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Introduction: RAD51D has been reported as a breast cancer (BC) and ovarian cancer (OC) predisposition gene, particularly among Caucasian populations. We studied the prevalence of RAD51D variants in Pakistani BC/OC patients. Materials and Methods: In total, 371 young or familial BC/OC patients were thoroughly analyzed for RAD51D sequence variants using denaturing high-performance liquid chromatography pursued by DNA sequencing of differentially eluted amplicons. We also assessed the pathogenic effects of novel variants using in-silico algorithms. All detected RAD51D variants were investigated in 400 unaffected controls. Results: No pathogenic RAD51D variant was detected. However, we identified nine unique heterozygous variants. Of these, two missense variants (p.Pro10Leu and p.Ile311Asn) and one intronic variant (c.481-26_23delGTTC) were classified as in silico-predicted variants of uncertain significance, with a frequency of 0.8% (3/371). The p.Pro10Leu variant was detected in a 28-year-old female BC patient of Punjabi ethnic background, whose mother and maternal cousin had BCs at ages 53 and 40, respectively. This variant was also detected in 1/400 (0.25%) healthy controls, where the control subject's daughter had acute lymphoblastic leukemia. The p.Ile311Asn variant was identified in a female BC patient at age 29 of Punjabi ethnicity and in 1/400 (0.25%) healthy controls, where the control subject's daughter had Hodgkin's disease at age 14. A novel intronic variant, c.481-26_-23delGTTC, was found in a 30-year-old Punjabi female BC patient but not in 400 healthy controls. Conclusion: No pathogenic RAD51D variant was identified in the current study. Our study data suggested a negligible association of RAD51D variants with BC/OC risk in Pakistani women.
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The fruit of the jujube tree is high in nutrients and has various health benefits. China is a major producer of jujube, and it is now cultivated all around the world. Numerous studies have demonstrated the nutritional value and potential health advantages of bioactive compounds found in the jujube tree. Furthermore, the jujube tree has a remarkable 7000-year agricultural history. The jujube plant has developed a rich gene pool, making it a valuable resource for germplasm. Different studies have focused on the developmental stages of jujube fruits to identify the optimal time for harvest and to assess the changes in their bioactive natural compounds or products during the process of development but the molecular mechanism underlying the production of bioactive natural products in Z. jujuba is still poorly understood. Moreover, the potential differential expressed genes (DEGs) identified as responsible for the synthesis of these compounds should be further functionally verified. It has been noticed that the contents of total flavonoids, total phenolic, and vitamin C increase significantly during the ripening process, while the contents of soluble sugars and organic acids decrease gradually. In this review, we have also scrutinized the challenges that hinder the utilization of jujube fruit resources and suggested potential areas for further research. As such, our review serves as a valuable resource for the future development of jujube-based nutritional compounds and the incorporation of their nutritional elements into the functional foods industry.
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Digital intervention has been shown to be helpful in improving perinatal mental health. However, the design characteristics of such interventions have not been systematically reviewed. Considering that a lack of support-especially from a partner-is one of the major contributing factors to perinatal depression and anxiety, it is crucial to determine whether digital interventions have included partner participation. In this review, we systematically examined the design characteristics of digital interventions related to perinatal depression and anxiety and aimed to determine whether partner participation was incorporated as part of the interventions. Based on the PRISMA 2020 guidelines, five databases (PubMed, EBSCO, Cochrane, ProQuest, and Scopus) were searched. Narrative results of design characteristics were developed to provide a framework for the design and evaluation of the studies. A total of 12 intervention studies from China, Sweden, Australia, New Zealand, Singapore, Norway, and the United Kingdom were included. Across all studies, internet cognitive behavioral therapy and mindfulness therapy were overwhelmingly utilized as the major intervention approaches. While all studies reported reduced depressive symptoms after the intervention, only four studies reported subsequent decreased levels of both depressive and anxiety symptoms. Only one study included partner support in the intervention. Cognitive behavioral therapy and mindfulness therapy, two of the most common intervention approaches, were found to be effective in alleviating perinatal depression and anxiety. Partner participation should be prioritized in designing digital interventions to ensure comprehensive and easily accessible social support for persons in need.
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BACKGROUND: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome. METHODS: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. RESULTS: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family. CONCLUSIONS: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.
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Factor C1 de la Célula Huésped , Discapacidad Intelectual , Linaje , Humanos , Pakistán , Masculino , Discapacidad Intelectual/genética , Femenino , Factor C1 de la Célula Huésped/genética , Proteínas Supresoras de Tumor/genética , Transactivadores/genética , Niño , Secuenciación del Exoma , PreescolarRESUMEN
Background: Existing research indicated a high prevalence of mental health issues among adolescents. Gender and parenting styles are two factors that may influence adolescents' mental health. Nonetheless, most published studies focused on either secondary school or university students. In contrast, there is a dearth of similar research involving pre-university students. This study aimed to determine the prevalence of mental disorders among pre-university students and their association with parenting styles. Methods: A cross-sectional study via online questionnaire survey was conducted among students from a pre-university college on the East Coast of Malaysia. Convenience sampling was used to recruit the participants. The questionnaire consisted of three parts: i) sociodemographic data, ii) the Parental Authority Questionnaire and Depression, and iii) the Anxiety and Stress Scale (DASS-21). An online invitation to answer the questionnaire was done via the Student Representative Council (SRC). Data were analysed using descriptive statistics and Pearson's chi-square test. Results: A total of 431 participants responded to the online survey. The prevalence of depression, anxiety and stress was 49.0% (n = 210), 68.0% (n = 293) and 37.6% (n = 162), respectively. In addition, father's educational level (χ2 = 10.332, P = 0.001) and the authoritarian parenting style (χ2 = 10.099, P = 0.006) were significantly associated with mental health disorders among adolescents. Conclusion: The prevalence of mental disorders among pre-university students is relatively high. Pre-university admission mental health screening is vital for early detection and intervention of mental disorders among this vulnerable group. Further research is imperative to establish a comprehensive plan of action that targets parental involvement in managing adolescent mental health disorders.
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Current uric acid detection methodologies lack the requisite sensitivity and selectivity for point-of-care applications. Plasmonic sensors, while promising, demand refinement for improved performance. This work introduces a biofunctionalized sensor predicated on surface plasmon resonance to quantify uric acid within physiologically relevant concentration ranges. The sensor employs the covalent immobilization of uricase enzyme using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) crosslinking agents, ensuring the durable adherence of the enzyme onto the sensor probe. Characterization through atomic force microscopy and Fourier transform infrared spectroscopy validate surface alterations. The Langmuir adsorption isotherm model elucidates binding kinetics, revealing a sensor binding affinity of 298.83 (mg/dL)-1, and a maximum adsorption capacity of approximately 1.0751°. The biofunctionalized sensor exhibits a sensitivity of 0.0755°/(mg/dL), a linear correlation coefficient of 0.8313, and a limit of detection of 0.095 mg/dL. Selectivity tests against potentially competing interferents like glucose, ascorbic acid, urea, D-cystine, and creatinine showcase a significant resonance angle shift of 1.1135° for uric acid compared to 0.1853° for interferents at the same concentration. Significantly, at a low uric acid concentration of 0.5 mg/dL, a distinct shift of 0.3706° was observed, setting it apart from the lower values noticed at higher concentrations for all typical interferent samples. The uricase enzyme significantly enhances plasmonic sensors for uric acid detection, showcasing a seamless integration of optical principles and biological recognition elements. These sensors hold promise as vital tools in clinical and point-of-care settings, offering transformative potential in biosensing technologies and the potential to revolutionize healthcare outcomes in biomedicine.
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Técnicas Biosensibles , Enzimas Inmovilizadas , Oro , Resonancia por Plasmón de Superficie , Urato Oxidasa , Ácido Úrico , Urato Oxidasa/química , Ácido Úrico/química , Ácido Úrico/análisis , Oro/química , Humanos , Enzimas Inmovilizadas/química , Técnicas Biosensibles/métodos , Límite de Detección , Nanopartículas del Metal/química , SuccinimidasRESUMEN
Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.
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Antibacterianos , Donantes de Sangre , Farmacorresistencia Bacteriana , Sífilis , Treponema pallidum , Treponema pallidum/genética , Treponema pallidum/efectos de los fármacos , Treponema pallidum/aislamiento & purificación , Humanos , Pakistán/epidemiología , Sífilis/microbiología , Sífilis/epidemiología , Sífilis/sangre , Sífilis/tratamiento farmacológico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Masculino , Femenino , Adulto , Macrólidos/farmacología , ARN Ribosómico 23S/genética , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Doxiciclina/farmacología , Doxiciclina/uso terapéutico , Adulto JovenRESUMEN
Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.
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Respuesta al Choque por Frío , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Ziziphus , Ziziphus/genética , Ziziphus/fisiología , Ziziphus/metabolismo , Respuesta al Choque por Frío/genética , Transcriptoma/genética , Frío , Malondialdehído/metabolismoRESUMEN
The enzyme glutamine synthetase (GLN) is mainly responsible for the assimilation and reassimilation of nitrogen (N) in higher plants. Although the GLN gene has been identified in various plants, there is little information about the GLN family in cotton (Gossypium spp.). To elucidate the roles of GLN genes in cotton, we systematically investigated and characterized the GLN gene family across four cotton species (G. raimondii, G. arboreum, G. hirsutum, and G. barbadense). Our analysis encompassed analysis of members, gene structure, cis-element, intragenomic duplication, and exploration of collinear relationships. Gene duplication analysis indicated that segmental duplication was the primary driving force for the expansion of the GhGLN gene family. Transcriptomic and quantitative real-time reverse-transcription PCR (qRT-PCR) analyses indicated that the GhGLN1.1a gene is responsive to N induction treatment and several abiotic stresses. The results of virus-induced gene silencing revealed that the accumulation and N use efficiency (NUE) of cotton were affected by the inactivation of GhGLN1.1a. This study comprehensively analyzed the GhGLN genes in Gossypium spp., and provides a new perspective on the functional roles of GhGLN1.1a in regulating NUE in cotton.
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Regulación de la Expresión Génica de las Plantas , Glutamato-Amoníaco Ligasa , Gossypium , Nitrógeno , Proteínas de Plantas , Duplicación de Gen , Genes de Plantas , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Gossypium/genética , Gossypium/metabolismo , Familia de Multigenes , Nitrógeno/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
The use of pesticides and the subsequent accumulation of residues in the soil has become a worldwide problem. Organochlorine (OC) pesticides have spread widely in the environment and caused contamination from past agricultural activities. This article reviews the bioremediation of pesticide compounds in soil using microbial enzymes, including the enzymatic degradation pathway and the recent development of enzyme-mediated bioremediation. Enzyme-mediated bioremediation is divided into phase I and phase II, where the former increases the solubility of pesticide compounds through oxidation-reduction and hydrolysis reactions, while the latter transforms toxic pollutants into less toxic or nontoxic products through conjugation reactions. The identified enzymes that can degrade OC insecticides include dehalogenases, phenol hydroxylase, and laccases. Recent developments to improve enzyme-mediated bioremediation include immobilization, encapsulation, and protein engineering, which ensure its stability, recyclability, handling and storage, and better control of the reaction.
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Biodegradación Ambiental , Plaguicidas , Microbiología del Suelo , Contaminantes del Suelo , Plaguicidas/química , Plaguicidas/metabolismo , Contaminantes del Suelo/química , Contaminantes del Suelo/metabolismo , Suelo/químicaRESUMEN
BACKGROUND: Glioblastoma multiforme (GBM), the most prevalent subgroup of neuroepithelial tumors, is characterized by dismal overall survival (OS). Several studies have linked O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation to OS in GBM patients. However, MGMT methylation frequencies vary geographically and across ethnicities, with limited data for South Asian populations, including Pakistan. This study aimed to analyze MGMT promoter methylation in Pakistani GBM patients. METHODS: Consecutive primary GBM patients diagnosed ≥ 18 years-of-age, with no prior chemotherapy or radiotherapy history, were retrospectively selected. DNA was isolated from formalin-fixed-paraffin-embedded tissues. MGMT promoter methylation was analyzed using methylation-specific PCR. Clinical, pathological, and treatment data were assessed using Fisher's exact/Chi-squared tests. OS was calculated using Kaplan-Meier analysis in SPSS 27.0.1. RESULTS: The study included 48 GBM patients, comprising 38 (79.2%) males and 10 (20.8%) females. The median diagnosis age was 49.5 years (range 18-70). MGMT methylation was observed in 87.5% (42/48) of all cases. Patients with MGMT methylation undergoing radiotherapy or radiotherapy plus chemotherapy exhibited significantly improved median OS of 7.2 months (95% CI, 3.7-10.7; P < 0.001) and 16.9 months (95% CI, 15.9-17.9; P < 0.001), respectively, compared to those undergoing surgical resection only (OS: 2.2 months, 95% CI, 0.8-3.6). CONCLUSION: This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.
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Neoplasias Encefálicas , Glioblastoma , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Glioblastoma/patología , Pakistán , Estudios Retrospectivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Metilasas de Modificación del ADN/genética , Metilación de ADN/genética , Enzimas Reparadoras del ADN/genética , ADN , Antineoplásicos Alquilantes/uso terapéutico , Proteínas Supresoras de Tumor/genéticaRESUMEN
Knowing the level of SARS-CoV-2 transmission is crucial for decision-making on Coronavirus disease (COVID-19) handling. Guidelines for measuring SARS-CoV-2 antibodies to estimate seroprevalence are conceptually straightforward and internationally available. However, challenges exist for developing countries with limited laboratory capacity, diverse geographical topography, fragmented health information systems and limited resources such as Indonesia. One year after the first case was confirmed in Indonesia, approximately ten infections were undiagnosed or underreported for every reported case. Under those circumstances, we described the method and lessons learned in conducting nationwide cohort COVID-19 serology surveys in a nation with limited resources, such as Indonesia. â¢Strong cross-sectoral collaboration between ministries and levels of governance (central and subnational) enables strategic use of civil registration database for efficient sampling.â¢All agglomeration districts (highly dense population and urban area) were selected as study sites, and additional non-agglomeration districts were selected using probability-proportional-to-size (PPS).â¢Involving the experienced phlebotomist in community health service provider and district laboratory cut down preparation time.
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Objective: To determine frequencies of causes and renal outcomes of pregnancy related acute kidney injury. Method: This descriptive case series study was conducted in Nephrology unit of a tertiary care hospital of Peshawar, from 1st August 2021 to 31st July 2022.A total of 100 patients with acute kidney injury secondary to obstetric conditions were enrolled via non-probability consecutive sampling technique. While patients with pre-existing renal disease, those with renal stones, or having bilateral small kidneys on ultrasound were excluded from the study. Patients were followed till 12 weeks postpartum period. Underlying obstetrical causes and outcome at 12 weeks postnatal period were determined. Results: The mean age of sample of 100 cases was 29.29 ± 6.45. Mean serum creatinine at presentation was 6.5± 3.13. Majority of patient, 89% were multigravidas. Seventy eight percent patients required hemodialysis. Primary postpartum hemorrhage remained the commonest underlying cause of pregnancy related acute kidney injury in this study. The frequency of persistent renal failure in Pr-AKI (pregnancy related acute kidney injury) in this study was 14%. In about 66% of cases complete recovery occurred. All the underlying obstetrical causes, when adjusted for age, gravidity, place and mode of delivery, had no association with persistent renal failure. Conclusion: Primary postpartum hemorrhage is the predominant cause of pregnancy related acute kidney injury. By the end of 12 weeks postpartum, two third patients recover completely from pregnancy related acute renal injury.
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Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the LTBP3 gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (LTBP3:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (CABP2: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (LTBP3:c.132delG; p.Pro45Argfs*25) and (LTBP3:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of LTBP3 in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of LTBP3. We are reporting LTBP3 variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of LTBP3.
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BACKGROUND: Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB-binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Clinicians need more clinical and genetic evidence to detect and comprehend the phenotypic spectrum of this disorder. METHODS: Exome sequencing was used to identify the disease-causing variants in two affected families A and B from District Kohat and District Karak, Khyber Pakhtunkhwa. Affected individuals from both families presented symptoms of ID, developmental delay and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. RESULTS: In the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP_004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605 + 1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild-type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function. CONCLUSIONS: RSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype-phenotype associations.
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Discapacidad Intelectual , Rabdomiólisis , Síndrome de Rubinstein-Taybi , Humanos , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/química , Discapacidad Intelectual/genética , Mutación , Mutación Missense , Fenotipo , Rabdomiólisis/genética , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/diagnóstico , Síndrome de Rubinstein-Taybi/patologíaRESUMEN
In this study, we present a comprehensive analysis of the laminar time-dependent magnetohydrodynamic (MHD) flow of ethylene glycol-based aluminum oxide nanofluid through a rectangular channel with contracting/expanding porous walls. We investigate the influence of aggregation/non-aggregation of nanoparticles, as well as the presence of thermal radiation. By imposing self-similarities in space and time, we obtain a system of nonlinear ordinary differential equations governing the flow. To solve these equations, we employ a well-known semi-analytical technique known as the Method of Moments (MoM). Additionally, we compare our results with the outcomes achieved through an application of another commonly utilized numerical approach (shooting technique with the Runge-Kutta-Fehlberg scheme). The comparison shows an excellent agreement that endorses the accuracy of the calculated solutions. The velocity and temperature profiles obtained from our analysis exhibit variations due to the changes in involved dimensionless parameters. We present these variations through graphical representations along with their explanations. Interestingly, our study reveals that the aggregation of nanoparticles influences the fluctuations caused by other parameters, and to some extent, suppresses them. Consequently, we observe less deviation among the velocity and temperature curves for the aggregation case compared to the non-aggregation case. These findings have significant implications in real-world engineering and industry. The understanding of the flow behavior of nanofluids through expanding/contracting rectangular channels can aid in the design and optimization of various engineering systems, such as heat exchangers and microfluidic devices. Additionally, our study provides valuable insights into the effects of nanoparticle aggregation and thermal radiation in such systems, offering opportunities for enhancing their efficiency and performance.
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BACKGROUND: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients. METHODS: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls. RESULTS: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers. CONCLUSIONS: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.
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In this research, we utilized artificial neural networks along with the Levenberg-Marquardt algorithm (ANN-LMA) to interpret numerical computations related to the efficiency of heat transfer in a regenerative cooling channel of a rocket engine. We used a mixture of Kerosene and carbon nanotubes (CNTs) for this purpose, examining both single-wall carbon nanotubes and multi-wall carbon nanotubes. The primary equations were converted into a dimensionless form using a similarity transformation technique. To establish a reference dataset for ANN- LMA and to analyze the movement and heat transfer properties of CNTs, we employed a numerical computation method called bvp4c, which is a solver for boundary value problems in ordinary differential equations using finite difference schemes combined with the Lobatto IIIA algorithm in MATLAB mathematical software. The ANN- LMA method was trained, tested and validated using these reference datasets to approximate the solutions of the flow model under different scenarios involving various significant physical parameters. We evaluated the accuracy of the proposed ANN- LMA model by comparing its results with the reference outcomes. We validated the performance of ANN- LMA in solving the Kerosene-based flow with CNTs in a rocket engine through regression analysis, histogram studies, and the calculation of the mean square error. The comprehensive examination of parameters undertaken in this research endeavor is poised to provide invaluable support to aerospace engineers as they endeavor to craft regenerative equipment with optimal efficiency. The pragmatic implications of our study are wide-ranging, encompassing domains as diverse as aerospace technology, materials science, and artificial intelligence. This research holds the potential to catalyze progress across multiple sectors and foster the evolution of increasingly efficient and sustainable systems.
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Adequate soil moisture around the root zone of the crops is essential for optimal plant growth and productivity throughout the crop season, whereas excessive as well as deficient moisture is usually detrimental. A field experiment was conducted on cotton (Gossipium hirsuttum) with three water regimes (viz. well-watered (control); rainfed after one post-sowing irrigation (1-POSI) and rainfed after two post-sowing irrigations (2-POSI)) in main plots and application of eight osmoprotectants in sub plots of Split plot design to quantify the loss of seed cotton yield (SCY) under high and mild moisture stress. The DSSAT-CROPGRO-cotton model was calibrated to validate the response of cotton crop to water stress. Results elucidated that in comparison of well watered (control) crop, 1-POSI and 2-POSI reduced plant height by 13.5-28.4% and lower leaf area index (LAI) by 21.6-37.6%. Pooled analysis revealed that SCY under control was higher by 1,127 kg ha-1 over 1-POSI and 597 kg ha-1 than 2-POSI. The DSSAT-CROPGRO-cotton model fairly simulated the cotton yield as evidenced by good accuracy (d-stat ≥ 0.92) along with lower root mean square error (RMSE) of ≤183.2 kg ha-1; mean absolute percent error (MAPE) ≤6.5% under different irrigation levels. Similarly, simulated and observed biomass also exhibited good agreement with ≥0.98 d-stat; ≤533.7 kg ha-1 RMSE; and ≤4.6% MAPE. The model accurately simulated the periodical LAI, biomass and soil water dynamics as affected by varying water regimes in conformity with periodical observations. Both the experimental and the simulated results confirmed the decline of SCY with any degree of water stress. Thus, a well calibrated DSSAT-CROPGRO-cotton model may be successfully used for estimating the crop performance under varying hydro-climatic conditions.