Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing and testing of a screening tool to predict people without IgE-mediated allergy: a quantitative analysis of the predictive value of a screening tool.

BACKGROUND Consultations in primary care for allergies are common. It can be difficult to differentiate between IgE-mediated (atopic) symptoms - which respond to allergen-specific interventions - and those that are non-atopic, without performing objective tests that are largely unavailable in UK general practice. AIM To develop and test a screening tool that can accurately discriminate between atopic and non-atopic individuals. DESIGN AND SETTING A validation study that took place in 2012 in adult volunteers aged >16 years in Scotland. METHOD A questionnaire screening tool was developed using questions from a large cohort study and through consultation with experts. Participants answered the questions and had skin prick tests for four aeroallergens (house dust mite, cat, dog, and mixed grasses). Participants were classified as atopic if any average wheal diameter was ≥3 mm bigger than the negative control. Sensitivity, specificity, and positive and negative predictive values of individual and combinations of questions were calculated. RESULTS In all, 143 participants completed the questionnaire and underwent skin prick testing. Of these, 81 (56.6%) were atopic. Negative predictive values for the individual questions ranged from 48.2% (55 not atopic out of 114 negative answers) to 72.0% (18/25). An optimum combination of four questions was identified, in which a negative answer to all four questions was reported by 24 participants, 21 (87.5%) of whom were not atopic. CONCLUSION The authors have identified a set of questions that correctly predict negative skin prick tests to common aeroallergens 88% of the time. These may be useful to exclude patients who do not warrant further investigation and who can reliably be advised that allergen avoidance is neither necessary nor helpful.
Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3 *

Within the ovarian follicle, granulosa cells (GCs) surround and support immature oocytes. FSH promotes the differentiation and proliferation of GCs and is essential for fertility. We recently reported that ERK activation is necessary for FSH to induce key genes that define the preovulatory GC. This research focused on the phosphoregulation by FSH of ERK within GCs. FSH-stimulated ERK phosphorylation on Thr202/Tyr204 was PKA-dependent, but MEK(Ser217/Ser221) phosphorylation was not regulated; rather, MEK was already active. However, treatment of GCs with the EGF receptor inhibitor AG1478, a dominant-negative RAS, an Src homology 2 domain-containing Tyr phosphatase inhibitor (NSC 87877), or the MEK inhibitor PD98059 blocked FSH-dependent ERK(Thr202/Tyr204) phosphorylation, demonstrating the requirement for upstream pathway components. We hypothesized that FSH via PKA enhances ERK phosphorylation by inhibiting the activity of a protein phosphatase that constitutively dephosphorylates ERK in the absence of FSH, allowing MEK-phosphorylated ERK to accumulate in the presence of FSH because of inactivation of the phosphatase. GCs treated with different phosphatase inhibitors permitted elimination of both Ser/Thr and Tyr phosphatases and implicated dual specificity phosphatases (DUSPs) in the dephosphorylation of ERK. Treatment with MAP kinase phosphatase (MKP3, DUSP6) inhibitors increased ERK(Thr202/Tyr204) phosphorylation in the absence of FSH to levels comparable with ERK phosphorylated in the presence of FSH. ERK co-immunoprecipitated with Myc-FLAG-tagged MKP3(DUSP6). GCs treated with MKP3(DUSP6) inhibitors blocked and PKA inhibitors enhanced dephosphorylation of recombinant ERK2-GST in an in vitro phosphatase assay. Together, these results suggest that FSH-stimulated ERK activation in GCs requires the PKA-dependent inactivation of MKP3(DUSP6).
Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation

Abstract Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.
Role of the polypill for secondary prevention in ischaemic heart disease

In 2011, for the first time in the history of humankind, non-communicable diseases became the leading cause of death worldwide. This change in trend is obviously multifactorial and very complex, as it is the paradoxical result of social, economic and health system growth worldwide. Vaccination and infectious diseases control, changing dietary habits worldwide, sedentary behaviour, globalisation, industrialisation (resulting in a shift from manual to sedentary labour), tobacco and sugary beverage surges in low- and middle-income countries and rapid urbanisation have all played a role in this epidemic transition. At the same time, the increase in cardiovascular risk factors, together with a decline in mortality in high-income countries in the past two decades, has led to a significant upsurge in the prevalence of secondary prevention of ischaemic heart disease. With this, the effect that non-adherence to cardioprotective drugs is having has become progressively clear, both in terms of clinical outcomes and as a driver of increased healthcare expenditure. The cardiovascular polypill, which was originally proposed as a strategy to improve accessibility to cardioprotective drugs worldwide, has proven to be a mainstay therapeutic approach for improving medication adherence in cardiovascular disease. In the current paper, we aim to review the need for a polypill strategy in the present scenario of cardiovascular disease, the available data that support such a strategy and the various clinical trials that are in progress that will help further shape future indications for the cardiovascular polypill.
Social variables exert selective pressures in the evolution and form of primate mimetic musculature

Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance ‘style’, and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber‐type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might reflect a compromise between the demands of the physical and the social environments.
Elucidating the role of hyposalivation and autoimmunity in oral candidiasis.

INTRODUCTION Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD). METHODS A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. RESULTS Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min-1 ) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P < 0.001) and NSGD (3.8, IQR: 3.8, P < 0.001) but comparable with that of Sicca (1.0, IQR: 1.5, P = 0.777) participants. The median total stimulated salivary flow rate (TSS, ml 15 min-1 ) was lowest in SS (7.0, IQR: 12.4, P < 0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n = 32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, P = 0.008). SS group had twice the risk of OC than NSGD (OR = 2.2, 95%CI: 1.1-4.2, P = 0.02) and Sicca (OR = 2.2, 95% CI: 1.0-4.8, P = 0.03), adjusting for confounders; hyposalivation [WUS (OR = 5.1, 95%CI: 2.5-10.4, P < 0.001), TSS (OR = 1.9, 95%CI: 1.0-3.5, P = 0.04)], history of other autoimmune disorders (OR = 4.4, 95%CI: 1.7-11.3, P = 0.002), medications for extraglandular manifestations (OR = 2.3, 95%CI: 1.1-4.9, P = 0.03), and diabetes mellitus (4.2, 95%CI: 1.2-15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13-0.67, P = 0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis. CONCLUSION Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population.
The relationship of regional hemoglobin A1c testing and amputation rate among patients with diabetes

Objective The risk of leg amputation among patients with diabetes has declined over the past decade, while use of preventative measures—such as hemoglobin A1c monitoring—has increased. However, the relationship between hemoglobin A1c testing and amputation risk remains unclear. Methods We examined annual rates of hemoglobin A1c testing and major leg amputation among Medicare patients with diabetes from 2003 to 2012 across 306 hospital referral regions. We created linear regression models to study associations between hemoglobin A1c testing and lower extremity amputation. Results From 2003 to 2012, the proportion of patients who received hemoglobin A1c testing increased 10% (74% to 84%), while their rate of lower extremity amputation decreased 50% (430 to 232/100,000 beneficiaries). Regional hemoglobin A1c testing weakly correlated with crude amputation rate in both years (2003 R = −0.20, 2012 R = −0.21), and further weakened with adjustment for age, sex, and disability status (2003 R = −0.11, 2012 R = −0.17). In a multivariable model of 2012 amputation rates, hemoglobin A1c testing was not a significant predictor. Conclusion Lower extremity amputation among patients with diabetes nearly halved over the past decade but only weakly correlated with hemoglobin A1c testing throughout the study period. Better metrics are needed to understand the relationship between preventative care and amputation.
Application of Epoxy/ Pb3O4 Composite for Gamma Ray Shielding

This paper aims to design types of shielding materials composites to protect public and personnel from the effect of scattered radiation during radiotherapy. It was found that 20% of lead oxide (Pb3O4) is the maximum percent finally mixed with Epoxy preserving good mechanical properties. Thermal characterization was discussed using thermal gravimetric analysis. Mechanical properties were studied by measuring hardness. Attenuation of gamma rays was carried out on synthesized composite, while some parameters such as thickness of composite, different sources and energies were discussed. Some shielding factors were measured such as half value layer (HVL), tenth value layer (TVL), attenuation coefficient (µ) and relaxation length (λ). Durability of the composite was determined by irradiation with gamma rays up to 500 KGy. Also, the change in gamma attenuation was carried out. Maximum calculated values of µ is 0.135 cm-1, λ is 7.61 cm, HVL is 5.66 cm and TVL is 17.06 cm were shown in case of 22 Na source for 0.551 keV energy which proved the availability for using the Pb3O4 composite as a gamma-ray shielding.
Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat

Prolonged translation arrest correlates with delayed neuronal death of hippocampal CA1 neurons following global cerebral ischemia and reperfusion. Many previous studies investigated ribosome molecular biology, but mRNA regulatory mechanisms after brain ischemia have been less studied. Here we investigated the embryonic lethal abnormal vision/Hu isoforms HuR, HuB, HuC, and HuD, as well as expression of mRNAs containing adenine and rich uridine elements following global ischemia in rat brain. Proteomics of embryonic lethal abnormal vision immunoprecipitations or polysomes isolated from rat hippocampal CA1 and CA3 from controls or following 10 min ischemia plus 8 h of reperfusion showed distinct sets of mRNA-binding proteins, suggesting differential mRNA regulation in each condition. Notably, HuB, HuC, and HuD were undetectable in NIC CA1. At 8 h reperfusion, polysome-associated mRNAs contained 46.1% of ischemia-upregulated mRNAs containing adenine and rich uridine elements in CA3, but only 18.7% in CA1. Since mRNAs containing adenine and rich uridine elements regulation are important to several cellular stress responses, our results suggest CA1 is disadvantaged compared to CA3 in coping with ischemic stress, and this is expected to be an important contributing factor to CA1 selective vulnerability. (Data are available via ProteomeXchange identifier PXD004078 and GEO Series accession number GSE82146).
Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort

OBJECTIVE Connective tissue growth factor (CTGF), also known as CCN2, is a potent chemotactic and extracellular matrix-inducing matricellular protein that has been implicated in progression of inflammatory and fibroproliferative disorders. An emerging role of CTGF/CCN2 is that of a prosclerotic factor implicated in the development of cardiac disease. Our objective was to determine the role of CTGF/CCN2 as a predictor of cardiovascular events in type 2 diabetes in the Veterans Affairs Diabetes Trial (VADT) cohort. RESEARCH DESIGN AND METHODS Levels of CTGF/CCN2 were measured in 952 VADT patients a median of 1.9 years after entry into the study. Participants were followed for an average of 3.3 years for vascular outcomes. CTGF/CCN2 categories were defined as below the detectable limit (referent, 54.5%), lower half of detectable values (22.8%), and upper half of detectable values (22.7%). Hazard ratios (HRs) for cardiovascular end points in relation to CTGF/CCN2 categories were calculated by Cox proportional hazards models. RESULTS During follow-up, 4.8% had a myocardial infarction (MI), 6.9% had an MI or cardiovascular death, and 6.9% died. After adjustments by conventional risk factors, individuals in the highest category of CTGF/CCN2 were at higher risk of MI (HR 2.43 [95% CI 1.15, 5.14]), MI or cardiovascular death (HR 2.71 [95% CI 1.44, 5.08]), and all-cause mortality (HR 2.70 [95% CI 1.43, 5.08]) relative to individuals with CTGF below the detectable limit. CONCLUSIONS Our study indicates that high levels of CTGF/CCN2 predict future MI and cardiovascular death in patients with type 2 diabetes.
Magnetic susceptibility anisotropy outside the central nervous system

Magnetic‐susceptibility‐based MRI has made important contributions to the characterization of tissue microstructure, chemical composition, and organ function. This has motivated a number of studies to explore the link between microstructure and susceptibility in organs and tissues throughout the body, including the kidney, heart, and connective tissue. These organs and tissues have anisotropic magnetic susceptibility properties and cellular organizations that are distinct from the lipid organization of myelin in the brain. For instance, anisotropy is traced to the epithelial lipid orientation in the kidney, the myofilament proteins in the heart, and the collagen fibrils in the knee cartilage. The magnetic susceptibility properties of these and other tissues are quantified using specific MRI tools: susceptibility tensor imaging (STI), quantitative susceptibility mapping (QSM), and individual QSM measurements with respect to tubular and filament directions determined from diffusion tensor imaging. These techniques provide complementary and supplementary information to that produced by traditional MRI methods. In the kidney, STI can track tubules in all layers including the cortex, outer medulla, and inner medulla. In the heart, STI detected myofibers throughout the myocardium. QSM in the knee revealed three unique layers in articular cartilage by exploiting the anisotropic susceptibility features of collagen. While QSM and STI are promising tools to study tissue susceptibility, certain technical challenges must be overcome in order to realize routine clinical use. This paper reviews essential experimental findings of susceptibility anisotropy in the body, the underlying mechanisms, and the associated MRI methodologies. Copyright © 2016 John Wiley & Sons, Ltd.
Parkin‐mediated mitophagy is downregulated in browning of white adipose tissue

Browning of white adipose tissue (WAT) promotes increased energy expenditure through the action of uncoupling protein 1 (UCP1) and is an attractive target to promote weight loss in obesity. Lowering of mitochondrial membrane potential by UCP1 is uniquely beneficial in this context; in other tissues, reduced membrane potential promotes mitochondrial clearance via mitophagy. It is unknown how parkin‐mediated mitophagy is regulated in beige adipocytes.
Validation of the V66.7 Code for Palliative Care Consultation in a Single Academic Medical Center.

BACKGROUND Use of administrative data to study the effectiveness of specialized palliative care is limited by the lack of a reliable method to identify patients receiving palliative care consultation. The International Classification of Diseases, Ninth Revision (ICD-9) code V66.7 has been used, but its validity for this purpose is unknown. OBJECTIVE To examine the validity of the ICD-9 code V66.7 for identifying whether hospitalized patients received palliative care consultation. DESIGN Retrospective cohort study. SETTING/SUBJECTS All patients of age ≥18 years admitted to a single academic medical center between August 2013 and August 2015. MEASUREMENTS Sensitivity and specificity of the V66.7 code for palliative care consultation for all patients and several a priori identified subgroups. The reference standard was the presence of a palliative care consultation note in the electronic medical record. RESULTS Of 100,910 admissions, 1999 received a palliative care consultation (2.0%) and 1846 (1.8%) had usage of the V66.7 code. Sensitivity and specificity for the V66.7 code were 49.9% and 99.1%, respectively. Sensitivity was considerably higher for certain subgroups, such as patients with dementia (76.3%) and metastatic cancer (66.3%); addition of age restrictions further improved sensitivity while maintaining high specificity. Specificity was substantially lower for patients who died during hospitalization (sensitivity 53.9%, specificity 75.1%). CONCLUSIONS In a single center, the ICD-9 code V66.7 had poor sensitivity and high specificity for identifying hospitalized patients who received a palliative care consultation. Appropriate use of this code for this purpose should take these characteristics into consideration.
Cografting astrocytes improves cell therapeutic outcomes in a Parkinson’s disease model

Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine model of Parkinson’s disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain. We show here that cografting astrocytes, especially those derived from the midbrain, remarkably enhanced NPC-based cell therapeutic outcomes along with robust DA neuron engraftment in PD rats for at least 6 months after transplantation. We further show that engineering of donor astrocytes with Nurr1 and Foxa2, transcription factors that were recently reported to polarize harmful immunogenic glia into the neuroprotective form, further promoted the neurotrophic actions of grafted astrocytes in the cell therapeutic approach. Collectively, these findings suggest that cografting astrocytes could be a potential strategy for successful cell therapeutic outcomes in neurodegenerative disorders.