bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24
Authors: Arnal Audrey , Villanueva‐Lizama Liliana , Teh‐Poot Christian , Herrera Claudia , Dumonteil Eric 
Published: July 2020

AbstractIntroductionChagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem in the Americas, and existing drugs have severe limitations. In this context, a vaccine would be an attractive alternative for disease control. One of the difficulties in developing an effective vaccine lies in the high genetic diversity of T. cruzi. In this study, we evaluated the level of sequence diversity of the leading vaccine candidate Tc24 in multiple parasite strains.Methods and ResultsWe quantified its level of polymorphism within and between T. cruzi discrete typing units (DTUs) and how this potential polymorphism is structured by different selective pressures. We observed a low level of polymorphism of Tc24 protein, weakly associated with parasite DTUs, but not with the geographic origin of the strains. In particular, Tc24 was under strong purifying selection pressure and predicted CD8+ T‐cell epitopes were mostly conserved. Tc24 strong conservation may be associated with structural/functional constrains to preserve EF hand domains and their calcium‐binding loops, and Tc24 is likely important for the parasite fitness.DiscussionTogether, these results show that a vaccine based on Tc24 is likely to be effective against a wide diversity of parasite strains across the American continent, and further development of this vaccine candidate should be a high priority.
Treatment options and long‐term outcomes of horses with subchondral lucencies of the medial femoral condyle
Authors: Santschi E. M. 
Published: July 2020

SummarySubchondral lucencies (SCL) occur in the equine medial femoral condyle (MFC) and can cause lameness and impair performance. Treatment of MFC SCL has evolved over the last 40 years from rest alone to cyst injection to several surgical procedures. Horses most commonly develop MFC SCL in the first 18 months of life, and expectations for performance and sales can impact therapeutic decisions. These complications mean that a single treatment plan cannot be applied to every SCL. An additional issue is accurate long‐term performance data. Long‐term follow‐up can also be difficult to obtain due to horse movement, confidentiality issues after sales, and the complexities of finding new owners and getting their cooperation. This short communication reviews available racing information from publications reporting treatment of MFC SCL and provides long‐term follow‐up racing data on 13 horses treated with a transcondylar screw. Horses receiving a transcondylar screw raced as well as horses treated with other procedures and had longer careers, further supporting the use of this technique in the treatment of MFC SCL.
Hair follicle immune privilege and its collapse in alopecia areata
Authors: Bertolini Marta , McElwee Kevin , Gilhar Amos , Bulfone‐Paus Silvia , Paus Ralf 
Published: July 2020

AbstractAnagen stage hair follicles (HFs) exhibit “immune privilege (IP)” from the level of the bulge downwards to the bulb. Both passive and active IP mechanisms protect HFs from physiologically undesired immune responses and limit immune surveillance. IP is relative, not absolute, and is primarily based on absent, or greatly reduced, intra‐follicular antigen presentation via MHC class I and II molecules, along with prominent expression of “no danger” signals like CD200 and the creation of an immunoinhibitory signalling milieu generated by the secretory activities of HFs. Perifollicular mast cells, Tregs and other immunocytes may also contribute to HF IP maintenance in healthy human skin. Collapse of anagen hair bulb IP is an essential prerequisite for the development of alopecia areata (AA). In AA, lesional HFs are rapidly infiltrated by NKG2D + T cells and natural killer (NK) cells, while perifollicular mast cells acquire a profoundly pro‐inflammatory phenotype and interact with autoreactive CD8+ T cells. Using animal models, significant functional evidence has accumulated that demonstrates the dominance of the immune system in AA pathogenesis. Purified CD8+T‐cell and NK cell populations alone, which secrete fγ, suffice to induce the AA phenotype, while CD4+T‐cells aggravate it, and Tregs and iNKT cells may provide relative protection against AA development. While IP collapse may be induced by exogenous agents, inherent IP deficiencies might confer increased susceptibility to AA for some individuals. Thus, a key goal for effective AA management is the re‐establishment of a functional HF IP, which will also provide superior protection from disease relapse.
Topical L‐thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy?
Authors: Paus Ralf , Ramot Yuval , Kirsner Robert S. , Tomic‐Canic Marjana 
Published: July 2020

AbstractTopical hormone therapy with natural or synthetic ligands of nuclear hormone receptors such as glucocorticoids, vitamin D analogues and retinoids has a long and highly successful tradition in dermatology. Yet the dermatological potential of thyroid hormone receptor (TR) agonists has been widely ignored, despite abundant clinical, cell and molecular biology, mouse in vivo, and human skin and hair follicle organ culture data documenting a role of TR‐mediated signalling in skin physiology and pathology. Here, we review this evidence, with emphasis on wound healing and hair growth, and specifically highlight the therapeutic potential of repurposing topical L‐thyroxine (T4) for selected applications in future dermatological therapy. We underscore the known systemic safety and efficacy profile of T4 in clinical medicine, and the well‐documented impact of thyroid hormones on, for example, human epidermal and hair follicle physiology, hair follicle epithelial stem cells and pigmentation, keratin expression, mitochondrial energy metabolism and wound healing. On this background, we argue that short‐term topical T4 treatment deserves careful further preclinical and clinical exploration for repurposing as a low‐cost, effective and widely available dermatotherapeutic, namely in the management of skin ulcers and telogen effluvium, and that its predictable adverse effects are well‐manageable.
Decreased suppression of CD8+ and CD4+ T cells by peripheral regulatory T cells in generalized vitiligo due to reduced NFATC1 and FOXP3 proteins
Authors: Giri Prashant S. , Dwivedi Mitesh , Begum Rasheedunnisa 
Published: July 2020

AbstractRegulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV).
The study was aimed to investigate Tregs functional defects in Treg:CD8+ and Treg:CD4+ T cells' co‐culture systems of 55 GV patients and 45 controls. CD8+ and CD4+ T‐cell proliferation was assessed by BrdU assay; production of IL‐10, TGF‐β and IFN‐γ cytokines was assessed by ELISA; and FOXP3, CD25, NFATC1 and CD44 proteins were measured by flow cytometry. Generalized vitiligo patients showed reduced suppression of CD8+ and CD4+ T cells (P = .0384, P = .0084), increased IFN‐γ (P < .0001, P = .0019), decreased IL‐10 and TGF‐β (P < .0001) and decreased FOXP3, CD25 and NFATC1 proteins (P < .0001). Active vitiligo (AV) patients showed reduced suppression of CD8+ & CD4+ T cells (P = .006, P = .015), increased IFN‐γ (P = .036, P = .045), decreased IL‐10 (P = .009, P = .021), FOXP3 (P = .0244) and NFATC1 (P = .019). Severe GV (50%‐75% VASI) patients showed reduced suppression of CD8+ and CD4+ T cells (P = .0003, P = .001), increased IFN‐γ (P = .0029, P < .0001), decreased IL‐10 (P = .0057, P = .0017), FOXP3 (P = .002) and NFATC1 (P = .0347). VASI score was positively correlated with the suppression of CD8+ and CD4+ T cells (P = .0006, P < .0001), IL‐10 (P = .0096, P = .029), FOXP3 (P = .0008) and NFATC1 (P = .043), whereas it was negatively correlated with IFN‐γ (P = .0029, P = .0017). Early age of onset patients' Tregs demonstrated decreased suppression of CD8+ and CD4+ T cells (P = .0156, P = .0074), decreased TGF‐β (P = .0212, P = .0083) and NFATC1 (P = .0103). NFATC1 was positively correlated with FOXP3 in Tregs (P < .0001). Our results suggest impaired Tregs suppressive function in GV patients due to decreased NFATC1, FOXP3, CD25, IL‐10 and TGF‐β resulting into increased CD8+ and CD4+ T‐cell proliferation and IFN‐γ production. For the first time, decreased NFATC1 levels were correlated with decreased FOXP3, thereby altering Treg cell function in GV patients. Additionally, decreased Treg cell function also affected onset, activity and severity of GV.
A synthesis of (non‐)compliance theories with applications to small‐scale fisheries research and practice
Authors: Oyanedel Rodrigo , Gelcich Stefan , Milner‐Gulland E. J. 
Published: July 2020

AbstractNon‐compliance in fisheries is a persistent challenge for the conservation and sustainable management of the oceans and has particularly acute impacts in small‐scale fisheries contexts. Small‐scale fisheries often suffer from chronic overexploitation, poor management, lack of enforcement and non‐compliance, but small‐scale fishers are highly dependent on the ocean as a source of employment and food. Improving our understanding of the determinants of non‐compliant behaviours in small‐scale fisheries can help develop strategies to prevent and reduce its consequences. Here, we review two main approaches for the study of non‐compliant behaviours and crimes more broadly, spanning criminology, economics and psychology. On the one hand, actor‐based approaches address the underlying motivations for people to comply or not with regulations. Opportunity‐based approaches, on the other hand, assume that non‐compliance is not distributed randomly across space and time and focuses on the role that the immediate environment plays in the performance of non‐compliant behaviours. We discuss potential applications of actor‐based and opportunity‐based approaches in guiding small‐scale fisheries non‐compliance research. Moreover, we provide guiding principles for integrating these approaches in a complementary way, highlighting opportunities and challenges for building a better non‐compliance research agenda for fisheries and beyond. Addressing non‐compliance is a common challenge for natural resource management in multiple ecosystems. Integrating these two perspectives has the potential to improve both research and practice.
Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis
Authors: Farrugia Cher , Stafford Graham P. , Potempa Jan , Wilkinson Robert N. , Chen Yan , Murdoch Craig , Widziolek Magdalena 
Published: July 2020

Several studies have shown a clear association between periodontal disease and increased risk of cardiovascular disease. Porphyromonas gingivalis (Pg), a key oral pathogen, and its cell surface‐expressed gingipains, induce oedema in a zebrafish larvae infection model although the mechanism of these vascular effects is unknown. Here, we aimed to determine whether Pg‐induced vascular damage is mediated by gingipains. In vitro, human endothelial cells from different vascular beds were invaded by wild‐type (W83) but not gingipain‐deficient (ΔK/R‐ab) Pg. W83 infection resulted in increased endothelial permeability as well as decreased cell surface abundance of endothelial adhesion molecules PECAM‐1 and VE‐cadherin compared to infection with ΔK/R‐ab. In agreement, when transgenic zebrafish larvae expressing fluorescently labelled PECAM‐1 or VE‐cadherin were systemically infected with W83 or ΔK/R‐ab, a significant reduction in adhesion molecule fluorescence was observed specifically in endothelium proximal to W83 bacteria through a gingipain‐dependent mechanism. Furthermore, this was associated with increased vascular permeability in vivo when assessed by dextran leakage microangiography. These data are the first to show that Pg directly mediates vascular damage in vivo by degrading PECAM‐1 and VE‐cadherin. Our data provide a molecular mechanism by which Pg might contribute to cardiovascular disease.
Time trends and other sources of variation in Helicobacter pylori infection in mainland China: A systematic review and meta‐analysis
Authors: Li Mengmeng , Sun Yuanyuan , Yang Jun , de Martel Catherine , Charvat Hadrien , Clifford Gary M , Vaccarella Salvatore , Wang Li 
Published: July 2020

AbstractBackgroundHelicobacter pylori (H pylori) is a carcinogen that causes a huge burden of gastric cancer in China. We aimed to evaluate the temporal trends and other sources of variation of H pylori infection in adults from mainland China.Materials and methodsFor this systematic review and meta‐analysis, we searched PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases for articles published from January 1983 to June 2020. We included studies reporting H pylori prevalence in adults and then applied random effect meta‐analyses to obtain pooled prevalence estimates for all studies and subgroups. Sources of heterogeneity were investigated by moderator analysis, and time trends were assessed through random effect meta‐regression.ResultsOf the 2121 studies identified, 98 were eligible for inclusion. The pooled estimate of 670 572 participants from 26 provinces during 1983‐2018 was 49.6% (95% CI: 46.9%, 52.4%). H pylori prevalence varied considerably, ranging from 20.6% to 81.8%. Periods, urban/rural status, detection method, and study design explained 18.8%, 24.0%, 17.8%, and 30.4% of the heterogeneity, respectively. Overall, H pylori prevalence declined by −0.9% (95% CI: −1.1%, −0.6%) annually. Consistent declines in prevalence were observed by sex, age, and study characteristics.ConclusionsHelicobacter pylori prevalence is slowly decreasing over time in mainland China, but the low declining speed is not enough to have a major impact on gastric cancer incidence for many years. The time trends and the large heterogeneity should be taken into account when conducting regional comparisons, disease burden estimations, and customized strategy making.
Health literacy experiences of multi‐ethnic patients and their health‐care providers in the management of type 2 diabetes in Malaysia: A qualitative study
Authors: Abdullah Adina , Liew Su May , Ng Chirk Jenn , Ambigapathy Subashini , V. Paranthaman P. Vengadasalam 
Published: July 2020

AbstractBackgroundPatients with type 2 diabetes mellitus (T2DM) require adequate health literacy to understand the disease and learn self‐management skills to optimize their health. However, the prevalence of limited health literacy is high in patients with T2DM, especially in Asian countries.ObjectiveThis study aimed to explore experiences related to health literacy in Asian patients with T2DM.DesignThis is a qualitative study using in‐depth interviews and focus group discussions. A framework analysis was used to analyse the data.Setting and participantsarticipants (n = 24) were multi‐ethnic patients with T2DM (n = 18) and their primary health‐care providers (n = 6). This study was conducted in four primary health‐care clinics in Malaysia.ResultsNine subthemes were identified within the four dimensions of health literacy: accessing, understanding, appraising and applying information.DiscussionMotivated patients actively sought information, while others passively received information shared by family members, friends or even strangers. Language and communication skills played important roles in helping patients understand this information. Information appraisal was lacking, with patients just proceeding to apply the information obtained. Patients' use of information was influenced by their self‐efficacy, and internal and external barriers.ConclusionIn conclusion, the experiences of multi‐ethnic patients with T2DM regarding health literacy were varied and heavily influenced by their cultures.
Thug life: bramble (Rubus fruticosus L. agg.) is a valuable foraging resource for honeybees and diverse flower‐visiting insects
Authors: Wignall Veronica R. , Arscott Natalie A. , Nudds Hayley E. , Squire Annabel , Green Thomas O. , Ratnieks Francis L. W. 
Published: July 2020

Abstract
Bramble (Rubus fruticosus L. agg.) is a common summer‐flowering plant native to the United Kingdom. Multiple complementary approaches were used to evaluate its ecological value to the honeybee (Apis mellifera), bumblebees (Bombus spp.) and other flower‐visiting insects in Sussex, England.
Regional surveys of insect groups at seven sites across 2 years showed that foraging activity on bramble was dominated by honeybees (60.2%; n = 28 surveys) and bumblebees (17.4%), compared to non‐Apis/Bombus bees (2.8%), hoverflies (Syrphidae, 7.9%), non‐syrphid flies (0.6%), butterflies (6.4%), wasps (0.4%) and beetles (4.4%). Foraging insect community structure was highly similar spatially, but varied significantly between survey months (June and July).
In detailed local surveys at one rural and one urban location, there was a diverse range of insect taxa foraging on the bramble flowers, including species of conservation concern (Bombus humilis, Coenonympha pamphilus and Limenitis camilla).
Pollen trapping at 12 honeybee hives in four locations showed that an average of 31% of pollen pellets collected by honeybees from late May to early August were bramble, with a peak of 66–86% per location.
Bramble was present in 54 out of 60 200 × 200 m randomly selected grid squares surveyed over a large area across Sussex. Plants were recorded in multiple habitat types in both urban and rural areas.
Bramble is sometimes considered an undesirable plant or a “thug” that outcompetes other wild flowers; however, these findings confirm that it is highly valuable for flower‐visiting insects. Wherever conflicts of interest and management strategies allow, bramble should be maintained and promoted for wildlife and insect conservation.
Effect of a high protein/low glycaemic index diet on insulin resistance in adolescents with overweight/obesity—A PREVIEW randomized clinical trial
Authors: Dorenbos Elke , Drummen Mathijs , Adam Tanja , Rijks Jesse , Winkens Bjorn , Martínez J. Alfredo , Navas‐Carretero Santiago , Stratton Gareth , Swindell Nils , Stouthart Pauline , Mackintosh Kelly , Mcnarry Melitta , Tremblay Angelo , Fogelholm Mikael , Raben Anne , Westerterp‐Plantenga Margriet , Vreugdenhil Anita 
Published: July 2020

SummaryBackgroundPubertal insulin resistance (IR) is associated with increased risk of type 2 diabetes mellitus development in adolescents with overweight/obesity.ObjectivesThe PREVIEW study was a randomized parallel trial assessing the change in IR, analyzed by Homeostatic Model Assessment of IR (HOMA‐IR), at 2 years after randomization to a high protein vs a moderate protein diet in adolescents with overweight/obesity. It was hypothesized that a high protein/low glycaemic index diet would be superior in reducing IR compared to a medium protein/medium GI diet, in insulin resistant adolescents with overweight or obesity.MethodsAdolescents with overweight/obesity and IR from the Netherlands, United Kingdom and Spain were randomized into a moderate protein/moderate GI (15/55/30En% protein/carbohydrate/fat, GI ≥ 56) or high protein/low GI (25/45/30En% protein/carbohydrate/fat, GI < 50) diet. Anthropometric and cardiometabolic parameters, puberty, dietary intake and physical activity (PA) were measured and effects on HOMA‐IR were analyzed.Results126 adolescents were included in this study (13.6 ± 2.2 years, BMI z‐score 3.04 ± 0.66, HOMA‐IR 3.48 ± 2.28, HP n = 68, MP n = 58). At 2 years, changes in protein intake were not significantly different between timepoints or intervention groups and no effects of the intervention on IR were observed. The retention rate was 39%, while no compliance to the diets was observed.ConclusionsThe PREVIEW study observed no effect of a high protein/low GI diet on IR in adolescents with overweight/obesity and IR because of lack of feasibility, due to insufficient retention and dietary compliance after 2 years.
Statins significantly alter urinary stone‐related urine biochemistry in calcium kidney stone patients with dyslipidemia
Authors: Liu Chan Jung , Huang Ho Shiang 
Published: July 2020

ObjectiveTo investigate whether the use of statins would alter 24‐h urine biochemistry in male patients with calcium kidney stones.MethodsWe prospectively recruited 78 male patients with calcium kidney stones between May 2017 and December 2017, and 30 male controls with matching sex and age, but without kidney stones. All patients were classified into higher‐ and lower‐risk groups of atherosclerotic cardiovascular disease according to the American College of Cardiology/American Heart Association guidelines. Atorvastatin 20 mg per day was prescribed for 12 weeks to the higher risk patients. For kidney stone group, 24‐h urine collections were carried out before and after statin therapy.ResultsA total of 78 patients and 30 controls were included. Higher‐risk patients had significantly higher urine uric acid and calcium levels than lower‐risk patients. After atorvastatin treatment for 12 weeks, urine citrate significantly increased (P < 0.001) accompanied with increased urine pH (P < 0.001), whereas urine uric acid significantly decreased after treatment. Although urine oxalate significantly increased after treatment (P = 0.037), we did not find any significant difference in urine calcium, ion activity product of calcium oxalate and ion activity product of calcium phosphate.ConclusionThese findings suggest that atorvastatin administration might increase urinary citrate and decrease urinary uric acid in patients with calcium kidney stones and dyslipidemia.
Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data
Authors: Toufiq Mohammed , Roelands Jessica , Alfaki Mohamed , Syed Ahamed Kabeer Basirudeen , Saadaoui Marwa , Lakshmanan Arun Prasath , Bangarusamy Dhinoth Kumar , Murugesan Selvasankar , Bedognetti Davide , Hendrickx Wouter , Al Khodor Souhaila , Terranegra Annalisa , Rinchai Darawan , Chaussabel Damien , Garand Mathieu 
Published: July 2020

SummaryAccording to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulatedin vitroafter exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observedin vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium‐dependent granules–phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase‐3‐dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis‐mediated organ damage.