Miracle-dz/UniFAR-FTUs huggingface dataset:
AN ANALYSIS OF ONE THOUSAND TESTICULAR SUBSTANCE IMPLANTATIONS

In presenting this phase of the study of internal secretions, one cannot be unmindful of the publicity which has been given the so-called interstitial gland during the past three years, and of the bad impression this has made upon the medical world. The rather doubting, skeptical—even intolerant—attitude of the medical profession toward a subject which has been so largely flouted before the public by newspapers, eager for sensational discoveries, particularly along sex lines, can well be condoned. In the past, physicians have had their fill of the “lost manhood” charlatans. And when word came from abroad in 1918 that youth could be renewed and many of the potentialities restored by the engrafting of interstitial glands of the monkey, the medical profession for the most part ridiculed it, feeling that it was similar in purpose and intent to the widely heralded tuberculosis cure with turtle serum coming from Germany in 1913.
4. Foundations of Care: Education, Nutrition, Physical Activity, Smoking Cessation, Psychosocial Care, and Immunization

Recommendations c People with diabetes should receive diabetes self-management education (DSME) and diabetes self-management support (DSMS) according to the national standards for DSME and DSMS when their diabetes is diagnosed and as needed thereafter. B c Effective self-management and quality of life are the key outcomes of DSME and DSMS and should be measured and monitored as part of care. C c DSME and DSMS should address psychosocial issues, as emotional well-being is associated with positive diabetes outcomes. C c DSME and DSMS programs are appropriate venues for people with prediabetes to receive education and support to develop and maintain behaviors that can prevent or delay the onset of diabetes. C c Because DSME and DSMS can result in cost-savings and improved outcomes B, DSME and DSMS should be adequately reimbursed by third-party payers. E
Gastrointestinal presentation of Kawasaki disease: A red flag for severe disease?

Background Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. Objective To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. Methods Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. Results 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). Conclusions This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population. Clinical trial registration 8/20014/O/OssN.
Long-term Microvascular Disease Outcomes in Patients With Type 2 Diabetes After Bariatric Surgery: Evidence for the Legacy Effect of Surgery

OBJECTIVE To identify and quantify any legacy effect of bariatric surgery on risk of incident microvascular disease in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a retrospective observational cohort study (n = 4,683; 40% racial/ethnic minority) of patients with type 2 diabetes who underwent bariatric surgery from 2001 through 2011. The primary outcome measure was incident microvascular disease defined as a composite indicator of the first occurrence of retinopathy, neuropathy, and/or nephropathy. The Cox proportional hazards framework was used to investigate the associations between type 2 diabetes remission/relapse status and time to microvascular disease. RESULTS Covariate-adjusted analyses showed that patients who experienced type 2 diabetes remission had 29% lower risk of incident microvascular disease compared with patients who never remitted (hazard ratio [HR] 0.71 [95% CI 0.60, 0.85]). Among patients who experienced a relapse after remission, the length of time spent in remission was inversely related to the risk of incident microvascular disease; for every additional year of time spent in remission prior to relapse, the risk of microvascular disease was reduced by 19% (HR 0.81 [95% CI 0.67, 0.99]) compared with patients who never remitted. CONCLUSIONS Our results indicate that remission of type 2 diabetes after bariatric surgery confers benefits for risk of incident microvascular disease even if patients eventually experience a relapse of their type 2 diabetes. This provides support for a legacy effect of bariatric surgery, where even a transient period of surgically induced type 2 diabetes remission is associated with lower long-term microvascular disease risk.
Return Intentions of University-Educated Turkish Expatriates

The study presents research findings on the return intentions of Turkish professionals residing abroad, where the targeted group comprises individuals working at a full time job abroad and possessing a tertiary-level degree. The data are obtained from an internet survey of Turkish professionals conducted by the authors during the first half of 2002. A total of 1224 usable responses were obtained from a combination of internet search and referral sampling methods. Student non-return appears to be more significant compared to professional migration, since participants with foreign degrees appear less likely to return. There is a strong, positive association between initial return intentions and current return intentions, although this weakens with the length of stay. The findings also tend to confirm that the recent economic crises in Turkey have had an adverse impact on the return intentions of university educated professionals working abroad.
Prefrontal cortex activation during a cognitive reappraisal task is associated with real-life negative affect reactivity

The neural substrate of cognitive reappraisal has been well-mapped. Individuals who successfully downregulate negative affect (NA) by reshaping their thoughts about a potentially emotional situation show augmented activity in the prefrontal cortex (PFC), with attenuated activity in the amygdala. We performed functional neuroimaging with experience sampling to determine whether individual differences in brain activation correspond to differences in real-life NA. While being scanned, 69 female students (aged 18–25 years) were asked to perform a cognitive reappraisal task. In addition, repeated assessments (5/day, 14 days) of affect and minor events in real-life were conducted. Individual t-maps were created for an instructed downregulation contrast (downregulate negative–attend negative) and an uninstructed regulation contrast (attend negative–attend neutral). Mean beta values were extracted from a priori defined regions of interest in the bilateral amygdala and PFC and were correlated with three daily life NA measures: baseline (mean) NA, NA variability, and NA reactivity to negative events. Only one out of twelve correlations for the amygdalae was nominally significant, which did not survive correction for multiple comparisons. PFC activation in the instructed and uninstructed regulation contrasts explained approximately 10% of the variance in NA reactivity; stronger recruitment during the attend-negative condition was correlated with lower reactivity levels. The degree to which individuals spontaneously engage frontal clusters may be a critical aspect of real-life emotional reactivity. The findings of this study provide a partial external validation of the cognitive reappraisal task, suggesting that frontal brain activation during implicit task conditions may have the strongest connection with real-life behaviors.
Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes

OBJECTIVE To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks’ gestation, respectively). RESULTS FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6–21.4] vs. 12.7 ng/mL [interquartile range 9.6–17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6–25.8] vs. 14.6 ng/mL [interquartile range 10.8–19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24–6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.
BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state

Malignant pleural mesothelioma is an aggressive cancer with poor prognosis. Here we have investigated in vitro efficacy of BAMLET and BLAGLET complexes (anti-cancer complexes consisting of oleic acid and bovine α-lactalbumin or β-lactoglobulin respectively) in killing mesothelioma cells, determined BAMLET and BLAGLET structures, and investigated possible biological mechanisms. We performed cell viability assays on 16 mesothelioma cell lines. BAMLET and BLAGLET having increasing oleic acid content inhibited human and rat mesothelioma cell line proliferation at decreasing doses. Most of the non-cancer primary human fibroblasts were more resistant to BAMLET than were human mesothelioma cells. BAMLET showed similar cytotoxicity to cisplatin-resistant, pemetrexed-resistant, vinorelbine-resistant, and parental rat mesothelioma cells, indicating the BAMLET anti-cancer mechanism may be different to drugs currently used to treat mesothelioma. Cisplatin, pemetrexed, gemcitabine, vinorelbine, and BAMLET, did not demonstrate a therapeutic window for mesothelioma compared with immortalised non-cancer mesothelial cells. We demonstrated by quantitative PCR that ATP synthase is downregulated in mesothelioma cells in response to regular dosing with BAMLET. We sought structural insight for BAMLET and BLAGLET activity by performing small angle X-ray scattering, circular dichroism, and scanning electron microscopy. Our results indicate the structural mechanism by which BAMLET and BLAGLET achieve increased cytotoxicity by holding increasing amounts of oleic acid in an active cytotoxic state encapsulated in increasingly unfolded protein. Our structural studies revealed similarity in the molecular structure of the protein components of these two complexes and in their encapsulation of the fatty acid, and differences in the microscopic structure and structural stability. BAMLET forms rounded aggregates and BLAGLET forms long fibre-like aggregates whose aggregation is more stable than that of BAMLET due to intermolecular disulphide bonds. The results reported here indicate that BAMLET and BLAGLET may be effective second-line treatment options for mesothelioma.
Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development

OBJECTIVE The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. RESEARCH DESIGN AND METHODS Clinically diagnosed patients with type 2 diabetes (n = 258; diabetes duration: 0.01–31 years) were evaluated using a new biomarker detecting autoantibodies directed to the extracellular domain of the neuroendocrine autoantigen IA-2 (IA-2ec). The proportion of IA-2ec autoantibodies was also evaluated in newly diagnosed patients with type 1 diabetes (n = 150; diabetes duration: 0.04–0.49 years). In addition, IA-2 (intracellular domain), GAD65, and zinc transporter 8 autoantibodies were assayed. RESULTS IA-2ec autoantibodies were detected in patients with type 1 diabetes and, surprisingly, in 5% of patients with type 2 diabetes without serologic responses to other IA-2 antigenic epitopes or other islet autoantigens. We also assessed the ability of IA-2ec–derived peptides to elicit CD4+ T-cell responses by stimulating peripheral blood mononuclear cells from patients with type 1 diabetes (n = 18) and HLA-matched healthy subjects (n = 13) with peptides and staining with the peptide/DQ8-specific tetramers, observing disease-associated responses to previously unreported epitopes within IA-2ec. CONCLUSIONS We developed a new antibody biomarker identifying novel antigenic determinants within the N terminus of IA-2. IA-2ec autoantibodies can be detected in patients with type 1 diabetes and in a subgroup of adult autoimmune patients with type 2 diabetes phenotype negative for conventional islet autoantibody testing. These observations suggest that islet autoimmunity may be more common in clinically diagnosed type 2 diabetes than previously observed.
Association of Visit-to-Visit Variability of Systolic Blood Pressure With Cardiovascular Disease and Mortality in Primary Care Chinese Patients With Type 2 Diabetes—A Retrospective Population-Based Cohort Study

OBJECTIVE This study aimed to evaluate the impact of visit-to-visit variability (VVV) of systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality among primary care Chinese patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS A retrospective cohort study was conducted in 124,105 Chinese adult primary care patients with T2DM and without prior diagnosed CVD from August 2008 to December 2009. The VVV of SBP was evaluated using SDs of SBP over 24 months. The risks of CVD and all-cause mortality associated with variability in SBP were evaluated using Cox proportional hazards regression. Subgroup analysis was conducted by the stratification of age, sex, duration of diabetes, the presence of chronic kidney disease, baseline SBP and trend, and the number and class of antihypertensive drugs. RESULTS A positive linear relationship between the VVV of SBP and the first incidence of CVD and all-cause mortality was identified over a median follow-up time of 39.5 months. Patients with a low SD of SBP of <5 mmHg had the lowest risks of CVD and all-cause mortality, and patients with an SD of SBP of ≥10 mmHg had significantly higher risks. For every 1 SD increase in the SD of SBP, the risks of CVD, all-cause mortality, and the composite of both events increased by 2.9% (95% CI 2.4–3.4%), 4.0% (95% CI 3.5–4.6%), and 3.4% (95% CI 3.0–3.8%), respectively. A direct linear relationship was also observed in all selected subgroups. CONCLUSIONS SBP variability, irrespective of the mean SBP level, is a potential predictor for the development of CVD and all-cause mortality in patients with diabetes. In addition to monitoring BP targets for their patients with diabetes, clinicians should also remain vigilant about the visit-to-visit fluctuation of BP.
1082O_PRWOMEN 4 ONCOLOGY IN GREECE: EXPLORING COMMON CHALLENGES- SURVEY OF THE HELLENIC SOCIETY OF MEDICAL ONCOLOGY AMONG WOMEN ONCOLOGY PROFESSIONALS

ABSTRACT Aim: More women doctors choose oncology as a career but few are in leadership posts. Following the successful ESMO W4O initiative, a Forum of Women in Oncology in Greece was developed within HeSMO under the auspices of ESMO. Is a professional network of women in all oncology specialties to identify common problems, advocate for solutions and support women in oncology but also women with cancer through educative, awareness and fundraising actions. Methods: A questionnaire adapted from the ESMO survey, was distributed to women members of the Hellenic Societies of Medical, Radiation and Surgical Oncology and other women oncology professionals. Results: HeSMO has 245 members, 19% women. There is increasing number of female young members (GYMO 161 members, 33.5% women) but women Board representation is very limited (1 woman in 7 Board members). Analysis of the initial 60 questionnaires most from women HeSMO members (78%) is presented; responses from all oncology societies will be included in the final presentation. Responders are certified oncologists (85%), 52% in public and university hospitals, 44% in private, 70% mothers usually of 2-3 kids (65%). Most have 1- 10 publications but their name is rarely first or last. Women participate in national conferences (86% in 1-10/yr) but less often in international (55% never) and fewer as invited speakers/ chairs. Women representation at work teams is increasing (38% majority women), but the team leader is usually man (79%). Key professional satisfaction factors are relationship with patients (87%), intellectual stimulation (70%) and fighting a challenging disease (51%), similar to the ESMO survey. More than 1/3 (34%) believe women offer multi-tasking ability and smoother communication (20%). Work-family balance is the main challenge to career progression (63%). More than 1/3 (38%) propose mentorship programs, dedicated posts in boards, women oncologists' network and flexible training. Conclusions: This survey on women oncologists in Greece, the 1st such national effort in Europe, reveals increasing presence of women in oncology workforce but under-representation in leadership similar to the ESMO report. The W4O initiatives identify common problems but also advocate national/ international actions to bridge career inequalities, promote work-family balance, recognize and develop women oncology leaders. Disclosure: All authors have declared no conflicts of interest.
Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies

Recent randomized trials have compared the newer antidiabetic agents to treatments involving sulfonylureas, drugs associated with increased cardiovascular risks and mortality in some observational studies with conflicting results. We reviewed the methodology of these observational studies by searching MEDLINE from inception to December 2015 for all studies of the association between sulfonylureas and cardiovascular events or mortality. Each study was appraised with respect to the comparator, the outcome, and study design–related sources of bias. A meta-regression analysis was used to evaluate heterogeneity. A total of 19 studies were identified, of which six had no major design-related biases. Sulfonylureas were associated with an increased risk of cardiovascular events and mortality in five of these studies (relative risks 1.16–1.55). Overall, the 19 studies resulted in 36 relative risks as some studies assessed multiple outcomes or comparators. Of the 36 analyses, metformin was the comparator in 27 (75%) and death was the outcome in 24 (67%). The relative risk was higher by 13% when the comparator was metformin, by 20% when death was the outcome, and by 7% when the studies had design-related biases. The lowest predicted relative risk was for studies with no major bias, comparator other than metformin, and cardiovascular outcome (1.06 [95% CI 0.92–1.23]), whereas the highest was for studies with bias, metformin comparator, and mortality outcome (1.53 [95% CI 1.43–1.65]). In summary, sulfonylureas were associated with an increased risk of cardiovascular events and mortality in the majority of studies with no major design-related biases. Among studies with important biases, the association varied significantly with respect to the comparator, the outcome, and the type of bias. With the introduction of new antidiabetic drugs, the use of appropriate design and analytical tools will provide their more accurate cardiovascular safety assessment in the real-world setting.
Ultrastructure of Meelsvirus: A nuclear virus of arrow worms (phylum Chaetognatha) producing giant “tailed” virions

Most known giant viruses, i.e., viruses producing giant virions, parasitize amoebae and other unicellular eukaryotes. Although they vary in the level of dependence on host nuclear functions, their virions self-assemble in the host cell’s cytoplasm. Here we report the discovery of a new prototype of giant virus infecting epidermal cells of the marine arrow worm Adhesisagitta hispida. Its 1.25 μm-long virions self-assemble and accumulate in the host cell’s nucleus. Conventional transmission electron microscopy reveals that the virions have a unique bipartite structure. An ovoid nucleocapsid, situated in a broad “head” end of the virion is surrounded by a thin envelope. The latter extends away from the head to form a voluminous conical “tail” filled with electron-dense extracapsidular material. The 31nm-thick capsid wall has a distinctive substructure resulting from a patterned arrangement of subunits; it bears no ultrastructural resemblance to the virion walls of other known giant viruses. The envelope self-assembles coincident with the capsid and remotely from all host membranes. We postulate that transmission to new hosts occurs by rupture of protruding virion-filled nuclei when infected arrow worms mate. Future genomic work is needed to determine the phylogenetic position of this new virus, which we have provisionally named Meelsvirus.