bluuebunny/crossref_metadata_2025_split huggingface dataset:
First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease
Authors: Greillier Sophie , Daniel Laurent , Caillaud Catherine , Dussol Bertrand , Touchard Guy , Goujon Jean-Michel , Jourde-Chiche Noémie , Bobot Mickaël 
Published: June 2020

Abstract
Background
Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes.

Case presentation
The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes’ lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography.

Conclusions
We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.
The Rajarata Pregnancy Cohort (RaPCo): study protocol
Authors: Agampodi Thilini Chanchala , Wickramasinghe Nuwan Darshana , Prasanna Rampathige Indika Ruwan , Irangani Malawara Kankanamalage Lasandha , Banda Jayasundara Mudiyanselage Samarakoo , Jayathilake Pradana Mudiyanselage Bandula , Hettiarachchi Ayesh , Amarasinghe Gayani , Jayasinghe Imasha , Koralagedara Iresha , Gunarathne Sajaan Praveena , Wickramage Sujanthi , Warnasekara Janith , Lokunarangoda Niroshan , Mendis Vasana , Dissanayaka Ajith Kumara , Premadasa Jagath , Hettigama Nandana , Koralagedara Dayaratne , Weerasinghe Manjula , Malawanage Krishanthi , Jayakodi Hemali , Wickramasinghe Anuprabha , Agampodi Suneth Buddhika 
Published: June 2020

AbstractBackgroundEnding preventable maternal deaths remains a global priority and in the later stages of obstetric transition, identifying the social determinants of maternal health outcomes is essential to address stagnating maternal mortality rates. Countries would hardly achieve the Sustainable Development Goal (SGD) targets on maternal health, unless the complex and context-specific socio-economic aetiologies associated with maternal mental health and suicide are identified. The Rajarata Pregnancy Cohort (RaPCo) is a prospective cohort study, designed to explore the interactions between social determinants and maternal mental health in determining pregnancy and new-born outcomes.MethodsThe study will recruit all eligible pregnant women in the maternal care programme of Anuradhapura district, Sri Lanka from July to September 2019. The estimated sample size is 2400. We will assess the socio-demographic and economic status, social capital, gender-based violence and mental health, including a clinical examination and biochemical investigations during the first trimester. Participants will undergo four follow-ups at 2nd and 3rd trimesters, at delivery and in early postpartum. The new-borns will be followed up at birth, neonatal period, at 6 six months and at 1 year. Pregnancy and child outcome data will be collected using direct contact. Qualitative studies will be carried out to understand the complex social factors and behavioural dimensions related to abortion, antenatal depression, maternal deaths and near misses.DiscussionThis is the first reported maternal cohort in Sri Lanka focusing on social determinants and mental health. As a country in stage four of obstetric transition, these findings will provide generalizable evidence on achieving SGD targets in low- and middle-income countries. The study will be conducted in a district with multi-cultural, multi-ethnic and diverse community characteristics; thus, will enable the evidence generated to be applied in many different contexts. The study also possesses the strength of using direct participant contact, data collection, measurement, examination and biochemical testing to minimise errors in routinely collected data. The RaPCo study will be able to generate evidence to strengthen policies to further reduce maternal deaths in the local, regional and global contexts particularly focusing on social factors and mental health, which are not optimally addressed in the global agenda.
MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma
Authors: Bissey Pierre-Antoine , Teng Mona , Law Jacqueline H. , Shi Wei , Bruce Jeff P. , Petit Valentin , Tsao Sai W. , Yip Kenneth W. , Liu Fei-Fei 
Published: June 2020

Abstract
Background
A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance.

Methods
Two hundred forty-six NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666–1, were used for miR-34c gain-of-function and loss-of-function experiments. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay.

Results
MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro. The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients.

Conclusion
miR-34c is downregulated in NPC. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.
Rationale and design of “Hearts & Parks”: study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity
Authors: Armstrong Sarah C. , Windom McAllister , Bihlmeyer Nathan A. , Li Jennifer S. , Shah Svati H. , Story Mary , Zucker Nancy , Kraus William E. , Pagidipati Neha , Peterson Eric , Wong Charlene , Wiedemeier Manuela , Sibley Lauren , Berchuck Samuel I. , Merrill Peter , Zizzi Alexandra , Sarria Charles , Dressman Holly K. , Rawls John F. , Skinner Asheley C. 
Published: June 2020

Abstract
Background
The prevalence of child and adolescent obesity and severe obesity continues to increase despite decades of policy and research aimed at prevention. Obesity strongly predicts cardiovascular and metabolic disease risk; both begin in childhood. Children who receive intensive behavioral interventions can reduce body mass index (BMI) and reverse disease risk. However, delivering these interventions with fidelity at scale remains a challenge. Clinic-community partnerships offer a promising strategy to provide high-quality clinical care and deliver behavioral treatment in local park and recreation settings. The Hearts & Parks study has three broad objectives: (1) evaluate the effectiveness of the clinic-community model for the treatment of child obesity, (2) define microbiome and metabolomic signatures of obesity and response to lifestyle change, and (3) inform the implementation of similar models in clinical systems.

Methods
Methods are designed for a pragmatic randomized, controlled clinical trial (n = 270) to test the effectiveness of an integrated clinic-community child obesity intervention as compared with usual care. We are powered to detect a difference in body mass index (BMI) between groups at 6 months, with follow up to 12 months. Secondary outcomes include changes in biomarkers for cardiovascular disease, psychosocial risk, and quality of life. Through collection of biospecimens (serum and stool), additional exploratory outcomes include microbiome and metabolomics biomarkers of response to lifestyle modification.

Discussion
We present the study design, enrollment strategy, and intervention details for a randomized clinical trial to measure the effectiveness of a clinic-community child obesity treatment intervention. This study will inform a critical area in child obesity and cardiovascular risk research—defining outcomes, implementation feasibility, and identifying potential molecular mechanisms of treatment response.

Clinical trial registration
NCT03339440.
The application research of xTAG GPP multiplex PCR in the diagnosis of persistent and chronic diarrhea in children
Authors: Wang Chunli , Zhou Xiaoying , Zhu Mengshu , Yin Hanjun , Tang Jiamei , Huang Yan , Zheng Bixia , Jin Yu , Liu Zhifeng 
Published: June 2020

Abstract
Background
Persistent and chronic diarrhea is difficult to treat, and infection is still the main cause. In this study, we investigate the application value of xTAG gastrointestinal pathogen panel (xTAG GPP) multiplex PCR in the early diagnosis of persistent and chronic diarrhea in children and to understand the epidemiology of intestinal diarrhea pathogens.

Methods
One hundred ninety-nine specimens were collected from Nanjing Children’s Hospital Affiliated to Nanjing Medical University (Nanjing, China). We compared the xTAG GPP multiplex PCR assay with traditional methods (culture, rapid enzyme immunoassay chromatography, and microscopic examination) and performed a statistical analysis.

Results
The positive rate of the xTAG GPP multiplex PCR assay of diarrhea specimens from 199 patients was 72.86% (145/199). The virus detection rate was 48.7%, and rotavirus A was the most common organism detected (34.67%), concentrated in winter, and was common in children. The second most common organism detected was norovirus GI/GII (20.6%). The positive rate of this bacteria was 40.2%, and Campylobacter (22.11%, 44/199) was most frequently detected. C. difficile toxins A/B and Salmonella was detected in 44 and 17 samples, respectively. Infections with Shigella occurred 4 times, and E. coli O157 was only detected once. Three samples were parasitic (1.51%), two samples were positive for Entamoeba histolytica, and one was positive for Cryptosporidium. Adenovirus 40/41, STEC, ETEC, Giardia, Yersinia enterocolitica and Vibrio cholerae were not detected. In total, 86 (43.2%) infected specimens with a single pathogen were detected. There were 59 coinfections (29.65% of the samples) of viruses and/or bacteria and/or parasites. Coinfections involved 49 double infections (24.62%), 9 triple infections (4.52%) and 1 quadruple infections (0.5%). Norovirus GI/GII was found to have the highest involvement, with 32 coinfections (16.08%).

Conclusion
The xTAG GPP multiplex PCR assay is simple, sensitive, and specific and can be used as a quick way to diagnose persistent and chronic diarrhea in children.
Characteristics and risk factors of children with sleep-disordered breathing in Wuxi, China
Authors: Guo Yun , Pan Zhenzhen , Gao Fei , Wang Qian , Pan Shanshan , Xu Shiyao , Hui Yu , Li Ling , Qian Jun 
Published: June 2020

Abstract
Background
Sleep-disordered breathing (SDB) is a common syndrome in children, related to their immune responses, cardiovascular function, and neurocognitive function. This study aimed to determine the prevalence of SDB among children in Wuxi, China, and to evaluate the protective and risk factors of SDB in children.

Methods
A cross-sectional study was conducted on children attending different schools across Wuxi, China, aged 3–14 years old. Of a total of 5630 questionnaires distributed to the parents of the children, 3997 (71.0%) were deemed to be valid. The data on the general sociodemographic factors, children’s allergy and sleep characteristics, and the parents’ sleep characteristics were also collected. The Paediatric Sleep Questionnaire (PSQ) score was used to identify children at high risk of SDB. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression.

Results
The prevalence of SDB in this cohort was 13.4% (N = 534). SDB prevalence significantly differed in children with asthma (28.2% vs. 12.8%, P < 0.001), eczema (19.0% vs. 10.0%, P < 0.001), urticaria (16.4% vs. 12.9%, P < 0.01) and rhinitis (21.4% vs. 10.7%, P < 0.001). No significant differences were found in SDB prevalence with respect to pillow material or quilt material. On multivariate logistic regression analysis, asthma (OR 1.986 (95% CI 1.312–3.007), P < 0.01), eczema (OR 1.675 (95% CI 1.377–2.037), P < 0.001), rhinitis (OR 1.998 (95% CI 1.635–2.441), suffered from familial sleep sickness (OR 2.416 (95% CI 1.975–2.955), P < 0.001) and whose mothers slept for a shorter duration (6 h–8 h: OR 1.370 (95% CI 1.089–1.724), P < 0.01; <6 h: OR 3.385(95% CI 2.098–5.461), P < 0.001) increased the odds of having SDB. The incidence of SDB significantly decreased with children’s age (6–11 years old: 0R 0.768 (95% CI 0.597–0.989), P < 0.05; 12–14 years old: OR 0.691 (95% CI 0.530–0.901), P < 0.01).

Conclusion
The results of this study demonstrated that atopic diseases (asthma, eczema, and rhinitis) and family sleep habits were risk factors for SDB in children in Wuxi, China.
An approach to estimating the environmental burden of cancer from known and probable carcinogens: application to Ontario, Canada
Authors: Greco Susan Lavinia , MacIntyre Elaina , Young Stephanie , Warden Hunter , Drudge Christopher , Kim JinHee , Candido Elisa , Demers Paul , Copes Ray 
Published: June 2020

Abstract
Background
Quantifying the potential cancer cases associated with environmental carcinogen exposure can help inform efforts to improve population health. This study developed an approach to estimate the environmental burden of cancer and applied it to Ontario, Canada. The purpose was to identify environmental carcinogens with the greatest impact on cancer burden to support evidence-based decision making.

Methods
We conducted a probabilistic assessment of the environmental burden of cancer in Ontario. We selected 23 carcinogens that we defined as “environmental” (e.g., pollutants) and were relevant to the province, based on select classifications provided by the International Agency for Research on Cancer. We evaluated population exposure to the carcinogens through inhalation of indoor/outdoor air; ingestion of food, water, and dust; and exposure to radiation. We obtained or calculated concentration-response functions relating carcinogen exposure and the risk of developing cancer. Using both human health risk assessment and population attributable fraction models in a Monte Carlo simulation, we estimated the annual cancer cases associated with each environmental carcinogen, reporting the simulation summary (e.g., mean and percentiles).

Results
We estimated between 3540 and 6510 annual cancer cases attributable to exposure to 23 environmental carcinogens in Ontario. Three carcinogens were responsible for over 90% of the environmental burden of cancer: solar ultraviolet (UV) radiation, radon in homes, and fine particulate matter (PM2.5) in outdoor air. Eight other carcinogens had an estimated mean burden of at least 10 annual cancer cases: acrylamide, arsenic, asbestos, chromium, diesel engine exhaust particulate matter, dioxins, formaldehyde, and second-hand smoke. The remaining 12 carcinogens had an estimated mean burden of less than 10 annual cancer cases in Ontario.

Conclusions
We found the environmental burden of cancer in Ontario to fall between previously estimated burdens of alcohol and tobacco use. These results allow for a comparative assessment across carcinogens and offer insights into strategies to reduce the environmental burden of cancer. Our analysis could be adopted by other jurisdictions and repeated in the future for Ontario to track progress in reducing cancer burden, assess newly classified environmental carcinogens, and identify top burden contributors.
Development of a TB vaccine trial site in Africa and lessons from the Ebola experience
Authors: Kaguthi G. , Nduba V. , Rabuogi P. , Okelloh D. , Ouma S. G. , Blatner G. , Gelderbloem S. , Mitchell Ellen M. H. , Scott Cherise P. , Verver S. , Hawkridge T. , de Steenwinkel J. E. M. , Laserson K. F. , Richardus J. H. 
Published: June 2020

AbstractTuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.
Factors associated with catastrophic total costs due to tuberculosis under a designated hospital service model: a cross-sectional study in China
Authors: Yang Tianchi , Chen Tong , Che Yang , Chen Qin , Bo Dingyi 
Published: June 2020

Abstract
Background
Certain districts and counties in China designated local general hospital as the designated hospital for tuberculosis (TB) management after the promulgation of the Law of Practicing Physicians in 2009. To our knowledge, there is limited research on catastrophic payments of TB patients under this service model, often with inconsistent conclusions. In addition, there has been no published studies from China using the updated 2018 World Health Organization (WHO) definition of catastrophic total costs due to TB. This study used the latest criterion recommended by the WHO to analyze the incidence of catastrophic total costs for households affected by TB under the designated hospital model and explore its influencing factors.

Methods
A cross-sectional analysis was carried out in all ten designated hospitals in Ningbo, China. Eligible pulmonary TB cases confirmed by sputum culture of Mycobacterium tuberculosis were recruited and surveyed from September 2018 to October 2018. We evaluated catastrophic total costs using total costs for TB treatment exceeding 20% of the household’s annual pre-TB income. A sensitivity analysis was performed while varying the thresholds. The least absolute shrinkage and selection operator (LASSO) regression were applied to select variables, and multiple logistic regression analysis were used to identify the determinants of catastrophic total costs.

Results
A total of 672 patients were included, with a median age of 41 years old. The rate of catastrophic total costs of surveyed households was 37.1%, and that of households affected by MDR was 69.6%. Medical cost accounted for more than 60% of the total cost. 57.7% cases were hospitalized. The hospitalization rates of patients with no comorbidities, no severe adverse drug reactions, and rifampin-sensitive TB were 53.9, 54.9, and 55.3%, respectively. Patients in the poorest households had the highest hospitalization rates (Q1:54.8%, Q2:61.4%, Q3:52.2%, Q4:49.5%, Q5:69.7%, P = 0.011) and the highest incidence of severe adverse drug reactions (Q1:29.6%, Q2:19.6%, Q3:28.0%, Q4:33.7%, Q5:35.3%, P = 0.034). Factors such as elderly, minimum living security, unemployed before or after illness, poor economic status, seeking medical care outside the city, hospitalization, absence of local basic medical insurance coverage and MDR were positively associated with catastrophic costs.

Conclusion
Substantial proportions of patients and households affected by pulmonary TB faced catastrophic economic risks in Ningbo, China. The existing policies that focus on expanding the coverage of basic medical insurance and economic protection measures (such as cash transfers to compensate low-income households for direct non-medical costs and income loss) might be insufficient. Tailored program that mitigate inappropriate healthcare and address equity of care delivery are worthy of attention.