bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review
Authors: Cheng Yue I. , Gan Yun Cui , Liu Dan , Davies Michael P. A. , Li Wei Min , Field John K.
Published: November 2019

Background

Accumulating evidence indicates inherited risk in the aetiology of lung cancer, although smoking exposure is the major attributing factor. Family history is a simple substitute for inherited susceptibility. Previous studies have shown some possible yet conflicting links between family history of cancer and EGFR mutation in lung cancer. As EGFR-mutated lung cancer favours female, never-smoker, adenocarcinoma and Asians, it may be argued that there may be some underlying genetic modifiers responsible for the pathogenesis of EGFR mutation.

Methods

We searched four databases for all original articles on family history of malignancy and EGFR mutation status in lung cancer published up to July 2018. We performed a meta-analysis by using a random-effects model and odds ratio estimates. Heterogeneity and sensitivity were also investigated. Then we conducted a second literature research to curate case reports of familial lung cancers who studied both germline cancer predisposing genes and their somatic EGFR mutation status; and explored the possible links between cancer predisposing genes and EGFR mutation.

Results

Eleven studies have been included in the meta-analysis. There is a significantly higher likelihood of EGFR mutation in lung cancer patients with family history of cancer than their counterparts without family history, preferentially in Asians (OR = 1.35[1.06–1.71], P = 0.01), those diagnosed with adenocarcinomas ((OR = 1.47[1.14–1.89], P = 0.003) and those with lung cancer-affected relatives (first and second-degree: OR = 1.53[1.18–1.99], P = 0.001; first-degree: OR = 1.76[1.36–2.28, P < 0.0001]). Familial lung cancers more likely have concurrent EGFR mutations along with mutations in their germline cancer predisposition genes including EGFR T790 M, BRCA2 and TP53. Certain mechanisms may contribute to the combination preferences between inherited mutations and somatic ones.

Conclusions

Potential genetic modifiers may contribute to somatic EGFR mutation in lung cancer, although current data is limited. Further studies on this topic are needed, which may help to unveil lung carcinogenesis pathways. However, caution is warranted in data interpretation due to limited cases available for the current study.
Nebulized hypertonic saline 3% for 1 versus 3 days in hospitalized bronchiolitis: a blinded non-inferiority randomized controlled trial
Authors: Beal Gaëlle , Barbier Catherine , Thoret Sophie , Rubio Amandine , Bonnet Mathilde , Mazet Roseline , Ego Anne , Pin Isabelle
Published: November 2019

Background

The use and optimal duration of treatment with nebulized hypertonic saline (HS) in infants hospitalized for acute bronchiolitis is unclear. The objective was to compare the efficacy of 1 versus 3 days of nebulized 3% HS at 72 h of treatment. We conducted a blinded non-inferiority randomized controlled trial including infants aged less than 12 months old, hospitalized for a moderate bronchiolitis.

Methods

Nebulisations of 3% HS for 1 day were followed by either the continuation of 3% HS (HS3d group) or switched to 0.9% normal isotonic saline (HS1d group) for 2 days Randomization was performed according to a predefined list with a 1:1 ratio, obtained with a random generator number with blocks.. Main outcome was mean Wang clinical severity score (CSS) after 72 h of treatment.

Results

One hundred sixteen infants (HS1d n = 59 and HS3d n = 57), were included over two epidemic seasons from 2014 to 2016, but recruitement did not reach the planned sample size. The difference for the Wang CSS score in the HS3d vs HS1d group was 0.71 [IC 90% 0.1; 1.3], above the precluded value of 0.4 set in the protocol defining the non-inferiority of shorter treatment duration. Clinical remission was more rapidly obtained in the HS3d than in HS1d (2.3 ± 1.6 vs 2.9 ± 1.4 days, p = 0.04), with a non-significant tendency for less need of nutritional support and supplemental oxygen in HS3d group. Clinical worsening and treatment intolerance were similar in the 2 groups.

Conclusions

Despite being underpowered, results seem not to be in favour of reducing the duration of nebulised HS treatment from 3 to 1 day in acute moderate bronchiolitis.

Trial registration

Clinical trials NCT 02538458, October 2014.
Predictors of professional help-seeking for emotional problems in Afghan and Iraqi refugees in Australia: findings from the Building a New Life in Australia Database
Authors: Slewa-Younan Shameran , Rioseco Pilar , Guajardo Maria Gabriela Uribe , Mond Jonathan
Published: November 2019

Background

Refugees are particularly vulnerable to poor mental health outcomes due to exposure to pre migration trauma and post migration stressors. Research has demonstrated evidence to suggest that the professional help-seeking among refugee groups is low or problematic. This study seeks to examine help-seeking for emotional problems in two large samples of Iraqi and Afghan refugees in Australia.

Methods

This study uses data from two waves of the Building a New Life in Australia, the longitudinal study of Humanitarian migrants. The data was collected face-to-face between 2013 and 2016, among humanitarian migrants. All participants held a permanent protection visa and had arrived in Australia or been granted their visa between period of May to December 2013. The study sample included 1288 participants born in Iraq and Afghanistan (aged 15 and over). In the Wave 3 interview (2015–2016) participants reported on professional help received to deal with emotional problems.

Results

Approximately 36 and 37% of the Iraqi and Afghan groups respectively, reported seeking help for emotional problems. Within the Iraqi group, associations between mental health status, namely general psychological distress and PTSD and help-seeking were found but this was not present in the Afghan group, where age seemed to play a role in help-seeking. Frequency of help received was low with approximately 47% of the Iraqi and 57% of the Afghan groups reporting having received help 5 times or less in the last 12 months.

Conclusions

Findings from this study provide clear directions on areas where culturally tailored mental health promotion programs should target in these two refugee communities. Further, the differences in help-seeking behaviour of these communities should be noted by both clinicians and policy makers as efforts to provide culturally responsive mental health services.
The effectiveness, suitability, and sustainability of non-pharmacological methods of managing pain in community-dwelling older adults: a systematic review
Authors: Tang Shuk Kwan , Tse Mimi Mun Yee , Leung Sau Fong , Fotis Theofanis
Published: November 2019

Background

Pain is common in older adults. To maintain their quality of life and promote healthy ageing in the community, it is important to lower their pain levels. Pharmacological pain management has been shown to be effective in older adults. However, as drugs can have various side effects, non-pharmacological pain management is preferred for community-dwelling older adults. This systematic review evaluates the effectiveness, suitability, and sustainability of non-pharmacological pain management interventions for community-dwelling older adults.

Methods

Five databases, namely, CINHAL, Journals@Ovid, Medline, PsycInfo, and PubMed, were searched for articles. The criteria for inclusion were: full-text articles published in English from 2005 to February 2019 on randomized controlled trials, with chronic non-cancer pain as the primary outcome, in which pain was rated by intensity, using non-pharmacological interventions, and with participants over 65 years old, community-dwelling, and mentally competent. A quality appraisal using the Jadad Scale was conducted on the included articles.

Results

Ten articles were included. The mean age of the older adults was from 66.75 to 76. The interventions covered were acupressure, acupuncture, guided imagery, qigong, periosteal stimulation, and Tai Chi. The pain intensities of the participants decreased after the implementation of the intervention. The net changes in pain intensity ranged from − 3.13 to − 0.65 on a zero to ten numeric rating scale, in which zero indicates no pain and ten represents the worst pain.

Conclusions

Non-pharmacological methods of managing pain were effective in lowering pain levels in community-dwelling older adults, and can be promoted widely in the community.
Time to poor treatment outcome and its predictors among drug-resistant tuberculosis patients on second-line anti-tuberculosis treatment in Amhara region, Ethiopia: retrospective cohort study
Authors: Ketema Daniel Bekele , Muchie Kindie Fentahun , Andargie Asrat Atsedeweyn
Published: November 2019

Background

Treatment of drug-resistant tuberculosis is often more complex and toxic with longer treatment time and poor treatment outcomes including treatment failure or death. Monitoring drug-resistant tuberculosis therapy including early identification of prognostic factors and close monitoring of body weight in resource-limited settings is crucial to ensure successful treatment. Therefore, this study was conducted to assess time to poor treatment outcome which is defined as the proportion of all patients who died or failed treatment and its predictors among drug-resistant tuberculosis patients on second-line anti-tuberculosis treatment in Amhara region, Ethiopia.

Methods

A retrospective cohort study was conducted on all patients who started drug-resistant tuberculosis therapy from September 1, 2010 through December 31, 2017, at the University of Gondar Comprehensive Specialized Hospital, Boru-Meda Hospital, and Debre-Markos Referral Hospital in Amhara Region, Ethiopia. Data were entered using Epi-data Version 3.1 and analyzed using R version 3.41 software. The survival time was estimated using Kaplan-Meier survival curve and the survival time between different categorical variables were compared using the log rank test. Event time ratio with 95% confidence interval (CI) and p-value less than 0.05 were used to measure the strength of association and to declare statistically significant predictors respectively.

Results

A total of 508 patients with a median age of 28.5 [IQR: 22–40] years were included in this study. The overall cumulative survival probability of patients at the end of 24 months was 79% [95% CI,75,84%]. Rate of body weight change [Adjusted time ratio (ATR) = 5; 95% CI: 3.2, 7.7], secondary and above level of education [ATR = 2.3;95% CI:1.2,2.9], being non-anemic [ATR = 2.8,95% CI:1.2,3.8], being non-diabetic [ATR = 3.4;95% CI:1.3,8.8], without clinical complications [ATR = 7.6;95% CI:4.2,13.9], HIV negative [ATR = 1. 94:95% CI:1.35,2.35] and residing in rural [ATR = 0.51,95% CI:0.30,0.86] were predictors of time to poor treatment outcomes.

Conclusion

The survival rate of tuberculosis patients was higher at end of follow up relative to other studies. However, poor treatment outcome was higher in early phase of therapy. Educational level, rural residence, HIV/AIDS, diabetes mellitus, previous treatment, clinical complication, rate of body weight change and smoking history were significant predictors of time to poor treatment outcome. Therefore, intervention programs should focus on the identified factors to improve survival time of drug-resistant tuberculosis patients.
Socioeconomic inequalities in maternal health service utilisation: a case of antenatal care in Nigeria using a decomposition approach
Authors: Nwosu Chijioke O. , Ataguba John E.
Published: November 2019

Background

Antenatal care (ANC) services are critical for maternal health but Nigeria performs poorly in ANC utilisation compared to other countries in sub-Saharan Africa. This study aimed to assess socioeconomic inequalities in ANC utilisation and the determinants of these inequalities in Nigeria.

Methods

The 2013 Nigeria Demographic and Health Survey data with 18,559 women was used for analysis. The paper used concentration curves and indices for different measures of ANC utilisation (no ANC visit, 1–3 ANC visits, at least four ANC visits, and the number of ANC visits). A positive (or negative) concentration index means that the measure of ANC utilisation was concentrated on the richer (poorer) population compared to their poorer (richer) counterparts. The concentration indices were also decomposed using standard methodologies to examine the significant determinants of the socioeconomic inequalities in no ANC visit, at least four ANC visits, and the number of ANC visits.

Results

No ANC visit was disproportionately concentrated among the poor (concentration index (CI) = − 0.573), whereas at least four ANC visits (CI = 0.582) and a higher number of ANC visits (CI = 0.357) were disproportionately concentrated among the rich. While these results were consistent across all the geopolitical zones and rural and urban areas, the inequalities were more prevalent in the northern zones (which also have the highest incidence of poverty in the country) and the rural areas. The significant contributors to inequalities in ANC utilisation were the zone of residence, wealth, women’s education (especially secondary) and employment, urban-rural residence, ethnicity, spousal education, and problems with obtaining permission to seek health care and distance to the clinic.

Conclusions

Addressing wealth inequalities, enhancing literacy, employment and mitigating spatial impediments to health care use will reduce socioeconomic inequalities in ANC utilisation in Nigeria. These factors are the social determinants of health inequalities. Thus, a social determinants of health approach is needed to address socioeconomic inequalities in ANC coverage in Nigeria.
Effects of biofeedback-based sleep improvement program on urinary symptoms and sleep patterns of elderly Korean women with overactive bladder syndrome
Authors: Park Jooyeon , Park Choal Hee , Jun Sang-Eun , Lee Eun-Ju , Kang Seung Wan , Kim Nahyun
Published: November 2019

Background

The prevalence of overactive bladder syndrome (OAB) increases with age. Sleep disturbances in elderly individuals with OAB is a common problem. The purpose of this study was to examine the effects of a biofeedback-based sleep improvement (BBSI) program on urinary symptoms and sleep patterns in elderly Korean women with OAB.

Methods

A non-equivalent control group pre−/post-test design was used. Elderly women with OAB were assigned to an intervention group (n = 20) or a control group (n = 18). The BBSI program was implemented in the intervention group for 12 weeks, while two educational sessions of general sleep hygiene and lifestyle modification were provided to the control group. Using SPSS 23.0, the data were analyzed by descriptive analysis using the chi-square test, Fisher’s exact test, Mann-Whitney test, and Wilcoxon test.

Results

After the 12-week BBSI program, significant improvements were found in the intervention group’s the square root of the mean squared differences of successive R-R intervals (p = 0.025), low frequency/high frequency ratio (p = 0.006), and epinephrine (p = 0.039). We also observed a significant difference in urinary symptoms, sleep efficiency, wake after sleep onset, number of awakenings, and number of awakenings within 3 h after sleep onset (p < 0.001,p = 0.004,p = 0.001,p = 0.001, andp = 0.048, respectively). However, no significant changes were found in these variables in the control group.

Conclusions

The BBSI program effectively improved urinary symptoms and sleep patterns of elderly Korean women with OAB. Further longitudinal research is required to investigate the sustainability and effects of the BBSI program.

Trial registration

KCT0003882. Date of registration: 02/05/2019. Retrospectively registered.
Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: a cohort study
Authors: Heredia-P Ana María , Lafaurie Gloria Inés , Bautista-Molano Wilson , Trujillo Tamy Goretty , Chalem-Choueka Philippe , Bello-Gualtero Juan M , Pacheco-Tena Cesar , Chila-Moreno Lorena , Romero-Sánchez Consuelo
Published: November 2019

Background

Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients.

Methods

Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up.

Results

C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p <  0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p <  0.0001). The predictive value of the generalised linear mixed model for progression was 85%.

Conclusions

Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA.
Determinants of early marriage among married women in Injibara town, north West Ethiopia: community-based cross-sectional study
Authors: Bezie Minale , Addisu Dagne
Published: November 2019

Background

Early marriage is occurred when one or both of the spouses are below the age of 18 years at the time of their first marriage. It is one of the major traditional practices in developing counties particularly in Ethiopia; which has significant physical, intellectual, psychological and emotional effects and reduces educational opportunities and the chance for personal growth for both boys and girls. Even though this traditional practice was the common cultural events in the study area, there is no prior study on the magnitude and its determinant factors. Hence, the study was aimed to determine the prevalence and determinant factors of early marriage among married women in Injibara town, North West Ethiopia.

Methods

A Community-based cross-sectional study was conducted from September to December 2018. A total of 373 women were included in the study. A multistage sampling procedure was applied to select the study participants. Data analysis was done by using SPSS versions 23. Both descriptive & analytical statistics were computed. Statistical significance was considered at P < 0.05 and the strength of association were assessed by using adjusted odds ratio with 95% confidence interval.

Result

The prevalence of early marriage was 167(44.8%). The minimum and maximum ages at first marriage were 9 and 23 years respectively. Non-formal educational level of the father [Adjusted Odd Ratio (AOR) =2.32; 95%CI = 1.33–4.05], family’s average monthly income <1000 Ethiopian birr [AOR = 2.32, 95%CI = 1.27–4.24], family size ≥7 [AOR = 3.59, 95%CI = 1.94–6.63] and non-formal education level of the respondents [AOR = 5.16; 95%CI = 2.87–9.28] were found to be associated with early marriage.

Conclusion

The prevalence of early marriage was high in Injibara town, Ethiopia. Factors that tend to facilitate early marriage in this town include family income, family size, educational level of the father and that of the respondent. Improving on the strategies that promote formal education will reduce the level of early marriage in Injibara town, Ethiopia.
Correlation of online assessment parameters with summative exam performance in undergraduate medical education of pharmacology: a prospective cohort study
Authors: Kühbeck Felizian , Berberat Pascal O. , Engelhardt Stefan , Sarikas Antonio
Published: November 2019

Background

Learning analytics aims to improve learning outcomes through the systematic measurement and analysis of learning-related data. However, which parameters have the highest predictive power for academic performance remains to be elucidated. The aim of this study was to investigate the correlation of different online assessment parameters with summative exam performance in undergraduate medical education of pharmacology.

Methods

A prospective study was conducted with a cohort of undergraduate medical students enrolled in a pharmacology course at Technical University of Munich, Germany. After a four-week teaching and learning period, students were given access to an online assessment platform consisting of 440 multiple choice (MC) questions. After 12 days, a final written summative exam was performed. Bivariate correlation and multiple regression analyses were performed for different online assessment parameters as predictors and summative exam performance as dependent variable. Self-perceived pharmacology competence was measured by questionnaires pre- and postintervention.

Results

A total of 224 out of 393 (57%) students participated in the study and were included in the analysis. There was no significant correlation for the parameters “number of logins” (r = 0.01, p = 0.893), “number of MC-questions answered” (r = 0.02, p = 0.813) and “time spent on the assessment platform” (r = − 0.05, p = 0.459) with exam performance. The variable “time per question” was statistically significant (p = 0.006), but correlated negatively (r = − 0.18) with academic performance of study participants. Only “total score” (r = 0.71, p < 0.001) and the “score of first attempt” (r = 0.72, p < 0.001) were significantly correlated with final grades. In a multiple regression analysis, “score first attempt” accounted for 52% of the variation of “score final exam”, and “time per question” and “total score” for additional 5 and 1.4%, respectively. No gender-specific differences were observed. Finally, online assessments resulted in improved self-perceived pharmacology competence of students.

Conclusion

In this prospective cohort study, we systematically assessed the correlation of different online assessments parameters with exam performance and their gender-neutrality. Our findings may help to improve predictive models of academic performance in undergraduate medical education of pharmacology.
To examine the associations between medical students’ conceptions of learning, strategies to learning, and learning outcome in a medical humanities course
Authors: Chiu Yu-Chun , Liang Jyh-Chong , Hsu Hong-Yuan , Chu Tzong-Shinn , Lin Kuan-Han , Chen Yen-Yuan , Tsai Chin-Chung
Published: November 2019

Background

By learning medical humanities, medical students are expected to shift from handling the diseases only to seeing a whole sick person. Therefore, understanding medical students’ learning process and outcomes of medical humanities becomes an essential issue of medical education. Few studies have been conducted to explore factors surrounding medical students’ learning process and outcomes of medical humanities. The objectives were: (1) to investigate the relationships between medical students’ conceptions of learning and strategies to learning; and (2) to examine the relationships between students’ strategies to learning and learning outcomes for medical humanities.

Methods

We used the modified Approaches to Learning Medicine (mALM) questionnaire and Conceptions of Learning Medicine (COLM) questionnaire to measure the medical students’ strategies to learning and conceptions of learning respectively. The learning outcome of medical humanities was measured using students’ weighted grade in a medical humanities course. The confirmatory factor analysis (CFA) was used to validate the COLM and mALM questionnaires, in which construct validity and reliability were assessed. Pearson’s correlation was used to examine the relationships among the factors of COLM, mALM, and the weighted grade. Path analysis using structural equation modeling technique (SEM) was employed to estimate the structural relationships among the COLM, mALM, and the weighted grade.

Results

Two hundred and seventy-five first-year medical students consented to participate in this study. The participants adopting surface strategies to learning were more likely to have unsatisfactory learning outcome (β = − 0.14,p = .04). The basic-level conception of “Preparing for Testing” was negatively (β = − 0.19,p < .01) associated with deep strategies of learning, and positively (β = 0.48,p < .01) associated with surface strategies of learning (β = 0.50,p < .01). The basic-level conception of “Skills Acquisition” was positively associated with deep strategies of learning (β = 0.23,p < .01).

Conclusion

Medical educators should wisely employ teaching strategies to increase students’ engagement with deep and self-directed learning strategies, and to avoid using surface learning strategies in the medical humanities course in order to achieve better learning outcomes.
Seroprevalence and associated risk factors of leptospirosis in slaughter pigs; a neglected public health risk, western Kenya
Authors: Ngugi Jeremiah N. , Fèvre Eric M. , Mgode Georgies F. , Obonyo Mark , Mhamphi Ginethon G. , Otieno Christina A. , Cook Elizabeth Anne Jessie
Published: November 2019

Background

Leptospirosis is a neglected zoonosis of public health importance transmitted through contact with contaminated soil, water or urine of infected animals. In pigs the disease is characterized by abortion, still births and weak piglets. A cross-sectional study was conducted in May to July 2018 to estimate the sero-prevalence of leptospirosis and factors associated with seropositivity in slaughter pigs. A questionnaire was used to collect information on animal demographics. Serum was tested for anti-leptospiral antibodies using microscopic agglutination test (MAT) with a panel of 8 serovars. Sera were considered positive for sero-reactivity at a MAT titre ≥1:40 against at least one serovar. Chi-square tests were used to measure the strength of association between the MAT test result and exploratory variables.

Results

A total of 252 pig serum samples from seven slaughterhouses were tested forLeptospiraantibodies by MAT. Of the 252 pigs sampled, 88.8% (244/252) were indigenous breeds; 55.6% (140/252) were female and 88.7% (220/252) were reared in extensive production systems. Eighty-three (32.9%; 83/252) sera samples tested positive on MAT against at least one serovar. Of the 8 serovars, the highest prevalence was recorded for serovar Lora 21.4% followed by Kenya 5.2%, Sokoine 3.6% and Grippotyphosa at 3.2%. Risk factors for leptospirosis seropositivity in pigs were: originating from farms with other types of livestock (OR 2.3; 95% CI 1.0–4.5) and mature pigs (OR 1.9; 95% CI 1.1–3.3).

Conclusion

This study demonstrates that there is a high prevalence of leptospirosis positive pigs at slaughter in a small-holder livestock keeping region of the Lake Victoria basin. The potential for cross species transmission of pathogenic serovars is highlighted as well as the potential for occupational exposure to slaughterhouse personnel. Improvements in husbandry practices (confinement and rodent control) and public health education among slaughterhouse workers and other high-risk groups is recommended.
A functional polymorphism in the promoter of miR-17-92 cluster is associated with decreased risk of ischemic stroke
Authors: Huang Huatuo , Wei Guijiang , Wang Chunfang , Lu Yulan , Liu Chunhong , Wang Rong , Shi Xiang , Yang Jun , Wei Yesheng
Published: November 2019

Background

The microRNA-17-92 (miR-17-92) cluster is one of the most extensively studied miRNA clusters. Abnormal expression of the cluster has been found to play important role in different kinds of human diseases, including ischemic stroke (IS). The aim of our study was to investigate the association between three polymorphisms (rs1491034, rs9301654 and rs982873) in the promoter of the miR-17-92 cluster and risk of IS.

Methods

Three hundred and ninety-eight patients with IS and 397 control subjects were included. The genotypes of the three polymorphisms were determined by Snapshot SNP genotyping assay. Relative expression of the cluster in peripheral blood mononuclear cells (PBMCs) of cases and controls were examined by quantitative real-time PCR.

Results

Significant association between rs9301654 polymorphism and risk of IS were observed basing on genotype, model and allele analyses (GA vs. AA: adjusted OR = 0.63, 95% CI: 0.41~0.97, P = 0.037; GG vs. AA: adjusted OR = 0.23, 95% CI: 0.07~0.78, P = 0.018; GA + GG vs. AA: adjusted OR = 0.57, 95% CI: 0.38~0.87, P = 0.009; GA + AA vs. GG: adjusted OR = 0.27, 95% CI: 0.08~0.89, P = 0.032; G vs. A: adjusted OR = 0.58, 95% CI: 0.40~0.83). Haplotype analysis showed that TGC and TGT haplotypes were associated with decreased risk of IS (OR = 0.59, 95% CI: 0.40~0.87, P = 0.007 for TGC haplotype; OR = 0.21, 95% CI: 0.06~0.75, P = 0.009 for TGT haplotype). Importantly, we found the expression of miR-17-5p was significant higher while miR-19a-3p was significant lower in patient with IS compared with the control group (P < 0.01), and patients with rs9301654GG or GA genotype displayed lower level of miR-19a-3p compared with the AA genotype (P < 0.01).

Conclusions

Our findings indicated that rs9301654 polymorphism in the promoter of miR-17-92 cluster may be associated with susceptibility of IS in the Chinese population. However, we found that rs9301654 polymorphism and its respective gene expression did not demonstrate consistent association with IS in the Chinese population. Further studies such as gene-gene interaction are warranted to reveal the role of miR-19a and its regulatory genes in the etiology of IS.
Engineering and characterising a novel, highly potent bispecific antibody iMab-CAP256 that targets HIV-1
Authors: Moshoette Tumelo , Ali Stuart Alvaro , Papathanasopoulos Maria Antonia , Killick Mark Andrew
Published: November 2019

The existing repertoire of HIV-1 patient derived broadly neutralising antibodies (bNAbs) that target the HIV-1 envelope glycoprotein (Env) present numerous and exciting opportunities for immune-based therapeutic and preventative strategies against HIV-1. Combination antibody therapy is required to ensure greater neutralization coverage and limit Env mediated escape mutations following treatment pressure. Engineered bispecific bNAbs (bibNAbs) assimilate the advantages of combination therapy into a single antibody molecule with several configurations reporting potency enhancement as a result of the increased avidity and simultaneous engagement of targeted epitopes. We report the engineering of a novel bibNAb (iMab-CAP256) comprising the highly potent, CAP256.VRC26.25 bNAb with anticipated extension in neutralization coverage through pairing with the host directed, anti-CD4 antibody, ibalizumab (iMab). Recombinant expression of parental monoclonal antibodies and the iMab-CAP256 bibNAb was performed in HEK293T (Human embryonic kidney 293 T antigen) cells, purified to homogeneity by Protein-A affinity chromatography followed by size exclusion chromatography. Antibody assembly and binding functionality of Fab moieties was confirmed by SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) and ELISA, respectively. Breadth and potency were evaluated against a geographical diverse HIV-1 pseudovirus panel (n = 20). Overall, iMab-CAP256 demonstrated an expanded neutralizing coverage, neutralizing single, parental antibody resistant pseudovirus strains and an enhanced neutralization potency against all dual sensitive strains (average fold increase over the more potent parental antibody of 11.4 (range 2 to 31.8). Potency enhancement was not observed for the parental antibody combination treatment (iMab + CAP256) suggesting the presence of a synergistic relationship between the CAP256 and iMab paratope combination in this bibNAb configuration. In addition, iMab-CAP256 bibNAbs exhibited comparable efficacy to other bibNAbs PG9-iMab and 10E08-iMab previously reported in the literature. The enhanced neutralization coverage and potency of iMAb-CAP256 over the parental bNAbs should facilitate superior clinical performance as a therapeutic or preventative strategy against HIV-1.
Beyond mapping: a case for geospatial analytics in humanitarian health
Authors: Greenough P. Gregg , Nelson Erica L.
Published: November 2019

The humanitarian sector is increasingly adopting geospatial data to support operations. However, the utilization of these data in the humanitarian health arena is predominantly in thematic map format, thereby limiting the full insight and utility of geospatial information.

Geospatial analytics, in contrast, including pattern analysis, interpolation, and predictive modeling, have tremendous potential within the field of humanitarian health. This paper explores a variety of historical and contemporary geospatial applications in the public health and humanitarian fields and argues for greater integration of geospatial analysis into humanitarian health research and programming. From remote sensing to create sampling frames, to spatial interpolation for environmental exposure analysis, and multi-objective optimization algorithms for humanitarian logistics, spatial analysis has transformed epistemological paradigms, research methods and programming landscapes across diverse disciplines.

The field of humanitarian health, which is inextricably bounded by geography and resource limitations, should leverage the unique capacities of spatial methods and strategically integrate geospatial analytics into research and programming not only to fortify the academic legitimacy and professionalization of the field but also to improve operational efficiency and mitigation strategies.
CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy
Authors: Liu Delong
Published: November 2019

New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibody-drug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CAR-T cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CAR-T cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a “do-not-eat-me” immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR- T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.
Prevalence of intestinal parasitic infection and associated factors among pregnant women attending antenatal care at public health facilities in Lalo Kile district, Oromia, Western Ethiopia
Authors: Yesuf Dejene Abraham , Abdissa Lensa Tesfaye , Gerbi Emiru Adeba , Tola Edosa Kifle
Published: November 2019

Objective

This study aimed to assess the prevalence of intestinal parasitic infection and associated factors among pregnant women attending antenatal care at public health facilities in Lalo Kile district, Oromia, Western Ethiopia.

Results

Out of the 315 respondents, the mean age was 24.7 ± 2.54 years ranging between 15 and 44 years. The majority of the respondents were Oromo in ethnicity (90.2%) and protestant in religion (83.2%) and almost all (99%) of the study participants were married. Two hundred twenty-six (72%) of pregnant women were attended at least primary school and two hundred forty-six (78.1%) of the respondents were from farmer households. About half of the households (51.7%) had a monthly income of greater than 35 USD. The overall prevalence of intestinal parasitic infection was 138 (43.8%) with the predominance of hookworm (33.7%) followed by Ascaris lumbricoides (7.3%). Being a farmer [AOR, 95% CI 7.3 (1.46, 37.00), P = 0.03], walking barefooted [AOR, 95% CI 6.13 (1.98, 19.00), P = 0.002] and absence of proper handwashing after latrine [AOR, 95% CI 5.36 (1.78, 16.00), P = 0.003] were significantly associated with occurrence of the intestinal parasitic infection.
FoxB, a new and highly conserved key factor in arthropod dorsal–ventral (DV) limb patterning
Authors: Heingård Miriam , Turetzek Natascha , Prpic Nikola-Michael , Janssen Ralf
Published: November 2019

Forkhead box (Fox) transcription factors evolved early in animal evolution and represent important components of conserved gene regulatory networks (GRNs) during animal development. Most of the researches concerning Fox genes, however, are on vertebrates and only a relatively low number of studies investigate Fox gene function in invertebrates. In addition to this shortcoming, the focus of attention is often restricted to a few well-characterized Fox genes such asFoxA(forkhead),FoxC(crocodile) andFoxQ2. Although arthropods represent the largest and most diverse animal group, most other Fox genes have not been investigated in detail, not even in the arthropod model speciesDrosophila melanogaster. In a general gene expression pattern screen for panarthropod Fox genes including the red flour beetleTribolium castaneum, the pill millipedeGlomeris marginata, the common house spiderParasteatoda tepidariorum, and the velvet wormEuperipatoides kanangrensis, we identified a Fox gene with a highly conserved expression pattern along the ventral ectoderm of arthropod and onychophoran limbs. Functional investigation ofFoxBinParasteatodareveals a hitherto unrecognized important function of FoxB upstream ofwingless(wg) anddecapentaplegic(dpp) in the GRN orchestrating dorsal–ventral limb patterning.
Microglial motility in Alzheimer’s disease and after Aβ42 immunotherapy: a human post-mortem study
Authors: Franco-Bocanegra Diana K. , George Bethany , Lau Laurie C. , Holmes Clive , Nicoll James A. R. , Boche Delphine
Published: November 2019

Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidence suggests impaired microglial motility in Alzheimer’s disease (AD) and therefore we have investigated whether the expression of proteins associated with motility is altered in AD and affected by the Aβ immunotherapy usingpost-mortembrain tissue of 32 controls, 44 AD cases, and 16 AD cases from our unique group of patients immunised against Aβ42 (iAD).

Sections of brain were immunolabelled and quantified for (i) the motility-related microglial proteins Iba1, cofilin 1 (CFL1), coronin-1a (CORO1A) and P2RY12, and (ii) pan-Aβ, Aβ42 and phosphorylated tau (ptau). The neuroinflammatory environment was characterised using Meso Scale Discovery multiplex assays. The expression of all four motility-related proteins was unmodified in AD compared with controls, whereas Iba1 and P2RY12, the homeostatic markers, were increased in the iAD group compared with AD. Iba1 and P2RY12 showed significant positive correlations with Aβ in controls but not in the AD or iAD groups. Pro- and anti-inflammatory proteins were increased in AD, whereas immunotherapy appears to result in a slightly less pro-inflammatory environment.

Our findings suggest that as Aβ appears during the ageing process, the homeostatic Iba1 and P2RY12 –positive microglia respond to Aβ, but this response is absent in AD. Aβ-immunisation promoted increased Iba1 and P2RY12 expression, likely reflecting increased baseline microglial motility but without restoring the profile observed in controls.
Modeling and control of planar slippage in object manipulation using robotic soft fingers
Authors: Fakhari Amin , Kao Imin , Keshmiri Mehdi
Published: November 2019

Slippage occurrence has an important roll in stable and robust object grasping and manipulation. However, in majority of prior research on soft finger manipulation, presence of the slippage between fingers and objects has been ignored. In this paper which is a continuation of our prior work, a revised and more general method for dynamic modeling of planar slippage is presented using the concept of friction limit surface. Friction limit surface is utilized to relate contact sliding motions to contact frictional force and moment in a planar contact. In this method, different states of planar contact are replaced with a second-order differential equation. As an example of the proposed method application, dynamic modeling and slippage analysis of object manipulation on a horizontal plane using a three-link soft finger is studied. Then, a controller is designed to reduce and remove the undesired slippage which occurs between the soft finger and object and simultaneously move the object on a predefined desired path. Numerical simulations reveal the acceptable performance of the proposed method and the designed controller.
A detection metric designed for O’Connell effect eclipsing binaries
Authors: Johnston Kyle B. , Haber Rana , Caballero-Nieves Saida M. , Peter Adrian M. , Petit Véronique , Knote Matt
Published: November 2019

We present the construction of a novel time-domain signature extraction methodology and the development of a supporting supervised pattern detection algorithm. We focus on the targeted identification of eclipsing binaries that demonstrate a feature known as the O’Connell effect. Our proposed methodology maps stellar variable observations to a new representation known as distribution fields (DFs). Given this novel representation, we develop a metric learning technique directly on the DF space that is capable of specifically identifying our stars of interest. The metric is tuned on a set of labeled eclipsing binary data from the Kepler survey, targeting particular systems exhibiting the O’Connell effect. The result is a conservative selection of 124 potential targets of interest out of the Villanova Eclipsing Binary Catalog. Our framework demonstrates favorable performance on Kepler eclipsing binary data, taking a crucial step in preparing the way for large-scale data volumes from next-generation telescopes such as LSST and SKA.
Predictors of undernutrition among the elderly in Sodo zuriya district Wolaita zone, Ethiopia
Authors: Wondiye Kidest , Asseffa Netsanet Abera , Gemebo Tsegaye Demisse , Astawesegn Feleke Hailemichael
Published: November 2019

Background

In any society, the elderly are among the vulnerable and high risk groups with regard to health status. In persons over the age of 60 years, nutrition is among the important determinants of health. However, undernutrition among the elderly is often under diagnosed and/or neglected. Hence, in this study, we looked at prevalence and factors associated with undernutrition among the elderly.

Methods

A community based cross-sectional study was conducted at Sodo Zuriya district. Multi-stage systematic sampling method was used to select 578 elderly. A structured questionnaire was used to collect data on socio-demographics, dietary diversity, and health status of the elderly.

Measurements of weight and height were taken using digital weighing scale and stadio-meter, respectively. Data was entered and cleaned in Epi-Data version3.1and exported to SPSS version 20 for analysis. Binary and multivariate logistic regressions were done and odds ratios with 95% confidence intervals were calculated.

Results

The overall prevalence of undernutrition was 17.1%. On multivariate logistic regression, being unable to read and write (AOR = 2.09), not being married (AOR = 2.02), history of decline in food intake (AOR = 2.1), smoking (AOR = 4.9) and monthly income <$20 (AOR = 7.5) were factors positively associated with undernutrition.

Conclusion

The study revealed that prevalence of undernutrition in the district was relatively high. Hence, it is among the major public health burdens in the district. Hence, to improve nutritional status of elderly the district health office and health professionals should consider behavioral support interventions to assist in cessation of smoking. There is also a need to financially empower the elderly in the district.
Changes in oncogenic protein levels in peri-implant oral malignancy: a case report
Authors: Seo Mi Hyun , Myoung Hoon , Lee Jong Ho , Kim Soung Min , Lee Suk Keun
Published: November 2019

Background

Oral squamous cell carcinoma (OSCC) constitutes a group of tumors that exhibit heterogeneous biology, histopathology, and clinical behaviors.

Case presentation

A 73-year-old male had a whitish leukoplakia-like lesion around inflamed peri-implant area (#42, #43, and #44), and this lesion had transformed to OSCC within 3 years. He underwent mass resection, selective neck dissection, and reconstructive surgery. To detect any carcinogenesis progression, we examined the removed tumor tissue as well as the patient’s preoperative and postoperative sera to identify causative oncogenic proteins using immunoprecipitation high-performance liquid chromatography (IP-HPLC).

Conclusions

The protein expression levels of p53, E-cadherin, β-catenin, MMP-10, HER2, NRAS, Met, HER2, and ERb were significantly lower in the serum collected on postoperative day 10 than in the preoperative serum, and if these proteins are consistently not elevated in the serum 3 months after surgery compared with the preoperative serum, these proteins can be potential oncogenic proteins. However, we also found that the serum extracted 3 months after the operation had elevated levels of oncogenic proteins compared with that of the preoperative and 10-day postoperative serum indicating the possibility of tumor recurrence. At postoperative follow-up period, ipsilateral neck metastasis and second primary lesion were found and additional surgery was performed to the patient. IP-HPLC using the patient’s serum shows the possibility of oncogenic protein detection. However, follow-up IP-HPLC data is needed to find out patient-specific prognostic factors.