Large-scale application of ClinGen-InSiGHT APC-specific ACMG/AMP variant classification criteria leads to substantial reduction in VUS.

Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open Variation Database (LOVD) variant database, which included a total of 10,228 unique APC variants. Among the ClinVar and LOVD variants with an initial classification of (likely) benign or (likely) pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUSs were reclassified into clinically meaningful classes, the vast majority as (likely) benign. The total number of VUSs was reduced by 37%. In 24 out of 37 (65%) promising APC variants that remained VUS despite evidence for pathogenicity, a data-mining-driven work-up allowed their reclassification as (likely) pathogenic. These results demonstrated that the application of APC-specific criteria substantially reduced the number of VUSs in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalizable model for other gene- or disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUSs that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.

The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10-9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10-10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10-6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations.

Omeprazole affects the expression of serotonin-1A in the brain regions and alleviates anxiety in rat model of immobilization-induced stress.

Omeprazole, a drug of choice for the management of gastric hyperacidity, influences serotonergic neurotransmission in brain regions and its long-term use is known to cause stress-related behavioral deficits including anxiety. Aim of the current study was to explore the effects of omeprazole treatment on immobilization-induced anxiety in rats, specifically on the role of serotonin (5-HT). In view of the role of serotonin-1A (5-HT1A) autoreceptor in the availability of 5-HT in brain regions, mRNA expression of this autoreceptor was performed in raphe nuclei. Similarly, because of the role of hippocampal 5-HT neurotransmission in anxiety-like disorders, expression of the 5-HT1A heteroreceptors was determined in this region. We found that the treatment with omeprazole reduces anxiety-like behavior in rats, increases the expression of 5-HT1A autoreceptor in the raphe and decreases the hippocampal expression of 5-HT1A heteroreceptor. This suggests a role of 5-HT1A receptor types in omeprazole-induced behavioral changes. It also indicates a potential role of omeprazole in the management of serotonergic disorders.

Quantitative analysis of loxoprofen sodium loaded microspheres comprising pectin and its thiolated conjugates: In-vivo evaluation of their sustained release behavior.

Continuous use of oral NSAIDs can damage mucosal membrane, which results in decreased bioavailability and non-compliance with the therapy. But the use of sustained release drug delivery systems might offer a solution. Objective was to synthesize mucoadhesive SR microspheres by using different combinations of pectin (PEC) and its thiolated derivative (T-PEC3100) for improved loxoprofen (LS) permeation. Thiolated pectin (T-PEC) was synthesized by the esterification method using thioglycolic acid. Thiolation was confirmed by thiol group quantification and charring point determination. Further characterization was done by Fourier Transform Infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Ex-vivo mucoadhesion study was performed to confirm the improved characteristics. Microspheres (MS) were prepared using different ratios of PEC/T-PEC by solvent evaporation method and their particle size and surface morphology were evaluated. Mucus permeation study was carried out using the trans-well plate method. Sustained release behavior of prepared microspheres was investigated through the edema inhibition method in albino rats. T-PEC3100 was considered the optimum formulation for further evaluation and contained maximum thiol group content. FTIR spectra showed a characteristic peak of -SH and charring point was also changed considerably confirming the successful thiolation of PEC. SEM results showed spherical microspheres in the size range of 2-10 µm. Thiol-rich formulation of MS exhibited more than 80 % release after 12 h and maximum absorbable dose (MAD) was calculated as 400 µg % inhibition of edema in MS treated group was slowly attained initially but the reduction in inflammation was detected even after 24 h as compared to control group. Promising results from In-vivo edema inhibition study suggest the possible use of these thiolated MS in formulating sustained release formulation for arthritis.

A yeast-malic acid crosslinker/polyacrylic acid hydrogel containing doxycycline for the treatment of periodontitis.

Doxycycline (DX) is a drug of choice for the treatment of periodontitis, with the limitation of requiring a high dose, which may be overcome by the preparation of a targeted controlled-release hydrogel containing a newly synthesized yeast-malic acid crosslinker (YMC). YMC was synthesized via thermochemical modification of yeast with malic acid at 100-140 °C and compared with glutaraldehyde-saturated toluene (GST). Swelling capacity, acid and carboxyl content, scanning electron microscopy (SEM) imaging, Brunauer-Emmett-Teller (BET) analysis, viscosity, cross-linking density, DX loading and release behavior at pH 6.5, mucoadhesion, and antimicrobial and periodontal efficacy of the glutaraldehyde hydrogel (HGG) and YMC hydrogel (HGY) were compared. Changes from C-O (1421 cm-1) to C[double bond, length as m-dash]OOR (1702 cm-1) in the infrared spectroscopy, along with changes in the degree of substitution from 0 to 0.39, degree of esterification from 0 to 40 ± 1.5 and COOH content from 129 ± 0.5 to 290 ± 0.5 (meq. per 100 g), were found between yeast to YMC, respectively. The results revealed 1.5 times more dynamic swelling, 0.25-fold decrease in acid content, 2.3-fold increase in carboxyl content, and 1.2- and 2.1-fold increases in cross-linking density and viscosity of HGY as compared to HGG, respectively. The SEM and BET results revealed that HGY had a 2 times greater porous surface than HGG. HGY/DX was 35 ± 2% more effective in controlling periodontitis bacteria, decreased periodontal depth from 4 to 3.2 mm, and gingival index from 3 to 1 as compared to HGG/DX in patients suffering from periodontitis. HGY/DX not only serves as a tool for the controlled release of DX in periodontal pockets but also contributes to the treatment of gingival periodontitis.

Comparative analysis of breeding patterns and reproductive efficiency of mares in subtropical conditions of Pakistan.

BACKGROUND AND AIM: The present study aimed to evaluate and compare the overall and breed-specific seasonal breeding patterns, fertility rates, cyclicity, and follicular dynamics of Arab, Thoroughbred, and Percheron mares under the subtropical conditions of Pakistan. MATERIALS AND METHODS: A retrospective analysis of climatic data and breeding records of eleven breeding studs spanning four years (2020-2023) was made to find out the overall seasonality in the breeding pattern of mares. Fifty mares of each breed (n = 150 in total) were scanned by ultrasonography for a calendar year to find the cyclicity pattern and follicular dynamics (follicular growth rate, size of ovulatory follicle, and days from estrus till ovulation). RESULTS AND DISCUSSION: The statistical analysis of breeding records demonstrated a clear pattern of seasonal breeding (p< 0.05). The highest monthly foalings were noted in March (247 ± 45.37), and overall breeding activities peaked in Spring season (p< 0.05). Breed-specific results of Arab, Thoroughbred, and Percheron mares revealed that Arab mares maintained stable breeding activity throughout the year, with the highest activity in spring and peak conception rate in winter (56.25% ± 32.78; p > 0.05). Thoroughbred mares experienced significant seasonal declines from spring to winter with a peak conception rate in winter (63.89% ± 27.37, p > 0.05). Percherons showed the most pronounced seasonal effects, especially with a high fall conception rate (73.04% ± 19.61) and a sharp decrease in winter breeding metrics (p< 0.05). Furthermore, Thoroughbred and Percheron mares displayed the most pronounced seasonal effects on the percentage of cyclic mares 77.3% and 56% in winters (p< 0.05). Moreover, the follicular dynamics of the three breeds also exhibited significant differences (p< 0.05). CONCLUSION: The current study concludes that seasonal and breed-specific variability exists among the reproductive parameters of Arab, Thoroughbred, and Percheron mares in subtropics, necessitating breed-specific reproductive management measures to maximize mare breeding efficiency.

Analysis of the expression patterns of AVP, IGF-1, and TNF-α, APP, CD44, IFN-ß IFN A ß-6, α-syn, and NFL and CLU genes in generalized and focal seizures.

Objective: The aim of our study was to investigate the relationship between clinical indicators and gene dysregulation in different types of epilepsy, while also seeking to identify a diagnostic model capable of distinguishing between focal and generalized seizures. This highlights the critical importance of understanding clinical indicators and gene dysregulation for targeted therapeutic interventions to effectively address the specific seizure types effectively. Materials and methods: In this study, we conducted a comprehensive analysis of the peripheral blood of epilepsy patients (n = 100) and a control group (n = 51) to determine the differential gene expression. Our analysis involved a range of statistical approaches, including correlation analysis to establish the association between clinical indicators and gene dysregulation, and principal component analysis to highlight distinct disease group from control group. Furthermore, we developed diagnostic models using logistic regression to aid in the accurate diagnosis of epilepsy. Results: Among several selected genes in this study such as AVP (AUC = 0.832, p < 0.0001), IGF-1 (AUC = 0.658, p = 0.0015), TNF-α (AUC = 0.8970, p < 0.0001), APP (AUC = 0.742, p < 0.0001), CD44 (AUC = 0.614, p = 0.021) and NfL (AUC = 0.937, p < 0.0001), and CLU (AUC = 0.923, p < 0.0001) have shown the outstanding discrimination. In addition to this, when all genes were included in the model, the overall diagnostic power increased significantly (AUC = 0.9968). A differential diagnostic model for focal and generalized seizures was established which discloses AUC = 0.7027, (95 % CL, 0.5765 to 0.8289, p = 0.0019). Conclusion: The conclusions drawn from these findings represented that this is the first study to highlight the distinctive gene patterns of both focal and generalized seizures, implying that peripheral blood can serve as a diagnostic source to distinguish between these seizures types, aiding in the accurate classification of epilepsy. The findings from this study indicate a promising direction for investigating more targeted pharmacological interventions directed to address the distinct needs of both focal and generalized epilepsy, which offers advancements in treatment strategies for distinctive seizure types.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels. Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants. All samples were assessed for COSMIC v3.2 SBS mutational signatures. Results: In biallelic MUTYH cases, SBS18+SBS36 signature proportions in adenomas (mean±standard deviation, 65.6%±29.6%) were not significantly different to those observed in CRCs (76.2%±20.5%, p-value=0.37), but were significantly higher compared with non-hereditary adenomas (7.6%±7.0%, p-value=3.4×10-4). Similarly, in biallelic NTHL1 cases, SBS30 signature proportions in adenomas (74.5%±9.4%) were similar to those in CRCs (78.8%±2.4%) but significantly higher compared with non-hereditary adenomas (2.8%±3.6%, p-value=5.1×10-7). Additionally, a compound heterozygote with the c.1187G>A p.(Gly396Asp) pathogenic variant and the c.533G>C p.(Gly178Ala) variant of unknown significance (VUS) in MUTYH demonstrated high levels of SBS18+SBS36 in four adenomas and one CRC, providing evidence for reclassification of the VUS to pathogenic. Conclusions: SBS18+SBS36 and SBS30 were enriched in adenomas at comparable proportions observed in CRCs from biallelic MUTYH and biallelic NTHL1 cases, respectively. Therefore, testing adenomas may improve the identification of biallelic cases and facilitate variant classification, ultimately enabling opportunities for CRC prevention.

Lipase-copper complex/chitosan microspheres; loaded with attapulgite used for the treatment of E. coli-induced diarrhea.

Diarrhea is a globally major problem especially Escherichia coli induced diarrhea becoming fatal nowadays in developing countries. Colon-targeted chitosan microspheres (Ms) comprising of lipase­zinc and lipase­copper complexes were prepared, loaded with Attapulgite (Cts-Li-Zn-ATG/Ms and Cts-Li-Cu-ATG/Ms) for the treatment of bacterial diarrhea. Thin layer chromatography (TLC) and Fourier-transform infrared spectroscopy (FTIR) studies were used for confirmation of proposed lipase-metal complexes. Ms showed particle size range 18 ± 0.24 to 23 ± 0.83 µm, zeta potential -13.7 ± 0.71 to -29.3 ± 1.34 mV, PDI 0.5 ± 0.04 to 1.0 ± 0.07 and hemolytic activity was found to be <5 ± 1.25 %. After coating with Eudragit S-100 for colon targeting, in-vitro % drug release of ATG at pH 7.4 was 80 ± 0.21 % for Eud-Cts-Li-Zn-ATG/Ms while it was increased to 83 ± 0.54 % for Eud-Cts-Li-Cu-ATG/Ms within 7 h, respectively. In-vivo anti-diarrheal activity of Eud-Cts-Li-Zn-ATG/Ms and Eud-Cts-Li-Cu-ATG/Ms was performed by oral challenge on albino mice having infectious diarrhea colonized with E. coli. Results revealed significant anti-diarrheal effect of proposed Eud-Cts-Li-Cu-ATG/Ms in terms of weight gain from 24 ± 0.12 g to 26.05 ± 0.31 g, which was 2-fold increase as compared to Eud-Cts-Li-Zn-ATG/Ms. Conclusively, Eud-Cts-Li-Cu-ATG/Ms provides an innovative alternate for the treatment of bacterial diarrhea with additional support of chitosan and lipase for nutritional support and immunity which was compromised in diarrheal patients.

Predictive Value of C-reactive Protein in the Spontaneous Passage of Lower Ureteric Stones: A Prospective Single-Centre Study.

INTRODUCTION: Ureteric stones, characterised by their presence in the ureter, present a common yet often painful urological condition requiring timely intervention. As C-reactive protein (CRP) emerges as a potential biomarker, its correlation with the spontaneous stone passage (SSP) offers valuable insights into patient management and treatment strategies. The present study aimed to assess if CRP levels can predict SSP in symptomatic lower ureteric calculi of size 5 mm-10 mm. MATERIALS AND METHODS: This prospective observational study, conducted at the Indira Gandhi Institute of Medical Sciences in Patna, India, from July 2022 to June 2023, focused on individuals aged 13 to 60 years presenting with ureteric colic and single distal ureteral stones (5 mm-10 mm). Patients underwent comprehensive initial assessment and monitoring, including diagnostic procedures such as a complete blood count, urinalysis, CRP levels, and renal function evaluations. Treatment consisted of hydration encouragement, tamsulosin (0.4 mg) daily administration, and diclofenac (50 mg) as needed. Follow-up assessments at one-month post-treatment involved clinical examination and imaging studies to evaluate treatment efficacy. RESULTS: This study analysed 157 patients with ureteric stones, finding that 76% experienced SSP. Lower CRP levels (≤6 mg/L), along with other laboratory parameters like low white blood cell counts, low neutrophil levels, absence of leukocyturia, absence of hematuria, and lower urine specific gravity, were associated with higher SSP rates. C-reactive protein levels ≤6 mg/L emerged as a strong predictor of SSP in multiple regression analysis. CONCLUSION: The findings underscore the potential utility of CRP as a predictive biomarker in guiding the management and treatment strategies for ureteric stones.

Assessing myBaits Target Capture Sequencing Methodology Using Short-Read Sequencing for Variant Detection in Oat Genomics and Breeding.

The integration of target capture systems with next-generation sequencing has emerged as an efficient tool for exploring specific genetic regions with a high resolution and facilitating the rapid discovery of novel alleles. Despite these advancements, the application of targeted sequencing methodologies, such as the myBaits technology, in polyploid oat species remains relatively unexplored. In this study, we utilized the myBaits target capture method offered by Daicel Arbor Biosciences to detect variants and assess their reliability for variant detection in oat genomics and breeding. Ten oat genotypes were carefully chosen for targeted sequencing, focusing on specific regions on chromosome 2A to detect variants. The selected region harbors 98 genes. Precisely designed baits targeting the genes within these regions were employed for the target capture sequencing. We employed various mappers and variant callers to identify variants. After the identification of variants, we focused on the variants identified via all variants callers to assess the applicability of the myBaits sequencing methodology in oat breeding. In our efforts to validate the identified variants, we focused on two SNPs, one deletion and one insertion identified via all variant callers in the genotypes KF-318 and NOS 819111-70 but absent in the remaining eight genotypes. The Sanger sequencing of targeted SNPs failed to reproduce target capture data obtained through the myBaits technology. Similarly, the validation of deletion and insertion variants via high-resolution melting (HRM) curve analysis also failed to reproduce target capture data, again suggesting limitations in the reliability of the myBaits target capture sequencing using short-read sequencing for variant detection in the oat genome. This study shed light on the importance of exercising caution when employing the myBaits target capture strategy for variant detection in oats. This study provides valuable insights for breeders seeking to advance oat breeding efforts and marker development using myBaits target capture sequencing, emphasizing the significance of methodological sequencing considerations in oat genomics research.

Drug carrier wonders: Synthetic strategies of zeolitic imidazolates frameworks (ZIFs) and their applications in drug delivery and anti-cancer activity.

With the rapid advancement of nanotechnology, stimuli-responsive nanomaterials have emerged as a feasible choice for the designing of controlled drug delivery systems. Zeolitic imidazolates frameworks are a subclass of Metal-organic frameworks (MOFs) that are recognized by their excellent porosity, structural tunability and chemical modifications make them promising materials for loading targeted molecules and therapeutics agents. The biomedical industry uses these porous materials extensively as nano-carriers in drug delivery systems. These MOFs not only possess excellent targeted imaging ability but also cause the death of tumor cells drawing considerable attention in the current framework of anticancer drug delivery systems. In this review, the outline of stability, porosity, mechanism of encapsulation and release of anticancer drug have been reported extensively. In the end, we also discuss a brief outline of current challenges and future perspectives of ZIFs in the biomedical world.

Comprehensive Surgical Audit of Live-Related Donor Nephrectomy: Procedural Parameters, Demographics, Health Assessments, Complications, and Postoperative Outcomes.

BACKGROUND AND OBJECTIVES: End-stage renal disease (ESRD) rates are on the rise globally, including in India. However, the affordability of dialysis treatment remains a significant challenge for many, with costs varying across different regions. Although cost-effective, kidney transplantation faces challenges like a surgeon shortage, lack of infrastructure, and lack of logistic support. The study examines Indian laparoscopic nephrectomy outcomes and their benefits for donor recovery. It covers kidney donor procedural details, demographics, preoperative health evaluations, complications, and one-month follow-up. METHODS: Ethical approval was obtained, and the study involved 102 cases at the Indira Gandhi Institute of Medical Science, Patna, Bihar, India, from 2019 to 2023. Detailed preoperative assessments, postoperative complications, and one-month follow-up analyses were conducted. Statistical analysis employed SPSS version 17 (IBM Corp., Armonk, NY). RESULTS: The results revealed an average surgery time of 152.3 min, blood loss of 205 ± 42 ml, and a hospital stay of 4.6 ± 2.2 days. The study found a female predominance (80.39%), with a mean donor age of 35.9 ± 5.2 years. Preoperative assessments showed robust patient health, with glomerular filtration rate (GFR) exceeding the expected threshold and normal urea levels, creatinine, electrolytes, liver enzymes, bilirubin, albumin, and total protein. Post-nephrectomy complications were reported, with females experiencing more difficulties than males. CONCLUSION: This study underscores the efficiency and safety of laparoscopic nephrectomy in the Indian context, providing valuable insights into donor demographics, preoperative health assessments, complications, and postoperative outcomes. The findings contribute to understanding laparoscopic nephrectomy outcomes and associated risk factors despite certain limitations.

Systematic large-scale application of ClinGen InSiGHT APC -specific ACMG/AMP variant classification criteria substantially alleviates the burden of variants of uncertain significance in ClinVar and LOVD databases.

Background: Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUS), APC-specific ACMG/AMP variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP). Methods: A streamlined algorithm using the APC -specific criteria was developed and applied to assess all APC variants in ClinVar and the InSiGHT international reference APC LOVD variant database. Results: A total of 10,228 unique APC variants were analysed. Among the ClinVar and LOVD variants with an initial classification of (Likely) Benign or (Likely) Pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUS were reclassified into clinically actionable classes, the vast majority as (Likely) Benign. The total number of VUS was reduced by 37%. In 21 out of 36 (58%) promising APC variants that remained VUS despite evidence for pathogenicity, a data mining-driven work-up allowed their reclassification as (Likely) Pathogenic. Conclusions: The application of APC -specific criteria substantially reduced the number of VUS in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalisable model for other gene-/disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUS that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

Molecular characterization of human adenoviruses associated with pediatric respiratory infections in Karachi, Pakistan.

Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic diversity and epidemiology of HAdVs in Pakistan. This study characterized HAdVs in pediatric patients with respiratory tract infections in Karachi, Pakistan, between 2022 and 2023. We analyzed 762 nasopharyngeal samples of children ≤ 5 years. DNA extraction, followed by PCR targeting E2B and hexon genes, was carried out. Data analysis was performed on SPSS 25.0, and phylogenetic analysis of hexon gene was performed on MEGA 11. HAdV was detected in 7.34% (56/762) of patients round the year, but at a significantly higher rate during the winter season. Age was insignificantly associated with HAdV incidence (p = 0.662), but more than 62.5% (35/56) of positive cases were younger than 10 months. The circulating HAdVs were identified as six different types from species B (78.57%) and C (21.42%), with the majority of isolates found to be like B3. HAdV was found to be co-infected with bocavirus (5.4%) and measles (7.14%). These findings revealed a high frequency and genetic diversity of respiratory HAdVs in Karachi, Pakistan. We conclude that periodic and continuous surveillance of adenoviruses and other respiratory pathogens is necessary to improve the prognosis and management of respiratory diseases, thereby reducing the child mortality rate in Pakistan.

Cognitive behaviour therapy as an evidence-based intervention for opioid use disorder: A systematic review.

Objective: To explore the effectiveness of cognitive behaviour therapy as an evidence-based intervention for patients with opioid use disorder and to estimate the effect of cognitive behaviour therapy in mental health care settings. METHODS: The systematic review was conducted from January to April 2023, and comprised search on Web of Science, PsycINFO, Medline, Embase, Google Scholar, Science Direct, PubMed, ClinicalTrials and OvidSP databases for experimental studies and randomised controlled trials related to opioid use disorders published in peer-reviewed English-language journals between December 2022 and April 2023. The studies' quality was assessed using the Modified Cochrane Collaboration risk of the bias assessment criteria. RESULTS: Of the 314 studies initially identified, 42(13%) were subjected to full-text assessment, and 10(23.8%) were analysed. There were 5(50%) studies done in the United States, 2(20%) in Iran, and 1(10%) each in Germany, China and England. All 10(100%) studies were randomised controlled trials with intervention-based cognitive behaviour therapy, and reported significant results in patients diagnosed with opioid use disorders. Conclusion: All the studies analysed were heterogeneous. Cognitive behaviour therapy had a short-term impact and remained influential in the long term as well in handling cognitive and behaviour setbacks among patients with opioid use disorders.

Towards classification and comprehensive analysis of AI-based COVID-19 diagnostic techniques: A survey.

The unpredictable pandemic came to light at the end of December 2019, known as the novel coronavirus, also termed COVID-19, identified by the World Health Organization (WHO). The virus first originated in Wuhan (China) and rapidly affected most of the world's population. This outbreak's impact is experienced worldwide because it causes high mortality risk, many cases, and economic falls. Around the globe, the total number of cases and deaths reported till November 12, 2022, were >600 million and 6.6 million, respectively. During the period of COVID-19, several diverse diagnostic techniques have been proposed. This work presents a systematic review of COVID-19 diagnostic techniques in response to such acts. Initially, these techniques are classified into different categories based on their working principle and detection modalities, i.e. chest X-ray imaging, cough sound or respiratory patterns, RT-PCR, antigen testing, and antibody testing. After that, a comparative analysis is performed to evaluate these techniques' efficacy which may help to determine an optimum solution for a particular scenario. The findings of the proposed work show that Artificial Intelligence plays a vital role in developing COVID-19 diagnostic techniques which support the healthcare system. The related work can be a footprint for all the researchers, available under a single umbrella. Additionally, all the techniques are long-lasting and can be used for future pandemics.

A Systematic Review on the Mental Health Status of Patients Infected With Monkeypox Virus.

Objectives: This study aims to extract and summarize the literature on the mental health status of patients with monkeypox. Methods: This review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using different databases and publishers such as Scopus, Sage, ScienceDirect, PubMed, BMJ, Wiley Online Library, Wolters Kluwer OVID-SP, and Google Scholar. The literature review was based on monkeypox and mental health. The year of publication was 2021-2023, during the monkeypox disease period. Data were extracted from opinions, editorials, empirical studies, and surveys. Results: Based on the literature related to the mental status of patients with monkeypox, the following themes and subthemes were identified: anxiety and depression, self-harm and suicidal tendencies, neuropsychiatric symptoms, mental health, social stigma, sex workers, vaccination, and stress-related diseases. Conclusion: A review of monkeypox virus infection studies reveals that 25%-50% of patients experience anxiety and depression due to isolation, boredom, and loneliness. Factors such as infected people, a lack of competence among healthcare professionals, and shame over physical symptoms exacerbate mental insults. The implications of society include increased self-harm, suicide, low productivity, fear of stigmatization, and transmission of infection.

Factors affecting the efficiency of equine embryo transfer (EET) in polo mares under subtropical conditions of Pakistan.

Equine embryo transfer (EET) is a prominent technology in the equine breeding industry, and its efficacy is affected by a number of factors. The current study aimed to determine the effects of the breed of donor/recipient mares, estrus/ovulation induction treatment, cooled transportation of embryos, and synchrony between donor and recipient mares on the efficiency of the EET under subtropical conditions of Pakistan. A total of eighty-four (n = 84) Polo-playing donor mares (Argentino-polo = 41 and Anglo-Arab = 43) and seventy (n = 70) recipient mares (light breed = 26 and heavy breed = 44) were used for EET. The donor mares exhibiting natural estrus (n = 28) were detected by teaser a stallion, and corpus luteum (CL) having mares (n = 56) were treated with prostaglandin (150 µg of Cloprostenol) for estrus induction. The mares' follicular growth was monitored through ultrasonography until the dominant follicle's size reached 35 mm or more with a moderate to obvious uterine edema score. Afterward, the mares were treated either with GnRH, i.e., 50 µg of Lecirelin acetate (n = 41) or Ovusyn, i.e., 1500 IU hCG (n = 43). Insemination with chilled semen was performed 24 hours later. The embryos were collected non-surgically, 7 or 8 days after ovulation, from the donor mares. The collected embryos were transferred into the well-synchronized recipient mares as fresh (n = 44) or chilled (n = 26) embryos. The pregnancy after ET was checked through ultrasonography. Statistical analysis revealed that the embryo recovery rate (ERR) remained significantly higher (P<0.05) for the Prostaglandin (PG) treated group of donors as compared to the natural heat group of donors. The breed of donor mares, type of ovulatory treatment given, and day of embryo collection did not significantly (P>0.05) affect the ERR. There was no significant effect of the type (fresh vs chilled), classification, and stage of development of embryo on pregnancy outcomes (P>0.05). ET pregnancy rate was significantly affected by the breed of recipient mares and ovulation synchrony between donor and recipient mares (P<0.05). In conclusion, under the subtropical conditions of Pakistan, PG-based estrus induction of donor mares, breed of recipient mares, and ovulation synchrony between the donor and recipient mares had a substantial effect on the efficiency of EET.

Scald resistance in hybrid rye (Secale cereale): genomic prediction and GWAS.

Rye (Secale cereale L.) is an important cereal crop used for food, beverages, and feed, especially in North-Eastern Europe. While rye is generally more tolerant to biotic and abiotic stresses than other cereals, it still can be infected by several diseases, including scald caused by Rhynchosporium secalis. The aims of this study were to investigate the genetic architecture of scald resistance, to identify genetic markers associated with scald resistance, which could be used in breeding of hybrid rye and to develop a model for genomic prediction for scald resistance. Four datasets with records of scald resistance on a population of 251 hybrid winter rye lines grown in 2 years and at 3 locations were used for this study. Four genomic models were used to obtain variance components and heritabilities of scald resistance. All genomic models included additive genetic effects of the parental components of the hybrids and three of the models included additive-by-additive epistasis and/or dominance effects. All models showed moderate to high broad sense heritabilities in the range of 0.31 (SE 0.05) to 0.76 (0.02). The model without non-additive genetic effects and the model with dominance effects had moderate narrow sense heritabilities ranging from 0.24 (0.06) to 0.55 (0.08). None of the models detected significant non-additive genomic variances, likely due to a limited data size. A genome wide association study was conducted to identify markers associated with scald resistance in hybrid winter rye. In three datasets, the study identified a total of twelve markers as being significantly associated with scald resistance. Only one marker was associated with a major quantitative trait locus (QTL) influencing scald resistance. This marker explained 11-12% of the phenotypic variance in two locations. Evidence of genotype-by-environment interactions was found for scald resistance between one location and the other two locations, which suggested that scald resistance was influenced by different QTLs in different environments. Based on the results of the genomic prediction models and GWAS, scald resistance seems to be a quantitative trait controlled by many minor QTL and one major QTL, and to be influenced by genotype-by-environment interactions.