bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovations in personalised diabetes care and risk management
Authors: Nijpels Giel , Beulens Joline WJ , van der Heijden Amber AWA , Elders Petra J 
Published: November 2019

AbstractType 2 diabetes is associated with an increased risk of developing macro and microvascular complications. Nevertheless, there is substantial heterogeneity between people with type 2 diabetes in their risk of developing such complications. Personalised medicine for people with type 2 diabetes may aid in efficient and tailored diabetes care for those at increased risk of developing such complications. Recently, progress has been made in the development of personalised diabetes care in several areas. Particularly for the risk prediction of cardiovascular disease, retinopathy and nephropathy, innovative methods have been developed for prediction and tailored monitoring or treatment to prevent such complications. For other complications or subpopulations of people with type 2 diabetes, such as the frail elderly, efforts are currently ongoing to develop such methods. In this review, we discuss the recent developments in innovations of personalised diabetes care for different complications and subpopulations of people with type 2 diabetes, their performance and modes of application in clinical practice.
Correction to: Interaction of the heterotrimeric G protein alpha subunit SSG-1 of Sporothrix schenckii with proteins related to stress response and fungal pathogenicity using a yeast two-hybrid assay
Authors: Pérez-Sánchez Lizaida , González Elizabeth , Colón-Lorenzo Emilee E. , González-Velázquez Waleska , González-Méndez Ricardo , Valle Nuri Rodríguez-del 
Published: November 2019

Following the publication of this article [1], it was brought to our attention that Fig. 7A lane 2 is identical to Fig. 7B lane 2 and Fig. 7B lane 4 is identical to Fig. 7C lane 4.
Determinants of effective organisational capacity training: lessons from a training programme on health workforce development with participants from three African countries
Authors: Amde Woldekidan Kifle , Marchal Bruno , Sanders David , Lehmann Uta 
Published: November 2019

Abstract
Background
Health systems in sub-Saharan Africa face multifaceted capacity challenges to fulfil their mandates of service provision and governance of their resources. Four academic institutions in Africa implemented a World Health Organisation-funded collaborative project encompassing training, curriculum development, and partnership to strengthen national leadership and training capacity for health workforce development. This paper looks into the training component of the project, a blended Masters programme in public health that sought to improve the capacity of personnel involved in teaching or management/development of human resources for health. The paper aims to explore factors influencing contribution of training to organisational capacity development.

Methods
We chose a case study design. Semi-structured interviews were held with 18 trainees that were enrolled in the training programme, and who were affiliated to health ministries or public health training institutions. We gathered additional data through document reviews, observation, and interviews with 14 key informants associated with the programme and/or working in the collaborating institutions. The evidence gathered were analysed thematically.

Results
Thirteen of the 18 training participants stayed in the target institutions and contributed to improved capacity of their institutions in the fields of management, policy, planning, research, training, or curriculum development. Five left for private and international agencies due to dissatisfaction with payment, work conditions, or career prospect.
Factors that were associated with the training, trainees, and the institutional and broader context, determine contribution of training to organisational capacity development. These include relevance of newly acquired knowledge and skills set of trainees to the role/position they assume in the organisation; recognition of trainees by employing organisations in terms of promotion or assignment of challenging tasks; and motivation and retention of trained staff.

Conclusion
Training, even if relevant and applicable, makes no more than a ‘latent’ contribution, one which is activated and realised through alignment of clusters of interacting contextual and relational factors related to the target institutions and trained personnel. While not predictable, implementers need to focus more deliberately on the likely interaction and best possible alignments between training relevance, student selection for potential to contribute, recognition and career advancement potential.
Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis
Authors: Negi Poonam , Sharma Ishita , Hemrajani Chetna , Rathore Charul , Bisht Alpna , Raza Kaisar , Katare O. P. 
Published: November 2019

Abstract
Background
Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model.

Methods
TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis.

Results
The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation.

Conclusions
The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.
Antimicrobial resistance patterns and biofilm formation of coagulase-negative Staphylococcus species isolated from subclinical mastitis cow milk samples submitted to the Onderstepoort Milk Laboratory
Authors: Phophi Lufuno , Petzer Inge-Marie , Qekwana Daniel Nenene 
Published: November 2019

AbstractBackgroundIncreased prevalence of antimicrobial resistance, treatment failure, and financial losses have been reported in dairy cows with coagulase-negativeStaphylococcus(CoNS) clinical mastitis, however, studies on CoNS infections are limited in South Africa. Therefore, the objectives of this study were to investigate the antimicrobial resistance patterns and biofilm formation in CoNS isolated from cow milk samples submitted to the Onderstepoort Milk Laboratory.ResultsA total of 142 confirmed CoNS isolates were used for this study. Biofilm formation was identified in 18% of CoNS tested.Staphylococcus chromogenes(11%) had the highest proportion of biofilm formation followed byS. haemolyticus(4.0%),S. epidermidis,S. hominis, S. xylosus, and S. simulanswith 1% respectively. Ninety percent (90%) of CoNS were resistant to at least one antimicrobial (AMR) and 51% were multidrug-resistant (MDR). Resistance among CoNS was the highest to ampicillin (90%) and penicillin (89%), few isolates resistant to cefoxitin and vancomycin, 9% respectively. Similarly, MDR-S. haemolyticus(44%), MDR-S. epidermidis(65%), and MDR-S.chromogenes(52%) were mainly resistant to penicillins. The most common resistance patterns observed were resistance to penicillin-ampicillin (16%) and penicillin-ampicillin-erythromycin (10%). Only 42% of biofilm positive CoNS were MDR.ConclusionThe majority of CoNS in this study were resistance to penicillins. In addition, most isolates were β-lactam resistant and MDR. Biofilm formation among the CoNS in this study was uncommon and there was no significant difference in the proportion of MDR-CoNS based on the ability to form a biofilm.
Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area
Authors: Brabin Bernard , Tinto Halidou , Roberts Stephen A. 
Published: November 2019

Abstract
Background
In view of recent evidence from a randomized trial in Burkina Faso that periconceptional iron supplementation substantially increases risk of spontaneous preterm birth (< 37 weeks) in first pregnancies (adjusted relative risk = 2.22; 95% CI 1.39–3.61), explanation is required to understand potential mechanisms, including progesterone mediated responses, linking long-term iron supplementation, malaria and gestational age.

Methods
The analysis developed a model based on a dual hit inflammatory mechanism arising from simultaneous malaria and gut infections, supported in part by published trial results. This model is developed to understand mechanisms linking iron supplementation, malaria and gestational age. Background literature substantiates synergistic inflammatory effects of these infections where trial data is unavailable. A path modelling exercise assessed direct and indirect paths influencing preterm birth and gestation length.

Results
A dual hit hypothesis incorporates two main pathways for pro-inflammatory mechanisms, which in this model, interact to increase hepcidin expression. Trial data showed preterm birth was positively associated with C-reactive protein (P = 0.0038) an inflammatory biomarker. The malaria pathway upregulates C-reactive protein and serum hepcidin, thereby reducing iron absorption. The enteric pathway results from unabsorbed gut iron, which induces microbiome changes and pathogenic gut infections, initiating pro-inflammatory events with lipopolysaccharide expression. Data from the trial suggest that raised hepcidin concentration is a mediating catalyst, being inversely associated with shorter gestational age at delivery (P = 0.002) and positively with preterm incidence (P = 0.007). A segmented regression model identified a change-point consisting of two segments before and after a sharp rise in hepcidin concentration. This showed a post change hepcidin elevation in women with increasing C-reactive protein values in late gestation (post-change slope 0.55. 95% CI 0.39–0.92, P < 0.001). Path modelling confirmed seasonal malaria effects on preterm birth, with mediation through C-reactive protein and (non-linear) hepcidin induction.

Conclusions
Following long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure. If correct, this model strongly suggests that in such areas, effective infection control is required prior to iron supplementation to avoid increasing preterm births.
Trial registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010
Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex
Authors: Ye Shi-Yang , Apple Joanna E. , Ren Xiao , Tang Fu-Lei , Yao Ling-Ling , Wang Yong-Gang , Mei Lin , Zhou Yuan-Guo , Xiong Wen-Cheng 
Published: November 2019

AbstractBackgroundVacuolar sorting protein 35 (VPS35), a critical component of retromer, is essential for selective endosome-to-Golgi retrieval of membrane proteins. It is highly expressed in microglial cells, in addition to neurons. We have previously demonstrated microglial VPS35’s functions in preventing hippocampal, but not cortical, microglial activation, and in promoting adult hippocampal neurogenesis. However, microglial VPS35’s role in the cortex in response to ischemic stroke remains largely unclear.MethodsWe used mice with VPS35 cKO (conditional knockout) in microglial cells and examined and compared their responses to ischemic stroke with control mice. The brain damage, cell death, changes in glial cells and gene expression, and sensorimotor deficits were assessed by a combination of immunohistochemical and immunofluorescence staining, RT-PCR, Western blot, and neurological functional behavior tests.ResultsWe found that microglial VPS35 loss results in an increase of anti-inflammatory microglia in mouse cortex after ischemic stroke. The ischemic stroke-induced brain injury phenotypes, including brain damage, neuronal death, and sensorimotor deficits, were all attenuated by microglial VPS35-deficiency. Further analysis of protein expression changes revealed a reduction in CX3CR1 (CX3C chemokine receptor 1) in microglial VPS35-deficient cortex after ischemic stroke, implicating CX3CR1 as a potential cargo of VPS35 in this event.ConclusionTogether, these results reveal an unrecognized function of microglial VPS35 in enhancing ischemic brain injury-induced inflammatory microglia, but suppressing the injury-induced anti-inflammatory microglia. Consequently, microglial VPS35 cKO mice exhibit attenuation of ischemic brain injury response.
BRCA1 mutation influences progesterone response in human benign mammary organoids
Authors: Davaadelger Batzaya , Choi Mi-Ran , Singhal Hari , Clare Susan E. , Khan Seema A. , Kim J. Julie 
Published: November 2019

AbstractBackgroundWomen, who carry a germline BRCA1 gene mutation, have a markedly increased risk of developing breast cancer during their lifetime. While BRCA1 carriers frequently develop triple-negative, basal-like, aggressive breast tumors, hormone signaling is important in the genesis of BRCA1 mutant breast cancers. We investigated the hormone response in BRCA1-mutated benign breast tissue using an in vitro organoid system.MethodsScaffold-free, multicellular human breast organoids generated from benign breast tissues from non-carrier or BRCA1 mutation carriers were treated in vitro with a stepwise menstrual cycle hormone regimen of estradiol (E2) and progesterone (P4) over the course of 28 days.ResultsBreast organoids exhibited characteristics of the native breast tissue, including expression of hormone receptors, collagen production, and markers of luminal and basal epithelium, and stromal fibroblasts. RNA sequencing analysis revealed distinct gene expression in response to hormone treatment in the non-carrier and BRCA1-mutated organoids. The selective progesterone receptor modulator, telapristone acetate (TPA), was used to identify specifically PR regulated genes. Specifically, extracellular matrix organization genes were regulated by E2+P4+TPA in the BRCA1-mutated organoids but not in the non-carrier organoids. In contrast, in the non-carrier organoids, known PR target genes such as the cell cycle genes were inhibited by TPA.ConclusionsThese data show that BRCA1 mutation influences hormone response and in particular PR activity which differs from that of non-carrier organoids. Our organoid model system revealed important insights into the role of PR in BRCA1-mutated benign breast cells and the critical paracrine actions that modify hormone receptor (HR)-negative cells. Further analysis of the molecular mechanism of BRCA1 and PR crosstalk is warranted using this model system.
Low coverage whole genome sequencing enables accurate assessment of common variants and calculation of genome-wide polygenic scores
Authors: Homburger Julian R. , Neben Cynthia L. , Mishne Gilad , Zhou Alicia Y. , Kathiresan Sekar , Khera Amit V. 
Published: November 2019

Abstract
Background
Inherited susceptibility to common, complex diseases may be caused by rare, pathogenic variants (“monogenic”) or by the cumulative effect of numerous common variants (“polygenic”). Comprehensive genome interpretation should enable assessment for both monogenic and polygenic components of inherited risk. The traditional approach requires two distinct genetic testing technologies—high coverage sequencing of known genes to detect monogenic variants and a genome-wide genotyping array followed by imputation to calculate genome-wide polygenic scores (GPSs). We assessed the feasibility and accuracy of using low coverage whole genome sequencing (lcWGS) as an alternative to genotyping arrays to calculate GPSs.

Methods
First, we performed downsampling and imputation of WGS data from ten individuals to assess concordance with known genotypes. Second, we assessed the correlation between GPSs for 3 common diseases—coronary artery disease (CAD), breast cancer (BC), and atrial fibrillation (AF)—calculated using lcWGS and genotyping array in 184 samples. Third, we assessed concordance of lcWGS-based genotype calls and GPS calculation in 120 individuals with known genotypes, selected to reflect diverse ancestral backgrounds. Fourth, we assessed the relationship between GPSs calculated using lcWGS and disease phenotypes in a cohort of 11,502 individuals of European ancestry.

Results
We found imputation accuracy r2 values of greater than 0.90 for all ten samples—including those of African and Ashkenazi Jewish ancestry—with lcWGS data at 0.5×. GPSs calculated using lcWGS and genotyping array followed by imputation in 184 individuals were highly correlated for each of the 3 common diseases (r2 = 0.93–0.97) with similar score distributions. Using lcWGS data from 120 individuals of diverse ancestral backgrounds, we found similar results with respect to imputation accuracy and GPS correlations. Finally, we calculated GPSs for CAD, BC, and AF using lcWGS in 11,502 individuals of European ancestry, confirming odds ratios per standard deviation increment ranging 1.28 to 1.59, consistent with previous studies.

Conclusions
lcWGS is an alternative technology to genotyping arrays for common genetic variant assessment and GPS calculation. lcWGS provides comparable imputation accuracy while also overcoming the ascertainment bias inherent to variant selection in genotyping array design.
The intestinal microbial community dissimilarity in hepatitis B virus-related liver cirrhosis patients with and without at alcohol consumption
Authors: Deng Yong-Dong , Peng Xue-Bin , Zhao Rong-Rong , Ma Chao-Qun , Li Jian-ning , Yao Li-Qiong 
Published: November 2019

Abstract
Background
Chronic hepatitis B virus (HBV) infection-reduced liver functions are associated with intestinal microbial community dissimilarity. This study aimed to investigate the microbial community dissimilarity in patients with different grades of HBV-related liver cirrhosis.

Results
Serum endotoxin was increased with Child–Pugh (CP) class (A, B, and C). Veillonellaceae and Lachnospiraceae families were reduced in patients compared with controls. Megamonas and Veillonella genus was reduced and increased in patients compared with controls, respectively, especially in CPB and CPC groups. Correlation analysis showed that endotoxin content was significantly correlated with alcohol consumption (95% CI 0.100, 0.493), CP class (95% CI 0.289, 0.687) and Lachnospiraceae family level (95% CI − 0.539, − 0.122). Firmicutes/Bacteroidetes ratio was correlated with the level of Lachnospiraceae family (95% CI 0.013, 0.481), Veillonellaceae family (95% CI 0.284, 0.696), Megamonas genus (95% CI 0.101, 0.518) and Veillonella genus (95% CI 0.134, 0.545). All aforementioned bacteria were independent risk or protective factors for hepatitis. Alcohol consumption changed microbial community.

Conclusions
Our study demonstrated that elevated Firmicutes/Bacteroidetes ratio, reduced Megamonas genus level and increased Veillonella genus level were indicators for HBV-related liver cirrhosis. Alcohol-related pathogenesis was associated with the changed microbial community.
Short-term skin problems in infants aged 0–3 months affect food allergies or atopic dermatitis until 2 years of age, among infants of the general population
Authors: Yonezawa Kaori , Haruna Megumi 
Published: November 2019

Abstract
Background
This study examined whether infants aged 0–3 months exhibited long-term effects of using a moisturizer skincare intervention and whether a short-term skin problem resulted in the subsequent development of food allergies or atopic dermatitis (AD) until the age of 2 years.

Methods
This study was a follow-up of a completed randomized control trial (RCT) of moisturizer skincare for infants aged 0–3 months. A self-reported questionnaire was mailed to the parents of children aged 1–2 years who had participated in the RCT. Data were analyzed using a Chi square test, by intention to treat analysis, and by multiple logistic regression.

Results
Of 155 infants, 22 (14.2%) and 28 (18.1%) had food allergies and AD/eczema until 2 years of age, respectively. No significant difference was seen in food allergies or AD between the group that received moisturizer skincare intervention and the control group. On the contrary, food allergies until 2 years of age were significantly associated with short-term (4–7 days) and long-term (more than 7 days) body skin problems occurring in the first 3 months of life, a family history of AD, and the time of starting complementary food. High value of face transepidermal water loss at 3 months of age was also associated with food allergies. Moreover, a short duration of severe diaper dermatitis during the first 3 months, a family history of AD, and being male were significantly associated with AD/eczema until the age of 2 years.

Conclusions
After adjusting for family history of AD, a short-term skin problem in the first 3 months of life was significantly associated with the development of food allergies or AD/eczema until the age of 2 years. Prevention or prompt treatment of skin problems in newborns is essential for preventing future allergic diseases.
Trial registration This was a follow-up study conducted 2 years after the completed RCT of a moisturizer skincare intervention for early infants, which was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013260)