Design and Performance Study of Improved Fuzzy System with Genetic Algorithm

Technical trading relies heavily on analysis, most of which is statistical in nature. When the data to be modeled is nonlinear, imprecise, or complicated, fuzzy inference systems (FISs) are used in conjunction with computational, mathematical, and statistical modeling methodologies to simulate technical trading. Fuzzy logic may be modeled using linear, nonlinear, geometric, dynamic, and integer programming. These techniques, when combined with fuzzy logic, help the decision-maker arrive at a better solution while still facing some degree of ambiguity or uncertainty. The moving average method is a useful metric that may give trade recommendations to aid investors further. While trading signals inform investors of when to purchase and sell, a simple moving average provides no such information. In this research, we suggest a fuzzy moving average approach in which the intensity of trading signals, measured in terms of trading volume, is determined by using the fuzzy logic rule. In this research, we propose using fuzzy logic technical trading rules, which are more resistant to decision-making mistakes, to mitigate the trading uncertainty inherent in the conventional technical indicators method

Simultaneous determination of anti-diabetic drugs

A novel reverse phase, isocratic HPLC method is described to separate five anti-diabetic drugs i.e., glimepiride, metformin, sitagliptin, rosiglitazone and pioglitazone. Nucleosil C18 analytical column was used as stationary phase, while mobile phase consisted of acetonitrile:phosphate buffer: methanol (40/40/20, v/v) pH 2.0. Effluent was monitored at a flow rate 1 mL/min and detected at wavelength of 240 nm. This research produced excellent chromatography over a wide concentration range of 25‑10000 ng/mL. Sepprated and well resolved quantifiable peaks were obtained and test results were linear in this range. Correlation coefficient of more than 0.9990 was witnessed as well as Low %RSD values i.e., maximum 2.0% documented excellent precision of the method. Good recoveries from pharmaecutical (99-101%), urine and plasma samples (>96%) in a range of concentrtion granted very good linearity, accuracy and precision. The projected method has satisfactory applications in quality control of these molecules as well as quantification of these molecules in urine and plasma samples

Experience of Emergency Peripartum Hysterectomies at a Tertiary Care Hospital in Quetta, Pakistan

Emergency peripartum hysterectomy (EPH) is associated with significant morbidity and mortality worldwide. The purpose of our paper was to determine the incidence, morbidity, and mortality of EPH done at our institution; the largest tertiary care government hospital in the city of Quetta, Pakistan. During the study period there were 12,642 deliveries, out of which 46 women had undergone an EPH, translating into an incidence of ∼4 per 1,000 births. Disturbingly, 82.6% of these patients had received no antenatal care prior to their presentation. There were 4 (8.7%) maternal deaths and 31 (67.4%) perinatal deaths. The commonest indication noted was uterine rupture in 21 (45.7%) cases. Lack of antenatal care is indeed a modifiable factor that needs to be addressed to help reduce maternal and fetal morbidity/mortality not only from emergency hysterectomies but also from all other preventable causes

Total Sialic Acid (TSA) Level as a Tumor Marker in the Diagnosis of Oral Cancer

Objective: To estimate serum Total Sialic Acid (TSA) levels in different grades of oral squamous cell carcinoma and to accessit`s utility as a tumor marker in this cancer.Materials and Methods: This study was conducted in 68 adult subjects equally divided into two groups, healthy individualsand patients with oral squamous cell cancer. Under aseptic precautions venous blood was drawn and serum was separated.Estimationof serum total sialic acid level was done according to Spectrophotometeric method of Plucinsky. Statistical analysis was carriedout by using SPSS 19.Results: Total subjects in the study included were 58.82% males and 41.17% females. Mean age of oral cancer patients was48.05 ± 8.82 years. There was significant male predominance with P<0.05. Oral cancer was most common in Tobacco+ Chaliya+ Areca nut and Gutka+pan groups. Mean serum total sialic acid (TSA) level in control group was 60.2 ± 4.27 mg/dl, whereasit was 99.1 ± 18.30 mg/dl in oral cancer group. It was significantly increased in oral cancer group when compared to controlgroup with P value < 0.01. There was progressive elevation in mean serum TSA level in oral squamous cell carcinoma,Conclusion:Estimation of serum total sialic acid level (TSA) in different grades of oral squamous cell carcinoma showedpositive relation with stage of malignancy, specifically with the tumor burden. It can be used as a diagnostic biomarker in oralsquamous cell cancers

Incidence, Management, and Outcome of Molar Pregnancies at a Tertiary Care Hospital in Quetta, Pakistan

Molar pregnancies represent a significant burden of disease on the spectrum of gestational trophoblastic diseases. The incidence appears to be higher in women from South Asia. The purpose of our prospective study was to determine the incidence, presentation, and outcomes of all molar pregnancies at our institution. During the study period, there were a total of 16,625 patients admitted to our department; out of whom 85 patients were diagnosed with a molar pregnancy. Vaginal bleeding was the commonest symptom (94.2%); theca lutein cysts were noted in 39% of the cases. Suction, dilatation, and curettage were noted to be the preferred method in almost all cases; hysterectomy was done in 12 (14.1%) patients. Single-agent chemotherapy was employed in high-risk patients and was well tolerated. Mean followup for these patients was 5.7 months (range 1–24 months). None of these patients developed persistent trophoblastic disease, invasive mole, or choriocarcinoma during the follow-up period

Pregabalin and Tranexamic Acid Evaluation by Two Simple and Sensitive Spectrophotometric Methods

This paper demonstrates colorimetric visible spectrophotometric quantification methods for amino acid, namely, tranexamic acid and pregabalin. Both drugs contain the amino group, and when they are reacted with 2,4-dinitrophenol and 2,4,6-trinitrophenol, they give rise to yellow colored complexes showing absorption maximum at 418 nm and 425 nm, respectively, based on the Lewis acid base reaction. Detailed optimization process and stoichiometric studies were conducted along with investigation of thermodynamic features, that is, association constant and standard free energy changes. The method was linear over the concentration range of 0.02-200 gmL −1 with correlation coefficient of more than 0.9990 in all of the cases. Limit of detection was in range from 0.0041 to 0.0094 gmL −1 and limit of quantification was in the range from 0.0137 to 0.0302 gmL −1 . Excellent recovery in Placebo spiked samples indicated that there is no interference from common excipients. The analytical methods under proposal were successfully applied to determine tranexamic acid and pregabalin in commercial products. -test and ratio were evaluated without noticeable difference between the proposed and reference methods

Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing β-propeller repeats. Despite constituting nearly half of disease-associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1221 in the general and 1/155 in the Jewish Ashkenazi populations. Based on clinical, neuroimaging, and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies

Concentrations of lead, mercury, arsenic, cadmium, manganese, and aluminum in the blood of Pakistani children with and without autism spectrum disorder and their associated factors

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with early onset in utero or childhood. Environmental exposure to six metals (Pb, Hg, As, Cd, Mn, Al) is believed to be associated with ASD directly or interactively with genes. Objective: To assess the association of ASD among Pakistani children with the six metals and genotype frequencies of three GST genes (GSTP1, GSTM1, GSTT1).Methods: We enrolled 30 ASD cases, age 2-12 years old, and 30 age- and sex-matched typically developing (TD) controls in Karachi, Pakistan. We assessed associations of ASD status with various factors using Conditional Logistic Regression models. We also used General Linear Models to assess possible interaction of blood Mn and Pb concentrations with the three GST genes in relation to ASD status.Results: The unadjusted difference between ASD and TD groups in terms of geometric mean blood Pb concentrations was marginally significant (p = 0.05), but for Al concentrations, the adjusted difference was marginally significant (p = 0.06).Conclusions: This is the first study reporting six blood metal concentrations of Pakistani children with ASD. Estimates provided for possible interactions of GST genes with Mn and Pb in relation to ASD status are valuable for designing future similar studies

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders