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Abstract The female reproductive system dysfunction considerably affects the overall health of women and children on a global scale. Over the decade, the incidence of reproductive disorders has become a significant source of suffering for women. Infertility in women may be caused by a range of acquired and congenital abnormalities. Ovaries play a central role in the female reproductive function. Any defect in the normal functioning of these endocrine organs causes health issues and reproductive challenges extending beyond infertility, as the hormones interact with other tissues and biological processes in the body. The complex pathophysiology of ovarian disorders makes it a multifactorial disease. The key etiological factors associated with the diseases include genetic factors, hormonal imbalance, environmental and lifestyle factors, inflammatory conditions, oxidative stress, autoimmune diseases, metabolic factors, and age. Oxidative stress is a major contributor to disease development and progression affecting the oocyte quality, fertilization, embryo development, and implantation. The choice of treatment for ovarian disorders varies among individuals and has associated complications. Reproductive tissue engineering holds great promise for overcoming the challenges associated with the current therapeutic approach to tissue regeneration. Furthermore, incorporating nanotechnology into tissue engineering could offer an efficient treatment strategy. This review provides an overview of incorporating antioxidant nanomaterials for engineering ovarian tissue to address the disease recurrence and associated pathophysiology. Cerium oxide nanoparticles (CeO2 NPs) are prioritized for evaluation primarily due to their antioxidant properties. In conclusion, the review explores the potential applications of CeO2 NPs for effective and clinically significant ovarian tissue regeneration. Graphical Abstract

Background: There is a paucity of data on the optimal threshold of oestradiol (E2) levels required for successful implantation as this is a valid question to be answered, considering that significant number of in vitro fertilisation cycles are deferred for FET cycles. Aim: The aim of this study is to investigate the serum E2 levels before starting exogenous progesterone in artificial autologous frozen thawed embryo transfers on pregnancy outcomes. Settings and Design: This was a cohort study wherein clinical data of 213 artificial autologous programmed hormone-regulated frozen embryo transfer (HR-FET) cycles were collected. Materials and Methods: The HR-FET cycles were divided into three groups based on the E2 levels before starting progesterone: Group A: E2 ≤300 pg/mL, Group B: E2 301–500 pg/mL and Group C: E2 >500 pg/mL. After adequate endometrial stripe was appreciated by transvaginal ultrasonography, single blastocyst transfer was performed in all the cycles. Statistical Analysis Used and Results: The clinical pregnancy rate (CPR) in Groups A, B and C were 41.8%, 73.5% and 0.95%, respectively (P = 0.0001). The live birth rate (LBR) in Groups A, B and C was 18.1%, 62.2% and 0%, respectively (P = 0.0001). The miscarriage rate (MR) was significantly lower (15.3%) when E2 was between 301 and 500 pg/mL (P = 0.001). At both the extremes of serum E2 values, the rate of miscarriage increased. If serum E2 levels were ≤300 pg/mL or >500 pg/mL, the rate of miscarriage was 56.5% and 100%, respectively. Conclusion: Serum E2 levels in the range of 301–500 pg/mL before starting progesterone in programmed FET cycle are associated with an improved CPR and LBR and also decreased MR as compared to the extreme values of E2 ≤300 pg/mL or >500 pg/mL.

Availability is the key system effectiveness measure in process industries, manufacturing plants, and treatment plants like sewage, e-waste etc. The nut-bolt manufacturing industry is very prominent in manufacturing sector. The present work is proposed with a motto to develop a stochastic framework for a nut manufacturing plant to derive steady state availability and its optimization. The Markov birth death approach is applied to develop the stochastic model as well as Chapman-Kolmogorov differential difference equations of the system. The availability function derived using Markov approach is treated as objective function of the optimization problem having decision parameters as failure and repair rates. All the decision variables are considered as exponentially distributed which are i.i.d. in nature. The objective function is optimized using particle swarm optimization to predict the optimal availability and estimated parametric values. The most sensitive component of the system is observed through making variation in failure and repair rates. It is revealed that PSO predicts the optimal availability 0.9999 at population size 50 after 50 iterations. The convergence rate of PSO is very fast in prediction of the availability of nut manufacturing plant. These findings are beneficial for system designers and maintenance engineers to propose the maintenance strategies. The proposed methodology can be utilized to predict the availability of other process industries.

Diabetic cardiomyopathy (DCM) represents a critical complication of Diabetes mellitus (DM), characterized by structural and functional changes in the myocardium independent of coronary artery disease or hypertension. Emerging evidence highlights the significant roles of phytochemicals, particularly astilbin and apigenin, in modulating key molecular pathways implicated in DCM. This review synthesizes current mechanistic insights and therapeutic potential of these compounds, focusing on their interactions with AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), O-linked N-acetylglucosamine (O-GlcNAc), sodium-glucose co-transporter 2 (SGLT2), protein kinase C (PKC), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways. Astilbin and apigenin have demonstrated the ability to improve cardiac function, mitigate oxidative stress, and reduce inflammatory responses in diabetic conditions. By activating AMPK and PPARs, these flavonoids enhance glucose uptake and fatty acid oxidation, contributing to improved metabolic homeostasis. Their inhibition of O-GlcNAcylation, SGLT2 activity, and PKC signaling further attenuates hyperglycemia-induced cellular damage. Additionally, suppression of NF-κB, MAPK, and JNK pathways by astilbin and apigenin results in reduced pro-inflammatory cytokine production and apoptotic cell death. Collectively, these interactions position astilbin and apigenin as promising therapeutic agents for ameliorating DCM, offering novel avenues for treatment strategies aimed at modulating multiple pathogenic pathways.

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications:: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Availability plays an imperative role in the effectiveness investigation and performance evaluation of any manufacturing plant. The bolt manufacturing industry is one such plant. The present study is conducted with the motto of building a novel stochastic model of a bolt manufacturing plant (BMP) to derive availability along with its optimisation using metaheuristic approaches. The Markov birth-death process is adopted to build the stochastic model, as the breakdown and restore rates of the parts exhibit constant behaviour. The availability function is treated as an objective function of the optimisation problem, considering breakdown and restore rates as determination parameters. The availability function is optimised using particle swarm optimisation (PSO) and a genetic algorithm (GA) to forecast the optimal availability and estimated parametric values. The highly susceptible part of the system is observed after a 10% deviation in breakdown and restoration rates. It is viewed that the PSO algorithm predicts the optimal value of availability as 0.999429 after 30 iterations at 100 swarm size, while GA reached only up to 0.94791544 at a population size of 1000 after 100 iterations. The convergence rate of PSO is very fast in predicting the availability of plants. These results are valuable for organisational engineers and maintenance engineers to propose maintenance strategies. The suggested approach can be employed to predict the availability of other process industries.

Summary: Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the development of disease pathology. Here, we report a novel antigen Plasmodium prohibitin “PfPHB2” and identify its cognate partner “Hsp70A1A” in host erythrocyte that plays a crucial role in mediating host-parasite interaction during merozoite invasion. Using small interfering RNA (siRNA)- and glucosamine-6-phosphate riboswitch (glmS) ribozyme-mediated approach, we show that loss of Hsp70A1A in red blood cells (RBCs) or PfPHB2 in infected red blood cells (iRBCs), respectively, inhibit PfPHB2-Hsp70A1A interaction leading to invasion inhibition. Antibodies targeting PfPHB2 and monoclonal antibody therapeutics against Hsp70A1A efficiently block parasite invasion. Recombinant PfPHB2 binds to RBCs which is inhibited by anti-PfPHB2 antibody and monoclonal antibody against Hsp70A1A. The validation of PfPHB2 to serve as antigen is further supported by detection of anti-PfPHB2 antibody in patient sera. Overall, this study proposes PfPHB2 as vaccine candidate and highlights the use of monoclonal antibody therapeutics for future malaria treatment.

Abstract Future targets are a promising prospect to overcome the limitation of conventional and current approaches by providing secure and effective treatment without compromising patient compliance. Diabetes mellitus is a fast-growing problem that has been raised worldwide, from 4% to 6.4% (around 285 million people) in past 30 years. This number may increase to 430 million people in the coming years if there is no better treatment or cure is available. Ageing, obesity and sedentary lifestyle are the key reasons for the worsening of this disease. It always had been a vital challenge, to explore new treatment which could safely and effectively manage diabetes mellitus without compromising patient compliance. Researchers are regularly trying to find out the permanent treatment of this chronic and life threatening disease. In this journey, there are various treatments available in market to manage diabetes mellitus such as insulin, GLP-1 agonist, biguanides, sulphonyl ureas, glinides, thiazolidinediones targeting the receptors which are discovered decade before. PPAR, GIP, FFA1, melatonin are the recent targets that already in the focus for developing new therapies in the treatment of diabetes. Inspite of numerous preclinical studies very few clinical data available due to which this process is in its initial phase. The review also focuses on the receptors like GPCR 119, GPER, Vaspin, Metrnl, Fetuin-A that have role in insulin regulation and have potential to become future targets in treatment for diabetes that may be effective and safer as compared to the conventional and current treatment approaches. Graphical Abstract

Introduction: In edentulous individuals, single implant-retained mandibular overdentures are an effective substitute for double implant-retained overdentures. In this current research, the oral health-related quality of life (OHRQoL) was assessed for the immediate loading overdenture using the implants. The comparisons are drawn between the single and double implants. Materials and Methods: Forty subjects received single and double implants for the placement of the mandibular overdentures. Within a week days of implant insertion, they were loaded with overdentures. Using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, the OHRQoL was measured before treatment, one month following treatment, and 12 months thereafter. Results: In both the single implant and double implant groups, participants' mean OHIP-14 scores decreased statistically significantly for the different timelines. For the single implant group, the baseline total mean OHIP-14 score was 14.33, and for double implants, it was 19.15. Following therapy, it decreased to 8.55 in the single implant group and 9.48 for the double implant group at one month, and at 12 months, it further decreased to 3.25 in the single implant group while it was 5.15 in the double implant group. Conclusions: Single and double implants increase the QoL for older subjects who are edentulous at the 1-month and 1-year recall points. When two implants are used by older individuals, the single implant might offer an equivalent quality of life.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder that is characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness is often restricted and may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible therapeutic agents for RA disease. The objective of this review is to summarize the existing preclinical and clinical evidence regarding the efficacy of naturally extracted compounds and plant extracts in the treatment of RA, focusing on their anti-inflammatory, anti-oxidative, and immunomodulatory properties. Some of the problems with using natural chemicals are the uneven quality of commercially available preparations and the poor bioavailability of these compounds. Future investigations should focus on improving the formulations, conducting thorough clinical trials, and exploring different techniques to fully utilize the intrinsic potential of naturally derived chemicals in treating RA.

Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases.

Purpose: Reliability and maintainability are the key system effectiveness measures in process and manufacturing industries, and treatment plants, especially in E-waste management plants. The present work is proposed with a motto to develop a stochastic framework for the e-waste management plant to optimize its availability integrated with reliability, availability, maintainability, and dependability (RAMD) measures and Markovian analysis to estimate the steady-state availability of the E-waste management plant. In the analysis an effort is also made to identify the best performing algorithm for availability optimization of the e-waste plant. Methodology: A stochastic model for a particular plant is developed and its availability is optimized using various metaheuristic approaches like a genetic algorithm (GA), particle swarm optimization (PSO), and differential evolutions (DE). The most sensitive component is identified using RAMD methodology while the effect of deviation in various failure and repair rates are observed by the proposed model. The failure and repair rates follow an exponential distribution. All time-dependent random variables are statistically independent. Originality/Novelties: A novel stochastic model is presented for an e-waste management plant and optimum availability is obtained using metaheuristic approaches. The proposed methodology is not so far discussed in the reliability analysis of process industries. Findings: The numerical results of the proposed model compared to identify the most efficient algorithm. It is observed that genetic algorithm provides the maximum value (0.92330969) of availability at a population size 2500 after 500 iterations. PSO algorithm attained the maximum value (0.99996744) of availability just after 50 iterations and 100 population size. So, its rate of convergence is faster than GA. The optimum value of availability is 0.99997 using differential evolution after 500 iterations and population size of more than 1000. These findings are very beneficial for system designers. Practical Implications: The proposed methodology can be utilized to find the reliability measures of other process industries.

Summary: Cold shock proteins are characterized by the presence of one or more cold shock domains that bestow them with nucleic acid binding ability. Although cold shock proteins are well characterized in bacteria, plants and humans, there is no information on their existence and role in malaria parasite. Here, we have identified and delineated the function of a cold shock protein of Plasmodium falciparum (Pf) ‘PfCoSP’. We demonstrate that PfCoSP exhibits nucleic acid binding properties and regulates gene expression. PfCoSP promotes microtubule assembly by interacting with Pf α/β tubulin. We identified a human cold shock protein LIN28A inhibitor ‘LI71’ as a binding partner of PfCoSP which inhibited PfCoSP–DNA and α/β tubulin interactions and, also inhibited the development of asexual blood stages and gametocyte stage of malaria parasite. Because PfCoSP is essential for parasite survival, characterization of its interacting partners may form the basis for development of future anti-malarials.

Metaheuristic algorithms are extensively utilized to find solutions and optimize complex industrial systems’ performance. In this paper, metaheuristic algorithms are utilized to predict the optimum value of the operational availability of a cooling tower in a steam turbine power plant. These techniques have some flaws like poor convergence speed, being stuck in local optima, and premature convergence. For this purpose, a novel efficient stochastic model is proposed for a cooling tower that is configured with six subsystems. The Markovian birth-death process is utilized to develop the Chapman-Kolmogorov differential-difference equations. All the random variables are statically independent, and repairs are perfect. Failure rates are exponentially distributed, while repair rates follow the arbitrary distribution. Steady-state availability (SSA) of the system is derived concerning various failure and repair rates. The sensitivity analysis of SSA is also performed to identify the most critical component. Further, system availability is optimized using genetic algorithm (GA) and particle swarm optimization (PSO) because they are found to be more suitable for such types of problems. It is revealed that the PSO outperforms GA in predicting the availability of cooling towers used in steam turbine power plants.

Background: Optimal incubation period for oocyte competence remains contentious despite intracytoplasmic sperm injection(ICSI) being in practice for 34 years. Dilemma exists as the current literature favors both early and delayed denudation with equivocal results. With ever-rising demand for the procedure this conundrum continues to plague the clinical outcomes. Aims: This study attempts to provide a consensus regarding optimal time duration required for incubating the oocytes after oocyte pickup(OPU) and time to perform ICSI. Settings and Design: A retrospective study in a tertiary centre. Materials and Methods: A retrospective 10-year cohort study including 726 ICSI cycles was conducted in a single tertiary care infertility centre. All cycles comprised at least one metaphase-II oocyte injected with one good quality sperm followed by fresh embryo transfer. The cohort was broadly divided into two groups: (a) Group 1: OPU-ICSI 4 hours(n=260). Statistical Analysis Used: The fertilization(FR) and clinical pregnancy rates(CPR) were compared using the Pearson Chi-square test. The OPU-ICSI interval were subdivided into one-hourly intervals and CPR was compared after adjustment for multiple comparisons by holm method. Results: The FR and CPR were similar between Group 1 and Group 2(p>0.05). Comparing CPR for each one-hourly OPU-ICSI interval revealed no significant clinical difference (p>0.05) amongst one another, however, the CPR was maximum for 2-3 hours as the OPU-ICSI interval. Conclusion: With no significant clinical difference amongst various temporal groups, this study advocates and reinstates 2-6 hours as the optimal timing for ICSI after the OPU. This will also translate into better time management for both embryologists and clinicians and help them prioritise the laboratory workflow.

Metaheuristic techniques have been utilized extensively to predict industrial systems' optimum availability. This prediction phenomenon is known as the NP-hard problem. Though, most of the existing methods fail to attain the optimal solution due to several limitations like slow rate of convergence, weak computational speed, stuck in local optima, etc. Consequently, in the present study, an effort has been made to develop a novel mathematical model for power generating units assembled in sewage treatment plants. Markov birth-death process is adopted for model development and generation of Chapman-Kolmogorov differential-difference equations. The global solution is discovered using metaheuristic techniques, namely genetic algorithm and particle swarm optimization. All time-dependent random variables associated with failure rates are considered exponentially distributed, while repair rates follow the arbitrary distribution. The repair and switch devices are perfect and random variables are independent. The numerical results of system availability have been derived for different values of crossover, mutation, several generations, damping ratio, and population size to attain optimum value. The results were also shared with plant personnel. Statistical investigation of availability results justifies that particle swarm optimization outdoes genetic algorithm in predicting the availability of power-generating systems. In present study a Markov model is proposed and optimized for performance evaluation of sewage treatment plant. The developed model is one that can be useful for sewage treatment plant designers in establishing new plants and purposing maintenance policies. The same procedure of performance optimization can be adopted in other process industries too.

The work reported in present study deals with the development of a novel stochastic model and estimation of parameters to assess reliability characteristics for a turbogenerator unit of thermal power plant under classical and Bayesian frameworks. Turbogenerator unit consists of five components namely turbine lubrication, turbine governing, generator oil system, generator gas system and generator excitation system. The concepts of cold standby redundancy and Weibull distributed random variables are used in development of stochastic model. The shape parameter for all the random variables is same while scale parameter is different. Regenerative point technique and semi-Markov approach are used for evaluation of reliability characteristics. Sufficient repair facility always remains available in plant as well as repair done by the repairman is considered perfect. As the life testing experiments are time consuming, so to highlight the importance of proposed model Monte Carlo simulation study is carried out. A comparative analysis is done between true, classical and Bayesian results of MTSF, availability and profit function.

Background and Aims: Various anecdotal cases have been reported regarding platelet rich plasma (PRP), demonstrating successful pregnancy outcomes. But the data still remains elusive, especially for women of Asian ethnicity, who have a rapid decline in ovarian reserve when compared to the Caucasian population. We aim to study the effect of intra-ovarian PRP on live birth rate (LBR) in POSEIDON-3 versus POSEIDON-4 group. Method: Prospective interventional study conducted at tertiary care institute (July 2020-April 2022). 72-women between 20-40 years with idiopathic poor ovarian reserve (AMH[Formula: see text]1.2 ng/ml; AFC[Formula: see text]5) and a normal uterine cavity were enrolled. A 1.5 ml-PRP prepared from 30 ml venous-blood, was instilled in each ovarian stroma between day 6-10 of menses with 3-consecutive months follow-up to assess ovarian-reserve parameters (FSH, AMH, AFC). Patients showing improvement (AFC[Formula: see text] 5) were enrolled in antagonist-IVF cycles and categorised into two groups: POSEIDON-3 vs 4 groups. Paired/signrank test and Independent/ranksum test compared clinical parameters between the two-groups. Results: Out of 72 participants, 16.67% responded in 1 [Formula: see text] month of follow-up (AFC: 5 vs 3, p[Formula: see text]0.001), 43% in 2 [Formula: see text] month (AFC: 6 vs 3, p[Formula: see text]0.001) and 12.5% in 3 [Formula: see text] month (AFC:4 vs 3, p[Formula: see text]0.001). 20 participants showed no improvement. Excluding one, 43 underwent antagonist-cycle. Although number of oocytes retrieved was similar (6.35 ± 1.83 vs 5.75 ± 1.35, p=0.21), the dose of HMG requirement was higher in POSEIDON-4 (1450 ± 96.53 vs 1190.3 ± 66.49, p=0.04) thus depicting the effect of advanced age. There was no significant difference in dose of rFSH requirement (2705.6 ± 48.93 vs 2737 ± 54.74, p=0.71), fertilisation rate (60.86% vs 57.86%, p=0.66), CPR (25% vs 25.8%, p=0.95) and LBR (22.6% vs 16.66%, p=0.66) between the two-groups. Conclusion: Intra-ovarian PRP improves the LBR in low-prognosis patients irrespective of age. PRP improves the ovarian reserve which translates into better reproductive outcomes in a population of women who were planned and counselled for donor-oocyte IVF.

Background and Aims: Recent studies suggests that cell free(cf)-DNA is secreted in the spent culture medium (SCM) during embryo development, this can be used as non-invasive approach for PGTA. We aimed to validate Non-invasive Preimplantation Genetic Testing for aneuploidies (niPGT-A) using cf-DNA from SCM Methods: Prospective cohort study, tertiary centre from January-August 2021-2022. A total of 23 aneuploid/high mosaic embryos were donated by couples who had Trophectoderm (TE) biopsy for aneuploidy testing. All aneuploid blastocyst (WB) that were donated for research were thawed and transferred to RNAase and DNAase free PCR tubes. DNA extraction and amplification are carried out using Sureplex DNA amplification system. Libraries prepared using VeriSeqTM PGS Library Prep kit. A total of 24 libraries were pooled, denatured subjected to Next Gen Sequencing (NGS) using MiSeq system. Copy Number Variation (CNV) visualization and analysis for each sample was carried out using BlueFuse Multi Software. Results: NGS results from SCM and TE were respectively used against same positive control to find out accuracy with corresponding WB. NGS profiles generated from aneuploid WB, were manually analysed for CNV. Quality control(qc) was performed using Illumina qc requirements, only samples satisfying were used for analysis. Out of 23 embryos, 14 were aneuploid and 9 were high mosaic based on TE biopsy. Out of 14 aneuploid blastocysts on TE biopsy, 9 (64%) showed corresponding aneuploidy (full chromosomal concordance) on WB NGS profile. The rest 5 showed aneuploidy or mosaicism of a different chromosome on WB NGS profile. Only 5 out of 23 (21.7%) had full chromosome concordance between SCM and WB. The ploidy concordance between WB vs TE and WB vs SCM was 100% and 69.5% (16/23), which was statistically significant (p[Formula: see text]0.05). The decreased ploidy concordance with SCM could be due to suspected maternal contamination. Conclusions: Aneuploidy testing using Cf DNA in SCM is a promising technique but needs more research.

The main aim of present analysis is to develop a novel efficient and intelligent irrigation system (EIIS). The proposed irrigation system configured using five components arranged in a series configuration along with the internal cold standby redundancy on sensor unit. The failure and repair rates are exponentially distributed. By using the Markovian birth-death process differential difference equations of the model are developed to derive the availability expressions and estimation of parameters. The availability of the system is optimized by employing Grey-Wolf optimization (GWO) and Dragon Fly algorithm (DA) for efficiency and performance evaluation. The derived results are helpful for the system designers.

Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI’s effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.

Reliability, Availability, Maintainability, and Dependability (RAMD) study of Tube-wells Integrated with Underground Pipelines (TIUP) is crucial as they are the backbone of the irrigation system. This study is carried out with an objective to perform RAMD analysis, and Failure Modes and Effects Analysis (FMEA) unified with the development of a novel stochastic model using Markovian approach to estimate the Steady-State Availability (SSA) of the TIUP. A real case study of a conventional TIUP system has been performed to validate theoretical and practical results of the proposed model. The failure and repair rates of all subsystems followed exponential distribution, and their impact on system/subsystem’s availability and other reliability measures has been investigated. All the repairs are perfect and random variables associated with failure and repair rates are statistically independent. The centrifugal pump and power supply units are the most critical components as far as reliability and maintainability aspects. The labor also plays a critical role in the operation of the TIUP system.

Abstract The sphingolipid pool is key regulator of vital cellular functions in Plasmodium falciparum a causative agent for deadly malaria. Erythrocytes, the host for asexual stage of Plasmodium, are major reservoir for Sphingosine-1-phosphate (S1P). Erythrocyte possesses Sphingosine kinase (SphK) that catalyzed its biosynthesis from sphingosine (Sph). Since, Plasmodium lacks SphK homologous protein it can be envisaged that it co-opts sphingolipids from both intraerythrocytic as well as extracellular pools for its growth and development. Herein, by sphingosine-NBD probing, we report that infected erythrocytes imports Sph from extracellular pool, which is converted to S1P and thereby taken by P. falciparum. Next, by targeting of the SphK through specific inhibitor N,N-Dimethylsphingosine DMS, we show a reduction in erythrocyte endogenous S1P pool and SphK-phosphorylation that led to inhibition in growth and development of ring stage P. falciparum. Owing to the role of S1P in erythrocyte glycolysis we analyzed uptake of NBD-Glucose and production of lactate in DMS treated and untreated plasmodium. DMS treatment led to decreased glycolysis in Plasmodium. Interestingly the host free Plasmodium did not show any effect on glycolysis with DMS treatment indicating its host-mediated effect. Further to understand the in-vivo anti-plasmodial effects of exogenous and endogenous erythrocyte S1P level, Sphingosine-1-phosphate lyase (S1PL) inhibitor (THI), S1P and SphK-1 inhibitor (DMS), were used in Plasmodium berghei ANKA (PbA) mice model. DMS treatment led to reduction of endogenous S1P conferred significant decrease in parasite load, whereas the plasma level S1P modulated by (THI) and exogenous S1P have no effect on growth of Plasmodium. This suggested erythrocyte endogenous S1P pool is important for Plasmodium growth whereas the plasma level S1P has no effect. Altogether, this study provides insight on cellular processes regulated by S1P in P. falciparum and highlights the novel mechanistically distinct molecular target i.e. SphK-1.

Aim of the present study was to assess physical activity, nutrition and psychological status of the population during lockdown due to covid-19. Online survey was conducted among 534 participants within the age range of 16-78 years using convenient sampling. Participants from varied regions within India and abroad were enrolled for the present study. Volunteered participants were solicited to take part in a survey that has to be carried out by filling an online questionnaire form available to them as a URL link in the invitation through WhatsApp/Messenger. The gathered data has been compiled, coded and cleaned using Microsoft Excel. Analysis has been carried out employing descriptive and inferential statistics in SPSS 17.0. Majority of participants in the studied population showed significant change in their nutrition and physical activity status due to lockdown. Covid-19 lockdown did limit their daily activities. It also had impacted their psychological status. The current investigation accentuates the need to pursue suitable life style for the maintenance of optimum metabolism and physiology. Sticking to more regular timetable of meals, effective management of stress levels and continued physical activity during the quarantine and in all the following phases of living is desirable.

In modern age of information technology, data is available everywhere in huge amount. Every sector generates lot of data every day. The investigation of each unit of data is not feasible due to limited resources like time, labor, and cost. In such situations, survey sampling is recommended to draw the information about the population parameters. Therefore, the main objective of present study is to develop an estimation method for obtaining the information about population parameter. We propose an optimum estimator for enhanced estimation of population mean in simple random sampling by utilizing the information of the two auxiliary attribute. The expression for bias, mean squared error (MSE) and minimum mean squared error of the proposed estimator are derived up to the first order of approximation and it is shown that the proposed estimator under derived conditions perform better than the existing estimators theoretically. Four population are demonstrated to assess the performance as well as applicability of the proposed estimator. The percentage relative efficiency (PRE) of proposed estimator for all the populations is 209.533, 163.852, 210.398 and 340.578, respectively. The numerical illustrations confirm that the proposed estimator dominates over the existing estimators. • The main objective of present study is to propose a new estimator/method for estimation of population mean using two auxiliary attributes under simple random sampling. • The bias and mean square error of the proposed estimator/method is derived and compared with the existing estimators to compare the efficiency theoretically. • Applications of the proposed method/estimator is highlighted using thorough the real data sets of various sectors.

Sphingosine-1-phosphate (S1P), a bioactive lipid mediator is involved in an array of biological processes and linked to pathological manifestations. Erythrocyte is known as the major reservoir for S1P as they lack S1P-degrading enzymes (S1P lyase and S1P phosphohydrolase) and harbor sphingosine kinase-1 (SphK-1) essential for sphingosine conversion to S1P. Reduced S1P concentration in serum was correlated with disease severity in patients with Plasmodium falciparum and Plasmodium vivax infections. Herein, we aimed to identify the underlying mechanism and contribution of host erythrocytes toward depleted S1P levels in Plasmodium-infected patients vs. healthy individuals. The level and activity of SphK-1 were measured in vitro in both uninfected and cultured P. falciparum-infected erythrocytes. Infected erythrocytes demonstrated a significant decrease in SphK-1 level in a time-dependent manner. We found that 10–42 h post invasion (hpi), SphK1 level was predominantly reduced to ∼50% in rings, trophozoites, and schizonts compared to uninfected erythrocytes. We next analyzed the phosphorylation status of SphK-1, a modification responsible for its activity and S1P production, in both uninfected control and Plasmodium-infected erythrocytes. Almost ∼50% decrease in phosphorylation of SphK-1 was observed that could be corroborated with significant reduction in the production and release of S1P in infected erythrocytes. Serum S1P levels were studied in parallel in P. falciparum (N = 15), P. vivax (N = 36)-infected patients, and healthy controls (N = 6). The findings revealed that S1P concentration was significantly depleted in uncomplicated malaria cases and was found to be lowest in complicated malaria and thrombocytopenia in both P. falciparum and P. vivax-infected groups (∗∗p < 0.01). The lower serum S1P level could be correlated with the reduced platelet count defining the role of S1P level in platelet formation. In conclusion, erythrocyte SphK-1 and S1P levels were studied in Plasmodium-infected individuals and erythrocytes that helped in characterizing the complications associated with malaria and thrombocytopenia, providing insights into the contribution of host erythrocyte biology in malaria pathogenesis. Finally, this study proposes the use of S1P and its analog as a novel adjunct therapy for malaria complications.

Semen contains epithelial cells that can be cultured in vitro. For somatic cell nuclear transfer applications, it is essential to know whether clone(s) produced from semen-derived epithelial cells (SedECs) are healthy and reproductively competent. In this study, the semen and fertility profile of a cloned bull (C1) that was produced from a SedEC were compared with its donor (D1) and with two cloned bulls (C2, C3) that were produced from commonly used skin-derived fibroblast cells (SkdFCs). We observed variations in some fresh semen parameters (ejaculated volume and mass motility), frozen-thawed sperm parameters (plasma membrane integrity, and computer-assisted semen analysis (CASA) indices), but values are within the normal expected range. There was no difference in sperm concentration of ejaculated semen and frozen-thawed semen parameters which include sperm motility, percentage of live and normal morphology sperm, and distance traveled through oestrus mucus. Following in vitro fertilization (IVF) experiments, zygotes from C1 had higher (P

Two biologically important molecules specioside (SS) and verminoside (VS) have been isolated from the ethanolic extract of stem bark of Kigelia pinnata. We have explored the electronic and spectroscopic properties of these two molecules on the basis of the Density Function Theory (DFT) quantum chemical calculations along with the correlations of biological efficacies and the results are presented in this paper. The structures of the molecules were established with the help of spectroscopic techniques (1H, 13C NMR, UV-VIS, FTIR) and chemical reactivity was compared by computed DFT theory using Becke3-Lee-Yang-Parr (B3LYP)/6-31G (d,p) data basis set. UV-Visible spectrum was obtained using Time Dependent DFT method. Electric dipole moment, polarizability, first static hyper polarizability and hyper conjugative interactions were also studied with the aid of natural bond orbital (NBO) analysis of these two compounds. The thermodynamic parameters of these compounds were determined at various temperatures. The HOMO, LUMO, chemical hardness (η), chemical potential (μ), electronegativity (χ), electrophilicity power (ω), the gap energy and NBO analysis of both the compounds have been discussed in this paper. Local reactivity was evaluated through the Fukui function i.

Handwriting is an acquired trait of an individual which is primarily culture and environment dependent. The present study attempts to assess the relative influence of schooling environment and culture upon handwriting features. The paper sets forth the computational and conventional analysis of handwriting samples obtained from two cultural/ethnic groups in India living in the same and different geographical regions. Striking significant differences were observed in key handwriting features between writers of the same cultures who were living in different regions and attended different school settings. Contrary to this, handwriting features were insignificant between writers of different cultures living in the same region at the same school.