bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank
Authors: Dashti Hassan S. , Miranda Nicole , Cade Brian E. , Huang Tianyi , Redline Susan , Karlson Elizabeth W. , Saxena Richa 
Published: January 2022

Abstract
Background
Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes.

Methods
The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes.

Results
Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m2), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m2). Each standard deviation increment in the PRS was associated with 0.83 kg/m2 unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m2 in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m2 in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes.

Conclusions
In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.
Price, quality, and market dynamics of malaria rapid diagnostic tests: analysis of Global Fund 2009–2018 data
Authors: Wittenauer Rachel , Nowak Spike , Luter Nick 
Published: January 2022

AbstractBackgroundRapid diagnostic tests (RDTs) for malaria are a vital part of global malaria control. Over the past decade, RDT prices have declined, and quality has improved. However, the relationship between price and product quality and their larger implications on the market have yet to be characterized. This analysis used purchase data from the Global Fund together with product quality data from the World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) Malaria RDT Product Testing Programme to understand three unanswered questions: (1) Has the market share by quality of RDTs in the Global Fund’s procurement orders changed over time? (2) What is the relationship between unit price and RDT quality? (3) Has the market for RDTs financed by the Global Fund become more concentrated over time?MethodsData from 10,075 procurement transactions in the Global Fund’s database, which includes year, product, volume, and price, was merged with product quality data from all eight rounds of the WHO-FIND programme, which evaluated 227 unique RDT products. To describe trends in market share by quality level of RDT, descriptive statistics were used to analyse trends in market share from 2009 to 2018. A generalized linear regression model was then applied to characterize the relationship between price and panel detection score (PDS), adjusting for order volume, year purchased, product type, and manufacturer. Third, a Herfindahl–Hirschman Index (HHI) score was calculated to characterize the degree of market concentration.ResultsLower-quality RDTs have lost market share between 2009 and 2018, as have the highest-quality RDTs. No statistically significant relationship between price per test and PDS was found when adjusting for order volume, product type, and year of purchase. The HHI was 3,570, indicating a highly concentrated market.ConclusionsAdvancements in RDT affordability, quality, and access over the past decade risk stagnation if health of the RDT market as a whole is neglected. These results suggest that from 2009 to 2018, this market was highly concentrated and that quality was not a distinguishing feature between RDTs. This information adds to previous reports noting concerns about the long-term sustainability of this market. Further research is needed to understand the causes and implications of these trends.
Co-creating a local environmental epidemiology study: the case of citizen science for investigating air pollution and related health risks in Barcelona, Spain
Authors: Gignac Florence , Righi Valeria , Toran Raül , Errandonea Lucía Paz , Ortiz Rodney , Nieuwenhuijsen Mark , Creus Javier , Basagaña Xavier , Balestrini Mara 
Published: January 2022

Abstract
Background
While the health risks of air pollution attract considerable attention, both scholarly and within the general population, citizens are rarely involved in environmental health research, beyond participating as data subjects. Co-created citizen science is an approach that fosters collaboration between scientists and lay people to engage the latter in all phases of research. Currently, this approach is rare in environmental epidemiology and when co-creation processes do take place, they are often not documented. This paper describes the first stages of an ongoing co-created citizen science epidemiological project in Barcelona (Spain), that included identifying topics that citizens wish to investigate as regards air pollution and health, formulating their concerns into research questions and co-designing the study protocol. This paper also reflects key trade-offs between scientific rigor and public engagement and provides suggestions to consider when applying citizen science to environmental health studies.

Methods
Experts created an online survey and analyzed responses with descriptive statistics and qualitative coding. A pop-up intervention was held to discuss with citizens their concerns about air pollution and health. Later on, a community meeting was organized to narrow down the research topics and list potential research questions. In an online survey, citizens were asked to vote for the research question they would like to investigate with the experts. A workshop was held to choose a study design in which citizens would like to partake to answer their preferred research question.

Results
According to 488 respondents from the first survey, cognitive and mental health were the main priorities of investigation. Based on the second survey, with 27% of the votes from 556 citizens, the most popular research question was, “How does air pollution together with noise and green/blue spaces affect mental health?”. The study design selected was an observational study in which citizens provide daily repeated measures of different cognitive and mental health outcomes and relate them to the air pollution concentrations.

Conclusions
Based on the co-creation activities and the results obtained, we conclude that applying citizen science in an environmental health project is valuable for researchers despite some challenges such as engaging citizens and maximizing representativity.
Depression, anxiety and health-related quality of life in paediatric intracranial germ cell tumor survivors
Authors: Lv Wenyi , Li Bo , Feng Jin , Chen Li , Qiu Xiaoguang , Liu Shuai 
Published: January 2022

Abstract
Background
Little is known about depression and anxiety among paediatric intracranial germ cell tumour (iGCT) survivors. We aimed to evaluate the risk factors associated with depression, anxiety and health-related quality of life (HRQoL) in paediatric iGCT survivors.

Methods
We recruited 200 iGCT patients (and their parents) from Beijing Tiantan Hospital and assessed their HRQoL using the Paediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales. The Children’s Depression Inventory, Screen for Child Anxiety Related Emotional Disorders, and Symptom Checklist 90 were used to evaluate depression and anxiety. The results were analysed based on disease recurrence, tumour location and treatment strategies.

Results
Survivors with recurrent tumours had worse HRQoL scores than those with non-recurrent tumours. Patients with tumours involving both the suprasellar and basal ganglia regions had the worst HRQoL scores. A large proportion of survivors had depression or anxiety. Both depression and anxiety scores were highly correlated with the HRQoL emotional functioning scores. The parent proxy-reports (PPR) and child self-reports were highly correlated in all domains.

Conclusions
This study demonstrated the clinical factors affecting paediatric iGCT survivors’ depression, anxiety, and HRQoL. Therefore, psychological interventions should be implemented. It also suggests that the PedsQL PPR would be helpful for routine screening.
Transcriptome analysis of eutopic endometrium in adenomyosis after GnRH agonist treatment
Authors: Tian Jiao , Kang Nannan , Wang Junxia , Sun Haixiang , Yan Guijun , Huang Chenyang , Mei Jie 
Published: January 2022

Abstract
Background
Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood.

Methods
Eutopic endometrial specimens were collected from patients with adenomyosis before and after GnRHa treatment in the midsecretory phase. RNA sequencing (RNA-Seq) of these specimens was performed for transcriptome analysis. The differentially expressed genes (DEGs) of interest were confirmed by real-time PCR and immunohistochemistry.

Results
A total of 132 DEGs were identified in the endometrium of patients with adenomyosis after GnRHa treatment compared with the control group. Bioinformatics analysis predicted that immune system-associated signal transduction changed significantly after GnRHa treatment. Chemokine (C-C motif) ligand 21 (CCL21) was found to be highly expressed in the eutopic endometrium after GnRHa treatment, which may be involved in the improvement of endometrial receptivity in adenomyosis.

Conclusion
This study suggests that molecular regulation related to immune system-associated signal transduction is an important mechanism of GnRHa treatment in adenomyosis. Immunoreactive CCL21 is thought to regulate inflammatory events and participate in endometrial receptivity in adenomyosis.
Agitation-dependent biomechanical forces modulate GPVI receptor expression and platelet adhesion capacity during storage
Authors: Hosseini Ehteramolsadat , Solouki Amin , Haghshenas Masood , Ghasemzadeh Mehran , Schoenwaelder Simone M. 
Published: January 2022

Abstract
Background
Continuous agitation during storage slows down the platelet storage lesions. However, in special circumstances, manual-mixing can be alternatively used to store products for short time periods without compromising platelet quality. Based on this finding, and given the role of shear stress in modulating receptor expression, we were interested in comparing the levels of platelet adhesion receptor, GPVI and platelet adhesion capacity under each storage condition.

Methods
Platelet concentrates (PCs) were divided into three groups: continuously-agitated PCs (CAG-PCs) with or without PP2 (Src kinase inhibitor) and manually-mixed PCs (MM-PCs). Platelet count/MPV, swirling, GPVI and P-selectin expression, GPVI shedding, platelet adhesion/spreading to collagen were examined during 5 days of storage.

Results
While MM- and CAG-PCs showed similar levels of P-selectin expression, GPVI expression was significantly elevated in MM-PCs with lower GPVI shedding/expression ratios, enhanced platelet adhesion/spreading and swirling in manually-mixed PCs. Of note, CAG-PCs treated with PP2 also demonstrated lower P-selectin expression and GPVI shedding, higher GPVI expression and attenuated swirling and spreading capability.

Conclusion
Given the comparable platelet activation state in MM and CAG-PCs as indicated by P-selectin expression, enhanced platelet adhesion/spreading in MM-PCs, along with relatively higher GPVI expression here, supports previous studies demonstrating a role for biomechanical forces in modulating GPVI-dependent function. Thus, lower GPVI expression in CAG-PCs may be due to shear forces induced by agitation, which keeps this receptor down-regulated while also attenuating platelet adhesion/spreading capacities during storage. Low platelet function in PP2-CAG-PCs also highlights the importance of Src-kinases threshold activity in maintaining platelets quality.
Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial
Authors: de Almeida Baptista Marcella Vassão , da Silva Laís Teodoro , Samer Sadia , Oshiro Telma Miyuki , Shytaj Iart Luca , Giron Leila B. , Pena Nathalia Mantovani , Cruz Nicolly , Gosuen Gisele Cristina , Ferreira Paulo Roberto Abrão , Cunha-Neto Edécio , Galinskas Juliana , Dias Danilo , Sucupira Maria Cecilia Araripe , de Almeida-Neto Cesar , Salomão Reinaldo , da Silva Duarte Alberto José , Janini Luís Mário , Hunter James R. , Savarino Andrea , Juliano Maria Aparecida , Diaz Ricardo Sobhie 
Published: January 2022

AbstractBackgroundWe developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses.MethodsPBMCs were obtained from 10 HIV+individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+and CD8+T-cells.ResultsThe protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+and CD8+T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+and CD8+T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined.ConclusionsMDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment.Trial registrationNCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure,https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016)
Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings
Authors: Shannon Caitlin , Hurt Chris , Soremekun Seyi , Edmond Karen , Newton Sam , Amenga-Etego Seeba , Tawiah-Agyemang Charlotte , Hill Zelee , Manu Alexander , Weobong Ben , Kirkwood Betty , Hurt Lisa 
Published: January 2022

Abstract
Background
Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes.

Main body
Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time.

Conclusion
High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies.
Integration of Aspergillus niger transcriptomic profile with metabolic model identifies potential targets to optimise citric acid production from lignocellulosic hydrolysate
Authors: Upton Daniel J. , Kaushal Mehak , Whitehead Caragh , Faas Laura , Gomez Leonardo D. , McQueen-Mason Simon J. , Srivastava Shireesh , Wood A. Jamie 
Published: January 2022

AbstractBackgroundCitric acid is typically produced industrially byAspergillus niger-mediated fermentation of a sucrose-based feedstock, such as molasses. The fungusAspergillus nigerhas the potential to utilise lignocellulosic biomass, such as bagasse, for industrial-scale citric acid production, but realising this potential requires strain optimisation. Systems biology can accelerate strain engineering by systematic target identification, facilitated by methods for the integration of omics data into a high-quality metabolic model. In this work, we perform transcriptomic analysis to determine the temporal expression changes during fermentation of bagasse hydrolysate and develop an evolutionary algorithm to integrate the transcriptomic data with the available metabolic model to identify potential targets for strain engineering.ResultsThe novel integrated procedure matures our understanding of suboptimal citric acid production and reveals potential targets for strain engineering, including targets consistent with the literature such as the up-regulation of citrate export and pyruvate carboxylase as well as novel targets such as the down-regulation of inorganic diphosphatase.ConclusionsIn this study, we demonstrate the production of citric acid from lignocellulosic hydrolysate and show how transcriptomic data across multiple timepoints can be coupled with evolutionary and metabolic modelling to identify potential targets for further engineering to maximise productivity from a chosen feedstock. The in silico strategies employed in this study can be applied to other biotechnological goals, assisting efforts to harness the potential of microorganisms for bio-based production of valuable chemicals.
MIND diet and the risk of dementia: a population-based study
Authors: de Crom Tosca O. E. , Mooldijk Sanne S. , Ikram M. Kamran , Ikram M. Arfan , Voortman Trudy 
Published: January 2022

Abstract
Background
Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors.

Methods
In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018.

Results
During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I.

Conclusion
Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by reverse causality and residual confounding by lifestyle. Further research is needed to unravel to which extent the MIND diet may affect the risk of dementia.
Tumor-induced osteomalacia: a case report
Authors: Aligail Khalid , Dave Joel A. , Ross Ian Louis 
Published: January 2022

Abstract
Background
Tumor-induced osteomalacia is a rare, acquired paraneoplastic syndrome, including hypophosphatemia, high serum alkaline phosphatase, reduced active vitamin D, suboptimal bone mineral density, bone pain, fragility fractures, and muscle weakness.

Case presentation
We report a case of 74–year–old male of mixed ancestry with hypophosphatemia resistant to treatment despite optimal compliance, associated with profound reduction of bone mineral density and multiple nontraumatic fractures, including bilateral rib fractures, lower-thoracic (T11, T12) vertebrae, and two fractures involving the surgical and anatomical neck of the right humerus. We discuss an approach to identifying the underlying cause of hypophosphatemia associated with fragility fractures, and options for management of this rare condition.

Conclusion
Although rare, tumor-induced osteomalacia can be diagnosed if a logical stepwise approach is implemented. Surgery could be curative if the tumor is properly located and is resectable.