Miracle-dz/UniFAR-FTUs huggingface dataset:
The uncanny valley effect in typically developing children and its absence in children with autism spectrum disorders

Robots and virtual reality are gaining popularity in the intervention of children with autism spectrum disorder (ASD). To shed light on children’s attitudes towards robots and characters in virtual reality, this study aims to examine whether children with ASD show the uncanny valley effect. We varied the realism of facial appearance by morphing a cartoon face into a human face, and induced perceptual mismatch by enlarging the eyes, which has previously been shown as an effective method to induce the uncanny valley effect in adults. Children with ASD and typically developing (TD) children participated in a two-alternative forced choice task that asked them to choose one they liked more from the two images presented on the screen. We found that TD children showed the effect, i.e., the enlargement of eye size and the approaching realism reduced their preference. In contrast, children with ASD did not show the uncanny valley effect. Our findings in TD children help resolve the controversy in the literature about the existence of the uncanny valley effect among young children. Meanwhile, the absence of the uncanny valley effect in children with ASD might be attributed to their reduced sensitivity to subtle changes of face features and their limited visual experience to faces caused by diminished social motivation. Last, our findings provide practical implications for designing robots and virtual characters for the intervention of children with ASD.
Climatic and topographic variables control soil nitrogen, phosphorus, and nitrogen: Phosphorus ratios in a Picea schrenkiana forest of the Tianshan Mountains

Knowledge about soil nitrogen (N) and phosphorus (P) concentrations, stocks, and stoichiometric ratios is crucial for understanding the biogeochemical cycles and ecosystem function in arid mountainous forests. However, the corresponding information is scarce, particularly in arid mountainous forests. To fill this gap, we investigated the depth and elevational patterns of the soil N and P concentrations and the N: P ratios in a Picea schrenkiana forest using data from soil profiles collected during 2012–2017. Our results showed that the soil N and P concentrations and the N: P ratios varied from 0.15 g kg−1 to 0.56 g kg−1 (average of 0.31 g kg−1), from 0.09 g kg−1 to 0.16 g kg−1 (average of 0.12 g kg−1), and from 2.42 g kg−1 to 4.36 g kg−1 (average of 3.42 g kg−1), respectively; additionally, values significantly and linearly decreased with soil depth. We did not observe a significant variation in the soil N and P concentrations and the N: P ratios with the elevational gradient. In contrast, our results revealed that the mean annual temperature and mean annual precipitation exhibited a more significant influence on the soil N and P concentrations and the N: P ratios than did elevation. This finding indicated that climatic variables might have a more direct impact on soil nutrient status than elevation. The observed relationship among the soil N and P concentrations and the N: P ratios demonstrated that the soil N was closely coupled with the soil P in the P. schrenkiana forest.
Evidence for protein kinase involvement in the 5‐HT–[Ca2+]i–pannexin‐1 signalling pathway in type II glial cells of the rat carotid body

What is the central question of this study? The mammalian carotid body (CB) is a peripheral chemoreceptor organ involved in O2 and CO2/H+ homeostasis. Recent studies suggest that 5‐HT, released from CB receptor cells, can stimulate adjacent glial‐like type II cells, leading to an increase in intracellular Ca2+ (Δ[Ca2+]i) and activation of ATP‐permeable pannexin‐1 (Panx‐1) channels. The aim of this study was to elucidate the role of protein kinases in the 5‐HT–[Ca2+]i–Panx‐1 signalling pathway. What is the main finding and its importance? Src family kinase and protein kinase A, acting downstream from Δ[Ca2+]i, played central roles in 5‐HT‐mediated Panx‐1 channel activation. This provides new insight into mechanisms regulating CB excitation, especially in pathophysiological conditions.
Complement-Activating Capacity of Autoantibodies Correlates With Disease Activity in Bullous Pemphigoid Patients

Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking. Therefore, the aim of this study was to investigate the pathogenic relevance of complement activation in patients with bullous pemphigoid. Complement activation by autoantibodies in vivo as measured by the intensity of complement C3 deposits in the patients' skin and ex vivo by the complement-fixation assay in serum was correlated with the clinical disease activity, evaluated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Bullous Pemphigoid Disease Area Index (BPDAI), as well as, with further immunopathological findings in patients with bullous pemphigoid. Results: Complement-activation capacity of autoantibodies ex vivo, but not deposition of complement in the perilesional skin of patients, correlates with the extent of skin disease (measured by ABSIS and BPDAI) and with levels of autoantibodies. Conclusions: Our study provides for the first time evidence in patients for a pathogenic role of complement activation in bullous pemphigoid and should greatly facilitate the development of novel diagnostic tools and of more specific therapies for complement-dependent autoimmune injury.
High Cancer Burden Among Antiretroviral Therapy Users in Malawi: a Record Linkage Study of Observational HIV Cohorts and Cancer Registry Data.

Background With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS defining cancers are now more frequent among HIV-infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users. Methods We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in the Malawi's two largest HIV cohorts, Lighthouse Trust (LT; 2007-2010) and Queen Elizabeth Central Hospital (QECH; 2000-2010). Age-adjusted cancer incidence rates (IR) and 95% confidence intervals were estimated by cancer site, early versus late incidence periods (4 -24 and >24 months after ART start), and WHO stage among naïve ART initiators enrolled for at least 90 days. Results We identified 4,346 cancers among 28,576 persons. Most people initiated ART at advanced WHO stage (LT stage 3/4: 55%; QECH stage 3/4: 66%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100,000 person-years), followed by cervical cancer (36.6). KS incidence was highest during the early period 4-24 months after ART initiation. Non-AIDS defining cancers (NADC) accounted for 6% of new cancers. Conclusions Under historical ART guidelines, NADC were observed at low rates, and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context.
Longitudinal Biochemical Assay Analysis of Mutant Huntingtin Exon 1 Protein in R6/2 Mice.

BACKGROUND Biochemical analysis of mutant huntingtin (mHTT) aggregation species in HD mice is a common measure to track disease. A longitudinal and systematic study of how tissue processing affects detection of conformers has not yet been reported. Understanding the homeostatic flux of mHTT over time and under different processing conditions would aid in interpretation of pre-clinical assessments of disease interventions. OBJECTIVE Provide a systematic evaluation of tissue lysis methods and molecular and biochemical assays in parallel with behavioral readouts in R6/2 mice to establish a baseline for HTT exon1 protein accumulation. METHODS Established biochemical methods were used to process tissue from R6/2 mice of specific ages following behavior tasks. Aggregation states and accumulation of mHTT exon 1 protein were evaluated using multiple break and assay methods to determine potential conformational flux assay specificity in detection of mHTT species, and tissue specificity of conformers. RESULTS Detection of mHTT exon 1 protein species varied based on biochemical processing and analysis providing a baseline for subsequent studies in R6/2 mice. Insoluble, high molecular weight species of mHTT exon 1 protein increased and tracked with onset of behavioral impairments in R6/2 mice using multiple assay methods. CONCLUSIONS Conformational flux from soluble monomer to high molecular weight, insoluble species of mHTT exon 1 protein was generally consistent for multiple assay methods throughout R6/2 disease progression; however, the results support the use of multiple biochemical techniques to detect mHTT exon 1 protein species for preclinical assessments in HD mouse models expressing mHTT exon 1 protein.
Effects of texting on accident risk during a sudden hazardous event: Analysis of predetection and postdetection phases

Abstract Objective: The present study aims to quantify the effects of texting and driver behavior on the accident risk associated with a sudden event. Further, the study attempts to compare the effects of driving behavior of inexperienced young and professional drivers on risk during predetection and postdetection phases of the event. Methods: Forty-nine drivers from 2 categories—inexperienced young drivers and experienced professional drivers—took part in simulated experiments. The participants drove in a free-flow road environment under 3 driving conditions: no distraction (baseline) and writing short and long texts while driving. The participants were exposed to a sudden hazardous event during each drive. Accident probability during the sudden event was modeled with a generalized linear mixed model (with a logit link function). Results: As expected, both texting tasks increased accident risk, and the risk was much higher for inexperienced young drivers than for professional drivers. Time lapsed in reducing speed increased the odds for accident risk significantly. A comparative analysis of the driver categories showed that impairment in driving behavior due to the texting tasks was similar for both groups during the predetection phase. However, the risk associated with the texting tasks was higher for young drivers during the postdetection phase. A possible reason could be that young drivers had 65% and 75% higher approach speeds (than the professional drivers) during the short and long text tasks, respectively. Conclusions: The results provide statistical evidence that increased speed is expressed as increased risk-taking behavior among young drivers, which subsequently is the main reason for their higher accident risk during texting tasks. Moreover, the results confirm that professional drivers are not able to mitigate the increased accident risk associated with texting tasks due to late detection of the event during the tasks.
Influence of CO2 Degassing on the Microbial Community in a Dry Mofette Field in Hartoušov, Czech Republic (Western Eger Rift)

The Cheb Basin (CZ) is a shallow Neogene intracontinental basin filled with fluvial and lacustrine sediments that is located in the western part of the Eger Rift. The basin is situated in a seismically active area and is characterized by diffuse degassing of mantle-derived CO2 in mofette fields. The Hartoušov mofette field shows a daily CO2 flux of 23–97 tons of CO2 released over an area of 0.35 km2 and a soil gas concentration of up to 100% CO2. The present study aims to explore the geo–bio interactions provoked by the influence of elevated CO2 concentrations on the geochemistry and microbial community of soils and sediments. To sample the strata, two 3-m cores were recovered. One core stems from the center of the degassing structure, whereas the other core was taken 8 m from the ENE and served as an undisturbed reference site. The sites were compared regarding their geochemical features, microbial abundances, and microbial community structures. The mofette site is characterized by a low pH and high TOC/sulfate contents. Striking differences in the microbial community highlight the substantial impact of elevated CO2 concentrations and their associated side effects on microbial processes. The abundance of microbes did not show a typical decrease with depth, indicating that the uprising CO2-rich fluid provides sufficient substrate for chemolithoautotrophic anaerobic microorganisms. Illumina MiSeq sequencing of the 16S rRNA genes and multivariate statistics reveals that the pH strongly influences microbial composition and explains around 38.7% of the variance at the mofette site and 22.4% of the variance between the mofette site and the undisturbed reference site. Accordingly, acidophilic microorganisms (e.g., OTUs assigned to Acidobacteriaceae and Acidithiobacillus) displayed a much higher relative abundance at the mofette site than at the reference site. The microbial community at the mofette site is characterized by a high relative abundance of methanogens and taxa involved in sulfur cycling. The present study provides intriguing insights into microbial life and geo–bio interactions in an active seismic region dominated by emanating mantle-derived CO2-rich fluids, and thereby builds the basis for further studies, e.g., focusing on the functional repertoire of the communities. However, it remains open if the observed patterns can be generalized for different time-points or sites.
Evaluation of D1/D5 Partial Agonist PF-06412562 in Parkinson’s Disease following Oral Administration

Background: PF-06412562 is a moderately potent, highly selective oral D1/D5 dopamine receptor partial agonist. Objective: To study the efficacy and safety of a single, oral, split dose of PF-06412562 in patients with Parkinson’s disease. Methods: Following overnight levodopa (L-dopa, Sinemet®) washout, subjects received a single dose of levodopa in open-label period 1. Periods 2 and 3 had a double-blinded, sponsor-open, randomized, 2-way cross-over, placebo-controlled design, during which subjects were randomized to PF-06412562 30 mg (+ 20 mg 4 h later) or placebo. Maximum percent improvement from baseline in finger-tapping speed (measure of bradykinesia) measured using KinesiaTM technology (as the primary end point) and change from baseline in the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III) motor section scores (the preferred exploratory end point) were evaluated. Results: Nineteen subjects received levodopa; 13 met the period 2/3 entry criteria and received PF-06412562, 30 + 20 mg, or placebo. The prespecified primary efficacy criterion for significant improvement in finger-tapping was not met due to inconsistencies in the task leading to large between-period fluctuations of within-patient baseline values. Change from baseline in MDS-UPDRS-III score with PF-06412562 resulted in a placebo-adjusted point estimate of –10.59 with a one-sided 90% upper CI of PF-06412562 versus placebo model-based contrast of (–inf, –7.44) at 1.5–2.5 h after the dose (p < 0.0001). All adverse events were mild-to-moderate. Conclusions: We report the first evidence of potential anti-parkinsonian efficacy of the oral selective D1/D5 partial agonist PF-06412562 without the significant acute changes in cardiovascular parameters reported with previous D1 agonists.
Genomic analyses in African populations identify novel risk loci for cleft palate

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.
Effect of bidi smoking on nasal mucociliary clearance: a comparative study

Abstract Objective To compare nasal mucociliary clearance in adult non-smokers, cigarette smokers and bidi smokers using the methylene blue dye test. Methods The study sample consisted of 20 non-smokers, 20 cigarette smokers and 20 bidi smokers (age range, 20–40 years). A single drop of the methylene blue dye was placed at the anterior end of the inferior turbinate of the participants’ nasal cavity. The distance travelled by the methylene blue in 15 minutes inside the nasal cavity was measured. Nasal mucociliary clearance of the three groups was compared using the Kruskal Wallis test. Results Nasal mucociliary clearance was significantly decreased in bidi smokers as compared to cigarette smokers and non-smokers (p < 0.05). Multivariate analysis revealed a significant association between nasal mucociliary clearance and bidi smoking, number of cigarettes or bidis smoked per day, and pack-years (all p < 0.05). Conclusion Nasal mucociliary clearance measurement is a simple and useful index for assessing the effect of smoking on the mucociliary activity of nasal mucosa.
Quantum chemical simulations revealed the toxicokinetic mechanisms of organic phosphorus flame retardants catalyzed by P450 enzymes

Abstract The metabolic fate and toxicokinetics of organic phosphorus flame retardants catalyzed by cytochrome P450 enzymes (CYPs) are here investigated by in silico simulations, leveraging an active center model to mimic the CYPs, triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphate and tris(1,3-dichloro-2-propyl) phosphate as substrates. Our calculations elucidated key main pathways and predicted products, which were corroborated by current in vitro data. Results showed that alkyl OPFRs are eliminated faster than aryl and halogenated alkyl-substituted OPFRs. In addition, we discovered a proton shuttle pathway for aryl hydroxylation of TPHP and P = O bond-assisted H-transfer mechanisms (rather than nonenzymatic hydrolysis) that lead to O-dealkylation/dearylation of phosphotriesters.
Radiotherapy for early stage diffuse large B-cell lymphoma with or without double or triple hit genetic alterations

Abstract We investigated whether adding radiation (RT) to systemic therapy improved outcomes in early stage diffuse large B-cell lymphoma (DLBCL) patients with or without double- or triple-hit lymphoma (DHL/THL) biology. This analysis included 183 patients profiled with fluorescent in situ hybridization (FISH) for alterations in MYC, BLC2, and/or BCL6. A total of 146 (80%) were non-DHL/THL, 27 (15%) were DHL, and 10 (6%) were THL. Systemic therapy without RT resulted in inferior freedom from relapse (FFR) (HR: 2.28; 95% CI, 1.10–4.77; p = .02). The median FFR for non-DHL/THL was not reached and was 33 and 22.3 months for DHL and THL, respectively; p < . 001. Low-risk (R-IPI <2) DHL/THL patients treated with rituximab-based therapy had 3-year FFR rates of 11% and 71% for systemic therapy without and with RT, respectively; p = . 04. No differences in overall survival were observed between the treatment groups. Treatment intensification with RT may improve early stage DHL/THL outcomes.
Preexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection Model

Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. ABSTRACT Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model. In contrast to A. fumigatus, a hypervirulent phenotype was found in all tested Mucorales upon preexposure to either voriconazole or isavuconazole. These findings may contribute to the explanation of breakthrough mucormycosis in isavuconazole-treated patients.
The Changes of Intrinsic Excitability of Pyramidal Neurons in Anterior Cingulate Cortex in Neuropathic Pain

To find satisfactory treatment strategies for neuropathic pain syndromes, the cellular mechanisms should be illuminated. Central sensitization is a generator of pain hypersensitivity, and is mainly reflected in neuronal hyperexcitability in pain pathway. Neuronal excitability depends on two components, the synaptic inputs and the intrinsic excitability. Previous studies have focused on the synaptic plasticity in different forms of pain. But little is known about the changes of neuronal intrinsic excitability in neuropathic pain. To address this question, whole-cell patch clamp recordings were performed to study the synaptic transmission and neuronal intrinsic excitability 1 week after spared nerve injury (SNI) or sham operation in male C57BL/6J mice. We found increased spontaneous excitatory postsynaptic currents (sEPSC) frequency in layer II/III pyramidal neurons of anterior cingulate cortex (ACC) from mice with neuropathic pain. Elevated intrinsic excitability of these neurons after nerve injury was also picked up, which was reflected in gain of input-output curve, inter-spike interval (ISI), spike threshold and Refractory period (RP). Besides firing rate related to neuronal intrinsic excitability, spike timing also plays an important role in neural information processing. The precision of spike timing measured by standard deviation of spike timing (SDST) was decreased in neuropathic pain state. The electrophysiological studies revealed the elevated intrinsic excitation in layer II/III pyramidal neurons of ACC in mice with neuropathic pain, which might contribute to central excitation.