Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling.

Transmembrane protein 184B (TMEM184B) is an endosomal 7-pass transmembrane protein with evolutionarily conserved roles in synaptic structure and axon degeneration. We report six pediatric cases who have de novo heterozygous variants in TMEM184B; five individuals harbor a rare missense variant, and one individual has an mRNA splice site change. This cohort is unified by overlapping neurodevelopmental deficits including developmental delay, corpus callosum hypoplasia, seizures, and/or microcephaly.

Comparison of Intravesical Bacillus Calmette-Guérin (BCG) and Mitomycin C for the Treatment of Non-Muscle-Invasive Bladder Cancer.

Background Bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) are the two most commonly used intravesical therapies for non-muscle-invasive bladder cancer (NMIBC), yet variability in treatment outcomes and tolerability continues to challenge clinical decision-making. Updated comparisons reflecting current treatment protocols and adherence patterns are needed to inform practice. Objective The objective of this study is to evaluate and compare the efficacy and safety of intravesical BCG versus MMC in the contemporary treatment of NMIBC, focusing on recurrence, progression, and adverse effects over a 24-month follow-up.

Investigating the Frequency of Placenta Previa and the Associated Risk Factors During Pregnancy.

Introduction: Placenta previa (PP) is the abnormal implantation of the placenta over the lower uterine segment, either partially or completely covering the internal os. It is a major cause of maternal and fetal morbidity and mortality. This study aimed to determine its frequency and evaluate the risk factors for PP among pregnant women.

Odontogenic carcinosarcoma: a comprehensive review of clinical and therapeutic insights.

Malignant odontogenic tumors are rare, accounting for only 1%-6.1% of all odontogenic tumors. Among them, odontogenic carcinosarcoma (OCS) is an exceptionally rare and aggressive malignant neoplasm originating from dental tissues.

Why ignore expiry dates on cosmetics? A qualitative study of perceived risk and its implications for cosmetics producers and regulators.

Consumers often use cosmetics long after their expiry date, despite the health risk. This paper aims to understand why and to suggest policy changes that can promote safer practices in cosmetics use. This is the first study to investigate risk perception in relation to expired cosmetics.

The conditionality of COVID-19 vaccine acceptance: A qualitative study in Pakistan.

Understanding both the motivations for vaccination and the causes of vaccine reluctance is necessary for the present worldwide immunization campaigns against the COVID-19 pandemic. The intention of the article is to compile local perspectives and misconceptions about vaccination choices. The intention of this study is to assemble what is usually recognized in cultural context as conspiracies and post-traumatic phase affects in decision making.

RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing.

Green supply chain management practices and triple bottom line performance: Insights from an emerging economy with a mediating and moderating model.

The current study explores the dynamics of business practices in Pakistan's Small and Medium Enterprises (SMEs). This research focusing on how "green supply chain management" (GSCM), Industry 4.0 technologies (IND), total quality management (TQM) and sustainable performance (SP) are interconnected.

Integration of Pakistan's stock market with the stock markets of top ten developed economies.

This study examines the integration of Pakistan's Stock Market with the stock markets of the top ten largest economies in the world-USA, China, Japan, Germany, the UK, India, France, Italy, Brazil, and Canada-from January 2015 to October 2020. To examine long- and short run integration, this study employed Johansen and Juselius co-integration and pair-wise Granger causality tests. In the long run, the results indicated that Pakistan's Stock Market is not integrated with these markets.

Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in (). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects.

A cross-disorder dosage sensitivity map of the human genome.

Rare copy-number variants (rCNVs) include deletions and duplications that occur infrequently in the global human population and can confer substantial risk for disease. In this study, we aimed to quantify the properties of haploinsufficiency (i.e.

An integrated approach towards marble waste management: GIS, SFA, and recycling options.

Marble units generate an enormous amount of non-biodegradable waste during the processing operations and are considered one of the environmentally unfriendly industrial sectors. This sector has become a global nuisance due to its multi-dimensional damaging nature. Therefore, a multidimensional approach is needed to geographically describe the pollution sources, their waste load, collection mechanism, and their proper disposal or reuse.

Marble waste site suitability assessment using the GIS-based AHP model.

Site suitability with regards to environmental protection, public concerns, and the legitimate prerequisite is a basic issue that has been tended to in this study. By and large, marble waste is being unloaded on accessible open spaces or released in water to the close by waterways in the territory, Mohmand marble zone (Shabqadar), Khyber Pakhtunkhwa, Pakistan. Suitability assessment for marble waste collection and disposal was carried out through the integrated approach of analytical hierarchy process (AHP) and geographic information system (GIS) to limit the ecological dangers, public, and government concerns related to marble waste.

Exogenous progesterone-dependent modulation in the follicular dynamics of Bos indicus cattle undergoing repeated ovum pick-up sessions.

The objective of the present study was to evaluate the role of serum progesterone (P4) in follicular dynamics, oocytes' recovery and quality and their in vitro developmental competence during consecutive ovum pick-up (OPU) sessions in Bos indicus dairy cows. Wave-synchronized Sahiwal cattle (n = 20) were randomly divided into treatment (n = 10) and control (n = 10) groups. CIDR was used as a source of external progesterone in the treatment group.

A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss.

Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essential bioenergetic supply to mitochondria, and apoptosis. Here, we present three affected individuals from a consanguineous family of Pakistani origin with variable seizures and intellectual disability.

A GDF5 frameshift mutation segregating with Grebe type chondrodysplasia and brachydactyly type C+ in a 6 generations family: Clinical report and mini review.

Different mutations in the Growth/Differentiation Factor 5 gene (GDF5) have been associated with varying types of skeletal dysplasia, including Grebe type chondrodysplasia (GTC), Hunter-Thompson syndrome, Du Pan Syndrome and Brachydactyly type C (BDC). Heterozygous pathogenic mutations exert milder effects, whereas homozygous mutations are known to manifest more severe phenotypes. In this study, we report a GDF5 frameshift mutation (c.

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy.

Effect of weaning method on body weight, testicular growth, sexual behavior, age of puberty, and testosterone concentration of Beetal bucks.

The current study evaluates the effects of early (8th week) and late (16th week of age) weaning of male goat kids on their body growth, testicular growth, sexual behavior, plasma testosterone concentration, and pubertal age. Early (n = 6) and late (n = 7) weaned Beetal bucks were weekly monitored from 18th to 38th week for their body weight, scrotal circumference, testicular volume, testicular echogenicity (via ultrasonography), sexual activities, and plasma testosterone concentration. In comparison to early-weaned, late-weaned bucks showed a marked increase (p < .

Effect of photoperiodicity and methods of follicular wave emergence on follicle turn-over, recovery and quality of oocytes, and early in-vitro developmental competence of embryos using ovum pick-up in Nili-Ravi buffaloes: Preliminary evidence.

The objectives of the present study were to evaluate the effects of photoperiodicity, gauge (G) of ovum pick-up (OPU) needle, and two methods of follicular wave emergence on follicular turn-over, oocyte recovery (OR), quality of the oocytes (OQ), and early in-vitro developmental competence of embryos in Nili-Ravi buffaloes (n = 20). In 1 experiment, buffaloes (n = 12; 4 buffaloes/season) were randomly assigned to optimize the OPU's (n) either with 17 G or 18 G needle in one of the following seasons: 1) peak breeding season (PBS; Sep-Nov; n = 31), 2) transition breeding season (TBS; Dec-Feb; n = 32), and 3) low breeding season (LBS; Apr-June; n = 32). During 2 experiment, buffaloes (n = 8) were enrolled randomly in a 2 × 2 cross-over design to compare the two methods of wave emergence either using follicular ablation (FA; n = 4), or synchronization protocol (CIDR-EB; n = 4) during PBS.

SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance.

Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features.

Cargo transport along the cytoplasmic microtubular network is essential for neuronal function, and cytoplasmic dynein-1 is an established molecular motor that is critical for neurogenesis and homeostasis. We performed whole-exome sequencing, homozygosity mapping, and chromosomal microarray studies in five individuals from three independent pedigrees and identified likely-pathogenic variants in DYNC1I2 (Dynein Cytoplasmic 1 Intermediate Chain 2), encoding a component of the cytoplasmic dynein 1 complex. In a consanguineous Pakistani family with three affected individuals presenting with microcephaly, severe intellectual disability, simplification of cerebral gyration, corpus callosum hypoplasia, and dysmorphic facial features, we identified a homozygous splice donor site variant (GenBank: NM_001378.