bluuebunny/crossref_metadata_2025 huggingface dataset:
The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models
Authors: Cho Shih-Feng , Lin Liang , Xing Lijie , Li Yuyin , Wen Kenneth , Yu Tengteng , Hsieh Phillip A. , Munshi Nikhil , Wahl Joachim , Matthes Katja , Friedrich Matthias , Arvedson Tara , Anderson Kenneth C. , Tai Yu-Tzu
Published: September 2020

We investigated here the novel immunomodulation and anti–multiple myeloma (MM) function of T cells engaged by the bispecific T-cell engager molecule AMG 701, and further examined the impact of AMG 701 in combination with immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide). AMG 701 potently induced T-cell–dependent cellular cytotoxicity (TDCC) against MM cells expressing B-cell maturation antigen, including autologous cells from patients with relapsed and refractory MM (RRMM) (half maximal effective concentration, <46.6 pM). Besides inducing T-cell proliferation and cytolytic activity, AMG 701 also promoted differentiation of patient T cells to central memory, effector memory, and stem cell–like memory (scm) phenotypes, more so in CD8 vs CD4 T subsets, resulting in increased CD8/CD4 ratios in 7-day ex vivo cocultures. IMiDs and AMG 701 synergistically induced TDCC against MM cell lines and autologous RRMM patient cells, even in the presence of immunosuppressive bone marrow stromal cells or osteoclasts. IMiDs further upregulated AMG 701–induced patient T-cell differentiation toward memory phenotypes, associated with increased CD8/CD4 ratios, increased Tscm, and decreased interleukin 10–positive T and T regulatory cells (CD25highFOXP3high), which may downregulate T effector cells. Importantly, the combination of AMG 701 with lenalidomide induced sustained inhibition of MM cell growth in SCID mice reconstituted with human T cells; tumor regrowth was eventually observed in cohorts treated with either agent alone (P < .001). These results strongly support AMG 701 clinical studies as monotherapy in patients with RRMM (NCT03287908) and the combination with IMiDs to improve patient outcomes in MM.
Prevalence and factors associated with effective helmet use among motorcyclists in Mysuru City of Southern India
Authors: Setty Naveen Kikkeri Hanumantha , Sukumar Gautham Melur , Majgi Sumanth Mallikarjun , Goel Akhil Dhanesh , Sharma Prem Prakash , Anand Manasa Brahmanandam
Published: September 2020

Background

Helmet use reduces the risk and severity of head injury and death due to road traffic crash among motorcyclists. The protective efficacy of different types of helmets varies. Wearing firmly fastened full-face helmet termed as effective helmet use provides greatest protection. This study estimates the prevalence and factors associated with effective helmet use among motorcyclists in Mysuru, a tier II city in Southern India.

Methods

Cross-sectional road side observational study of 3499 motorcyclists (2134 motorcycle riders and 1365 pillion riders) at four traffic intersections was done followed by interview of random sample of 129 of the above riders. Effective helmet use proportion and effective helmet use per 100 person-minute of observation was calculated. Multivariate logistic regression analysis was done to identify factors associated with effective helmet use.

Results

Prevalence of effective helmet use was 28 per 100 riders and 19.5 per 100 person-minute of observation in traffic intersections. Prevalence rates of effective helmet use was higher among riders (34.5% vs pillion riders 18.1%), female riders (51.3% vs male riders 26.8%), and male pillion riders (30.5% vs female pillion riders 13.7%). Riders commuting for work and school and those ever stopped by the police in the past 3 months had significantly higher odds of effective helmet use.

Conclusion

Despite helmet use being compulsory by law for motorcyclists, the effective helmet use was low in Mysore. Strict enforcement and frequent checks by the police are necessary to increase the effective helmet use.
Isolation and characterization of antibody fragments selective for human FTD brain derived TDP-43 variants
Authors: Venkataraman Lalitha , He Ping , Khan Galam , Harris Brent T. , Sierks Michael R.
Published: September 2020

Background

Frontotemporal dementia (FTD) is the second leading cause of early onset dementia following Alzheimer’s disease. It involves atrophy of the frontal and temporal regions of the brain affecting language, memory, and behavior. Transactive response DNA-binding protein 43 (TDP-43) pathology is found in most FTD and ALS cases. It plays a role in transcription, translation and serves as a shuttle between the nucleus and cytoplasm. Prior to its aggregation, TDP-43 exists as polyubiquitinated, hyperphosphorylated C-terminal fragments that correlate well with FTD disease progression. Because of the importance of TDP-43 in these diseases, reagents that can selectively recognize specific toxic TDP variants associated with onset and progression of FTD can be effective diagnostic and therapeutic tools.

Results

We utilized a novel atomic force microscopy (AFM) based biopanning protocol to isolate single chain variable fragments (scFvs) from a phage display library that selectively bind TDP variants present in human FTD but not cognitively normal age matched brain tissue. We then used the scFvs (FTD-TDP1 through 5) to probe post-mortem brain tissue and sera samples for the presence of FTD related TDP variants. The scFvs readily selected the FTD tissue and sera samples over age matched controls. The scFvs were used in immunohistochemical analysis of FTD and control brain slices where the reagents showed strong staining with TDP in FTD brain tissue slice. FTD-TDP1, FTD-TDP2, FTD-TDP4 and FTD-TDP5 all protected neuronal cells against FTD TDP induced toxicity suggesting potential therapeutic value.

Conclusions

These results show existence of different disease specific TDP variants in FTD individuals. We have identified a panel of scFvs capable of recognizing these disease specific TDP variants in postmortem FTD tissue and sera samples over age matched controls and can thus serve as a biomarker tool.
Bioinformatics and expression analysis of histone modification genes in grapevine predict their involvement in seed development, powdery mildew resistance, and hormonal signaling
Authors: Wang Li , Ahmad Bilal , Liang Chen , Shi Xiaoxin , Sun Ruyi , Zhang Songlin , Du Guoqiang
Published: September 2020

Background

Histone modification genes (HMs) play potential roles in plant growth and development via influencing gene expression and chromatin structure. However, limited information is available about HMs genes in grapes (Vitis vinifera L.).

Results

Here, we described detailed genome-wide identification of HMs gene families in grapevine. We identified 117 HMs genes in grapevine and classified these genes into 11 subfamilies based on conserved domains and phylogenetic relationships with Arabidopsis. We described the genes in terms of their chromosomal locations and exon-intron distribution. Further, we investigated the evolutionary history, gene ontology (GO) analysis, and syntenic relationships between grapes and Arabidopsis. According to results 21% HMs genes are the result of duplication (tandem and segmental) events and all the duplicated genes have negative mode of selection. GO analysis predicted the presence of HMs proteins in cytoplasm, nucleus, and intracellular organelles. According to seed development expression profiling, many HMs grapevine genes were differentially expressed in seeded and seedless cultivars, suggesting their roles in seed development. Moreover, we checked the response of HMs genes against powdery mildew infection at different time points. Results have suggested the involvement of some genes in disease resistance regulation mechanism. Furthermore, the expression profiles of HMs genes were analyzed in response to different plant hormones (Abscisic acid, Jasmonic acid, Salicylic acid, and Ethylene) at different time points. All of the genes showed differential expression against one or more hormones.

Conclusion

VvHMs genes might have potential roles in grapevine including seed development, disease resistance, and hormonal signaling pathways. Our study provides first detailed genome-wide identification and expression profiling of HMs genes in grapevine.
Can patients make heads or tails of enhanced primary health care (EnPHC)? Experience through their own journey
Authors: Johari Mohammad Zabri , Abdullah Zalilah , Mohd Hanafiah Ainul Nadziha , Mohammed Nadzri Nur Izzati , Razli Siti Aisyah , Kong Yuke Lin
Published: September 2020

Background

Implementation of the new Enhanced Primary Health Care (EnPHC) intervention aims to improve service quality and experience at primary healthcare clinics; especially to newly diagnosed patients. This was achieved by restructuring and improving existing services to better manage non-communicable diseases amongst patients. Objectives of this study are to explore patients’ experiences of the EnPHC intervention, to document their feedback and to determine effects of EnPHC intervention on patients.

Methods

This phenomenological qualitative study focussed on patients’ experiences in relation to EnPHC interventions. Participants were purposely selected from a group of patients who attended the eight intervention primary healthcare clinics in Johor and Selangor regularly for treatment. Data collection was conducted between April to July 2018. Semi-structured interviews were conducted at average an hour per interview for four to five patients per clinic. Interviews were audio recorded, transcribed verbatim, coded and analysed using a thematic analysis approach.

Results

A total of 35 patients participated. Analysis revealed five main themes about patient experiences receiving the EnPHC intervention. These are: (1) health assessment in disease progress monitoring, (2) patient-doctor relationship and continuity of care, (3) professionalism in service delivery, (4) ensuring compliance in achieving health targets and (5) communication skills. Each theme represents an important aspect of the service, how it should be delivered within the patient expectations and how it can improve patient’s health through their lens.

Conclusion

Even though patients were not able to exactly identify the EnPHC intervention components implemented, they are able to describe the process changes that occurred; enabling them to improve their healthcare status. Engagement is necessary to better inform patients of the EnPHC intervention, its purpose, mechanisms, changes and importance for healthcare. It would reduce resistance and increase awareness amongst patients at the clinic.
Effectiveness of exercise intervention on fall-related fractures in older adults: a systematic review and meta-analysis of randomized controlled trials
Authors: Wang Qiang , Jiang Xiaowei , Shen Yingchao , Yao Ping , Chen Jun , Zhou Yuan , Gu Yunfeng , Qian Zhiyuan , Cao Xi
Published: September 2020

Background

Exercise intervention can significantly improve physical function and bone strength; however, the effect of exercise on fall-related fractures in older adults remains controversial. This study aimed to assess the effectiveness of exercise intervention on fall-related fractures in older adults by conducting a meta-analysis of randomized controlled trials (RCTs).

Methods

PubMed, EMBASE, and Cochrane databases were systematically searched for RCTs through November 24, 2019 to investigate the effectiveness of exercise intervention on fall-related fractures in older adults. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also conducted.

Results

A total of 7704 older adults and 428 fall-related fracture events from 20 RCTs were selected for the final meta-analysis. The follow-up duration across included trials ranged from 6.0 months to 7.0 years. The pooled RR suggested that exercise intervention was associated with a reduced fall-related fracture risk in older adults (RR: 0.74; 95% CI: 0.59–0.92; P = 0.007; I2 = 12.6%). The pooled conclusion was robust and not affected by any individual trial. Subgroup analysis revealed that the significant effect of exercise intervention on fall-related fractures was mainly detected when the study reported results from both male and female subjects, when it did not report the baseline body mass index, when individuals received both home- and center-based interventions, when the follow-up duration was > 1.0 year, and when it was a high-quality study.

Conclusions

Regular exercise intervention could prevent fall-related fractures in older adults. Further large-scale RCTs should be conducted to assess the effectiveness of different exercise programs on fall-related fractures at various sites.
Mother-to-child HIV transmission and its correlates in India: systematic review and meta-analysis
Authors: Bhatta Mihir , Dutta Nalok , Nandi Srijita , Dutta Shanta , Saha Malay Kumar
Published: September 2020

Background

In India, preventing mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) remains one of the foremost challenge in community health. Countrywide MTCT of HIV is estimated to be > 10,000 annually. Aims of present study are to find out the prevalence of HIV and correlates of HIV transmission among children given birth by HIV infected mother through systematic review along with meta-analysis.

Methods

All avaiable articles are retrieved using MEDLINE, Cochrane Library, Science Direct, EMBASE, Google Scholar and PUBMED following guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) are applied to critically reviewing the selected articles. STATA 13.0 is used to preparation of forest plot for Meta-analysis. For assessment of heterogeneity and publication biases I2statistics along with Begg and Mazumdar’s test and Egger’s tests are used. Odds ratio (OR) along with forest plots have been showing with 95% confidence interval (CI).

Results

All together 10 studies including 1537 pairs of mothers and new births are assessed in present meta-analysis. Present analysis revealed the prevalence of HIV due to MTCT in India as 8.76% (95% CI; 5.76, 12.31). Analysis of subgroups exhibit a higher pooled prevalence in eastern region of India, 10.83% (95% CI: 5.9, 17.81) and lower in in Western region in India, 6.37% (95% CI: 4.65, 8.49). Status of MTCT before and after initiation of universal ART are 10.23% (95% CI 6.61, 14.55) and 7.93% (95% CI 4.18, 12.76) respectively. Associated factors with MTCT of HIV include absence of maternal prevention of MTCT intervention, OR = 10.82 (95% CI: 5.28, 22.17), lacking in administration of infant ARV (antiretroviral), OR = 8.21 (95% CI: 4.82, 14.0) and absence of medical facility during childbirth OR = 3.73 (95% CI: 1.67, 8.33).

Conclusions

In India, pooled HIV prevalence of MTCT as high as 8.78% (95% CI; 5.76, 12.31) among babies born to infected mothers warrants urgent need of focused intervention for providing ART (PMTCT intervention), ensuring proper infant ARV prophylaxis, and avoiding delivery without proper medical facility to pregnant women with HIV for reduction of occurrence in HIV transmission from mothers to children.
Predictors of response to exposure and response prevention-based cognitive behavioral therapy for obsessive-compulsive disorder
Authors: Hamatani Sayo , Tsuchiyagaito Aki , Nihei Masato , Hayashi Yuta , Yoshida Tokiko , Takahashi Jumpei , Okawa Sho , Arai Honami , Nagaoka Maki , Matsumoto Kazuki , Shimizu Eiji , Hirano Yoshiyuki
Published: September 2020

Background

Cognitive behavioral therapy (CBT), which includes exposure and response prevention (ERP), is effective in improving symptoms of obsessive-compulsive disorder (OCD). However, whether poor cognitive functions and autism spectrum disorder (ASD) traits affect the therapeutic response of patients with OCD to ERP-based CBT remains unclear. This study aimed to identify factors predictive of the therapeutic response of Japanese patients with OCD to ERP-based CBT.

Methods

Forty-two Japanese outpatients with OCD were assessed using the Wechsler Adult Intelligence Scale-III (WAIS-III), Yale-Brown Obsessive-Compulsive Scale, Patient Health Questionnaire 9-item scale, and Autism Spectrum Quotient (AQ) at pre- and post-treatment. We used multiple regression analyses to estimate the effect on therapeutic response change. The treatment response change was set as a dependent variable in multiple regression analyses.

Results

Multiple regression analyses showed that among independent variables, communication as an AQ sub-scale and Letter Number Sequencing as a WAIS-III sub-test predict the therapeutic response to ERP-based CBT .

Conclusions

Our results suggest that diminished working memory (Letter Number Sequencing), poor communication skill (AQ sub-scale) may undermine responsiveness to ERP-based CBT among patients with OCD.

Trial registration

UMIN, UMIN00024087. Registered 20 September 2016 - Retrospectively registered (including retrospective data).
Bayesian spatial analysis of socio-demographic factors influencing pregnancy termination and its residual geographic variation among ever-married women of reproductive age in Bangladesh
Authors: Zahan Rifat , Feng Cindy Xin
Published: September 2020

Background

Unsafe pregnancy termination is a major public health concern among reproductive-aged women in many developing countries. This study evaluated the socio-demographic characteristics, as well as residual spatial correlation in pregnancy termination among Bangladeshi women.

Methods

Secondary data was obtained from the Bangladesh Demographic and Health Survey for the survey year 2014. Data included 17,863 samples of ever-married women between the ages of 15-49 years, which is a national representative sample in Bangladesh. Bayesian spatial logistic regression was used to assess the associations between socio-demographic characteristics and pregnancy termination. We flexibly modeled the non-linear effects of the continuous covariates while accounting for residual spatial correlation at the district level.

Results

Our findings revealed that about 19% of the respondents in Bangladesh reported ever had a pregnancy terminated. The risk of pregnancy termination was higher among women who had been working, had a higher wealth index, were in a conjugal relationship, had no children, were older and started their cohabitation earlier. Residual spatial patterns revealed the areas at a higher risk of pregnancy termination, including Panchagarh, Habiganj, and Sylhet after adjusting for covariates.

Conclusions

Prevalence of pregnancy termination remains considerably high in Bangladesh. The study revealed significant associations of women’s age at survey time, age at first cohabitation, occupational status, socio-economic status, marital status and the total number of children ever born with reporting having a history of terminated pregnancy among Bangladeshi ever-married women. The identified socio-demographic characteristics and districts at an increased likelihood of pregnancy termination can inform localized intervention and prevention strategies to improve the reproductive healthcare of women in Bangladesh.
The acromioclavicular ligament shows an early and dynamic healing response following acute traumatic rupture
Authors: Maier Dirk , Tuecking Lars-Rene , Bernstein Anke , Lang Gernot , Wagner Ferdinand Christian , Jaeger Martin , Ogon Peter , Südkamp Norbert Paul , Izadpanah Kaywan
Published: September 2020

Purpose

Symptomatic horizontal instability is clinically relevant following acute acromioclavicular joint dislocations. However, the intrinsic healing response is poorly understood. The present study sought to investigate time-dependent healing responses of the human acromioclavicular ligament following acute traumatic rupture.

Methods

Biopsies of the acromioclavicular ligament were obtained from patients undergoing surgical treatment for acute acromioclavicular joint dislocations. Specimens were stratified by time between trauma and surgery: group 1, 0–7 days (n = 5); group 2, 8–14 days (n = 6); and group 3, 15–21 days (n = 4). Time-dependent changes in cellularity, collagen (type 1 and 3) concentration, and histomorphological appearance were evaluated for the rupture and intact zone of the acromioclavicular ligament.

Results

Group 1 was characterized by cellular activation and early inflammatory response. The rupture zone exhibited a significantly higher count of CD68-positive cells than the intact zone (15.2 vs 7.4; P ≤ 0.05). Consistently, synovialization of the rupture end was observed. Within the second week, the rupture zone was subject to proliferation showing more fibroblast-like cells than the intact zone (66.8 vs 43.8; P ≤ 0.05) and a peak of collagen type 3 expression (group 1: 2.2 ± 0.38, group 2: 3.2 ± 0.18, group 3: 2.8 ± 0.57; P ≤ 0.05). Signs of consolidation and early remodeling were seen in the third week.

Conclusions

The acromioclavicular ligament exhibits early and dynamic healing responses following acute traumatic rupture. Our histological findings suggest that surgical treatment of acute ACJ dislocations should be performed as early as possible within a timeframe of 1 week after trauma to exploit the utmost biological healing potential. Prospective clinical studies are warranted to investigate whether early surgical treatment of ACJ dislocations translates into clinical benefits.
Online Cost-Effectiveness ANalysis (OCEAN): a user-friendly interface to conduct cost-effectiveness analyses for cervical cancer
Authors: Moriña David , Martí José Ignacio , Puig Pedro , Diaz Mireia
Published: September 2020

Background

Most cost-effectiveness analyses in the context of cervical cancer prevention involve the use of mathematical models to simulate HPV infection, cervical disease and prevention strategies. However, it is common for professionals who would need to perform these analyses to not be familiar with the models. This work introduces the Online Cost-Effectiveness ANalysis tool, featuring an easy-to-use web interface providing health professionals, researchers and decision makers involved in cervical cancer prevention programmes with a useful instrument to conduct complex cost-effectiveness analyses, which are becoming an essential tool as an approach for supporting decision-making that involves important trade-offs.

Results

The users can run cost-effectiveness evaluations of cervical cancer prevention strategies without deep knowledge of the underlying mathematical model or any programming language, obtaining the most relevant costs and health outcomes in a user-friendly format. The results provided by the tool are consistent with the existing literature.

Conclusions

Having such a tool will be an asset to the cervical cancer prevention community, providing researchers with an easy-to-use instrument to conduct cost-effectiveness analyses.
Cost-effectiveness of the Namaste care family program for nursing home residents with advanced dementia in comparison with usual care: a cluster-randomized controlled trial
Authors: El Alili Mohamed , Smaling Hanneke J. A. , Joling Karlijn J. , Achterberg Wilco P. , Francke Anneke L. , Bosmans Judith E. , van der Steen Jenny T.
Published: September 2020

Background

Dementia is a progressive disease that decreases quality of life of persons with dementia and is associated with high societal costs. The burden of caring for persons with dementia also decreases the quality of life of family caregivers. The objective of this study was to assess the societal cost-effectiveness of Namaste Care Family program in comparison with usual care in nursing home residents with advanced dementia.

Methods

Nursing homes were randomized to either Namaste Care Family program or usual care. Outcome measures of the cluster-randomized trial in 231 residents included Quality of Life in Late-Stage Dementia (QUALID) and the Gain in Alzheimer Care Instrument (GAIN) for family caregivers over 12 months of follow-up. Health states were measured using the EQ-5D-3L questionnaire which were translated into utilities. QALYs were calculated by multiplying the amount of time a participant spent in a specific health state with the utility score associated with that health state. Healthcare utilization costs were estimated using standard unit costs, while intervention costs were estimated using a bottom-up approach. Missing cost and effect data were imputed using multiple imputation. Bootstrapped multilevel models were used after multiple imputation. Cost-effectiveness acceptability curves were estimated.

Results

The Namaste Care Family program was more effective than usual care in terms of QUALID (− 0.062, 95%CI: − 0.40 to 0.28), QALY (0.0017, 95%CI: − 0.059 to 0.063) and GAIN (0.075, 95%CI: − 0.20 to 0.35). Total societal costs were lower for the Namaste Care Family program as compared to usual care (− 552 €, 95%CI: − 2920 to 1903). However, these differences were not statistically significant. The probability of cost-effectiveness at a ceiling ratio of 0 €/unit of effect extra was 0.70 for the QUALID, QALY and GAIN.

Conclusions

The Namaste Care Family program is dominant over usual care and, thus, cost-effective, although statistical uncertainty was considerable.

Trial registration

Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp, identifier: NL5570, date of registration: 2016/03/23).
Cost-effectiveness of a lifestyle intervention in high-risk individuals for diabetes in a low- and middle-income setting: Trial-based analysis of the Kerala Diabetes Prevention Program
Authors: Sathish Thirunavukkarasu , Oldenburg Brian , Thankappan Kavumpurathu R. , Absetz Pilvikki , Shaw Jonathan E. , Tapp Robyn J. , Zimmet Paul Z. , Balachandran Sajitha , Shetty Suman S. , Aziz Zahra , Mahal Ajay
Published: September 2020

Background

Data on the cost-effectiveness of lifestyle-based diabetes prevention programs are mostly from high-income countries, which cannot be extrapolated to low- and middle-income countries. We performed a trial-based cost-effectiveness analysis of a lifestyle intervention targeted at preventing diabetes in India.

Methods

The Kerala Diabetes Prevention Program was a cluster-randomized controlled trial of 1007 individuals conducted in 60 polling areas (electoral divisions) in Kerala state. Participants (30–60 years) were those with a high diabetes risk score and without diabetes on an oral glucose tolerance test. The intervention group received a 12-month peer-support lifestyle intervention involving 15 group sessions delivered in community settings by trained lay peer leaders. There were also linked community activities to sustain behavior change. The control group received a booklet on lifestyle change. Costs were estimated from the health system and societal perspectives, with 2018 as the reference year. Effectiveness was measured in terms of the number of diabetes cases prevented and quality-adjusted life years (QALYs). Three times India’s gross domestic product per capita (US$6108) was used as the cost-effectiveness threshold. The analyses were conducted with a 2-year time horizon. Costs and effects were discounted at 3% per annum. One-way and multi-way sensitivity analyses were performed.

Results

Baseline characteristics were similar in the two study groups. Over 2 years, the intervention resulted in an incremental health system cost of US$2.0 (intervention group: US$303.6; control group: US$301.6), incremental societal cost of US$6.2 (intervention group: US$367.8; control group: US$361.5), absolute risk reduction of 2.1%, and incremental QALYs of 0.04 per person. From a health system perspective, the cost per diabetes case prevented was US$95.2, and the cost per QALY gained was US$50.0. From a societal perspective, the corresponding figures were US$295.1 and US$155.0. For the number of diabetes cases prevented, the probability for the intervention to be cost-effective was 84.0% and 83.1% from the health system and societal perspectives, respectively. The corresponding figures for QALY gained were 99.1% and 97.8%. The results were robust to discounting and sensitivity analyses.

Conclusions

A community-based peer-support lifestyle intervention was cost-effective in individuals at high risk of developing diabetes in India over 2 years.

Trial registration

The trial was registered with Australia and New Zealand Clinical Trials Registry (ACTRN12611000262909). Registered 10 March 2011.
Association of relapse-linked ARID5B single nucleotide polymorphisms with drug resistance in B-cell precursor acute lymphoblastic leukemia cell lines
Authors: Tamai Minori , Huang Meixian , Kagami Keiko , Abe Masako , Somazu Shinpei , Shinohara Tamao , Harama Daisuke , Watanabe Atsushi , Akahane Koshi , Goi Kumiko , Sugita Kanji , Goto Hiroaki , Minegishi Masayoshi , Iwamoto Shotaro , Inukai Takeshi
Published: September 2020

Background

The genetic variants of theARID5Bgene have recently been reported to be associated with disease susceptibility and treatment outcome in childhood acute lymphoblastic leukemia (ALL). However, few studies have explored the association of ARID5B with sensitivities to chemotherapeutic agents.

Methods

We genotyped susceptibility-linked rs7923074 and rs10821936 as well as relapse-linked rs4948488, rs2893881, and rs6479778 ofARDI5Bby direct sequencing of polymerase chain reaction (PCR) products in 72 B-cell precursor-ALL (BCP-ALL) cell lines established from Japanese patients. We also quantified theirARID5Bexpression levels by real-time reverse transcription PCR, and determined their 50% inhibitory concentration (IC50) values by alamarBlue assays in nine representative chemotherapeutic agents used for ALL treatment.

Results

No significant associations were observed in genotypes of the susceptibility-linked single nucleotide polymorphisms (SNPs) and the relapsed-linked SNPs withARID5Bgene expression levels. Of note, IC50 values of vincristine (VCR) (median IC50: 39.6 ng/ml) in 12 cell lines with homozygous genotype of risk allele (C) in the relapse-linked rs4948488 were significantly higher (p = 0.031 in Mann–Whitney U test) than those (1.04 ng/ml) in 60 cell lines with heterozygous or homozygous genotypes of the non-risk allele (T). Furthermore, the IC50 values of mafosfamide [Maf; active metabolite of cyclophosphamide (CY)] and cytarabine (AraC) tended to be associated with the genotype of rs4948488. Similar associations were observed in genotypes of the relapse-linked rs2893881 and rs6479778, but not in those of the susceptibility-linked rs7923074 and rs10821936. In addition, the IC50 values of methotrexate (MTX) were significantly higher (p = 0.023) in 36 cell lines with lowerARID5Bgene expression (median IC50: 37.1 ng/ml) than those in the other 36 cell lines with higher expression (16.9 ng/ml).

Conclusion

These observations in 72 BCP-ALL cell lines suggested that the risk allele of the relapse-linked SNPs ofARID5Bmay be involved in a higher relapse rate because of resistance to chemotherapeutic agents such as VCR, CY, and AraC. In addition, lowerARID5Bgene expression may be associated with MTX resistance.
The role of extracellular vesicles in cholangiocarcinoma
Authors: Bai Mingzhen , Fu Wenkang , Su Gang , Cao Jie , Gao Long , Huang Chongfei , Ma Haidong , Zhang Jinduo , Yue Ping , Bai Bing , Lin Yanyan , Meng Wenbo , Li Xun
Published: September 2020

Cholangiocarcinoma (CCA) is a rare tumor that arises from cholangiocytes, the epithelial cells of the bile duct. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis and high recurrence rate. Due to the lack of specific biomarkers, it is difficult to diagnose CCA early and evaluate prognosis. Extracellular vesicles (EVs), which include apoptotic bodies, microvesicles and exosomes, have emerged as having important roles in cell-to-cell communication in both normal physiology and pathological conditions. Some research has found that EVs play a crucial role in the occurrence and development of CCA. EVs can carry specific molecular substances such as nucleic acids and proteins, which have potential for the diagnosis and therapy of CCA. This article reviews the current knowledge on the role of EVs in CCA. We highlight EVs and their functions in the physiology and pathophysiology of CCA, and discuss their therapeutic potential and their role as biomarkers.
Correction to: Use of a NAT-based assay to improve the surveillance system and prevent transfusion-transmitted malaria in blood banks
Authors: Rocha Daniele , de Melo Gisely Cardoso , Carneiro José Marcelo Hipólito , Ribeiro Marisa , Ribeiro Sthefanie , de Godoy Daniela Tupy , Costa Elaine , de Almeida Anne Cristine Gomes , de Andrade Elisabete Ferreira , de Moura Abrahim Cláudia Maria , Fraiji Nelson Abrahim , Ferreira Antonio Gomes Pinto , Monteiro Wuelton Marcelo , Brindeiro Rodrigo , Tanuri Amilcar , de Lacerda Marcus Vinicius Guimarães , Alvarez Patrícia
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
The role of extracelluar matrix in osteosarcoma progression and metastasis
Authors: Cui Juncheng , Dean Dylan , Hornicek Francis J. , Chen Zhiwei , Duan Zhenfeng
Published: September 2020

Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS.
Protocol for the measurement of changes in knowledge and engagement in the stepped wedge cluster randomised trial for childhood obesity prevention in Australia: (Reflexive Evidence and Systems interventions to Prevent Obesity and Non-communicable Disease (RESPOND))
Authors: Whelan Jillian , Strugnell Claudia , Allender Steven , Korn Ariella R. , Brown Andrew D. , Orellana Liliana , Hayward Josh , Brown Vicki , Bell Colin , Moodie Marj , Peeters Anna , Nichols Melanie
Published: September 2020

Background

Community-based interventions have shown promise in addressing the childhood obesity epidemic. Such efforts rely on the knowledge of key community members and their engagement with the drivers of obesity in their community. This paper presents the protocol for the measurement and evaluation of knowledge and engagement among community leaders within a whole-of-community systems intervention across 10 large intervention communities in Australia.

Methods

We will investigate the role of stakeholder knowledge and engagement in the implementation and effectiveness of the stepped wedge cluster randomised trial in ten communities in Victoria, Australia. Data will be collected using the Stakeholder-driven Community Diffusion Survey (SDCD) to measure levels of knowledge and engagement prior to commencement (2019), across the three separate levels of governance within the intervention at five time points. Primary outcomes will be baseline overall knowledge and engagement scores across the three levels of governance and change in overall knowledge and engagement over time.

Discussion

We hypothesise there will be heterogeneity between intervention sites on levels of knowledge and engagement and that these differences will be associated with variability in implementation success.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12618001986268. Registered on 11 December 2018
A 3D mobile positioning method based on deep learning for hospital applications
Authors: Zhang Qingqing , Wang Yuan
Published: September 2020

In this study, a 3D positioning method is proposed for hospital applications, such as navigation within a hospital building. It employs deep learning algorithms to analyze the received signal strength from cellular networks and Wi-Fi access points in order to estimate the positions of mobile stations. A two-stage deep learning procedure (level classification and location determination) is constructed to obtain the exact position information (building level, longitude, and latitude) in multiple-level buildings. To evaluate the performance of the proposed method, an experiment was conducted in the hospital of Xi’an Polytechnic University. In total, 36,985 records, 42 sampling location points, 28 different cellular networks, and 289 different Wi-Fi access points were considered. A deep learning neural network was trained for the first stage of level classification. Three deep learning neural networks were trained to obtain the distinct location coordinates (longitude and latitude) for three different building levels. To compare the efficacy of heterogeneous networks, three kinds of neural networks with different inputs (only cellular, only Wi-Fi APs, and a conjunction of cellular and Wi-Fi APs) were implemented. The accuracy of level classification was shown to be 100% for only Wi-Fi APs as an input. The average distance error of the location determination for different floors was 0.28 m for only Wi-Fi APs and for the conjunction of Wi-Fi APs and cellular networks in the second stage.
An improved fast transform algorithm based on adaptive hybrid channel allocation in TSCH networks
Authors: Gu Junxin , Xu Yong , Zhu Yujun , Mei Fan , Kang Longlong , Liu Yiyang
Published: September 2020

Time Slotted Channel Hopping (TSCH) is one of the five access behavior technologies defined in the IEEE 802.15.4e standard. Research shows that the wireless sensor network with single dynamic and static channel allocation in TSCH mode has higher performance. The clogging rate results in unnecessary energy waste. Therefore, this paper proposes an adaptive hybrid channel allocation strategy (AHCA) to measure the link quality change of wireless sensor networks in TSCH mode. The strategy estimates the part of the channel quality and determines whether the node wants to transmit on this channel and the optimal channel for node information transmission. According to the change of the amount of information transmitted, the hybrid channel allocation scheme of the dynamic and static channel ratio is adaptively adjusted to reduce the energy consumption of the information transmission process. This article performs experimental simulation on Contiki-NG. The experimental results show that the proposed scheme has shorter transmission time and lower congestion rate than the single dynamic static channel allocation wireless sensor network. The more reasonable and effective measurement, analysis and use of channel resources can fundamentally increase the amount of information transfer in wireless sensor networks per unit time, and thus extend the lifetime of wireless sensor networks.
Blending type approximation by τ-Baskakov-Durrmeyer type hybrid operators
Authors: Mohiuddine S. A. , Kajla Arun , Mursaleen M. , Alghamdi Mohammed A.
Published: September 2020

In this work, we construct a Durrmeyer type modification of the τ-Baskakov operators depends on two parameters $\alpha >0$
α
>
0
and $\tau \in [0,1]$
τ
∈
[
0
,
1
]
. We derive the rate of approximation of these operators in a weighted space and also obtain a quantitative Voronovskaja type asymptotic formula as well as a Grüss Voronovskaya type approximation.
Organic polymer monolithic columns with incorporated bare and cyano-modified fumed silica nanoparticles for use in hydrophilic interaction liquid chromatography
Authors: Ganewatta Nisansala , El Rassi Ziad
Published: September 2020

This research article presents the preparation and characterization of monolithic columns with incorporated bare fumed silica nanoparticles (FSNPs) and cyano-modified FNSPs (CN-FSNPs) and their subsequent use in hydrophilic interaction liquid chromatography (HILIC) of neutral, polar, and low molecular weight solutes. The monolithic support was based on the in situ polymerization of glyceryl monomethacrylate (GMM) and ethylene glycol dimethacrylate (EDMA) yielding the poly(GMM-co-EDMA) monolith for the incorporation of bare FNSPs and of CN-FSNPs. The poly(GMM-co-EDMA) functioned as a “true support” for bare FSNPs and CN-FSNPs “stationary phases” as manifested by bare FSNPs and CN-FSNPs being the major contributors to solute retention and column selectivity. Overall, the prepared bare FSNPs and CN-FSNPs stationary phases proved useful in HILIC of small polar solutes including dimethylformamide, formamide, thiourea, nucleobases, nucleosides, organic acids, food additives, vitamins, and biological amines.
Prostatic artery embolization with polyethylene glycol microspheres: evaluation in a canine spontaneous benign prostatic hyperplasia model
Authors: Lucas Cava Vanesa , Sánchez Margallo Francisco Miguel , Báez Díaz Claudia , Dávila Gómez Luis , Lima Rodríguez Juan Rafael , Sun Fei
Published: September 2020

Background

Prostatic artery embolization (PAE) is a minimally invasive technique for the management of symptomatic benign prostatic hyperplasia (BPH) relieving the lower urinary tract symptoms in patients. Various embolic agents have been tested in animal models and subsequently used in human patients. The purpose of this study was to evaluate the technical feasibility, effectiveness, and safety of PAE with polyethylene glycol microspheres in a canine spontaneous BPH model.

Results

Five adult male Beagle dogs (4.78 ± 1.11 years) were diagnosed by tranrectal ultrasonography of spontaneous BPH (prostate volume > 18 ml) and underwent PAE with polyethylene glycol microspheres (400 ± 75 μm). PAE procedures were performed successfully in all dogs. After PAE, all dogs were inspected for potential procedure-related complications during 1 month of follow-up. No major complications were observed any animal. Follow-up angiography was performed in each animal at 1 month of follow-up. Recanalization was demonstrated in all the embolized prostatic arteries or main branches at the end of the study. Magnetic Resonance Imaging (MRI) evaluations were performed immediately before PAE as baseline data, and 1 week, 2 weeks and 1 month after PAE. MRI study showed that the prostate shrank substantially with ischemic necrosis in each dog. There was a significant reduction in the mean prostate volume at 2 weeks and 1 month compared with the baseline data, from 19.95 ± 1.89 mL to 13.14 ± 2.33 and 9.35 ± 2.69 mL (p < 0.001), respectively. Histopathological study was conducted after 1-month follow-up angiography and confirmed the therapeutic responses with diffuse glandular atrophy and interstitial fibrosis.

Conclusions

The findings of the present study support that PAE with the use of polyethylene glycol microspheres is a safe and feasible procedure that may induce a significant shrinkage of prostate due to the local ischemia and secondary glandular atrophy. Early recanalization of target arteries remains to be further addressed in both laboratory investigation and clinical practice.
Effect of sowing time on productivity of Bt and non Bt cotton under climate change
Authors: Sankaranarayanan K , Prakash A H , Rajendran K
Published: September 2020

Background

Climate change affects cotton production systems in multiple ways, and the impacts are expected to influence the national economy of India. The weather conditions prevailing during squaring, flowering and boll development stages determine the seed cotton yield. The needs for adaptation connected to optimizing the timing of critical growth stages to minimize stresses and enhance resource utilization. The adjusting of sowing times proved to be an important management technique for improving seed cotton yield.

Results

The combined results for 3 years revealed that seed cotton yield was not influenced significantly by genotypes and interaction effect. However, the effect of date of sowing was significant. The best date of sowing was on 28 July which recorded the highest significant mean seed cotton yield (24.8 q/ha) compared with other sowing dates.

Conclusions

Three years results of experiments show that the best date for sowing is 28 July which is optimum to realize higher productivity and profitability. Sowing window of cotton was re-standardized as from 21 July to 18 August. The existing recommendation of sowing window is 1 August to 31 August.
Optimum conditions of killer toxins produced by Torulaspora delbrueckii and Wickerhamomyces anomalus and their action as antifungal agents
Authors: Abu-Mejdad Najwa Mohammed Jameel Ali , Al-Saadoon Abdullah H. , Al-Badran Adnan I. , Minati Mohammed Hussein
Published: September 2020

Background

This study was conducted to estimate the antifungal activity and efficiency of purified killer toxins (TK and WK) produced by Torulaspora delbrueckii and Wickerhamomyces anomalus as alternative drugs of resistant strains against several pathogenic fungi (Candida albicans, Aspergillus niger, and Aspergillus flavus). A specific focus was on the antifungal activity of such purified proteins by using a simple and economical tools under controlled conditions of fermentations.

Results

The results showed that the optimum conditions of these experiments were detected at 30 °C, 150 rpm, pH 4.5, 3 days incubation period and by using one culture medium (yeast malt extract broth with 2% SDS). The extracted crude toxin had an excellent effect on Candida albicans, Aspergillus niger, and Aspergillus flavus. The inhibition zone values were 35 and 30 mm for WK and TK, respectively, against Candida albicans. While the lowest values of inhibition zone were recorded at 25 mm for WK and 18 mm for TK against Aspergillus flavus. The WK killer toxins were in general more active against the three clinical strains compared to the TK that had the lowest inhibitory effect.

Conclusion

This study is conducted for the first time in Iraq to determine the optimum conditions for producing two types of killer toxins and testing their antifungal activity. The optimal killer activity was obtained at low pH and mesophilic temperature. The two yeast strains had a good role in the reduction of radial growth of tested pathogenic fungi