Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect Sizes of Deletions and Duplications on Autism Risk Across the Genome.

OBJECTIVE Deleterious copy number variants (CNVs) are identified in up to 20% of individuals with autism. However, levels of autism risk conferred by most rare CNVs remain unknown. The authors recently developed statistical models to estimate the effect size on IQ of all CNVs, including undocumented ones. In this study, the authors extended this model to autism susceptibility. METHODS The authors identified CNVs in two autism populations (Simons Simplex Collection and MSSNG) and two unselected populations (IMAGEN and Saguenay Youth Study). Statistical models were used to test nine quantitative variables associated with genes encompassed in CNVs to explain their effects on IQ, autism susceptibility, and behavioral domains. RESULTS The "probability of being loss-of-function intolerant" (pLI) best explains the effect of CNVs on IQ and autism risk. Deleting 1 point of pLI decreases IQ by 2.6 points in autism and unselected populations. The effect of duplications on IQ is threefold smaller. Autism susceptibility increases when deleting or duplicating any point of pLI. This is true for individuals with high or low IQ and after removing de novo and known recurrent neuropsychiatric CNVs. When CNV effects on IQ are accounted for, autism susceptibility remains mostly unchanged for duplications but decreases for deletions. Model estimates for autism risk overlap with previously published observations. Deletions and duplications differentially affect social communication, behavior, and phonological memory, whereas both equally affect motor skills. CONCLUSIONS Autism risk conferred by duplications is less influenced by IQ compared with deletions. The model applied in this study, trained on CNVs encompassing >4,500 genes, suggests highly polygenic properties of gene dosage with respect to autism risk and IQ loss. These models will help to interpret CNVs identified in the clinic.
Conditioned place preference for cocaine and methylphenidate in female mice from lines selectively bred for high voluntary wheel‐running behavior

Behavioral addictions can come in many forms, including overeating, gambling and overexercising. All addictions share a common mechanism involving activation of the natural reward circuit and reinforcement learning, but the extent to which motivation for natural and drug rewards share similar neurogenetic mechanisms remains unknown. A unique mouse genetic model in which four replicate lines of female mice were selectively bred (>76 generations) for high voluntary wheel running (High Runner or HR lines) alongside four non‐selected control (C) lines were used to test the hypothesis that high motivation for exercise is associated with greater reward for cocaine (20 mg/kg) and methylphenidate (10 mg/kg) using the conditioned place preference (CPP) test. HR mice run ~three times as many revolutions/day as C mice, but the extent to which they have increased motivation for other rewards is unknown. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Taken together, results suggest that selective breeding for increased voluntary running has modified the reward circuit in the brain in a way that increases motivation for running without affecting cocaine or methylphenidate reward.
FREE AMINO ACIDS IN SOME AQUATIC INVERTEBRATES

1. Free amino acids of 17 species of aquatic invertebrates were determined by chromatographic methods.2. Qualitative differences in some amino acids were detected in organisms of different species. The concentration of alanine, arginine, aspartic acid, glutamic acid, glycine and taurine was measured and significant differences recorded.3. Taurine was found in high concentration in all the marine organisms studied but was not found in several fresh-water and terrestrial organisms.4. The possible role of taurine and other free amino acids in aquatic organisms is discussed.
The amplex red/horseradish peroxidase assay requires superoxide dismutase to measure hydrogen peroxide in the presence of NAD(P)H

Abstract A sensitive fluorescence assay based on Amplex Red (AR) oxidation by horseradish peroxidase (AR/HRP) is described which continuously monitor rates of H2O2 production by microsomal enzymes in the presence of relatively high concentrations of NADPH. NADPH and NADH are known to interact with HRP and generate significant quantities of superoxide anion, a radical that spontaneously dismutates to form H2O2 which interferes with the AR/HRP assay. Microsomal enzymes generate H2O2 as a consequence of electron transfer from NADPH to cytochrome P450 hemoproteins with subsequent oxygen activation. We found that superoxide anion formation via the interaction of NADPH with HRP was inhibited by superoxide dismutase (SOD) without affecting H2O2 generation by microsomal enzymes. Using SOD in enzyme assays, we consistently detected rates of H2O2 production using microgram quantities of microsomal proteins (2.62 ± 0.20 picomol/min/µg protein for liver microsomes from naïve female rats, 12.27 ± 1.29 for liver microsomes from dexamethasone induced male rats, and 2.17 ± 0.25 picomol/min/µg protein for human liver microsomes). This method can also be applied to quantify rates of H2O2 production by oxidases where superoxide anion generation by NADH or NADPH and HRP can interfere with enzyme assays.
Storage Stability Assessment of Red Palm Olein in Comparison to Palm Olein.

Sixty-four bottles of red palm olein and palm olein (constituted as control) samples were stored at permutations of common home setting variables which are: temperature (room temperature (24°C) or 8°C), light (kept in dark or exposure under light) and oxygen (opened or sealed caps). The effects of temperature, oxygen and light on the stability of red palm olein and palm olein were studied over 4 months of storage at simulated domestic conditions. The degree of auto- and photo-oxidations was evaluated by monitoring the following quality parameters: acidity, peroxide and p-anisidine values, fatty acids composition, carotenes and vitamin E. It is noted from the study that opened bottles of red palm olein was found to be stable for 4 months in comparison to its counterpart (palm olein) evidenced from their primary oxidative constituents (peroxides) and hydrolytic behavior (free fatty acids). Opened bottles are better off when stored at 8°C and protected from light for a longer shelf life. Sealed bottles of palm olein showed better storage stability in the dark at 8°C; whereas sealed bottles of red palm olein was found to be stable at both temperatures studied without the influence of light. After 4 months of varying storage conditions, the fatty acid composition, vitamin E and carotenes of both oils remained unchanged. The phytonutrients in red palm olein rendered better storage stability when compared to palm olein.
Targeting SARS CoV2 (Indian isolate) genome with miRNA: An in silico study

The newly identified SARS CoV2 has become a global pandemic since December 2019. Various researchers are trying to design a vaccine candidate against the virus. On the other hand, another group is focussing on repurposing approved or clinically tested drugs for treatment. However, there is always a search for alternative therapies. Thus, we propose an alternative approach apart from chemotherapy that is the usage of miRNA as novel antisense therapy to cure SARS CoV2 infected patients. To address the objective, miRNAs have been designed by targeting the genome of SARS CoV2 (Indian isolate). First, the open reading frames in the viral genome have been identified, and the proteins encoded by those open reading frames have been predicted. Using computational biology, several miRNAs have been designed and their probability to bind to a viral gene has been predicted. In addition, miRNA target mining in the host cell has been done to rule out the possibility of non‐specific binding of the miRNAs. The miRNAs having the highest chances to bind to the viral genome have been converted into pre‐miRNAs, and their interaction with dicer endoribonuclease has been studied by molecular docking. Results revealed that the pre‐miRNAs interact with the RNAse III 2 domain of dicer. Thus, it is predicted that the pre‐miRNAs after delivery to the infected host cell will be processed by dicer to generate mature miRNAs that will target the SARS CoV2 viral genome. Therefore, miRNA therapy can be an alternative approach for the treatment of SARS CoV2 infection.
Hiérarchiser les risques de zoonoses alimentaires : une approche quantitative. Application aux dangers bactériens transmis par les viandes porcine et bovine

Les zoonoses alimentaires constituent une preoccupation de sante publique majeure. L'analyse des risques, fondement des politiques internationales relatives a la securite sanitaire et aux echanges commerciaux des denrees d'origine animale, demande d'evaluer la gravite et l'occurrence des cas humains en fonction de la denree. Les outils de quantification des risques disponibles sont limites a l'estimation des consequences de certaines maladies. Les auteurs proposent une demarche generique quantitative de hierarchisation des risques de zoonoses alimentaires reposant sur la construction d'une typologie des dangers et le calcul d'une note de risque. La quantification de la gravite des cas humains utilise la combinaison des taux d'hospitalisation et de letalite moyens. Le calcul de la part alimentaire permet d'estimer l'incidence des cas specifiquement lies a la denree evaluee. Cette methode, illustree par une application au couple « dangers zoonotiques bacteriens - viandes porcine et bovine », constitue une aide a la decision en sante publique veterinaire.
How do cyclin D1, EGFR, and COX-2 attribute to colorectal carcinoma prognosis? An immunohistochemical study on tissue microarray

Colorectal cancer is the third most common cancer in the world and the second most common cause of cancer-related death. In patients with colon cancer, histological stage has been considered as the most important predictor of recurrence. However, additional factors should be examined. According to the previously published studies, the role of cyclin D1 remains controversial. Two other proteins that are known to play an important role in the growth and development of many tumors are cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR). Fifty cases of colorectal carcinomas were prepared by the tissue microarray technique to study the expression of cyclin D1, EGFR, and COX-2 and to evaluate their correlation with clinicopathological characteristics. Cyclin D1 was positively expressed in 96% of total studied cases and showed lack of correlation with the clinicopathological tumor characteristics. EGFR was positively expressed in 74% of cases. In grade 2 cases, 71.1% showed positive EGFR staining, whereas all grade 3 cases were positively stained (P<0.05). In addition, cases with lymphovascular emboli showed positive EGFR staining in 87.1% of cases (P<0.05). COX-2 expression was noticed in 92% of cases, mostly of grade 2 cases (P<0.05) and mostly located in the left colon (90.9%; P<0.05). From this study, we concluded that cyclin D1 expression does not correlate with any of the studied patients' characteristics. EGFR overexpression correlated with higher tumor grade and presence of lymphovascular invasion. Thus, it could be considered as a poor prognostic factor. Finally, COX-2 overexpression correlates with lower tumor grade and tumors located in the left colon, and therefore COX-2 could be considered as a good prognostic factor for colorectal carcinoma.
Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon.

INTRODUCTION Data about the genotypes of circulating Mycobacterium tuberculosis isolates (MTB) in Lebanon are scarce. This study was undertaken to reveal the spoligotypes of MTB isolates recovered from patients in Lebanon. METHODOLOGY MTB isolates from 49 patients living in Lebanon were recovered and identified. The samples were heat killed and subjected to DNA extraction. Spoligotyping was performed using microbeads from TB-SPOL Kit and the fluorescence intensity was measured using Luminex 200®. Generated patterns were assigned to families using the SITVIT2 international database of the Pasteur Institute of Guadeloupe and compared. RESULTS The spoligotyping of the 49 MTB isolates revealed that 31 isolates belonged to Lineage 4 (Euro-American, 63.3%), 12 to Lineage 3 (East- African Indian, 24.5%), 3 to Lineage 2 (East Asian, 6%) and 2 were unknown. Over half of the genotypes (16 of 30) harbored SIT127 supposed to belong to the L4.5 sublineage. One isolate belonging to the rare Manu-Ancestor SIT523 was recovered for the first time in Lebanon, being associated with highly virulent extensively drug-resistant (XDR) MTB phenotype. CONCLUSION The application of the Spoligotyping Multiplex Luminex® method is an efficient, discriminatory and rapid method to use for first-lane genotyping of MTB isolates. Though humble numbers were tested, this study is one of the first to describe the genomic diversity and epidemiology of MTB isolates of Lebanon, and suggests an increasing prevalence of SIT127 in the country.
Pain during physical examination of a healing upper extremity fracture

The evidence that symptom intensity and magnitude of limitations correlate with thoughts and emotions means that subjective signs, such as pain with physical examination, reflect both physical and mental health. During a 1-month evaluation of a rapidly healing upper extremity fracture with no risk of nonunion, 117 people completed measures of adaptiveness to pain and pain during the physical examination. Greater pain during examination correlated with less adaptive responses to pain and older age. This finding raises questions about using tenderness to assess fracture union. Level of evidence: II
Racial and Ethnic Differences in Health Care Utilization Following Severe Acute Brain Injury in the United States

Objective: To examine racial and ethnic differences in the utilization of 3 interventions (tracheostomy placement, gastrostomy tube placement, and hospice utilization) among patients with severe acute brain injury (SABI). Design: Retrospective cohort study. Setting: Data from the National Inpatient Sample, from 2002 to 2012. Patients: Adult patients with SABI defined as a primary diagnosis of stroke, traumatic brain injury, or post-cardiac arrest who received greater than 96 hours of mechanical ventilation. Exposure: Race/ethnicity, stratified into 5 categories (white, black, Hispanic, Asian, and other). Measurements and Main Results: Data from 86 246 patients were included in the cohort, with a mean (standard deviation) age of 60 (18) years. In multivariable analysis, compared to white patients, black patients had an 20% increased risk of tracheostomy utilization (relative risk [RR]: 1.20, 95% CI: 1.16-1.24, P < .001), Hispanic patients had a 10% increased risk (RR: 1.10, 95% CI: 1.06-1.14, P < .001), Asian patients had an 8% increased risk (RR: 1.08, 95% CI: 1.01-1.16, P = .02), and other race patients had an 10% increased risk (RR: 1.10, 95% CI: 1.04-1.16, P < .001). A similar relationship was observed for gastrostomy utilization. In multivariable analysis, compared to white patients, black patients had a 25% decreased risk of hospice discharge (RR: 0.75, 95% CI: 0.67-0.85, P < .001), Hispanic patients had a 20% decreased risk (RR: 0.80, 95% CI: 0.69-0.94, P < .01), and Asian patients had a 47% decreased risk (RR: 0.53, 95% CI: 0.39-0.73, P < .001). There was no observed relationship between race/ethnicity and in-hospital mortality. Conclusions: Minority race was associated with increased utilization of tracheostomy and gastrostomy, as well as decreased hospice utilization among patients with SABI. Further research is needed to better understand the mechanisms underlying these race-based differences in critical care.
Development and validation of a digits-in-noise hearing test in Persian

Abstract Objective The prevalence of unrecognised and late-diagnosed hearing loss is higher in low- and middle-income than in high-income countries, due in part to lack of access to hearing services. Because hearing screening is important for early identification of hearing loss, development of an accessible, self-screening test that can detect hearing loss reliably and quickly would provide significant benefits, especially for underserved populations. This study aimed to develop and validate a new version of the digits-in-noise (DIN) test for Persian speaking countries. Design Recordings of Persian digits 0–9 were binaurally presented in broadband speech-shaped noise. Using fitted speech intelligibility functions, digits were homogenised to achieve equal perceptual difficulty across stimuli. The evaluation was established by reference to existing English DIN tests. Study sample Thirty Persian speaking young adults with normal hearing thresholds (≤20 dB HL, 0.25–8 kHz). Results Speech intelligibility functions produced a mean speech reception threshold (SRT) of −7.7 dB, corresponding closely to previously developed DIN tests. There was no significant difference between test and retest SRTs, indicating high reliability of the test. Our findings suggest that language-specific factors need to be considered for cross-language comparison of DIN-SRTs. Conclusion This study introduces a convenient tool for future hearing screening in Persian speaking countries with limited access to audiology services.
Comparing Smartphone, WhatsApp, Facebook, Instagram, and Snapchat: Which Platform Elicits the Greatest Use Disorder Symptoms?

In recent years, smartphone and social networking services (SNS) use have received a great amount of scholarly attention regarding their potentially addictive effects. Conceptualized as smartphone or SNS use disorder, research has consistently demonstrated relations with daily-life impairments. However, Smartphone Use Disorder (SmUD), WhatsApp Use Disorder (WAUD), Facebook Use Disorder (FBUD), Instagram Use Disorder (IGUD), or Snapchat Use Disorder (SCUD) scores have not been compared with each other. This comparison could provide insight into which device/platform could be most related to daily-life impairments. The effective sample of this study comprised 439 German-speaking individuals (age M = 25.08, SD = 9.74; 271 women) who reported actively using a smartphone, as well as WhatsApp, Facebook, Instagram, and Snapchat, and responded to the respective use disorder scales. Within-subjects analysis of variance and post hoc tests (p values adjusted with the Holm method) were used to compare smartphone and SNS use disorder scale scores. The results suggest that SmUD scores are highest in comparison with other SNS platforms. Although WAUD and IGUD scores did not differ from each other, these scores were higher than for FBUD and SCUD. SCUD scores were higher than FBUD scores. These results provide novel insight into how the smartphone and different SNSs may relate to engagement in problematic digital technology use.
An efficient variance estimator of AUC and its applications to binary classification

The area under the ROC (receiver operating characteristic) curve, AUC, is one of the most commonly used measures to evaluate the performance of a binary classifier. Due to sampling variation, the model with the largest observed AUC score is not necessarily optimal, so it is crucial to assess the variation of AUC estimate. We extend the proposal by Wang and Lindsay and devise an unbiased variance estimator of AUC estimate that is of a two‐sample U‐statistic form. The proposal can be easily generalized to estimate the variance of a K‐sample U‐statistic (K ≥ 2). To make our developed variance estimator more applicable, we employ a partition‐resampling scheme that is computationally efficient. Simulation studies suggest that the developed AUC variance estimator yields much better or comparable performance to jackknife and bootstrap variance estimators, and computational times that are about 10 to 30 times faster than the times of its counterparts. In practice, the proposal can be used in the one‐standard‐error rule for model selection, or to construct an asymptotic confidence interval of AUC in binary classification. In addition to conducting simulation studies, we illustrate its practical applications using two real datasets in medical sciences.
Dispersal of juvenile cougars in fragmented habitat

There is little information on the spatiotemporal pattern of dispersal of juvenile cougars (Felis concolor) and no data on disperser use of habitat corridors. I investigated dispersal of radio-tagged juvenile cougars (8 M, 1 F) in a California landscape containing 3 corridors (1.5, 4.0, and 6.0 km long) and several habitat peninsulas created by urban growth. Dispersal was usually initiated by the mother abandoning the cub near an edge of her home range. The cub stayed within 300 m of that site for 13-19 days and then dispersed in the direction opposite that taken by the mother. Mean age at dispersal was 18 months (range 13-21 months). Each disperser traveled from its natal range to the farthest part of the urban-wildland edge, Dispersing males occupied a series of small (<30% the area used by ad M in the same time span), temporary (10-298 days) home ranges, usually near the urban-wildland interface, and often with its longest border along that edge. Each of the 3 corridors was used by 1-3 dispersers, 5 of the 9 dispersers found and successfully used corridors, and 2 dispersers entered but failed to traverse corridors. Dispersing cougars will use corridors that are located along natural travel routes, have ample windy cover, include an underpass integrated with roadside fencing at high-speed road crossings, lack artificial outdoor lighting, and have <1 dwelling unit/ 16 ha
A cat’s scratch or a wolf’s bite?

Bartonella henselae endocarditis mimicking systemic vasculitis has been reported in patients with valvulopathy. Herein, we describe a patient with B. henselae endocarditis involving a prosthetic pulmonic valve with positive anti-dsDNA antibodies misdiagnosed with systemic lupus erythematosus (SLE) based on the revised classification SLE criteria.
Annual cycle of wrack supply to sandy beaches: effect of the physical environment

Connectivity between ecosystems has been widely recognised as an important issue in ecological studies. Sandy beaches are very dynamic and open ecosystems, mainly supported by allochthonous subsidies of stranded organic matter (mostly macroalgae), also termed wrack supply. The magnitude and composition of algal wrack biomass throughout the annual cycle was assessed for 6 sandy beaches on the Galician coast, NW Spain. The effect of wave action and the topographical features of each beach in the wrack deposition process were investigated. Wrack species composi- tion, biomass and coverage were measured monthly along 6 transects at each beach. Mean dry weight of wrack fluctuated from 14 ± 5.3 to 9189 ± 3594 g m -1 (along transects) between locations. Wrack was predominantly composed of brown algae, which accounted for 70% of the average bio- mass year round; the dominant species were Cystoseira sp. (30.3 ± 17.4%) and Sargassum muticum (14.2 ± 7.1%). A cyclical pattern in wrack composition, coupled with the life cycle of the predominant macroalgae, was observed. Wrack biomass and species composition were mostly explained by wave height and the ratio of beach length to beach area. Small, wave-sheltered beaches received the largest inputs of wrack, and had the lowest relative contribution of brown algae. These results provide evidence that variability in wrack supply on sandy beaches can be explained through inter- actions between wave exposure, coastal topography and seasonality.