bluuebunny/crossref_metadata_2025 huggingface dataset:
Permethrin resistance in Aedes aegypti: Genomic variants that confer knockdown resistance, recovery, and death
Authors: Saavedra-Rodriguez Karla , Campbell Corey L. , Lozano Saul , Penilla-Navarro Patricia , Lopez-Solis Alma , Solis-Santoyo Francisco , Rodriguez Americo D. , Perera Rushika , Black IV William C.
Published: June 2021

Pyrethroids are one of the few classes of insecticides available to controlAedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur inAe.aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site—the voltage-gated sodium channel (VGSC)—and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations atVGSCand moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.
Diagnosing point-of-care diagnostics for neglected tropical diseases
Authors: Bharadwaj Mitasha , Bengtson Michel , Golverdingen Mirte , Waling Loulotte , Dekker Cees
Published: June 2021

Inadequate and nonintegrated diagnostics are the Achilles’ heel of global efforts to monitor, control, and eradicate neglected tropical diseases (NTDs). While treatment is often available, NTDs are endemic among marginalized populations, due to the unavailability or inadequacy of diagnostic tests that cause empirical misdiagnoses. The need of the hour is early diagnosis at the point-of-care (PoC) of NTD patients. Here, we review the status quo of PoC diagnostic tests and practices for all of the 24 NTDs identified in the World Health Organization’s (WHO) 2021–2030 roadmap, based on their different diagnostic requirements. We discuss the capabilities and shortcomings of current diagnostic tests, identify diagnostic needs, and formulate prerequisites of relevant PoC tests. Next to technical requirements, we stress the importance of availability and awareness programs for establishing PoC tests that fit endemic resource-limited settings. Better understanding of NTD diagnostics will pave the path for setting realistic goals for healthcare in areas with minimal resources, thereby alleviating the global healthcare burden.
Impacts of an Amazonian hydroelectric dam on frog assemblages
Authors: Dayrell Jussara Santos , Magnusson William Ernest , Bobrowiec Paulo Estefano Dineli , Lima Albertina Pimentel
Published: June 2021

About 90% of the Amazon’s energy potential remains unexploited, with many large hydroelectric dams yet to be built, so it is important to understand how terrestrial vertebrates are affected by reservoir formation and habitat loss. We investigated the influence of the construction of the Santo Antônio Hydroelectric dam on the Madeira River in southwestern Amazonia on the structure of frog assemblages based on samples collected in two years before the dam flooded (pre-stage) and one (post1-stage) and four years (post2-stage) after its construction. We surveyed five 500-ha plot systems three times during each stage; in the pre-stage we sampled 19 plots in low-lying areas that would be flooded by the dam, (from now called flooded pre-stage plots) and 45 plots in terra-firme forest (from now called unflooded pre-stage plots). At the post1-stage we sampled the 45 unflooded plots and in the post2-stage we sampled the remaining 39 unflooded plots. We detected frogs by active visual and acoustic searches standardized by both time and sampling area. Few species recorded in the pre-stage flooded plots were not found in the pre-stage unflooded plots or in stages after flooding. However, the composition of frog assemblages based on relative densities in flooded pre-stage plots did not re-establish in plots on the new river margins. In unflooded areas, frog assemblages were distinct among the flooding stages with no tendency to return to the original assemblage compositions even four years after the dam was filled. For the areas that were not flooded, there was an increase in species richness in 82% of the plots between the surveys before dam construction and the first surveys after dam completion, and 65% between the pre-stage and surveys four years after dam completion. Lack of understanding by the controlling authorities of the long-term effects of landscape changes, such as water-table rises, means that studies covering appropriate periods post construction are not required in legislation, but the data from Santo Antônio indicate that changes due to dam construction are either long-term or difficult to distinguish from natural fluctuations. Future environmental-impact studies should follow strict BACI designs.
Efficacy and safety of anticoagulants for postoperative thrombophylaxis in total hip and knee arthroplasty: A PRISMA-compliant Bayesian network meta-analysis
Authors: He Tailai , Han Fei , Wang Jiahao , Hu Yihe , Zhu Jianxi
Published: June 2021

Objective

To search, review, and analyze the efficacy and safety of various anticoagulants from randomized clinical trials (RCTs) of anticoagulants for THA and TKA.

Design

PRISMA-compliant Bayesian Network Meta-analysis.

Data sources and study selection

The databases of The Medline, Embase, ClinicalTrial, and Cochrane Library databases were searched until March 2017 for RCTs of patients undergoing a THA or TKA.

Main outcomes and measures

The primary efficacy measurement was the venous thromboembolism Odds ratio (OR). The safety measurement was the odds ratio of major or clinically relevant bleeding. OR with 95% credibility intervals (95%CrIs) were calculated. Findings were interpreted as associations when the 95%CrIs excluded the null value.

Results

Thirty-five RCTs (53787 patients; mean age range, mostly 55–70 years; mean weight range, mostly 55–90 kg; and a higher mean proportion of women than men, around 60%) included the following Anticoagulants categories: fondaparinux, edoxaban, rivaroxaban, apixaban, dabigatran, low-molecular-weight heparin, ximelagatran, aspirin, warfarin. Anticoagulants were ranked for effectiveness as follows: fondaparinux (88.89% ± 10.90%), edoxaban (85.87% ± 13.34%), rivaroxaban (86.08% ± 10.23%), apixaban (68.26% ± 10.82%), dabigatran (41.63% ± 12.26%), low-molecular-weight heparin (41.03% ± 9.60%), ximelagatran (37.81% ± 15.87%), aspirin (35.62% ± 20.60%), warfarin (9.89% ± 9.07%), and placebo (4.56% ± 6.37%). Ranking based on clinically relevant bleeding events was as follows: fondaparinux (14.53% ± 15.25%), ximelagatran (18.93% ± 17.49%), rivaroxaban (23.86% ± 15.14%), dabigatran (28.30% ± 14.18%), edoxaban (38.76% ± 24.25%), low-molecular-weight heparin (53.28% ± 8.40%), apixaban (71.81% ± 10.92%), placebo (76.26% ± 14.61%), aspirin (86.32% ± 25.74%), and warfarin (87.95% ± 11.27%). No statistically significant heterogeneity was observed between trials.

Conclusions and relevance

According to our results, all anticoagulant drugs showed some effectiveness for VTE prophylaxis. Our ranking indicated that fondaparinux and rivaroxaban were safer and more effective than other anticoagulant drugs for patients undergoing THA or TKA.
Three heads are better than two: Comparing learning properties and performances across individuals, dyads, and triads through a computational approach
Authors: Harada Tsutomu
Published: June 2021

Although it is considered that two heads are better than one, related studies argued that groups rarely outperform their best members. This study examined not only whether two heads are better than one but also whether three heads are better than two or one in the context of two-armed bandit problems where learning plays an instrumental role in achieving high performance. This research revealed that a U-shaped correlation exists between performance and group size. The performance was highest for either individuals or triads, but the lowest for dyads. Moreover, this study estimated learning properties and determined that high inverse temperature (exploitation) accounted for high performance. In particular, it was shown that group effects regarding the inverse temperatures in dyads did not generate higher values to surpass the averages of their two group members. In contrast, triads gave rise to higher values of the inverse temperatures than their averages of their individual group members. These results were consistent with our proposed hypothesis that learning coherence is likely to emerge in individuals and triads, but not in dyads, which in turn leads to higher performance. This hypothesis is based on the classical argument by Simmel stating that while dyads are likely to involve more emotion and generate greater variability, triads are the smallest structure which tends to constrain emotions, reduce individuality, and generate behavioral convergences or uniformity because of the ‘‘two against one” social pressures. As a result, three heads or one head were better than two in our study.
Duration of SARS-CoV-2 shedding: A population-based, Canadian study
Authors: Phillips Susan P. , Wei Xuejiao , Kwong Jeffrey C. , Gubbay Jonathan , Schwartz Kevin L. , Majury Anna , Groome Patti A.
Published: June 2021

Introduction

There is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset.

Methods

Laboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences.

Results

In Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12–28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18–34). Long-term care residents had 3–5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2–4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2–3 days were observed at the 25th% of the distribution in those aged 20–49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14.

Conclusions

Viral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.
Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda
Authors: Muttamba Winters , Lusiba John , Namakula Loryndah Olive , Byakika-Kibwika Pauline , Ssali Francis , Ddungu Henry , Mugenyi Levicatus , Kiwanuka Noah , Sekibira Rogers , Kityo Cissy , Keyune Dorothy , Acana Susan , Musinguzi Ambrose , Masasi Ayub , Byamugisha Joseph , Mpanju David , Musoki Walter Jack , Tukamuhebwa Hellen Aanyu , Nakwagala Fred , Bagaya Bernard Sentalo , Kayongo Alex , Kimuli Ivan , Nantanda Rebecca , Katagira Winceslaus , Buregyeya Esther , Byanyima Rosemary , Byarugaba Baterana , Siddharthan Trishul , Mwebesa Henry , Charles Olaro , Joloba Moses Lutaakome , Bazeyo William , Kirenga Bruce
Published: June 2021

Introduction

Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda.

Methods

In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.

Results

192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant.

Conclusion

CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.
Could teacher-perceived parental interest be an important factor in understanding how education relates to later physiological health? A life course approach
Authors: Joannès Camille , Castagné Raphaële , Lepage Benoit , Delpierre Cyrille , Kelly-Irving Michelle
Published: June 2021

Education is associated with later health, and notably with an indicator of physiological health measuring the cost of adapting to stressful conditions, named allostatic load. Education is itself the result of a number of upstream variables. We examined the origins of educational attainment through the lens of interactions between families and school i.e. parents’ interest in their child’s education as perceived by teachers. This study aims to examine whether parental interest during a child’s educational trajectory is associated with subsequent allostatic load, and whether education or other pathways mediate this relationship. We used data from 9 377 women and men born in 1958 in Great Britain and included in the National Child Development Study to conduct secondary data analyses. Parental interest was measured from questionnaire responses by teachers collected at age 7, 11 and 16. Allostatic load was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Linear regression analyses were carried out on a sample of 8 113 participants with complete data for allostatic load, missing data were imputed. Participants whose parents were considered to be uninterested in their education by their teacher had a higher allostatic load on average in midlife in both men (β = 0,41 [0,29; 0,54]) and women (β = 0,69 [0,54; 0,83]). We examined the role of the educational and other pathways including psychosocial, material/financial, and behavioral variables, as potential mediators in the relationship between parental interest and allostatic load. The direct link between parental interest and allostatic load was completely mediated in men, but only partially mediated in women. This work provides evidence that parents’ interest in their child’s education as perceived by teachers is associated with subsequent physiological health in mid-life and may highlight a form of cultural dissonance between family and educational spheres.
Comparison of neutrophil to lymphocyte ratio and prognostic nutritional index with other clinical and molecular biomarkers for prediction of glioblastoma multiforme outcome
Authors: Garrett Celine , Becker Therese M. , Lynch David , Po Joseph , Xuan Wei , Scott Kieran F. , de Souza Paul
Published: June 2021

Objective

Pre- and post-operative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) and other prognostic clinicopathological variables were correlated with progression free survival (PFS) and overall survival (OS) of Glioblastoma Multiforme (GBM) patients.

Methods

GBM patients (n = 87, single-centre, recruited 2013–2019) were retrospectively divided into low and high groups using literature-derived cut-offs (NLR = 5.07, PNI = 46.97). Kaplan-Meier survival curves and log rank tests assessed PFS and OS. Univariate and multivariate analyses identified PFS and OS prognosticators.

Results

High vs low post-operative PNI cohort was associated with longer PFS (279 vs 136 days, p = 0.009), but significance was lost on multivariate analysis. Post-operative ECOG (p = 0.043), daily dexamethasone (p = 0.023) and IDH mutation (p = 0.046) were significant on multivariate analysis for PFS. High pre- and post-operative PNI were associated with improved OS (384 vs 114 days, p = 0.034 and 516 vs 245 days, p = 0.001, respectively). Low postoperative NLR correlated with OS (408 vs 249 days, p = 0.029). On multivariate analysis using forward selection process, extent of resection (EOR) (GTR vs biopsy, p = 0.004 and STR vs biopsy, p = 0.011), and any previous surgery (p = 0.014) were independent prognostic biomarkers for OS. On multivariate analysis of these latter variables with literature-derived prognostic biomarkers, EOR remained significantly associated with OS (p = 0.037).

Conclusions

EOR, followed by having any surgery prior to GBM, are the most significant independent predictors of GBM patient’s OS. Post-operative ECOG, daily dexamethasone and IDH mutation are independent prognostic biomarkers for PFS. PNI may be superior to NLR. Post- vs pre-operative serum inflammatory marker levels may be associated with survival.
The price penalty for red meat substitutes in popular dishes and the diversity in substitution
Authors: Lemken Dominic
Published: June 2021

Life cycle assessments (LCA) often highlight the environmental and health benefits for consumers if western diets substitute red meat. However, the specific trade-off consumer face when asked to substitute a red meat dish is scarcely researched, often neglecting the bouquet of substitution options and/or the price component involved. Four substitution strategies are evaluated within an individually adapted choice based conjoint: the substitution by (1) the same red meat dishes with a halved meat portion size, (2) novel plant-based products that mimic the functionality and taste, (3) authentic plant-based components that just mimic the functionality, and (4) vegetarian dishes that just neglect the meat component if still familiar to consumers. The analysis is executed for three popular red meat dishes to account for consistency across meal scenarios, namely Meatballs, Spaghetti Bolognese and Sausage Buns. The analysis is sensitive to red meat consumption habits to better understand the preferences of consumers that can actually substitute a red meat intake.
Post-infectious and post-acute sequelae of critically ill adults with COVID-19
Authors: Ibrahim Halah , Athar Syed , Harhara Thana , Elhag Shahad Abasaeed , MElnour Salma , Sukkar Hoor H. , Kamour Ashraf M.
Published: June 2021

Background

Data on the post-acute and post-infectious complications of patients who have recovered from severe coronavirus disease 2019 (COVID-19) are limited. While studies report that approximately 5–15% of COVID-19 hospitalized patients require intensive care and mechanical ventilation, a substantially higher number need non-invasive ventilation and are subject to prolonged hospitalizations, with long periods of immobility and isolation. The purpose of this study is to describe the post-infectious sequelae of severe viral illness and the post-acute complications of intensive care treatments in critically ill patients who have recovered from severe COVID-19 infection.

Methods

We performed a retrospective chart review of adult patients initially hospitalized with confirmed COVID-19 infection, who recovered and were transferred to a general medical ward or discharged home between March 15, 2020 and May 15, 2020, dates inclusive, after an intensive care unit (ICU) or high dependency unit (HDU) admission in a designated COVID-19 hospital in the United Arab Emirates. Demographic data, underlying comorbidities, treatment, complications, and outcomes were collected. Descriptive statistical analyses were performed.

Results

Of 71 patients transferred out of ICU (n = 38, 54%) and HDU (n = 33, 46%), mean age was 48 years (SD, 9.95); 96% men; 54% under age 50. Mean ICU stay was 12.4 days (SD, 5.29), HDU stay was 13.4 days (SD, 4.53). Pre-existing conditions were not significantly associated with developing post-acute complications (Odds Ratio [OR] 1.1, 95% confidence interval [CI] 0.41, 2.93, p = 1.00). Fifty nine percent of patients had complications; myopathy, swallowing impairments, and pressure ulcers were most common. Delirium and confusion were diagnosed in 18% (n = 13); all were admitted to the ICU and required mechanical ventilation. Of note, of all patients studied, 59.2% (n = 42/71) had at least 1 complication, 32.4% (n = 23) had at least 2 complications, and 19.7% (n = 14) suffered 3 or more sequelae. Complications were significantly more common in ICU patients (n = 33/38, 87%), compared to HDU patients (n = 9/33, 27%) (OR 17.6, 95% CI 5.23, 59.21, p <0.05).

Conclusion

In a subset of critically ill patients who recovered from severe COVID-19 infection, there was considerable short-term post-infectious and post-acute disability. Long-term follow-up of COVID-19 survivors is warranted.
CDK4/6 inhibition synergizes with inhibition of P21-Activated Kinases (PAKs) in lung cancer cell lines
Authors: Wright Gabriela M. , Gimbrone Nick T. , Sarcar Bhaswati , Percy Trent R. , Gordián Edna R. , Kinose Fumi , Sumi Natália J. , Rix Uwe , Cress W. Douglas
Published: June 2021

Theoretically, small molecule CDK4/6 inhibitors (CDK4/6is) represent a logical therapeutic option in non-small cell lung cancers since most of these malignancies have wildtype RB, the key target of CDKs and master regulator of the cell cycle. Unfortunately, CDK4/6is are found to have limited clinical activity as single agents in non-small cell lung cancer. To address this problem and to identify effective CDK4/6i combinations, we screened a library of targeted agents for efficacy in four non-small cell lung cancer lines treated with CDK4/6 inhibitors Palbociclib or Abemaciclib. The pan-PAK (p21-activated kinase) inhibitor PF03758309 emerged as a promising candidate with viability ratios indicating synergy in all 4 cell lines and for both CDK4/6is. It is noteworthy that the PAKs are downstream effectors of small GTPases Rac1 and Cdc42 and are overexpressed in a wide variety of cancers. Individually the compounds primarily induced cell cycle arrest; however, the synergistic combination induced apoptosis, accounting for the synergy. Surprisingly, while the pan-PAK inhibitor PF03758309 synergizes with CDK4/6is, no synergy occurs with group I PAK inhibitors FRAX486 or FRAX597. Cell lines treated only with Ribociclib, FRAX486 or FRAX597 underwent G1/G0 arrest, whereas combination treatment with these compounds predominantly resulted in autophagy. Combining high concentrations of FRAX486, which weakly inhibits PAK4, and Ribociclib, mimics the autophagy and apoptotic effect of PF03758309 combined with Ribociclib. FRAX597, a PAKi that does not inhibit PAK4 did not reduce autophagy in combination with Ribociclib. Our results suggest that a unique combination of PAKs plays a crucial role in the synergy of PAK inhibitors with CDK4/6i. Targeting this unique PAK combination, could greatly improve the efficacy of CDK4/6i and broaden the spectrum of cancer treatment.
Visible colorimetric growth indicators of Neisseria gonorrhoeae for low-cost diagnostic applications
Authors: Oeschger Taylor Mae , Erickson David Carl
Published: June 2021

N. gonorrhoeae is one of the most pressing antibiotic resistant threats of our time and low-cost diagnostics that can easily identify antibiotic resistance are desperately needed. However, N. gonorrhoeae responds so uniquely to growth conditions that it cannot be assumed gonorrhea will respond to common microbiological methods used for other pathogenic organisms. In this paper, we explore visual colorimetric indicators of N. gonorrhoeae growth that can be seen without a microscope or spectrophotometer. We evaluate growth media, pH indicators, resazurin-based dyes, and tetrazolium-based dyes for their use in simple colorimetric system. Overall, we identified Graver Wade media as the best at supporting robust gonococcal growth while also providing the least background when analyzing results of colorimetric tests. XTT, a tetrazolium-based dye, proved to show to brightest color change over time and not negatively impact the natural growth of N. gonorrhoeae. However, other dyes including PrestoBlue, MTT, and NBT are less expensive than XTT and work well when added after bacterial growth has already occurred. By identifying the specific use cases of these dyes, this research lays the groundwork for future development of a color-based antibiotic susceptibility low-cost test for N. gonorrhoeae.
A novel miRNA-disease association prediction model using dual random walk with restart and space projection federated method
Authors: Li Ang , Deng Yingwei , Tan Yan , Chen Min
Published: June 2021

A large number of studies have shown that the variation and disorder of miRNAs are important causes of diseases. The recognition of disease-related miRNAs has become an important topic in the field of biological research. However, the identification of disease-related miRNAs by biological experiments is expensive and time consuming. Thus, computational prediction models that predict disease-related miRNAs must be developed. A novel network projection-based dual random walk with restart (NPRWR) was used to predict potential disease-related miRNAs. The NPRWR model aims to estimate and accurately predict miRNA–disease associations by using dual random walk with restart and network projection technology, respectively. The leave-one-out cross validation (LOOCV) was adopted to evaluate the prediction performance of NPRWR. The results show that the area under the receiver operating characteristic curve(AUC) of NPRWR was 0.9029, which is superior to that of other advanced miRNA–disease associated prediction methods. In addition, lung and kidney neoplasms were selected to present a case study. Among the first 50 miRNAs predicted, 50 and 49 miRNAs have been proven by in databases or relevant literature. Moreover, NPRWR can be used to predict isolated diseases and new miRNAs. LOOCV and the case study achieved good prediction results. Thus, NPRWR will become an effective and accurate disease–miRNA association prediction model.
A modified filter nonmonotone adaptive retrospective trust region method
Authors: Ding Xianfeng , Qu Quan , Wang Xinyi
Published: June 2021

In this paper, aiming at the unconstrained optimization problem, a new nonmonotone adaptive retrospective trust region line search method is presented, which takes advantages of multidimensional filter technique to increase the acceptance probability of the trial step. The new nonmonotone trust region ratio is presented, which based on the convex combination of nonmonotone trust region ratio and retrospective ratio. The global convergence and the superlinear convergence of the algorithm are shown in the right circumstances. Comparative numerical experiments show the better effective and robustness.
Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study
Authors: Godtman Rebecka Arnsrud , Persson Erik , Cazzaniga Walter , Sandin Fredrik , Carlsson Stefan , Ahlgren Göran , Johansson Eva , Robinsson David , Hugosson Jonas , Stattin Pär
Published: June 2021

Background and objective

Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group.

Methods

9,810 RARP’s registered in the National Prostate Cancer Register of Sweden (2015–2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection.

Results

Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11–11.91), hospital (OR 2.16, 95% CI 1.53–3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07–3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34–3.57), hospital (OR 2.02, 95% CI 1.66–2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54–2.35), hospital (OR 1.28, 95% CI 1.07–1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment.

Conclusions

High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.
Factors associated with births protected against neonatal tetanus in Africa: Evidences from Demographic and health surveys of five African countries
Authors: Yeshaw Yigizie , Jemere Tadeg , Dagne Henok , Andualem Zewudu , Akalu Yonas , Dewau Reta , Teshale Achamyeleh Birhanu , Tesema Getayeneh Antehunegn , Dagnew Baye
Published: June 2021

Introduction

Maternal and neonatal tetanus remains a global public health problem affecting mainly the poorest and most marginalized subpopulations. In spite of the problem, studies conducted on the associated factors of births protected against neonatal tetanus are scarce in Africa. Therefore, this study aimed to identify both individual and community-level factors associated with births protected against neonatal tetanus in the region.

Methods

The most recent Demographic and Health Survey datasets of five African countries (Ethiopia, Burundi, Comoros, Zimbabwe and Zambia) were used to investigate the associated factors of births protected from neonatal tetanus. STATA Version 14 statistical software was used for the analysis. The data were weighted before doing any statistical analysis and deviance was used for model comparison. Multilevel binary logistic regression was used to identify the associated factors of births protected against neonatal tetanus. Finally, the adjusted odds ratio (AOR) with its 95% confidence interval (CI) was calculated for each potential factors included in the multivariable multilevel logistic regression model.

Results

A total weighted sample of 30897 reproductive age women who had a birth within 5 years preceding the survey were included in the analysis. Those women with age of 20–34 (AOR = 1.32, 95%CI: 1.18–1.48) and 35–49 years (AOR = 1.26, 95% CI: 1.10–1.44), high community level of women education (AOR = 1.13, 95%CI: 1.04–1.23), being from poorer(AOR = 1.23, 95% CI: 1.14–1.33), middle (AOR = 1.31, 95%CI: 1.21–1.43), richer (AOR = 1.21, 95%CI: 1.11–1.32) and richest households (AOR = 1.59, 95%CI: 1.44–1.74), having antenatal care follow up (AOR = 9.62, 95% CI: 8.79–10.54), not perceiving distance to health facility as a big problem (AOR = 1.18, 95% CI: (1.11–1.25) had higher odds of having births protected against neonatal tetanus.

Conclusion

Both individual and community level factors were found to be associated with births protected against neonatal tetanus in Africa. This suggests that a variety of factors are affecting births protected against neonatal tetanus in the region. Hence, the impact of these factors should be recognized while developing strategies to reduce neonatal tetanus in the region.
Economic evaluation of point-of-care testing and treatment for sexually transmitted and genital infections in pregnancy in low- and middle-income countries: A systematic review
Authors: Saweri Olga P. M. , Batura Neha , Al Adawiyah Rabiah , Causer Louise M. , Pomat William S. , Vallely Andrew J. , Wiseman Virginia
Published: June 2021

Background

Sexually transmitted and genital infections in pregnancy are associated with adverse pregnancy and birth outcomes. Point-of-care tests for these infections facilitate testing and treatment in a single antenatal clinic visit and may reduce the risk of adverse outcomes. Successful implementation and scale-up depends on understanding comparative effectiveness of such programmes and their comparative costs and cost effectiveness. This systematic review synthesises and appraises evidence from economic evaluations of point-of-care testing and treatment for sexually transmitted and genital infections among pregnant women in low- and middle-income countries.

Methods

Medline, Embase and Web of Science databases were comprehensively searched using pre-determined criteria. Additional literature was identified by searching Google Scholar and the bibliographies of all included studies. Economic evaluations were eligible if they were set in low- and middle-income countries and assessed antenatal point-of-care testing and treatment for syphilis, chlamydia, gonorrhoea, trichomoniasis, and/or bacterial vaginosis. Studies were analysed using narrative synthesis. Methodological and reporting standards were assessed using two published checklists.

Results

Sixteen economic evaluations were included in this review; ten based in Africa, three in Latin and South America and three were cross-continent comparisons. Fifteen studies assessed point-of-care testing and treatment for syphilis, while one evaluated chlamydia. Key drivers of cost and cost-effectiveness included disease prevalence; test, treatment, and staff costs; test sensitivity and specificity; and screening and treatment coverage. All studies met 75% or more of the criteria of the Drummond Checklist and 60% of the Consolidated Health Economics Evaluation Reporting Standards.

Conclusions

Generally, point-of-care testing and treatment was cost-effective compared to no screening, syndromic management, and laboratory-based testing. Future economic evaluations should consider other common infections, and their lifetime impact on mothers and babies. Complementary affordability and equity analyses would strengthen the case for greater investment in antenatal point-of-care testing and treatment for sexually transmitted and genital infections.
Investigate the risk factors of stunting, wasting, and underweight among under-five Bangladeshi children and its prediction based on machine learning approach
Authors: Rahman S. M. Jubaidur , Ahmed N. A. M. Faisal , Abedin Md. Menhazul , Ahammed Benojir , Ali Mohammad , Rahman Md. Jahanur , Maniruzzaman Md.
Published: June 2021

Aims

Malnutrition is a major health issue among Bangladeshi under-five (U5) children. Children are malnourished if the calories and proteins they take through their diet are not sufficient for their growth and maintenance. The goal of the research was to use machine learning (ML) algorithms to detect the risk factors of malnutrition (stunted, wasted, and underweight) as well as their prediction.

Methods

This work utilized malnutrition data that was derived from Bangladesh Demographic and Health Survey which was conducted in 2014. The selected dataset consisted of 7079 children with 13 factors. The potential risks of malnutrition have been identified by logistic regression (LR). Moreover, 3 ML classifiers (support vector machine (SVM), random forest (RF), and LR) have been implemented for predicting malnutrition and the performance of these ML algorithms were assessed on the basis of accuracy.

Results

The average prevalence of stunted, wasted, and underweight was 35.4%, 15.4%, and 32.8%, respectively. It was noted that LR identified five risk factors for stunting and underweight, as well as four factors for wasting. Results illustrated that RF can be accurately classified as stunted, wasted, and underweight children and obtained the highest accuracy of 88.3% for stunted, 87.7% for wasted, and 85.7% for underweight.

Conclusion

This research focused on the identification and prediction of major risk factors for stunting, wasting, and underweight using ML algorithms which will aid policymakers in reducing malnutrition among Bangladesh’s U5 children.
Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys
Authors: Blessing Natalya A. , Wu Zhenzhen , Madhavan Sethu M. , Choy Jonathan W. , Chen Michelle , Shin Myung K. , Hoek Maarten , Sedor John R. , O’Toole John F. , Bruggeman Leslie A.
Published: June 2021

The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 expressed in renal cells. Of the kidney cells reported to express APOL1, the proximal tubule expression patterns are inconsistent in published reports, and whether APOL1 is synthesized by the proximal tubule or possibly APOL1 protein in the blood is filtered and reabsorbed by the proximal tubule remains unclear. Using both protein and mRNA in situ methods, the kidney expression pattern of APOL1 was examined in normal human and APOL1 bacterial artificial chromosome transgenic mice with and without proteinuria. APOL1 protein and mRNA was detected in podocytes and endothelial cells, but not in tubular epithelia. In the setting of proteinuria, plasma APOL1 protein did not appear to be filtered or reabsorbed by the proximal tubule. A side-by-side examination of commercial antibodies used in prior studies suggest the original reports of APOL1 in proximal tubules likely reflects antibody non-specificity. As such, APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies in the APOL1-mediated kidney diseases.
Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus
Authors: Khan Md Tahsin , Islam Rahatul , Jerin Tarhima Jahan , Mahmud Araf , Khatun Sahara , Kobir Ahasanul , Islam Md Nahidul , Akter Arzuba , Mondal Shakhinur Islam
Published: June 2021

West Nile Virus (WNV) is a life threatening flavivirus that causes significant morbidity and mortality worldwide. No preventive therapeutics including vaccines against WNV are available for human use. In this study, immunoinformatics approach was performed to design a multi epitope-based subunit vaccine against this deadly pathogen. Human (HLA) and Mice (H-2) allele specific potential T-cell and B-cell epitopes were shortlisted through a stringent procedure. Molecular docking showed selected epitopes that have stronger binding affinity with human TLR-4. Molecular dynamics simulation confirmed the stable nature of the docked complex. Furthermore, in silico cloning analysis ensures efficient expression of desired gene in the microbial system. Interestingly, previous studies showed that two of our selected epitopes have strong immune response against WNV. Therefore, selected epitopes could be strong vaccine candidates to prevent WNV infections in human. However, further in vitro and in vivo investigations could be strengthening the validation of the vaccine candidate against WNV.
Retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma
Authors: Pan Xin-Bin , Huang Shi-Ting , Qu Song , Chen Kai-Hua , Jiang Yan-Ming , Zhu Xiao-Dong
Published: June 2021

Purposes

To evaluate retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma (NPC).

Methods

NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of retropharyngeal lymph node metastasis were investigated. The included patients were divided into N1a and N1b groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method and propensity score matching (PSM) analyses.

Results

This retrospective cohort study examined 759 patients: 70 who were stage N1a and 689 who were stage N1b. Before PSM, N1a group was associated with similar 5-year OS (77.7% vs. 72.4%; P = 0.15) and CSS (85.6% vs. 79.9%; P = 0.09) compared to N1b group. After PSM, a similar OS (75.0% vs. 60.7%; P = 0.12) was found between the radiotherapy and chemoradiotherapy groups. However, N1a group showed a better 5-year CSS (83.8% vs. 71.1%; P = 0.04) compared to N1b group. Stage N1b was an independent risk prognostic factor for CSS (hazard ratio = 2.54, 95% confidence interval: 1.02–6.34; P = 0.04).

Conclusions

OS was not different between N1a and N1b groups. Retropharyngeal lymph node metastasis defined as stage N1 of the 8th edition American Joint Committee on Cancer staging system is reasonable.
Reduced muscle mass as predictor of intensive care unit hospitalization in COVID-19 patients
Authors: Giraudo Chiara , Librizzi Giovanni , Fichera Giulia , Motta Raffaella , Balestro Elisabetta , Calabrese Fiorella , Carretta Giovanni , Cattelan Anna Maria , Navalesi Paolo , Pelloso Michela , Plebani Mario , Rea Federico , Vettor Roberto , Vianello Andrea , Stramare Roberto
Published: June 2021

Purpose

To evaluate if reduced muscle mass, assessed with Computed Tomography (CT), is a predictor of intensive care unit (ICU) hospitalization in COVID-19 patients.

Methods

In this Institution Review Board approved study, we retrospectively evaluated COVID-19 patients treated in our tertiary center from March to November 2020 who underwent an unenhanced chest CT scan within three weeks from hospitalization.We recorded the mean Hounsfield Unit (Hu) value of the right paravertebral muscle at the level of the 12th thoracic vertebra, the hospitalization unit (ICU and COVID-19 wards), clinical symptoms, Barthel Index, and laboratory findings.Logistic regression analysis was applied to assess if muscle loss (Hu<30) is a predictor of ICU admission and outcome.Fisher’s exact and Student’s tests were applied to evaluate if differences between patients with and without muscle loss occurred (p<0.05).

Results

One-hundred-fifty patients matched the inclusion criteria (46 females; mean age±SD 61.3±15 years-old), 36 treated in ICU. Patients in ICU showed significantly lower Hu values (29±24 vs 39.4±12, p = 0.001). Muscle loss was a predictor of ICU admission (p = 0.004).Patients with muscle loss were significantly older (73.4±10 vs 56.4±14 years), had lower Barthel Index scores (54.4±33 vs 85.1±26), red blood-cell count (3.9±1 vs 4.6±1×1012L−1), and Hb levels (11.5±2 vs 13.2±2g/l) as well as higher white blood-cell count (9.4±7 vs 7.2±4×109L−1), C-reactive protein (71.5±71 vs 44±48U/L), and lactate dehydrogenase levels (335±163 vs 265.8±116U/L) (p<0.05, each).

Conclusions

Muscle loss seems to be a predictor of ICU hospitalization in COVID-19 patients and radiologists reporting chest CT at admission should note this finding in their reports.
Traditional Latvian herbal medicinal plants used to treat parasite infections of small ruminants: A review
Authors: Kļaviņa Alīna , Keidāne Dace , Šukele Renāte , Bandere Dace , Kovaļčuka Līga
Published: June 2021

Numerous treatment agents offering prophylaxis against livestock parasites are commercially available. However, because of increasing antiparasitic drug resistance, the increased popularity of environmentally friendly lifestyle choices, and organic farming, there is more demand for new alternatives to livestock anthelmintic control strategies and medications. It is important to develop antiparasitics that are safe, effective, inexpensive, and environmentally safe. Local, traditional herbal plants such as tansy, mugwort, wormwood, and heather may serve as treatments for intestinal parasites of sheep. This overview provides knowledge of traditional Latvian plants with antiparasitic activities to establish a database for further research to develop new herbal antiparasitic drugs.
COCOA (Theobroma cacao) POLYPHENOL-RICH EXTRACT INCREASES THE CHRONOLOGICAL LIFESPAN OF Saccharomyces cerevisiae
Authors: BAIGES I. , AROLA L.
Published: June 2021

Background:Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. Objective: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. Measurements: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. Results: CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, (+)-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. Conclusion: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate the search for biomolecules with potential anti-aging effects.