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Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the childs future language ability.

Intercellular interactions and cell-cell communication are critical to regulating cell functions, especially in normal immune cells and immunotherapies. Ligand-receptor pairs mediating these cell-cell interactions can be identified using diverse experimental and computational approaches. Here, we reconstructed the intercellular interaction network between Mus musculus immune cells using publicly available receptor-ligand interaction databases and gene expression data from the immunological genome project. This reconstructed network accounts for 50,317 unique interactions between 16 cell types between 731 receptor-ligand pairs. Analysis of this network shows that cells of hematopoietic lineages use fewer communication pathways for interacting with each other, while nonhematopoietic stromal cells use the most network communications. We further observe that the WNT, BMP, and LAMININ pathways are the most significant contributors to the overall number of cell-cell interactions among the various pathways in the reconstructed communication network. This resource will enable the systematic analysis of normal and pathologic immune cell interactions, along with the study of emerging immunotherapies.

Autism Spectrum Disorder (ASD) diagnosis remains behavior-based and the median age of diagnosis is ~52 months, nearly 5 years after its first-trimester origin. Accurate and clinically-translatable early-age diagnostics do not exist due to ASD genetic and clinical heterogeneity. Here we collected clinical, diagnostic, and leukocyte RNA data from 240 ASD and typically developing (TD) toddlers (175 toddlers for training and 65 for test). To identify gene expression ASD diagnostic classifiers, we developed 42,840 models composed of 3570 gene expression feature selection sets and 12 classification methods. We found that 742 models had AUC-ROC ≥ 0.8 on both Training and Test sets. Weighted Bayesian model averaging of these 742 models yielded an ensemble classifier model with accurate performance in Training and Test gene expression datasets with ASD diagnostic classification AUC-ROC scores of 85-89% and AUC-PR scores of 84-92%. ASD toddlers with ensemble scores above and below the overall ASD ensemble mean of 0.723 (on a scale of 0 to 1) had similar diagnostic and psychometric scores, but those below this ASD ensemble mean had more prenatal risk events than TD toddlers. Ensemble model feature genes were involved in cell cycle, inflammation/immune response, transcriptional gene regulation, cytokine response, and PI3K-AKT, RAS and Wnt signaling pathways. We additionally collected targeted DNA sequencing smMIPs data on a subset of ASD risk genes from 217 of the 240 ASD and TD toddlers. This DNA sequencing found about the same percentage of SFARI Level 1 and 2 ASD risk gene mutations in TD (12 of 105) as in ASD (13 of 112) toddlers, and classification based only on the presence of mutation in these risk genes performed at a chance level of 49%. By contrast, the leukocyte ensemble gene expression classifier correctly diagnostically classified 88% of TD and ASD toddlers with ASD risk gene mutations. Our ensemble ASD gene expression classifier is diagnostically predictive and replicable across different toddler ages, races, and ethnicities; out-performs a risk gene mutation classifier; and has potential for clinical translation.

ImportanceCaregivers have long captured the attention of their infants by speaking in motherese, a playful speech style characterized by heightened affect. Reduced attention to motherese in toddlers with autism spectrum disorder (ASD) may be a contributor to downstream language and social challenges and could be diagnostically revealing.ObjectiveTo investigate whether attention toward motherese speech can be used as a diagnostic classifier of ASD and is associated with language and social ability.Design, setting, and participantsThis diagnostic study included toddlers aged 12 to 48 months, spanning ASD and non-ASD diagnostic groups, at a research center. Data were collected from February 2018 to April 2021 and analyzed from April 2021 to March 2022.ExposuresGaze-contingent eye-tracking test.Main outcomes and measuresUsing gaze-contingent eye tracking wherein the location of a toddler's fixation triggered a specific movie file, toddlers participated in 1 or more 1-minute eye-tracking tests designed to quantify attention to motherese speech, including motherese vs traffic (ie, noisy vehicles on a highway) and motherese vs techno (ie, abstract shapes with music). Toddlers were also diagnostically and psychometrically evaluated by psychologists. Levels of fixation within motherese and nonmotherese movies and mean number of saccades per second were calculated. Receiver operating characteristic (ROC) curves were used to evaluate optimal fixation cutoff values and associated sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Within the ASD group, toddlers were stratified based on low, middle, or high levels of interest in motherese speech, and associations with social and language abilities were examined.ResultsA total of 653 toddlers were included (mean [SD] age, 26.45 [8.37] months; 480 males [73.51%]). Unlike toddlers without ASD, who almost uniformly attended to motherese speech with a median level of 82.25% and 80.75% across the 2 tests, among toddlers with ASD, there was a wide range, spanning 0% to 100%. Both the traffic and techno paradigms were effective diagnostic classifiers, with large between-group effect sizes (eg, ASD vs typical development: Cohen d, 1.0 in the techno paradigm). Across both paradigms, a cutoff value of 30% or less fixation on motherese resulted in an area under the ROC curve (AUC) of 0.733 (95% CI, 0.693-0.773) and 0.761 (95% CI, 0.717-0.804), respectively; specificity of 98% (95% CI, 95%-99%) and 96% (95% CI, 92%-98%), respectively; and PPV of 94% (95% CI, 86%-98%). Reflective of heterogeneity and expected subtypes in ASD, sensitivity was lower at 18% (95% CI, 14%-22%) and 29% (95% CI, 24%-34%), respectively. Combining metrics increased the AUC to 0.841 (95% CI, 0.805-0.877). Toddlers with ASD who showed the lowest levels of attention to motherese speech had weaker social and language abilities.Conclusions and relevanceIn this diagnostic study, a subset of toddlers showed low levels of attention toward motherese speech. When a cutoff level of 30% or less fixation on motherese speech was used, toddlers in this range were diagnostically classified as having ASD with high accuracy. Insight into which toddlers show unusually low levels of attention to motherese may be beneficial not only for early ASD diagnosis and prognosis but also as a possible therapeutic target.

Coronavirus disease 2019 (COVID-19) has emerged since December 2019 and was later characterized as a pandemic by WHO, imposing a major public health threat globally. Our study aimed to identify common signatures from different biological levels to enlighten the current unclear association between COVID-19 and Parkinsons disease (PD) as a number of possible links, and hypotheses were reported in the literature. We have analyzed transcriptome data from peripheral blood mononuclear cells (PBMCs) of both COVID-19 and PD patients, resulting in a total of 81 common differentially expressed genes (DEGs). The functional enrichment analysis of common DEGs are mostly involved in the complement system, type II interferon gamma (IFNG) signaling pathway, oxidative damage, microglia pathogen phagocytosis pathway, and GABAergic synapse. The protein-protein interaction network (PPIN) construction was carried out followed by hub detection, revealing 10 hub genes (MX1, IFI27, C1QC, C1QA, IFI6, NFIX, C1S, XAF1, IFI35, and ELANE). Some of the hub genes were associated with molecular mechanisms such as Lewy bodies-induced inflammation, microglia activation, and cytokine storm. We investigated regulatory elements of hub genes at transcription factor and miRNA levels. The major transcription factors regulating hub genes are SOX2, XAF1, RUNX1, MITF, and SPI1. We propose that these events may have important roles in the onset or progression of PD. To sum up, our analysis describes possible mechanisms linking COVID-19 and PD, elucidating some unknown clues in between.

Few clinically validated biomarkers of ASD exist which can rapidly, accurately, and objectively identify autism during the first years of life and be used to support optimized treatment outcomes and advances in precision medicine. As such, the goal of the present study was to leverage both simple and computationally-advanced approaches to validate an eye-tracking measure of social attention preference, the GeoPref Test, among 1,863 ASD, delayed, or typical toddlers (12-48 months) referred from the community or general population via a primary care universal screening program. Toddlers participated in diagnostic and psychometric evaluations and the GeoPref Test: a 1-min movie containing side-by-side dynamic social and geometric images. Following testing, diagnosis was denoted as ASD, ASD features, LD, GDD, Other, typical sibling of ASD proband, or typical. Relative to other diagnostic groups, ASD toddlers exhibited the highest levels of visual attention towards geometric images and those with especially high fixation levels exhibited poor clinical profiles. Using the 69% fixation threshold, the GeoPref Test had 98% specificity, 17% sensitivity, 81% PPV, and 65% NPV. Sensitivity increased to 33% when saccades were included, with comparable validity across sex, ethnicity, or race. The GeoPref Test was also highly reliable up to 24 months following the initial test. Finally, fixation levels among twins concordant for ASD were significantly correlated, indicating that GeoPref Test performance may be genetically driven. As the GeoPref Test yields few false positives (~ 2%) and is equally valid across demographic categories, the current findings highlight the ability of the GeoPref Test to rapidly and accurately detect autism before the 2nd birthday in a subset of children and serve as a biomarker for a unique ASD subtype in clinical trials.

BACKGROUND: Liver cirrhosis is a major public health problem, accounting for high rates of morbidity and mortality worldwide. The cirrhosis etiology is a broad and essential step in planning a treatment strategy. Many recent studies have documented that gut microbiome alterations play a vital role in the development and progression of cirrhosis and its complications. Nevertheless, there is insufficient data on the correlation between liver cirrhosis and gut phageome alterations in patients with advanced liver diseases. This study aimed to analyze the taxonomic structure and functional attributes of the gut phageome in six different etiologies of advanced liver cirrhosis. METHODS: We first retrieved metagenomic sequencing data from three datasets of fecal samples taken from cirrhotic patients with various etiologies. Subsequently, several bioinformatics pipelines were used to analyze bacteriophage composition and determine their functionality. RESULTS: A gene catalog of 479,425 non-redundant genes was developed as a reference to measure gene prevalence. The results of the analysis revealed a few significant differences among the cohorts at the phage species level. However, the alternations were more evident as there were more in-depth analyses of the functional resolution of the gut phageome. CONCLUSIONS: Our findings suggest that the functional analysis of the gut phageome would provide meaningful markers to predict the progression of liver cirrhosis and facilitate the development of novel treatment approaches.

BACKGROUND: Moonlighting proteins (MPs) are a subclass of multifunctional proteins in which more than one independent or usually distinct function occurs in a single polypeptide chain. Identification of unknown cellular processes, understanding novel protein mechanisms, improving the prediction of protein functions, and gaining information about protein evolution are the main reasons to study MPs. They also play an important role in disease pathways and drug-target discovery. Since detecting MPs experimentally is quite a challenge, most of them are detected randomly. Therefore, introducing an appropriate computational approach to predict MPs seems reasonable. RESULTS: In this study, we introduced a competent model for detecting moonlighting and non-MPs through extracted features from protein sequences. We attempted to set up a well-judged scheme for detecting outlier proteins. Consequently, 37 distinct feature vectors were utilized to study each proteins impact on detecting MPs. Furthermore, 8 different classification methods were assessed to find the best performance. To detect outliers, each one of the classifications was executed 100 times by tenfold cross-validation on feature vectors; proteins which misclassified 90 times or more were grouped. This process was applied to every single feature vector and eventually the intersection of these groups was determined as the outlier proteins. The results of tenfold cross-validation on a dataset of 351 samples (containing 215 moonlighting and 136 non-moonlighting proteins) reveal that the SVM method on all feature vectors has the highest performance among all methods in this study and other available methods. Besides, the study of outliers showed that 57 of 351 proteins in the dataset could be an appropriate candidate for the outlier. Among the outlier proteins, there were non-MPs (such as P69797) that have been misclassified in 8 different classification methods with 16 different feature vectors. Because these proteins have been obtained by computational methods, the results of this study could reduce the likelihood of hypothesizing whether these proteins are non-moonlighting at all. CONCLUSIONS: MPs are difficult to be identified through experimentation. Using distinct feature vectors, our method enabled identification of novel moonlighting proteins. The study also pinpointed that a number of non-MPs are likely to be moonlighting.

Today smartphones are inseparable parts of modern life and are capable of performing many desktop computers' tasks such as scientific analysis with greater convenience. Here, we present OligoCOOL, which is an Android application for analyzing nucleic sequences. This application enables users to perform several common biomedical analyses for a given nucleotide sequence. OligoCOOL is a freely accessible Android app at http://bioinf.modares.ac.ir/software/OligoCOOL, which can be a suitable tool for the experimental design in the laboratories. This application also can be used to learn the basics of nucleotide sequence analysis.

Because heavy metals can build up within the bodies of living things, and because of chemical reactions, they can become poisonous and carcinogenic. Among other things, heavy metal-containing salts are one way these elements enter the body. In Khuzestan Province, Iran, the Shorbarik River is one of the most significant rivers from which salt is mined. In order to assess the health and quality of the salt taken from the Shorbarik River in accordance with national regulations, this study looked into the concentration of heavy metals (lead and cadmium) in these salts. The Shorbarik River was the study region, and the surface salts of the dried bed were sampled in four stages. After drying in an oven, they were injected with acid into an atomic absorption device. Due to the high concentration of cadmium in the region's salts, the risk of cancer from exposure to heavy metals through salt consumption is serious. Ecologically, the Shorbarik River's salt is generally low in lead contamination and considerably high in cadmium contamination, with high levels in the spring and summer. Therefore, it is recommended to consume refined salt. [ABSTRACT FROM AUTHOR]

Background and Objectives: The occurrence of phenomena such as surges in complex devices such as turbines, and problems caused by neglecting safety precautions, may result in significant economic damage and losses to the transmission system. On the other hand, electricity production is very important for developing countries, and energy production is a key factor for economic and social development of these countries. Recently, institutions involved in electricity supply have recommended pump as turbine projects as hydroelectric power plant for supplying electricity to rural areas due to their economic benefits. The issue under investigation in this study is the effect of pump shutdown on surge occurrence and its effects on the water transmission line. Materials and Methods: The case study project is the water transmission line to the city of Masjed Soleyman located in the northeast of Khuzestan province. In this study, by using WaterGEMS software, the route of the transmission line, the type and diameter of the pipes, pressure relief valves, tanks, etc., have been defined and modeled in steady state. After processing the line in steady state, in order to investigate the replacement of the pressure relief valve with a reverse pump and its shutdown effect on the created water hammer impact phenomenon, the designed model is called in Bentley HAMMER CONNECT software to analyze and investigate the unsteady state. Since the Hammer software does not have the ability to model the reverse pump, the turbine is used as a reverse pump in the modeling. The phenomenon of surge has been investigated in three scenarios as follows: The first scenario involves studying the flow conditions in a steady state without any changes in the transmission line. The second scenario involves replacing the pressure relief valve at kilometer 0+054 from the Tang-e Mo reservoir with a reverse pump. The third scenario involves replacing the pressure relief valve at kilometer 3+700 from the Tang-e Mo reservoir with a reverse pump. Results: As the downstream pressure wave reaches the upstream side, the pressure in the pipes before and after the reverse pump located at 3+700 km from the Tang-e Mo reservoir increases in the second state and reaches its maximum when the valve is fully closed. Over time, due to the friction of the fluid with the pipe wall, the pressure wave created will be dissipated until the flow will return to the initial steady state. In the mentioned pipes, the maximum pressure created is estimated to be about 22.5 bar. The modeling of the third mode shows that if the reverse pump valves are closed, the pressure before the pump increases up to 20 bar momentarily. As a result of the start of the surge impact and the decrease in flow rate, the pipe pressure decreases to minus 10 meters. The shutdown of the 3+700 reverse pump does not cause significant pressure changes in the pipes before and after the 0+054 reverse pump. About 14 cubic meters of water vapor will accumulate in the area of the pipe after the 3+700 reverse pump. Without the air valve in the line, the volume of steam created will prevent the fluid passage. Conclusions: The results indicate that the occurrence of the surge due to the failure of the PAT(s) installed in the transmission line, despite the creation of positive and negative pressure waves in the transmission line, does not cause serious disturbance in the pipeline. It is also concluded that the thickness of the steel material selected for the pipeline has the required strength to withstand the maximum and minimum pressures. As a result, it is possible to replace the reverse pump with a pressure relief valve and extract energy without causing any problems. In the event of a ram impact, the transmission line will have the ability to withstand the double pressure wave created, and water supply to downstream cities will be possible without disruption. [ABSTRACT FROM AUTHOR]

Background and Objectives: Iran's average annual evaporation rate is 2100 millimeters, which is three times the global average. This figure indicates that if the evaporation rate of reservoirs decreases with appropriate methods, we can better use these resources. Neglecting the high evaporation rate in the country has caused billions of cubic meters of water to evaporate from the reservoirs of more than 600 dams in the country every year. This research studied the effectiveness of composite plates in reducing evaporation from the free surface of water under real conditions. Materials and Methods: The present study was conducted in the meteorological station of Ahvaz airport, with a geographical latitude of 31° 32', a geographical longitude of 48° 66', and an altitude of 16 meters above sea level. Class A evaporation pans made of galvanized iron with a diameter of 120.7 millimeters and a depth of 25 centimeters were used. All experiments were conducted between July and December 2022. In this study, composite plates with aluminum coating were used to reduce evaporation from the water surface with a thickness of 4 millimeters and consisted of two layers of aluminum sheet in the outer shell and a layer of polyethylene in the middle. Floating balls, a relatively common method of reducing evaporation, are used to investigate the effectiveness of composite plates. In addition, the effect of various meteorological variables such as temperature, relative humidity percentage, average vapor pressure, wind speed, and solar radiation on the efficiency of composite panels was investigated. Two-way analysis of variance was used to investigate the effect of various weather variables on the performance of composite plates. Results: Experiments showed that square composite plates had an efficiency of 69%, triangular composite plates had an efficiency of 67%, and floating balls had an efficiency of 73% in reducing evaporation from the water surface. Therefore, floating balls had a slightly greater effect on reducing evaporation from the free surface. The empty space between square composites, due to their larger dimensions compared to triangular composites, is less, which can be considered as one of the reasons for the reduction of evaporation in square composites compared to triangular composites. According to the analysis of variance, two parameters, relative humidity, and wind speed, significantly affect the efficiency of composite plates in reducing evaporation from the water surface. Based on the analysis of variance considering the interaction effects, none of the interaction effects significantly affect the efficiency of composite plates. However, considering the interaction effects in addition to the main effects, the R-squared value of the created model increased to 0.669, indicating that the interaction effects contributed about 0.2 to this value. Conclusion: Based on the analysis of variance considering the main effects, two parameters, relative humidity and wind speed, have a significant effect on the efficiency of composite panels in reducing evaporation from the water surface. Relative humidity has an effect of 0.182, and wind speed has an effect of 0.197 on the efficiency of composite panels. Relative humidity and wind speed are among the parameters that significantly impact the rate of evaporation from the water surface, causing a decrease and an increase in evaporation from the water surface, respectively. The presence of composite panels has greatly reduced these two parameters' effect on the water surface's evaporation rate. [ABSTRACT FROM AUTHOR]