Miracle-dz/UniFAR-FTUs huggingface dataset:
Eyes shut homolog is important for the maintenance of photoreceptor morphology and visual function in zebrafish

Mutations in eyes shut homolog (EYS), a gene predominantly expressed in the photoreceptor cells of the retina, are among the most frequent causes of autosomal recessive (ar) retinitis pigmentosa (RP), a progressive retinal disorder. Due to the absence of EYS in several rodent species and its retina-specific expression, still little is known about the exact function of EYS and the pathogenic mechanism underlying EYS-associated RP. We characterized eys in zebrafish, by RT-PCR analysis on zebrafish eye-derived RNA, which led to the identification of a 8,715 nucleotide coding sequence that is divided over 46 exons. The transcript is predicted to encode a 2,905-aa protein that contains 39 EGF-like domains and five laminin A G-like domains, which overall shows 33% identity with human EYS. To study the function of EYS, we generated a stable eysrmc101/rmc101 mutant zebrafish model using CRISPR/Cas9 technology. The introduced lesion is predicted to result in premature termination of protein synthesis and lead to loss of Eys function. Immunohistochemistry on retinal sections revealed that Eys localizes at the region of the connecting cilium and that both rhodopsin and cone transducin are mislocalized in the absence of Eys. Electroretinogram recordings showed diminished b-wave amplitudes in eysrmc101/rmc101 zebrafish (5 dpf) compared to age- and strain-matched wild-type larvae. In addition, decreased locomotor activity in response to light stimuli was observed in eys mutant larvae. Altogether, our study shows that absence of Eys leads to a disorganized retinal architecture and causes visual dysfunction in zebrafish.
New records of the endemic Sicilian land snail species Marmorana (Murella) muralis (O. F. Müller, 1774) from the north of Tunisia (Pulmonata, Gastropoda)

Abstract Marmorana (Murella) muralis is known as an endemic species of Sicily Island, which is introduced in many European countries. Here, M. (M.) muralis is recorded from the north of Tunisia. In order to confirm the identification of samples collected from several localities, shell morphology, details of genital organs and two mitochondrial markers (COI and 16S) were investigated. The results of the molecular study, as well as the morphological and anatomical studies confirm the identification of all Tunisian samples as M. (M.) muralis. The analysis of mitochondrial markers shows a low divergence between Sicilian and Tunisian samples suggesting a recent introduction of M. (M.) muralis to the North of Tunisia. The comparison of morphological characters of M. (M.) muralis with shell characters of Murella nicollei described by Pallary (1926) confirms that the latter should be considered as synonym of M. (M.) muralis.
Thirty minutes of handgrip exercise potentiates flow‐mediated dilatation in response to sustained and transient shear stress stimuli to a similar extent

What is the central question of this study? This study sought to determine whether enhancement of brachial artery flow‐mediated dilatation (FMD) after acute exposure to a sustained elevation in shear stress is greater when the shear stress stimulus for FMD is also sustained. What is the main finding and its importance? Brachial artery FMD in response to a sustained (handgrip exercise) and transient (reactive hyperaemia) shear stress stimulus was enhanced to a similar extent 10 min after a 30 min handgrip exercise intervention. This suggests that prior exposure to a sustained elevation in shear stress results in a similar acute augmentation of the ability of the endothelium to transduce sustained and transient shear stress stimuli.
Hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease.

Background Few studies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. Methods We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011-16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. Results The proportion of CKD Stages 1-5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) -0.021 to -0.004; P = 0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005-0.040; P = 0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI -0.122 to -0.039; P < 0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257-0.932; P = 0.001), -0.270 (-0.431 to -0.108; P = 0.001) and 0.115 (0.004-0.226; P = 0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. Conclusions Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies.
Incomplete Kawasaki Disease in an Adult South Asian Patient

Kawasaki disease is an acute multisystemic vasculitis occurring predominantly in children and rarely in adults, with sequelae of potentially life-threatening coronary artery aneurysms. “Incomplete” Kawasaki disease is a novel concept and considered a diagnosis of exclusion as it alludes to patients with fever lasting ⩾5 days and 2 or 3 clinical criteria without another reasonable explanation for the illness. The multidisciplinary team should be vigilant for this oligosymptomatic clinical presentation, specifically within this subgroup despite age and ethnicity, and the syndrome should be considered as a differential diagnosis in challenging cases presenting as infectious or autoimmune disease.
The acute anti-inflammatory action of xylopic acid isolated from Xylopia aethiopica

Abstract Background Our earlier studies had given evidence of the traditional application of Xylopia aethiopica in the management of inflammation. The principal constituent obtained from its bio-fractionation is xylopic acid. It is a crystalline diterpene that belongs to the class of kauranes. This work sets out to investigate the anti-inflammatory potential of the xylopic acid isolated from the dried fruit of X. aethiopica. Methods A preliminary anti-inflammatory study, using the protein denaturation model, and in vivo anti-inflammatory assay were employed in the investigation of acute inflammation. The modulation of the effect of the pro-inflammatory markers histamine, serotonin, bradykinin, and prostaglandin E2 by xylopic acid was investigated by in vivo mice paw oedema models. Results Xylopic acid showed a concentration-dependent inhibition of albumen denaturation with an IC50 of 15.55 μg mL−1. Xylopic acid (10, 30, 100 mg kg−1) inhibited the maximal oedema and the average paw thickness (oedema) over the period of each study considerably for all phlogistic agents employed (i.e. carrageenan, histamine, serotonin, bradykinin, and prostaglandin E2) in the inflammation induction for both prophylactic and therapeutic protocols. Conclusion This study establishes that xylopic acid has anti-inflammatory action in acute inflammation.
Real-world vs. randomized trial outcomes in similar populations of rivaroxaban-treated patients with non-valvular atrial fibrillation in ROCKET AF and XANTUS

AIMS Based on Phase III data, non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with atrial fibrillation. To determine whether trial outcomes translate into similar event rates in unselected patients, this analysis compared outcomes from the real-world XANTUS study with those from the Phase III ROCKET AF study. METHODS AND RESULTS Individual patient data from 4020 XANTUS patients were re-weighted to match the proportion of selected baseline characteristics in 7061 rivaroxaban-treated patients from ROCKET AF, using the matching-adjusted indirect comparison (MAIC) method. For the primary analysis, CHADS2 scores and gender were selected as relevant variables. Adjusted annualized incidence rates for XANTUS were calculated and compared with incidence rates from ROCKET AF-the ratio of these rates ('MAIC ratio') was used as a relative effect estimate. Rates of major bleeding [3.10%/year vs. 3.60%/year; MAIC ratio 0.86; 95% confidence interval (CI) 0.67-1.12] and stroke/non-central nervous system systemic embolism (1.54%/year vs. 1.70%/year; MAIC ratio 0.91; 95% CI 0.62-1.32) were similar between XANTUS and ROCKET AF. The rate of all-cause death was higher in XANTUS (3.22%/year vs. 1.87%/year; MAIC ratio 1.72; 95% CI 1.31-2.27), but the rates of vascular death were similar (1.83%/year vs. 1.53%/year; MAIC ratio 1.19; 95% CI 0.84-1.70). Sensitivity analyses weighted by different baseline characteristics supported these results. CONCLUSION The low rates of major bleeding and stroke in XANTUS were consistent with results from ROCKET AF. All-cause death, but not vascular death, was higher in XANTUS, as expected in an unselected real-world population.
Inherent variations in the cellular events at the site of amputation orchestrate scar‐free wound healing in the tail and scarred wound healing in the limb of lizard Hemidactylus flaviviridis

Lizards are unique in having both—regeneration competent (tail) as well as non‐regenerating appendages (limbs) in adults. They therefore present an appropriate model for comparing processes underlying regenerative repair and nonregenerative healing after amputation. In the current study, we use northern house gecko Hemidactylus flaviviridis to compare major cellular and molecular events following amputation of the limb and of the tail. Although the early response to injury in both cases comprises apoptosis, proliferation, and angiogenesis, the temporal distribution of these processes in each remained obscure. In this regard, observations were made on the anatomy and gene expression levels of key regulators of these processes during the healing phase of the tail and limb separately. It was revealed that cell proliferation markers like fibroblast growth factors were upregulated early in the healing tail, coinciding with the growing epithelium. The amputated limb, in contrast, showed weak expression of proliferation markers, limited only to fibroblasts in the later stage of healing. Additionally, apoptotic activity in the tail was limited to the very early phase of healing, as opposed to that in the limb, wherein high expression of caspase‐3 was observed throughout the healing process. Early rise in VEGF‐α expression reflected an early onset of angiogenesis in the tail, while it was seen to occur at a later stage in case of the limb. Moreover, the expression pattern of transforming growth factor beta members points toward a pro‐fibrotic response being induced very early in the amputated limb. Collectively, these results explain why regenerating appendages are able to heal without scars and if we are to induce scar‐free healing in nonregenerating limbs, what interventions can be envisaged. This is crucial to the field of regenerative medicine since it is the initial stages of repair following amputation, which decide whether the appendage will be restored or only covered with a scab.
The Art of Analgesia: A Pilot Study of Art Museum Tours to Decrease Pain and Social Disconnection Among Individuals with Chronic Pain

Objective. This mixed‐methods study examines the feasibility of art museum tours (Art Rx) as an intervention for individuals with chronic pain. Methods. Art Rx provided 1‐hour docent‐led tours in an art museum to individuals with chronic pain. Survey data were collected pre‐tour, immediately post‐tour, and at three weeks post‐tour. Pain intensity and unpleasantness were measured with a 0–10 numerical rating scale. Social disconnection was measured with a 12‐item social disconnection scale. Participants also reported percent pain relief during the tour and program satisfaction in the post‐tour survey. Change in pain and social disconnection was analyzed with paired t tests, bias‐corrected and accelerated bootstrap confidence intervals (BCa CIs), and Cohen's d. Thematic analysis of semistructured interviews with participants explored the feasibility and perceived impact of the program. Results. Fifty‐four individuals participated in this study (mean age [SD] = 59 [14.5] years, 64.8% female), and 14 were interviewed. Fifty‐seven percent of participants reported pain relief during the tour, with an average pain relief (SD) of 47% (34.61%). Participants reported decreased social disconnection and pain unpleasantness pre‐ to post‐tour (3.65, BCa 95% CI = 1.70–5.73, P < 0.001, d = 0.37; and 0.49, BCa 95% CI = 0.06–0.90, P = 0.016, d = 0.20, respectively). Participants indicated high satisfaction with the program. Interviewees remarked on the isolating impact of chronic pain and how negative experiences with the health care system often compounded this sense of isolation. Participants experienced Art Rx as a positive and inclusive experience, with potential lasting benefit. Conclusions. Art museum tours for individuals with chronic pain are feasible, and participants reported positive effects on perceived social disconnection and pain.
In Screening for Celiac Disease, Deamidated Gliadin Rarely Predicts Disease When Tissue Transglutaminase Is Normal

Objective: While tissue transglutaminase (tTG) antibodies are the most established serological test for celiac disease, newer deamidated gliadin peptide (DGP) screening tests are increasingly being completed. No pediatric study has systematically assessed the incidence of celiac disease in patients with an isolated positive DGP result. We sought to determine the positive predictive value of DGP serology for biopsy-confirmed celiac disease in pediatric patients with elevated DGP and normal tTG, to help guide clinicians’ decision making when screening for this common condition and avoid unnecessary invasive follow-up diagnostic testing. Methods: A multicenter retrospective review of children, from birth to age 18, with isolated DGP immunoglobulin G (IgG) positive serology referred to 3 Canadian centers was completed. The positive predictive value of an isolated elevated DGP result was calculated. Results: Forty patients with DGP positive, tTG negative serology underwent endoscopy with duodenal biopsy. Of these, only 1 patient had biopsy-confirmed celiac disease. This patient was IgA deficient. This yields a positive predictive value of 2.5% (95% confidence interval 0.1%–14.7%) for isolated DGP IgG positive serology. Conclusions: In isolation, DGP positive serology has a poor positive predictive value for celiac disease in children, especially in IgA sufficient individuals. Our findings suggest that DGP IgG testing should not be completed as part of the initial screening for celiac disease in the pediatric population as it does not effectively differentiate between individuals with and without the disease. Further research is needed to clarify to role of DGP IgG in children under the age of 2 and those with IgA deficiency.
Comparative study of the differential cell death protecting effect of various ROS scavengers

Abstract Oxidative stress has for a long time been associated with cell death, especially classical necrosis, however, its role in other cell death pathways is less clear. Here, we evaluated in a comparative way, the effect of four different reactive oxygen species (ROS) scavengers, N-acetyl-L-cysteine (NAC), α-tocopherol and two superoxide dismutase mimetics, n(III)tetrakis(4-benzoic acid)porphyrin chloride, and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol), in four different cell death models, including menadione-triggered necrosis, staurosporine-induced apoptosis and tumor necrosis factor (TNF)-induced apoptosis and necroptosis. While menadione-triggered necrosis was completely prevented by the classical ROS scavenger NAC and to a substantial amount by the other scavengers, ROS targeting was found to have a marginal effect on the other cell death modalities investigated. Despite its side-effects at higher concentrations, Tempol was able to substantially prevent TNF-induced apoptosis and to a somewhat lesser extent TNF-induced necroptosis. However, this seems to be separated from its ROS-scavenging function.
Therapeutic interventions for acute complete ruptures of the ulnar collateral ligament of the thumb: a systematic review

Background: The aim of this study was to evaluate the effectiveness of interventions for acute complete rupture of the ulnar collateral ligament (UCL) of the thumb in adults. Methods: The following databases were searched: MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO, from database inception to 31 st January 2018. Inclusion criteria were: (i) randomised controlled clinical trials (RCTs) or study of intervention with a comparator; (ii) participants with diagnosis of acute complete rupture of the UCL of the thumb; (iii) participants aged 18 years of age or older at enrolment; and (iv) published in a peer-reviewed English-language journal. Results: In total, six studies were identified for inclusion after screening. All studies had a high risk of bias. Three studies were retrospective comparative case series which compared two different surgical techniques (bone anchor versus pull out suture, suture versus pull out suture, suture versus steel wire). Of these studies, three were RCTs, two of which compared different rehabilitation regimes in patients managed surgically (plaster versus early mobilization, new spica versus standard spica). The remaining RCT compared two different rehabilitation regimes in a mixed group of surgically/non-surgically treated patients. The RCT comparing a standard spica with a new spica demonstrated a statistically significant improvement in outcomes with the new spica at all time points (range of motion, Dreiser index and VAS); this was also the only study to provide sufficient outcome data for further analysis. Conclusion: There is no prospective evidence comparing surgery to non-operative treatment for acute complete ruptures of the ulnar collateral ligament of the thumb. There is weak evidence to suggest that early mobilisation may be beneficial following surgical repair. Further research is necessary to better define which patients benefit from which specific interventions.
The utility of saliva testing in the estimation of uremic toxin levels in serum

Abstract Background p-Cresol sulfate (pCS) and indoxyl sulfate (IS) are uremic toxins, high concentrations of which are related to renal failure progression. Saliva could become the first-line diagnostic sample of choice, especially for monitoring purposes. Recently, a method for determination of pCS and IS in saliva was developed. Since no data exist on correlations between the levels of toxins in saliva and serum, the applicability of saliva as a diagnostic material is yet to be established. Here, we present a study on the assessment of the utility of saliva testing in the estimation of uremic toxin levels in serum. Methods The study material included serum and unstimulated, fasting saliva obtained from healthy volunteers (n=26) and patients at all stages of chronic kidney diseases (CKD, n=93). The concentration of pCS and IS in saliva and serum (total and unbound fractions) was determined. The daytime variation of the toxins was studied. Results A correlation was found between pCS and IS in saliva and biological active fractions in serum (0.74; 0.81). The variation of the serum/saliva ratio during the day was negligible, with a median of 10% for pCS and 6% for IS, making saliva a reliable material for the estimation of the uremic toxins in circulation at any time of the day. Significant correlations were observed between salivary toxin levels and estimated glomerular filtration rate (pCS: −0.61; IS: −0.70) as well as significant differences in toxin levels between the stages of CKD. Conclusions Saliva could be a valuable diagnostic material for the estimation of toxin levels in circulation.
Using event-related potentials to track morphosyntactic development in second language learners: The processing of number and gender agreement in Spanish

We used event-related potentials to investigate morphosyntactic development in 78 adult English-speaking learners of Spanish as a second language (L2) across the proficiency spectrum. We examined how development is modulated by the similarity between the native language (L1) and the L2, by comparing number (a feature present in English) and gender agreement (novel feature). We also investigated how development is impacted by structural distance, manipulating the distance between the agreeing elements by probing both within-phrase (fruta muy jugosa “fruit-FEM-SG very juicy-FEM-SG”) and across-phrase agreement (fresa es ácida “strawberry-FEM-SG is tart-FEM-SG”). Regression analyses revealed that the learners’ overall proficiency, as measured by a standardized test, predicted their accuracy with the target properties in the grammaticality judgment task (GJT), but did not predict P600 magnitude to the violations. However, a relationship emerged between immersion in Spanish-speaking countries and P600 magnitude for gender. Our results also revealed a correlation between accuracy in the GJT and P600 magnitude, suggesting that behavioral sensitivity to the target property predicts neurophysiological sensitivity. Subsequent group analyses revealed that the highest-proficiency learners showed equally robust P600 effects for number and gender. This group also elicited more positive waveforms for within- than across-phrase agreement overall, similar to the native controls. The lowest-proficiency learners showed a P600 for number overall, but no effects for gender. Unlike the highest-proficiency learners, they also showed no sensitivity to structural distance, suggesting that sensitivity to such linguistic factors develops over time. Overall, these results suggest an important role for proficiency in morphosyntactic development, although differences emerged between behavioral and electrophysiological measures. While L2 proficiency predicted behavioral sensitivity to agreement, development with respect to the neurocognitive mechanisms recruited in processing only emerged when comparing the two extremes of the proficiency spectrum. Importantly, while both L1-L2 similarity and hierarchical structure impact development, they do not constrain it.
Clinical Remission and Low Disease Activity Outcomes Over 10 Years in Systemic Lupus Erythematosus

A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years).