Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of Long Noncoding RNAs (lncRNA) NF-κβ-Interacting Long Noncoding RNA (NKILA) in Ankylosing Spondylitis is Correlated with Transforming Growth Factor β1 (TGF-β1), Active Disease and Predicts Length of Treatment

Background Long noncoding RNAs (lncRNA) NF-κβ-interacting long noncoding RNA (NKILA) is downregulated in various types of cancers, while its involvement in other diseases is unknown. In the present study we found that plasma lncRNA NKILA was expressed at higher levels in active ankylosing spondylitis patients than in healthy controls. Material/Methods According to Youden’s index, active disease patients were divided into high and low lncRNA NKILA groups. Results Patients in the high lncRNA NKILA level group had significantly longer length of treatment and higher re-hospitalization rate at 3 years after discharge. Plasma levels of TGF-β1 were also higher in active ankylosing spondylitis patients than in healthy controls. Levels of plasma lncRNA NKILA and TGF-β1 were significantly and positively correlated in ankylosing spondylitis patients but not in healthy controls. Conclusions Overexpression of lncRNA NKILA in ankylosing spondylitis is correlated with active disease and predicts length of treatment. LncRNA NKILA may participate in ankylosing spondylitis through the interaction with TGF-β1, which is a key player in this disease.
Development of an intravaginal ring delivering simultaneously anastrozole and levonorgestrel: a pharmacokinetic perspective

Abstract Intravaginal rings (IVRs) are an option for continuous administration of drugs in women. As an attractive approach for the treatment of endometriosis-associated pelvic pain, IVRs delivering a combination of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG) have been developed. This article describes the developmental pharmacokinetic (PK) aspects covering the characterization of in vitro release, preclinical IVR PK investigations in monkeys, and clinical PK considerations. An IVR for ATZ has been developed and investigated in healthy menstruating female cynomolgus monkeys showing effective in vivo release. PK data from the size-adapted IVR used in these animals can be translated into a human context as confirmed in human studies where predefined exposure levels of ATZ were reached. As ATZ may cause harm to the fetus, use of effective contraception has to be assured in women of childbearing potential. Therefore, the IVR delivers a low dose of LNG as a contraceptive. Although the daily dose differed strongly between both drugs (20 µg LNG/d to >1 mg ATZ/d), simultaneous delivery of ATZ and LNG in vitro and in vivo was observed with a high correlation between the in vitro release and PK profiles. The PK characteristics successfully guided the design of clinical studies investigating the drug–drug interaction (DDI) potential. No relevant DDI between both the investigated or other vaginally administered drugs were identified.
Effect of Extraneous Affect on Health Message Reception

People often avoid paying attention to health messages. One reason is that health messages can evoke negative affect, which produces avoidance. Prior efforts to reduce disengagement focused on changing message content or buffering the self from threat, producing mixed effects. The present studies test whether inducing positively valenced, low-arousal affect independently of the message or the self, labeled extraneous affect, promotes health message receptivity. Across four studies (total N = 1,447), participants who briefly meditated (vs. a control listening task) paid more attention to messages (Study 1). Increased positive valence facilitated attention, which subsequently increased message comprehension (Studies 2-4), whereas reduced arousal directly increased message comprehension. These effects generalized across extraneous affect manipulations, settings, information domains, and levels of message threat. Taken together, extraneous affect can be leveraged to promote message receptivity. This contributes to a theoretical understanding of how affect impacts persuasion.
How should clinicians rehabilitate patients after ACL reconstruction? A systematic review of clinical practice guidelines (CPGs) with a focus on quality appraisal (AGREE II)

Objectives To summarise recommendations and appraise the quality of international clinical practice guidelines (CPGs) for rehabilitation after ACL reconstruction. Design Systematic review of CPGs (PROSPERO number: CRD42017020407). Data sources Pubmed, EMBASE, Cochrane, SPORTDiscus, PEDro and grey literature databases were searched up to 30 September 2018. Eligibility criteria English-language CPGs on rehabilitation following ACL reconstruction that used systematic search of evidence to formulate recommendations. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to report the systematic review. Two appraisers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to report comprehensiveness, consistency and quality of CPGs. We summarised recommendations for rehabilitation after ACL reconstruction. Results Six CPGs with an overall median AGREE II total score of 130 points (out of 168) and median overall quality of 63% were included. One CPG had an overall score below the 50% (poor quality score) and two CPGs scored above 80% (higher quality score). The lowest domain score was ‘applicability’ (can clinicians implement this in practice? ) (29%) and the highest ‘scope and purpose’ (78%) and ‘clarity of presentation’ (75%). CPGs recommended immediate knee mobilisation and strength/neuromuscular training. Early full weight-bearing exercises, early open and closed kinetic-chain exercises, cryotherapy and neuromuscular electrostimulation may be used according individual circumstances. The CPGs recommend against continuous passive motion and functional bracing. Conclusion The quality of the CPGs in ACL postoperative rehabilitation was good, but all CPGs showed poor applicability. Immediate knee mobilisation and strength/neuromuscular training should be used. Continuous passive motion and functional bracing should be eschewed.
Utility of preoperative exercise therapy in reducing postoperative morbidity after surgery; a clinical overview of current evidence

ABSTRACT Introduction: Surgery is a major stressor especially for older patients that are prone for postoperative complications and mortality. Hospitalization due to surgery and illness can be major life events, and the age-related impairments in physiological function and the decreased ability to respond to metabolic and hormonal perturbations in response to surgery often lead to a longer convalescence. Areas covered: This article gives an overview of the effects of PET in various surgical fields and also what to account for and expect of PET after various types of surgery. A comprehensive literature search was performed in Pubmed, Embase, Medline, Cochrane Library, and PEDro database (from the earliest date of each database to March 2019) using search words ‘Preoperative Exercise Therapy’, ‘Physical Therapy’ and ‘surgery’. Secondly, the literature searches were modified depending on the surgical specialty. Expert opinion: Evidence is growing that preoperative exercise therapy in various surgical specialties is well tolerated and effective, with by far the most evidence in the cardiac surgical field. Future improvements in standards of care and optimal pre-operative preparation should not only focus on the surgical team and the hospital organization but also on incorporating the active role of the patient.
Risk Factors and Long-Term Clinical Outcomes of Second-Generation Drug-Eluting Stent Thrombosis.

Background The risk factors and long-term clinical outcomes of patients with definite stent thrombosis (ST) after second-generation drug-eluting stent (DES) implantation have not yet been adequately assessed. Methods and Results The REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation DES Implantation) included 313 definite ST of second-generation DES (early ST, n=179; late ST, n=66; very late ST, n=68). Four patients without definite ST of second-generation DES were identified as control patients for each ST case. Risk factors of definite ST were mostly different according to the timing of ST: ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina at presentation, current smoking, left ventricular ejection fraction <40%, prior percutaneous coronary intervention, stent overlap, severely calcified lesion, left main coronary artery lesion, proximal left anterior descending lesion, postdiameter stenosis ≥20%, for early ST; age <70 years, ST-segment-elevation myocardial infarction at presentation, hemodialysis, left ventricular ejection fraction <40%, in-stent restenosis, and severely calcified lesion for late ST; and proximal left anterior descending lesion and in-stent restenosis for very late ST. Cumulative 4-year incidence of death after the index ST events was significantly higher in the ST patients than control patients (33.0% versus 12.3%, P<0.001 for early ST versus control; 30.6% versus 14.2%, P<0.001 for late ST versus control; and 28.0% versus 13.0%, P<0.001 for very late ST versus control, respectively). Conclusions Risk factors of definite ST after second-generation DES implantation were mostly different according to the timing of ST. Definite ST patients showed unfavorable long-term clinical outcomes compared with those without definite ST. Clinical Trial Registration URL: https://www.umin. ac.jp . Unique identifier: UMIN000025181.
Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial

PURPOSE In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy. PATIENTS AND METHODS A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (gBRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed gBRCAmut (non–gBRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to gBRCAmut status and response to their last platinum-based therapy. Ovarian cancer–specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy–Ovarian Symptom Index. RESULTS Progression-free survival was improved in patients treated with niraparib compared with placebo in both the gBRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non–gBRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes. CONCLUSION Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.
The knowledge of Polish medical students about digital rectal examination.

BACKGROUND The digital rectal examination (DRE) is a part of the standard physical examination and a useful diagnostic tool for detecting various lower gastrointestinal tract abnormalities. However nowadays it has been observed that medical students might not be properly prepared for performing and interpreting of DRE. The purpose of the study was to evaluate the knowledge and experience of Polish medical students about DRE. MATERIAL AND METHODS A prospective study was carried out using a questionnaire accessible via internet platform. The survey consisted of 12 questions and considered experience as well as practical and theoretical knowledge about DRE. 976 responses from nine Polish medical universities were included in the study. RESULTS 38.68% of students have never performed DRE with "lack of opportunity during courses" (71.09%) as the most common reason. Among responders who performed this examination only 12.72% had done it more than two times. Usefulness of DRE was mostly assessed as high and very high (55.63%). Students in the self-assessment part indicated low and very low (18.72% and 39.61%) technical abilities and also low (25.34%) interpretation skills. Conclusiosion: The knowledge of Polish medical students about DRE is insuffcient. Medical universities should pay particular attention to this field of examination to improve theoretical as well as practical skills of future doctors.
The relationship between chronotype and obesity in children and adolescent with attention deficit hyperactivity disorder

ABSTRACT Children and adolescents with Attention Deﬁcit Hyperactivity Disorder (ADHD) have a high prevalence of obesity, but the relationship between these two problems is not clear. Chronotype preferences may be one of the possible mechanisms underlying the link between ADHD and obesity. This is the ﬁrst study to investigate whether chronotype preferences are a mechanism linking ADHD symptoms to obesity in children and adolescents. This cross-sectional study included 110 drug-naive children and adolescents aged 7–17 years with ADHD. The Kiddie Schedule for Affective Disorders and Schizophrenia‐Present and Lifetime Version (K‐SADS‐PL) was used to diagnose ADHD or to exclude psychiatric comorbidity. The Conners’ Parents Rating Scale-Revised Short Version (CPRS-RS) and Children’s Chronotype Questionnaire (CCQ) were used to assess the severity of ADHD symptoms and chronotype preferences. Body mass index (BMI) was calculated and classified according to national age- and gender-specific reference values. The participants were divided into three groups as normal weight (<85%, n = 38), overweight (85%-95%, n = 30) and obesity (>95%, n = 42) according to their BMI percentile. There were statistically significant differences between the three groups in terms of chronotype preference (p = .000). Morningness preference was 86.84% in the normal BMI group and 26.19% in the obese BMI group. Eveningness preference was 7.89% in the normal BMI group and 61.90% in the obese BMI group. There was a correlation between the BMI percentile scores and the morningness/eveningness scale (M/E) scores. Moreover, there was a correlation between the BMI percentile scores and the oppositional and ADHD index scores. According to logistic regression analysis, the odds ratio of having evening type for obesity was 5.66 and the odds ratio of having morning type for normal weight was 13.03. Independently from ADHD symptoms, eveningness was directly related to obesity and morningness was directly related to normal weight. Prospective studies should be performed to better understand the relationship between ADHD, overweight/obesity and chronotype.
Clinical efficacy and safety of ranibizumab in the treatment of wet age-related macular degeneration

ABSTRACT Introduction: Although several approaches have been studied for treating wet age-related macular degeneration (w-AMD), currently, the most effective strategy in the management of this visual disorder is represented by anti-VEGF drugs. Among them, ranibizumab (RBZ) is widely adopted in clinical practice for treating w-AMD. Areas covered: VEGF (vascular endothelial growth factor) is a hypoxia-induced growth factor promoting neoangiogenesis, which has been correlated to the pathogenesis of w-AMD. RBZ is a humanized, recombinant, monoclonal antibody fragment (Fab), which binds all the isoform of VEGF-A and, therefore, exerts an inhibitory activity on the growth of new pathological vessels leading to the reabsorption of VEGF-related macular edema. The pivotal trials ANCHOR and MARINA revealed its clinical efficacy and good safety profile for treating w-AMD, leading ultimately to its FDA approval. Further trials have analyzed the best dosage and regimen modality, reporting RBZ at 0.5 mg with a ‘pro re nata’ regimen (PRN) to be non-inferior to the 0.5 mg formulation administered monthly. The treat-to-extend (TAE) regimen has also been investigated, demonstrating encouraging results in terms of clinical efficacy and nonetheless, it was proven to be a well-tolerated option with the possibility of reducing the treatment burden for the patients. Conclusions: RBZ has been proven to be an effective anti-VEGF agent for treating w-AMD; however, more optimal therapeutic regimens and drug delivery systems are being investigated in order to improve patients’ compliance and treatment burden.
Insight into the biochemical characterization of phytocystatin from Glycine max and its interaction with Cd+2 and Ni+2

Phytocystatins are cysteine proteinase inhibitors ubiquitously present in plants and animals. They are known to carry out various significant physiological functions and also maintain the balance of protease‐antiprotease activity. In the present disquisition, a phytocystatin after preliminary treatment has been isolated and purified to homogeneity from soybean (Glycine max) by a simple two‐step stratagem using ammonium sulfate fractionation and gel filtration chromatography performed on Sephacryl S‐100‐HR. Soybean phytocystatin (SBPC) was purified with a fold purification of 635 and percent yield of 77.6%. A single band was observed on native gel electrophoresis confirming the homogeneity of the purified SBPC. The molecular weight of SBPC was found to be 19.05 kDa as determined by SDS‐PAGE. The SBPC was found to be devoid of carbohydrate moieties and sulfhydryl group content. The binding stoichiometry of SBPC‐papain interaction was determined by isothermal calorimetry suggesting 1:1 complex, and the value of binding constant (K) was found to be 2.78 × 105 M−1 The affinity of binding (Kd) value obtained through ITC was 3.59 × 10−6 M. The purified SBPC was found to be stable in the pH range of 3 to 7 and is thermostable up to 50°C. The UV‐visible and fluorescence studies showed significant changes in the conformation upon the formation of the SBPC‐papain complex. Furthermore, fluorescence spectroscopy, ANS binding, and caseinolytic activity assay were conducted out to explore the effect of metal ions on SBPC which showed that there was a loss in the inhibitory activity along with conformational changes of SBPC upon complex formation with Cd+2 and Ni+2.
Vitamin D Supplementation and Prevention of Type 2 Diabetes.

BACKGROUND Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (0.95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).
Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

In mammals, ejaculated sperm acquire their fertilizing ability during migration through the female reproductive tract, which secretes several factors that contribute to sperm capacitation. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter in the central nervous system, but additionally enhances the sperm acrosome reaction in the rat and cow. However, the detailed effects of GABA concentration on sperm function remain unclear. In this study, we detected the presence of the GABA type A receptor (GABA A) in mouse epididymal sperm by western blot analysis and in the sperm acrosome by immunocytochemistry. We also investigated the effects of GABA on sperm fertilizing ability. We found that GABA facilitated the tyrosine phosphorylation of sperm proteins, which is an index of sperm capacitation. GABA also promoted the acrosome reaction, which was suppressed by a selective GABA A receptor antagonist. We then found that the effective GABA concentration for the acrosome reaction corresponds to sperm concentration, but we did not detect any marked effect of GABA on sperm motility using a computer-assisted sperm analysis system. Using immunohistochemistry, we also detected GABA expression in the epithelia of the mouse uterus and oviduct. Furthermore, we found that the mRNA levels of glutamate decarboxylase (Gad), which generates GABA from L-glutamate, were higher in the oviduct than in the uterus, and that Gad mRNA levels were higher at estrus than at the diestrus stage. These results indicate that the GABA concentration can act as a modulator of the acrosome reaction and sperm capacitation in the female reproductive tract.
Elevated maternal retinoic acid-related orphan receptor-γt enhances the effect of polyinosinic-polycytidylic acid in inducing fetal loss

T helper 17 (Th17) cells have been suggested to play a crucial role in various complications during pregnancy by participating in maternal immune activation (MIA). To test a possible role for Th17 cells in MIA-mediated abortion, we analyzed transgenic mice overexpressing retinoic acid receptor-related orphan receptor gamma-t (RORγt), a master regulator of IL-17 producing cell development. These mutant mice (RORγt Tg mice) exhibited a constitutive upregulation of serum IL-17A and decreased E-cadherin expression in cell–cell junctions of placental tissues. Abortion after the administration of a viral-mimicking synthetic double-stranded RNA polyinosinic–polycytidylic acid was more frequent in RORγt Tg mice than wild-type mice. These results suggest that excessive Th17 cell activity alters immune responsiveness and increases the rate of abortion during gestation.