Miracle-dz/UniFAR-FTUs huggingface dataset:
The relationship of the adiponectin +45 nucleotide T/G polymorphism with insulin resistance ,obesity and type 2 diabetes

Objective To study the relationship of the adiponectin+45 T/G polymorphism with insulin resistance ,obesity and type 2 diabetes. Methods The 100 type 2 diabetics and 101 healthy subjects with normal glucose tolerance were enrolled. All subjects were genotyped for the polymorphism of adiponectin by PCR-RFLP assay. Body mass index (BMI) and insulin resistance index (HOMA-IR) were evaluated. Results (1)The frequency of GG genotype was higher in type 2 diabetic group than in normal controls(P0.01). The frequency of G allele was higher in type 2 diabetic group than in normal controls(P0.01). (2)The BMI and HOMA-IR in the type 2 diabetic group was higher in TG+GG genotype than in TT genotype(P0.01). The frequencies of TG+GG genotype and G allele of the type 2 diabetic group were higher in BMI≥25 subgroup than in BMI25 subgroup(P0.01). Conclusion The polymorphism of adiponectin +45 nucleotide T/G is associated with obesity,insulin resistance, and type 2 diabetes.
Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study

Objective To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE). Methods This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected. Results Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K). Conclusion The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.
Effect of disease-associated P123H and V70M mutations on β-synuclein fibrillation.

Synucleinopathies are a class of neurodegenerative diseases, including Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA). The common pathological hallmark of synucleinopathies is the filamentous α-synuclein (α-Syn) aggregates along with membrane components in cytoplasmic inclusions in the brain. β-Synuclein (β-Syn), an isoform of α-Syn, inhibits α-Syn aggregation and prevents its neurotoxicity, suggesting the neuroprotective nature of β-Syn. However, this notion changed with the discovery of disease-associated β-Syn mutations, V70M and P123H in the patients with DLB. It is still unclear how these missense mutations alter the structural and amyloidogenic properties of β-Syn, leading to neurodegeneration. Here, we characterized the biophysical properties and investigated the effect of mutations on β-Syn fibrillation under different conditions. V70M and P123H show high membrane binding affinity compared to wild-type β-Syn, suggesting their potential role in membrane interactions. β-Syn and its mutants do not aggregate under normal physiological conditions; however, the proteins undergo self-polymerization in a slightly acidic microenvironment and/or in the presence of an inducer, forming long unbranched amyloid fibrils similar to α-Syn. Strikingly, V70M and P123H mutants exhibit accelerated fibrillation compared to native β-Syn under these conditions. NMR study further revealed that these point mutations induce local perturbations at the site of mutation in β-Syn. Overall, our data provide insight into the biophysical properties of disease-associated β-Syn mutations and demonstrate that these mutants make the native protein more susceptible to aggregation in an altered microenvironment.
Understanding the role of GPs’ gut feelings in diagnosing cancer in primary care: a systematic review and meta-analysis of existing evidence

Background Growing evidence for the role of GPs’ gut feelings in cancer diagnosis raises questions about their origin and role in clinical practice. Aim To explore the origins of GPs’ gut feelings for cancer, their use, and their diagnostic utility. Design and setting Systematic review and meta-analysis of international research on GPs’ gut feelings in primary care. Method Six databases were searched from inception to July 2019, and internet searches were conducted. A segregated method was used to analyse, then combine, quantitative and qualitative findings. Results Twelve articles and four online resources were included that described varied conceptualisations of gut feelings. Gut feelings were often initially associated with patients being unwell, rather than with a suspicion of cancer, and were commonly experienced in response to symptoms and non-verbal cues. The pooled odds of a cancer diagnosis were four times higher when gut feelings were recorded (OR 4.24, 95% confidence interval = 2.26 to 7.94); they became more predictive of cancer as clinical experience and familiarity with the patient increased. Despite being included in some clinical guidelines, GPs had varying experiences of acting on gut feelings as some specialists questioned their diagnostic value. Consequently, some GPs ignored or omitted gut feelings from referral letters, or chose investigations that did not require specialist approval. Conclusion GPs’ gut feelings for cancer were conceptualised as a rapid summing up of multiple verbal and non-verbal patient cues in the context of the GPs’ clinical knowledge and experience. Triggers of gut feelings not included in referral guidance deserve further investigation as predictors of cancer. Non-verbal cues that trigger gut feelings appear to be reliant on continuity of care and clinical experience; they tend to remain poorly recorded and are, therefore, inaccessible to researchers.
Philometroides khalili n. sp., a new philometrid nematode (Philometridae) from the operculum of the cyprinid fish Labeo rosae in Zimbabwe

Summary A new nematode species, Philometroides khalili n. sp. (Philometridae), is described from female specimens recovered from the operculum of the freshwater cyprinid fish Labeo rosae Steindachner (Cyprinidae, Cypriniformes) caught in the Bubi River, Zimbabwe. Based on light and scanning electron microscopical examination, the new species mainly differs from the only other African congeneric species P. africanus Moravec et Van As, 2001 in the body shape (filiform), length of gravid female (56 - 71 mm), in possessing a large oesophageal gland with a conspicuously large cell nucleus and in the shape (transversely oval), size (up to 33 - 36 μm high) and distribution of cuticular bosses. From other congeners it differs by a combination of morphological and biometrical features
High-Dose Dabigatran Is an Effective Anticoagulant for Simulated Cardiopulmonary Bypass Using Human Blood.

BACKGROUND Currently no ideal alternative exists for heparin for cardiopulmonary bypass (CPB). Dabigatran is a direct thrombin inhibitor for which a reversal agent exists. The primary end point of the study was to explore whether Dabigatran was an effective anticoagulant for 120 minutes of simulated CPB. METHODS The study was designed in 2 sequential steps. Throughout, human blood from healthy donors was used for each experimental step. Initially, increasing concentrations of Dabigatran were added to aliquots of fresh whole blood, and the anticoagulant effect measured using kaolin/tissue factor-activated thromboelastography (rapidTEG). The dynamics of all thromboelastography (TEG) measurements were studied with repeated measures analysis of variance (ANOVA). Based on these data, aliquots of blood were treated with high-concentration Dabigatran and placed in a Chandler loop as a simple ex vivo bypass model to assess whether Dabigatran had sufficient anticoagulant effects to maintain blood fluidity for 2 hours of continuous contact with the artificial surface of the PVC tubing. Idarucizumab, humanized monoclonal antibody fragment, was used to verify the reversibility of Dabigatran effects. Finally, 3 doses of Dabigatran were tested in a simulated CPB setup using a heart-lung machine and a commercially available bypass circuit with an arteriovenous (A-V) loop. The primary outcome was the successful completion of 120 minutes of simulated CPB with dabigatran anticoagulation, defined as lack of visible thrombus. Thromboelastographic reaction (R) time was measured repeatedly in each bypass simulation, and the circuits were continuously observed for clot. Scanning Electron Microscopy (SEM) was used to visualize fibrin formation in the filters meshes during CPB. RESULTS In in vitro blood samples, Dabigatran prolonged R time and reduced the dynamics of clot propagation (as measured by speed of clot formation [Angle], maximum rate of thrombus generation [MRTG], and time to maximum rate of thrombus generation [TMRTG]) in a dose-dependent manner. In the Chandler Loop, high doses of Dabigatran prevented clot formation for 120 minutes, but only at doses higher than expected. Idarucizumab decreased R time and reversed anticoagulation in both in vitro and Chandler Loops settings. In the A-V loop bypass simulation, Dabigatran prevented gross thrombus generation for 120 minutes of simulated CPB. CONCLUSIONS Using sequential experimental approaches, we showed that direct thrombin inhibitor Dabigatran in high doses maintained anticoagulation of blood for simulated CPB. Idarucizumab reduced time for clot formation reversing the anticoagulation action of Dabigatran.
Contribution of T-Type Calcium Channels to Spinal Cord Injury-Induced Hyperexcitability of Nociceptors

A hyperexcitable state and spontaneous activity of nociceptors have been suggested to play a critical role in the development of chronic neuropathic pain following spinal cord injury (SCI). In male rats, we employed the action potential-clamp technique to determine the underlying ionic mechanisms responsible for driving SCI-nociceptors to a hyperexcitable state and for triggering their spontaneous activity. We found that the increased activity of low voltage activated T-type calcium channels induced by the injury sustains the bulk (∼60–70%) of the inward current active at subthreshold voltages during the interspike interval in SCI-nociceptors, with a modest contribution (∼10–15%) from tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In current-clamp recordings, inhibition of T-type calcium channels with 1 μm TTA-P2 reduced both the spontaneous and the evoked firing in response to current injections in SCI-nociceptors to a level similar to sham-nociceptors. Electrophysiology in vitro was then combined with the conditioned place preference (CPP) paradigm to determine the relationship between the increased activity of T-type channels in SCI-nociceptors and chronic neuropathic pain following SCI. The size of the interspike T-type calcium current recorded from nociceptors isolated from SCI rats showing TTA-P2-induced CPP (responders) was ∼6 fold greater than the interspike T-type calcium current recorded from nociceptors isolated from SCI rats without TTA-P2-induced CPP (non-responders). Taken together, our data suggest that the increased activity of T-type calcium channels induced by the injury plays a primary role in driving SCI-nociceptors to a hyperexcitable state and contributes to chronic neuropathic pain following SCI. SIGNIFICANCE STATEMENT Chronic neuropathic pain is a major comorbidity of spinal cord injury (SCI), affecting up to 70–80% of patients. Anticonvulsant and tricyclic antidepressant drugs are first line analgesics used to treat SCI-induced neuropathic pain, but their efficacy is very limited. A hyperexcitable state and spontaneous activity of SCI-nociceptors have been proposed as a possible underlying cause for the development of chronic neuropathic pain following SCI. Here, we show that the increased activity of T-type calcium channels induced by the injury plays a major role in driving SCI-nociceptors to a hyperexcitable state and for promoting their spontaneous activity, suggesting that T-type calcium channels may represent a pharmacological target to treat SCI-induced neuropathic pain.
A systematic review of in vitro studies evaluating the inhibitory effects of polyphenol-rich fruit extracts on carbohydrate digestive enzymes activity: a focus on culinary fruits consumed in Europe

Abstract Evidence shows that polyphenols can attenuate postprandial blood glucose responses to meals containing digestible carbohydrate. Polyphenol-rich plant extracts are emerging as potential ingredients in functional foods and/or beverages despite limited understanding of their physiological effects. Many studies have investigated the mechanisms of polyphenol-rich fruit extracts on inhibition of digestive enzymes. However, the evidence available has yet to be critically evaluated systematically. This report reviews the in vitro literature to quantify the effect of fruit polyphenol extracts on the activities of digestive carbohydrases. A systematic literature search was conducted using six science databases. Included studies, totaling 34 in number, were in vitro digestion models which quantified gut digestive enzyme(s) activity on starch digestion in the presence of fruit polyphenol extracts. Most studies assessed the effects of fruit extracts on either α-amylase (n = 30) or α-glucosidase (n = 30) activity. Studies were consistent overall in showing stronger inhibition of α-amylase compared to α-glucosidase by proanthocyanidin- and/or ellagitannin-rich fruit extracts. Recommendations are proposed for future reporting of this type of research to enable meaningful synthesis of the literature as a whole. Such knowledge could allow effective choices to be made for development of novel functional foods and beverages.
Sentinel surveillance strategies for early detection of coronavirus disease in fever clinics: experience from China

Abstract Sentinel surveillance system plays a key role in screening and monitoring emerging and acute infectious diseases in order to identify the suspected cases in time. During SARS period in 2003, fever clinics emerged in many cities in mainland China with the purpose to screen the suspected SARS patients and to transfer the confirmed cases to designated hospitals for professional management. Shanghai city has reserved the fever clinics and the designated hospitals since then. Hence, clinicians in the front line are able to respond quickly to the emerging COVID-19 outbreak with their accumulated knowledge and experiences from the past. One hundred seventeen fever clinics distributed in various district areas in Shanghai have played a vital ‘sentinel’ role to fight against the COVID-19 epidemic. Most of suspected patients were identified in fever clinics and thereafter among these suspected patients the COVID-19 cases were confirmed and were isolated quickly to avoid the spread. We would like to share the sentinel roadmap for screening and diagnosis of COVID-19 to medical healthcare workers around the world, especially countries who are facing great challenges to cope with COVID-19 and meanwhile with limited medical resources. These sentinel surveillance strategies will certainly provide insight into the early detection and timely isolation of suspected cases from the others.
Clinical course and characteristics of patients with coronavirus disease 2019 in Wuhan, China: a single-centered, retrospective, observational study

Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is the virus responsible for the coronavirus disease 2019(COVID-19) pandemic. Despite the extensive studies aiming to understand the pathology of COVID-19, the clinicopathological characteristics and risk factors associated with COVID-19 remain mostly unclear. In this study, we assessed the clinical course and features of COVID-19 patients. Findings: There were 59 patients (54.1%) that had no fever. One-hundred(91.7%) patients required oxygen therapy, which improved percutaneous oxygen saturation (SpO2). Seventy-two (66.1%) patients aged over 60; these patients were more likely to develop respiratory symptoms. Only 13(11.9%) patients were positive for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleic acid, and computed tomography (CT) findings. We found significant differences in age, respiratory symptoms, and heart rates between patients with and without underlying conditions. Conclusions: Our findings suggest that oxygen plays an important role in the treatment of COVID-19 patients and that age and underlying diseases are significant risk factors for COVID-19. Most COVID-19 patients have no fever, and CT provides higher detection rates than antibody- and nucleic acid-based detection methods. Methods: We analyzed data from 109 confirmed COVID-19 cases. We compared the clinicopathological characteristic of patients stratified according to age and underlying diseases, as well as assessed the detection rates of different diagnostic methods.
Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19

Supplemental Digital Content is available in the text. Objective: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9–3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4–2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9–3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6–2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). Conclusions: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.
Radiotherapy after breast‐conserving surgery for elderly patients with early‐stage breast cancer: A national registry‐based study

Considerable controversies exist regarding whether elderly patients with early‐stage breast cancer receiving breast‐conserving surgery (BCS) should forgo radiotherapy. We utilized the National Cancer Database to analyze data of 115 516 women aged ≥70 years, treated with BCS for T1‐2N0‐1M0 breast cancer between 2004 and 2014. Multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality 3, 5 and 10 years after 90 days of BCS associated with radiotherapy. Patients who received no radiotherapy had a higher mortality rate than those who received radiotherapy (5‐year survival rate: 71.2% vs 83.8%), with multivariable‐adjusted HRs of 1.65 (95% CI: 1.57‐1.72) for 3‐year mortality, 1.53 (1.47‐1.58) for 5‐year mortality and 1.43 (1.39‐1.48) for 10‐year mortality. The association held even for patients ≥90 years. This association was observed in all strata by reasons for radiotherapy omission, receipt of endocrine therapy or chemotherapy, calendar period and other clinical characteristics, with 40% to 65% increased 5‐year mortality for patients without radiotherapy. This positive association persisted when analyses were restricted to patients with T1N0 and estrogen‐receptor‐positive disease who had received endocrine therapy (5‐year mortality: HR 1.47 [1.39‐1.57]) and in propensity score weighted analyses. Our study shows, in routine practice, elderly patients who received no post‐BCS radiotherapy had higher total mortality than those who received radiotherapy. These findings suggest that the current recommendation of omission of post‐BCS radiotherapy for elderly women with early‐stage breast cancer may need to be reconsidered, particularly for those without contraindication.
Annual dry-matter production by three apple cultivars at four within-row spacings in New Zealand

Summary Annual dry-matter production was estimated from eight year old apple trees of ‘Fuji’, ‘Braeburn’ and ‘Royal Gala’ on rootstock M.9, trained as slender spindles, in a spacing trial with trees spaced at 1.3, 1.5, 1.9 and 2.4 m within the row with tree rows 3.5 m apart. Light interception was recorded at intervals during the season. Both fresh weight yield and total dry-matter production were linear functions of light interception, with a higher slope recorded for the two late season cultivars compared with the early maturing ‘Royal Gala’. Comparison of the relationship between mid-season light interception and apple yields with published values from elsewhere, reveals that the slope of the relationship is enhanced under New Zealand conditions. The relationship suggests an upper limit of yield of 169 t ha–1 at 90% light interception, slightly higher than the maximum yield recorded of 163 t ha–1. Energy conversion of intercepted light over the growing season into dry-matter production was similar to that observed in the United Kingdom, suggesting that the major climatic advantage in New Zealand over the United Kingdom is the higher growing season radiation integral. Dry matter was allocated in the order fruit>woody tissue>leaves, with partitioning to the fruit of 74, 72 and 63% for ‘Braeburn’, ‘Fuji’ and ‘Royal Gala’, respectively. Under New Zealand conditions, sustainable 70% harvest index values may be achievable for mature apple trees on dwarfing rootstock with late maturing cultivars.