Miracle-dz/UniFAR-FTUs huggingface dataset:
Social Cognition, Social Skill, and Social Motivation Minimally Predict Social Interaction Outcomes for Autistic and Non-Autistic Adults

Social cognition, social skill, and social motivation have been extensively researched and characterized as atypical in autistic people, with the assumption that each mechanistically contributes to the broader social interaction difficulties that diagnostically define the condition. Despite this assumption, research has not directly assessed whether or how these three social domains contribute to actual real-world social interaction outcomes for autistic people. The current study administered standardized measures of social cognition, social skill, and social motivation to 67 autistic and 58 non-autistic (NA) adults and assessed whether performance on these measures, both individually and relationally between dyadic partners, predicted outcomes for autistic and NA adults interacting with unfamiliar autistic and NA partners in a 5 minute unstructured “get to know you” conversation. Consistent with previous research, autistic adults scored lower than NA adults on the three social domains and were evaluated less favorably by their conversation partners. However, links between autistic adults' performance on the three social domains and their social interaction outcomes were minimal and, contrary to prediction, only the social abilities of NA adults predicted some interaction outcomes within mixed diagnostic dyads. Collectively, results suggest that reduced performance by autistic adults on standardized measures of social cognition, social skill, and social motivation do not correspond in clear and predictable ways with their real-world social interaction outcomes. They also highlight the need for the development and validation of more ecological assessments of autistic social abilities and the consideration of relational dynamics, not just individual characteristics, when assessing social disability in autism.
A System Dynamics Approach to Understanding the deep Magma Plumbing System Beneath Dominica (Lesser Antilles)

To understand the dynamics of magmatic systems, one must first seek to characterize the time-dependent behavior of magma storage and ascent. Herein, we do this through a combination of the Crystal System Approach and careful study of Fe-Mg interdiffusion in orthopyroxene. This allows us to trace the pre-eruptive dynamics of magma plumbing systems, both in space and time. We apply this novel approach on two large silicic eruptions (about 3–5 km3 DRE/eruption) that occurred in the central part of Dominica Island (Lesser Antilles Arc): the eruptions of Layou (∼51 ka) from Morne Diablotins, and Roseau (∼33 ka) from Morne Trois Pitons-Micotrin. For the Roseau eruption, two magmatic environments (MEs) are identified on the basis of orthopyroxene composition, with a dominant reverse-zoning pattern from 50 to 54 to 54–59 mol% enstatite (En), indicating interaction with hotter magma. For the Layou eruption, three MEs are observed as represented by three populations of pyroxenes: En47-51, En51-53 and En53-58. The normal-zoning pathway from En51-53 to En47-51 is significantly registered by crystals, interpreted as convective mixing in a zoned reservoir. The reverse-zoning pathway from En47-51 to En51-53 and also En53-58 is also significantly present, supporting the mixing within the zoned reservoir but also suggesting mixing with a hotter magma, possibly stored in another part of a sub-volcanic mush. The crystal and glass compositions (melt inclusion and matrix glass) from both studied eruptions suggest heating and mixing between different magma pockets located within the mush that were the dominant process for mobilizing eruptible magma. In parallel, we constrain the associated pre-eruptive timescales by modeling the diffusive relaxation of Fe-Mg chemical gradients that originated within the zonation of the same orthopyroxene crystals. Diffusion modeling was considered along the b-axis of 66 zoned orthopyroxene crystals for these two eruptions, at a magmatic temperature of 850 ± 25°C. In light of these results, we propose that the Layou and the Roseau magma reservoirs were rejuvenated and heated by ∼25–50°C about 10 years prior to eruption by the injection of an underplating, hotter magma, creating the observed dominant reverse-zoning patterns of the erupted orthopyroxenes. We thus have evidence that silicic mush can be re-mobilized over timescales of decades prior to eruption, as previously suggested for Santorini and Taupo volcanoes.
The Multifaceted Nature of Streptococcal Antigen I/II Proteins in Colonization and Disease Pathogenesis

Streptococci are Gram-positive bacteria that belong to the natural microbiota of humans and animals. Certain streptococcal species are known as opportunistic pathogens with the potential to cause severe invasive disease. Antigen I/II (AgI/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrata, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Here we will review the literature including recent work that has demonstrated the multifaceted nature of AgI/II family proteins, focusing on their overlapping and distinct functions and their important contribution to streptococcal colonization and disease.
HYSTERESIS IN REPOLARIZATION OF CARDIAC ACTION POTENTIALS: EFFECTS OF SPATIAL HETEROGENEITY AND SLOW REPOLARIZATION CURRENTS

OF DISSERTATION HYSTERESIS IN REPOLARIZATION OF CARDIAC ACTION POTENTIALS: EFFECTS OF SPATIAL HETEROGENEITY AND SLOW REPOLARIZATION CURRENTS Repolarization alternans, i.e. beat-to-beat variation of repolarization of action potential, is proposed as a predictor of life-threatening arrhythmias. Restitution relates repolarization duration with its previous relaxation time, i.e. diatstolic interval (DI), and is considered a dominant mechanism for alternans. Previously, we observed that different repolarization durations at the same DI during decelerating and accelerating pacing, i.e. restitution displays hysteresis, which is a measure of “cardiac memory”. Objective of the current study was to investigate in the pig 1) the mechanism for a previously observed hysteresis type phenomenon, where alternans, once started at higher heart rate, persists even when heart rate decreases below its initiating rate, 2) regional differences in expression of hysteresis, i.e. memory in restitution in the heart, and 3) changes in restitution and memory during manipulation of an important repolarization current, the slow delayed rectifier, IKs. Action potentials were recorded in pig ventricular tissues using microelectrodes. Regional differences were explored in endocardial and epicardial tissues from both ventricles. DIs were explicitly controlled in real time to separate restitution mechanism from non-restitution related effects. Stepwise protocols were used to explore the existence in hysteresis in alternans threshold, where DIs were held constant for each step and progressively decreased and then increased. Quantification of cardiac memory was achieved by sinusoidally changing DI protocols, which were used to investigate memory changes among myocytes from different regions of the heart and during IKs manipulation. Results show that during stepwise protocol, hysteresis in alternans still existed, which indicates that restitution is not the only mechanism underlying the hysteresis. When comparing hysteresis obtained from sinusoidally oscillatory DIs among different regions, results show memory is expressed differently with endocardium expressing the most and epicardium the least memory. This provides important implications about the location where arrhythmia would initiate. Results also show that measures for hysteresis loops obtained by sinusoidal DI protocols decreased (increased) after enhancement (attenuation) of IKs, suggesting decreased (increased) hysteresis, i.e. memory in restitution. This effect needs to be considered during drug development.
Mesure et analyse de l'émittance spectrale d'oxydes diélectriques à haute température : une approche des phénomènes préfusionnels

L'emittance spectrale, image directe de l'absorptance optique, donne acces aux origines microscopiques caracteristiques des echanges de chaleur par transfert radiatif. Son evolution en temperature doit permettre de suivre les changements survenant a la fusion d'un materiau et de caracteriser d'eventuels effets prefusionnels. Ce travail s'est appuye sur ces possibilites pour aborder l'etude des proprietes optiques jusque dans la phase liquide de materiaux dielectriques oxydes a haute temperature de fusion (superieure a 1200 K). L'etude a ete rendue possible d'une part par le dispositif experimental developpe au laboratoire et d'autre part par les outils d'analyse utilises pour l'interpretation des resultats. En effet la gamme spectrale couverte par le spectrometre permet de mesurer l'emittance entre 10 et 10 000 cm-1 sur un domaine de temperature allant de l'ambiante a 2600 K. Les proprietes optiques ont ete deduites quant a elles de la connaissance unique de la fonction dielectrique du materiau, obtenue grâce a un nouvel outil de simulation des spectres base sur un modele de fonction dielectrique semi-quantique. Le choix des materiaux s'est porte sur des monocristaux d'alumine et de magnesie ainsi que sur des verres de silice, de CaSiO3 et de Borofloat®. Dans le cas du corindon et de la magnesie une augmentation surprenante de l'emittance est observee dans la zone de transparence, parfaitement simulee en introduisant un terme de relaxation de Debye dans le modele de fonction dielectrique. La discussion met en avant un phenomene particulier de relaxation electronique interprete comme un effet prefusionnel qui n'existe pas pour les composes amorphes etudies.
A treatment protocol for minimizing duration and complications of adenoviral epidemic keratoconjunctivitis

PURPOSE: The purpose of the study was to assess the treatment protocol of topical 2.5% Povidone-Iodine (PovI) and 0.1% fluorometholone (FluM) for Adenoviral Epidemic keratoconjunctivitis (EKC) in reducing the duration and severity of the disease as compared to conventional treatment. This was a retrospective case–control study. MATERIALS AND METHODS: Cases were defined as patients with EKC receiving the treatment protocol and conjunctival swab taken for polymerase chain reaction. Controls were defined as similar patients receiving conventional treatment protocol. Forty-one cases and 35 controls were identified for analysis. Cases were treated with a protocol using 2.5% povidone-iodine eye drops and 0.1% FluM eye drops. Controls received conventional treatment until resolution of signs and symptoms. Both the groups were followed up for 1 month. Data collected were analyzed for effect of the two treatment protocols on the duration of EKC, rate of recovery, and incidence of complications. RESULTS: The treatment protocol was significantly better than conventional treatment protocol in achieving cure (P = 0.002) with large effect size. The proportion of cases achieving cure was significantly higher with treatment protocol (64% vs. 11% at 5 days, P < 0.001) by 5 days. There was a significant reduction of the subepithelial infiltrates (SEI) incidence group (10% vs. 57%, P < 0.001). There were no SEI at 1 month in the treatment group (0% vs. 31%). CONCLUSION: Treatment protocol used in our study can significantly reduce the severity and duration of EKC. It can prevent chronic keratitis in majority of cases. Since povidone-iodine is nonspecific and virucidal for adenovirus, this therapy can be used for other types of adenoviral conjunctivitis.
MSK1 negatively regulates hippocampal neurogenesis

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The Evaluation of AREG, MMP-2, CHI3L1, GFAP, and OPN Serum Combined Value in Astrocytic Glioma Patients’ Diagnosis and Prognosis

Gliomas account for approximately 70% of primary brain tumors in adults. Of all gliomas, grade IV astrocytoma, also called glioblastoma, has the poorest overall survival, with <5% of patients surviving five years after diagnosis. Due to the aggressiveness, lethal nature, and impaired surgical accessibility of the tumor, early diagnosis of the tumor and, in addition, prediction of the patient’s survival time are important. We hypothesize that combining the protein level values of highly recognizable glioblastoma serum biomarkers could help to achieve higher specificity and sensitivity in predicting glioma patient outcome as compared to single markers. The aim of this study was to select the most promising astrocytoma patient overall survival prediction variables from five secretory proteins—glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2), chitinase 3-like 1 (CHI3L1), osteopontin (OPN), and amphiregulin (AREG)—combining them with routinely used tumor markers to create a Patient Survival Score calculation tool. The study group consisted of 70 astrocytoma patients and 31 healthy controls. We demonstrated that integrating serum CHI3L1 and OPN protein level values and tumor isocitrate dehydrogenase 1 IDH1 mutational status into one parameter could predict low-grade astrocytoma patients’ two-year survival with 93.8% accuracy.
Wild-type APC is associated with poor survival in metastatic microsatellite stable colorectal cancer.

BACKGROUND The prognostic implication of wild type APC (APC-WT) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) is not well defined. METHODS APC prognostic value was evaluated retrospectively in two independent cohorts of patient with MSS mCRC with a confirmatory analysis from a public data set from Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS In comparison to the APC-mutant (APC-MT) population (n=255), APC-WT patients (n = 86) tended to be younger (59% of age <40 vs 26% of age > 50), right-sided (41.7% vs. 27%), BRAF-V600E mutated (23.3% vs. 0.8%), and KRAS WT (65.1% vs. 49.8%). Alternative WNT pathway alterations, RNF43 and CTNNB1 were over-represented in the APC-WT vs APC-MT population (7% vs 0.4% and 4.7% vs 0.4%, respectively). APC-WT patients had a worse overall survival (OS) than APC-MT patients (22.6 vs 45.6 months, p<0.0001). Using a multivariate model correcting for primary tumor location, RAS and BRAF status, APC-WT was predictive of poor survival (APC-MT vs APC-WT, HR=0.62, 95%CI 0.44-0.86, P=0.0037). The prognostic implication of APC-WT on OS was confirmed further in a similar multivariate model of 934 stage IV patients from MSKCC public database (APC-MT vs APC-WT, HR=0.63, 95%CI 0.49-0.81, p<0.0001). CONCLUSION APC-WT is associated with poor OS in MSS mCRC regardless of RAS and BRAF status. Compared with APC-MT mCRC tumors, APC-WT tumors were associated with other Wnt activating alterations, including RNF43 and CTNBB1. Our data suggest alternative therapy needs to be investigated in APC-WT patients. IMPLICATIONS FOR PRACTICE MSS mCRC patients with APC-WT had a worse OS than patients with APC-MT regardless of RAS/RAF status. APC status should be considered as a stratification factor in prospective trials and novel therapeutic strategies need to be developed for this subgroup of patients.
Psychiatric and psychosocial morbidity 1 year after epilepsy surgery

Abstract Objectives: There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication. Methods: This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery. Results: There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001). Conclusions: This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.
Mapping of Diabetes Susceptibility Loci in a Domestic Cat Breed with an Unusually High Incidence of Diabetes Mellitus

Genetic variants that are associated with susceptibility to type 2 diabetes (T2D) are important for identification of individuals at risk and can provide insights into the molecular basis of disease. Analysis of T2D in domestic animals provides both the opportunity to improve veterinary management and breeding programs as well as to identify novel T2D risk genes. Australian-bred Burmese (ABB) cats have a 4-fold increased incidence of type 2 diabetes (T2D) compared to Burmese cats bred in the United States. This is likely attributable to a genetic founder effect. We investigated this by performing a genome-wide association scan on ABB cats. Four SNPs were associated with the ABB T2D phenotype with p values <0.005. All exons and splice junctions of candidate genes near significant single-nucleotide polymorphisms (SNPs) were sequenced, including the genes DGKG, IFG2BP2, SLC8A1, E2F6, ETV5, TRA2B and LIPH. Six candidate polymorphisms were followed up in a larger cohort of ABB cats with or without T2D and also in Burmese cats bred in America, which exhibit low T2D incidence. The original SNPs were confirmed in this cohort as associated with the T2D phenotype, although no novel coding SNPs in any of the seven candidate genes showed association with T2D. The identification of genetic markers associated with T2D susceptibility in ABB cats will enable preventative health strategies and guide breeding programs to reduce the prevalence of T2D in these cats.
Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naïve Patients with Aplastic Anemia in Japan

Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naïve and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.
Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6

Significance Low-complexity and repetitive elements are difficult to study using existing sequencing technologies. Determination of the boundaries and structures of the termini of inherited chromosomally integrated HHV-6 (iciHHV-6) genomes is particularly challenging, as it integrates into highly repetitive human telomeres. We therefore developed a genome imaging approach that revealed the chromosomal location of the virus, its orientation, the presence of long internal telomeres at the host−virus junction, and the lengths of the distal telomeres capping the integrated virus genome. This genome imaging approach has wide applications for mapping transposable elements or large viruses that integrate into low-complexity regions of host genomes. Next-generation sequencing technologies allowed sequencing of thousands of genomes. However, there are genomic regions that remain difficult to characterize, including telomeres, centromeres, and other low-complexity regions, as well as transposable elements and endogenous viruses. Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) are closely related viruses that infect most humans and can integrate their genomes into the telomeres of infected cells. Integration also occurs in germ cells, meaning that the virus can be inherited and result in individuals harboring the virus in every cell of their body. The integrated virus can reactivate and cause disease in humans. While it is well established that the virus resides in the telomere region, the integration locus is poorly defined due to the low sequence complexity (TTAGGG)n of telomeres that cannot be easily resolved through sequencing. We therefore employed genome imaging of the integrated HHV-6A and HHV-6B genomes using whole-genome optical site mapping technology. Using this technology, we identified which chromosome arm harbors the virus genome and obtained a high-resolution map of the integration loci of multiple patients. Surprisingly, this revealed long telomere sequences at the virus−subtelomere junction that were previously missed using PCR-based approaches. Contrary to what was previously thought, our technique revealed that the telomere lengths of chromosomes harboring the integrated virus genome were comparable to the other chromosomes. Taken together, our data shed light on the genetic structure of the HHV-6A and HHV-6B integration locus, demonstrating the utility of optical mapping for the analysis of genomic regions that are difficult to sequence.