bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral health risk factor profiles in general hospital patients: identifying the need for screening and brief intervention
Authors: Freyer-Adam Jennis , Noetzel Florian , Baumann Sophie , Aghdassi Ali Alexander , Siewert-Markus Ulrike , Gaertner Beate , John Ulrich
Published: November 2019

Background

Little is known about the clustering of behavioral health risk factors (HRFs), namely the occurrence of 16 specific combinations of tobacco smoking, at-risk alcohol use, overweight and physical inactivity in general hospital patients. Furthermore, social inequalities in HRFs, health and life expectancy are a major concern in public health. In order to establish the need for screening and intervention in general hospital care, the study aimed to determine the co-occurrence of HRFs in patients in four medical departments, and to investigate differences by gender, age and socio-economic characteristics.

Methods

Over 17 months, a systematic multiple HRF screening was conducted at one general hospital in northeastern Germany. In total, 6251 18–64 year old patients (92% of eligibles) participated. Proportions and confidence intervals were calculated for all 16 HRF profiles stratified by department, gender, age group, school education, and employment status.

Results

In total, 92.2% of the participants (58.6% male) reported ≥1 HRF, and 65.7% ≥2 HRFs. Men (71.2%), patients aged 35–49 (67.9%) and 50–64 years (69.5%), lower educated (79.0%), and unemployed (77.8%) patients had larger proportions of ≥2 HRFs than their counterparts. In all departments, the most common HRF profiles included overweight. HRF profiles that included alcohol and/ or smoking were more common in ear-nose-throat and trauma surgery than in internal medicine and general surgery patients. Men had higher rates concerning almost all HRF profiles including ≥2 HRFs and alcohol; women concerning profiles that included ≤2 HRFs and inactivity. In older patients, profiles with ≥2 HRFs including overweight; and in younger patients, profiles with smoking and/or alcohol were more common. In lower educated patients, profiles with ≥2 HRFs including inactivity; and in higher educated patients profiles with ≤2 HRFs including alcohol were more common. Compared to others, unemployed patients had higher rates of profiles with ≥3 HRFs including smoking.

Conclusions

Two in three patients require interventions targeting two or more HRFs. The findings help to develop screening and brief intervention for patients with specific health risk profiles, that can reach most patients, including those most in need and those most hard to reach, with socio-economically disadvantaged people in particular.

Registry

clinicaltrials.gov: NCT01291693.
Clinicopathological features, survival and risk in breast cancer survivors with thyroid cancer: an analysis of the SEER database
Authors: Li Shuting , Yang Jiao , Shen Yanwei , Zhao Xiaoai , Zhang Lingxiao , Wang Biyuan , Li Pan , Wang Yunmei , Yi Min , Yang Jin
Published: November 2019

Background

The co-occurrence of breast cancer (BC) and thyroid cancer (TC) has been mentioned for several years, researchers observed an increased risk of BC patients to develop TC, but few researches concern about the features, survival of BC patients followed by TC and the influent factors of the incidence risk. The present study aimed to estimate the clinicopathological features, survival of BC survivors who had primary TC and the predictive factors on the risk of BC patients to develop TC.

Methods

Women diagnosed with BC between 1992 and 2011, and then developed TC from the Surveillance, Epidemiology, and End Results Database were included. Standardized incidence ratios (SIRs) was used to perform multiple primary analyses, generated from the multiple primary-SIR program in SEER*Stat.

Results

A total of 842 BC then TC patients were included, the median age was 54 years. Additionally, 78.39% were white, 60.45% had T1 cancer, 62.47% had negative lymph nodes, and more than 75% had infiltrating duct carcinoma, 5-year survival rate was 95.4%. Compared with BC only patients, they were younger, had smaller tumor size and a relatively better prognosis. The risk of developing TC was higher in BC patients than in the general population (SIR 1.22, 95% CI [1.14, 1.31]), especially within 3 years. The influent factors of SIR were black race, BC tumor site, grade and ER/PR positive expression.

Conclusions

BC patients followed by TC had its particular clinicopathological features. Compared with the features and survival of BC only patients, they were younger, had a smaller tumor size and a relatively better prognosis. Furthermore, BC patients had a high risk of developing TC, especially within 3 years. Black women, primary tumor located in an upper-outer, central, or overlapping site, high grade tumor and with positive hormone receptor expression were predictive factors to develop TC.
Physical activity calorie expenditure (PACE) labels in worksite cafeterias: effects on physical activity
Authors: Deery Christopher B. , Hales Derek , Viera Laura , Lin Feng-Chang , Liu Zhaopei , Olsson Emily , Gras-Najjar Julie , Linnan Laura , Noar Seth M. , Ammerman Alice S. , Viera Anthony J.
Published: November 2019

Background

Regular physical activity is an important component of healthy living and wellbeing. Current guidelines recommend that adults participate in at least 150 min of moderate or vigorous-intensity physical activity weekly. In spite of the benefits, just over half of U.S. adults meet these recommendations. Calorie-only food labels at points of food purchase have had limited success in motivating people to change eating behaviors and increase physical activity. One new point of purchase approach to promote healthy behaviors is the addition of food labels that display the physical activity requirement needed to burn the calories in a food item (e.g. walk 15 min).

Methods

The Physical Activity Calorie Expenditure (PACE) Study compared activity-based calorie-expenditure food labels with calorie-only labels at three Blue Cross and Blue Shield of North Carolina worksite cafeterias. After 1 year of baseline data collection, one cafeteria had food items labeled with PACE labels, two others had calorie-only food labels. Cohort participants were asked to wear an accelerometer and complete a self-report activity questionnaire on two occasions during the baseline year and twice during the intervention year.

Results

A total of 366 study participants were included in the analysis. In the PACE-label group, self-reported physical activity increased by 13–26% compared to the calorie-only label group. Moderate-to-vigorous physical activity (MVPA) increased by 24 min per week in the PACE-label group compared to the calorie-label group (p = 0.06). Changes in accelerometer measured steps, sedentary time, and MVPA had modest increases. Change ranged from 1 to 12% with effect size values from 0.08 to 0.15. Baseline physical activity level significantly moderated the intervention effects for all physical activity outcomes. Participants in both label groups starting in the lowest tertile of activity saw the largest increase in their physical activity.

Conclusion

Results suggest small positive effects for the PACE labels on self-reported and objective physical activity measures. Minutes of weekly MVPA, strength training, and exercise activities showed modest increases. These results suggest that calorie-expenditure food labels may result in some limited increases in physical activity.
Tuberculosis infectious pool and associated factors in East Gojjam Zone, Northwest Ethiopia
Authors: Asemahagn Mulusew Andualem , Alene Getu Degu , Yimer Solomon Abebe
Published: November 2019

Background

Globally, tuberculosis (TB) lasts a major public health concern. Using feasible strategies to estimate TB infectious periods is crucial. The aim of this study was to determine the magnitude of TB infectious period and associated factors in East Gojjam zone.

Methods

An institution-based prospective study was conducted among 348 pulmonary TB (PTB) cases between December 2017 and December 2018. TB cases were recruited from all health facilities located in Hulet Eju Enesie, Enebse Sarmider, Debay Tilatgen, Dejen, Debre-Markos town administration, and Machakel districts. Data were collected through an exit interview using a structured questionnaire and analyzed by IBM SPSS version25. The TB infectious period of each patient category was determined using theTB management timeand sputum smear conversion time. The sum of the infectious period of each patient category gave the infectious pool of the study area. A multivariable logistic regression analysis was used to identify factors associated with the magnitude of TB infectious period.

Results

Of the total participated PTB cases, 209(60%) were male, 226(65%) aged < 30 years, 205(59%) were from the rural settings, and 77 (22%) had comorbidities. The magnitude of the TB infectious pool in the study area was 78,031 infectious person-days. The undiagnosed TB cases (44,895 days), smear-positive (14,625 days) and smear-negative (12,995 days) were major contributors to the infectious pool. The overall average medianTB management timewas 142.4 days (IQR, 98–238 days). Similarly, the average sputum smear conversion time of PTB cases (new and repeat) was 46 days. Residence, knowledge, form of TB, smoking, alcohol history, distance from the facility, comorbidity history and stigma were statistically significant factors TB infectious period (p-value< 0.05).

Conclusions

The magnitude of the TB infectious pool is high even if it is lower than the findings of previous studies. This might be an indicator of poor access to TB services, service delays, low community awareness, impaired facility readiness, and poor transportation. Improving personal awareness and behavior, timely management of commodities, and using theTB management timein TB control are crucial to improving TB control activities.
Comparison of disease progression subgroups in idiopathic pulmonary fibrosis
Authors: Kärkkäinen Miia , Kettunen Hannu-Pekka , Nurmi Hanna , Selander Tuomas , Purokivi Minna , Kaarteenaho Riitta
Published: November 2019

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia with an unpredictable course. The aims of this study were to retrospectively re-evaluate a cohort of patients with IPF according to the 2011 international IPF guidelines and 1) to characterize the subgroups of patients when classified according to their observed survival times and 2) to evaluate whether Composite Physiologic Index (CPI), Gender-Age-Physiology (GAP) Index or clinical variables could predict mortality.

Methods

Retrospective data was collected and patients were classified into subgroups according to their observed lifespans. Differences in clinical variables, CPI and GAP stages as well as in comorbidities were investigated between the subgroups. Predictors of mortality were identified by COX proportional hazard analyses.

Results

A total of 132 patients were included in this study. The disease course was rapid (≤ 2 years) in 30.0%, moderate (2–5 years) in 28.0% and slow (≥ 5 years) in 29.0% of the patients. Pulmonary function tests (PFT) and CPI at baseline differentiated significantly between the rapid disease course group and those patients with longer survival times. However, the predictive accuracy of the investigated clinical variables was mainly less than 0.80. The proportions of patients with comorbidities did not differ between the subgroups, but more patients with a rapid disease course were diagnosed with heart failure after the diagnosis of IPF. Most patients with a rapid disease course were categorized in GAP stages I and II, but all patients in GAP stage III had a rapid disease course. The best predictive multivariable model included age, gender and CPI. GAP staging had slightly better accuracy (0.67) than CPI (0.64) in predicting 2-year mortality.

Conclusions

Although the patients with a rapid disease course could be differentiated at baseline in terms of PFT and CPI, the predictive accuracy of any single clinical variable as well as CPI and GAP remained low. GAP staging was unable to identify the majority of patients with a rapid disease progression. It is challenging to predict disease progression and mortality in IPF even with risk prediction models.
Tuning the performance of CAR T cell immunotherapies
Authors: Richardson Noah H. , Luttrell Jordan B. , Bryant Jonathan S. , Chamberlain Damian , Khawaja Saleem , Neeli Indira , Radic Marko
Published: November 2019

Background

Simultaneous advances in gene editing, T cell engineering and biotechnology currently provide an opportunity for rapid progress in medicine. The approval of chimeric antigen receptor (CAR) T cell therapies by the US Food and Drug Administration (FDA) and the European Commission have generated substantial momentum for these first-in-class therapies to be used in patients with B cell malignancies.

Main body

Considerable efforts focus on improved outcomes and reduced side effects of the newly approved therapies. Using innovative strategies, researchers aim to extend CAR T cell use to tackle difficulties inherent in solid tumors. Efforts are underway to broaden the applications of CAR T cells, and the strategy has been successful in chronic viral infections and preclinical models of autoimmunity. Research is in progress to generate “off-the-shelf” CAR T cells, an advance, which would greatly increase patient availability and reduce treatment cost.

Conclusions

In this thematic review, we highlight advances that may help develop genetically engineered cells into a new category of medical therapies.
Assessment of knowledge and practice of nurses on initial management of acute poisoning in Dessie referral hospital Amhara region, Ethiopia, 2018
Authors: Abebe Ayele Mamo , Kassaw Mesfin Wudu , Shewangashaw Nathan Estifanos
Published: November 2019

Introduction

Poisoning is a major health problem worldwide, and it causes significant morbidity and mortality. It is estimated that 350,000 people died worldwide from unintentional poisoning. The purpose of this study is to assess nurses’ knowledge and practice on the initial management of acute poisoning among nurses in Dessie referral hospital, Amhara region, Ethiopia.

Methods

Hospital based cross sectional study was conducted from January 2018 to June 2018. Simple Random sampling technique was used to select the samples. Data was collected by using self-administered structured questioners. Data were cleansed, checked for completeness and entered into SPSS version 20 for analyses. Statistical measures of Central tendency, T-test and ANOVA were used in determining the association between independent and dependent variables.

Results

Based on the given 13 items to assess the general knowledge of nurses on poisoning, the score ranges from 2 to 9 with the range of 7 with the mean score of 7.48(SD-0. 0.839) for the entire respondents that was 57.5% for the given items that was less than 75% which was unsatisfactory level of knowledge. The mean score of general knowledge on poisoning was high among nurses who had training on initial management of poisoning than those nurses who had not the training.

Conclusion and recommendation

All Dessie referral nurses that participated in this study had unsatisfactory general knowledge on poisoning, knowledge on initial management of acute poisoning and self-reported practice. The major implication of these study findings on the health system is the importance of ensuring support to nurses’ health care services for early detection and management of poisoning.
Rapid, large-scale species discovery in hyperdiverse taxa using 1D MinION sequencing
Authors: Srivathsan Amrita , Hartop Emily , Puniamoorthy Jayanthi , Lee Wan Ting , Kutty Sujatha Narayanan , Kurina Olavi , Meier Rudolf
Published: November 2019

Background

More than 80% of all animal species remain unknown to science. Most of these species live in the tropics and belong to animal taxa that combine small body size with high specimen abundance and large species richness. For such clades, using morphology for species discovery is slow because large numbers of specimens must be sorted based on detailed microscopic investigations. Fortunately, species discovery could be greatly accelerated if DNA sequences could be used for sorting specimens to species. Morphological verification of such “molecular operational taxonomic units” (mOTUs) could then be based on dissection of a small subset of specimens. However, this approach requires cost-effective and low-tech DNA barcoding techniques because well-equipped, well-funded molecular laboratories are not readily available in many biodiverse countries.

Results

We here document how MinION sequencing can be used for large-scale species discovery in a specimen- and species-rich taxon like the hyperdiverse fly family Phoridae (Diptera). We sequenced 7059 specimens collected in a single Malaise trap in Kibale National Park, Uganda, over the short period of 8 weeks. We discovered > 650 species which exceeds the number of phorid species currently described for the entire Afrotropical region. The barcodes were obtained using an improved low-cost MinION pipeline that increased the barcoding capacity sevenfold from 500 to 3500 barcodes per flowcell. This was achieved by adopting 1D sequencing, resequencing weak amplicons on a used flowcell, and improving demultiplexing. Comparison with Illumina data revealed that the MinION barcodes were very accurate (99.99% accuracy, 0.46% Ns) and thus yielded very similar species units (match ratio 0.991). Morphological examination of 100 mOTUs also confirmed good congruence with morphology (93% of mOTUs; > 99% of specimens) and revealed that 90% of the putative species belong to the neglected, megadiverse genusMegaselia. We demonstrate for oneMegaseliaspecies how the molecular data can guide the description of a new species (Megaselia sepsioidessp. nov.).

Conclusions

We document that one field site in Africa can be home to an estimated 1000 species of phorids and speculate that the Afrotropical diversity could exceed 200,000 species. We furthermore conclude that low-cost MinION sequencers are very suitable for reliable, rapid, and large-scale species discovery in hyperdiverse taxa. MinION sequencing could quickly reveal the extent of the unknown diversity and is especially suitable for biodiverse countries with limited access to capital-intensive sequencing facilities.
A novel PCR-based point-of-care method enables rapid, sensitive and reliable diagnosis of Babesia gibsoni infection in dogs
Authors: Liu I-Li , Chi Nai-Yu , Chang Chia-Ling , Hung Ming-Long , Chiu Chun-Ta , Chen Hui-Wen
Published: November 2019

Background

Babesia gibsoni (B. gibsoni)is an intraerythrocytic protozoan parasite of dogs that causes fever and hemolytic illness. A timely diagnosis is essential for the disease management.

Results

Here, we report a QubeMDx PCR system which enables a rapid, sensitive and reliable diagnosis ofB. gibsoninear the dog patient. Within 30 min, this diagnostic assay was able to detect as low as 0.002% parasitemia of the dog blood. Using clinical samples, this new assay was validated to demonstrate 100% agreement with real-time PCR.

Conclusions

This novel diagnostic method provides a reliable point-of-care test to assist in the identification ofB. gibsoni.
LncRNA UCA1 facilitated cell growth and invasion through the miR-206/CLOCK axis in glioma
Authors: Huang Zhi , Zhao Xuya , Wu Xiaowen , Xiang Lei , Yuan Yingnan , Zhou Shi , Yu Wenfeng
Published: November 2019

Background

Glioma is a lethal malignant brain tumor, which affects the brain functions and is life-threatening. LncRNA UCA1 was identified as a pivotal regulator for tumorigenesis of glioma. MiR-206 was discovered to promote tumorigenesis and is critical in the regulation of cell proliferation in glioma. This study will discuss the expression of UCA1 regarding miR-206 and CLOCK, and their integrative effects in the proliferation and cell cycle of glioma cells.

Methods

qRT-PCR was conducted to measure the mRNA expressions of IgG and Ago2 in cells co-transfected with UCA1, and miR-216 in U251. Bioinformation was analyzed for the prediction of association between UCA1 and miR-206. Transwell migrations assays and invasion assays were utilized to observe the cell invasive ability. Western blot and immunofluorescence imaging were used to examine the protein expressions. In vivo comparisons and observations were also performed to investigate the role of UCA1 in glioma growth.

Results

LncRNA UCA1 was up-regulated in glioma cell lines and tissues. It elevated cell invasion via the inducing of epithelial-mesenchymal transition. We found that UCA1 can modulate miR-206 expression and serve as an endogenous sponge of miR-206. The EMT-inducer CLOCK was validated as a messenger RNA target of miR-206. At last, we demonstrated that UCA1 exerted the biology function through regulating miR-206 and CLOCK in vivo.

Conclusions

Overall, the results demonstrated that UCA1/miR-206/CLOCK axis participated in the progressing of glioma and could act as a promising therapeutic target.
Trends in horizontal inequity in access to public health care services by immigrant condition in Spain (2006–2017)
Authors: Pinilla Jaime , Negrín Miguel A. , Abásolo Ignacio
Published: November 2019

Background

The objective of this research is to analyse trends in horizontal inequity in access to public health services by immigration condition in Spain throughout the period 2006–2017. We focus on “economic immigrants” because they are potentially the most vulnerable group amongst immigrants.

Methods

Based on the National Health Surveys of 2006–07 (N = 29,478), 2011–12 (N = 20,884) and 2016–17 (N = 22,903), hierarchical logistic regressions with random effects in Spain’s autonomous communities are estimated to explain the probability of using publicly-financed health care services by immigrant condition, controlling by health care need and other socioeconomic and demographic variables.

Results

Our results indicate that there are several horizontal inequities, though they changed throughout the decade studied. Regarding primary care services, the period starts (2006–07) with no global evidence of horizontal inequity in access (although the analysis by continent shows inequity that is detrimental to Eastern Europeans and Asians), giving way to inequity favouring economic immigrants (particularly Latin Americans and Africans) in 2011–12 and 2016–17. An opposite trend happens with specialist care, as the period starts (2006–07) with evidence of inequity that is detrimental to economic immigrants (particularly those from North of Africa) but this inequity disappears with the economic crisis and after it (with the only exception of Eastern Europeans in 2011–12, whose probability to visit a specialist is lower than for natives). Regarding emergency care, our evidence indicates horizontal inequity in access that favours economic immigrants (particularly Latin Americans and North Africans) that remains throughout the period. In general, there is no inequity in hospitalisations, with the exception of 2011–12, where inequity in favour of economic immigrants (particularly those from Latin America) takes place.

Conclusions

The results obtained here may serve, firstly, to prevent alarm about negative discrimination of economic immigrants in their access to public health services, even after the implementation of the Royal Decree RD Law 16/2012. Conversely, our results suggest that the horizontal inequity in access to specialist care that was found to be detrimental to economic immigrants in 2006–07, disappeared in global terms in 2011–12 and also by continent of origin in 2016–17.
Effects of extended stance time on a powered knee prosthesis and gait symmetry on the lateral control of balance during walking in individuals with unilateral amputation
Authors: Brandt Andrea , Huang He ( Helen)
Published: November 2019

Background

Individuals with lower limb amputation commonly exhibit large gait asymmetries that are associated with secondary health issues. It has been shown that they are capable of attaining improved temporal and propulsive symmetry when walking with a powered knee prosthesis and visual feedback, but they perceive this pattern of gait to be more difficult. Rather than improving the efficiency of gait, improved gait symmetry may be increasing individuals’ effort associated with maintaining lateral balance.

Methods

In this study, we used a simple visual feedback paradigm to increase the prosthesis-side stance time of six individuals with unilateral TFA or KD as they walked on a powered knee prosthesis at their self-selected speed. As they walked more symmetrically, we evaluated changes in medial-lateral center-of-mass excursion, lateral margin of stability, stride width, and hip abductor activity.

Results

As the subjects increased their prosthesis-side stance time, their center-of-mass excursion and hip abductor activity significantly increased, while their lateral margin of stability significantly decreased on the prosthesis-side only. Stride width remained relatively unchanged with testing condition.

Conclusions

Extended stance time on a powered knee prosthesis (yielding more symmetric gait) challenged the lateral balance of individuals with lower limb amputation. Lateral stability may be a reason they prefer an asymmetric gait, even with more advanced technology. Hip muscular changes post-amputation may contribute to the decline in stability on the prosthesis side. Interventions and advancements in prosthesis control aimed at improving their control of lateral balance may ameliorate the difficulty in walking with improved gait symmetry.
A home visit program versus a non-home visit program in total knee replacement patients: a randomized controlled trial
Authors: Sindhupakorn Bura , Numpaisal Piya-on , Thienpratharn Suwittaya , Jomkoh Darawan
Published: November 2019

Background

The goals in total knee replacement (TKR) are pain relief, restore functions, and improve quality of life. Surgical outcomes were not related to patients’ satisfaction. Low 1-year WOMAC especially in the first 6 weeks and painful TKR related to patient dissatisfied. To improve satisfaction, we created the home visit program (TKR-H) after hospital discharge. INHOMESSS was the rationale for home visit activities.

Methods

We recruited 52 TKRs. Four TKRs were excluded. We used simple randomization for 24 patients as a home visit (TKR-H) and 24 patients as a non-home visit (TKR). Patients were evaluated by general demographics, pain intensity scores (VAS), range of motion (ROM), WOMAC, knee scores, and functional scores as a primary objective. A duration for gait aid independent and patient’s satisfaction score as secondary objective. The study was 6 weeks after surgery.

Results

TKR-H and TKR had significant differences in the mean of WOMAC score (88.29 ± 10.66 vs. 68.00 ± 12.47, respectively, P <  0.001), pain score (VAS) (6.25 ± 10.13 vs. 35.67 ± 22.05, respectively, P <  0.001), knee score (81.67 ± 10.08 vs. 68.38 ± 6.45, respectively, P <  0.001), functional score (77.83 ± 4.22 vs. 73.70 ± 7.48, respectively, P = 0.037), and range of motion (107.71 ± 8.47 vs. 98.17 ± 9.57, respectively, P = 0.001). The patient’s satisfaction score in TKR-H group (4.71 ± 0.46) was significantly higher than the TKR group (4.13 ± 0.45) (P <  0.001) and time to gait aid independent (2.75 ± 0.99 vs. 3.71 ± 1.23, respectively, P = 0.005).

Conclusion

Our TKR-H showed better clinical outcomes and satisfaction than non-home visit. The rationale in TKR-H improves satisfaction after total knee replacement.

Trial registration

TCTR20190514001.
Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy
Authors: Han Xiao , Wang Yao , Wei Jianshu , Han Weidong
Published: November 2019

The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the application of CAR-T cells has been limited by antigen escape and on-target, off-tumor toxicities. Therefore, it may be a potentially effective strategy to select appropriate targets and to combine multi-antigen-targeted CAR-T cells with “OR”, “AND” and “NOT” Boolean logic gates. We summarize the current limitations of CAR-T cells as well as the efficacy and safety of logic-gated CAR-T cells in antitumor therapy. This review will help to explore more optimized strategies to expand the CAR-T cell therapeutic window.
Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity
Authors: Shi Xiaojuan , Zhang Daiqun , Li Feng , Zhang Zhen , Wang Shumin , Xuan Yujing , Ping Yu , Zhang Yi
Published: November 2019

Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein. Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells. Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells. Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells. Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo. Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
The impact of shoe flexibility on gait, pressure and muscle activity of young children. A systematic review
Authors: Cranage Simone , Perraton Luke , Bowles Kelly‐Ann , Williams Cylie
Published: November 2019

Background

There is limited evidence of shoe impact in younger children, particularly in the context of immature gait patterns. It is unclear if the impact from shoes in younger children is similar to what has been seen in older children. This systematic review aims to identify any impact of shoe features on younger children's gait, and if there are any differences between shoe sole flexibility compared to barefoot.

Methods

Study inclusion criteria included: typically developing children aged ≤6 years; comparison of barefoot and shod conditions (walking and/or running) with shoe features or style of shoe described; sample size > 1. Novelty types of footwear were excluded, as was any mention of in shoe support or modifications. Studies were located from six databases. Study methodology was assessed using the McMasters critical review form. Sample size weighted standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated.

Results

Four studies were included. Participant age ranged from 15.2 to 78.7 months, with 262 participants across all studies. All studies had limited methodological bias based on their design type. Compared to barefoot walking, shoes increased velocity, step time and step length. Shod walking decreased cadence. Peak plantar pressure was generally lower in the stiff shoe design and there was a higher peak plantar pressure in the Ultraflex shoes. No studies were found investigating muscle activation.

Conclusions

Shoes affect younger children's gait in spatiotemporal gait aspects, similar to those seen in older children. There is limited evidence on effects of particular shoe features such as sole hardness, on gait, and no evidence of any changes in muscle activation patterns. Further research is required to evaluate the impact of different types of shoe and shoe features in this population to provide clinical advice on the type of shoe that is appropriate in this age group.
Trends and determinants of teenage childbearing in Ethiopia: evidence from the 2000 to 2016 demographic and health surveys
Authors: Kassa Getachew Mullu , Arowojolu Ayodele O. , Odukogbe Akin-Tunde Ademola , Yalew Alemayehu Worku
Published: November 2019

Background

Teenage childbearing among adolescents aged 15 to 19 is a common sexual and reproductive health (SRH) issue among young people, particularly in developing countries. It is associated with higher maternal and neonatal complications. Almost half (47%) of the population in Ethiopia are young people under 15 years old. Therefore, a clear understanding of the trend and determinants of teenage childbearing is essential to design proper intervention programs.

Methods

Secondary analysis of the 2000 to 2016 Ethiopia Demographic and Health Survey (DHS) data were conducted. A total of 3710 (DHS 2000), 3266 (DHS 2005), 4009 (DHS 2011) and 3381 (DHS 2016) adolescents (aged 15 to 19 years old) were included from the four surveys. The main outcome variable of this study was teenage childbearing, and independent variables were categorized into individual- and community-level factors. The 2016 DHS was used to identify the factors associated with teenage childbearing. Multi-level logistic regression analysis technique was used to identify the factors associated with teenage childbearing. The analysis was adjusted for different individual- and community- level factors affecting teenage childbearing. Data analysis was conducted using STATA software.

Results

The prevalence of adolescents who started childbearing reduced from 16.3% in 2000 DHS to 12.5% in 2016 DHS, p-value = < 0.0001. From the 2016 DHS, the percentage of adolescents who have had a live birth was 10.1%, and the percentage of adolescents who were currently pregnant was 2.4%. The highest percentage of teenage childbearing was in Affar region (23.4%), and the lowest was in Addis Ababa city (3%). The odds of teenage childbearing was higher among adolescents in the age range of 18–19 years old (AOR = 2.26; 95% CI: 1.29, 3.94, p-value < 0.01), those who started sexual intercourse before their eighteenth birthday (AOR = 12.74; 95% CI: 4.83, 33.62, p-value < 0.001), who were married or living together (AOR = 8.98; 95% CI: 2.49, 32.41, p-value < 0.01), and among those who were widowed, divorced or separated (AOR = 4.89; 95% CI: 1.36, 17.61, p-value < 0.05).

Conclusions

One in ten teenage girls have already started childbearing in Ethiopia. Variations were observed in the percentage of teenage childbearing across different sociodemographic- and economic variables. Factors like age, early sexual initiation before 18 years of age, ever married, and geographical region were significant factors associated with teenage childbearing. School- and community- based intervention programs aimed at prevention of early marriage and early sexual intercourse is essential to reduce teenage childbearing and its complications.
Disentangling Trypanosoma cruzi transmission cycle dynamics through the identification of blood meal sources of natural populations of Triatoma dimidiata in Yucatán, Mexico
Authors: Moo-Millan Joel Israel , Arnal Audrey , Pérez-Carrillo Silvia , Hernandez-Andrade Anette , Ramírez-Sierra María-Jesús , Rosado-Vallado Miguel , Dumonteil Eric , Waleckx Etienne
Published: November 2019

Background

In the Yucatán Peninsula, Mexico, Triatoma dimidiata is the main vector of Trypanosoma cruzi, the causative agent of Chagas disease. Little effort has been made to identify blood meal sources of T. dimidiata in natural conditions in this region, although this provides key information to disentangle T. cruzi transmission cycles and dynamics and guide the development of more effective control strategies. We identified the blood meals of a large sample of T. dimidiata bugs collected in different ecotopes simultaneously with the assessment of bug infection with T. cruzi, to disentangle the dynamics of T. cruzi transmission in the region.

Methods

A sample of 248 T. dimidiata bugs collected in three rural villages and in the sylvatic habitat surrounding these villages was used. DNA from each bug midgut was extracted and bug infection with T. cruzi was assessed by PCR. For blood meal identification, we used a molecular assay based on cloning and sequencing following PCR amplification with vertebrate universal primers, and allowing the detection of multiple blood meals in a single bug.

Results

Overall, 28.7% of the bugs were infected with T. cruzi, with no statistical difference between bugs from the villages or from sylvatic ecotopes. Sixteen vertebrate species including domestic, synanthropic and sylvatic animals, were identified as blood meal sources for T. dimidiata. Human, dog and cow were the three main species identified, in bugs collected in the villages as well as in sylvatic ecotopes. Importantly, dog was highlighted as the main blood meal source after human. Dog was also the most frequently identified animal together with human within single bugs, and tended to be associated with the infection of the bugs.

Conclusions

Dog, human and cow were identified as the main mammals involved in the connection of sylvatic and domestic transmission cycles in the Yucatán Peninsula, Mexico. Dog appeared as the most important animal in the transmission pathway of T. cruzi to humans, but other domestic and synanthropic animals, which most were previously reported as important hosts of T. cruzi in the region, were evidenced and should be taken into account as part of integrated control strategies aimed at disrupting parasite transmission.
Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease
Authors: Sudhagar Arun , Ertl Reinhard , Kumar Gokhlesh , El-Matbouli Mansour
Published: November 2019

Background

Tetracapsuloides bryosalmonae is a myxozoan parasite which causes economically important and emerging proliferative kidney disease (PKD) in salmonids. Brown trout, Salmo trutta is a native fish species of Europe, which acts as asymptomatic carriers for T. bryosalmonae. There is only limited information on the molecular mechanism involved in the kidney of brown trout during T. bryosalmonae development. We employed RNA sequencing (RNA-seq) to investigate the global transcriptome changes in the posterior kidney of brown trout during T. bryosalmonae development.

Methods

Brown trout were exposed to the spores of T. bryosalmonae and posterior kidneys were collected from both exposed and unexposed control fish. cDNA libraries were prepared from the posterior kidney and sequenced. Bioinformatics analysis was performed using standard pipeline of quality control, reference mapping, differential expression analysis, gene ontology, and pathway analysis. Quantitative real time PCR was performed to validate the transcriptional regulation of differentially expressed genes, and their correlation with RNA-seq data was statistically analyzed.

Results

Transcriptome analysis identified 1169 differentially expressed genes in the posterior kidney of brown trout, out of which 864 genes (74%) were upregulated and 305 genes (26%) were downregulated. The upregulated genes were associated with the regulation of immune system process, vesicle-mediated transport, leucocyte activation, and transport, whereas the downregulated genes were associated with endopeptidase regulatory activity, phosphatidylcholine biosynthetic process, connective tissue development, and collagen catabolic process.

Conclusion

To our knowledge, this is the first RNA-seq based transcriptome study performed in the posterior kidney of brown trout during active T. bryosalmonae development. Most of the upregulated genes were associated with the immune system process, whereas the downregulated genes were associated with other metabolic functions. The findings of this study provide insights on the immune responses mounted by the brown trout on the developing parasite, and the host molecular machineries modulated by the parasite for its successful multiplication and release.
Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels
Authors: Kanavy Dona M. , McNulty Shannon M. , Jairath Meera K. , Brnich Sarah E. , Bizon Chris , Powell Bradford C. , Berg Jonathan S.
Published: November 2019

Background

The 2015 American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that “well-established” functional studies can be used as evidence in variant classification. These guidelines articulated key attributes of functional data, including that assays should reflect the biological environment and be analytically sound; however, details of how to evaluate these attributes were left to expert judgment. The Clinical Genome Resource (ClinGen) designates Variant Curation Expert Panels (VCEPs) in specific disease areas to make gene-centric specifications to the ACMG/AMP guidelines, including more specific definitions of appropriate functional assays. We set out to evaluate the existing VCEP guidelines for functional assays.

Methods

We evaluated the functional criteria (PS3/BS3) of six VCEPs (CDH1, Hearing Loss, Inherited Cardiomyopathy-MYH7,PAH,PTEN, RASopathy). We then established criteria for evaluating functional studies based on disease mechanism, general class of assay, and the characteristics of specific assay instances described in the primary literature. Using these criteria, we extensively curated assay instances cited by each VCEP in their pilot variant classification to analyze VCEP recommendations and their use in the interpretation of functional studies.

Results

Unsurprisingly, our analysis highlighted the breadth of VCEP-approved assays, reflecting the diversity of disease mechanisms among VCEPs. We also noted substantial variability between VCEPs in the method used to select these assays and in the approach used to specify strength modifications, as well as differences in suggested validation parameters. Importantly, we observed discrepancies between the parameters VCEPs specified as required for approved assay instances and the fulfillment of these requirements in the individual assays cited in pilot variant interpretation.

Conclusions

Interpretation of the intricacies of functional assays often requires expert-level knowledge of the gene and disease, and current VCEP recommendations for functional assay evidence are a useful tool to improve the accessibility of functional data by providing a starting point for curators to identify approved functional assays and key metrics. However, our analysis suggests that further guidance is needed to standardize this process and ensure consistency in the application of functional evidence.
Fostering international collaboration in implementation science and research: a concept mapping exploratory study
Authors: Aarons Gregory A. , Seijo Chariz , Green Amy E. , Moullin Joanna C. , Hasson Henna , von Thiele Schwarz Ulrica , James Sigrid , Ehrhart Mark G. , Ducarroz Simon , Sevdalis Nick , Willging Cathleen
Published: November 2019

Objective

International collaboration in science has received increasing attention given emphases on relevance, generalizability, and impact of research. Implementation science (IS) is a growing discipline that aims to translate clinical research findings into health services. Research is needed to identify efficient and effective ways to foster international collaboration in IS. Concept-mapping (CM) was utilized with a targeted sample for preliminary exploration of fostering international collaboration. Concept-mapping is a mixed-method approach (qualitative/quantitative) particularly suited for identifying essential themes and action items to facilitate planning among diverse stakeholders. We sought to identify key factors likely to facilitate productive and rewarding international collaborations in implementation research.

Results

We identified eleven dimensions: Strategic Planning; Practicality; Define Common Principles; Technological Tools for Collaboration; Funding; Disseminate Importance of Fostering International Collaboration in IS; Knowledge Sharing; Innovative & Adaptive Research; Training IS Researchers; Networking & Shared Identity; Facilitate Meetings. Strategic Planning and Funding were highest rated for importance and Strategic Planning and Networking and Shared Identity were rated most feasible to institute. Fostering international collaboration in IS can accelerate the efficiency, relevance, and generalizability of implementation research. Strategies should be developed and tested to improve international collaborations and engage junior and experienced investigators in collaborations advancing implementation science and practice.
Proteomic analysis of Nrk gene-disrupted placental tissue cells explains physiological significance of NRK
Authors: Denda Kimitoshi , Ida Kanako , Tanno Masataka , Nakao-Wakabayashi Kanako , Komada Masayuki , Hayashi Nobuhiro
Published: November 2019

Objective

NRK is a unique X chromosome-linked protein kinase expressed predominantly in placenta. The gene knockout causes placental overgrowth and delayed labor of Nrk-null fetuses from dams in mouse. To clarify unknown mechanisms behind the Nrk-null phenotypes, protein expression profiles were analyzed in the Nrk-null placenta using a high-performance two-dimensional electrophoresis methodology.

Results

Among around 1800 spots detected, we characterized a dozen protein spots whose expression levels were significantly altered in the Nrk-null placenta compared to wild-type. Analyzing these data sets is expected to reflect the difference physiologically in the presence or absence of NRK, facilitating the development of therapeutic strategies.
The effect of an active video game intervention on physical activity, motor performance, and fatigue in children with cancer: a randomized controlled trial
Authors: Hamari Lotta , Järvelä Liisa S. , Lähteenmäki Päivi M. , Arola Mikko , Axelin Anna , Vahlberg Tero , Salanterä Sanna
Published: November 2019

Objective

To evaluate the effect of active video games in promoting physical activity and motor performance, and reducing fatigue in children with cancer. A randomized controlled trial was conducted. The intervention included playing Nintendo Wii™Fit (Nintendo Co., Ltd., Kyoto, Japan) for 30 min/day for 8 weeks. Physical activity was estimated with accelerometers, physical activity diaries and questionnaires. Movement-ABC2 and PedsQL™ were used to examine motor performance and fatigue. Intervention experiences and fidelity were examined with an interview.

Results

Participants (n = 36 children with cancer, 3–16 years-old) were randomly assigned to the intervention and control groups. The median [min–max] accelerometer counts/h (500 [131–1130] vs 385 [116–1012], p = 0.63) and physical activity min/day (34 [0–150] vs 23 [0–260], p = 0.95) did not differ between the groups. Change between the pre-test and post-test regarding motor performance and fatigue was similar in both groups (motor performance p = 0.77; fatigue p = 1.00). Participants experienced playing active video games meaningful, but the intervention was not followed completely as instructed. Overall, the physical activity levels were low and one fourth of the children had or were at risk of having movement difficulties.

Trial registration: ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012)