bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative transcriptome and metabolome analyses provide new insights into the molecular mechanisms underlying taproot thickening in Panax notoginseng
Authors: Li Xue-Jiao , Yang Jian-Li , Hao Bing , Lu Ying-Chun , Qian Zhi-Long , Li Ying , Ye Shuang , Tang Jun-Rong , Chen Mo , Long Guang-Qiang , Zhao Yan , Zhang Guang-Hui , Chen Jun-Wen , Fan Wei , Yang Sheng-Chao
Published: October 2019

Background

Taproot thickening is a complex biological process that is dependent on the coordinated expression of genes controlled by both environmental and developmental factors. Panax notoginseng is an important Chinese medicinal herb that is characterized by an enlarged taproot as the main organ of saponin accumulation. However, the molecular mechanisms of taproot enlargement are poorly understood.

Results

A total of 29,957 differentially expressed genes (DEGs) were identified during the thickening process in the taproots of P. notoginseng. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment revealed that DEGs associated with “plant hormone signal transduction,” “starch and sucrose metabolism,” and “phenylpropanoid biosynthesis” were predominantly enriched. Further analysis identified some critical genes (e.g., RNase-like major storage protein, DA1-related protein, and Starch branching enzyme I) and metabolites (e.g., sucrose, glucose, fructose, malate, and arginine) that potentially control taproot thickening. Several aspects including hormone crosstalk, transcriptional regulation, homeostatic regulation between sugar and starch, and cell wall metabolism, were identified as important for the thickening process in the taproot of P. notoginseng.

Conclusion

The results provide a molecular regulatory network of taproot thickening in P. notoginseng and facilitate the further characterization of the genes responsible for taproot formation in root medicinal plants or crops.
Disease burden and associated risk factors for metabolic syndrome among adults in Ethiopia
Authors: Solomon Samrawit , Mulugeta Wudeneh
Published: October 2019

Background

Metabolic Syndrome (MetS) and Non-communicable diseases (NCDs) are alarmingly increasing in low-income countries. Yet, very limited is known about the prevalence and risk factors associated with MetS in Ethiopia.

Methods

A cross-sectional study was conducted among adult outpatients (N = 325) at St. Paul’s Hospital Millennium Medical College in Addis Ababa, Ethiopia. The study was conducted in accordance with STEPwise approach of the World Health Organization. MetS was defined using modified National Cholesterol Education Program’s Adult Treatment Panel III criteria. Univariate and multivariate analyses were performed.

Results

The overall prevalence of MetS was 20.3%. Among the 325 participants, 76.9% had at least one MetS components. Reduced high-density lipoprotein cholesterol was the most common MetS component at 48.6%, followed by elevated blood pressure at 36.3%, and elevated fasting glucose at 32.6%. Older age (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.43–12.04), Amhara ethnicity (OR = 2.36; 95%CI = 1.14–4.88), overweight status (OR = 2.21; 95%CI = 1.03–4.71), higher income (OR = 3.31; 95%CI = 1.11–9.84) and higher education levels (OR = 2.19; 95%CI = 1.05–4.59) were risk factors for MetS.

Conclusion

The disease burden of MetS among Ethiopians is high, and is associated with age, weight, income, education and ethnicity. Comprehensive screening and assessment of MetS is needed along with effective preventive and treatment strategies in low-income countries, such as Ethiopia.
A comparison of the statistical performance of different meta-analysis models for the synthesis of subgroup effects from randomized clinical trials
Authors: da Costa Bruno R. , Sutton Alex J.
Published: October 2019

Background

When investigating subgroup effects in meta-analysis, it is unclear whether accounting in meta-regression for between-trial variation in treatment effects, but not between-trial variation in treatment interaction effects when such effects are present, leads to biased estimates, coverage problems, or wrong standard errors, and whether the use of aggregate data (AD) or individual-patient-data (IPD) influences this assessment.

Methods

Seven different models were compared in a simulation study. Models differed regarding the use of AD or IPD, whether they accounted for between-trial variation in interaction effects, and whether they minimized the risk of ecological fallacy.

Results

Models that used IPD and that allowed for between-trial variation of the interaction effect had less bias, better coverage, and more accurate standard errors than models that used AD or ignored this variation. The main factor influencing the performance of models was whether they used IPD or AD. The model that used AD had a considerably worse performance than all models that used IPD, especially when a low number of trials was included in the analysis.

Conclusions

The results indicate that IPD models that allow for the between-trial variation in interaction effects should be given preference whenever investigating subgroup effects within a meta-analysis.
Spatiotemporal multi-disease transmission dynamic measure for emerging diseases: an application to dengue and zika integrated surveillance in Thailand
Authors: Rotejanaprasert Chawarat , Lawson Andrew B. , Iamsirithaworn Sopon
Published: October 2019

Background

New emerging diseases are public health concerns in which policy makers have to make decisions in the presence of enormous uncertainty. This is an important challenge in terms of emergency preparation requiring the operation of effective surveillance systems. A key concept to investigate the dynamic of infectious diseases is the basic reproduction number. However it is difficult to be applicable in real situations due to the underlying theoretical assumptions.

Methods

In this paper we propose a robust and flexible methodology for estimating disease strength varying in space and time using an alternative measure of disease transmission within the hierarchical modeling framework. The proposed measure is also extended to allow for incorporating knowledge from related diseases to enhance performance of surveillance system.

Results

A simulation was conducted to examine robustness of the proposed methodology and the simulation results demonstrate that the proposed method allows robust estimation of the disease strength across simulation scenarios. A real data example is provided of an integrative application of Dengue and Zika surveillance in Thailand. The real data example also shows that combining both diseases in an integrated analysis essentially decreases variability of model fitting.

Conclusions

The proposed methodology is robust in several simulated scenarios of spatiotemporal transmission force with computing flexibility and practical benefits. This development has potential for broad applicability as an alternative tool for integrated surveillance of emerging diseases such as Zika.
‘Weighty issues’ in GP-led antenatal care: a qualitative study
Authors: Walker Ruth , Choi Tammie S. T. , Alexander Karyn , Mazza Danielle , Truby Helen
Published: October 2019

Background

Approximately 50% of women gain weight in excess of gestational weight gain (GWG) recommendations during pregnancy leading to adverse maternal and foetal outcomes and the perpetuation of the cycle of obesity. Antenatal care provided by a general practitioner (GP) in the primary care setting is an important model of care, particularly for women in regional areas where rates of overweight and obesity are highest. The aim of this study is to explore GPs’ perceptions and experiences of implementing GWG recommendations in GP-led antenatal care.

Methods

A qualitative exploratory approach recorded GPs’ experiences and insights regarding the application of GWG recommendations in practice. Data were collected via semi-structured interviews informed by the revised Theoretical Domains Framework (TDF). Deductive thematic analysis grouped coded text into TDF domains from which main themes were generated.

Results

Twenty GPs (13 female, 7 male) from metropolitan and regional Victoria, Australia participated. Codes related to at least one of 11 TDF domains. Five main themes were apparent: 1) Despite low awareness of guidelines, GWG advice is provided; 2) ‘I should do this more’; 3) Lack of everyday resources; 4) Working ‘against the odds’ at times; and 5) Optimism and reality. GPs were aware of the importance of optimal GWG however, other pregnancy-related issues are given precedence during consultations. Enablers for the implementation of GWG guidelines were practitioner-based and included GPs’ strong sense of their professional role to provide advice, and ongoing and trusting relationships with women throughout pregnancy. Barriers were mostly health system-based with limited time, remuneration, and restrictive referral pathways being limiting factors.

Conclusions

There is a need to support GPs to provide GWG advice in accordance with current national guidelines. Solutions potentially lie in strategies that promote the effective dissemination and uptake of guidelines, and changes to policy and funding within the health-system so that longer GP-led antenatal care consultations are remunerated and referrals to allied health are accessible to women who require additional support to optimise GWG.
Population structure of drug-resistant Mycobacterium tuberculosis in Central Asia
Authors: Engström Anna , Antonenka Uladzimir , Kadyrov Abdylat , Kalmambetova Gulmira , Kranzer Katharina , Merker Matthias , Kabirov Olim , Parpieva Nargiza , Rajabov Asliddin , Sahalchyk Evgeni , Sayfudtinov Zayniddin , Niemann Stefan , Hoffmann Harald
Published: October 2019

Background

Drug-resistant tuberculosis (TB) is a major public health concern threathing the success of TB control efforts, and this is particularily problematic in Central Asia. Here, we present the first analysis of the population structure of Mycobacterium tuberculosis complex isolates in the Central Asian republics Uzbekistan, Tajikistan, and Kyrgyzstan.

Methods

The study set consisted of 607 isolates with 235 from Uzbekistan, 206 from Tajikistan, and 166 from Kyrgyzstan. 24-loci MIRU-VNTR (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats) typing and spoligotyping were combined for genotyping. In addition, phenotypic drug suceptibility was performed.

Results

The population structure mainly comprises strains of the Beijing lineage (411/607). 349 of the 411 Beijing isolates formed clusters, compared to only 33 of the 196 isolates from other clades. Beijing 94–32 (n = 145) and 100–32 (n = 70) formed the largest clusters. Beijing isolates were more frequently multidrug-resistant, pre-extensively resistant (pre-XDR)- or XDR-TB than other genotypes.

Conclusions

Beijing clusters 94–32 and 100–32 are the dominant MTB genotypes in Central Asia. The relative size of 100–32 compared to previous studies in Kazakhstan and its unequal geographic distribution support the hypothesis of its more recent emergence in Central Asia. The data also demonstrate that clonal spread of resistant TB strains, particularly of the Beijing lineage, is a root of the so far uncontroled MDR-TB epidemic in Central Asia.
An updated systematic review and meta-analysis of the prevalence of hepatitis B virus in Ethiopia
Authors: Yazie Teshiwal Deress , Tebeje Mekonnen Girma
Published: October 2019

Background

Hepatitis B virus is one of the major public health concerns globally. It is highly infectious and can be transmitted from person to person through vertically or horizontally via contaminated body fluids. Despite the provision of an effective vaccine, it remains a major problem worldwide, particularly among the developing countries.

Methods

Online electronic databases including PubMed, Google Scholar, Science Direct, African Index Medicus, African Journals Online, and WHO Afro Library were searched and published articles from 2010 to June 8, 2019, were considered. Both authors independently screened articles and extracted the data. Funnel-Plots and Egger’s test statistics were used to determine the presence of small-study effects and publication bias. The pooled prevalence of HBV was analyzed using the random-effects model. The possible sources of heterogeneity was analyzed through subgroup analysis, sensitivity analysis, and meta-regression.

Results

The overall pooled prevalence of HBV was 6% and among subgroups, pregnant women, healthcare workers, and HIV positive patients accounted for 5% for each group. Relatively low prevalence (4%) was obtained among blood donors. The Egger’s test statistics (p = 0.747) indicated the absence of publication bias. In addition, from the sensitivity analysis, there was no influence on the overall effect estimate while removing a single study at a time. The level of heterogeneity was reduced among pregnant women, HIV positive and studies with unknown sampling techniques. After conducting meta-regression, province, study group, screening method, and quality of papers were identified as sources of heterogeneity.

Conclusions

The overall pooled prevalence of HBV in Ethiopia was high. Strengthening and scaling up of the scope of the existing vaccination program and implementing novel approaches including screen-and-treat could be implemented to reduce the burden of the disease. Generally, the study can provide current prevalence estimate of HBV that could vital for intervention to tackle the disease.
Early and late mortality after malaria in young children in Papua, Indonesia
Authors: Patriani Dewi , Arguni Eggi , Kenangalem Enny , Dini Saber , Sugiarto Paulus , Hasanuddin Afdhal , Lampah Daniel Adrian , Douglas Nicholas M. , Anstey Nicholas M. , Simpson Julie Anne , Price Ric N. , Poespoprodjo Jeanne Rini
Published: October 2019

Background

In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown.

Methods

Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods.

Results

In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307–1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896–944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946–2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124–1158] per 1000 patient years in those surviving.

Conclusions

Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.
Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool
Authors:   on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), Grebe Eduard , Facente Shelley N. , Bingham Jeremy , Pilcher Christopher D. , Powrie Andrew , Gerber Jarryd , Priede Gareth , Chibawara Trust , Busch Michael P. , Murphy Gary , Kassanjee Reshma , Welte Alex
Published: October 2019

Background

It is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the ‘Fiebig staging’ system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results using tests of different sensitivity. To develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the same or different dates, and arbitrary current or future tests – as long as the test sensitivity is known. For this purpose, test sensitivity is the probability of a positive result as a function of time since infection.

Methods

The present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time ‘point estimates’ and referred to as Estimated Dates of Detectable Infection (EDDIs). The tool is designed for easy bulk processing of information (as may be appropriate for research studies) but can also be used for individual patients (such as in clinical practice).

Results

In many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of diagnostic testing histories into infection time estimates, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic.

Conclusions

This tool, available at https://tools.incidence-estimation.org/idt/, is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.
A foodborne outbreak of gastroenteritis caused by Norovirus and Bacillus cereus at a university in the Shunyi District of Beijing, China 2018: a retrospective cohort study
Authors: Chen Dongwan , Li Yongjin , Lv Jinchang , Liu Xiufeng , Gao Peng , Zhen Guoxin , Zhang Wenzeng , Wu Dan , Jing Hongbo , Li Ying , Zhao Yao , Ma Xiaochen , Ma Huilai , Zhang Lijie
Published: October 2019

Background

On September 4, 2018, a boarding school in the Shunyi District of Beijing, China reported an outbreak of acute gastroenteritis. At least 209 suspected students caused of diarrhea and vomiting. The case was investigated, and control measures were taken to prevent further spread.

Methods

A retrospective cohort study was conducted among the school students and staff in order to test hypothesis that high risk of food served at the school canteen. We collected information on demographics, refectory records, person to person transmission by uniform epidemiological questionnaire. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Stool specimens of cases and canteen employees, retained food, water, and environmental swabs were investigated by laboratory analysis.

Results

We identified 209 cases (including 28 laboratory-confirmed cases) which occurred from August 29 to September 10. All cases were students, and the average age was 20, 52% were male. The outbreak lasted for 13 days, and peaked on September 5. Consumption of Drinks stall and Rice flour stall on September 1 (RR:3.4, 95%CI:1.5–7.8, and RR:7.6, 95%CI:2.8–20.2), Rice flour stall and Fish meal stall on September 2 (RR:4.0, 95%CI:1.2–13.6, and RR:4.6, 95%CI:1.7–12.5), muslim meal stall on September 4 (RR:2.7, 95%CI:1.3–5.4), Barbeque stall on September 5 (RR:3.0, 95%CI:1.2–7.0) were independently associated with increased risk of disease within the following 2 days. Among 35 specimens of rectal swabs or feces from students, 28 specimens were positive. Norovirus GI.6 alone was detected in 23 specimens, Bacillus cereus alone in 3 specimens and both norovirus GI.6 and Bacillus cereus in 2 specimens. Ten specimens of rectal swabs from canteen employees were positive for norovirus GI, and 2 specimens were positive for Bacillus cereus. Four retained food specimens were positive for Bacillus cereus, and environmental samples were negative for any viruses or bacteria.

Conclusion

Our investigation indicated that canteen employees were infected by two pathogens (norovirus and Bacillus cereus) and transmission may have been possible due to unhygienic practices. Student consumption of food or drink at high-risk stalls was determined as the probable cause of the outbreak.
Prenatal maternal stress and birth outcomes in rural Ghana: sex-specific associations
Authors: Ae-Ngibise Kenneth Ayuurebobi , Wylie Blair J. , Boamah-Kaali Ellen , Jack Darby W. , Oppong Felix Boakye , Chillrud Steven N. , Gyaase Stephaney , Kaali Seyram , Agyei Oscar , Kinney Patrick L. , Mujtaba Mohammed , Wright Rosalind J. , Asante Kwaku Poku , Lee Alison G.
Published: October 2019

Background

In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana.

Methods

Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined.

Results

In all children, high prenatal maternal stress was associated with reduced birth length (β = − 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = − 0.16, p = 0.02; β = − 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = − 0.66, p = 0.05; β = − 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys.

Conclusions

All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies.

Trial registration

NCT01335490 (prospective registration).

Date of Registration: April 14, 2011.

Status of Registration: Completed.
Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer
Authors: Xiao Yuanyuan , Yang Haijun , Lu Jian , Li Dehui , Xu Chuanzhi , Risch Harvey A.
Published: October 2019

Background

Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC.

Methods

We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC.

Results

Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT > 48 U/L yielded a hazard ratio of 1.53 (95% CI: 1.19–1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level.

Conclusion

Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.
Exploring new potential role of DDB2 by host cell reactivation assay in human tumorigenic cells
Authors: Bassi Elisabetta , Perucca Paola , Guardamagna Isabella , Prosperi Ennio , Stivala Lucia A. , Cazzalini Ornella
Published: October 2019

Background

The Host Cell Reactivation assay (HCR) allows studying the DNA repair capability in different types of human cells. This assay was carried out to assess the ability in removing UV-lesions from DNA, thus verifying NER efficiency. Previously we have shown that DDB2, a protein involved in the Global Genome Repair, interacts directly with PCNA and, in human cells, the loss of this interaction affects DNA repair machinery. In addition, a mutant form unable to interact with PCNA (DDB2PCNA-), has shown a reduced ability to interact with a UV-damaged DNA plasmid in vitro.

Methods

In this work, we have investigated whether DDB2 protein may influence the repair of a UV-damaged DNA plasmid into the cellular environment by applying the HCR method. To this end, human kidney 293 stable clones, expressing DDB2Wtor DDB2PCNA-, were co-transfected with pmRFP-N2 and UV-irradiated pEGFP-reported plasmids. Moreover, the co-localization between DDB2 proteins and different NER factors recruited at DNA damaged sites was analysed by immunofluorescence and confocal microscopy.

Results

The results have shown that DDB2Wtrecognize and repair the UV-induced lesions in plasmidic DNA transfected in the cells, whereas a delay in these processes were observed in the presence of DDB2PCNA-, as also confirmed by the different extent of co-localization of DDB2Wtand some NER proteins (such as XPG), vs the DDB2 mutant form.

Conclusion

The HCR confirms itself as a very helpful approach to assess in the cellular context the effect of expressing mutant vs Wt NER proteins on the DNA damage response. Loss of interaction of DDB2 and PCNA affects negatively DNA repair efficiency.
Expression and clinical significance of PD-L1 and BRAF expression in nasopharyngeal carcinoma
Authors: Cao Yabing , Chan Kin Iong , Xiao Gungli , Chen Yanqun , Qiu Xibin , Hao Hu , Mak Sao Chi , Lin Tongyu
Published: October 2019

Background

The prognostic value of programmed death-ligand 1 (PD-L1) and BRAF expression in nasopharyngeal carcinoma (NPC) is not well-defined. In this study we investigated alterations in PD-L1, BRAF and EGFR by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients.

Methods

A retrospective review of 154 NPC patients form our previous study (BMC Cancer. 2013; 13:226) were conducted. Survival and prognostic impacts were analyzed based on PD-L1, BRAF and EGFR expression levels.

Results

One hundred fifty four patients were included in this study. PD-L1 expression was detected in 87.7% of patients; 14.3% had 1–5% PD-L1 expression, 47.4% had 5–49% expression while 26% had ≥50% expression Higher PD-L1 expression was significantly associated with shorter PFS and OS. The median PFS was 25 months (95% CI 15.7–34.3 months) and OS was 35 months (95% CI 22.60–47.4 months) for patients with PD-L1 expression ≥50%; both median PFS and OS were not yet reached for patients with PD-L1 expression < 50%. PFS was significantly higher in BRAF mutation positive patients (5-year PFS: 55.1% vs. 30.8%, P = 0.044).

Conclusion

Tumor PD-L1 expression and BRAF mutation are associated with poor outcomes in patients with NPC. This study was retrospectively registered in ClinicalTrials.gov (NCT03989297) on 2019-6-18.
A descriptive study to explore working conditions and childcare practices among informal women workers in KwaZulu-Natal, South Africa: identifying opportunities to support childcare for mothers in informal work
Authors: Horwood Christiane , Haskins Lyn , Alfers Laura , Masango-Muzindutsi Zandile , Dobson Richard , Rollins Nigel
Published: October 2019

Background

Although women working in the informal economy are a large and vulnerable group, little is known about infant feeding and childcare practices among these women. The aim of this study was to explore childcare practices among mothers in informal work.

Methods

A cross-sectional survey among mothers with children aged < 2 years working in the informal economy in an urban and a rural site in KwaZulu-Natal, South Africa. Participants were selected using purposive and snowball sampling.

Results

A total of 247 interviews were conducted with 170 informal traders and 77 domestic workers. Most mothers lived with their child (225/247, 91.1%), had initiated breastfeeding (208/247; 84.2%) and many were still breastfeeding (112/247; 45.3%). Among 96 mothers who had stopped breastfeeding, the most common reason was returning to work (34/96; 35.4%). Many mothers relied on family members, particularly grandmothers, to care for their child while they were working (103/247, 41.7%) but some mothers took their child with them to work (70/247; 28.1%). Few fathers participated in the care of their child: 54 mothers (21.9%) reported that the father had ever looked after the child while she was away from home. Domestic workers were less likely than informal traders to take their child to work (p = 0.038).

Women reported receiving a salary from an informal employer (119), or being own-account workers (120) or being unpaid/paid in kind (8). Most participants were in stable work (> 4 years) with regular working hours, but received very low pay. Domestic workers were more likely than informal traders to have regular working hours (p = 0.004), and to be earning >$240 per month (p = 0.003). Mothers reported high levels of food insecurity for themselves and their child: 153 mothers (61.9%) reported having missed a meal in the past month due to lack of resources to buy food, and 88 (35.6%) mothers reported that their child had missed a meal for this reason.

Conclusion

This study provides a preliminary description of informal women workers who, despite having stable work, are vulnerable, low paid and food insecure. These women may require support to provide optimal childcare and nutrition for their children.
Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study
Authors: Green Nancy S. , Munube Deogratias , Bangirana Paul , Buluma Linda Rosset , Kebirungi Bridget , Opoka Robert , Mupere Ezekiel , Kasirye Philip , Kiguli Sarah , Birabwa Annet , Kawooya Michael S. , Lubowa Samson K. , Sekibira Rogers , Kayongo Edwards , Hume Heather , Elkind Mitchell , Peng Weixin , Li Gen , Rosano Caterina , LaRussa Philip , Minja Frank J. , Boehme Amelia , Idro Richard
Published: October 2019

Background

Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited.

Methods

We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1–12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second).

Results

Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5–12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23–1.68),p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ −2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01–1.86,p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95–24.3,p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30,p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected.

Conclusions

The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.
Motor and cognitive functioning in children treated for idiopathic clubfoot at the age of 3 years
Authors: Dillmann Julia , Schwarzer Gudrun , Peterlein Christian-Dominik
Published: October 2019

Background

Several studies have investigated motor and cognitive skills in infants as well as gross motor abilities in schoolchildren treated for congenital idiopathic clubfoot, mostly indicating specific impairments in those children. However, until now, little is known about the motor and cognitive abilities of preschool children treated for idiopathic clubfoot. Thus, it was the aim of this study to examine gross motor, fine motor and cognitive skills of 3-year-old-children treated for idiopathic clubfoot.

Method

We tested gross motor, fine motor and cognitive functioning of 10 children treated for idiopathic clubfoot and 10 typically developing children at the age of 40 months (SD = 1) with the Bayley Scales of Infant and Toddler Development.

Results

The children treated for idiopathic clubfoot showed a slight delay in gross motor development. In particular, they demonstrated difficulties in tiptoeing, walking upstairs and walking downstairs. Moreover, we found some slight deficits in cognitive development, particularly in visual-spatial memory.

Discussion

Children treated for idiopathic clubfoot appear to have an increased risk of gross motor and spatial cognitive deficits. Orthopedic pediatrics should incorporate measures of gross motor functioning, for example tiptoeing, in their orthopedic setting. Moreover, future studies are needed to clarify whether the observed deficits persist through childhood. If so, some kind of a motor training for children with idiopathic clubfoot might be required.
Association between benzodiazepines and suicide risk: a matched case-control study
Authors: Cato Ville , Holländare Fredrik , Nordenskjöld Axel , Sellin Tabita
Published: October 2019

Background

It is unclear whether benzodiazepines increase the risk of suicide. The aim of this study was to test the hypothesis that benzodiazepines are associated with an increased risk of suicide, by comparing psychopharmacological interventions between psychiatric patients who committed suicide and a group of matched controls.

Methods

The case group comprised 154 psychiatric patients (101 men, 53 women; age range: 13–96 years) who had committed suicide in Örebro County, Sweden. Control psychiatric patients matched by age, sex, and main psychiatric diagnosis were selected for each case. Binary logistic regression was used to calculate odds ratios in unadjusted and adjusted models.

Results

Benzodiazepine prescriptions were more common among cases than controls (65/154 [42.2%] versus 43/154 [27.9%], p = 0.009, odds ratio: 1.89 [95% CI: 1.17–3.03]). This association remained significant in a model adjusted for previous suicide attempts and somatic hospitalizations (odds ratio: 1.83 [95% CI: 1.06–3.14]). No statistically significant differences were seen between the groups in the use of any other subtype of psychopharmaceutical agent.

Conclusions

These data indicate that benzodiazepine use may increase the risk of suicide. However, this study is limited by the potential for indication bias.
Comparative analysis of trends and determinants of anaemia between adult and teenage pregnant women in two rural districts of Ghana
Authors: Ampiah Millicenta K. M. , Kovey Jerry J. , Apprey Charles , Annan Reginald A.
Published: October 2019

Background

The prevalence of iron deficiency anaemia remains high in pregnant women and the situation may be worse for pregnant adolescents. This study aimed to comparatively analyse the trends and determinants of anaemia between adult and teenage pregnant women in rural Ghana.

Methods

A retrospective study design was employed. Data including primarily pregnancy history, haemoglobin levels and anaemia status were collected from the manual medical records of 1002 women stored in the repositories of two rural district hospitals in the Ashanti Region of Ghana over the years 2011–2015. Data was analysed using chi-square analysis, t-test, two-way ANOVA and binary logistic regression. Bivariate and multivariate analyses were also done to establish associations and predictors of anaemia.

Results

An overall drop in mean haemoglobin from 11.1 g/dl in 2011 to 10.6 g/dl in 2015 was observed for adults, while an overall increase from 9.4 g/dl to 10.2 g/dl occurred in teenagers. Further, anaemia prevalence declined at the 36th week of pregnancy, and from 2011 to 2015, for both teenagers and adults. Among factors tested for association with haemoglobin levels using bivariate and multivariate analyses, gestational age alone was significant (P = 0.028). Between-subject effects determined using 2-way ANOVA indicated year of pregnancy alone, as well as in combination with age group (F = 3.1, P = 0.019) significantly affected haemoglobin levels. From binary regression analysis, BMI (OR 0.967, 95% CI:0.936–0.999, P = 0.042), gestational age (OR 1.058, 95% CI:1.013–1.106, P = 0.011) and pregnancy year (OR-2012(0.402); 2013(0.53); 2014(0.569); 2015(0.817), 95% CI: 2012(0.256–0.631); 2013(0.338–0.829); 2014(0.366–0.886); 2015(0.501–1.333), P = 0.001) were found to be significant predictors of anaemia at first antenatal visit. Also, the trimester of reporting for antenatal care, specifically the second trimester (OR-0.261, 95% CI: 0.072–0.951, P = 0.042) and the pregnancy year (OR-2012(0.235); 2013(0.206); 2014(0.530); 2015(0.222), 95% CI: 2012(0.101–0.545); 2013(0.081–0.522); 2014(0.197–1.428); 2015(0.049–1.018), P = 0.003) were more significant at the 36th pregnancy week.

Conclusions

Although the trends observed were decreasing in both adults and teenagers in the years reported, anaemia levels remained high for each year in either group. Anaemia, therefore remains a major health problem, especially in the areas studied, and antenatal interventions need a second look to know what might make them more effective.
Spatial association between outdoor air pollution and lung cancer incidence in China
Authors: Xing D. F. , Xu C. D. , Liao X. Y. , Xing T. Y. , Cheng S. P. , Hu M. G. , Wang J. X.
Published: October 2019

Background

Lung cancer is the most common cancer in China. Previous studies have indicated that lung cancer incidence exhibits remarkable spatial heterogeneity, and lung cancer is related to outdoor air pollution. However, the non-linear spatial association between outdoor air pollution and lung cancer incidence in China remains unclear.

Methods

In this study, the relationships between the lung cancer incidence of males and females from 207 counties in China in 2013 with annual concentrations of PM2.5, PM10, SO2, NO2, CO and O3 were analysed. GeoDetector q statistic was used for examining the non-linear spatial association between outdoor air pollution and incidence of lung cancer.

Results

An apparent spatial and population gender heterogeneity was found in the spatial association between outdoor air pollution and lung cancer incidence. Among the six selected pollutants, SO2 has the greatest influence on lung cancer (q = 0.154 in females) in north China. In the south, each selected pollutant has a significant impact on males or females, and the mean q value in the south is 0.181, which is bigger than that in the north (q = 0.154). In addition, the pollutants have evident non-linear interaction effects on lung cancer. In north China, the interaction between SO2 and PM2.5 is the dominant interaction, with q values of 0.207 in males and 0.334 in females. In the south, the dominant interactive factors are between SO2 and O3 in males and between SO2 and CO in females, with q values of 0.45, 0.232 respectively. Smoking is a substantial contributor to lung cancer among men, either in South or North China, with q value of 0.143 and 0.129 respectively, and the interaction between smoking and air pollutants increases this risk.

Conclusions

This study implies that the influence of SO2 and PM2.5 on lung cancer should be focused on in north China, and in the south, the impact of O3 and CO as well as their interaction with SO2 need to be paid more attention. Smoking, particularly in men, remains a significant risk factor for lung cancer in both North and South China.
UPRIGHT, a resilience-based intervention to promote mental well-being in schools: study rationale and methodology for a European randomized controlled trial
Authors:   on behalf of the UPRIGHT consortium, Las Hayas Carlota , Izco-Basurko Irantzu , Fullaondo Ane , Gabrielli Silvia , Zwiefka Antoni , Hjemdal Odin , Gudmundsdottir Dora G. , Knoop Hans Henrik , Olafsdottir Anna S. , Donisi Valeria , Carbone Sara , Rizzi Silvia , Mazur Iwona , Krolicka-Deregowska Anna , Morote Roxanna , Anyan Frederick , Ledertoug Mette Marie , Tange Nina , Kaldalons Ingibjorg , Jonsdottir Bryndis Jona , González-Pinto Ana , Vergara Itziar , González Nerea , Mar Medina Javier , de Manuel Keenoy Esteban
Published: October 2019

Background

Adolescence is crucial period for laying the foundations for healthy development and mental well-being. The increasing prevalence of mental disorders amongst adolescents makes promotion of mental well-being and prevention interventions at schools important. UPRIGHT (Universal Preventive Resilience Intervention Globally implemented in schools to improve and promote mental Health for Teenagers) is designed as a whole school approach (school community, students and families) to promote a culture of mental well-being and prevent mental disorders by enhancing resilience capacities. The present article aims at describing the rationale, conceptual framework, as well as methodology of implementation and evaluation of the UPRIGHT intervention.

Methods

UPRIGHT project is a research and innovation project funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 754919 (Duration: 48 months). The theoretical framework has been developed by an innovative and multidisciplinary approach using a co-creation process inside the UPRIGHT Consortium (involving seven institutions from Spain, Italy, Poland, Norway, Denmark, and Iceland). Resulted is the UPRIGHT programme with 18 skills related to 4 components: Mindfulness, Coping, Efficacy and Social and Emotional Learning.

Among the five Pan-European regions, 34 schools have been currently involved (17 control; 17 intervention) and around 6000 adolescents and their families are foreseen to participate along a 3-year period of evaluation. Effectiveness of the intervention will be evaluated as a randomized controlled trial including quantitative and qualitative analysis in the five Pan-European regions representative of the cultural and socioeconomic diversity. The cost-effectiveness assessment will be performed by simulation modelling methods.

Discussion

We expect a short- to medium-term improvement of mental well-being in adolescents by enhancing resilience capacities. The study may provide robust evidence on intrapersonal, familiar and social environmental resilience factors promoting positive mental well-being.

Trial registration

ClinicalTrials.gov Identifier: NCT03951376. Registered 15 May 2019.
Standardised snus packaging reduces brand differentiation: a web-based between-subject experiment
Authors: Halkjelsvik Torleif , Scheffels Janne
Published: October 2019

Background

Perceptions of tobacco packaging may be consequential for consumption and initiation. We explored the potential effect of standardised packaging on young adults’ ratings of the appeal of brands of snus (Swedish moist snuff) and on their perceptions of typical users of these brands. We were interested in both the effects on average levels of ratings and on the within-subject variability of the ratings. The latter was used as a measure of the extent to which individuals can differentiate between brands.

Methods

A sample of 625 Norwegians aged 16–30 were randomly allocated to one of three between-subject conditions: Branded Packaging, Standardised Packaging, or Standardised Packaging with Health Warnings. The participants rated 10 snus brands on measures of general appeal and on their perceptions of the typical brand user (e.g., “… is sporty and active”).

Results

The standardised packages (without health warnings) were not rated more negatively than the branded packages, while the standardised packages with health warnings were rated slightly more negatively than the branded packages. However, in terms of within-subject standard deviations, the variability of the brand ratings across the packages was substantially lower for standardised packaging types in comparison to branded packages.

Conclusions

Even in cases where standardised tobacco packaging appears to have little overall effect on the valence of the average ratings, it can have a strong effect on the variability of the ratings. This suggests that standardised packaging can reduce the potential for brand differentiation.