Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies

Autistic spectrum disorder (ASD) is a complex neurodevelopmental disability with a genetic basis, and several studies have suggested a potential role of the reelin gene (RELN) in ASD susceptibility. Accordingly, genetic association studies have explored this potential association, but the results have been controversial thus far. For this reason, we assessed the association of four genetic variants of RELN (the 5′UTR CGG triplet repeat and polymorphisms rs736707, rs362691, and rs2229864) with ASD by means of a systematic review and meta-analysis. We retrieved studies comparing the distribution of the above-mentioned genetic variants between ASD patients and healthy controls. A meta-analysis was conducted using a random effects model, and calculations of the odds ratios (ORs) and confidence intervals (CIs) were performed. A sensitivity analysis and tests to determine the heterogeneity of the results were also performed. Eleven previous studies fulfilled the inclusion criteria and analyzed the association of the above-mentioned genetic variants and ASD. We did not find any significant association between the allele or genotype frequencies of the analyzed polymorphisms and ASD, and large heterogeneity was found for the rs736707 polymorphism. Moreover, no significant differences were found between the 5′UTR triplet repeat and this disorder. In light of current evidence, no single genetic variant within this gene is clearly associated with the development of ASD, and ethnic differences may explain part of the observed heterogeneity. Larger studies among different ethnic groups are needed to establish the role of specific genetic variants within RELN in the etiology of this disorder.
Gastrointestinal helminth parasites of cattle and buffalo in kashmir valley, india: overall, seasonal & monthly prevalence

During the present study for two years on the epidemiology of gastro-intestinal helminths in cattle and buffalo of Kashmir Valley, a total of 18 helminths species were recorded. Nematode and trematode species were dominant helminths followed by cestode species. The overall prevalence of trematodes was found 53.96% & 49.64% in cattle & buffalo. Data on monthly incidence of helminth infection showed that higher infection of helminths occurred in the month of June, July and August. Regarding the seasonal fluctuation of helminths, trematode infection was highest (63.26%) in autumn and summer (67.80%) and lowest in winter (47.51% & 26.92%) in cattle. While as in buffaloes, the highest infection was reported in summer (44.68% & 68.51%) and lowest in winter (21.73% & 52.94%). In case of cattle the cestode infection was maximum in summer (9.58%) & winter (13.04%). While as in case of buffaloes, the highest infection was found in summer (9.25%) and in autumn (9.52%). In both hosts, the lowest prevalence was found during winter (3.54% & 5.12%); autumn (4.16%) and in spring (8.00%) respectively. The highest gastrointestinal nematode infection in cattle was reported in summer (53.84%) of first year and again in summer (70.54%) of next year. The lowest infection in both the years in case of cattle was reported in winter (39.74% & 32.62%). In buffaloes, the highest nematode infection as per the gut examination was found in spring in both the years (60.00% & 54.05%) and the lowest infection was reported in winter (34.78% & 25.49%) respectively.
Fluid Shear Stress Induces EMT of Circulating Tumor Cells via JNK Signaling in Favor of Their Survival during Hematogenous Dissemination

Tumor cells metastasize to distal organs mainly through hematogenous dissemination, where they experience considerable levels of fluid shear stress. Epithelial–mesenchymal transition (EMT) plays a critical role in tumor metastasis. However, how fluid shear stress influences the EMT phenotype of circulating tumor cells (CTCs) in suspension has not been fully understood. The role of shear-induced EMT in cell survival under blood shear flow remains unclear. This study shows that the majority of breast CTCs underwent apoptosis under shear flow and the surviving cells exhibited mesenchymal phenotype, suggesting that fluid shear stress induces EMT. Mechanistically, fluid shear stress-activated Jun N-terminal kinase (JNK) signaling, inhibition/activation of which suppressed/promoted the EMT phenotype. In particular, shear flow facilitated the JNK-dependent transition of epithelial CTCs into the mesenchymal status and maintained the pre-existing mesenchymal cells. Importantly, the induction of EMT suppressed the pro-apoptosis gene p53 upregulated modulator of apoptosis (PUMA) and enhanced the survival of suspended CTCs in fluid shear stress, which was rescued by overexpressing PUMA or silencing JNK signaling, suggesting that shear-induced EMT promotes CTC survival through PUMA downregulation and JNK activation. Further, the expressions of EMT markers and JUN were correlated with poor patient survival. In summary, our findings have demonstrated that fluid shear stress induces EMT in suspended CTCs via JNK signaling that promotes their survival in shear flow. This study thus unveils a new role of blood shear stress in CTC survival and facilitates the development of novel therapeutics against tumor metastasis.
The development of constructions from the right edge: a multinomial regression analysis of clitic left and right dislocation in child French

Abstract The aim of the present research is to investigate the development of left and right dislocation in child French through a corpus study of three children until age 2;7 from the corpus of Lyon (Demuth & Tremblay, 2008). We extracted a total of 704 dislocations and analysed their syntactic properties. We show that (i) right dislocations are more frequent than left dislocations and (ii) left dislocations are significantly more complete than right dislocations (fewer omissions of verbs or pronouns). We compare these results to the hypothesis of Freudenthal, Pine, Jones & Gobet (2015, 2016) according to which some properties of child language can be explained by a learning mechanism from the right edge of the sentences from the input. We will show that this hypothesis can explain the general trend found in our data, but it is not sufficient to account for the entire development of dislocation in French.
Adaptive mutations promote hepatitis C virus assembly by accelerating core translocation to the endoplasmic reticulum

The envelopment of hepatitis C virus (HCV) is believed to occur primarily in the endoplasmic reticulum (ER)-associated membrane, and the translocation of viral Core protein from lipid droplets (LDs) to the ER is essential for the envelopment of viral particles. However, the factors involved are not completely understood. Herein, we identified eight adaptive mutations that enhanced virus spread and infectivity of genotype 1a clone TNcc in hepatoma Huh7 cells through long-term culture adaptation and reverse genetic study. Of eight mutations, I853V in NS2 and C2865F in NS5B were found to be minimal mutation sets that enabled an increase in virus production without apparently affecting RNA replication, thus suggesting its roles in the post-replication stage of the HCV life cycle. Using a protease K protection and confocal microscopy analysis, we demonstrated that C2865F and the combination of I853V/C2865F enhanced virus envelopment by facilitating Core translocation from the LDs to the ER. Buoyant density analysis revealed that I853V/C2865F contributed to the release of virion with a density of ∼1.10 g/ml. Moreover, we demonstrated that NS5B directly interacted with NS2 at the protease domain and that mutations I853V, C2865F, and I853V/C2865F enhanced the interaction. In addition, C2865F also enhanced the interaction between NS5B and Core. In conclusion, this study demonstrated that adaptive mutations in NS2 and NS5B promoted HCV envelopment by accelerating Core translocation from the LDs to the ER and reinforced the interaction between NS2 and NS5B. The findings facilitate our understanding of the assembly of HCV morphogenesis.
Differentiating the abnormalities of social and monetary reward processing associated with depressive symptoms

Abstract Background Reward dysfunction is a major dimension of depressive symptomatology, but it remains obscure if that dysfunction varies across different reward types. In this study, we focus on the abnormalities in anticipatory/consummatory processing of monetary and social reward associated with depressive symptoms. Methods Forty participants with depressive symptoms and forty normal controls completed the monetary incentive delay (MID) and social incentive delay (SID) tasks with event-related potential (ERP) recording. Results In the SID but not the MID task, both the behavioral hit rate and the ERP component contingent negative variation (CNV; indicating reward anticipation) were sensitive to the interaction between the grouping factor and reward magnitude; that is, the depressive group showed a lower hit rate and a smaller CNV to large-magnitude (but not small-magnitude) social reward cues compared to the control group. Further, these two indexes were correlated with each other. Meanwhile, the ERP components feedback-related negativity and P3 (indicating reward consumption) were sensitive to the main effect of depression across the MID and SID tasks, though this effect was more prominent in the SID task. Conclusions Overall, we suggest that depressive symptoms are associated with deficits in both the reward anticipation and reward consumption stages, particularly for social rewards. These findings have a potential to characterize the profile of functional impairment that comprises and maintains depression.
Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats

Abstract Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.
Assessing the impact of institution-specific guidelines for antimicrobials on doctors’ prescribing behavior at a German tertiary-care center and the additional benefits of providing a mobile application

Objective To assess usage patterns, perceived usability, and effects of institution-specific guidelines (ISGs) for antimicrobials on clinicians’ prescribing behavior and the additional benefits of the mobile application (app), a single-center survey among medical doctors was performed. Methods The study was carried out in a 1451-bed tertiary-care academic medical center in Leipzig, Germany. To ensure optimal empirical antibiotic therapies, appropriate diagnostics, and targeted antimicrobial prophylaxis, ISGs were provided as printed pocket guides (since 2014), a PDF version on ward computers, and a mobile app (since 2017). For the survey, we used an electronically structured cross-sectional questionnaire with 31 items, ordinal Likert scales, and percent bars, allowing for quantitative comparisons. Results Of the 914 doctors contacted by email, 282 (31%) responded, and 254 (28%) surveys were eligible. ISGs were reported to be the most commonly used source of information for antimicrobial prescribing among the respondents. Ninety-four percent used ISGs at least once and 55% at least weekly. On average, participants reported using them in 38% of antibiotic prescriptions and to adhere to consulted recommendations in 87% of cases. Young clinicians (≤ 30 years) reported significantly higher use of the ISGs than their older colleagues (47% vs. 35% of antibiotic prescriptions, p = 0.004). Ninety-six percent of users found ISGs to be user-friendly, and nearly 100% recommended ISGs to other colleagues. Forty-five percent regarded the app as the most user-friendly way to access ISGs, and app users were significantly more likely to use ISGs regularly (p = 0.024). Eighty-four percent reported behavioral changes regarding at least one aspect of antimicrobial therapy (e.g. duration, application mode, prescription frequency), while 54% reported changes regarding the choice of specific substance groups. Conclusions ISGs are used regularly and appear to have a relevant impact on clinicians’ prescribing habits. A mobile app may be the most effective way to provide ISGs, although multiple platforms seem to add value. While the majority of participants reported perceived effects on their prescribing behavior, this study does not allow any conclusions to be drawn about the extent of the effects of ISGs on antibiotic use and patient outcomes.
Complex Mandibular Reconstruction for Head and Neck Squamous Cell Carcinoma—The Ongoing Challenge in Reconstruction and Rehabilitation

Simple Summary Cancer therapy includes a broad range of microvascular free flaps that may restore defects and improve patients’ quality of life. This is particularly important for head and neck squamous cell carcinoma (HNSCC) and composite mandibular reconstructions, containing tissues of bone, muscle, and skin, which may be problematic due to their magnitude and sensitive location. The subscapular system offers a highly valuable donor site with the most versatility and the potential for rapid rehabilitation. Interestingly, other donor sites are more commonly used internationally. Therefore, we evaluated the use of the subscapular system free flap (SFF), which is the most commonly used free flap at our department. To our knowledge, this retrospective study represents the largest number of SFF cases reported to date in the literature. Furthermore, we examined the quality of life in a subgroup of patients, combining prospective occurrences to provide insight into overall rehabilitation from the patients’ viewpoints. Abstract Large head and neck squamous cell carcinoma (HNSCC) tumors affecting the mandible require a versatile reconstruction to maintain form, function, and quality of life. Large defect reconstruction of soft and hard tissue in the head and neck necessitates, at best, one vascular system including various tissues by large dimensions. The subscapular flap system seems to meet these standards. A retrospective study was conducted focusing on clinical data, including an analysis of the quality of life with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires, (QLQ-C30 and QLQ-H&N43). A total of 154 patients (122 males, 32 females; age range: 31–71 years, mean: 54.5 years) treated at our department from 1983 through to 2019 were included. Of the subscapular system free flaps (SFFs), 147 were based on the angular artery branch of the thoracodorsal pedicle (95.45%), and the remaining seven cases (4.55%) were lateral scapular border flaps. Mean mandible defect length was 7.3 cm. The mean skin paddle dimension was 86.8 cm2. The most common recipient artery was the thyroid superior artery (79.22%). Major postoperative complications occurred in 13 patients (8.44%). This study confirms that SFFs offer excellent soft and hard tissue quality, component independence, a large arc of rotation length, and a large gauge of pedicle, making them the gold standard for the reconstruction of large composite defects of mandibular HNSCC tumors.
Decision‐making around admission to intensive care in the UK pre‐COVID‐19: a multicentre ethnographic study

Predicting who will benefit from admission to an intensive care unit is not straightforward and admission processes vary. Our aim was to understand how decisions to admit or not are made. We observed 55 decision‐making events in six NHS hospitals. We interviewed 30 referring and 43 intensive care doctors about these events. We describe the nature and context of the decision‐making and analysed how doctors make intensive care admission decisions. Such decisions are complex with intrinsic uncertainty, often urgent and made with incomplete information. While doctors aspire to make patient‐centred decisions, key challenges include: being overworked with lack of time; limited support from senior staff; and a lack of adequate staffing in other parts of the hospital that may be compromising patient safety. To reduce decision complexity, heuristic rules based on experience are often used to help think through the problem; for example, the patient’s functional status or clinical gestalt. The intensive care doctors actively managed relationships with referring doctors; acted as the hospital generalist for acutely ill patients; and brought calm to crisis situations. However, they frequently failed to elicit values and preferences from patients or family members. They were rarely explicit in balancing burdens and benefits of intensive care for patients, so consistency and equity cannot be judged. The use of a framework for intensive care admission decisions that reminds doctors to seek patient or family views and encourages explicit balancing of burdens and benefits could improve decision‐making. However, a supportive, adequately resourced context is also needed.
High-dimensional single-cell analysis reveals the immune characteristics of COVID-19

Coronavirus disease 2019 (COVID-19), driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry (CyTOF). Using a combination of algorithm-guided data analyses, we identified peripheral immune cell subsets in COVID-19 and revealed CD4+ T-cell depletion, T-cell differentiation, plasma cell expansion, and the reduced antigen presentation capacity of innate immunity. Notably, COVID-19 induces a dysregulation in the balance of monocyte populations by the expansion of the monocyte subsets. Collectively, our results represent a high-dimensional, single-cell profile of the peripheral immune response to SARS-CoV-2 infection.
Caudal Septal Division and Batten Graft Application: A Technique to Correct Caudal Septal Deviations.

Objective The aim of the study was to evaluate the surgical outcomes in patients who underwent in one session caudal septal division, strip excision and unilateral bony batten graft procedures, a method described for the correction of caudal septal deviations. Methods In this retrospective study, 27 patients with C-shaped caudal septal deviation who underwent endonasal septoplasty using caudal septal division, strip excision and unilateral bony batten grafting in our hospital in the period from August 2014 through October 2018 were reviewed. Patients were included in the study if their pre-operative and post-operative questionnaires and post-operative follow-up data (average follow-up period was 13.9 months) were available in full. Results The average age of the 27 patients (6 women and 21 men) was 29.6±12.4 years. Postoperative observations revealed that a straight septum was achieved in 23 patients (85.1%). Average pre- and post-operative Nasal Obstruction Symptom Evaluation (NOSE) scores were 85.1±20.4 and 22.4±4.2, respectively (p<0.0001). Septal hematoma developed in one patient in the postoperative period. Conclusion The surgical outcomes of patients in whom we used caudal septal division, strip excision and unilateral bony batten graft to correct caudal septal deviations demonstrated the potential of this technique as an alternative to be used by surgeons.
Exposure‐Response and Population Pharmacokinetic Analyses of a Novel Subcutaneous Formulation of Daratumumab Administered to Multiple Myeloma Patients

We report the population pharmacokinetic (PK) and exposure‐response analyses of a novel subcutaneous formulation of daratumumab (DARA) using data from 3 DARA subcutaneous monotherapy studies (PAVO Part 2, MMY1008, COLUMBA) and 1 combination therapy study (PLEIADES). Results were based on 5159 PK samples from 742 patients (DARA 1800 mg subcutaneously, n = 487 [monotherapy, n = 288; combination therapy, n = 199]; DARA 16 mg/kg intravenously, n = 255 [all monotherapy, in COLUMBA]; age, 33‐92 years; weight, 28.6‐147.6 kg). Subcutaneous and intravenous DARA monotherapies were administered once every week for cycles 1‐2, once every 2 weeks for cycles 3‐6, and once every 4 weeks thereafter (1 cycle is 28 days). The subcutaneous DARA combination therapy was administered with the adaptation of corresponding standard‐of‐care regimens. PK samples were collected between cycle 1 and cycle 12. Among monotherapy studies, throughout the treatment period, subcutaneous DARA provided similar/slightly higher trough concentrations (Ctrough) versus intravenous DARA, with lower maximum concentrations and smaller peak‐to‐trough fluctuations. The PK profile was consistent between subcutaneous DARA monotherapy and combination therapies. The exposure‐response relationship between daratumumab PK and efficacy or safety end points was similar for subcutaneous and intravenous DARA. Although the ≤65‐kg subgroup reported a higher incidence of neutropenia, no relationship was found between the incidence of neutropenia and exposure, which was attributed, in part, to the preexisting imbalance in neutropenia between subcutaneous DARA (45.5%) and intravenous DARA (19%) in patients ≤50 kg. A flat relationship was observed between body weight and any grade and at least grade 3 infections. The results support the DARA 1800‐mg subcutaneous flat dose as an alternative to the approved intravenous DARA 16 mg/kg.
Risk factors for postoperative pneumonia after laparoscopic gastrectomy in patients aged 75 years and over with gastric cancer

The proportion of patients aged 75 years and over who undergo minimally invasive surgery for gastric cancer is increasing. However, the safety and feasibility of laparoscopic gastrectomy (LG) in this age group is controversial. This study aimed to evaluate whether LG is safe and effective in patients aged 75 years and over.