Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors That Drive Youth Specialization

Background: Specialization in young athletes has been linked to overuse injuries, burnout, and decreased satisfaction. Despite continued opposition from the medical community, epidemiological studies suggest the frequency is increasing. Hypothesis: Extrinsic pressures in addition to individual aspirations drive this national trend in sports specialization. Study Design: Descriptive epidemiology study. Level of Evidence: Level 3. Methods: A novel instrument assessing the driving factors behind youth specialization was generated by an interdisciplinary team of medical professionals. Surveys were administered to patients and athletes in the department’s sports medicine clinic. Results: The survey was completed by 235 athletes between 7 and 18 years of age, with a mean age of 13.8 ± 3.0 years. Athletes specialized at a mean age of 8.1 years, and 31% of athletes played a single sport while 58% played multiple sports but had a preferred sport. More than 70% of athletes had collegiate or professional ambitions, and 60% played their primary sport for 9 or more months per year, with players who had an injury history more likely to play year-round (P < 0.01). Approximately one-third of players reported being told by a coach not to participate in other sports, with specialized athletes reporting this significantly more often (P = 0.04). Half of the athletes reported that sports interfered with their academic performance, with older players stating this more frequently (P < 0.01). Conclusion: Young athletes are increasingly specializing in a single sport before starting high school. While intrinsic drive may identify healthy aspirations, extrinsic influences are prevalent in specialized athletes. Clinical Relevance: Extrinsic factors contributing to youth specialization were identified and compounded the deleterious sequelae of youth athlete specialization.
How relevant is panallergen sensitization in the development of allergies?

Panallergens comprise various protein families of plant as well as animal origin and are responsible for wide IgE cross‐reactivity between related and unrelated allergenic sources. Such cross‐reactivities include reactions between various pollen sources, pollen and plant‐derived foods as well as invertebrate‐derived inhalants and foodstuff. Here, we provide an overview on the most clinically relevant panallergens from plants (profilins, polcalcins, non‐specific lipid transfer proteins, pathogenesis‐related protein family 10 members) and on the prominent animal‐derived panallergen family, tropomyosins. In addition, we explore the role of panallergens in the sensitization process and progress of the allergic disease. Emphasis is given on epidemiological aspects of panallergen sensitization and clinical manifestations. Finally, the issues related to diagnosis and therapy of patients sensitized to panallergens are outlined, and the use of panallergens as predictors for cross‐reactive allergy and as biomarkers for disease severity is discussed.
Combined Inhibition of mTOR and CDK4/6 Is Required for Optimal Blockade of E2F Function and Long-term Growth Inhibition in Estrogen Receptor–positive Breast Cancer

The cyclin dependent kinase (CDK)–retinoblastoma (RB)–E2F pathway plays a critical role in the control of cell cycle in estrogen receptor–positive (ER+) breast cancer. Small-molecule inhibitors of CDK4/6 have shown promise in this tumor type in combination with hormonal therapies, reflecting the particular dependence of this subtype of cancer on cyclin D1 and E2F transcription factors. mTOR inhibitors have also shown potential in clinical trials in this disease setting. Recent data have suggested cooperation between the PI3K/mTOR pathway and CDK4/6 inhibition in preventing early adaptation and eliciting growth arrest, but the mechanisms of the interplay between these pathways have not been fully elucidated. Here we show that profound and durable inhibition of ER+ breast cancer growth is likely to require multiple hits on E2F-mediated transcription. We demonstrate that inhibition of mTORC1/2 does not affect ER function directly, but does cause a decrease in cyclin D1 protein, RB phosphorylation, and E2F-mediated transcription. Combination of an mTORC1/2 inhibitor with a CDK4/6 inhibitor results in more profound effects on E2F-dependent transcription, which translates into more durable growth arrest and a delay in the onset of resistance. Combined inhibition of mTORC1/2, CDK4/6, and ER delivers even more profound and durable regressions in breast cancer cell lines and xenografts. Furthermore, we show that CDK4/6 inhibitor–resistant cell lines reactivate the CDK–RB–E2F pathway, but remain sensitive to mTORC1/2 inhibition, suggesting that mTORC1/2 inhibitors may represent an option for patients that have relapsed on CDK4/6 therapy. Mol Cancer Ther; 17(5); 908–20. ©2018 AACR.
Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8+ T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32-/- mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8+ T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8+ effector T cells that is required for the balanced regulation of effector versus memory responses to infection.
Differentiation between Clinical and Academic Myocardial Viability. Complementary Myocardial Perfusion SPECT and Low Dose Dobutamine Echocardiography Role vs. Histopathological Study

Background: Rest-Redistribution thallium(R-RD Tl) imaging has high negative predictive value (NPV) but low positive predictive value (ppv) for the prediction of recovery of regional myocardial dysfunction after revascularization (Rev). Combining myocardial perfusion (MP) and functional data with nitrate-enhanced gated SPECT MIBI (GSM) at rest appears to be a promising approach for viability detection. Aim of the Study: Differentiate between clinical and academic viability. Methods: Total of 66 patients with CAD underwent R-RD Tl,2 sets of resting GSM using 2 MIBI injections, and echocardiography at rest andafter low dose dobutamine (LDD). One hour before GSM2, trimetazidine (TMZ) andnitrate, had been given. All pts had their echo repeated after (Rev) as a golden standard for clinical viability one year later. Myocardial biopsy was taken for mitochondrial assessment as a golden standard for academic viability. Results: 389/1122 segments were found to have abnormal resting wall motion (RWM) on echo. 165/217 hypokinetic, 48/102 akinetic and 6/66 dyskinetic showed contractile response for LDD echo. The MP images showed normal uptake, complete, partial reversibility and poor uptake in Tl, GSM1 and GSM2 images as following:(58,31,47), (36,22,35), (198,119,190) and (32,148,50) of segments respectively. Sensitivity and specificity of Tl, GSM1 and GSM2 and LDD echo for clinical viability had been found respectively to be (94.9%,74.1%), (59.9%,93.6%), (93.5%, 90%) and (78.5%,100%). Mitochondrial degeneration had been found to be more in the segments with partial reversibility and those with poor uptake with sensitivity and specificity of (90,85.6%), (57.2%,94.2%), (89.4%,98%) and (75%, 88.2%) respectively. From this data we can grade viability into 4 grades. Conclusion: Clinical definition of viability is better looked for in GSM2. Viability could be assessed into 4 grades.
Efficient Grid-Based Rao–Blackwellized Particle Filter SLAM With Interparticle Map Sharing

In this paper, we propose a novel and efficient grid-based Rao–Blackwellized particle filter simultaneous localization and mapping (RBPF-SLAM) with interparticle map shaping (IPMS). The proposed method aims at saving the computational memory in the grid-based RBPF-SLAM while maintaining the mapping accuracy. Unlike conventional RBPF-SLAM in which each particle has its own map of the whole environment, each particle has only a small map of the nearby environment called an individual map in the proposed method. Instead, the map of the remaining large environment is shared by the particles. The part shared by the particles is called a base map. If the individual small maps become reliable enough to trust, they are merged with the base map. To determine when and which part of an individual map should be merged with the base map, we propose two map sharing criteria. Finally, the proposed IPMS RBPF-SLAM is applied to the real-world datasets and benchmark datasets. The experimental results show that our method outperforms conventional methods in terms of map accuracy versus memory consumption.
Endoscopic ultrasound-guided gallbladder drainage reduces adverse events compared with percutaneous cholecystostomy in patients who are unfit for cholecystectomy

Abstract Background and study aim There are no data comparing endoscopic ultrasound (EUS)-guided gallbladder drainage (EGBD) with percutaneous cholecystostomy as a treatment for patients with acute cholecystitis. Patients and methods This was a 1 : 1 matched cohort study of all patients who were unfit for cholecystectomy and underwent EGBD or percutaneous cholecystostomy instead for the treatment of acute cholecystitis. The outcomes were matched for age, sex, and American Society of Anesthesiologists grade. Outcome measures included the technical and clinical success rates, adverse events, hospital stay, the number of unplanned admissions, and mortality. Results Between November 2011 and August 2014, a total of 118 patients were included in the study (59 EGBD, 59 percutaneous cholecystostomy). Technical and clinical success rates were similar. In the EGBD group, significantly fewer patients suffered from overall adverse events (19 [32.2 %] vs. 44 [74.6 %]; P < 0.001) and serious adverse events (14 [23.7 %] vs. 44 [74.6 %]; P < 0.001) compared to the percutaneous cholecystostomy group. Patients in the EGBD group required fewer unplanned admissions (4 [6.8 %] vs. 42 [71.2 %]; P < 0.001), which were due to problems related to the cholecystostomy tube in 95.2 %. The 30-day adverse event rates were similar between the groups (17 [28.8 %] vs. 10 [16.9 %]; P = 0.13). For instance, recurrent acute cholecystitis occurred in 0 patients in the EGBD group and in 4 (6.8 %) patients in the percutaneous cholecystostomy group (P = 0.12). The 30-day mortality rates were non-significantly higher in the EGBD group (5 [8.5 %] vs. 1 [1.7 %]; P = 0.21). Conclusions EGBD and percutaneous cholecystostomy were both effective means of achieving gallbladder drainage. EGBD may be a promising alternative to percutaneous cholecystostomy for treatment of acute cholecystitis in patients who are unfit for surgery, provided that experienced endosonographers are available.
Alternative splice variants of DCLK1 mark cancer stem cells, promote self‐renewal and drug‐resistance, and can be targeted to inhibit tumorigenesis in kidney cancer

Renal cell carcinoma (RCC) is a common and devastating disease characterized by a hypoxic microenvironment, epithelial‐mesenchymal transition and potent resistance to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC markers have been studied in RCC, but overall there is limited data on their role and most markers studied have been relatively nonspecific. Doublecortin‐like kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and evidence for an equivalent role in other cancers is accumulating. We used bioinformatics, immunohistochemistry, flow cytometry, spheroid self‐renewal and chemoresistance assays in combination with overexpression and siRNA‐knockdown to study the stem cell‐supportive role of DCLK1 alternative splice variants (DCLK1 ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed a novel monoclonal antibody (CBT‐15) and delivered it systemically to RCC tumor xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and predictive of overall and recurrence‐free survival in RCC patients. In vitro, DCLK1 ASVs were able to directly stimulate essential molecular and functional characteristics of renal CSCs including expression of aldehyde dehydrogenase, self‐renewal and resistance to FDA‐approved receptor tyrosine kinase and mTOR inhibitors, while targeted downregulation of DCLK1 reversed these characteristics. Finally, targeting DCLK1 ASV‐positive cells with the novel CBT‐15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings establish DCLK1 as a CSC marker with implications for therapy, disease progression and survival in RCC and demonstrate the therapeutic value of DCLK1‐targeted monoclonal antibodies against renal CSCs.
A New Conserved Player in Lymphatic Morphogenesis.

The lymphatic system comprises a network of interconnected and blind-ended vessels whose central function is to maintain fluid homeostasis.1 Similar to the vessels of the circulatory system, the lymphatic system consists of a hierarchical network of small and large caliber vessels, which function together to allow fluid drainage. Lymphatic capillaries are lined by endothelial cells that are highly discontinuous, making them permeable to surrounding fluid to facilitate resorption. By contrast, larger lymphatic collecting ducts possess a thin smooth muscle layer and valves to promote unidirectional transport of fluid toward connection points with the circulatory system at the subclavian veins. In addition to fluid homeostasis, the lymphatic system and the constituent lymph nodes are a portal for lymphocytes, as well as antigen-presenting cells, while also functioning in lipid absorption in the digestive system.1 Given their wide-ranging importance in these normal physiological processes, it is not surprising that the lymphatic system is implicated in several pathological conditions. Indeed, inflammation is intimately associated with lymphatic function and is a central cause of lymphedema in a wide range of acquired and congenital diseases.1 Notably, congenital forms of lymphedema are associated with mutations in several genes important for lymphatic vessel formation, including those encoding the receptor tyrosine kinase FLT4 and its ligand, VEGFC.2 Articles, see p 1263 and 1276 The lymphatic system is also essential for cardiac homeostasis and has been increasingly implicated in related diseases. Importantly, lymphatic vessels can play a central role to facilitate repair of cardiac tissue after myocardial infarction.3 Indeed, injection of VEGFC after myocardial infarction can lead to sustained improvement in cardiac function, including increased ejection fraction, and reduction in both end-systolic volume and hypertrophy. In these cases, the presence of additional lymphatic vessels induced by VEGFC is thought to better resolve post-myocardial infarction edema …
Bariatric surgery in solid organ transplant patients: Long‐term follow‐up results of outcome, safety, and effect on immunosuppression

The surgical risk of transplanted patients is high, and the modified gastrointestinal anatomy after bariatric surgery (BS) may lead to pharmacokinetic alterations in the absorption of immunosuppressive drugs. Data on outcomes of BS and the safety and feasibility of maintaining immunosuppression and graft safety among solid organ transplanted patients are scarce. In the current study, weight loss, improvement in comorbidities, and changes in dosage and trough levels of immunosuppression drugs before and after BS were analyzed for all transplanted patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux‐en‐Y gastric bypass (LRYGB) in our institution between November 2011 and January 2017. Thirty‐four patients (13 females, 21 males, average age 53 years) were included in the study. A successful weight loss (>50% excess weight loss in 28 of them [82%]) was recorded at the last follow‐up. Comorbidities improved significantly. Immunosuppressive stability increased from 39% to 47% among all patients. The tacrolimus blood trough levels declined slightly, but remained within therapeutic range. These data suggest that LSG and LRYGB ensure good immunosuppressive maintenance together with significant weight loss and improvement in comorbidities without serious graft rejection or dysfunction. The surgical risk is higher than in the regular BS population.
Diabetes UK evidence‐based nutrition guidelines for the prevention and management of diabetes

A summary of the latest evidence‐based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes‐related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non‐nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted ‘GRADE’ methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes. org.uk/nutrition-guidelines.
Impact of dietary fat composition on prediabetes: a 12-year follow-up study

Abstract Objective Dietary fatty acid composition likely affects prediabetic conditions such as isolated impaired fasting glucose (IFG) or impaired glucose tolerance (IGT); however, this risk has not been evaluated in a large population nor has it been followed prospectively. Design Diet, physical activity, anthropometric, socio-economic and blood glucose data from the Atherosclerosis Risk in Communities (ARIC) study were obtained from BioLINCC. Cox proportional hazards regression models were used to evaluate associations of dietary SFA, MUFA, PUFA, n-3 fatty acid (FA) and n-6 FA intakes with incidence of one (isolated IFG) or two (IFG with IGT) prediabetic conditions at the end of 12-year follow-up. Setting Study volunteers were from counties in North Carolina, Mississippi, Minnesota and Maryland, USA. Subjects Data from 5288 volunteers who participated in the ARIC study were used for all analyses reported herein. Results The study population was 62% male and 84 % white, mean age 53·5 (sd 5·7) years and mean BMI 26·2 (sd 4·6) kg/m2. A moderately high intake of dietary MUFA (10–15 % of total daily energy) was associated with a 10 % reduced risk of isolated IFG incidence, while a high intake of n-3 FA (>0·15 % of total daily energy) was associated with a 10 % increase in risk. Curiously, moderately high intake of n-6 PUFA (4–5 % of total daily energy) was associated with a 12 % reduction in IFG and IGT incidence. Conclusions MUFA, n-3 and n-6 FA contribute differently to the development of isolated IFG v. IFG with IGT; and their mechanism may be more complex than originally proposed.
Parenting in the face of childhood life-threatening conditions: The ordinary in the context of the extraordinary

Abstract Objective: Uncovering what it means to be a parent during the extraordinary time of a child's life-threatening condition (LTC) is important for understanding family goals, decision making, and the work of parenting within this context. Method: Qualitative descriptive methods were employed to describe the everyday experience of parenting both children who have an LTC and their healthy siblings. Results: Some 31 parents of 28 children with an LTC who have healthy siblings participated in our study. Four themes emerged from the data that describe a parental desire to maintain emotional connection with all of their children, how parents use cues from their children to know them better and develop parenting strategies, how parents change as a result of caring for a child with an LTC, and how they strive to decrease suffering for all of their children. Significance of results: The findings of our study have implications for clinical practice, family-focused research, and health policy pertaining to families of children with life-threatening conditions.
The occurrence of Culicoides species, the vectors of arboviruses, at selected trap sites in Zimbabwe

Abstract A study of the distribution of Culicoides species was conducted by establishing 12 light trap sites over five rainy seasons between 1998 and 2003 covering all the geo-climatic natural regions of Zimbabwe. In total, 279 919 specimens of Culicoides were trapped over a total of 163 trapping nights. The highest median counts of Culicoides per trapping night were recorded in natural region III, which has climatic conditions conducive to the successful development of the larvae. Culicoides imicola, the major vector of bluetongue and African horse sickness viruses in Africa, was found to be the most abundant species (80.4%), followed by Culicoides enderleini (5.9%) and Culicoides milnei (5.2%). This study identified 10 species of Culicoides that had not been previously described in Zimbabwe, including Culicoides loxodontis and Culicoides miombo, which are members of the C. imicola complex. A total of 23 994 Culicoides midges were collected from five trap sites in Harare, Zimbabwe, with the dominant species, C. imicola, representing 91.6% of the total collection. Seventeen arboviruses were isolated from these midges, 15 of which were bluetongue virus. The predominant bluetongue virus serotype was serotype 11, followed by serotypes 1, 8, 12 and 15. Bluetongue virus serotypes 1, 2, 8, 10, 12, 15, 16 and 18, detected in this study, had not been previously reported in Zimbabwe.