direction or strength of the magnetic field. In addition, the Kerr nonlinearity index under the influence of the temperature, the intensity, and detuning of the control field is also considered. The proposed model can be useful for applications in optical switching and nonlinear optical devices as well as possible experimental implementations.
Molecular convolutional neural networks with DNA regulatory circuits
Authors: Pei Hao , Xiong Xiewei , Zhu Tong , Zhu Yun , Cao Mengyao , Xiao Jin , Li Li , Wang Fei , Fan Chunhai
Published: October 2021

Complex biomolecular circuits enable cells with intelligent behavior for survival before neural brains evolved. Synthesized DNA circuits in liquid phase developed as computational hardware can perform neural-network-like computation that harness the collective properties of complex biochemical systems, however the scaling up in complexity remains challenging to support more powerful computation. we present a systematic molecular implementation of the convolutional neural network (ConvNet) algorithm with synthetic DNA regulatory circuits based on a simple DNA switching gate architecture. We experimentally demonstrated that a DNA-based ConvNet based on shared-weight architecture of a 3×6 sized kernel can simultaneously implement parallel multiply-accumulate (MAC) operations for 144 bits inputs and recognize patterns up to 8 categories autonomously. Furthermore, it can connect with another DNA circuits to construct hierarchical networks, which can recognize patterns up to 32 categories with a two-step classification approach of performing coarse classification on language (Arabic numerals, Chinese oracles, English alphabets and Greek alphabets) and then classifying them into specific handwritten symbols. With a simple cyclic freeze/thaw approach, we can decrease computation time from hours to minutes. Our approach shows great promise in the realization of high computing power molecular computer with ability to classify complex and noisy information.
Distribution of Extreme Rainfall Events and Their Environmental Controls in The West African Sahel
Authors: Vizy Edward K. , Cook Kerry H.
Published: October 2021

West African Sahel extreme rainfall events are impactful when strong mesoscale convective systems (MCSs) produce large amounts of rainfall in short periods. NASA IMERG rainfall estimates and the ERA5 reanalysis are examined to understand where the top 100 highest 12Z – 12Z 24-h rainfall totals and MCS storm genesis occur, and to assess the relative importance of environmental conditions in their generation including the influence of atmospheric moisture and vertical wind shear. Most of the top 100 events are located south of 14°N. Events cluster over three regions, namely, Mali, Burkina Faso, and northern Nigeria. The associated MCSs are typically not locally generated, forming instead at distances greater than 100 km upstream. Composites reveal that a significant increase in atmospheric moisture content occurs prior to development, but there is no evidence of significant changes in the 600 – 925 hPa vertical wind shear. This indicates that vertical wind shear is less influential in extreme storm development than atmospheric moisture preconditioning. The top 10 events are further evaluated. A change in these storms’ direction and speed near the maximum rainfall location is common, suggesting the MCSs are reorganizing around peak rainfall intensity time. Three atmospheric conditions are associated with these events. They are (1) moisture preconditioning of the atmosphere, (2) interaction of the storm in the wake of a region of anticyclonic flow, and (3) interaction of the storm in the wake of a region of anticyclonic flow and the Sahel/tropical dryline boundary.
Exploratory study of the factors affecting quality of life in patients with chronic musculoskeletal pain
Authors: Takahashi Naoto , Takatsuki Kozue , Kasahara Satoshi , Yabuki Shoji
Published: October 2021

Background

A therapeutic target for patients with chronic musculoskeletal pain is the improvement of quality of life (QOL). A multidisciplinary approach to pain management is implemented at the Pain Management Center, Hoshi General Hospital, Japan. We consistently evaluate not only biological pain factors but also pain levels, psychosocial factors associated with pain, and QOL using questionnaires. The study aim was to explore the factors affecting QOL in patients with chronic musculoskeletal pain.
Methods

Subjects were 166 patients attending checkups at our pain management center from April 2015 to March 2020 who had valid questionnaire responses. We evaluated age, scores on the Brief Pain Inventory (BPI), Pain Catastrophizing Scale, Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale, Pain Self-Efficacy Questionnaire (PSEQ), EuroQol Five Dimensions Questionnaire, and Athens Insomnia Scale (AIS). Descriptive statistics were calculated for the 166 patients’ scores. Pearson’s product-moment coefficient correlations were calculated to examine associations among the variables. Subsequent multiple regression analysis, in which QOL was the dependent variable, resulted in a coefficient of determination (R2) of 0.58, indicating strong relationships among the variables (p < 0.01).
Results

The standardized regression (beta) coefficients showed significant associations (p < 0.05) among BPI, PDAS, PSEQ, and AIS scores and QOL (EuroQol Five Dimensions Questionnaire scores). However, Hospital Anxiety and Depression Scale and Pain Catastrophizing Scale scores were not strongly associated with QOL.
Conclusions

QOL in patients with chronic musculoskeletal pain was strongly related to BPI, PDAS, PSEQ, and AIS scores. We should focus on these factors to improve QOL.
Predictors of hydrocephalus after lateral ventricular tumor resection
Authors: Zhang Chengda , Ge Lingli , Zhang Tingbao , Li Zhengwei , Chen Jincao
Published: October 2021

The aim of this study was to identify the predictors of postoperative hydrocephalus in patients with lateral ventricular tumors (LVTs) and to guide the management of perioperative hydrocephalus. We performed a retrospective analysis of patients who received LVT resection at the Department of Neurosurgery, Zhongnan Hospital of Wuhan University between January 2011 and March 2021. Patients were divided between a prophylactic external ventricular drainage (EVD) group and a non-prophylactic EVD group. We analyzed the non-prophylactic EVD group to identify predictors of acute postoperative hydrocephalus. We analyzed all enrolled patients to determine predictors of postoperative ventriculoperitoneal shunt placement. A total of 97 patients were included in this study. EVD was performed in 23 patients with postoperative acute obstructive hydrocephalus, nine patients with communicative hydrocephalus, and two patients with isolated hydrocephalus. Logistic regression analysis showed that tumor anterior invasion of the ventricle (P = 0.020) and postoperative hemorrhage (P = 0.004) were independent risk factors for postoperative acute obstructive hydrocephalus, while a malignant tumor (P = 0.004) was an independent risk factor for a postoperative ventriculoperitoneal shunt. In conclusion, anterior invasion of the lateral ventricle and postoperative hemorrhage are independent risk factors for acute obstructive hydrocephalus after LVT resection. Patients with malignant tumors have a greater risk of shunt dependence after LVT resection.
Recovery and Long Term Functional Outcome in Subjects With Critical Illness Polyneuropathy and Myopathy: a Scoping Review
Authors: Intiso Domenico , Centra Marco , Bartolo Michelangelo , Gatta Maria Teresa , Gravina Michele , Rienzo Filomena Di
Published: October 2021

Background: Intensive care unit acquired weakness (ICUAW), embraces an array of disorders labeled “critical illness polyneuropathy” (CIP), “critical illness myopathy” (CIM) or “critical illness polyneuromyopathy” (CIPNM). Several studies have addressed the various characteristics of CIPNM, but the recovery is still unclear. Objective: The present review investigated the recovery and the long-term functional outcome of subjects with CIPNM, whether the types of CIPNM have different outcomes and whether there is any supporting evidence. Methods: Literature search was performed from MEDLINE/PubMed, CINAHL, EMBASE, PeDro, Web of Science and Scopus. Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from CIPNM and/or CIP, CIM and CIP/CIM; iii) CIPNM ascertained by EMG. Follow-ups longer than one year were defined as long-term.Results: Twenty-nine studies met the inclusion criteria. In total, 788 subjects with CIPNM were enrolled: 159 (20.1%) died and 588 (74.6%) were followed. Of all the included patients, 613 (77.7%) had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Overall, 70.3% of the subjects with CIPNM fully recovered. Seven (24.1%) studies had a follow-up longer than 1 year (range 2-8) with 173 (21.9%) subjects enrolled globally and 108 followed. Of these subjects, 88.8% gained full recovery. Most of the studies did not use proper functional scales and only 4 and 3 studies employed the Barthel scale and the FIM scale. Differentiation between the types of CIPNM was performed in 7 studies, but only 3 studies reported that subjects with CIM had a better prognosis and earlier recovery than subjects with CIP/CIM.Conclusions: Subjects with CIPNM could achieve good recovery and could further improve at follow-up. The quality of the published studies due to short follow-ups and the paucity of defined outcome measures limit the evidence.
Im2Mesh GAN: Accurate 3D Hand Mesh Recovery from a Single RGB Image
Authors: Pemasiri Akila , Nguyen Kien , Sridha Sridha , Fookes Clinton
Published: October 2021

This work addresses hand mesh recovery from a single RGB image. In contrast to most of the existing approaches where parametric hand models are employed as the prior, we show that the hand mesh can be learned directly from the input image. We propose a new type of GAN called Im2Mesh GAN to learn the mesh through end-to-end adversarial training. By interpreting the mesh as a graph, our model is able to capture the topological relationship among the mesh vertices. We also introduce a 3D surface descriptor into the GAN architecture to further capture the associated 3D features. We conduct experiments with the proposed Im2Mesh GAN architecture in two settings: one where we can reap the benefits of coupled groundtruth data availability of the images and the corresponding meshes; and the other which combats the more challenging problem of mesh estimation without the corresponding groundtruth. Through extensive evaluations we demonstrate that even without using any hand priors the proposed method performs on par or better than the state-of-the-art.
Determining Staffing Standards for Primary Care Services Using Workload Indicators of Staffing Needs in the Philippines
Authors: Aytona Ma Graziella Cardano , Politico Mary Ruth , McManus Leah , Ronquillo Kenneth , Okech Mollent
Published: October 2021

Background
Health services cannot be delivered without an adequate, competent health workforce. Evidence suggests a direct relationship between density of health workforce and health outcomes. The Philippines is faced with health workforce challenges including shortages, inequitable distribution and inadequate skill mix which hinder health service delivery. Evidence-based workforce planning is therefore critical to achieve universal health care.
Methods
The Philippines adopted the World Health Organization’s workload indicators of staffing need methodology. Using a multistage sampling method, nine regions with poor health indicators in tuberculosis, family planning, and maternal child health were identified. Physicians, nurses, midwives, and medical technologists were prioritized in the study from 89 primary care health facilities (barangay health stations, rural health units, and city health offices). Data was collected using in-depth interviews, document reviews, observations, and field visits. The workload indicators of staffing need software were used for data analysis to determine staffing requirements and analyse workforce pressure.
Results
The study showed varied results in terms of staffing requirements and workload pressure across cadres and facility types. Some health facilities exhibited staff shortages and high workload pressure. Out of the 40 rural health units and city health offices, only three had the required physicians needed and 22 facilities had a shortage of physicians working under high workload pressure. Other facilities had excess staff compared to the calculated requirements. Nurses at the rural health units showed high workload pressure. Ten rural health units had no medical technologists. Midwives at barangay health stations exhibited extremely low workload pressures.
Conclusion
The study identifies the need for the Philippine Health System, both through the Department of Health and the local governments to efficiently optimize the available health workers by revising the services offered at the primary health care facilities. The results provide evidence for staffing requirements at various levels of care based on workloads, scope of practice and time taken to undertake specific tasks at the barangay health stations, rural health units and city health offices to be integrated into the human resources for health management systems.
Oxidized Linoleic Acid Interacts With Gut Microbiota to Promote Colitis and Colorectal Cancer
Authors: Wang Weicang , Wang Yuxin , Sanidad Katherine Z. , Zhang Jianan , Yang Haixia , Johnson David , Sherman Heather L. , Kim Daeyoung , Minter Lisa M. , Decker Eric A. , Zhang Guodong
Published: October 2021

Background: Emerging human studies support that a high intake of linoleic acid (LA), which is an essential fatty acid and the most abundant polyunsaturated fatty acid (PUFA) in human diet, is associated with increased risks of developing inflammatory bowel disease (IBD). As a PUFA, LA is highly prone to oxidation; to date, it remains unknown whether the observed IBD-enhancing effect of dietary LA is caused by LA itself (un-oxidized LA) or oxidized LA. Answering this question will help us to identify the exact risk factor of IBD and to develop targeted strategies to reduce the risks of IBD; in addition, the obtained information could have important implications for optimizing dietary recommendations. Results: Here we show that oxidized LA, rather than LA itself, exacerbates colitis and colorectal tumorigenesis, via gut microbiota- and microbial receptor Toll-like receptor 4 (TLR4)-dependent mechanisms. Administration of a diet containing oxidized LA, at low human-consumption levels, increases the severity of colitis and exaggerates the development of colorectal tumorigenesis in mice. In addition, oxidized LA alters gut microbiota and fails to promote colitis in antibiotic-treated mice. Finally, oxidized LA activates TLR4 signaling in vivo and fails to promote colitis in Tlr4-/- mice. Conclusions: Overall, these results support that oxidized LA could be a risk factor of IBD and associated diseases, highlighting the need to develop novel strategies to further control oxidation of dietary LA and potentially update policies regulating the levels of oxidized LA in food products.
Risk Factors Associated with Intraoperative Iatrogenic Fracture in Patients Undergoing Intramedullary Nailing for Diaphyseal Atypical Femoral Fractures
Authors: Joo Yong Bum , Chung Hyung Jin , Jeon Yoo Sun , Lee Woo Yong , Kim Dong Hwan
Published: October 2021

The authors have requested that this preprint be removed from Research Square.
Effects of Carbonylation on the Freshness of Milk and Carbonylation Prevention Measures
Authors: Wen Gu , Hui Liu
Published: October 2021

Objective: To study the effects of carbonylation on freshness during milk storage and develop methods for keeping milk fresh. Methods: The effects of storage temperature, time, vacuum and repeated freeze-thaw on milk carbonylation were determined. Levels of carbonylation were measured. Results: The carbonylation content increased with storage time at room temperature. Vacuum protection and antibacterial protection decreased the protein carbonylation content. The carbonylation content increased with the number of freeze-thaw cycles under low-temperature storage conditions. Conclusion: Vacuum freezing delays oxidative damage to milk protein.
Efficient Screening of Pesticide Diazinon-Binding Aptamers Using The Sol-Gel Coated Nanoporous Membrane-Assisted SELEX Process and Next-Generation Sequencing
Authors: Lim Min-Cheol , Lim Eun Seob , Lim Jeong-A , Choi Sung-Wook , Chang Hyun-Joo
Published: October 2021

BackgroundAptamer-based methods for detecting pesticides are more efficient than antibody-based methods as aptamers have high thermal stability, low molecular weight, easy modification, and low cost. However, only few studies on SELEX performed in combination with next generation sequencing (NGS) to screen aptamers specific for pesticides have been reported. Therefore, this study aimed to develop the systematic evolution of ligands by exponential enrichment (SELEX) process, combined with NGS, to select aptamers specific to the pesticide, diazinon, which was fixed on a sol-gel-coated nanoporous anodized aluminum oxide membrane. Methods and resultsThe frequency of specific nucleotide sequences obtained after SELEX rounds was analyzed using NGS. Nine sequences with the highest frequency after SELEX round 10 followed by NGS were selected and tested to derive their binding affinity with the target, diazinon, through circular dichroism (CD) spectrophotometry. The CD signal difference of the aptamer candidates ranged from 0.13 to 2.242 mdeg between diazinon-only treated and diazinon-aptamer-treated samples at a wavelength near 270 nm. Aptamer D-4, which had the highest binding affinity from CD spectrophotometry analysis, showed no cross-reactivity with non-target pesticides, such as baycarb, bifenthrin, and pyridaben, but interacted with the other pesticides, fipronil and 2-phenylphenol.ConclusionsThe proposed SELEX process combined with NGS for the discovery of aptamers for new targets can shorten the SELEX cycle by reducing the number of SELEX rounds to 10 or less. Therefore, an efficiently selected aptamer is highly expected to be used for the detection of pesticides in foods in the field.
Comprehensive Analysis of Sinonasal Inverted Papilloma Expression Profiles Identified Long Noncoding RNA AKTIP as a Potential Biomarker
Authors: He Hanyi , Wang Xinlu , Lu Yueyue , Lin Xiaojiang , Li Yuandong , Li Yong , Lin Zhihong , Ma Zhiqi , Cao Xiaolin , Teng Yaoshu
Published: October 2021

Background: Long noncoding RNAs (lncRNAs) are a novel class of potential biomarkers and therapeutic targets for the treatment of neoplasms. The purpose of this study was to explore the expression profile, potential functions, and diagnostic and clinicopathological significance of lncRNAs in sinonasal inverted papilloma (SNIP).Methods The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods.Results Microarray analysis identified 1,668 significantly upregulated and 1,767 downregulated lncRNAs in SNIP. Several mRNAs coexpressed with lncRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Lnc-AKTIP might interact with a variety of tumor-associated proteins and transcription factors, such as PCBP2, IRF-1, and p53.Receiver operating characteristic curve analysis for lnc-AKTIP showed an area under the curve of 0.939. Notably, its expression level was significantly decreased in SNIP tissues versus normal tissues and was associated with SNIP staging.Conclusion Lnc-AKTIP may serve as a valuable diagnostic biomarker and a therapeutic target for SNIP.
Progressive Compressive Sensing of Large Images with Multiscale Deep Learning Reconstruction
Authors: Kravets Vladislav , Stern Adrian
Published: October 2021

Compressive sensing (CS) is a sub-Nyquist sampling framework that has been employed to improve the performance of numerous imaging applications during the last fifteen years. Yet, its application for large and high-resolution imaging remains challenging in terms of the computation and acquisition effort involved. Often, low-resolution imaging is sufficient for most of the considered tasks and only a fraction of cases demand high resolution, but the problem is that the user does not know in advance when high-resolution acquisition is required. To address this, we propose a multiscale progressive CS method for the high-resolution imaging. The progressive sampling refines the resolution of the image, while incorporating the already sampled low-resolution information, making the process highly efficient. Moreover, the multiscale property of the progressively sensed samples is capitalized for a fast, deep learning (DL) reconstruction, otherwise infeasible due to practical limitations of training on high-resolution images. The progressive CS and the multiscale reconstruction method are analyzed numerically and demonstrated experimentally with a single pixel camera imaging system. We demonstrate 4-megapixel size progressive compressive imaging with about half the overall number of samples, more than an order of magnitude faster reconstruction, and improved reconstruction quality compared to alternative conventional CS approaches.
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Authors: Debette Stéphanie , Duperron Marie-Gabrielle , Knol Maria , Grand Quentin Le , Evans Tavia , Mishra Aniket , Roshchupkin Gennady , Konuma Takahiro , Trégouët David-Alexandre , Romero Jose , Frenzel Stefan , Luciano Michelle , Hofer Edith , Bourgey Mathieu , Dueker Nicole , Delgado Pilar , Hilal Saima , Tankard Rick , Dubost Florian , Shin Jean , Saba Yasaman , Armstrong Nicola , Bordes Constance , Bastin Mark , Beiser Alexa , Brodaty Henry , Bülow Robin , Carrera Caty , Chen Christopher P. , Cheng Ching-Yu , Deary Ian , Gampawar Piyush G. , Himali Jayandra , Jiang Jiyang , Li Shuo , Macalli Melissa , Marquis Pascale , Morris Zoe , Maniega Susanna Muñoz , Paradise Matthew , Pedram Parva , Rundek Tatjana , Sargurupremraj Murali , Schilling Sabrina , Soukarieh Omar (TBC) , Teumer Alexander , Thalamuthu Anbupalam , Trollor Julian , Tsuchida Ami , Hernández Maria Valdés , Vernooij Meike , Völker Uwe , Wittfeld Katharina , Wong Tien Yin , Wright Margaret , Yang Qiong , Zhang Junyi , Zhao Wanting , Zhu Ycheng , Schmidt Helena , Sachdev Perminder , Wen Wei , JOUTEL Anne , Satizabal Claudia , Sacco Ralph , Bourque Guillaume , Lathrop Mark , Paus Tomas , Fernandez-Cadenas Israel , Mazoyer Bernard , Okada Yukinori , Grabe Hans , Mather Karen , Schmidt Reinhold , Ikram M. Arfan , Tzourio Christophe , Wardlaw Joanna , Seshadri Sudha , Adams Hieab
Published: October 2021

Perivascular space burden (PVS) is an emerging and possibly the earliest magnetic resonance imaging (MRI)-marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Its molecular underpinnings are unknown. Genome-wide and whole-exome association studies in 40,095 participants (21 population-based cohorts, 66.3±8.6 years) revealed 24 genome-wide significant PVS risk loci. These showed association with white matter PVS already at age 20, suggesting an important role of early-life factors. PVS loci were enriched in genes causing early-onset leukodystrophies and genes expressed in fetal brain endothelial cells. Mendelian randomization analyses supported causal associations of high blood pressure with basal ganglia (BG) and hippocampal PVS, and of BG PVS with stroke. Transcriptome-wide association studies suggest causal implication of 11 genes, to prioritize for experimental follow-up as putative biotargets for cSVD. Two-thirds of PVS loci point to novel pathways, involving extracellular matrix, membrane transport, and developmental processes, with enrichment in targets of existing drugs for vascular/cognitive disorders.
Acquisition of resistance to wild-type spike-immune sera by emerging SARS-CoV-2 variants
Authors: Arase Hisashi , Liu Yafei , Arase Noriko , Kishikawa Jun-ichi , Hirose Mika , Li Songling , Tada Asa , Matsuoka Sumiko , Arakawa Akemi , Akamatsu Kanako , Ono Chikako , Jin Hui , Kishida Kazuki , Nakai Wataru , Kohyama Masako , Nakagawa Atsushi , Takagi Junichi , Yamagishi Yoshiaki , Nakagami Hironori , Kumanogoh Atsushi , Matsuura Yoshiharau , Standley Daron M. , Kato Takayuki , Okada Masato , Fujimoto Manabu
Published: October 2021

Breakthrough infection is often observed for the SARS-CoV-2 Delta variant, and neutralizing antibody levels are associated with vaccine efficiency1. Recent studies revealed that not only anti-receptor binding domain (RBD) antibodies2 but also antibodies against the N-terminal domain (NTD) play important roles in positively3,4 or negatively4-8 controlling SARS-CoV-2 infectivity. Here, we found that the Delta variant completely escaped from anti-NTD neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Cryo-EM analysis of the Delta spike revealed that epitopes for anti-NTD neutralizing antibodies are structurally divergent, whereas epitopes for enhancing antibodies are well conserved with wild-type spike protein. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the original Delta variant, when major anti-RBD neutralizing antibody epitopes remaining in the Delta variant were disrupted, some BNT162b2-immune sera not only lost neutralizing activity but became infection-enhanced. The enhanced infectivity disappeared when the Delta NTD was substituted with the wild-type NTD. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta variant lacking anti-RBD antibody epitopes without enhancing infectivity. Importantly, SARS-CoV-2 variants with similar mutations in the RBD have already emerged according to the GISAID database and their pseudoviruses were resistant to some BNT162b2-immune sera. These findings demonstrate that mutations in the NTD, as well as the RBD, play an important role in antibody escape by SARS-CoV-2. Development of effective vaccines against emerging variants will be necessary, not only to protect against infection, but also to prevent further mutation of SARS-CoV-2.
Association of Alcohol Consumption with the Incidence of Proteinuria and Chronic Kidney Disease: A Retrospective Cohort Study in Japan
Authors: Tanaka Akio , Yamaguchi Makoto , Ishimoto Takuji , Katsuno Takayuki , Nobata Hironobu , Iwagaitsu Shiho , Sugiyama Hirokazu , Kinashi Hiroshi , Banno Shogo , Ando Masahiko , Kubo Yoko , Ito Yasuhiko
Published: October 2021

Background

The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex.
Methods

This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥1) and incidence of chronic kidney disease (an estimated glomerular filtration rate <60 mL/min per 1.73 m2 and a 25% decrease from the baseline estimated glomerular filtration rate).
Results

During a median observational period of 4 years (interquartile range: 2–6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed chronic kidney disease. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥40 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.65; 95% confidence interval, 1.09–2.51) and chronic kidney disease (hazard ratio, 1.77; 95% confidence interval, 1.09–2.85). However, no significant association between alcohol consumption and primary outcomes was observed in men.
Conclusions

In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and chronic kidney disease among women. Women might be prone to high alcohol consumption with kidney dysfunction.
Systematic Proteomics Analysis of Colorectal Cancer: to Recognize Potential Biomarkers and Remedial Target
Authors: Jahromi Noosha Zia , Mandani Amin Mahmoudi , Kaji Nahid Sadeghi Moghadam , Teshnizi Hadis Abbasi , Zamani Atefeh , Fattahi Nasrin , Sazegar Hossein
Published: October 2021

BackgroundColorectal Cancer (CRC) is a high prevalence malignant of the digestive system. Notwithstanding huge investigation, the precise involved mechanisms are still blunted. It emerges that more research is needed to understand the underlying mechanisms of CRC better. In this investigation, a systems biology method was applied to provide a comprehensive insight through making a multilayer network to recognize novel biomarkers and potential drug targets.MethodTo identify the affected proteins in this disease, an existing protein expression profile on CRC was attained from ProteomeXchange. In the first step, the quality of the dataset was assessed, and then differentially expressed proteins (DEPs) were recognized based on FDR<0.05 as the statistically significant threshold. Subsequently, all identified DEPs were subjected to further enrichment analysis for finding the involved biomedical phenomena. In the following action, lncRNAs and miRNAs related to DEPs were predicted as regulatory layers via Cytoscape to make an integrative network.ResultThe empirical findings in this study indicated that the identified DEPs were mainly associated with two biomedical terms, such as “Mitochondrial dysfunction” and “Extracellular matrix organization.” Additionally, several hub molecules were introduced in the constructed multilayer network, hub-DEPs (ITGB1, ACTG1, ...), hub-miRs (miR-16-5p, miR-26b-5p, ...), and hub-lncRNAs (KCNQ1OT1, NEAT1, …) that Can be deemed as a potential biomarker in the pathogenesis of CRC, further research should concentrate on the investigation of their role in CRC development.ConclusionThe attained results of this study may be paving a way to provide a deeper understanding of the vaguely involved mechanisms through an integrative insight into the interaction of proteins with regulatory layers.
Optimization of Enzymatic Fragmentation is Crucial To Maximize Genome Coverage: A Comparison of Library Preparation Methods for Illumina Sequencing
Authors: Ribarska Teodora , Bjørnstad Pål Marius , Sundaram Arvind Y.M. , Gilfillan Gregor D.
Published: October 2021

Background
Novel commercial kits for whole genome library preparation for next-generation sequencing on Illumina platforms promise shorter workflows, lower inputs and cost savings. Time savings are achieved by employing enzymatic DNA fragmentation and by combining end-repair and tailing reactions. Fewer cleanup steps also allow greater DNA input flexibility (1 ng-1 µg), PCR-free options from 100 ng DNA, and lower price as compared to the well-established sonication and tagmentation-based DNA library preparation kits.
Results
We compared the performance of four enzymatic fragmentation-based DNA library preparation kits (from New England Biolabs, Roche, Swift Biosciences and Quantabio) to a tagmentation-based kit (Illumina) using low input DNA amounts (10 ng) and PCR-free reactions with 100 ng DNA. With four technical replicates of each input amount and kit, we compared the kits` fragmentation sequence-bias as well as performance parameters such as sequence coverage and the clinically relevant detection of single nucleotide and indel variants. While all kits produced high quality sequence data and demonstrated similar performance, several enzymatic fragmentation methods produced library insert sizes which deviated from those intended. Libraries with longer insert lengths performed better in terms of coverage, SNV and indel detection. Lower performance of shorter-insert libraries could be explained by loss of sequence coverage to overlapping paired-end reads, exacerbated by the preferential sequencing of shorter fragments on Illumina sequencers. We also observed that libraries prepared with minimal or no PCR performed best with regard to indel detection.
Conclusions
The enzymatic fragmentation-based DNA library preparation kits from NEB, Roche, Swift and Quantabio are good alternatives to the tagmentation based Nextera DNA flex kit from Illumina, offering reproducible results using flexible DNA inputs, quick workflows and lower prices. Libraries with insert DNA fragments longer than the cumulative sum of both read lengths avoid read overlap, thus produce more informative data that leads to strongly improved genome coverage and consequently also increased sensitivity and precision of SNP and indel detection. In order to best utilize such enzymatic fragmentation reagents, researchers should be prepared to invest time to optimize fragmentation conditions for their particular samples.
Direct Cyclodextrin Based Powder Extrusion 3D Printing for One-step Production of the BCS Class II Model Drug Niclosamide
Authors: Pistone Monica , Racaniello Giuseppe Francesco , Arduino Ilaria , Laquintana Valentino , Lopalco Antonio , Cutrignelli Annalisa , Rizzi Rosanna , Franco Massimo , Lopedota Angela , Denora Nunzio
Published: October 2021

Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic active principle for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug, and is consequently characterised by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, Direct Powder Extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (Fused Deposition Modelling, FDM) to achieve direct extrusion of pharmaceutical grade powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-b-cyclodextrin (HP-β-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-β-CD was explored. For all tablets, in vitro dissolution studies showed sustained drug release over 48 hours, but for tablets containing HP-β-CD, the release was faster. Solid-state characterisation studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets exhibited good mechanical and physical features and guarantee stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalised pharmaceutical dosage forms starting directly from powders, avoiding the use of filament used by FDM.
Experimental Investigations on the Wall-attached Bubble Growth Process in Water With Supersaturated Total Dissolved Gas
Authors: Lin Lu , Li Ran , Feng Jingjie , Zou Qin , Cheng Xiaolong , Lin Honghui
Published: October 2021

Due to dam discharge, waterfalls, sudden increases in water temperature and oxygen production by photosynthesis, the total dissolved gas (TDG) in water is often supersaturated, which may have serious effects on aquatic ecology. When the atmospheric pressure is lower than the TDG pressure in water, the supersaturated dissolved gas in water will slowly release into air. Wall-attached bubbles were formed during the TDG release process. The generation and departure of wall-attached bubbles influence the release process of TDG in water. To simulate the growth period of the wall-attached bubbles under different pressures, a decompression experimental device was designed to record the supersaturated TDG release process. Based on experimental data and mathematical calculations, the quantitative relationship between the bubble growth rate and environmental pressure was obtained. The supersaturated TDG dissipation rate increases monotonically with increasing relative vacuum degree. Based on the wall-attached bubble growth rate calculation method applied in this paper, a formula of the supersaturated TDG adsorption flux based on wall-attached bubbles was proposed, and a prediction method of the TDG release coefficient was established. The simulation results show that with increasing relative vacuum degree, the TDG coefficient increases correspondingly, and the adsorption mechanism of vegetation surface area can be obviously promoted under lower environmental pressure. This study provides an important theoretical basis for the accurate calculation of the TDG release process and provides a scientific basis for the accurate prediction of the spatial and temporal distribution of supersaturated TDG under different environmental conditions.
Efficacy of tuina, cupping and acupuncture therapy on pain, anxiety, depression and quality of life in patients with neck pain: A protocol for systematic review and network meta-analysis
Authors: Qin Shi-xin , Li An , Zhan Mao-Lin , Wu Yi-Cheng , Zhao Yong-Hua , Lv Zi-Meng , Zhang Yu
Published: October 2021

Background: Neck pain is a common disorder and is more frequent in females than in males worldwide. Recently, more attention is being paid to precautions for and treatment of neck pain. Current therapeutic methods for neck pain include pharmaceutical, complementary and alternative therapies. Tuina, acupuncture and cupping are effective in the treatment of neck pain, which enrich patients’ options. In this study, we aim to evaluate the efficacy of different interventions using randomised controlled trials to identify a prioritised treatment for neck pain.Methods: We will search five English databases (Web of Science, MEDLINE, EMBASE, OVID and Cochrane Library) and four Chinese databases (CNKI, SinoMed, Wanfang Database and VIP) from database inception to December 2020. Two reviewers will independently perform article screening (title, keywords, abstract and full text); data extraction; risk of bias (RoB) assessment and grading of recommendations assessment, development and evaluation. We will use RevMan 5.3 software to carry out statistical analysis of the RoB and risk ratio to analyse the dichotomous data. Finally, we will use GeMTC V.0.8.1 package of R-3.3.2 software for network meta-analysis based on a Bayesian framework.Discussion: We will compare these three interventions to determine the most effective therapy for neck pain in terms of improving pain, anxiety, depression and QoL. In this way, we will provide powerful evidence for future clinical practice guidelines for patients with neck pain who want to receive a suitable treatment.Systematic review registration: PROSPERO CRD42020206853.