Various pharmacological agents in the pipeline against intractable epilepsy.

Epilepsy is a noncommunicable chronic neurological disorder affecting people of all ages, with the highest prevalence in low and middle-income countries. Despite the pharmacological armamentarium, the plethora of drugs in the market, and other treatment options, 30%-35% of individuals still show resistance to the current medication, termed intractable epilepsy/drug resistance epilepsy, which contributes to 50% of the mortalities due to epilepsy. Therefore, the development of new drugs and agents is needed to manage this devastating epilepsy. We reviewed the pipeline of drugs in "ClinicalTrials. gov," which is the federal registry of clinical trials to identify drugs and other treatment options in various phases against intractable epilepsy. A total of 31 clinical trials were found regarding intractable epilepsy. Among them, 48.4% (15) are about pharmacological agents, of which 26.6% are in Phase 1, 60% are in Phase 2, and 13.3% are in Phase 3. The mechanism of action or targets of the majority of these agents are different and are more diversified than those of the approved drugs. In this article, we summarized various pharmacological agents in clinical trials, their backgrounds, targets, and mechanisms of action for the treatment of intractable epilepsy. Treatment options other than pharmacological ones, such as devices for brain stimulation, ketogenic diets, gene therapy, and others, are also summarized.

Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease.

Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long-term potentiation (iLTP) and excitatory long-term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.

Lived experiences of COVID-19 patients admitted in isolation wards of healthcare centers in Peshawar, Pakistan: A phenomenological perspective.

The emergence of COVID-19 caused a significant global threat, affecting populations worldwide. Its impact extended beyond just physical health, as it inflicted severe damage and challenges to individuals' well-being, leading to a deterioration in mental health. The lived experiences of patients hold a paramount position to explore and understand their perception of care which can ultimately strengthen the health system's delivery domain. This study explores the lived experiences of patients in the isolation ward, their recovery, and the quality of care being provided in the hospital and its effects on their mental health. Study design: A phenomenological qualitative study using in-depth interviews. Methods: We conducted 11 in-depth interviews of COVID-19 patients admitted to the isolation ward of the public hospitals of Peshawar, Pakistan. Participants who stayed for a minimum of 10 days in an isolation ward were included in this study. Interviews were transcribed and analyzed using NVivo 12 software and generated five themes through inductive analysis. Results: Five themes emerged from the participants' lived experiences: Heading towards the hospital, Health Care Quality, Impact on Mental Health, Recovering from COVID-19 and Back on one's feet. These included all the positive and negative lived experiences. Socio-environmental factors along with their experiences of the disease itself and with the healthcare providers guided their reaction which was important conciliators in their experiences during the pandemic. Conclusion: Based on the findings, the environment of isolation had a major influence on the mental well-being of the individuals involved. Considering the important role of the ward environment in shaping patient experiences and outcomes prompts a reevaluation of healthcare practices and policies. By addressing these factors healthcare systems can strive for greater effectiveness, resilience, and compassion in managing the pandemic's impact on patient care.

CAPTURE: Comprehensive anti-cancer peptide predictor with a unique amino acid sequence encoder.

Anticancer peptides (ACPs) key properties including bioactivity, high efficacy, low toxicity, and lack of drug resistance make them ideal candidates for cancer therapies. To deeply explore the potential of ACPs and accelerate development of cancer therapies, although 53 Artificial Intelligence supported computational predictors have been developed for ACPs and non ACPs classification but only one predictor has been developed for ACPs functional types annotations. Moreover, these predictors extract amino acids distribution patterns to transform peptides sequences into statistical vectors that are further fed to classifiers for discriminating peptides sequences and annotating peptides functional classes. Overall, these predictors remain fail in extracting diverse types of amino acids distribution patterns from peptide sequences. The paper in hand presents a unique CARE encoder that transforms peptides sequences into statistical vectors by extracting 4 different types of distribution patterns including correlation, distribution, composition, and transition. Across public benchmark dataset, proposed encoder potential is explored under two different evaluation settings namely; intrinsic and extrinsic. Extrinsic evaluation indicates that 12 different machine learning classifiers achieve superior performance with the proposed encoder as compared to 55 existing encoders. Furthermore, an intrinsic evaluation reveals that, unlike existing encoders, the proposed encoder generates more discriminative clusters for ACPs and non-ACPs classes. Across 8 public benchmark ACPs and non-ACPs classification datasets, proposed encoder and Adaboost classifier based CAPTURE predictor outperforms existing predictors with an average accuracy, recall and MCC score of 1%, 4%, and 2% respectively. In generalizeability evaluation case study, across 7 benchmark anti-microbial peptides classification datasets, CAPTURE surpasses existing predictors by an average AU-ROC of 2%. CAPTURE predictive pipeline along with label powerset method outperforms state-of-the-art ACPs functional types predictor by 5%, 5%, 5%, 6%, and 3% in terms of average accuracy, subset accuracy, precision, recall, and F1 respectively. CAPTURE web application is available at https://sds_genetic_analysis.opendfki.de/CAPTURE.

Long extrachromosomal circular DNA identification by fusing sequence-derived features of physicochemical properties and nucleotide distribution patterns.

Long extrachromosomal circular DNA (leccDNA) regulates several biological processes such as genomic instability, gene amplification, and oncogenesis. The identification of leccDNA holds significant importance to investigate its potential associations with cancer, autoimmune, cardiovascular, and neurological diseases. In addition, understanding these associations can provide valuable insights about disease mechanisms and potential therapeutic approaches. Conventionally, wet lab-based methods are utilized to identify leccDNA, which are hindered by the need for prior knowledge, and resource-intensive processes, potentially limiting their broader applicability. To empower the process of leccDNA identification across multiple species, the paper in hand presents the very first computational predictor. The proposed iLEC-DNA predictor makes use of SVM classifier along with sequence-derived nucleotide distribution patterns and physicochemical properties-based features. In addition, the study introduces a set of 12 benchmark leccDNA datasets related to three species, namely Homo sapiens (HM), Arabidopsis Thaliana (AT), and Saccharomyces cerevisiae (SC/YS). It performs large-scale experimentation across 12 benchmark datasets under different experimental settings using the proposed predictor, more than 140 baseline predictors, and 858 encoder ensembles. The proposed predictor outperforms baseline predictors and encoder ensembles across diverse leccDNA datasets by producing average performance values of 81.09%, 62.2% and 81.08% in terms of ACC, MCC and AUC-ROC across all the datasets. The source code of the proposed and baseline predictors is available at https://github.com/FAhtisham/Extrachrosmosomal-DNA-Prediction . To facilitate the scientific community, a web application for leccDNA identification is available at https://sds_genetic_analysis.opendfki.de/iLEC_DNA/.

Shedding light on cholecystokinin's role in hippocampal neuroplasticity and memory formation.

The hippocampus is a crucial brain region involved in the process of forming and consolidating memories. Memories are consolidated in the brain through synaptic plasticity, and a key mechanism underlying this process is called long-term potentiation (LTP). Recent research has shown that cholecystokinin (CCK) plays a role in facilitating the formation of LTP, as well as learning and memory consolidation. However, the specific mechanisms by which CCK is involved in hippocampal neuroplasticity and memory formation are complicated or poorly understood. This literature review aims to explore the role of LTP in memory formation, particularly in relation to hippocampal memory, and to discuss the implications of CCK and its receptors in the formation of hippocampal memories. Additionally, we will examine the circuitry of CCK in the hippocampus and propose potential CCK-dependent mechanisms of synaptic plasticity that contribute to memory formation.

Barriers and facilitators to accessing adolescents' mental health services in Karachi: users and providers perspectives.

INTRODUCTION: Adolescents' Mental Healthcare (MHC) is influenced by numerous factors, and adolescents occasionally seek professional help for mental health (MH) issues. These factors become more complex within low-middle-income countries (LMICs); therefore, this study aims to understand barriers and facilitators to access mental health services among adolescents aged 10 to 19 years old from the perspective of users (parents) and providers (Mental Healthcare Providers - MHPs). METHOD: Using a qualitative exploratory design, a semi-structured interview guide was developed using Andersen's health service utilization model. In-depth interviews were conducted with MHPs (n = 21) and parents of adolescents (n = 19) in the psychiatry department of public and private hospitals in Karachi, from October-December 2021. Data was thematically analyzed using an inductive approach. RESULT: The findings revealed a consensus of users and providers in all three categories of the Andersen model and referred the compulsion as the major driving force to MHC access and utilization rather than personal choices. Within pre-disposing, need, and enabling factors; the participants highlighted a unique perspective; users regarded frequent migration, daily wage loss, and women's societal status as barriers while the need for marriage and patient willingness were stated as facilitators. Whereas, MHPs indicated societal tolerance, the burden on the health system, and the absence of Child and Adolescent Mental Health (CAMH) services as major gaps in service delivery. CONCLUSION: Service utilization is mainly facilitated by the severity of illness rather than healthy choices and beliefs, and accessibility and affordability. It is therefore imperative to prioritize adolescent MH through promotion and prevention approaches and address service delivery gaps to prevent treatment delays via task-shifting and capacity building of the health workforce.

Revolutionizing Cancer Care: Advances in Carbon-Based Materials for Diagnosis and Treatment.

Cancer involves intricate pathological mechanisms marked by complexities such as cytotoxicity, drug resistance, stem cell proliferation, and inadequate specificity in current chemotherapy approaches. Cancer therapy has embraced diverse nanomaterials renowned for their unique magnetic, electrical, and optical properties to address these challenges. Despite the expanding corpus of knowledge in this area, there has been less advancement in approving nano drugs for use in clinical settings. Nanotechnology, and more especially the development of intelligent nanomaterials, has had a profound impact on cancer research and treatment in recent years. Due to their large surface area, nanoparticles can adeptly encapsulate diverse compounds. Furthermore, the modification of nanoparticles is achievable through a broad spectrum of bio-based substrates, including DNA, aptamers, RNA, and antibodies. This functionalization substantially enhances their theranostic capabilities. Nanomaterials originating from biological sources outperform their conventionally created counterparts, offering advantages such as reduced toxicity, lower manufacturing costs, and enhanced efficiency. This review uses carbon nanomaterials, including graphene-based materials, carbon nanotubes (CNTs) based nanomaterials, and carbon quantum dots (CQDs), to give a complete overview of various methods used in cancer theranostics. We also discussed their advantages and limitations in cancer diagnosis and treatment settings. Carbon nanomaterials might significantly improve cancer theranostics and pave the way for fresh tumor diagnosis and treatment approaches. More study is needed to determine whether using nano-carriers for targeted medicine delivery may increase material utilization. More insight is required to explore the correlation between heightened cytotoxicity and retention resulting from increased permeability.

Biochemical characterization of bioinspired nanosuspensions from Swertia chirayita extract and their therapeutic effects through nanotechnology approach.

Swertia chirayita is used as a traditional medicinal plant due to its pharmacological activities, including antioxidant, antidiabetic, antimicrobial, and cytotoxic. This study was aimed to evaluate the therapeutic efficacy of newly synthesized nanosuspensions from Swertia chirayita through nanotechnology for enhanced bioactivities. Biochemical characterization was carried out through spectroscopic analyses of HPLC and FTIR. Results revealed that extract contained higher TPCs (569.6 ± 7.8 mg GAE/100 g)) and TFCs (368.5 ± 9.39 mg CE/100 g) than S. chirayita nanosuspension, TPCs (500.6 ± 7.8 500.6 ± 7.8 mg GAE/100 g) and TFCs (229.5± 3.85 mg CE/100 g). Antioxidant activity was evaluated through DPPH scavenging assay, and nanosuspension exhibited a lower DPPH free radical scavenging potential (06 ±3.61) than extract (28.9± 3.85). Anti-dabetic potential was assessed throughα-amylase inhibition and anti-glycation assays. Extract showed higher (41.4%) antiglycation potential than 35.85% nanosuspension and 19.5% α-amylase inhibitory potential than 5% nanosuspension. Biofilm inhibition activity against E. coli was higher in nanosuspension (69.12%) than extract (62.08%). The extract showed high cytotoxicity potential (51.86%) than nanosuspension (33.63%). These nanosuspensions possessed enhanced bioactivities for therapeutic applications could be explored further for the development of new drugs.

Dynamics of Malaria Incidence in Khyber Pakhtunkhwa, Pakistan: Unveiling Rapid Growth Patterns and Forecasting Future Trends.

BACKGROUND: Malaria remains a formidable worldwide health challenge, with approximately half of the global population at high risk of catching the infection. This research study aimed to address the pressing public health issue of malaria's escalating prevalence in Khyber Pakhtunkhwa (KP) province, Pakistan, and endeavors to estimate the trend for the future growth of the infection. METHODS: The data were collected from the IDSRS of KP, covering a period of 5 years from 2018 to 2022. We proposed a hybrid model that integrated Prophet and TBATS methods, allowing us to efficiently capture the complications of the malaria data and improve forecasting accuracy. To ensure an inclusive assessment, we compared the prediction performance of the proposed hybrid model with other widely used time series models, such as ARIMA, ETS, and ANN. The models were developed through R-statistical software (version 4.2.2). RESULTS: For the prediction of malaria incidence, the suggested hybrid model (Prophet and TBATS) surpassed commonly used time series approaches (ARIMA, ETS, and ANN). Hybrid model assessment metrics portrayed higher accuracy and reliability with lower MAE (8913.9), RMSE (3850.2), and MAPE (0.301) values. According to our forecasts, malaria infections were predicted to spread around 99,301 by December 2023. CONCLUSIONS: We found the hybrid model (Prophet and TBATS) outperformed common time series approaches for forecasting malaria. By December 2023, KP's malaria incidence is expected to be around 99,301, making future incidence forecasts important. Policymakers will be able to use these findings to curb disease and implement efficient policies for malaria control.

Structural and thermal investigation of lignocellulosic biomass conversion for enhancing sustainable imperative in progressive organic refinery paradigm for waste-to-energy applications.

The depletion of finite fossil fuel reserves and the severe environmental degradation resulting from human activities have compelled the expeditious development and application of sustainable waste to energy technologies. To encapsulate energy and environment in sustainability paradigm, bio waste based energy production is need to be forged in organic bio refinery setup. According to world bioenergy association, biomass can cover 50 % of the primary energy demand of the world. Therefore, the present study focuses on reforming the energy mix for a clean energy generation, where, sample composition of cotton stalk was acidified in dilute (5% wt.) hydrochloric acid (HCL) for analyzing material burnout patterns in biomass conversion systems utilized in organic bio refinery sector. Advanced thermochemical burning technique, which includes pyrolysis and combustion was applied at four different leaching times from 0 to 180 min under nitrogen environment from 0 °C to 500 °C and air from 500 °C to 900 °C, respectively. Different analyses including proximate, ultimate, gross calorific value (GCV), thermos-gravimetric, kinetic, XRD, FTIR, SEM-EDS were used for analyzing the degradation of demineralized cotton stalk at different treatment rates. Proximate study demonstrated that cotton stalk leaching for 180 min has efficiently infused HCL, leading in a significant increase in fixed carbon and higher heating value of 20.23 % and 12.48%, respectively, as well as a reduction in carbon footprint of around 54.80%. The findings of proximate was validated by GCV analysis and CHNS analysis as value of carbon and hydrogen has shown increasing behavior with the time delay in demineralization Thermo-gravimetric and derivative thermo-gravimetric data analyses shows an increasing trend of conversion efficiency, with the maximum increase of 98 % reported for sample 3H.TT.DEM. XRD characterization has reported 23° to 25° angle for all the observed peaks. Sample 3H.TT.DEM has shown maximum angle inclination along with matured crystalline peak. The latter observations has been validated by FTIR spectroscopy as sample 3H.TT.DEM has reported maximum O-H group formation. Sample 3H.TT.DEM has reported lowest activation energy of 139.51 kJ*mole-1 and lowest reactivity of 0.000293649%*min 0C, due to moderate and stable reactiveness. In SEM examination, increment in pore size and number of pores within the structural matrix of cotton stalk was observed with the enhancement in acidulation process. Furthermore, in EDS analysis, 3H.TT.DEM has shown most balanced distribution of the elements. In this research, sustainable transformation of biomass is envisioned to improve the waste bio refinery system, significantly contributing to the achievement of Sustainable Development Goals 7, 12 and 13.

Association between maternal experiences of intimate partner violence and child stunting: a secondary analysis of the Demographic Health Surveys of four South Asian countries.

OBJECTIVES: To determine the association between maternal exposure to intimate partner violence (IPV) and child stunting using the Demographic Health Survey (DHS) data comparing four South Asian countries. DESIGN: A secondary analysis. SETTING: Data from the seventh round of the DHS data of four South Asian countries; Pakistan, Nepal, India and Maldives. PARTICIPANTS: Married women of reproductive age (15-49 years) from each household were randomly selected, having at least one child less than 5 years of age for whom all anthropometric measures were available. OUTCOME MEASURE: The exposure variable was maternal IPV including, sexual violence, physical violence or both. The outcome variable was moderate or severe stunting, measured based on the height-for-age Z-score of children aged 6-59 months old . Multiple Cox proportional regression analyses were used separately on each country's data to determine the association between maternal IPV and child stunting. RESULTS: The prevalence of IPV among women ranged from 10.17% in the Maldives to 31% in India. The burden of child stunting was the lowest in the Maldives at 14.04% and the highest in Pakistan at 35.86%. The number of severely stunted children was the highest in Pakistan (16.60%), followed by India (14.79%). In India, children whose mothers were exposed to IPV showed a 7% increase in the prevalence of moderate to severe child stunting (OR 1.07; 95% CI 1.01 to 1.14). Additionally, in Nepal, severe stunting was strongly associated with the prevalence of physical IPV (OR 1.66; 95% CI 1.01 to 2.87). CONCLUSION: Our study findings suggest that maternal exposure to IPV is associated with child stunting. Further research investigating the relationship between IPV and child outcomes using improved and advanced statistical analyses can provide substantial evidence to enhance public awareness and potentially reduce the burden of child stunting in South Asian countries.

NTpred: a robust and precise machine learning framework for in silico identification of Tyrosine nitration sites in protein sequences.

Post-translational modifications (PTMs) either enhance a protein's activity in various sub-cellular processes, or degrade their activity which leads toward failure of intracellular processes. Tyrosine nitration (NT) modification degrades protein's activity that initiates and propagates various diseases including neurodegenerative, cardiovascular, autoimmune diseases and carcinogenesis. Identification of NT modification supports development of novel therapies and drug discoveries for associated diseases. Identification of NT modification in biochemical labs is expensive, time consuming and error-prone. To supplement this process, several computational approaches have been proposed. However these approaches fail to precisely identify NT modification, due to the extraction of irrelevant, redundant and less discriminative features from protein sequences. This paper presents the NTpred framework that is competent in extracting comprehensive features from raw protein sequences using four different sequence encoders. To reap the benefits of different encoders, it generates four additional feature spaces by fusing different combinations of individual encodings. Furthermore, it eradicates irrelevant and redundant features from eight different feature spaces through a Recursive Feature Elimination process. Selected features of four individual encodings and four feature fusion vectors are used to train eight different Gradient Boosted Tree classifiers. The probability scores from the trained classifiers are utilized to generate a new probabilistic feature space, which is used to train a Logistic Regression classifier. On the BD1 benchmark dataset, the proposed framework outperforms the existing best-performing predictor in 5-fold cross validation and independent test evaluation with combined improvement of 13.7% in MCC and 20.1% in AUC. Similarly, on the BD2 benchmark dataset, the proposed framework outperforms the existing best-performing predictor with combined improvement of 5.3% in MCC and 1.0% in AUC. NTpred is publicly available for further experimentation and predictive use at: https://sds_genetic_analysis.opendfki.de/PredNTS/.

Potentiated GABAergic neuronal activities in the basolateral amygdala alleviate stress-induced depressive behaviors.

AIMS: Major depressive disorder is a severe psychiatric disorder that afflicts ~17% of the world population. Neuroimaging investigations of depressed patients have consistently reported the dysfunction of the basolateral amygdala in the pathophysiology of depression. However, how the BLA and related circuits are implicated in the pathogenesis of depression is poorly understood. METHODS: Here, we combined fiber photometry, immediate early gene expression (c-fos), optogenetics, chemogenetics, behavioral analysis, and viral tracing techniques to provide multiple lines of evidence of how the BLA neurons mediate depressive-like behavior. RESULTS: We demonstrated that the aversive stimuli elevated the neuronal activity of the excitatory BLA neurons (BLACAMKII neurons). Optogenetic activation of CAMKII neurons facilitates the induction of depressive-like behavior while inhibition of these neurons alleviates the depressive-like behavior. Next, we found that the chemogenetic inhibition of GABAergic neurons in the BLA (BLAGABA ) increased the firing frequency of CAMKII neurons and mediates the depressive-like phenotypes. Finally, through fiber photometry recording and chemogenetic manipulation, we proved that the activation of BLAGABA neurons inhibits BLACAMKII neuronal activity and alleviates depressive-like behavior in the mice. CONCLUSION: Thus, through evaluating BLAGABA and BLACAMKII neurons by distinct interaction, the BLA regulates depressive-like behavior.

Low phosphorus impact on Moso bamboo (Phyllostachys edulis) root morphological polymorphism and expression pattern of the related genes.

Moso bamboo typically grows in phosphorus (P)-deficient soil that limits its growth and development. In this study, 10 Moso bamboo genotypes (Ph-1 to Ph-10) were evaluated for their responses to P deficiency during the seedling stage by growing them in both P-sufficient and P-deficient conditions. Adaptive responses to low P (LP) conditions were observed in the majority of genotypes. Under P deficiency conditions, the total biomass decreased in several genotypes, but at the same time, the root-to-shoot ratio increased. Principal component analysis identified two main comprehensive traits (PC1 and PC2) related to the root volume and surface area and P concentration and accumulation. Based on the analysis, two genotypes (Ph-6 and Ph-10) were identified with significantly different levels of tolerance to P deficiency. The results revealed that the genotype Ph-10 responded to P deficiency by significantly increasing the root surface area and volume, while simultaneously reducing the number of root cortex cells when compared with the genotype Ph-6, which showed the lowest tolerance (intolerant). The genotype Ph-10 exhibited a robust response to external LP conditions, marked by elevated expression levels of PHOSPHATE TRANSPORTERs and SYG1/PHO81/XPR1s. In situ Polymerase Chain Reaction (PCR) analysis also revealed distinct tissue-specific expression patterns of the genes in the roots, particularly highlighting the differences between Ph-6 and Ph-10. The results provide a foundation for elucidating the mechanism of LP tolerance, thus potentially contributing to developing high P-use efficiency in Moso bamboo species.

Securing Smart Healthcare Cyber-Physical Systems against Blackhole and Greyhole Attacks Using a Blockchain-Enabled Gini Index Framework.

The increasing reliance on cyber-physical systems (CPSs) in critical domains such as healthcare, smart grids, and intelligent transportation systems necessitates robust security measures to protect against cyber threats. Among these threats, blackhole and greyhole attacks pose significant risks to the availability and integrity of CPSs. The current detection and mitigation approaches often struggle to accurately differentiate between legitimate and malicious behavior, leading to ineffective protection. This paper introduces Gini-index and blockchain-based Blackhole/Greyhole RPL (GBG-RPL), a novel technique designed for efficient detection and mitigation of blackhole and greyhole attacks in smart health monitoring CPSs. GBG-RPL leverages the analytical prowess of the Gini index and the security advantages of blockchain technology to protect these systems against sophisticated threats. This research not only focuses on identifying anomalous activities but also proposes a resilient framework that ensures the integrity and reliability of the monitored data. GBG-RPL achieves notable improvements as compared to another state-of-the-art technique referred to as BCPS-RPL, including a 7.18% reduction in packet loss ratio, an 11.97% enhancement in residual energy utilization, and a 19.27% decrease in energy consumption. Its security features are also very effective, boasting a 10.65% improvement in attack-detection rate and an 18.88% faster average attack-detection time. GBG-RPL optimizes network management by exhibiting a 21.65% reduction in message overhead and a 28.34% decrease in end-to-end delay, thus showing its potential for enhanced reliability, efficiency, and security.

Understanding the Mechanisms of Change in the Supportive and Respectful Maternity Care Intervention in Sindh, Pakistan: Provider Perspectives.

INTRODUCTION: We conducted this qualitative investigation to explore the mechanisms of change in providing respectful care resulting from the supportive and respectful maternity care intervention (S-RMC) in Sindh, Pakistan. METHODS: We applied the principles of realist evaluation methodology with a descriptive explanatory research design. We conducted in-depth interviews with 36 maternity care providers at secondary-level public health facilities where S-RMC was implemented for 6 months. The S-RMC broad components included capacity-building of maternity teams and systemic changes for improvements in governance and accountability within public health facilities. Data were analyzed using a deductive content analysis approach. RESULTS: We identified mechanisms of change, categorized by the S-RMC components: (1) S-RMC training: insight into women's feelings and rights, realization of the value that nonclinical staff can play, understanding of team coordination, orientation in psychosocial components of maternity care; (2) assessment of women's psychosocial vulnerabilities: identification of women's differential needs beyond routine care to provide woman-centered care; (3) psychosocial support: effective engagement with women and within maternity teams and the customization of woman- and companion-focused care; (4) care coordination: improved coordination among clinical and nonclinical staff to provide personalized care and psychosocial support and proper handover to ensure continuity of care; (5) assessment of quality of care: identification of service gaps from women's feedback; and (6) performance review and accountability: monthly performance review meetings to establish team member communication, systematic awareness of the maternity team's performance and challenges, and implementation of collective corrective actions. CONCLUSION: Our findings pointed to S-RMC working along multiple pathways-and concertedly with various health system components-to enable positive processes and behavioral change in maternity teams.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Support, networks, and relationships: Findings from a mixed-methods evaluation of a mentorship programme for early career women researchers in sexual and reproductive health and rights.

Low research output among women researchers in health research has been linked to inadequate mentorship opportunities for early career women researchers and particularly in sexual and reproductive health and rights (SRHR) field. Mentorship has been recognized as a contributor to strengthening research capacity and as beneficial for both mentors and mentees. Women researchers oftentimes experience negative impacts of organizational and structural gender inequities related to formal and informal mentoring. In 2020, the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction at WHO launched a mentorship programme for early career SRHR women researchers from low- and middle-income countries. The programme sought to provide professional skill-building, promote and share networking opportunities, and offer support in navigating personal and professional life. We conducted a convergent parallel mixed-methods evaluation of the 2020 pilot programme, which included 26 participants, through an online survey and semi-structured in-depth interviews (IDIs). Data collection occurred between March and May 2022. Nineteen responded to the online survey (12 mentees, 7 mentors) and 11 IDIs (7 mentees, 4 mentors) were completed. Based on a preliminary framework, we used deductive and inductive methods to identify six themes: views on mentorship; reasons for applying and expectations of participation in the programme; preferred aspects of programme implementation; challenges with the programme implementation; perceived lasting benefits of the programme; and recommendations for improvement. All participants found the initial training useful, most discussed work-life prioritization throughout the mentorship relationship, and most planned to continue with the relationship. There appear to be ample benefits to mentorship, especially when planned and implemented in a structured manner. These attributes can be particularly beneficial when they are conceived as a two-way relationship of mutual learning and support, and especially for women at the start of their research careers as they navigate structural gender inequities.