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.

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.

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.

Urinary Tract Infections in Patients Undergoing Invasive Urodynamic Study: A Prospective Observational Study at a Tertiary Care Centre in Eastern India.

OBJECTIVE: The aim of the study was to find the estimate of the prevalence of urinary tract infections following invasive urodynamic studies (UDS) in a hospital setup and to identify the risk factors related to it. METHOD: A total of 100 patients were enrolled in this prospective observational study after standard preoperative work, which included both urine analysis and culture procedure. The study was carried out from April 2022 to April 2023 at the Department of Urology, Indira Gandhi Institute of Medical Sciences, India. Three days following the UDS test, all the patients underwent repeat urine analysis and culture, besides screening for any lower urinary tract symptoms, abdominal pain, and fever. RESULT: Among all, 14 patients (i.e., 6.1% of 85 individuals) had significant bacteriuria, and six patients (4.7%) developed symptoms of UTI. However, a strong association was observed between the maximal detrusor pressure during voiding (Pdet at Q max) and post-void residue (PVR), which were >20 mL before UDS, along with positive urine cultures after UDS, which was significant at <0.05. CONCLUSION: The study demonstrated that the risk of UTIs with this diagnostic technique is minimal and that prophylactic antibiotic medication is not necessary prior to UDS in all patients.

One pot application of a green chemistry-based finish for cotton fabric, providing hydrophobic, flame retardant, and antimicrobial properties.

Fluorinated and formaldehyde-based compounds impart excellent hydrophobicity and flame-retardant properties to cotton fabrics. However, they come with various health and environmental risks. A novel hydrophobic, flame retardant, and antimicrobial finishing agent free from fluorine and formaldehyde was synthesized. The diammonium phosphate octadecyl citrate (DAPOC) was synthesized by using stearic acid (octadecanoic acid), citric acid (propane-1,2,3-tricarboxylic acid), and diammonium hydrogen phosphate. It was grafted onto the cotton fabrics by employing the conventional pad-dry-cure method. The results indicated that this newly developed finish could be chemically bonded to cotton fabrics through C-O-C covalent bonds. The contact angle of the cotton fabric finished with a 12% concentration of the finishing agent reached 151.9°. Additionally, the finished cotton fabrics displayed evident flame-retardant properties. After undergoing 20 laundering cycles, DAPOC maintained strong hydrophobic and flame-retardant characteristics, demonstrating its durability. The chemical structure of DAPOC was verified by nuclear magnetic resonance spectroscopy (1H-NMR). The thermogravimetric analysis confirmed the flame-retardant nature of the treated cotton fabric samples. Scanning electron microscopy (SEM), Energy dispersive X-ray analysis (EDX), and Fourier-transform infrared spectroscopy (FTIR) results demonstrated the successful grafting of the newly created finish onto the cotton fiber. X-ray diffraction (XRD) spectra depicted that the crystalline structure of finished cotton fabric remained mostly unaltered. Furthermore, the finished cotton fabric exhibited commendable antimicrobial properties due to the inclusion of citric acid.

Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer.

BACKGROUND: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). METHODS: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. RESULTS: Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). CONCLUSION: Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.

Context-dependent accuracy of the cobas plasma separation card for HCV RNA viral load measurement.

Collection and preservation of plasma are challenging in remote or under-resourced settings. The cobas® Plasma Separation Card (PSC) is an alternative specimen type for blood-borne pathogen nucleic acid quantitation. We assessed PSC as a specimen type for HCV RNA quantitation in Pakistan. Plasma from venous blood and PSC from finger prick blood were prepared at two sites: Site 1 (in Lahore, n = 199) consisted of laboratory-based outpatient clinics. Specimens were prepared in the same facility and stored frozen. Site 2 was a catchment area within a resource-limited, semi-urban locality of Islamabad with limited access to healthcare services (n = 151). Community public health outreach staff collected blood and prepared the PSC in the participants' homes. Specimens were transported to the central hepatitis laboratory in Lahore to be stored frozen until tested. HCV RNA testing was performed using the cobas HCV RNA test in a central laboratory. Concordance with respect to RNA detectability was high at Site 1 (97.4%), but lower at Site 2 (82.4%). At Site 1, HCV viral load in plasma and PSC were well correlated across the linear range with a 0.21 log10 IU/mL mean bias toward higher concentrations in PSC. At Site 2, HCV viral load in plasma and PSC were poorly correlated. There was a 0.11 log10 IU/mL mean bias toward higher concentrations in PSC. PSC performance can be excellent in underserved settings where refrigerated transport of traditional specimens is difficult. In very challenging field settings, extra support must be provided to ensure correct specimen collection and handling.

Genotoxic colibactin mutational signature in colorectal cancer is associated with clinicopathological features, specific genomic alterations and better survival.

Background and Aims: The microbiome has long been suspected of a role in colorectal cancer (CRC) tumorigenesis. The mutational signature SBS88 mechanistically links CRC development with the strain of Escherichia coli harboring the pks island that produces the genotoxin colibactin, but the genomic, pathological and survival characteristics associated with SBS88-positive tumors are unknown. Methods: SBS88-positive CRCs were identified from targeted sequencing data from 5,292 CRCs from 17 studies and tested for their association with clinico-pathological features, oncogenic pathways, genomic characteristics and survival. Results: In total, 7.5% (398/5,292) of the CRCs were SBS88-positive, of which 98.7% (392/398) were microsatellite stable/microsatellite instability low (MSS/MSI-L), compared with 80% (3916/4894) of SBS88 negative tumors (p=1.5x10-28). Analysis of MSS/MSI-L CRCs demonstrated that SBS88 positive CRCs were associated with the distal colon (OR=1.84, 95% CI=1.40-2.42, p=1x10-5) and rectum (OR=1.90, 95% CI=1.44-2.51, p=6x10-6) tumor sites compared with the proximal colon. The top seven recurrent somatic mutations associated with SBS88-positive CRCs demonstrated mutational contexts associated with colibactin-induced DNA damage, the strongest of which was the APC:c.835-8A>G mutation (OR=65.5, 95%CI=39.0-110.0, p=3x10-80). Large copy number alterations (CNAs) including CNA loss on 14q and gains on 13q, 16q and 20p were significantly enriched in SBS88-positive CRCs. SBS88-positive CRCs were associated with better CRC-specific survival (p=0.007; hazard ratio of 0.69, 95% CI=0.52-0.90) when stratified by age, sex, study, and by stage. Conclusion: SBS88-positivity, a biomarker of colibactin-induced DNA damage, can identify a novel subtype of CRC characterized by recurrent somatic mutations, copy number alterations and better survival. These findings provide new insights for treatment and prevention strategies for this subtype of CRC.

Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel.

PURPOSE: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. METHODS: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. RESULTS: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). CONCLUSION: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use.

Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family.

Genetic susceptibility to familial colorectal cancer (CRC), including for individuals classified as Familial Colorectal Cancer Type X (FCCTX), remains poorly understood. We describe a multi-generation CRC-affected family segregating pathogenic variants in both BRCA1, a gene associated with breast and ovarian cancer and RNF43, a gene associated with Serrated Polyposis Syndrome (SPS). A single family out of 105 families meeting the criteria for FCCTX (Amsterdam I family history criteria with mismatch repair (MMR)-proficient CRCs) recruited to the Australasian Colorectal Cancer Family Registry (ACCFR; 1998-2008) that underwent whole exome sequencing (WES), was selected for further testing. CRC and polyp tissue from four carriers were molecularly characterized including a single CRC that underwent WES to determine tumor mutational signatures and loss of heterozygosity (LOH) events. Ten carriers of a germline pathogenic variant BRCA1:c.2681_2682delAA p.Lys894ThrfsTer8 and eight carriers of a germline pathogenic variant RNF43:c.988 C > T p.Arg330Ter were identified in this family. Seven members carried both variants, four of which developed CRC. A single carrier of the RNF43 variant met the 2019 World Health Organization (WHO2019) criteria for SPS, developing a BRAF p.V600 wildtype CRC. Loss of the wildtype allele for both BRCA1 and RNF43 variants was observed in three CRC tumors while a LOH event across chromosome 17q encompassing both genes was observed in a CRC. Tumor mutational signature analysis identified the homologous recombination deficiency (HRD)-associated COSMIC signatures SBS3 and ID6 in a CRC for a carrier of both variants. Our findings show digenic inheritance of pathogenic variants in BRCA1 and RNF43 segregating with CRC in a FCCTX family. LOH and evidence of BRCA1-associated HRD supports the importance of both these tumor suppressor genes in CRC tumorigenesis.

Synthesis, characterization, computational assay and anti-inflammatory activity of thiosemicarbazone derivatives: Highly potent and efficacious for COX inhibitors.

Multiple studies in the literature have demonstrated that synthetic compounds containing heterocyclic rings possess a reparative potential against acute and chronic inflammation. In the present study, two novel thiosemicarbazone derivatives based on l-ethyl-6-(thiophen-2-yl)indoline-2,3-dione with different phenyl substituted thiosemicarbazides were synthesized by condensation reaction and the structures of proposed target compounds (KP-2 and KP-5) were confirmed by UV-VIS, FTIR, 1H-NMR and 13C-NMR. In-vitro anti-inflammatory behavior of KP-2 and KP-5 was confirmed by bovine serum albumin (BSA) and ovine serum albumin (OSA) analysis. Acute and chronic anti-inflammatory potential of synthesized compounds were evaluated by using carrageenan and complete Freund's adjuvant (CFA) as inflammation-inducing agents, respectively. Inhibition of pro-inflammatory mediators and prevention of protein denaturation owing to synchronization of more electronegative flouro-groups substituted on phenyl rings along with heterocyclic indoline ring provides anti-inflammatory effects and are corroborated by radiological, histopathological analysis. Additional support was provided through density functional theory (DFT) and molecular docking. KP-5 exhibited excellent lead-likeness based on its physicochemical parameters, making it a viable drug candidate. The synthesized compounds also showed promising ADMET properties, enhancing their potential as therapeutic agents. These findings emphasize the pivotal role of new compounds for drug design and development.

A cost effective communication model for requirements elicitation in global software development.

Requirement elicitation stands as a pivotal activity within requirement engineering, gaining even greater significance in the context of global software development. Effective communication among stakeholders assumes paramount importance in this arena. Factors such as time zone disparities, cultural variations, and language differences exert a formidable impact on communication within the sphere of global software development. These dynamics inevitably impinge upon timely coordination, potentially compromising the software's quality. In response, researchers have proffered communication models tailored for requirement elicitation within the ambit of global software development. The purpose of this study is to conduct an in-depth critical review of existing communication models for demand elicitation in global software development. Through this comprehensive review, we aim to discern prevailing publication trends, provide an introductory overview, and illuminate the strengths and limitations inherent in the existing communication models. By identifying these limitations, we seek to advance a novel, low-cost communication approach designed primarily for demand elicitation in global software development. To culminate our endeavor, we will undertake a case study-based experiment, meticulously designed to assess the efficacy and practical utility of the proposed techniques.

Are pharmacists on the front lines of the opioid epidemic? A cross-sectional study of the practices and competencies of community and hospital pharmacists in Punjab, Pakistan.

INTRODUCTION: Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues. STUDY DESIGN: A cross-sectional study, conducted across Punjab, Pakistan. METHOD: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists. RESULTS: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'. CONCLUSION: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce.

Botanical biopesticides have an influence on tomato quality through pest control and are cost-effective for farmers in developing countries.

Synthetic insecticides heavily applied to manage agricultural pests are highly hazardous to the environment and non-target organisms. Their overuse through repeated treatments in smallholder farming communities is frequent. Botanical biopesticides are ideal for sustainable pest management in agricultural environments by keeping synthetic insecticide use at a minimum. Here we evaluated a locally prepared neem seed extract (NSE) alongside emamectin benzoate against both lepidopteran pests Helicoverpa armigera (Hübner) and Spodoptera exigua (Hübner) on tomato Lycopersicon esculentum Mill under natural field conditions in Pakistan. We compared pest severity, fruit injury, quality, marketability, and cost:benefit ratio (CBR) between treatments. The concentration of azadirachtin A in the NSE was 26.5 ppm. NSE at 2% (20 mL/L) and the emamectin benzoate at the recommended field rate in Pakistan were sprayed weekly throughout the fruiting stage. The pest larvae were significantly more abundant on fruits than on flowers and leaves. Fruit injury and losses were significantly more important in untreated control compared to NSE and emamectin benzoate treatments. NSE efficacy varied with respect to the cultivars used and the seasons. Cultivar Eden harboured more pests than Adventa, and emamectin benzoate suppressed more pest individuals than NSE. Both the insecticidal treatments were comparable in terms of marketable yield productions as well as unmarketable, uninjured, and recovered fruit yields. NSE generated a higher CBR (1: 9.26) than emamectin benzoate (1: 3.23). NSE suppressed pests by acting as an antifeedant, similar to its synthetic counterpart. Smallholder growers can thus use NSE as a cost-effective solution in tomato pest management in Pakistan.

DNA Mismatch Repair Gene Variant Classification: Evaluating the Utility of Somatic Mutations and Mismatch Repair Deficient Colonic Crypts and Endometrial Glands.

Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability to support the ACMG/InSiGHT framework in classifying variants of uncertain clinical significance (VUS) in the MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6xMLH1, 9xMSH2, 6xMSH6, 4xPMS2), underwent targeted tumor sequencing for the presence of microsatellite instability/MMR-deficiency (MSI-H/dMMR) status and identification of a somatic MMR mutation (second hit). Immunohistochemical testing for the presence of dMMR crypts/glands in normal tissue was also performed. The ACMG/InSiGHT framework reclassified 7/25 (28%) VUS to likely pathogenic (LP), three (12%) to benign/likely benign, and 15 (60%) VUS remained unchanged. For the seven re-classified LP variants comprising nine tumors, tumor sequencing confirmed MSI-H/dMMR (8/9, 88.9%) and a second hit (7/9, 77.8%). Of these LP reclassified variants where normal tissue was available, the presence of a dMMR crypt/gland was found in 2/4 (50%). Furthermore, a dMMR endometrial gland in a carrier of an MSH2 exon 1-6 duplication provides further support for an upgrade of this VUS to LP. Our study confirmed that identifying these Lynch syndrome features can improve MMR variant classification, enabling optimal clinical care.

Exploring the role of ranking systems towards university performance improvement: A focus group-based study.

The development of multiple university ranking systems at national and global levels has been driven by increasing interest in improving efficiency in the national educational sector without compromising the demand for international standards. Global university ranking systems play an important role by providing the foundation for competing in this global era. One approach could be developing and evaluating criteria to reduce the unnecessary use of standard, less productive indicators. This study aims to systematically exploit national and global university ranking systems in terms of their indicators and relevance to national educational needs. This study uses two online qualitative focus groups with 10 participants each. The participants were purposively sampled, and the transcribed data from the focus group were thematically analyzed. Findings indicate that university ranking should include indicators like governance and digital presence, as these are missing in global ranking indicators. These findings will guide the development of a university ranking framework that policymakers and universities can implement to improve institutional performance.

Blockchain and PUF-based secure key establishment protocol for cross-domain digital twins in industrial Internet of Things architecture.

INTRODUCTION: The Industrial Internet of Things (IIoT) is a technology that connects devices to collect data and conduct in-depth analysis to provide value-added services to industries. The integration of the physical and digital domains is crucial for unlocking the full potential of the IIoT, and digital twins can facilitate this integration by providing a virtual representation of real-world entities. OBJECTIVES: By combining digital twins with the IIoT, industries can simulate, predict, and control physical behaviors, enabling them to achieve broader value and support industry 4.0 and 5.0. Constituents of cooperative IIoT domains tend to interact and collaborate during their complicated operations. METHODS: To secure such interaction and collaborations, we introduce a blockchain-based cross-domain authentication protocol for IIoT. The blockchain maintains only each domain's dynamic accumulator, which accumulates crucial materials derived from devices, decreasing the overhead. In addition, we use the on-chain accumulator to effectively validate the unlinkable identities of cross-domain IIoT devices. RESULTS: The implementation of the concept reveals the fact that our protocol is efficient and reliable. This efficiency and reliability of our protocol is also substantiated through comparison with state-of-the-art literature. In contrast to related protocols, our protocol exhibits a minimum 22.67% increase in computation cost efficiency and a 16.35% rise in communication cost efficiency. CONCLUSION: The developed protocol guarantees data transfer security across the domain and thwarts IoT devices from potential physical attacks. Additionally, in order to protect privacy, anonymity and unlinkability are also guaranteed.

Predictive value of α-synuclein expression in peripheral blood of multiple sclerosis patients: A two-dimensional assessment of a selected biomarker.

INTRODUCTION: Our study aimed to evaluate whether assessing α-synuclein expression levels in blood samples could provide a reliable and straightforward alternative to existing diagnostic and prognostic methods for neurodegenerative disorders, including multiple sclerosis (MS). We specifically investigated if α-synuclein and IL-6 expression levels from serum and peripheral blood mononuclear cells (PBMCs) could accurately predict MS severity in patients using a two-dimensional approach. METHODS: We designed a case-control study to analyze the expression of α-synuclein and IL-6 in the peripheral blood of an MS patient group (n = 51) and a control group (n = 51). We statistically evaluated the PBMCs and serum profiles of α-synuclein and IL-6 in MS patients, along with their age of onset, disease duration, tobacco exposure, and Expanded Disability Status Scale (EDSS) score, using SPSS V22.0 software and GraphPad Prism V9.0. RESULTS: Our findings indicate that α-synuclein production was significantly downregulated in MS patients. Principal component analysis also revealed distinct profiles between MS patients and controls. PBMCs and serum profiles of α-synuclein correlated with the EDSS score, suggesting that disease severity can be predicted using α-synuclein profiles. Moreover, α-synuclein showed a significant correlation with IL-6 and age of onset. Lastly, receiver operating characteristic curves of PBMCs and serum activity of α-synuclein profiles displayed discrimination with area under the curve values of 0.856 and 0.705, respectively. CONCLUSION: Our results imply that measuring α-synuclein levels in both serum and PBMCs could be a valuable method for diagnosing and predicting MS severity, potentially serving as a non-invasive biomarker for the disease.

A comparison of the ocular features in Pierson and Alport syndrome: a case report and literature review.

BACKGROUND: Pierson syndrome and X-linked Alport syndrome result from pathogenic variants in LAMB2 and COL4A5, respectively, and both affect basement membranes in the kidney and the eye. This study describes the ocular features in an individual with a homozygous LAMB2 pathogenic variant and compares the reported abnormalities in Pierson syndrome with those in Alport syndrome. METHODS: A 28-year-old man who developed kidney failure 10 years previously and subsequently had an atrial septal defect repair was suspected of having genetic kidney disease on the basis of his likely diagnosis of Focal and Segmental Glomerulosclerosis (FSGS), his young age at presentation, and his cardiac anomaly. He then underwent Whole Exome Sequencing and a formal ophthalmological examination. RESULTS: The patient was found to have a homozygous Likely Pathogenic missense variant (p.(Arg1719Cys)) in LAMB2 consistent with the diagnosis of Pierson syndrome. He had normal visual acuity, normal optic globe and cornea size, and normal lens appearance on direct examination. Upon further testing, his cornea demonstrated central thinning. There was also increased corneal endothelial pleomorphism, a reduced foveal reflex, and a blunted foveal curvature, similar to the features seen in X-linked Alport syndrome. CONCLUSION: Our patient had a later onset form of Pierson syndrome or "FSGS type 5, with or without ocular abnormalities," consistent with his "milder" LAMB2 missense variant. The resemblance of the ocular features in Pierson syndrome and X-linked Alport syndrome suggests that mutations in LAMB2 and COL4A5 have similar effects on basement membranes and the pathogenesis of ocular damage.