Miracle-dz/UniFAR-FTUs huggingface dataset:
Shotgun Lipidomics Revealed Altered Profiles of Serum Lipids in Systemic Lupus Erythematosus Closely Associated with Disease Activity

The pathogenesis of systemic lupus erythematosus (SLE) remains elusive. It appears that serum lipid metabolism is aberrant in SLE patients. Determination of lipid profiles in the serum of SLE patients may provide insights into the underlying mechanism(s) leading to SLE and may discover potential biomarkers for early diagnosis of SLE. This study aimed to identify and quantify the profile of serum lipids in SLE patients (N = 30) with our powerful multi-dimensional mass spectrometry-based shotgun lipidomics platform. Multivariate analysis in the form of partial least squares-discriminate analysis was performed, and the associations between the changed lipids with cytokines and SLE disease activity index (SLEDAI) were analyzed using a multiple regression method. The results of this study indicated that the composition of lipid species including diacyl phosphatidylethanolamine (dPE) (16:0/18:2, 18:0/18:2, 16:0/22:6, 18:0/20:4, and 18:0/22:6), 18:2 lysoPC (LPC), and ceramide (N22:0 and N24:1) was significantly altered in SLE patients with p < 0.05 and variable importance of the projection (VIP) > 1 in partial least squares-discriminate analysis (PLS-DA). There existed significant associations between IL-10, and both 18:0/18:2 and 16:0/22:6 dPE species with p < 0.0001 and predicting 85.7 and 95.8% of the variability of IL-10 levels, respectively. All the altered lipid species could obviously predict IL-10 levels with F (8, 21) = 3.729, p = 0.007, and R2 = 0.766. There was also a significant correlation between the SLEDAI score and 18:0/18:2 dPE (p = 0.031) with explaining 22.6% of the variability of SLEDAI score. Therefore, the panel of changed compositions of dPE and ceramide species may serve as additional biomarkers for early diagnosis and/or prognosis of SLE.
Kinetic analysis of push-up exercises: a systematic review with practical recommendations

ABSTRACT Push-ups represent one of the simplest and most popular strengthening exercise. The aim of this study was to systematically review and critically appraise the literature on the kinetics-related characteristics of different types of push-ups, with the objective of optimising training prescription and exercise-related load. A systematic search was conducted in the electronic databases PubMed, Google Scholar and Science Direct up to April 2018. Studies that reported kinetic data (e.g. initial and peak-force supported by the upper-limbs, impact-force, peak-flexion-moment of the elbow-joint, rate of propulsive- and impact-, and vertebral-joint compressive-forces) related to push-ups and included trained, recreational and untrained participants, were considered. The risk of bias in the included studies was assessed using the Critical Appraisal Skills Programme scale. From 5290 articles retrieved in the initial search, only 26 studies were included in this review. Kinetic data for 46 push-up variants were assessed. A limitation of the current review is that the relationship between our findings and actual clinical or practical consequences is not statistically proven but can only be inferred from our critical descriptive approach. Overall, this review provides detailed data on specific characteristics and intensities of push-up variations, in order to optimise exercise prescription for training and rehabilitation purposes.
Primary Osteoporosis in Young Adults: Genetic Basis and Identification of Novel Variants in Causal Genes

Genetic determinants contribute to osteoporosis and enhance the risk of fracture. Genomewide association studies of unselected population‐based individuals or families have identified polymorphisms in several genes related to low bone density, but not in osteoporotic patients with Z‐score < −2.0 SD with fragility fracture(s). The aim of this study was to determine the causal genes of idiopathic osteoporosis in the adulthood. Also, we used next‐generation sequencing of candidate genes in a cohort of 123 young or middle‐aged adults with idiopathic osteoporosis. All patients were included if they had a low bone mineral density (Z‐score < −2 SD), a diagnosis before age 55 years (mean ± SD, 48.4 ± 10.6 years; mean ± SD age at first fracture, 30.4 ± 17.4 years) and fracture or not. We found that 11 patients carried rare or novel variants in COL1A2 (n = 4), PLS3 (n = 2), WNT1 (n = 4), or DKK1 (n = 1). We showed a high prevalence of pathogenic variants in LRP5: 22 patients (17.8%) had the p.Val667Met variant, including three at the homozygous level and 16 (13%) carrying a novel or very rare variant. Functional analysis revealed that the LRP5 missense variants resulted in reduced luciferase activity, which indicates reduced activation of canonical WNT signaling. The clinical phenotype of patients carrying causal gene variants was indistinguishable. In conclusion, molecular screening of young osteoporotic adults revealed several variants and could be useful to characterize susceptibility genes for personalizing treatment, in particular for the new anabolic drugs. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China

We assessed the prevalence characteristics of single and multiple high‐risk human papillomavirus (HR‐HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR‐HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2‐3, and 76 with squamous cell carcinoma (SCC), with HR‐HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR‐HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR‐HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2‐3, and SCC, respectively, had a single HR‐HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR‐HPV infections in women attending a gynecological outpatient clinic in Beijing.
The ability to recognise emotions predicts the time-course of sarcasm processing: Evidence from eye movements

A core feature of sarcasm is that there is a discrepancy between the literal meaning of the utterance and the context in which it is presented. This means that a sarcastic statement embedded in a story introduces a break in local coherence. Previous studies have shown that sarcastic statements in written stories often elicit longer processing times than their literal counterparts, possibly reflecting the difficulty of integrating the statement into the story’s context. In the present study, we examined how sarcastic statements are processed when the location of the local coherence break is manipulated by presenting the sarcastic dialogues either before or after contextual information. In total, 60 participants read short text paragraphs containing sarcastic or literal target statements, while their eye movements were recorded. Individual differences in ability to recognise emotions and working memory capacity were measured. The results suggest that longer reading times with sarcastic statements not only reflect local inconsistency but also attempt to resolve the meaning of the sarcastic statement. The ability to recognise emotions was reflected in eye-movement patterns, suggesting that readers who are poor at recognising emotions are slower at categorising the statement as sarcastic. Thus, they need more processing effort to resolve the sarcastic meaning.
Human Atrial Arrhythmogenesis and Sinus Bradycardia in KCNQ1-Linked Short QT Syndrome: Insights From Computational Modelling

Atrial fibrillation (AF) and sinus bradycardia have been reported in patients with short QT syndrome variant 2 (SQT2), which is underlain by gain-of-function mutations in KCNQ1 encoding the α subunit of channels carrying slow delayed rectifier potassium current, IKs. However, the mechanism(s) underlying the increased atrial arrhythmogenesis and impaired cardiac pacemaking activity arising from increased IKs remain unclear. Possible pharmacological interventions of AF in the SQT2 condition also remain to be elucidated. Using computational modelling, we assessed the functional impact of SQT2 mutations on human sinoatrial node (SAN) pacemaking, atrial repolarisation and arrhythmogenesis, and efficacy of the anti-arrhythmic drug quinidine. Markov chain formulations of IKs describing two KCNQ1 mutations – V141M and V307L – were developed from voltage-clamp experimental data and then incorporated into contemporary action potential (AP) models of human atrial and SAN cells, the former of which were integrated into idealised and anatomically detailed tissue models. Both mutations shortened atrial AP duration (APD) through distinct IKs ‘gain-of-function’ mechanisms, whereas SAN pacemaking rate was slowed markedly only by the V141M mutation. Differences in APD restitution steepness influenced re-entry dynamics in tissue – the V141M mutation promoted stationary and stable spiral waves whereas the V307L mutation promoted non-stationary and unstable re-entrant waves. Both mutations shortened tissue excitation wavelength through reduced effective refractory period but not conduction velocity, which served to increase the lifespan of re-entrant excitation in a 3D anatomical human atria model, as well as the dominant frequency (DF), which was higher for the V141M mutation. Quinidine was effective at terminating arrhythmic excitation waves associated with the V307L but not V141M mutation, and reduced the DF in a dose-dependent manner under both mutation conditions. This study provides mechanistic insights into different AF/bradycardia phenotypes in SQT2 and the efficacy of quinidine pharmacotherapy.
Asymmetries in Gender and NumberAgreement Processing in Late Bilinguals

Although gender agreement is covered in the first lessons of gendered second languages (L2), adult learners demonstrate a persistent difficulty acquiring this linguistic feature (Bartning, 2000; Carroll, 1989; Dewaele & Véronique, 2001). Late bilinguals’ reduced sensitivity to morphosyntactic information has been associated with several factors, including age of acquisition (Hawkins & Chan, 1997; Clahsen & Felser, 2006), language proficiency (Ojima, Nakata, & Kakigi, 2005), similarity of linguistic structures in the L1 and the L2 (Sabourin, 2003; Tokowicz & MacWhinney, 2005), reliance on semantic rather than morphophonological and syntactic cues (Lew-Williams & Fernald, 2007; Ojima, Nakata, & Kakigi, 2005), and limitations of cognitive resources such as working memory (McDonald, 2006; Miyake & Friedman, 1998). Despite much research, the relative importance and interaction of these factors is still unclear and online studies examining these issues with nounadjective agreement are scarce. The present study examines the role of age of acquisition (whether late bilinguals can show native-like processing patterns); level of proficiency (whether bilinguals with more L2 experience behave qualitatively more like native speakers than those with less L2 exposure); and working memory (whether higher span bilinguals are more sensitive to agreement violations than lower span. Our working memory (WM) experiment also reveals whether gender disagreement consumes more attentional resources than number disagreement for late bilinguals compared to monolinguals. To investigate these variables, we measured the reading times (RTs) of adult native speakers of an ungendered language (English) reading sentences with noun-adjective gender and number agreement/disagreement in a gendered second language (L2), Spanish.
Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review

Importance Data on neurologic manifestations of fibromuscular dysplasia (FMD) are rare, and current knowledge remains limited. Objectives To present a comprehensive review of the epidemiologic characteristics, management, and prognosis of the neurologic manifestations associated with cerebrovascular FMD (ie, involving cervical or intracranial arteries) and to guide future research priorities. Evidence Review References were identified through searches of PubMed from inception to December 2017 using both the medical subject headings and text words. Additional sources were also identified by reviewing reference lists of relevant articles and through searches of the authors’ personal files. Selected articles described at least 1 clinical or radiologic feature and/or outcome of cerebrovascular FMD. Isolated case reports could be included if they described interesting or noteworthy manifestations of FMD. Findings A total of 84 relevant references were identified. Diagnosis of cerebrovascular FMD is based on the appearance of alternating arterial dilatation and constriction (“string of beads”) or of focal narrowing, with no sign of atherosclerotic or inflammatory lesions. Although the diagnosis is easily apparent on results of radiographic imaging, making a diagnosis can be challenging in children or individuals with atypical phenotypes, such as purely intracranial FMD and arterial diaphragm. Involvement of multiple arteries is common, and there is increased incidence of cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1 gene has been associated with FMD as well as cervical artery dissection and migraine, although less than 5% of cases of FMD are familial. Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD. Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic manifestations include transient ischemic attack and ischemic stroke, notably in the presence of associated cervical artery dissection. Other conditions associated with FMD include subarachnoid hemorrhage and, rarely, intracranial hemorrhage. Management relies on observational data and expert opinion. Antiplatelet therapy is considered reasonable to prevent thromboembolic complications. Endovascular therapy is typically restricted to cases with symptomatic stenosis despite optimal medical therapy or in those with rupture of an intracranial aneurysm. Conclusions and Relevance Longitudinal cohort studies of individuals of multiple ethnicities with biosampling are needed to better understand the risk factors, pathophysiological features, and outcomes of FMD. Patient advocacy groups could assist researchers in answering patient-centered questions regarding FMD.
Evolution of bacteria specialization along an antibiotic dose gradient

Antibiotic and pesticide resistance of pathogens are major and pressing worldwide issues. Resistance evolution is often considered in simplified ecological contexts: treated versus nontreated environments. In contrast, antibiotic usually present important dose gradients: from ecosystems to hospitals to polluted soils, in treated patients across tissues. However, we do not know whether adaptation to low or high doses involves different phenotypic traits, and whether these traits trade‐off with each other. In this study, we investigated the occurrence of such fitness trade‐offs along a dose gradient by evolving experimentally resistant lines of Escherichia coli at different antibiotic concentrations for ∼400 generations. Our results reveal fast evolution toward specialization following the first mutational step toward resistance, along with pervasive trade‐offs among different evolution doses. We found clear and regular fitness patterns of specialization, which converged rapidly from different initial starting points. These findings are consistent with a simple fitness peak shift model as described by the classical evolutionary ecology theory of adaptation across environmental gradients. We also found that the fitness costs of resistance tend to be compensated through time at low doses whereas they increase through time at higher doses. This cost evolution follows a linear trend with the log‐dose of antibiotic along the gradient. These results suggest a general explanation for the variability of the fitness costs of resistance and their evolution. Overall, these findings call for more realistic models of resistance management incorporating dose‐specialization.
Discontinuation of antidepressants in suicides findings from the Friuli Venezia Giulia Region, Italy, 2005‐2014

Although continued use of antidepressants (AD) has been found to be associated with a lower risk of suicide, AD discontinuation is reported repeatedly. The aim of this case‐control study, thus, was to assess whether discontinuation to AD was associated with an increased risk of suicide, according to different genders and age groups. The Social and Health Information System of Friuli Venezia Giulia Region, Italy, was used to collect data on suicides, diagnoses and AD use from 2005 to 2014. We selected, as cases, all suicides that had at least one prescription of AD in the 730 days before death (N = 876), and we matched with regard to age and sex each case with five controls from the general population. Conditional logistic regression analyses were used to assess the association between suicide and modifications of AD treatment. We found that 70% of suicides and controls from the general population discontinued AD in the 2 years before the index date. In two‐thirds of them, discontinuations were two or more. Discontinuation of AD, however, did not represent a significant risk factor for suicide. More appropriate care of depression, particularly by primary care physicians who widely prescribe AD, should be fostered in order to prevent suicide. However, more research is needed to assess to which extent AD discontinuation can affect suicidal risk.
Immediate and early implant placement in single‐tooth gaps in the anterior maxilla: A prospective study on ridge dimensional, clinical, and aesthetic changes

OBJECTIVES This prospective study evaluated the impact of timing of placement (immediate and early) on the horizontal ridge dimensional changes, clinical, and aesthetic outcomes of implants placed in single-tooth gaps in the anterior maxilla. MATERIALS AND METHODS Implants were placed in single-tooth gaps in the anterior maxilla of 30 patients, either immediately after extraction (Group A, n = 15) or after a healing period of 4-8 weeks (Group B, n = 15). In both groups, implant placement was followed by a 3- to 4-month period of non-submerged healing, after which definitive crowns were placed. Study models were obtained before extraction (T0), at implant placement (T1), at the insertion of a definitive crown (T2), and 1-year thereafter (T3). Horizontal ridge dimensional changes were measured by superimposing the optical scans of the study models from different time-points. Radiographs and photographs were used to evaluate changes in marginal bone levels and soft tissue recession. Aesthetic evaluation was carried out using the Pink and White Esthetic Score (PES and WES) indices. Patient-reported outcomes were measured using a subjective questionnaire. RESULTS A 100% implant survival rate was observed in both groups after a 1-year follow-up. Analysis showed a labial horizontal tissue dimensional change of 0.61 mm and 0.72 mm from T0 to T3 in Groups A and B, respectively. Acceptable PES values were observed in both groups (Group A: 9.40; Group B: 9.27) after the 1-year follow-up period. No incidence of advanced mucosal recession was observed between definitive crown insertion and 1-year follow-up in both groups. No significant changes were observed for all other measured variables at different time-points. CONCLUSIONS Immediate and early placed implants in single-tooth gaps in the anterior maxilla showed similar ridge dimensional changes as well as acceptable clinical, aesthetic, and patient-centred outcomes in the short-term (1-year follow-up).
A1899, PK‐THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type‐1 cells

Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BKCa) potassium channels which leads to membrane depolarization, voltage‐gated Ca‐entry, and neurosecretion. Here, we investigate the effects of pharmacological inhibitors on TASK channel activity and [Ca2+]i‐signaling in isolated neonatal rat type‐1 cells. PK‐THPP inhibited TASK channel activity in cell attached patches by up to 90% (at 400 nmol/L). A1899 inhibited TASK channel activity by 35% at 400 nmol/L. PK‐THPP, A1899 and Ml 365 all evoked a rapid increase in type‐1 cell [Ca2+]i. These [Ca2+]i responses were abolished in Ca2+‐free solution and greatly attenuated by Ni2+ (2 mM) suggesting that depolarization and voltage‐gated Ca2+‐entry mediated the rise in [Ca2+]i. Doxapram (50 μmol/L), a respiratory stimulant, also inhibited type‐1 cell TASK channel activity and increased [Ca2+]i. We also tested the effects of combined inhibition of BKCa and TASK channels. TEA (5 mmol/L) slightly increased [Ca2+]i in the presence of PK‐THPP and A1899. Paxilline (300 nM) and iberiotoxin (50 nmol/L) also slightly increased [Ca2+]i in the presence of A1899 but not in the presence of PK‐THPP. In general [Ca2+]i responses to TASK inhibitors, alone or in combination with BKCa inhibitors, were smaller than the [Ca2+]i responses evoked by hypoxia. These data confirm that TASK channel inhibition is capable of evoking membrane depolarization and robust voltage‐gated Ca2+‐entry but suggest that this, even with concomitant inhibition of BKCa channels, may be insufficient to account fully for the [Ca2+]i‐response to hypoxia.
Primary Intracranial Manifestation of a Carcinosarcoma

Carcinosarcomas are tumors comprising part adenocarcinoma and part sarcoma; the presence of carcinosarcoma in the head-and-neck region is very rare. These tumors are typically highly aggressive (G3) and arise most frequently from the salivary gland. Here, we present a case report on a brain metastasis as the primary manifestation of a carcinosarcoma. Magnetic resonance imaging showed a tumor of the pineal region with infiltration of the brainstem and the corpus. The staging following the histopathological diagnosis revealed the origin of the tumor in the left parotid gland. We present an overview of the significance of published treatment strategies in carcinosarcoma.