Practical diets for California yellowtail, Seriola dorsalis: Use of advanced soybean meal products on growth performance, body composition, intestinal morphology, and immune gene expression.

California yellowtail (CYT), Seriola dorsalis, is a promising candidate for aquaculture due to its rapid growth and high-quality flesh, particularly in markets like Japan, Australia, China, and the United States. Soy protein has shown success as a replacement for marine protein sources in CYT diets, reducing fishmeal levels, though concerns about potential intestinal inflammation persist with the inclusion of solvent-extracted soybean meal. To address this, processing strategies like fractionation, enzymatic treatment, heat treatment, and microbial fermentation have been employed to mitigate the negative impacts of soybean meal on fish nutrition and immune systems. This study focuses on optimizing soybean meal inclusion levels by incorporating advanced soy variants into CYT diets. The eight-week feeding trial, conducted in a recirculation system, featured six diets with sequential inclusion levels (0, 50, 100%) of high protein low oligosaccharide soybean meal (Bright Day, Benson Hill, St Louis, MO) and enzyme-treated soybean meal (HP 300, Hamlet Protein Inc., Findlay, OH), replacing solvent-extracted soybean. The study compares these formulations against a soy-free animal protein-based diet. At the end of the trial, fish were sampled for growth performance, body proximate composition, intestinal morphology, and immune response from gut samples. Results showed consistent FCR (P = 0.775), weight gain (P = 0.242), and high survival rate (99.4 ± 0.5%) among dietary treatments (P>0.05). Histological evaluations revealed no gut inflammation and gene expression analysis demonstrated no significant variations in immune, physiological, and digestive markers apn (P = 0.687), mga (P = 0.397), gpx1 (P = 0.279), atpase (P = 0.590), il1ß (P = 0.659). The study concludes that incorporating advanced soybean meal products, replacing up to 20% of fishmeal does not negatively affect CYT's growth and intestinal health. This suggests that all three soy sources, contributing 35% of total protein (15.4 g 100 g-1 diet), can be included in practical diets without compromising CYT's intestinal integrity or growth. These findings have positive implications for the commercial production of CYT and future research on the incorporation of plant-based proteins in aquaculture diets.

Investigation of dietary exogenous protease and humic substance on growth, disease resistance to Flavobacterium covae and immune responses in juvenile channel catfish (Ictalurus punctatus).

Many bacterial pathogens impact the US catfish industry, and disease control can be challenging for producers. Columnaris disease in channel catfish, Ictalurus punctatus, is primarily caused by Flavobacterium covae (formerly F. columnare). Immunostimulants may enhance nonspecific immune responses and offer an alternative to antibiotic treatments in catfish. Furthermore, dietary protein sources and inclusions are also essential to fish health and nutrition and may enhance overall fish performance in pond culture. The current project evaluated two immunostimulants: a protease complex (PC) and a humic substance (HS) derived from a reed-sedge peat product. A 60-day trial examined the effects of five diets on growth performance, immune response and resistance to experimental F. covae infection in channel catfish. Diets included a high-quality fishmeal diet (32%; CF32), a high-protein soy-based diet (32%; C32), a low-protein soy-based diet (28%; C28; predominately used in industry), a low-protein soy diet supplemented with C28 + PC at 175 g metric ton-1 and C28 + HS in a low-protein diet at 23 g metric ton-1 . Following feeding for 60 d, juvenile channel catfish were sampled for growth performance and baseline health indicators (n = 3; body mucus, blood for sera, kidney and spleen). A subset of fish was then subjected to an immersion-based in vivo challenge trial with F. covae (ALG-00-530; 106 CFU mL-1 exposure). At 60d post-initiation, there were no dietary differences in the relative growth rate (p = .063) or thermal growth coefficient (p = .055), but the 32% diets generally appeared to perform best. Post-challenge, the C32 group's mortality was higher than the C28 + PC (p = .006) and C28 + HS diets (p = .005). Although not significant, the C28 and CF32 groups also demonstrated higher mortality compared to both PC and HS diets. Sera lysozyme concentration was found to increase following pathogen challenge (p < .001) and in comparison with mock-challenged catfish (p < .001). Elevated expression levels of proinflammatory cytokines (il-1ß, il-8, tnf-α and tgf-ß) were observed at trial midpoint and post-infection when compared to 60d. The C28 treatment was found to have lower tnf-α expression than the C28 + PC (p = .042) and C28 + HS (p = .042) groups following exposure to F. covae. These challenge data suggest that the immunostimulants (PC and HS) in plant-based protein may be beneficial in protecting against F. covae when offered in low-protein channel catfish diets.

Concomitant intra-aortic balloon pump and veno-arterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock.

We aimed to compare the outcomes of ECMO with and without IABP for postcardiotomy cardiogenic shock. The study included 103 patients who needed ECMO for postcardiotomy cardiogenic shock. Patients were grouped according to the use of IABP into ECMO without IABP (n = 43) and ECMO with IABP (n = 60). The study endpoints were hospital complications, successful weaning, and survival. Patients with IABP had lower preoperative ejection fraction (p = 0.002). There was no difference in stroke (p = 0.97), limb ischemic (p = 0.32), and duration of ICU stay (p = 0.11) between groups. Successful weaning was non-significantly higher with IABP (36 (60%) vs 19 (44.19%); p = 0.11). Predictors of successful weaning were inversely related to the high pre-ECMO lactate levels (OR: 0.89; p = 0.01), active endocarditis (OR: 0.06; p = 0.02), older age (OR: 0.95; p = 0.02), and aortic valve replacement (OR: 0.26; p = 0.04). There was no difference in survival between groups (p = 0.80). Our study did not support the routine use of IABP during ECMO support.

ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression.

Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, understanding the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investigated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4 promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.

Boosting Tadalafil Bioavailability via Sono-Assisted Nano-Emulsion-Based Oral Jellies: Box-Behnken Optimization and Assessment.

Tadalafil (TAD) is a poorly soluble, phosphodiesterase inhibitor used to treat erectile dysfunction. The primary goal of this project was to prepare nano-emulsions using ultrasonic technology to address TAD bioavailability concerns. The Box−Behnken design was employed to find prominent correlations between factors impacting the sono-emulsification process. The emulsifier concentration, amplitude level, and ultrasonication time were the independent factors, whereas the average droplet size (ADS) and polydispersity index (PDI) were designated as the response variables. TAD-loaded nano-emulsions (93−289 nm) were generated and the emulsifier concentration showed a crucial role in directing emulsion droplet size. The model desirability function was utilized to optimize a nano-emulsion with a small ADS (99.67 ± 7.55 nm) and PDI (0.45 ± 0.04) by adjusting the emulsifiers concentration, amplitude level, and ultrasonication time at 9.85%, 33%, 49 s, respectively. The optimized nano-emulsions did not demonstrate any precipitation or phase separation after stability stress tests. TAD jellies were formulated based on the optimized nano-emulsion and subjected to in vitro evaluation for physical characteristics; TAD content, pH, spreadability, viscosity, syneresis, and taste-masking ability. An optimized nano-emulsion-based jelly (NEJ) formulation showed more than 96% drug dissolution in 30 min relative to 14% for the unprocessed TAD. In vivo assessment of NEJ in experimental rats demonstrated a significant enhancement (p < 0.05) of TAD bioavailability with an AUC0−24h of 2045 ± 70.2 vs. 259.9 ± 17.7 ng·h·mL−1 for the unprocessed TAD. Storage stability results revealed that NEJ remained stable with unremarkable changes in properties for 3 months. Overall, NEJ can be regarded as a successful therapeutic option for TAD administration with immediate-release properties and improved bioavailability.

Acquired Brown Syndrome After a Fist Punch: A Case Report.

A 15-year-old male presented with double vision in the left and upward gaze following a hit in the right orbital region. The orthoptic assessment revealed -2 limitation of elevation in the adduction position of the right eye and right hypotropia of 20 prism diopter (PD) in the left gaze and right hypotropia of 10 PD in the upward gaze. He was diagnosed with traumatic Brown syndrome and planned for superior oblique lengthening surgery for the right eye. Two months postoperatively, the patient has a normal extra-ocular motor function with the elimination of diplopia and significant improvement of elevation of the right eye in the adduction position. Herein, we discuss the clinical features, etiologies, tailored evaluation, and management for the patient with traumatic Brown syndrome.

Prevalence of coronary artery disease and its risk factors in Majmaah City, Kingdom of Saudi Arabia.

Objective: This study was carried out with an aim to outline the prevalence of coronary artery diseases, its risk of one region of the Saudi Arabia. Methods: A retrospective observational study conducted across five secondary medical centers located in the city of Majmaah. Hospital medical records and ministry of health records were screened over a 6-month period for data on patients admitted for Coronary artery disease (CAD). Data collected included sociodemographic characteristics, medical profile, and laboratory findings. Results: A total of 327 participants were included in this study with a median age of 64 and the majority being male participants (59.8%). The majority were married, held a primary school degree and earned a salary for living. A large number (82.9%) were hypertensive and diabetic (66.7%) and one-fourth had a previous MI (25.1%). A large number (73.7%) had heart failure with a mean ejection fraction of 44% (SD = 13). The causes of heart failure were mainly ischemic (56.3%) and hypertensive (28.1%). Readmission rates at 30 and 90 days then at 6 and 12 months were 22, 53.8, 68.8, and 75.8%, respectively. The mortality rates at the same time intervals were 5.5, 8.9, 14.1, and 22.9%, respectively. Predictors of readmission are age, CCI, and NYHA class. Conclusion: Coronary artery disease is the leading cause of heart failure. End stage CAD can have similar results in terms of readmission and mortality as heart failure. Future research should target patients in different stages of the condition and monitor their comorbidities which may impact the study findings.

Fabric phase sorptive extraction coupled with UPLC-ESI-MS/MS method for fast and sensitive quantitation of tadalafil in a bioequivalence study.

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 µm) column and the flow rate was adjusted at 0.4 mL min-1. The total run time per sample was 1.0 min. The method was validated by FDA standards for bioanalytical method validation over a concentration range of 0.1-100 ng mL-1 with a correlation coefficient of 0.9993 and the lower limit of quantitation (LLOQ) was 0.1 ng mL-1 in rat plasma. Intra- and inter-assay precision (%RSD) were lower than 4.1% and accuracy (%RE) was within 2.4%. The developed FPSE-UPLC-ESI-MS/MS method was effectively used in a randomized, two-way, single-dose, crossover study to compare the bioequivalence of two TAD formulations from different companies in male rats and verified to be bioequivalent.

Tadalafil-Loaded Self-Nanoemulsifying Chewable Tablets for Improved Bioavailability: Design, In Vitro, and In Vivo Testing.

This research aimed to develop innovative self-nanoemulsifying chewable tablets (SNECT) to increase oral bioavailability of tadalafil (TDL), a nearly insoluble phosphodiesterase-5 inhibitor. Cinnamon essential oil, PEG 40 hydrogenated castor oil (Cremophor® RH 40), and polyethylene glycol 400 served as the oil, surfactant, and cosurfactant in the nanoemulsifying system, respectively. Primary liquid self-nanoemulsifying delivery systems (L-SNEDDS) were designed using phase diagrams and tested for dispersibility, droplet size, self-emulsifying capability, and thermodynamic stability. Adsorption on a carrier mix of silicon dioxide and microcrystalline cellulose was exploited to solidify the optimum L-SNEDDS formulation as self-nanoemulsifying granules (SNEG). Lack of crystalline TDL within the granules was verified by DSC and XRPD. SNEG were able to create a nanoemulsion instantaneously (165 nm), a little larger than the original nanoemulsion (159 nm). SNECT were fabricated by compressing SNEG with appropriate excipients. The obtained SNECT retained their quick dispersibility dissolving 84% of TDL within 30 min compared to only 18% dissolution from tablets of unprocessed TDL. A pharmacokinetic study in Sprague−Dawley rats showed a significant increase in Cmax (2.3-fold) and AUC0−24 h (5.33-fold) of SNECT relative to the unprocessed TDL-tablet (p < 0.05). The stability of TDL-SNECT was checked against dilutions with simulated GI fluids. In addition, accelerated stability tests were performed for three months at 40 ± 2 °C and 75% relative humidity. Results revealed the absence of obvious changes in size, PDI, or other tablet parameters before and after testing. In conclusion, current findings illustrated effectiveness of SNECT to enhance TDL dissolution and bioavailability in addition to facilitating dose administration.

Unravelling the Effect of Triacontanol in Combating Drought Stress by Improving Growth, Productivity, and Physiological Performance in Strawberry Plants.

To explore the effects of triacontanol (TR) on drought tolerance of strawberry plants (cv Fertona), two field experiments were carried out to study the effects of three supplementary foliar TR rates (0, 0.5, and 1 ppm) under the following three levels of water irrigation: 11 m3/hectare (40% of water holding capacity (WHC) severe as a drought treatment, 22 m3/hectare (80% of WHC) as moderate drought stress, and normal irrigation with 27 m3/hectare (100% of WHC) server as a control treatment. TR treatments were applied five times after 30 days from transplanting and with 15-day intervals. The results showed that drought stress (40% and 80%) markedly decreased the growth, fruit yield, and chlorophyll reading, as well as the gas exchange parameters (net photosynthetic rate, stomatal conductance, and transpiration rate). Meanwhile, drought stress at a high rate obviously increased antioxidant enzyme activities such as superoxide dismutase (SOD), peroxidase (POX), and catalase (CAT) contents in the leaves of the strawberry plants. The moderate and high drought stress rates enhanced some strawberry fruit quality parameters such as total soluble solids (TSS), vitamin C, and anthocyanin content compared to the control. Additionally, TR increased the activities of SOD, POX, and CAT. TR treatment significantly increased the chlorophyll contents, gas exchange parameters (photosynthetic rate and stomatal conductance), and water use efficiency (WUE). Plant height, fruit weight, and total biomass were increased also via TR application. Total yield per plant was increased 12.7% using 1 ppm of TR compared with the control. In conclusion, our results suggested that TR application could relieve the adverse effects of drought stress on the growth of strawberry plants by enhancing the antioxidant enzymes, photosynthesis rate, and WUE of the leaves.

The Diagnostic Yield of Abdominal Ultrasounds Requested by Family Physicians at an Academic Hospital in Riyadh, Saudi Arabia.

BACKGROUND: Abdominal ultrasound is a non-invasive, relatively inexpensive, and widely available diagnostic modality in family medicine settings. OBJECTIVES: Our study aimed to identify the most common indications for requesting abdominal ultrasounds by family physicians, determine the frequency of abdominal ultrasound with abnormal findings, identify the most common findings, and determine patients' characteristics associated with abnormal findings. METHODS: This retrospective chart-based study was conducted from January 2020 to June 2020 to analyze patients' abdominal ultrasounds reports requested by family physicians in 2019 at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. RESULTS: We assessed abdominal ultrasound reports of 1,113 patients. There were 620 (55.7%) female patients. The mean age and body mass index (BMI) were 46.35 years ± 15.04 and 29.33 kg/m2 ± 7.06, respectively. The most common indications were abdominal pain (43.2%), suspicion of gallbladder and biliary system diseases (18.5%), and abnormal liver function tests (14.6%). The frequency of abnormal findings was 793 (71.2%), and the most common findings were fatty liver infiltration (49.7%), liver enlargement (20.1%), and gallstones (13.3%). Females had a lower likelihood to have abnormal findings compared to males (odds ratio (OR)=0.688, p=0.009). Lastly, the likelihood of abnormal findings increased with age and was highest among patients aged 71 years or more (OR=25.9, p< 0.001). CONCLUSION: Abnormal findings were more prevalent in our study compared with other studies. Abnormal findings were more common among males and older age groups. We recommend future studies on patients from community-based family medicine settings, and to examine the association of abnormal findings with patient-centered endpoints. Finally, disseminating the results of this study will inform family physicians with the most common abnormal abdominal ultrasound findings, and will enhance the discussion with patients undergoing an abdominal ultrasound examination.

Hyponatremia management among patients admitted to tertiary hospital: A retrospective evaluation.

Objective: The aim of this study is to compare the adherence to the guidelines in patients presenting with hyponatremia defined as a sodium (Na) level ⩽120 mEq/L, treated with 3% hypertonic saline or normal saline. The comparison included 3% hypertonic saline use, safe serum sodium increases within 24 and 48 h, frequency of hyponatremia-related complications, and length of stay. Methods: This retrospective observational study enrolled 122 patients with serum sodium ⩽120 mEq/L admitted to the Internal Medicine Department, King Abdulaziz Medical City, National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia, from January 2016 to December 2017. The patients were treated with either 3% hypertonic saline or normal saline. Results: Of the 122 patients, 105 (83.3%) received normal saline, and 17 (13.5%) received hypertonic saline. In the normal saline group, the mean serum sodium increase at 24 h was lower (6.60 ± 4.75) compared to the hypertonic saline group (9.24 ± 5.04). The length of stay was longer in the normal saline group (10.35 ± 13.90) compared to the hypertonic saline group (4.35 ± 3.39). A small proportion (8.7%) of the normal saline group had a serum sodium increase >12 mg/dL at 24 h compared to 29.4% for the hypertonic saline group, and the difference was statistically significant (p value = 0.013). Almost one-third of the sample (36%) presented with complications, the majority (77.3%, n = 34) had a serum sodium of ⩽115 mg/dL, and 22.7% (n = 10) with a serum sodium of 116-120 mg/dL (p value = 0.041). Conclusion: Despite the strong recommendation for 3% hypertonic saline use in severe hyponatremia, many practitioners still use normal saline, even in patients with serum sodium ⩽120 mEq/L. Normal saline showed some efficacy in managing hyponatremia in asymptomatic cases; however, severe cases may have a delayed correction, hyponatremia-related complications, and an extended length of stay.

Intra-soil waste recycling provides safety of environment.

Amelioration and remediation technology was developed for phosphogypsum utilization in Haplic Chernozem of South-European facies (Rostov Region). The technology comprises phosphogypsum dispersed application into the soil layer of 20-45 cm during intra-soil milling. In the model experiment, the phosphogypsum doses 0 (control), 10, 20, and 40 t ha-1 were studied. The Cd thermodynamic forms in soil solution were calculated via the developed mathematical chemical-thermodynamic model and program ION-3. The form of ion in soil solution (or water extract) was considered accounting the calcium-carbonate equilibrium (CCE) and association of ion pairs CaCO30; CaSO40, MgCO30, MgSO40, CaHCO3+, MgHCO3+, NaCO3-, NaSO4-, CaOH+, MgOH+. For calculation of the equilibrium of microelements concentration in soil solution ion including heavy metals (HMs), the coefficient of microelement association kas was proposed. According to calculations, Cd2+ ion in soil solution was mostly bounded to associates CdOH+, partly to associates CdCO30 and CdHCO3+. The calculated kas of Cd was 1.24 units in the control option of experiment and decreased to 0.95 units at phosphogypsum dose 40 t ha-1. The ratio of "active [Cd2+] to total Cd" reduced from 33.5% in control option to 28.0% in the option of phosphogypsum dose 40 t ha-1. The biogeochemical barrier for penetration of HMs from soil to plant roots was high after application of phosphogypsum. According to calculation by ION-3, the standard soil environmental limitations overestimate the toxicity of Cd in soil solution. New decision for intra-soil milling and simultaneous application of phosphogypsum was developed to provide the environmentally safe waste recycling.

Factors associated with patients bypassing primary healthcare centres in Qassim Region, KSA.

OBJECTIVE: This study investigates the reasons for bypassing local primary healthcare centres (PHCs) by patients with minor illnesses in Qassim Region, KSA. METHODS: A cross-sectional study was performed on 266 patients that visited emergency departments in public hospitals in Qassim Region. The patients were randomly selected and categorised as level five patients (LFPs) using the Canadian Triage and Acuity Scale (CTAS) for patient characterisation. RESULTS: Of the 266 patients, 85.7% had previous experience of visiting PHC facilities. The majority of these patients were not satisfied with their treatment in PHCs. Approximately 52.9% of the patients reported that the working hours at PHCs were not sufficient, 38.1% mentioned a lack of experienced staff, and 31.7% believed that PHCs were insufficient for diagnostic tests. Another 13.8% of the patients reported the unavailability of prescribed medicines. Interestingly, 17.7% of the patients reported that they never bypassed PHCs. In general, the data demonstrate that patients' gender, employment, and marital status have no significant role in their decision to skip PHCs in favor of emergency departments of public hospitals (p > 0.05). CONCLUSIONS: Patients bypassing PHCs without a referral form is a serious concern that have a deleterious effect on the healthcare system, particularly emergency departments. If bypassing continues, it will increase the burden on emergency departments, particularly on healthcare services for the general population.

Severe Urosepsis Secondary to Xanthogranulomatous Pyelonephritis: A Case Report.

Xanthogranulomatous pyelonephritis (XGP) is considered to be a rare variant of chronic pyelonephritis, which results in non-functioning kidneys in patients. The exact etiology of this disease is still unknown, and hence even its pathophysiology remains unclear. We present a case of a 27-year-old Saudi male patient who had been bed-bound with a known case of a congenital anomaly with severe kyphoscoliosis, bilateral lower limbs deformity with paraplegia, and a ventriculoperitoneal shunt since childhood. The patient was brought to the emergency department (ED) with right flank pain associated with fever and difficulty in breathing. The patient had a past medical history of recurrent urinary tract infection (UTI) with up to two incidences per year and renal stones. He had been recently discharged from the ICU of another hospital with sepsis due to UTI. An abdominal CT scan was performed, which showed a mass in the upper lobe of the right kidney measuring about 9 x 8 x 6 cm, suggestive of XGP. The final diagnosis was severe urosepsis secondary to right obstructive pyelonephritis. Patients with XGP usually present with nonspecific symptoms including back and abdominal pain, fever, UTI, and the condition is more common among middle-aged women. Ultimately, early detection and diagnosis, followed by prompt treatment with partial or total nephrectomy are associated witha good prognosis for patients with XGP.

A Systematic Literature Review on the Application of Machine-Learning Models in Behavioral Assessment of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with significant social, communication, and behavioral challenges. The insufficient number of trained clinicians coupled with limited accessibility to quick and accurate diagnostic tools resulted in overlooking early symptoms of ASD in children around the world. Several studies have utilized behavioral data in developing and evaluating the performance of machine learning (ML) models toward quick and intelligent ASD assessment systems. However, despite the good evaluation metrics achieved by the ML models, there is not enough evidence on the readiness of the models for clinical use. Specifically, none of the existing studies reported the real-life application of the ML-based models. This might be related to numerous challenges associated with the data-centric techniques utilized and their misalignment with the conceptual basis upon which professionals diagnose ASD. The present work systematically reviewed recent articles on the application of ML in the behavioral assessment of ASD, and highlighted common challenges in the studies, and proposed vital considerations for real-life implementation of ML-based ASD screening and diagnostic systems. This review will serve as a guide for researchers, neuropsychiatrists, psychologists, and relevant stakeholders on the advances in ASD screening and diagnosis using ML.

Pharmacy Students Perceptions of Their Distance Online Learning Experience During the COVID-19 Pandemic: A Cross-Sectional Survey Study.

INTRODUCTION: The COVID-19 pandemic imposed dramatic changes on educational practices worldwide. Many universities and schools have moved into the delivery of their courses and educational programs utilizing fully electronic online modes. This study aims to evaluate the pharmacy student distance online learning experience during the COVID-19 pandemic. METHODS: A cross-sectional survey was utilized where a 3-domain survey questionnaire focused on preparedness, attitude and barriers was distributed to students at the time of conclusion of the semester. Each domain consists of multiple questions that made up a score that reflects their preparedness, attitude as well as barriers relevant to distance online learning experience. The survey was voluntarily, and all data were collected and recorded via google forms with maintaining anonymity. RESULTS: The response rate was about 75% (n = 309). The results' analysis revealed no gender differences in any of these domains. However, there were some variable responses among different educational levels. The average preparedness score was 32.8 ± 7.2 (Max 45), the average attitude score was 66.8 ± 16.6 (Max 105), and the average barrier score was 43.6 ± 12.0 (Max 75). There was statistical significance difference in both preparedness score and attitude scores between different professional years (P-value <.05). However, there was no difference in barrier scores among all professional years. The results indicated that about 61.4% of the students agreed on that college of pharmacy was well-prepared and ready for the online education during the emerging COVID-19 pandemic with complete transition into online education. The results also indicated that 49.2% of the students showed positive attitude toward the provided online learning. The results indicated that about 34% of the students identify some barriers toward the provided online learning. Finally, there were strong association between the need for training on how to receive online courses and preparedness and barriers scores. DISCUSSION AND CONCLUSION: E-learning experience pose challenges and presents opportunities during emergency situations. The need for training for students and faculty was highly associated with the preparedness and barriers domains rather than the infrastructure or computer literacy, so the school can improve their experience by addressing these needs.

Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway.

Recent data suggest that the transcription factor Zfp148 represses activation of the tumor suppressor p53 in mice and that therapeutic targeting of the human orthologue ZNF148 could activate the p53 pathway without causing detrimental side effects. We have previously shown that Zfp148 deficiency promotes p53-dependent proliferation arrest of mouse embryonic fibroblasts (MEFs), but the underlying mechanism is not clear. Here, we showed that Zfp148 deficiency downregulated cell cycle genes in MEFs in a p53-dependent manner. Proliferation arrest of Zfp148-deficient cells required increased expression of ARF, a potent activator of the p53 pathway. Chromatin immunoprecipitation showed that Zfp148 bound to the ARF promoter, suggesting that Zfp148 represses ARF transcription. However, Zfp148 preferentially bound to promoters of other transcription factors, indicating that deletion of Zfp148 may have pleiotropic effects that activate ARF and p53 indirectly. In line with this, we found no evidence of genetic interaction between TP53 and ZNF148 in CRISPR and siRNA screen data from hundreds of human cancer cell lines. We conclude that Zfp148 deficiency, by increasing ARF transcription, downregulates cell cycle genes and cell proliferation in a p53-dependent manner. However, the lack of genetic interaction between ZNF148 and TP53 in human cancer cells suggests that therapeutic targeting of ZNF148 may not increase p53 activity in humans.

TMX2 Is a Crucial Regulator of Cellular Redox State, and Its Dysfunction Causes Severe Brain Developmental Abnormalities.

The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain.