bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons learned from implementation of the Workload Indicator of Staffing Need (WISN) methodology: An international Delphi study of expert users.
Authors: Namaganda Grace Nyendwoha , Whitright Audrey , Maniple Everd Bikaitwoha
Published: October 2021

BackgroundStaffing of health services ought to consider the workload experienced to maximize efficiency. However, this is rarely the case, due to lack of an appropriate approach. The World Health Organization (WHO) developed and has promoted the Workload Indicators of Staffing Need (WISN) methodology globally. Due to its relative simplicity compared to previous methods, the WISN has been used extensively, particularly after its computerization in 2010. Many lessons have been learnt from the introduction and promotion of the methodology across the globe but have, hitherto, not been synthesized for technical and policy consideration. This study gathered, synthesized, and now shares the key adaptations, innovations, and lessons learned. These could facilitate lesson-learning and motivate the WHO’s WISN Thematic Working Group to review and further ease its application.MethodsThe study aimed to answer four questions: (1) how easy is it for the users to implement each step of the WISN methodology? (2) what innovations have been used to overcome implementation challenges? (3) what lessons have been learned that could inform future WISN implementation? and (4) what recommendations can be made to improve the WISN methodology? We used a three-round traditional Delphi method to conduct a case study of user-experiences during the adoption of the WISN methodology. We sent three email iterations to 23 purposively selected WISN expert users across 21 countries in five continents. Thematic analysis of each round was done simultaneously with data collection.ResultsParticipants rated seven of the eight technical steps of the WISN as either “very easy” or “easy” to implement. The step considered most difficult was obtaining the Category Allowance Factors (CAF). Key lessons learned were that: the benefits gained from applying the WISN outweigh the challenges faced in understanding the technical steps; benchmarking during WISN implementation saves time; data quality is critical for successful implementation; and starting with small-scale projects sets the ground better for more effective scale-up than attempting massive national application of the methodology the first time round. ConclusionsThe study provides a good reference for easing WISN implementation for new users and for WHO to continue promoting and improving upon it.
Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features
Authors: Cuppen Edwin , Nguyen Luan , Hoeck Arne van
Published: October 2021

Tumor tissue of origin (TOO) is an important factor for guiding treatment decisions. However, TOO cannot be determined for ~3% of metastatic cancer patients and are categorized as cancers of unknown primary (CUP). As whole genome sequencing (WGS) of tumors is now transitioning from the research domain to diagnostic practice in order to address the increasing demand for biomarker detection, its use for detection of TOO in routine diagnostics also starts becoming within reach. While proof of concept for the use of genome-wide features has been demonstrated before, more complex WGS mutation features, including structural variant (SV) driver and passenger events, have never been integrated into TOO-classifiers even though they bear highly characteristic links with tumor TOO. Using a uniformly processed dataset containing 6820 whole-genome sequenced primary and metastatic tumors, we have developed Cancer of Unknown Primary Location Resolver (CUPLR), a random forest based TOO classifier that employs 502 features based on simple and complex somatic driver and passenger mutations. Our model is able to distinguish 33 cancer (sub)types with an overall accuracy of 91% and 89% based on cross-validation (n=6139) and hold out set (n=681) predictions respectively. We found that SV derived features increase the accuracy and utility of TOO classification for specific cancer types. To ensure that predictions are human-interpretable and suited for use in routine diagnostics, CUPLR reports the top contributing features and their values compared to cohort averages. The comprehensive output of CUPLR is complementary to existing histopathological procedures and may thus improve diagnostics for patients with CUP.
Synthesis of Sodium Titanates and Their Use in the Photocatalytic Degradation of No
Authors: Bastida Marco Antonio Cueto , Maldonado Yadira Guadalupe , Reyes-Vidal Yolanda , Solís-López Myriam , Coutino-González Eduardo , Ayala Fabricio Espejel
Published: October 2021

The synthesis and characterization of sodium titanates (ST), and their evaluation in the photocatalytic reduction of nitric oxide (NO) are described herein. The materials were synthesized by a hydrothermal route using 5 M NaOH as the mineralizer agent and a TiO2 content of 0.06 mg/mL (expressed as the mass ratio of TiO2/mL of NaOH), at 170 °C for 48 hours, resulting in sodium tri- and hexa-titanates. A nanotubular morphology was observed for the ST, as proved by scanning electron microscopy (SEM); a subsequent heat-treatment at 400 °C allowed a complete transformation of sodium tri- to hexa-titanates and an increase in bandgap. The obtained ST were impregnated with Ag+ and Zn+ cations, ST-Ag and ST-Zn, respectively, to tune the materials’ bandgap. XPS analysis of the ST-Ag materials showed evidence of metallic Ag, pointing to the formation of silver nanoparticles, whereas for ST-Zn oxide phases were mainly spotted. The materials were evaluated for the photocatalytic reduction of NO using a reactor fed with a continuous flow rate of NO, generated in situ at a flow of 280 mL/min using nitrogen and a 253 nm UV irradiation source. The photocatalytic tests showed that pristine ST (tri- and hexa-titanates) displayed better performance in the reduction of NO with respect to the impregnated samples (ST-Ag, ST-Zn). Maximum degradation efficiencies of 80% were achieved when 1 g of photocatalyst was used with a flow of 280 mL/min and a 253 nm UV lamp.
Seeing pre-screened, regular clients associated with lower odds of workplace sexual violence and condom refusal amidst sex work criminalization: Findings of a community-based cohort of sex workers in Metro Vancouver, Canada (2010-2019)
Authors: McBride Bronwyn , Shannon Kate , Pearson Jennie , Krüsi Andrea , Braschel Melissa , Goldenberg Shira
Published: October 2021

Background
Research that accurately represents how characteristics of sex work clients relate to sex workers’ labour conditions is crucial for informing evidence-based legislation which upholds sex workers’ human rights. However, little quantitative research has examined how seeing regulars (repeat clients) impacts sex workers’ occupational safety, particularly under ‘end-demand’ criminalization.
Methods
Drawing on longitudinal data from a community-based cohort of 900+ sex workers in Vancouver, we used logistic regression analyses to 1) describe correlates of seeing mostly pre-screened, regular clients, 2) identify associations between seeing mostly regulars and odds of experiencing occupational outcomes of workplace sexual violence and client condom refusal, and 3) examine the interaction between seeing mostly regulars and work environment on workplace sexual violence and client condom refusal.
Results
Over the 9-year study (N=925), seeing mostly regulars was associated with reduced odds of sexual violence (AOR 0.73, 95%CI 0.53-1.02) and client condom refusal (AOR 0.70, 95%CI 0.57-0.86) in multivariable GEE confounder models. These associations were strongest among sex workers in outdoor/informal indoor workspaces.
Conclusion
Our findings highlight protective effects of seeing pre-screened regulars within a criminalized setting. Removal of ‘end-demand’ client criminalization is needed to enable sex workers to effectively screen clients, support HIV/STI prevention, and advance sex workers’ human rights.
DnaK response to expression of protein mutants is dependent on translation rate and stability
Authors: Christensen Signe , Rämisch Sebastian , André Ingemar
Published: October 2021

Chaperones play a central part in the quality control system in cells by clearing misfolded and aggregated proteins. The chaperone DnaK acts as a sensor for molecular stress by recognising short hydrophobic stretches of misfolded proteins. As the level of unfolded protein is a function of protein stability, we hypothesised that the level of DnaK response upon overexpression of recombinant proteins would be correlated to stability. Using a set of mutants of the lambda-repressor with varying thermal stabilities and a fluorescent reporter system, the effect of stability on DnaK response and protein abundance was investigated. Our results demonstrate that the initial DnaK response is largely dependent on protein synthesis rate but as the recombinantly expressed protein accumulates and homeostasis is approached the response correlates strongly with stability. Furthermore, we observe a large degree of cell-cell variation in protein abundance and DnaK response in more stable proteins.
Experimental device-independent quantum key distribution between distant users
Authors: Lim Charles , Zhang Wei , Leent Tim , Redeker Kai , Garthoff Robert , Schwonnek Rene , Fertig Florian , Eppelt Sebastian , Scarani Valerio , Weinfurter Harald , Rosenfeld Wenjamin
Published: October 2021

Device-independent quantum key distribution (DIQKD) is the art of using untrusted devices to establish secret keys over an untrusted channel. So far, the real-world implementation of DIQKD remains a major challenge, as it requires a loophole-free Bell test with very high quality entanglement and detection efficiency across two remote locations to ensure secure key exchange. Here, we demonstrate for the first time the distribution of a secure key, based on asymptotic security estimates, in a fully device-independent way between two users separated by 400 metres. The experiment is based on heralded entanglement between two independently trapped single Rubidium 87 atoms. The implementation of a robust DIQKD protocol indicates an expected secret key rate of r=0.07 per entanglement generation event. Furthermore, we analyse the experiment’s capability to distribute a secret key with finite-size security against collective attacks.
Development and Validation of a Novel 3-Gene Prognostic Model for Pancreatic Adenocarcinoma Based on Ferroptosis-Related Genes
Authors: Yang Jihua , Wei Xiaohong , Hu Fang , Wei Dong , Sun Liao
Published: October 2021

Background: Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. Methods: RNA-sequence data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The R software package clusterProfiler was used for functional enrichment analysis. By LASSO regression, we established a multi-gene prognostic model, and the model was validated by qPCR and immunohistochemistry and T3M4 cell line. Results: Three molecular subtypes were identified, and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. Finally, qPCR and immunohistochemical staining and cell function results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. Conclusions: We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.
Gene expression trend changes in breast cancer populations over two decades: insights from The Cancer Genome Atlas database
Authors: Wu Jinbo , Hu Taobo , Wang Shu
Published: October 2021

Background: Breast cancer has remained the most common malignancy in women over the past two decades. As lifestyle and living environments have changed, alterations to the disease spectrum have inevitably occurred in this time. As molecular profiling has become a routine diagnostic and objective indicator of breast cancer etiology, we analyzed changes in gene expression in breast cancer populations over two decades using The Cancer Genome Atlas (TCGA). Methods: We performed Heatmap and Venn diagram analyses to identify constantly up- and down-regulated genes in this cohort. We used Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. Results: We determined that three oncogenes, PD-L2, ETV5, and MTOR and 113 long intergenic non-coding RNAs (lincRNAs) were constantly up-regulated, whereas two oncogenes, BCR and GTF2I, one tumor suppression gene (TSG) MEN1, and 30 lincRNAs were constantly down-regulated. Up-regulated genes were enriched in “focal adhesion” and “PI3K-Akt signaling” pathways, et al, and down-regulated genes were significantly enriched in “metabolic pathways” and “viral myocarditis”. Eight up-regulated genes exhibited doubled or higher expression, and the expression of three down-regulated genes was halved or lowered and correlated with long-term survival. Conclusions: In this study, we determined that genes and molecular pathways are constantly changing, importantly, some altered genes were associated with prognostics and are potential therapeutic targets, suggesting molecular typing technologies must keep pace with this dynamic situation.
Effect of acupuncture therapy on regulating serum cytokines : a systematic review and meta-analysis protocol
Authors: Feng Xiaoteng , Du Min , Zhang Yifan , Li Sijin , Ding Jie , Wang Jiarou , Wang Yiru , Liu Ping
Published: October 2021

Introduction: There is still a lack of evidence-based, safe, and high benefit/harm ratio full-term prevention and treatment methods to effectively inhibit the release of the inflammatory factors. Serum cytokine level indicates the severity of inflammatory activities in surgery, infection, and many diseases. Accumulating evidence has shown that acupuncture, which has the advantages of safety, simplicity, and low price, can reduce serum cytokine levels. Methods and analysis: We will search three English databases (PubMed, EMBASE and Cochrane Library) and four Chinese databases (Chinese biomedical literature database, VIP database for Chinese technical periods, China National Knowledge Infrastructure, and Wanfang) to obtain all RCT studies. Research of other types will not be included. But no literature will be excluded due to the publication date. Two independent reviewers will conduct research screening of three levels (title, abstract and full text), data extraction and bias risk assessment according to the inclusion/exclusion criteria, and their differences will be resolved by a senior researcher. Random or fixed-effect models will be used according to data heterogeneity. The data will be expressed as the risk ratio of binary data or the average difference of continuous data, and the confidence interval (CI) of all results is 95%. Ethics and dissemination: Since only the data in the published literature are used for secondary analysis, there is no need to re-apply for ethical review. We will publish the results of this study and share the findings with our peers at international conferences. PROSPERO registration title and number: Effect of acupuncture therapy on regulating serum cytokines: a systematic review and meta-analysis CRD42021268894
Impact of Toothbrush Age on Clinical Indicators of Oral Health, a Protocol for a Systematic Review
Authors: Zayandeh Sepideh , Yaghoubi Zahra , Hosseini Kosar
Published: October 2021

Background: Dental caries is the most common chronic untreated disease worldwide. The simplest and most important factor in preventing dental caries is maintaining oral hygiene and removing microbial plaque using a toothbrush. Despite the relationship between toothbrush filament wear and plaque removal effectiveness as a potentially important factor in maintaining oral health, there is little objective standard evidence as to 1) what constitutes a worn-out brush and 2) the degree of loss in plaque removal effectiveness due to brush wear. Contradictions in the results of studies on toothbrushing and the loss of its effectiveness in removing plaque based on the time spent using the toothbrush have led to conflicting recommendations for changing toothbrushes after different periods. While some studies generally question the relationship between toothbrush age and effectiveness. The lack of comprehensive evidence in this area necessitates a structured review study.Methods: We will search the electronic databases ISI, Scopus, and PubMed to find related articles. Our main inclusion criterion is Clinical trial and observational studies investigating manual toothbrush longevity in the natural toothbrush-worn model on each objective indicator of oral health (including plaque removal and gingival indices ...). All funded citations are entered into the Endnote software. the full texts of potentially relevant studies are prepared. study selection and extracting the data will be performed by two reviewers. Also, the studies quality will be assessed. The findings will be displayed using figures, summary tables and narrative summaries. If the similarity of studies and their quality is desirable, meta-analysis will be performed. We will assess the heterogeneity on the bias of the magnitude of heterogeneity variance parameter. We are also going to conduct subgroup analysis and sensitivity analysis if needed.Discussion: The final systematic review highlights the gaps in the available evidence about the effectiveness of toothbrush longevity on each oral indices to provide the best recommendation for toothbrush renewal periods. Registration: The review subject has been submitted in PROSPERO database
De novo and comparative transcriptomic analysis explain morphological differences in Panax notoginseng taproots
Authors: Yang Lifang , Wang Hanye , Wang Panpan , Gao Mingju , Huang Luqi , Cui Xiuming , Liu Yuan
Published: October 2021

Background: Panax notoginseng (Burk.) F. H. Chen (PN) belonging to the genus Panax of family Araliaceae is widely used in traditional Chinese medicine to treat various diseases. PN taproot, as the most vital organ for the accumulation of bioactive components, presents a variable morphology (oval or long), even within the same environment. However, no related studies have yet explained the molecular mechanism of phenotypic differences. To investigate the cause of differences in the taproot phenotype, de novo and comparative transcriptomic analysis on PN taproot was performed. Results: A total of 133,730,886 and 114,761,595 paired-end clean reads were obtained based on high-throughput sequencing from oval and long taproot samples, respectively. 121,955 unigenes with contig N50 = 1,774 bp were generated by using the de novo assembly transcriptome. The annotation results showed 38,313 BLASTX hits and 24,820 BLASTP hits. KEGG analysis identified 52 genes encoding class III peroxidase (PRX) family members, 13 genes encoding L-Ascorbate peroxidase (APX) family members, and 99 genes encoding a series of mitogen-activated protein kinase (MAPK) family members. Differentially expressed genes analysis indicated substantial upregulation of genes encoding APX3 and PRX45 enzymes, which are related to reactive oxygen species metabolism, and the MPK3 enzyme, which is related to cell proliferation and plant root development, in long taproots compared with that in oval taproots. Furthermore, the determination results of real-time quantitative PCR, enzyme activity, and H2O2 content verified transcriptomic analysis results. Conclusion: These results collectively demonstrate that reactive oxygen species (ROS) metabolism and the MPK3 enzyme may play vital roles in regulating the taproot phenotype of PN. This study provides further insights into the genetic mechanisms of phenotypic differences in other species of the genus Panax.
Identifying Key Features of Telepresence Robot Systems in Intensive Care Units: a Scoping Review Protocol
Authors: Avilés Héctor , Hernández-Méndez Sergio , Vargas-Martinez Héctor Simón , Negrete-Villanueva Marco Antonio , de Anda Gilberto Felipe Vázquez
Published: October 2021

Background: The progress of robotics in the last decades and the current Covid-19 outbreak have contributed to an increasing interest in integrating telepresence robot systems into healthcare. However, it is still needed to better understand how robotic features contribute to medical practice and to the wellness of patients. Hence, we propose a scoping review to spot features of telepresence robot systems that impact the fulfillment of goals in health care for patients in intensive care units. Methods and analysis: Our review will be guided by Arksey and O'Malley’s framework and the revisions by Levac et al., and Peters et al. We will search in 18 scientific databases specialized on either medicine or digital technology, plus another 5 online sources of grey literature. We will consider documents dated between 2000 and 2021, in English and Spanish, and we will perform a quantitative analysis and a thematic synthesis of the papers included in this study.Discussion: This work will help to recognize characteristics, components and capabilities of telepresence robots that are relevant in medical practice, to guide new research and development avenues and boost cooperation between health providers and roboticists. Results will be submitted to a peer-reviewed journal and included in promotional activities of our universities. This study does not require ethics review, however, we will be very attentive to feedback from patients, caregivers, health providers and decision makers involved in this scoping review. OSF Registration: DOI: 10.17605/OSF.IO/S3FHR (Submitted on October 4, 2021)
Incidence, Outcome And Risk Factors of Postoperative Delirium Subtypes, A Systematic Review And Meta-Analysis
Authors: Li Qian , Guo Jingfei , Shi Jia
Published: October 2021

Objective: Systematic review and meta-analysis methodology was used to estimate the pooled incidence, outcome, risk factors of postoperative delirium, including three delirium subtypes: hyperactive delirium, hypoactive delirium, mixed delirium.Methonds: This systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses(PRISMA) guideline. MEDLINE、EMBASE、CENTRAL were searched for relevant studies. Thirty-two studies from 2714 searched results with 9049 patients were enrolled in this systematic review and meta-analysis. Inclusion criteria were:1) elective surgery population;2) the incidence of delirium subtypes was recorded ;3) cohort studies.;4) language restricted to English. In addition, studies that were randomized control trials (RCT), case reports, or uncertainty in the incidence of delirium subtypes were excluded. The related information was extracted by two reviewers independently.All the analyses were conducted by the STATA (Version 16.0; Stata Corporation, College Station, TX).Result: The study we have performed showed that the highest incidence of postoperative delirium was hypoactive (14%[95%CI,12-16%]), followed by hyperactive (12%[95%CI,10-14%]), and the lowest was mixed delirium(9%[95%CI,7-11%]).Conclusion : The highest incidence of postoperative delirium was hypoactive (14%[95%CI,12-16%]), followed by hyperactive (12%[95%CI,10-14%]), and the lowest was mixed delirium(9%[95%CI,7-11%]). Therefore, it is definitely necessary to update and unify the diagnosis of delirium subtypes based on current tremendous clinical research, thus controlling and adjusting the risk factors of subtypes to reduce the incidence of postoperative delirium and improve patients' prognoses.
Convenience, usability and complications of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation: A questionnaire-based, patient-centric study
Authors: Hajiabadi Mohammad Mehdi , Jakobs Martin , Vicheva Petya , Unterberg Andreas , Ahmadi Rezvan
Published: October 2021

IntroductionSpinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience.Material & MethodsStandardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates.ResultsQuestionnaires of 6 patients were returned and eligible for data analysis. The mean age of patients was 61.3 ± 6.7 (± SD) years. The duration of therapy was 20.3 ± 15.9 months (mean ± SD). The mean duration of daily stimulation was 17 ± 5.9 hours (mean ± SD). n=5 patients rated the overall convenience as "easy" (4) and evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). n=5 patients considered the wearing and charging process as an active participation in their (personal) therapy. n=5 patients would choose an extracorporeal device again over a conventional SCS system. Early or late surgical complications did not occur in this patient collective.ConclusionOverall, patients felt confident using extracorporeal wSCS devices without any complications. Effort to maintain therapy with this system was rated as low. The results of this pilot study need to be verified with a larger cohort in a prospective trial.
Study on Electromagnetic Radiation Interference Caused by Rocket Fuel
Authors: Cui Yuanbo , Kong Deren , Jiang Jian , Gao Shang , Wang Shuai
Published: October 2021

During the launch and return of a spacecraft, the intense combustion of propellants generates strong electromagnetic radiation, which interferes with the operation of electronic equipment in the spacecraft. To improve the electromagnetic compatibility of electronic equipment in spacecraft, it is necessary to study the electromagnetic radiation characteristics of rocket fuel. An electromagnetic radiation measurement system based on antennas is designed to measure the electromagnetic radiation generated by rocket fuel, and the electromagnetic radiation characteristics are obtained through data analysis. The mechanism of the electromagnetic radiation generated by rocket fuel is comprehensively analysed through the spatial, time-domain, frequency-domain, and energy-domain characteristics. A characterization model is established to provide a reliable scheme for evaluating the influence of rocket fuel electromagnetic radiation on electronic equipment in spacecraft.
Achieving Submicrometer Spatial Resolution for Neutron Imaging With Nuclear Emulsion
Authors: Muneem Abdul , Yoshida Junya , Ekawa Hiroyuki , Hino Masahiro , Hirota Katsuya , Ichikawa Go , Kasagi Ayumi , Kitaguchi Masaaki , Muto Naoto , Mishima Kenji , Nabi Jameel , Nakagawa Manami , Naganawa Naotaka , Saito Takehiko
Published: October 2021

Neutron imaging is a non-destructive inspection technique with a wide range of potential applications. One of the key technical interests concerning neutron imaging is to achieve micrometer-scale spatial resolution. However, developing a neutron detector with a high spatial resolution is a challenging task. Recent efforts are focused on achieving this milestone or even submicrometer spatial resolution. Herein, we introduce our technique for neutron imaging using a fine-grained nuclear emulsion and evaluate the spatial resolution. We used the fine-grained nuclear emulsion with a gadolinium-based Siemens star test pattern and a grating with a periodic structure of 9 μm. The deduced value of the spatial resolution is less than 1 μm using the developed technique. To the best of our knowledge, the submicrometer spatial resolution that we achieved using our method is the best among all reported neutron imaging devices.
Diversity of Prokaryotic Microorganisms in Alkaline Saline Soil of the Qarhan Salt Lake Area in the Qinghai-Tibet Plateau
Authors: Wang Yaqiong , Bao Guoyuan
Published: October 2021

Microbial metabolism is the driving force for biogeochemical cycles in the biosphere. The composition of microbial communities varies greatly in various ecological environments, particularly in extreme environments where animals and plants cannot survive. Unique microorganisms are often used as indicators to reflect environmental conditions, but the ecological reasons for the differences in microbial communities are still largely unknown. Here, we analyzed taxonomic and functional community profiles via high-throughput sequencing to determine the alkaline saline soil bacterial and archaeal communities in the Qarhan Salt Lake area in the Qinghai-Tibet Plateau. The results showed that Betaproteobacteria (Proteobacteria) and Halobacteria (Euryarchaeota) were most abundant in the soils of this area, which are most common in high salinity environments. Accordingly, microorganisms in this area that can adapt to local extremes often have functions such as chemoheterotrophy, aerobic chemoheterotrophy, nitrogen fixation, ureolysis, nitrate reduction, fermentation, methanogenesis, hydrogenotrophic methanogenesis, methanogenesis by CO2 reduction with H2, methanogenesis using formate, and dark hydrogen oxidation. There is no doubt that prokaryotic microorganisms in high salinity environments play an irreplaceable role in nitrogen and carbon cycling through special metabolic pathways.
Synthesis, Antifungal Activity and Molecular Dynamics Study of Novel Aromatic Geranyl Sulfonamide Compounds as Potential Complex III Inhibitors
Authors: Song Xinning , Li Jianing , Lu Xingxing , Jiang Zhiyang , Han Qing , Zhu Kai , Li Huilin , Ling Yun , Duan Hongxia
Published: October 2021

Essential oils (EOs), as unique natural products, are promising resources for the discovery of green agrochemicals. Geraniol was found to exhibit substantial fungicidal activities within citronella oil in this study. A series of novel geranyl benzenesulfonamide compounds were synthesized and found to display considerable fungicidal activities. Some aromatic geranyl sulfonamide derivatives were further optimized and then evaluated the bioactivities against six phytopathogenic fungi. Geranyl thiofuran-sulfonamide compounds 4d-1 (median effective concentration (EC50) against Rhizoctonia solani: 24.97 mg/L and EC50 against Sclerotinia sclerotiorum: 27.26 mg/L), 4d-2 (EC50 against S. sclerotiorum: 18.53 mg/L) and Geranyl pyridine-sulfonamide compound 4e-2 (EC50 against R. solani: 29.31 mg/L and EC50 against S. sclerotiorum: 29.98 mg/L) were screened as “star molecules” with highly efficient fungicidal activities. The structure-activity relationship (SAR) study revealed that the electron-rich thiofuran ring and chlorine-substituted piperidine played remarkable roles on increasing the fungicidal activities. The molecular mechanisms of the “star molecules” were also clarified by performing molecular docking and molecular dynamics (MD) simulations, and these geranyl sulfonamide compounds were identified as potential Complex III inhibitors. The main component originating from the natural plant EOs ought to be studied to discover novel pathogenic fungicidal candidates used to control agricultural plant diseases.
A Refined, Controlled 16S RRNA Gene Sequencing Approach Reveals Limited Detection of Cerebrospinal Fluid Microbiota in Children with Bacterial Meningitis
Authors: Pope Christopher E. , Whitlock Kathryn B. , Hodor Paul , Limbrick David L. , McDonald Patrick J. , Hauptman Jason , Hoffman Lucas R. , Simon Tamara
Published: October 2021

Background:Advances inboth laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads such as human cerebrospinal fluid (CSF). The objectives of this work were to (1) optimize the performance of 16S HTS in CSFsamples with low bacterial loads by defining and addressing potential sources of error; and (2) perform refined16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures.Results:Several bench and computational approaches were taken to address potential sources of error for low bacterial load samples. We compared DNA yields and sequencing results after applying three different DNA extraction approaches to an artificially-constructed (“mock”) bacterial community. We also comparedtwo post-sequencing computational contaminant removal strategies, decontam R and full contaminant sequence removal. All three extraction techniques followed by decontam R yielded similar results for the mock community.We then applied these methods to 22 CSF samples from children diagnosed with meningitis, which has low bacterial loads relative to other clinical infection samples. The refined 16S HTS pipelines identified the cultured bacterial genus as the dominant organism for only 3 of these samples.Conclusions:We found that all three DNA extraction techniques followed by decontam R generated similar DNA yields for mock communities at the low bacterial loads representative of CSF samples. However, the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches despite rigorous controls and sophisticated computational approaches. Although we did not find current DNA-based diagnostics to be useful for pediatric meningitis samples, the utility of these methods for CSF shunt infection remains undefined. Future advances in sample processing methods to minimize or eliminate contamination will be required to improve the sensitivity and specificity of these methods for pediatric meningitis.
Implementation of Buprenorphine Services in NYC Syringe Services Programs: a qualitative process evaluation
Authors: Jakubowski Andrea , Rath Caroline , Harocopos Alex , Wright Monique , Welch Alice , Kattan Jessica , Behrends Czarina Navos , Lopez-Castro Teresa , Fox Aaron D.
Published: October 2021

Background

Syringe services programs (SSPs) hold promise for providing buprenorphine treatment access to people with opioid use disorder (OUD) who are reluctant to seek care elsewhere. In 2017, the New York City Department of Health and Mental Hygiene (DOHMH) provided funding and technical assistance to nine SSPs to develop “low-threshold” buprenorphine services as part of a multipronged initiative to lower opioid-related overdose rates. The aims of this study were to 1) Describe characteristics of SSP-based buprenorphine services; and 2) Identify barriers to and facilitators of implementing SSP-based buprenorphine services.
Methods

We conducted 26 semi-structured qualitative interviews from April 2019 - November 2019 at eight SSPs in NYC that received funding and technical assistance from DOHMH. Interviews were conducted with three categories of staff: leadership (8 interviews); staff (11), and providers (6). We used thematic analysis to identify themes within pre-identified domains: program characteristics and barriers and facilitators to program implementation. We make recommendations for implementation based on our findings.
Results

Programs differed in their stage of development, location of services provided, and provider type, availability, and practices. Barriers to providing buprenorphine services at SSPs included gaps in staff knowledge and comfort communicating with participants about buprenorphine, difficulty hiring providers, managing tension between harm reduction and traditional OUD treatment philosophies, and financial constraints. Challenges also arose from serving a population with unmet psychosocial needs. Implementation facilitators included technical assistance from DOHMH, designated buprenorphine coordinators, offering other supportive services to participants, and telehealth to bridge gaps in provider availability. Key recommendations include: 1) health departments should provide support for SSPs in training staff, building health service infrastructure and developing policies and procedures, 2) SSPs should designate a buprenorphine coordinator and ensure regular training on buprenorphine for their frontline staff, and 3) providers should be selected or supported to use a harm reduction approach to buprenorphine treatment.
Conclusions

Despite encountering challenges, eight SSPs implemented buprenorphine services outside of conventional OUD treatment settings. Our findings have implications for health departments, SSPs, and other community organizations implementing buprenorphine services. Expansion of low-threshold buprenorphine services is a promising strategy to address the opioid overdose epidemic.
Association Between Moderate Physical Activity Level and Subsequent Frailty Incidence Among Community-Dwelling Older Adults: A Population-Based Cohort Study
Authors: Zhao Wenjing , Ukawa Shigekazu , Sasaki Sachiko , Okada Emiko , Kishi Tomoko , Kondo Kastunori , Tamakoshi Akiko
Published: October 2021

Background

The evidence concerning longitudinal association between physical activity (PA) and frailty is scarce, and variation in the scales, tools, or modules of PA made it challenging to obtain consistent results. This association among the individules who reached an older age where age-related cumulative chronic diseases and physical function declines were common, was unclear. Our study aimed to demonstrate the association between PA and frailty incidence among Japanese community-dwelling older adults with narrow age range of 70–74 years.
Mothods:

About 485 participants aged 70–74 years from the Japan Gerontological Evaluation Study were included in this study. Frailty was assessed at baseline and 3 years later by using the Kaigo-Yobo Checklist. PA was assessed using the short-term International Physical Activity Questionnaire. Logistic regression was performed to calculate relative risk (RR) with 95% confidence intervals (CIs) after adjusting for potential confounders.
Results

After a 3-year follow-up, 46 new frailty cases were recorded. The association of frailty incidence with both PA volume and daily walking time presented a U-shaped curve, albeit statistically insignificant. After adjusting for potential confounders, walking for 0.5–1 h/d displayed a greater association with decreased frailty risk (OR, 0.35; 95% CI, 0.12–0.98) than higher levels of daily walking time. No association between PA volume and subsequent frailty was observed.
Conclusions

Incorporating moderate regular walking levels of 0.5–1 h/d in older adults may delay the onset of frailty and improve the aging process. Further studies are needed to investigate the effect of higher PA levels on frailty risk.
Numerical Simulation of The Response of An Underground Pipeline Connector With a Super-Large Section Under Complex Geological Conditions
Authors: Ma Long , Ai Ping , Xiong ChuanSheng
Published: October 2021

Aiming at the low simulation accuracy of the numerical simulation method of the joint response of the super-large section underground comprehensive pipeline gallery under the current complicated geological conditions, a numerical simulation method of the joint response of the super-large section underground comprehensive pipe gallery joint response under the complicated geological conditions based on the finite element model was proposed. According to the analysis process for the super-large section underground comprehensive pipe gallery, the viscous boundary of the comprehensive pipe gallery is determined. Additionally, by analyzing soil and structural parameters, the optimal combined dynamic boundary is used as the model boundary. The HSS model is used to describe the constitutive structure of the soil, and by improving the Goodman element to describe the contact surface of the model, the finite element model of the joint response of the comprehensive pipe gallery is constructed. Furthermore, based on the internal force balance and deformation coordination conditions, considering the influence of the deformation shape of the joint joints and the elongation of the prestressed tendons on the finite element model, the response model of the integrated pipe gallery joint is optimized. Experimental results show that the proposed method has higher numerical simulation accuracy.
Unintended Pregnancies Among HIV Positive Women In Sub Saharan Africa: A Scoping Review Protocol
Authors: Tomilola Oguntade Racheal , Bolanle Ojewole Elizabeth , Olufunmi Ogunrombi Modupe
Published: October 2021

Background: Unintended pregnancies pose a severe threat to the well-being of HIV-positive women and their unborn children. Factors contributing to the high incidence of unintended pregnancies include contraceptive failure, low uptake of contraceptives, and misuse of contraceptives. Despite various contraceptive options, an increased incidence of unintended pregnancies is rampant among HIV-positive women in the region of sub-Saharan Africa. This study seeks to present evidence of unintended pregnancies among women living with HIV in sub-Saharan Africa, including those using contraceptives.Method: This study entails a scoping review to survey and interrogate the literature to provide evidence for the incidence of unintended pregnancies among HIV-positive women in sub-Saharan Africa. A proposed framework by Arksey and O'Malley will guide this scoping review. Peer-reviewed articles which address the research questions will constitute the main search. Electronic databases such as EBSCOhost, Cochrane Library, World of Science, World Health Organization (WHO) library databases, Science Direct, Google Scholar PubMed, and grey literature search will be involved. References list from studies included will also be searched. The investigation of articles will be done employing keywords from the studies included. The inclusion and exclusion criteria will guide two separate reviewers with the screening of abstracts and full papers. To summarize the findings from this review, thematic content analysis will be done using NVivo version 11.Discussion: We expect that this review will add to the current body of knowledge on the incidence of unintended pregnancies among HIV-positive women, identify gaps for further future research, and show evidence that may contribute to strengthening the health system's regulations, guidelines, and policies that may help prevent unintended pregnancies among HIV positive women. Registration DOI: 10.17605/OSF.IO/EY3R5
Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy
Authors: Chen Ying-Chen , Lu Bing-Ze , Shu Yu-Chen , Sun Yuan-Ting
Published: October 2021

Objective
Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral permeability (Ktrans) in the progression of diabetes-related CSVD.
Methods
Cerebral vascular permeability was crossectional measured in diabetic patients with or without CSVD, and non-diabetic patients with or without CSVD by using dynamic contrast-enhanced MRI (DCE-MRI).
Results
In all diabetic patients, the Ktrans of white matter (WM) was increased. However, the Ktrans of gray matter (GM) was only increased in those with CSVD. This suggested the earlier involvement of WM than GM and indicated the development of diabetes-related cerebral microangiopathy was prior to it could be visualized as features of CSVD on MRI. To broaden the application of cerebral permeability and overcome the limitations of DCE-MRI, the commonly available CSVD items of MRI were used to indicate the increase in Ktrans. Among all CSVD items, the presence of microbleeds was most correlated with the increased permeability in all patients. In contrast to non-diabetic patients, increased Ktrans in diabetes was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.
Conclusions
This study highlights the early development of cerebral microangiopathy in diabetes and broadens the applicability of cerebral permeability. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.
Effects of Magnetic Minerals Exposure and Microbial Responses in Surface Sediment Across Bohai Sea
Authors: Chen Lei , Wang Mingpeng , Li Yuntao , Shang Weitao , Tang Jianhui , Zhang Zhaojie , Liu Fanghua
Published: October 2021

Extensive production and application of magnetic minerals produce significant amounts of magnetic wastes to the environment. These magnetic minerals exposure could affect microbial community composition and geographic distribution. Here, we reported magnetic susceptibility is involved in determining bacterial α-diversity and community composition in surface sediment across Bohai Sea. Environmental factors (explained 9.80%) played a larger role than spatial variables (explained 6.72%) in conditioning the bacterial community composition. Exposure of magnetite center may shape geographical distribution of five dissimilatory iron reducing bacteria (DIRB). Microbial iron reduction ability and electroactive activity in sediment close to magnetite center are stronger than those far away. Our study provides novel understanding for response of DIRB and electroactive bacteria to magnetic minerals exposure.