A Novel Homozygous Loss-of-Function Variant in GPR156 Delineates Non-syndromic Hearing Loss.

Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder accounting for almost 70% of the total congenital hearing loss. The implementation of rapid advanced sequencing methods has significantly contributed to the correct molecular diagnosis for several rare genetic disorders, including NHSL. Features of two probands with NHSL were clinically and genetically evaluated.

Green synthesis of carbon dots (CDs) and their use for selective determination of Pb.

Carbon dots were synthesized from fenugreek seeds through a single step hydrothermal method. The method is simple, fast, pleasant to the environment and cheaper. The CDs were characterized by Fourier Transform Infrared (FTIR), UV-visible spectrophotometer, X-ray diffraction (XRD), High Resolution Transmission electron microscopy (HR-TEM), and fluorescence.

The genetic cause of neurodevelopmental disorders in 30 consanguineous families.

Objective: This study aims to clinically and genetically assess 30 unrelated consanguineous Pakistani families from various ethnic backgrounds, all exhibiting features of neurodevelopmental disorders (NDDs).

Methods: We conducted clinical, genetic, biochemical, and molecular analyses on 30 consanguineous families with NDDs enrolled from various regions of Pakistan. The likely molecular causes of primary microcephaly and NDDs were identified.

Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination.

Background: Threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) are common essential kinases that collaborate in activating the spindle assembly checkpoint (SAC) at the kinetochore, ensuring appropriate chromosome alignment and segregation prior to mitotic exit. Targeting of either TTK or PLK1 has been clinically evaluated in cancer patients; however, dual inhibitors have not yet been pursued. Here we present the and characterization of a first in class, dual TTK/PLK1 inhibitor (BAL0891).

The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells.

OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR) 4 in vitro and in vivo.

Loss-of-function variant in the LRR domain of SLITRK2 implicated in a neurodevelopmental disorder.

Neurodevelopmental disorders are characterized by different combinations of intellectual disability (ID), communication and social skills deficits, and delays in achieving motor or language milestones. SLITRK2 is a postsynaptic cell-adhesion molecule that promotes neurite outgrowth and excitatory synapse development. In the present study, we investigated a single patient segregating Neurodevelopmental disorder.

Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.

Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins.

Prevalence and Association of Transfusion-Transmissible Infections with Age of Blood Donors: A Regional Transfusion Centre Study in Northern Pakistan.

Objective: To evaluate the prevalence and association of Transfusion-Transmissible Infections (TTIs) with age of blood donors in a regional transfusion centre located in Northern Pakistan.

Study Design: Descriptive study. Place and Duration of the Study: Armed Forces Institute of Transfusion, Rawalpindi, Pakistan, from January 2017 to December 2021.

Comparison of Creatine Kinase-MB, Troponin-I, Troponin-T, Triiodothyronine, Thyroxine, Apoprotein-B and Homocysteine between Non-smokers, Smokers at High Altitudes, and Smokers at Sea Level.

Earlier diagnosis of heart disease can occur via awareness of biochemical changes. Keeping this in view, we wanted to determine if there was any difference between biochemical heart parameters between non-smokers (the control group), smokers who live at a high altitude, or smokers who live at sea level. There were 180 participants categorised into three groups, A, B, and C, depending upon their smoking/non-smoking classification, or distance from sea level.

Overlapping neurological phenotypes in two extended consanguineous families with novel variants in the CNTNAP1 and ADGRG1 genes.

Background: Population diversity is important and rare disease isolates can frequently reveal novel homozygous or biallelic mutations that lead to expanded clinical heterogeneity, with diverse clinical presentations.

Methods: The present study describes two consanguineous families with a total of seven affected individuals suffering from a clinically similar severe syndromic neurological disorder, with abnormal development and central nervous system (CNS) and peripheral nervous system (PNS) abnormalities. Whole exome sequencing (WES) and Sanger sequencing followed by 3D protein modeling was performed to identify the disease-causing gene.

Comparative biochemical kinase activity analysis identifies rivoceranib as a highly selective VEGFR2 inhibitor.

Vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis, is highly expressed across numerous tumor types and has been an attractive target for anti-cancer therapy. However, clinical application of available VEGFR2 inhibitors has been challenged by limited efficacy and a wide range of side effects, potentially due to inadequate selectivity for VEGFR2. Thus, development of potent VEGFR2 inhibitors with improved selectivity is needed.

Synthesis of Thieno[3,2-d]pyrimidine Derivatives through Sequential S Ar and Suzuki Reactions as Selective h-NTPDase Inhibitors.

In this study various of thieno[3,2-d]pyrimidine derivatives have been synthesized by treating different secondary amines through aromatic nucleophilic substitution reaction (S Ar) followed by Suzuki reaction with aryl and heteroaryl boronic acids. A bis-Suzuki coupling was also performed to generate bis-aryl thienopyrimidine derivatives. The synthesized compounds were screened for the hydrolytic activity of h-NTPdase1, h-NTPdase2, h-NTPdase3, and h-NTPdase8.

Antimicrobial susceptibility pattern and genotypic characterisation of quinolone and ceftriaxone resistant genes among Salmonella typhi from various regions of Pakistan.

Objective: To determine the current antibiotic resistance patterns and identification of quinolone and ceftriaxone resistant genes among Salmonella enterica subspecies serovar Typhi.

Methods: The prospective study was conducted from September 2018 to March 2019 and comprised samples collected from major hospitals and laboratories in Karachi, Quetta, Lahore, Kharia, Rawalpindi, Islamabad and Peshawar after approval from the institutional ethics review board of Hazara University, Mansehra, Pakistan. Antimicrobial susceptibility of isolates collected from the health facilities was checked using the Kirby Bauer disc diffusion method in line with the Clinical and Laboratory Standards Institute guidelines at the Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan.

Effect of Wide-Spectrum Monochromatic Lights on Growth, Phytochemistry, Nutraceuticals, and Antioxidant Potential of In Vitro Callus Cultures of .

, also called miracle tree, is a pharmaceutically important plant with a multitude of nutritional, medicinal, and therapeutic attributes. In the current study, an in-vitro-based elicitation approach was used to enhance the commercially viable bioactive compounds in an in vitro callus culture of . The callus culture was established and exposed to different monochromatic lights to assess the potentially interactive effects on biomass productions, biosynthesis of pharmaceutically valuable secondary metabolites, and antioxidant activity.

Clinical Application of Rapid Upper Limb Assessment and Nordic Musculoskeletal Questionnaire in Work-Related Musculoskeletal Disorders: A Bibliometric Study.

Assessment of work-related musculoskeletal disorders (WMSDs) using the Rapid Upper Limb Assessment (RULA) and the Nordic Musculoskeletal Questionnaire (NMQ) has become widely accepted and reported in the literature. The objectives of this study are to (1) recognize and describe the topmost 50 cited scientific articles in WMSDs using the RULA and NMQ and (2) explore the factors that contribute to making an article influential. In this bibliometric study, we used the Web of Science and MEDLINE databases to identify the top 50 cited articles published from 1993 to 2022.

Amino Acid-Metabolizing Enzymes in Advanced High-Grade Serous Ovarian Cancer Patients: Value of Ascites as Biomarker Source and Role for IL4I1 and IDO1.

The molecular mechanisms contributing to immune suppression in ovarian cancer are not well understood, hampering the successful application of immunotherapy. Amino acid-metabolizing enzymes are known to contribute to the immune-hostile environment of various tumors through depletion of amino acids and production of immunosuppressive metabolites. We aimed to collectively evaluate the activity of these enzymes in high-grade serous ovarian cancer patients by performing targeted metabolomics on plasma and ascites samples.

The Effect of Melatonin on Analgesia, Anxiety, and Intraocular Pressure (IOP) in Cataract Surgery Under Topical Anesthesia.

Purpose: This study investigated the effect of oral melatonin as a premedication before cataract surgery on pain score, anxiety, surgical conditions, and intraocular pressure (IOP) during cataract surgery with phacoemulsification under topical anesthesia.

Design: This randomized, double-blind prospective study was conducted among 120 patients aged 50 to 80.

Methods: Patients were randomly assigned to receive either sublingual melatonin 3 mg or placebo 60 min before surgery.

Polymorphism and phylogenetic analysis of FecB and FecG genes in native sheep of Meghalaya, India.

The present study was conducted to identify the polymorphism of two major fecundity genes, viz. FecB and FecG, in indigenous sheep of Meghalaya and to assess phylogenetic relationship with 15 breeds of sheep and to estimate the sequence distances between them. Blood samples were collected from 50 adult ewes and PCR-RFLP was performed to detect the polymorphism of these genes.

Comparative kinase and cancer cell panel profiling of kinase inhibitors approved for clinical use from 2018 to 2020.

During the last two decades, kinase inhibitors have become the major drug class for targeted cancer therapy. Although the number of approved kinase inhibitors increases rapidly, comprehensive profiling and comparison of inhibitor activities is often lacking in the public domain. Here we report the extensive profiling and comparison of 21 kinase inhibitors approved by the FDA for oncology indications since June 2018 and 13 previously approved comparators on panels of 255 biochemical kinase assays and 134 cancer cell line viability assays.

Correlated stochastic epidemic model for the dynamics of SARS-CoV-2 with vaccination.

In this paper, we propose a mathematical model to describe the influence of the SARS-CoV-2 virus with correlated sources of randomness and with vaccination. The total human population is divided into three groups susceptible, infected, and recovered. Each population group of the model is assumed to be subject to various types of randomness.

Heat transfer analysis: convective-radiative moving exponential porous fins with internal heat generation.

The efficiency, temperature distribution, and temperature at the tip of straight rectangular, growing and decaying moving exponential fins are investigated in this article. The influence of internal heat generation, surface and surrounding temperatures, convection-conduction, Peclet number and radiation-conduction is studied numerically on the efficiency, temperature profile, and temperature at the tip of the fin. Differential transform method is used to investigate the problem.

Haematological Traits in Symptomatic and Asymptomatic COVID-19 Positive Patients for Predicting Severity and Hospitalization.

Objective: The present investigation aims on the clinical attributes and haematological parameters between symptomatic (COVID-19 ICU) and asymptomatic (COVID-19 homes isolation) patients as predisposing sign for COVID-19 related mortality.

Materials And Methods: A retrospective cohort research was conducted of admitted patients to ICU, who were suffering from severe COVID-19 in Aseer Central Hospital, Abha, Kingdom of Saudi Arabia (KSA) from July 2020 until September 2020. The study included individuals with COVID -19 and ICU admission as symptomatic group and others who are COVID-19 positives with quarantine as asymptomatic group.

Screening of the antioxidant and antibacterial effects of extracted essential oils from Thunbergia coccinea, Acacia polyacantha, Polygonum micrpcephallum, Abies spectabilis and Clerodendrum colebrookianum.

During the previous few decades, it has been seen that there is a rapid emergence of pathogens resistant to multiple antibiotics. This has now become a global crisis. Some unexplored or less explored plants also provide some antibacterial, bactericidal and antioxidant properties.

Health care associated Clostridioides difficile infection and colonization in patients admitted at tertiary care hospital Pakistan.

Objectives: To evaluate the epidemiology of clostridioides difficile infections and colonisation in a tertiary-care setting.

Methods: The cross-sectional study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, from June 1, 2017, to October 31, 2019, and comprised adult patients admitted in high-risk units of the hospital for any disease experiencing watery stools after 48 hours of hospital admission and passing more than 3 stools per day with no other recognised aetiology. Stool samples of the participants, diagnosed with antibiotic associated diarrhoea, were submitted for glutamate dehydrogenase antigen assay and clostridioides toxin A/B assay detected by enzyme-linked immunosorbent assay and clostridioides difficile toxin gene detection by polymerase chain reaction.