bluuebunny/crossref_metadata_2025 huggingface dataset:
European violence risk and mental disorders (EU-VIORMED): a multi-centre prospective cohort study protocol
Authors: de Girolamo Giovanni , Carrà Giuseppe , Fangerau Heiner , Ferrari Clarissa , Gosek Pawel , Heitzman Janusz , Salize Hans , Walker Margaret , Wancata Johannes , Picchioni Marco
Published: December 2019

Background

The link between schizophrenia spectrum disorders (SSD) and violence is a core issue for most forensic psychiatric services. However, the drivers of violence in this population remain unclear, and, to date tools to predict violence risk have a range of limitations. Perhaps because of this uncertainty about the nature of violence risk, treatment programmes and care pathways for mentally disordered offenders vary substantially across the European Union, and differences in legal and policy frameworks are highly relevant.

Methods

The three-year EU-VIORMED project (Grant Number PP-2-3-2016, November 2017–October 2020) involves forensic centres in Italy, Austria, Germany, Poland, and the U.K. It aims to: (a) identify and compare violence risk factors, clinical needs, and decision making capacity in violent (N = 200, “cases”) and nonviolent patients with SSD (N = 200; “controls”) using a case-control design; (b) test the predictive validity of the HCR-20v3, OxMIS and FoVOx among cases alone (N = 200), using a prospective cohort study; and (c) compare forensic-psychiatric care pathways across the EU, in a continent wide service mapping study.

Discussion

Data collection started in September 2018 and continues. By September 2019, 333 participants have been enrolled (201 cases and 132 controls were recruited). Experts from 23 countries provided data for the service mapping exercise.

Trial registration

Retrospectively registered on January 2, 2019 as researchregistry4604 January 2, 2019
Migration to the US among rural Puerto Ricans who inject drugs: influential factors, sources of support, and challenges for harm reduction interventions
Authors: Abadie R. , Habecker P. , Gelpi-Acosta C. , Dombrowski K.
Published: December 2019

Background

While PWID of Puerto Rican origin have been migrating to the US for decades, the range of factors influencing their migration to the US and the resources they draw on to do so are not well understood. This is particularly true for rural Puerto Rican PWID, and the present study is the first empirical research to document migration patterns among this population. The specificities of their migration raise important challenges that need to be documented in order to implement more effective harm reduction policies at home (Puerto Rico) and abroad (US).

Methods

This paper draws from data obtained employing a modified NHBS survey which was administered to (N =296) PWID in four rural municipalities of Puerto Rico with participants 18 years or older. The primary dependent variables for this paper are the number of times a person has lived in the continental US, and if they are planning on moving to the continental US in the future.

Results

Findings suggest that 65% of the sample reported ever lived in the US and that 49% are planning on moving in the future. The number of times living in the US is associated with higher education and older age, but not with self-reported positive HIV or HCV statuses. Planning to move to the US is associated with knowing PWID who have moved or plan to move, negatively associated with age, and is not associated with HIV or HCV status. Around one third of those that lived in the US reported having some sort of support, with the majority receiving support from family sources. No participant received help to enter HIV/HCV treatment.

Conclusions

A multi-region approach to prevention is required to make a dent in curbing HIV/HCV transmission in this population. Understanding PWID migration patterns, risk behaviors, and health care needs in the US is now more important than ever as natural disasters prompted by human-made climate change will only increase in the future, raising demands not only for service providers but also harm reduction policies to cope with an increasing influx of “climate refugees” as PWID move across national borders.
“Development in well-being and social function among Danish hemophilia patients with HIV: a three-wave panel study spanning 24 years”
Authors: Ingvorsen Emilie B. , Schnohr Christina , Andersen Terkel , Lehrmann Lars , Funding Eva , Poulsen Lone H. , Holm Karen B. , Laursen Alex L. , Gerstoft Jan , Bjorner Jakob B.
Published: December 2019

Background

Between 1975 and 1985 a total of 91 Danish patients with moderate and severe hemophilia (PWH) was infected with HIV constituting a major scandal in the Danish health care system. This study describes the burden of HIV infection among Danish PWH by evaluating changes from 1988 to 2012 in well-being, social function, experiencing stigma and openness about disease among Danish HIV+ PWH.

Methods

Three anonymous surveys were conducted in 1988, 2001 and 2012 targeting all Danish patients with moderate to severe hemophilia. Survey responses were received from 53, 21 and 18 HIV+ PWH respectively. A matched comparison sample of HIV− PWH was identified for each survey-year, using propensity score matching. Differences for each survey-year and trends over time were analyzed using ordinal logistic regression.

Results

In 1988, HIV+ PWH had more psychosomatic symptoms than HIV− PWH, but in 2001 life satisfaction was higher among HIV+ PWH than among HIV− PWH. Tests of differences in trend over time showed larger improvements in life satisfaction among HIV+ PWH than HIV− PWH, while HIV− PWH showed an increase in educational level compared to HIV+ PWH. Analysis restricted to HIV+ PWH showed an increase in perceived stigmatization.

Conclusions

Differences between Danish HIV+ and HIV− PWH regarding well-being and psychosomatic symptoms seem to have evened out between 1988 and 2012. However, results suggest that HIV+ PWH still experience stigmatization and lower levels of education.
Reframing healthy food choices: a content analysis of Australian healthy eating blogs
Authors: Mete Rebecca , Curlewis Jayne , Shield Alison , Murray Kristen , Bacon Rachel , Kellett Jane
Published: December 2019

Background

Blogs are widely being used by health professionals and consumers to communicate and access nutrition information. There are numerous benefits for dietitians to establish and contribute to healthy eating blogs. In particular, to disseminate evidence-based nutrition information to promote healthier dietary practices. The aim of this study was to explore characteristics of popular healthy eating blogs and inform the provision of healthy eating information in the Australian context.

Methods

A content analysis approach was used to identify characteristics of popular Australian healthy eating blogs. A purposive and snowball sampling approach was used to identify healthy eating blogs from search engines including Google, Bing and Yahoo. Blogs were deemed eligible if: (1) the author self-identified as a health professional; (2) the blog was written by a single author; (3) the blog was written by an Australian author; (4) the blog had a minimum of one post per month, and (5) the blog focused on communicating healthy eating information to the general adult population.

Results

Five popular blogs were followed over a three-month period (December 2017–March 2018), with 76 blog posts included for analysis. Characteristics of these popular blogs were examined and four main features were identified: (i) clearly conveying the purpose of each post; (ii) developing a strong understanding of the reader base and their preferences; (iii) employing a consistent writing style; use of vocabulary and layout; and (iv) communicating healthy eating information in a practical manner. These findings reveal important insight into the features that promote effective nutrition communication within this context.

Conclusion

Findings from this study highlight common characteristics of popular healthy eating blogs. Future research into the development of blog guidelines which incorporate the characteristics identified in this study can support dietitians in establishing or contributing to the successful provision of evidence-based nutritional information through blogs.
Associations between dietary patterns and 10-year cardiovascular disease risk score levels among Chinese coal miners——a cross-sectional study
Authors: Sun Qian , Ma Jin-Sha , Wang Hui , Xu Shu-Hong , Zhao Jun-Kang , Gao Qian , Huang Jian-Jun , Wang Tong
Published: December 2019

Background

Diet-related cardiovascular diseases have produced a large health burden in China. Coal miners are a high-risk population for cardiovascular disease, but there is little evidence concerning associations between coal miners’ dietary patterns and their 10-year cardiovascular disease risk score levels.

Methods

The study included 2632 participants and focused on dietary patterns associated with higher 10-year cardiovascular disease risk score levels. A valid semi-quantitative food frequency questionnaire was used to collect data regarding dietary intake, and dietary patterns were identified using factor analysis combined with cluster analysis. Logistic regression was used to assess associations between dietary patterns and 10-year cardiovascular disease risk score levels.

Results

For ground workers, compared with the ‘Healthy’ pattern, the ‘High-salt’ and ‘Refined grains’ patterns were significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.50, 95% CI: 1.02–2.21; OR: 1.92, 95% CI: 1.26–2.93) and 10-year ischemic cardiovascular disease risk score level (OR: 2.18, 95% CI: 1.25–3.80; OR: 2.64, 95% CI: 1.48–4.72) adjusted for gender, and behavioural and socioeconomic factors. The ‘High-fat and salt’ pattern was significantly associated with higher 10-year ischemic cardiovascular disease risk score level (OR: 1.97, 95% CI: 1.13–3.42). For underground workers, the ‘High-salt’ pattern was significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.65, 95% CI: 1.16–2.36) and 10-year ischemic cardiovascular disease risk score level (OR: 1.76, 95% CI: 1.09–2.84).

Conclusions

This study provides evidence for dietary patterns associated with higher 10-year cardiovascular disease risk score levels in Chinese miners, and facilitates relevant departments in designing effective dietary guidelines to ameliorate dietary structures.
Extent of misuse and dependence of codeine-containing products among medical and pharmacy students in a Nigerian University
Authors: Akande-Sholabi Wuraola , Adisa Rasaq , Ilesanmi Olayinka S. , Bello Ayomide E.
Published: December 2019

Background

Misuse and dependency of opioids especially codeine-containing products is of increasing global concern. Inappropriate use of opioids among healthcare students could affect quality of service and ethical conducts of these future professionals, thereby putting the society at risk. This study aimed to evaluate knowledge and perception of medical and pharmacy students in a Nigerian tertiary University on use of opioids with focus on codeine-containing products.

Methods

A cross-sectional survey among 335-medical and 185-pharmacy students from University of Ibadan, Nigeria, between September and December 2018, using a self-administered semi-structured questionnaire.

Results

A total of 178 (34.2%) in multiple responses had used opioid-containing products among the respondents, of this, 171 (96.1%) used codeine-containing formulation. Precisely, 146 (28.1%) of the students had used codeine-containing products before, of this, 16 (11.0%) used the products for non-medical or recreational purpose regarded as a misuse/abuse. In all, 201 (38.7%) had good knowledge of opioid use, with 51 (34.9%) among those who had used opioids and 150 (40.1%) among those who had not used opioids (X2 = 1.186; p = 0.276). Majority (469; 90.2%) had good perception of risks associated with opioid use; comprising (130; 89.0%) among those who had taken opioids and (339; 90.6%) among those who had not taken opioids before (X2 = 0.304; p = 0.508). Logistic-regression shows that students who experienced some side effects to be experienced again 22.1 [AOR = 22.1, 95% CI: (5.98–81.72)] as well as those pressured into using codeine-containing products 10.6 [AOR = 10.6, 95% CI: (1.36–82.39)] had more tendency of misuse.

Conclusion

There is a potential for misuse of codeine-containing products among medical and pharmacy students. Peer-influence and experience of some side effects are possible predictors of misuse among the students. Thus, healthcare students’ curriculum should incorporate preventive programme, while public education and policy that favours peer-support programme on medication misuse is advocated for healthcare students.
Anti-inflammatory, analgesic and acute toxicity effects of fermented soybean
Authors: Yusof Hamidah Mohd , Ali Norlaily Mohd , Yeap Swee Keong , Ho Wan Yong , Beh Boon Kee , Koh Soo Peng , Long Kamariah , Alitheen Noorjahan Banu
Published: December 2019

Background

Tempeh is a widely known fermented soybean that contains elevated level of bioactive contents. Our previous study has shown that anaerobic fermented Nutrient Enriched Soybean Tempeh (NESTE) with increase amino acid and antioxidant levels possessed better hepatoprotective effect than raw soybean.

Methods

In this study, the anti-inflammatory effect of the NESTE aqueous extract and raw soybean aqueous extract (SBE) were evaluated by quantifying the inhibition of IL-1β, TNF-α and nitric oxide (NO) secretion in LPS treated RAW 264.7 cell in vitro. On the other hand, in vivo oral acute toxicity effect of the extract was tested on mice at the dose of 5000 mg/kg body weight. In vivo oral analgesic effect of both aqueous extracts at 200 and 1000 mg/kg body weight was evaluated by the hot plate test.

Results

In the in vitro anti-inflammatory study, 5 mg/mL NESTE was able to inhibit 25.50 ± 2.20%, 35.88 ± 3.20% and 28.50 ± 3.50% of NO, IL-1β and TNF-α production in LPS treated RAW 264.7 cells without inducing cytotoxic effect on the cells. However, this effect was lower than 4 μg/mL of curcumin, which inhibited NO, IL-1β and TNF-α production by 89.50 ± 5.00%, 78.80 ± 6.20% and 87.30 ± 4.00%, respectively. In addition, 1.5 to 2.5-fold increase of latency period up to 120 min for mice in the hot plate test was achieved by 1000 mg/kg NESTE. The analgesic effect of NESTE was better than 400 mg/kg of acetyl salicylic acid, which only increased ~ 1.7-fold of latency period up to 90 min. Moreover, NESTE did not show acute toxicity (no LD50) up to 5000 mg/kg body weight.

Conclusion

NESTE is a nutritious food ingredient with potential anti-inflammatory and analgesic effects.
Incorporating medical code descriptions for diagnosis prediction in healthcare
Authors: Ma Fenglong , Wang Yaqing , Xiao Houping , Yuan Ye , Chitta Radha , Zhou Jing , Gao Jing
Published: December 2019

Background

Diagnosis aims to predict the future health status of patients according to their historical electronic health records (EHR), which is an important yet challenging task in healthcare informatics. Existing diagnosis prediction approaches mainly employ recurrent neural networks (RNN) with attention mechanisms to make predictions. However, these approaches ignore the importance of code descriptions, i.e., the medical definitions of diagnosis codes. We believe that taking diagnosis code descriptions into account can help the state-of-the-art models not only to learn meaning code representations, but also to improve the predictive performance, especially when the EHR data are insufficient.

Methods

We propose a simple, but general diagnosis prediction framework, which includes two basic components: diagnosis code embedding and predictive model. To learn the interpretable code embeddings, we apply convolutional neural networks (CNN) to model medical descriptions of diagnosis codes extracted from online medical websites. The learned medical embedding matrix is used to embed the input visits into vector representations, which are fed into the predictive models. Any existing diagnosis prediction approach (referred to as the base model) can be cast into the proposed framework as the predictive model (called the enhanced model).

Results

We conduct experiments on two real medical datasets: the MIMIC-III dataset and the Heart Failure claim dataset. Experimental results show that the enhanced diagnosis prediction approaches significantly improve the prediction performance. Moreover, we validate the effectiveness of the proposed framework with insufficient EHR data. Finally, we visualize the learned medical code embeddings to show the interpretability of the proposed framework.

Conclusions

Given the historical visit records of a patient, the proposed framework is able to predict the next visit information by incorporating medical code descriptions.
Heterogeneous information network based clustering for precision traditional Chinese medicine
Authors: Chen Xintian , Ruan Chunyang , Zhang Yanchun , Chen Huijuan
Published: December 2019

Background

Traditional Chinese medicine (TCM) is a highly important complement to modern medicine and is widely practiced in China and in many other countries. The work of Chinese medicine is subject to the two factors of the inheritance and development of clinical experience of famous Chinese medicine practitioners and the difficulty in improving the service capacity of basic Chinese medicine practitioners. Heterogeneous information networks (HINs) are a kind of graphical model for integrating and modeling real-world information. Through HINs, we can integrate and model the large-scale heterogeneous TCM data into structured graph data and use this as a basis for analysis.

Methods

Mining categorizations from TCM data is an important task for precision medicine. In this paper, we propose a novel structured learning model to solve the problem of formula regularity, a pivotal task in prescription optimization. We integrate clustering with ranking in a heterogeneous information network.

Results

The results from experiments on the Pharmacopoeia of the People’s Republic of China (ChP) demonstrate the effectiveness and accuracy of the proposed model for discovering useful categorizations of formulas.

Conclusions

We use heterogeneous information networks to model TCM data and propose a TCM-HIN. Combining the heterogeneous graph with the probability graph, we proposed the TCM-Clus algorithm, which combines clustering with ranking and classifies traditional Chinese medicine prescriptions. The results of the categorizations can help Chinese medicine practitioners to make clinical decision.
Prevalence of child marriage and its impact on fertility outcomes in 34 sub-Saharan African countries
Authors: Yaya Sanni , Odusina Emmanuel Kolawole , Bishwajit Ghose
Published: December 2019

Background

The issue of child marriage is a form of human rights violation among young women mainly in resource-constrained countries. Over the past decades, child marriage has gained attention as a threat to women’s health and autonomy. This study explores the prevalence of child marriage among women aged 20–24 years in sub-Saharan Africa countries and examines the association between child marriage and fertility outcomes.

Methods

Latest DHS data from 34 sub-Saharan African countries were used in this study. Sixty thousand two hundred and fifteen women aged 20–24 years were included from the surveys conducted 2008–2017. The outcome variables were childbirth within the first year of marriage (early fertility), first preceding birth interval less than 24 months (rapid repeat of childbirth), unintended pregnancy, lifetime pregnancy termination, the use of modern contraceptive methods, lifetime fertility and any childbirth. The main explanatory variable was child marriage (< 18 years) and the associations between child marriage and fertility outcomes were examined from the ever-married subsample to estimate odds ratios (ORs) and 95% CIs using binary logistic regression models.

Results

In the study population, the overall prevalence of women who experience child marriage was 54.0% while results showed large disparities across sub-Saharan African countries ranging from 16.5 to 81.7%. The prominent countries in child marriage were; Niger (81.7%), Chad (77.9%), Guinea (72.8%), Mali (69.0%) and Nigeria (64.0%). Furthermore, women who experience child marriage were 8.00 times as likely to have ≥3 number of children ever born (lifetime fertility), compared to women married at ≥18 years (OR = 8.00; 95%CI: 7.52, 8.46). Women who experience child marriage were 1.13 times as likely to use modern contraceptive methods, compared to adult marriage women (OR = 1.13; 95%CI: 1.09, 1.19). Those who married before the legal age were 1.27 times as likely to have lifetime terminated pregnancy, compared to women married at ≥18 years (OR = 1.27; 95%CI: 1.20, 1.34). Also women married at < 18 years were more likely to experience childbirth, compared to women married later (OR = 5.83; 95%CI: 5.45, 6.24). However, women married at < 18 years had a reduction in early childbirth and a rapid repeat of childbirth respectively.

Conclusion

Implementing policies and programmmes against child marriage would help to prevent adverse outcomes among women in sub-Saharan Africa. Also, social change programmes on child-marriage would help to reduce child marriage, encourage the use of modern contraceptive, which would minimize lifetime terminated pregnancy and also children ever born.
Suicide prevention and depression apps’ suicide risk assessment and management: a systematic assessment of adherence to clinical guidelines
Authors: Martinengo Laura , Van Galen Louise , Lum Elaine , Kowalski Martin , Subramaniam Mythily , Car Josip
Published: December 2019

Background

There are an estimated 800,000 suicides per year globally, and approximately 16,000,000 suicide attempts. Mobile apps may help address the unmet needs of people at risk. We assessed adherence of suicide prevention advice in depression management and suicide prevention apps to six evidence-based clinical guideline recommendations: mood and suicidal thought tracking, safety plan development, recommendation of activities to deter suicidal thoughts, information and education, access to support networks, and access to emergency counseling.

Methods

A systematic assessment of depression and suicide prevention apps available in Google Play and Apple’s App Store was conducted. Apps were identified by searching 42matters in January 2019 for apps launched or updated since January 2017 using the terms “depression,” “depressed,” “depress,” “mood disorders,” “suicide,” and “self-harm.” General characteristics of apps, adherence with six suicide prevention strategies identified in evidence-based clinical guidelines using a 50-question checklist developed by the study team, and trustworthiness of the app based on HONcode principles were appraised and reported as a narrative review, using descriptive statistics.

Results

The initial search yielded 2690 potentially relevant apps. Sixty-nine apps met inclusion criteria and were systematically assessed. There were 20 depression management apps (29%), 3 (4%) depression management and suicide prevention apps, and 46 (67%) suicide prevention apps. Eight (12%) depression management apps were chatbots. Only 5/69 apps (7%) incorporated all six suicide prevention strategies. Six apps (6/69, 9%), including two apps available in both app stores and downloaded more than one million times each, provided an erroneous crisis helpline number. Most apps included emergency contact information (65/69 apps, 94%) and direct access to a crisis helpline through the app (46/69 apps, 67%).

Conclusions

Non-existent or inaccurate suicide crisis helpline phone numbers were provided by mental health apps downloaded more than 2 million times. Only five out of 69 depression and suicide prevention apps offered all six evidence-based suicide prevention strategies. This demonstrates a failure of Apple and Google app stores, and the health app industry in self-governance, and quality and safety assurance. Governance levels should be stratified by the risks and benefits to users of the app, such as when suicide prevention advice is provided.
Validation of an equine serum amyloid A assay with an unusually broad working range
Authors: Jacobsen Stine , Vinther Anne Mette , Kjelgaard-Hansen Mads , Nielsen Lise Nikolic
Published: December 2019

Background

Serum amyloid A (SAA) is a major equine acute phase protein and of great value in detection and monitoring of inflammation. A new immunoturbidometric assay based on monoclonal antibodies (VET-SAA, Eiken Chemical Co., Japan) may be useful for SAA measurements in routine diagnostic laboratories. The aim of the study was to validate the VET-SAA immunoturbidometric assay and use it to measure serum SAA concentrations in a variety of clinical cases. Precision was assessed by intra- and interassay coefficients of variation of repeated measurements of serum pools (low, intermediate, high concentrations of SAA). Accuracy was estimated by linearity under dilution. Detection limit was determined by replicate determinations of ionized water. Measurements were compared to measurements performed in a previously validated SAA assay (LZSAA assay, Eiken Chemical Co., Japan). Subsequently, the VET-SAA assay was used for measuring serum SAA concentrations in horses with and without inflammation.

Results

Detection limit was 1.2 mg/L. Without modifications, the assay measured SAA concentrations with acceptable reliability in a broad concentration range (0 to > 6000 mg/L). In the 0–3000 mg/L range, the assay demonstrated good precision and accuracy, and concentrations correlated well with those obtained in the LZSAA assay, albeit with a slight systematic bias. Concentrations of SAA assessed in horses with and without inflammation followed the expected pattern, with significantly higher concentrations in horses with systemic inflammation than in healthy horses and horses with non-inflammatory disease.

Conclusions

The assay was unique in its ability to measure SAA concentrations with acceptable reliability over an extreme concentration range. This is relevant in the equine species, where SAA concentrations may reach very high concentrations.
AGI-134: a fully synthetic α-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models
Authors: Shaw Stephen M. , Middleton Jenny , Wigglesworth Kim , Charlemagne Amber , Schulz Oliver , Glossop Melanie S. , Whalen Giles F. , Old Robert , Westby Mike , Pickford Chris , Tabakman Rinat , Carmi-Levy Irit , Vainstein Abi , Sorani Ella , Zur Arik A. , Kristian Sascha A.
Published: December 2019

Background

Treatments that generate T cell-mediated immunity to a patient’s unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galα1-3Galβ1-4GlcNAc (α-Gal) in situ leading to opsonization with pre-existing natural anti-α-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity.

Methods

Various immunological effects of coating tumor cells with α-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (α1,3GT−/−) mice. CDC and phagocytosis data were analyzed by one-way ANOVA, ADCC results by paired t-test, distal tumor growth by Mantel–Cox test, C5a data by Mann–Whitney test, and single tumor regression by repeated measures analysis.

Results

In vitro, α-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8α+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in α1,3GT−/−mice, intratumoral AGI-134 administration leads to primary tumor regression and has a robust abscopal effect, i.e., it protects from the development of distal, uninjected lesions. Combinations of AGI-134 and anti-PD-1 antibody shows a synergistic benefit in protection from secondary tumor growth.

Conclusions

We have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment.
Hyperglycemia promotes Snail-induced epithelial–mesenchymal transition of gastric cancer via activating ENO1 expression
Authors: Xu Xin , Chen Bang , Zhu Shaopu , Zhang Jiawei , He Xiaobo , Cao Guodong , Chen Bo
Published: December 2019

Background

Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear.

Method

Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion.

Results

Among the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC.

Conclusions

Our results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.
High cases of submicroscopic Plasmodium falciparum infections in a suburban population of Lagos, Nigeria
Authors: Umunnakwe Florence A. , Idowu Emmanuel T. , Ajibaye Olusola , Etoketim Blessed , Akindele Samuel , Shokunbi Aminat O. , Otubanjo Olubunmi A. , Awandare Gordon A. , Amambua-Ngwa Alfred , Oyebola Kolapo M.
Published: December 2019

Background

Asymptomatic malaria parasites are significant sources of infections for onward malaria transmission. Conventional tools for malaria diagnosis such as microscopy and rapid diagnostic test kits (RDT) have relatively low sensitivity, hence the need for alternative tools for active screening of such low-density infections.

Methods

This study tested var acidic terminal sequence-based (varATS) quantitative polymerase chain reaction (qPCR) for screening asymptomatic Plasmodium falciparum infections among dwellers of a sub-urban community in Lagos, Nigeria. Clinically healthy participants were screened for malaria using microscopy, RDT and varATS qPCR techniques. Participants were stratified into three age groups: 1–5, 6–14 and > 14 years old.

Results

Of the 316 participants screened for asymptomatic malaria infection, 78 (24.68%) were positive by microscopy, 99 (31.33%) were positive by RDT and 112 (35.44%) by varATS qPCR. Participants aged 6–14 years had the highest prevalence of asymptomatic malaria, with geometric means of ~ 116 parasites/µL and ~ 6689 parasites/µL as detected by microscopy and varATS, respectively.

Conclusion

This study has revealed high prevalence of asymptomatic malaria in the study population, with varATS detecting additional sub-microscopic infections. The highest concentration of asymptomatic malaria was observed among school-age children between 6 and 14 years old. A large-scale screening to identify other potential hotspots of asymptomatic parasites in the country is recommended.
KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3
Authors: Lan Tian , Li Hui , Zhang Delin , Xu Lin , Liu Hailing , Hao Xiangyong , Yan Xiaokai , Liao Haotian , Chen Xiangzheng , Xie Kunlin , Li Jiaxin , Liao Mingheng , Huang Jiwei , Yuan Kefei , Zeng Yong , Wu Hong
Published: December 2019

Background

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined.

Methods

Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitroandin vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429.

Results

KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as acis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3.

Conclusion

Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
A client-centered relational framework on barriers to the integration of HIV and substance use services: a systematic review
Authors: Pinto Rogério Meireles , Chen Yun , Park Sunggeun ( Ethan)
Published: December 2019

Background

Given the close connection between human immunodeficiency virus (HIV) infection and substance use disorder (SUD), access to integrated HIV and SUD services is critical for individuals experiencing both challenges and their biopsychosocial conditions.

Method

Adopting an integrative method, this systematic review included 23 empirical studies published between 2000 and 2018. Articles investigated providers’ and clients’ perspectives on barriers to accessing integrated HIV and SUD services in various service settings (e.g., HIV primary care, SUD treatment, pharmacy).

Results

Using a client-centered relational framework, we identified barriers in three relational domains with “the client” as the focus of each: client-provider, client-organization, and client-system. The review shows that (1) barriers to HIV and SUD services do not exist in isolation, but in the dynamics within and across three relational domains; (2) service providers and clients often have different perceptions about what constitutes a barrier and the origin of such barriers; and (3) interprofessional and interorganizational collaborations are crucial for integrating HIV and SUD services.

Conclusion

This review points out the limitations of the conventional paradigm grouping barriers to service integration into isolated domains (client, provider, organization, or system). Reforms in service arrangements and provider training are recommended to address barriers to integrated services.
Development and validation of a prognostic nomogram for predicting early recurrence after curative resection of stage II/III gastric cancer
Authors: Ma Min , Xiao Haifan , Li Liang , Yin Xianli , Zhou Huijun , Quan Hu , Ouyang Yongzhong , Huang Gang , Li Xiaorong , Xiao Hua
Published: December 2019

Background

The biological behavior of early recurrence is more invasive and the prognosis is worse in gastric cancer (GC). The risk of early recurrence (ER) for GC in stage II/III has not been reported of which the majority of GC patients are in China. Therefore, it is necessary to analyze the ER of gastric cancer in stage II/III.

Methods

The medical records of 1511 consecutive stage II/III GC patients who received resections were retrospectively reviewed. They were randomly classified into either a development or validation group at a ratio of 7:3. The nomogram was constructed based on prognostic factors using logistic regression analysis and was validated by bootstrap resampling and validation dataset, respectively. Concordance index (C-index) values and calibration curves were used to evaluate the predictive accuracy and discriminatory capability.

Results

Three hundred eleven patients experienced ER, accounting for 20.58% of the GC patients investigated. Multivariate logistic regression analysis identified tumors located at upper, middle third, or mixed, a positive lymph node ratio ≥ 0.335, pTNM stage III, lymphocyte count < 1.5 × 109/L, postoperative infection complications and adjuvant chemotherapy < 6 cycles were all independent predictors for ER after curative resection of stage II/III GC. The C-index value obtained for the model was 0.780 (95% CI, 0.747–0.813), and the calibration curves of validation group yielded a C-index value of 0.739 (95% CI, 0.684–0.794), suggesting the practicability of the model.

Conclusions

The nomogram which was developed for predicting ER of stage II/III GC after surgery had good accuracy and was verified through both internal and external validation. The nomogram established can assist clinicians in determining the optimal therapy strategies in counseling, adjuvant treatments, and subsequent follow-up planning.
Fluorescent analysis of boar sperm capacitation process in vitro
Authors: Ded Lukas , Dostalova Pavla , Zatecka Eva , Dorosh Andrej , Komrskova Katerina , Peknicova Jana
Published: December 2019

Background

Capacitation involves physiological changes that spermatozoa must undergo in the female reproductive tract or in vitro to obtain the ability to bind, penetrate and fertilize the egg. Up to date, several methods have been developed to characterize this complex biological process. The goal of the presented study is to mutually compare several fluorescent techniques, check their ability to detect changes in molecular processes during the capacitation progress and determine their ability to predict the percentage of acrosome reacted (AR) sperm after the exposure to solubilized zona pellucida (ZP). The capacitation process was analyzed using four fluorescent techniques: 1. chlortetracycline (CTC) staining, 2. anti-acrosin antibody (ACR.2) assay, 3. anti-phosphotyrosine (pY) antibody assay, 4. fluorescein isothiocyanate-conjugated phalloidin (FITC-phall) assay. All these methods were tested using fluorescent microscopy and flow cytometry.

Results

All selected methods are capable to detect the capacitation progress of boar sperm in vitro, but there are significant differences in their outcome when using fluorescent microscopy or flow cytometry experimental arrangements and subsequent statistical analysis (KW-ANOVA). Also, the ability to predict the absolute numbers of sperm which will undergo ZP-induced AR differ significantly (CTC and ACR.2 gave the best predictions).

Conclusions

Our study compared four largely used methods used to characterize capacitation process, highlighted their differences and showed that all are able to detect capacitation progress, CTC and ACR.2 are furthermore able to accurately predict the percentage of AR sperm after ZP-induced AR.
The effects of small-scale physical and social environmental interventions on walking behaviour among Dutch older adults living in deprived neighbourhoods: results from the quasi-experimental NEW.ROADS study
Authors: Prins R. G. , Kamphuis C. B. M. , Van Lenthe F. J.
Published: December 2019

Purpose

Improving the physical and social conditions of residential neighbourhoods may increase walking, especially among older people. Evidence on the effects of physical and social environmental interventions, and particularly the combination of both, on walking behaviour is scarce. We evaluated the effects of a small-scale physical environmental intervention (designated walking route), a social environmental intervention (neighbourhood walking group) and the combination of both on walking behaviour of older adults living in deprived neighbourhoods.

Methods

Survey data of 644 older adults residing in four deprived neighbourhoods of Rotterdam, the Netherlands, were used to compare changes in walking behaviour over time (weekly minutes spent recreational walking, utilitarian walking and total walking) of those exposed to 1) a designated walking route (physical condition), 2) walking groups (social condition), 3) walking routes and walking groups (combined condition), and 4) no intervention (control condition). Measurements took place at baseline (T0), and 3 months (T1) and 9 months (T2) after the intervention. Data were analysed on a multiple imputed dataset, using multi-level negative binomial regression models, adjusting for clustering of observations within individuals. All models were adjusted for demographic covariates.

Results

Total time spent walking per week increased between T0 and T1 for all conditions. The Incidence Rate Ratio (IRR) for the physical condition was 1.46 (95% CI:1.06;2.05) and for the social intervention 1.52 (95%CI:1.07;2.16). At T2, these differences remained significant for the physical condition, but not for the social condition and the combined condition. These findings were mirrored for utilitarian walking. No evidence was found for an effect on recreational walking.

Conclusion

Implementing small scale, feasible, interventions in a residential neighbourhood may increase total and utilitarian walking behaviour among older adults.
Effect of workplace physical activity interventions on the cardio-metabolic health of working adults: systematic review and meta-analysis
Authors: Mulchandani Rubina , Chandrasekaran Ambalam M. , Shivashankar Roopa , Kondal Dimple , Agrawal Anurag , Panniyammakal Jeemon , Tandon Nikhil , Prabhakaran Dorairaj , Sharma Meenakshi , Goenka Shifalika
Published: December 2019

Background

Adults in urban areas spend almost 77% of their waking time being inactive at workplaces, which leaves little time for physical activity. The aim of this systematic review and meta-analysis was to synthesize evidence for the effect of workplace physical activity interventions on the cardio-metabolic health markers (body weight, waist circumference, body mass index (BMI), blood pressure, lipids and blood glucose) among working adults.

Methods

All experimental studies up to March 2018, reporting cardio-metabolic worksite intervention outcomes among adult employees were identified from PUBMED, EMBASE, COCHRANE CENTRAL, CINAHL and PsycINFO. The Cochrane Risk of Bias tool was used to assess bias in studies. All studies were assessed qualitatively and meta-analysis was done where possible. Forest plots were generated for pooled estimates of each study outcome.

Results

A total of 33 studies met the eligibility criteria and 24 were included in the meta-analysis. Multi-component workplace interventions significantly reduced body weight (16 studies; mean diff: − 2.61 kg, 95% CI: − 3.89 to − 1.33) BMI (19 studies, mean diff: − 0.42 kg/m2, 95% CI: − 0.69 to − 0.15) and waist circumference (13 studies; mean diff: − 1.92 cm, 95% CI: − 3.25 to − 0.60). Reduction in blood pressure, lipids and blood glucose was not statistically significant.

Conclusions

Workplace interventions significantly reduced body weight, BMI and waist circumference. Non-significant results for biochemical markers could be due to them being secondary outcomes in most studies. Intervention acceptability and adherence, follow-up duration and exploring non-RCT designs are factors that need attention in future research.

Prospero registration number: CRD42018094436.
The legacy of Malcolm Beverley Segal (1937–2019) on the science and fields concerned with choroid plexus and cerebrospinal fluid physiology
Authors: Chodobski Adam , Ghersi-Egea Jean-François , Preston-Kennedy Jane , Redzic Zoran , Strazielle Nathalie , Szmydynger-Chodobska Joanna , Thorne Robert G.
Published: December 2019

This article highlights the scientific achievements, professional career, and personal interactions of Malcolm B. Segal who passed away in July this year. Born in 1937 in Goodmayes, Essex, UK, Segal rose to the Chairman position in the Division of Physiology at United Medical and Dental School of Guy’s and St. Thomas’ Hospitals, retiring in 2006 after his long professional career in biomedical science. Being trained in Hugh Davson’s laboratory, Segal became one of the pioneers in research on cerebrospinal fluid physiology and the choroid plexus. During the course of his career, Segal himself trained a number of young scientists and collaborated with many colleagues around the world, making long-lasting friendships along the way. In addition to his professional accomplishments as a researcher and educator, Segal was an avid sailor and wine connoisseur, and enjoyed teaching classes on navigation and wine tasting.
MicroRNA-937 is overexpressed and predicts poor prognosis in patients with colon cancer
Authors: Liu Huiya , Ma Lin , Wang Ling , Yang Yizuo
Published: December 2019

Background

Colon cancer is a heterogeneous tumor and a leading cause of cancer-related mortality. MicroRNA (miRNA) has been proposed as the biomarker in cancers. The aim of this study was to investigate the clinical significance and potential functional role of miR-937 in colon cancer.

Methods

In the present study, reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of miR-937 in colon cancer tissues and cell lines. Kaplan-Meier curve and Cox regression analyses were used to determine the prognostic impact of miR-937 on survival. Cell Counting Kit-8 and Transwell assays were performed to examine cell proliferation, migration, and invasion, respectively.

Results

miR-937 was significantly upregulated in colon cancer tissues and cell lines. Clinical analysis results showed that miR-937 expression was associated with lymph node metastasis and TNM stage. Patients with high miR-937 expression predicted a shorter overall survival rate. Functionally, overexpression of miR-937 promoted cell proliferation, migration, and invasion, while inhibition of miR-937 inhibited these cellular behaviors in vitro.

Conclusions

These results suggested that miR-937 may act as a prognostic biomarker and a potential target for therapeutic strategy, as well as promote proliferation, migration, and invasion of colon cancer.