Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. METHODS: Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator's Global Assessment or Evaluator's Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. RESULTS: Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: - 11.5; 95% confidence interval [CI]: - 14.39, - 8.62), NILC (MD: - 12.25; 95% CI: - 15.21, - 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: - 12.8, - 11.2, and - 10.1, respectively), NILC (MD: - 11.6, - 13.9, and - 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). CONCLUSION: No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12 weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions.

Advancements in oligometastatic breast cancer: a comprehensive review of current strategies and the role of artificial intelligence.

In the dynamic landscape of Breast Cancer (BC), Oligo- Metastatic Breast Cancer (OMBC) presents unique challenges and opportunities. This comprehensive review delves into current strategies for addressing OMBC, covering locoregional and site-specific metastasis management, and addressing both surgical and minimally invasive therapies as essential components. Moreover, the transformative role of Artificial Intelligence (AI) is spotlighted. However, while the future looks promising, several limitations need addressing, including the need for further research, especially in diverse patient populations and resource-challenged settings. AI implementation may require overcoming the lack of Electronic Health Records acceptance in resource-challenged countries, which contributes to a scarcity of large datasets for AI training. As AI continues to evolve, validation and regulatory aspects must be continually addressed for seamless integration into clinical practice. In summary, this review outlines the evolving landscape of OMBC management, emphasizing the need for comprehensive research, global collaboration, and innovative AI solutions to enhance patient care and outcomes.

Return to play after head injury in adolescent sports: evaluating football versus other sports.

OBJECTIVE: Increased adolescent sports participation has raised concerns about higher rates of concussions, a prevalent injury among young athletes with potential long-term effects. Discrepancies in concussion recovery and management protocols across various sports underscore a critical issue in youth athletics. This study aimed to examine the relationship between sport type and the number of games missed following a concussion to inform targeted management strategies. METHODS: Data from 7445 postinjury ImPACT tests for athletes aged 12-22 years, collected from 2009 to 2019, were analyzed across different sports: baseball, basketball, cheerleading, football, ice hockey, lacrosse, soccer, softball, swimming, track and field, volleyball, and wrestling. The number of days and normalized missed games (NMG), a metric accounting for the different number of games in a season for different sports, were used to evaluate the effect of concussions across different sports. ANOVA, t-tests, and linear regression analyses were performed to model the effect of sport type on games missed in a season while controlling for sex, age, concussion history, diagnosed learning disability (DLD), and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Multivariable linear regression analysis demonstrated that football participation significantly increased NMG (ß 1.681, 95% CI 0.807-2.554; p < 0.001) and days missed (ß 1.637, 95% CI 1.044-2.231; p < 0.001) after head injury. Concussion diagnoses were also found to significantly increase NMG (ß 2.344, 95% CI 1.629-3.059; p < 0.001) and days missed (ß 1.560, 95% CI 1.074-2.045; p < 0.001), as well as history of prior concussion (NMG: ß 7.791, 95% CI 7.368-8.215; p < 0.001; days missed: ß 5.232, 95% CI 4.945-5.520; p < 0.001). In contrast, factors such as age, sex, DLD, ADHD, and concussions causing loss of consciousness did not significantly affect NMG or days missed. ANOVA with Tukey Honest Significant Difference indicated that compared with football, ice hockey (mean difference [MD] 5.4 days, p = 0.011) and track and field (MD 4.1 days, p = 0.006) were associated with significantly more days being missed after head injury. Conversely, basketball (MD -3.0, p < 0.001) and volleyball (MD -2.6, p = 0.005) were associated with fewer missed games. CONCLUSIONS: Adolescents playing football missed fewer days and games after concussion than other contact and noncontact sports, including ice hockey and track and field, raising questions about variations in return-to-play protocols and cultural attitudes within sports. Further research is needed to determine the factors affecting games missed across sport types in adolescent athletics and return-to-play protocols.

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.

An approach to optimizing dietary protein to growth and body composition in walking catfish, Clarias batrachus (Linneaeus, 1758).

Clarias batrachus is a commercially important food fish. In the present study, effect of varying dietary protein levels was evaluated on the survival, growth parameters and proximate composition of C. batrachus. Diets comprising 25%, 30%, 35%, 40%, 45%, and 50% crude protein (CP) were supplied to fish in T1, T2, T3, T4, T5, and T6, respectively, at the rate of 5% of fish body weight for the entire 90 days, twice daily. Size of each stocked C. batrachus was recorded after 15 days. Results revealed 100% survival rate of C. batrachus in all treatments. Significantly highest (P<0.001) mean value of weight gain (g/fish), percent weight gain, daily growth rate, specific growth rate and protein efficiency ratio (PER) in C. batrachus were recorded, reared in T4 by feeding 40% CP in diet. The best FCR value (1.90±0.02) for C. batrachus was obtained in T4 by feeding 40%CP in diet. Mean value of water, ash, fat and protein contents (wet mass) were ranged 74.10-79.23%, 3.12-4.68%, 3.90-4.43% and 13.09-16.79% for C. batrachus in the studied treatment groups. Water content (%) was found significantly (P<0.05) higher in the body of C. batrachus for T1, T2, T3 and T6 than for T4 and T5. Ash was found significantly (P<0.05) higher in the fish reared in T4 and T5. Fat content in the wet body mass of C. batrachus was found significantly higher in T4 and T1. While, significant higher (P<0.05) values of mean protein content was noted in C. batrachus reared in T4 and T5. Body composition of C. batrachus was also categorically affected by body size, however, condition factor showed non-significant correlation in most of the relationships in the present study. Overall, results indicated that feeding appropriate diet (containing 40% CP) to the fish resulted good growth performance, lower FCR and higher protein content in the fish. Present study provides valuable knowledge of optimal dietary protein level in C. batrachus which will help in commercial success of aquaculture.

Genome wide analysis of carotenoid cleavage oxygenases (CCO) gene family in Arachis hypogaea (peanut) under biotic stress.

Carotenoid cleavage oxygenases (CCOs) enzymes play a vital role in plant growth and development through the synthesis of apocarotenoids and their derivative. These chemicals are necessary for flower and fruit coloration, as well as the manufacture of plant hormones such as abscisic acid (ABA) and strigolactones, which control a variety of physiological processes. The CCOs gene family has not been characterized in Arachis hypogaea. Genome mining of A. hypogaea identifies 24 AhCCO gene members. The AhCCO gene family was divided into two subgroups based on the recent study of the Arabidopsis thaliana CCO gene family classification system. Twenty-three AhCCO genes, constituting 95.8% of the total, were regulated by 29 miRNAs, underscoring the significance of microRNAs (miRNAs) in governing gene expression in peanuts. AhCCD19 is the only gene that lacks a miRNA target site. The physicochemical characteristics of CCO genes and their molecular weights and isoelectric points were studied further. The genes were then characterized regarding chromosomal distribution, structure, and promoter cis-elements. Light, stress development, drought stress, and hormone responsiveness were discovered to be associated with AhCCO genes, which can be utilized in developing more resilient crops. The investigation also showed the cellular location of the encoded proteins and discovered that the peanut carotenoid oxygenase gene family's expansion was most likely the result of tandem, segmental, and whole-genome duplication events. The localization expresses the abundance of genes mostly in the cytoplasm and chloroplast. Expression analysis shows that AhCCD7 and AhCCD14 genes show the maximum expression in the apical meristem, lateral leaf, and pentafoliate leaf development, while AhNCED9 and AhNCED13 express in response to Aspergillus flavus resistance. This knowledge throws light on the evolutionary history of the AhCCO gene family and may help researchers better understand the molecular processes behind gene duplication occurrences in plants. An integrated synteny study was used to find orthologous carotenoid oxygenase genes in A. hypogaea, whereas Arabidopsis thaliana and Beta vulgaris were used as references for the functional characterization of peanut CCO genes. These studies provide a foundation for future research on the regulation and functions of this gene family. This information provides valuable insights into the genetic regulation of AhCCO genes. This technology could create molecular markers for breeding programs to develop new peanut lines.

Current updates on genetic spectrum of usher syndrome.

Usher syndrome (USH) is a genetic disorder that is characterized by sensorineural hearing loss (HL) and visual abnormality, i.e., loss of night vision and side (peripheral) vision. Usher syndrome is categorized into four subtypes (USH1, USH2, USH3, USH4) on the basis of phenotypic spectrum. Profound hearing loss (HL), vestibular are flexia and language disturbance are typically associated with Usher type 1, while USH2 is linked with moderate to severe level of congenital HL. USH3 has late onset of deafness in life (referred to as "postlingual"), inconstant vestibular abnormality and onset of retinitis pigmentosa (RP) typically in 2nd decade of life. Patients with USH4 have no vestibular impairment and have late onset of retinitis pigmentosa (RP) and sensorineural hearing loss. Until now, 15 genetic loci have been reported to be linked with all types of USH. Among reported USH loci, nine are related to be involved in USH1, three in USH2, two in USH3 and one locus in USH4, respectively. Current review has described different types of Usher syndrome and their molecular genetics, and role of usher proteins in sensory organs. Moreover, we also suggested certain candidate genes for uncharacterized loci that may help the molecular geneticist to reach their target easily. Conclusion: The current catalogue of USH genetic data may assist in genetic counseling, genetic diagnosis, and genotype-phenotype correlation.

Resilient event-triggered observer-based control of non-linear systems under denial-of-service attacks with actuator saturation.

This paper studies the control problem for a continuous-time networked system with non-linearity in the state equation as well as in the input, as saturation. The system is considered under denial-of-service (DoS), attacks which cause the blockage of input and/or output components in the overall closed-loop model. An event-triggering scheme that is resilient in nature, along with an observer-based control, has been considered under DoS attacks. The resultant scheme ensures efficient network resources and excludes Zeno behavior naturally due to the presence of a minimum positive interevent delay. Then, an event-based switched non-linear model is presented to address both the event-triggering scheme and the presence of DoS blocking attacks. A piece-wise Lyapunov-Krasovskii functional method on the described non-linear model, resulting in the switched system, is considered for achieving an exponentially stable response by driving the required feasibility conditions. In the presence of a non-linear system with saturation in the actuator, the presented design establishes quantitative relationships among the exponential decay rate, active/sleeping intervals of attacks, parameters of the event-triggering condition, and sampling period of the system. After that, linear matrix inequalities are presented for designing an event-triggered controller with an observer, while the design also includes the region of convergence for dealing with the input non-linearity. Finally, comparative results for an offshore structure model with non-linearity in states as well as in actuator, are demonstrated to verify the results of the control scheme that is developed. It has been verified that our design is less conservative than the previous designs, and can handle the non-linearities in the dynamics of plant and actuator saturation more efficiently, while DoS attacks are also present. By applying our proposed method, the overshoot and undershoot are less than ±2.5 percent, while system states converge to the origin within 55 s.

Effects of hours of sleep on ImPACT concussion testing: comparing baseline with postinjury scores.

OBJECTIVE: The influence of sleep on baseline and postconcussion neurocognitive performance prior to Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is poorly understood. Since ImPACT is widely used in youth sport to assess neurocognitive performance before and after head injury, it is important to delineate factors that affect testing performance. While some have reported correlations between fewer hours of sleep and lower scores on baseline tests, others have not observed any such associations. Therefore, the authors sought to compare the relationship between sleep and neurocognitive performance on ImPACT at both baseline and postinjury. METHODS: The authors queried a database of 25,815 ImPACT tests taken from 2009 to 2019 by athletes aged 12-22 years. There were 11,564 baseline concussion tests and 7446 postinjury concussion ImPACT tests used in the analysis. Linear regression was used to model the effect of sleep on baseline and postconcussion ImPACT scores adjusting for sex, age, learning disability, attention-deficit/hyperactivity disorder, number of prior concussions, number of games missed, and strenuous exercise before testing. RESULTS: Mean composite scores expectedly were all significantly lower in the post-head injury group compared with the baseline group. In the multivariable analysis, at baseline, hours of sleep significantly affected symptom scores (ß = -1.050, 95% CI -1.187 to -0.9138; p < 0.0001). In the postinjury multivariable analysis, verbal memory (ß = 0.4595, 95% CI 0.2080-0.7110; p = 0.0003), visual memory (ß = 0.3111, 95% CI 0.04463-0.5777; p = 0.0221), impulse control (ß = -0.2321, 95% CI -0.3581 to -0.1062; p = 0.0003), and symptom scores (ß = -0.9168, 95% CI -1.259 to -0.5750; p < 0.0001) were all affected by hours of sleep. CONCLUSIONS: Hours of sleep did not alter neurocognitive metrics at baseline but did have an impact on post-head injury metrics. These findings suggest that individuals may be able to compensate for lack of sleep at baseline but not immediately after concussion. Concussions may reduce cognitive reserve or detract from the brain's resources, making sleep even more important for proper neurocognitive functioning postconcussion. Future work will analyze the effects of sleep on postconcussion test performance.

Methylotrophic bacteria from rice paddy soils: mineral-nitrogen-utilizing isolates richness in bulk soil and rhizosphere.

Methanol, the second most abundant volatile organic compound, primarily released from plants, is a major culprit disturbing atmospheric chemistry. Interestingly, ubiquitously found methanol-utilizing bacteria, play a vital role in mitigating atmospheric methanol effects. Despite being extensively characterized, the effect of nitrogen sources on the richness of methanol-utilizers in the bulk soil and rhizosphere is largely unknown. Therefore, the current study was planned to isolate, characterize and explore the richness of cultivable methylotrophs from the bulk soil and rhizosphere of a paddy field using media with varying nitrogen sources. Our data revealed that more genera of methylotrophs, including Methylobacterium, Ancylobacter, Achromobacter, Xanthobacter, Moraxella, and Klebsiella were enriched with the nitrate-based medium compared to only two genera, Hyphomicrobium and Methylobacterium, enriched with the ammonium-based medium. The richness of methylotrophic bacteria also differed substantially in the bulk soil as compared to the rhizosphere. Growth characterization revealed that majority of the newly isolated methanol-utilizing strains in this study exhibited better growth at 37 °C instead of 30 or 45 °C. Moreover, Hyphomicrobium sp. FSA2 was the only strain capable of utilizing methanol even at elevated temperature 45 °C, showing its adaptability to a wide range of temperatures. Differential carbon substrate utilization profiling revealed the facultative nature of all isolated methanol-utilizer strains with Xanthobacter sp. TS3, being an important methanol-utilizer capable of degrading toxic compounds such as acetone and ethylene glycol. Overall, our study suggests the role of nutrients and plant-microbial interaction in shaping the composition of methanol-utilizers in terrestrial environment.

Mechanistic approach of tannery wastewater and sulfadiazine mutual toxicity in wheat (Triticum aestivum L.) and mitigation through exogenous application of gallic acid.

Excessive release of chromium (Cr) from the tanning industry and antibiotics from livestock caused severe hazards to humans. Gallic acid (GA 10 mM) alleviated alone/combined SDZ 30 mg kg-1 and TWW 40, 60, and 100% stress in wheat. GA (10 mM) decreased the TSP 12 and 13%, TFAA 8 and 10%, TSS 14 and 16%, RS 18 and 16%, and NRS 11 and 9% in shoots and grains under SDZ + TWW (30 mg kg-1+100%), compared without foliar. GA (10 mM) declined the MDA 20 and 31, EL 13 and 36%, H2O2 17 and 15%, O2•- 10 and 11% in leaves and roots, under combined SDZ + TWW (30 mg kg-1+100%), compared without foliar. GA (10 mM) improved the POD 106 and 30%, SOD 145 and 31%, CAT 78, and 35%, APX 100 and 25% in leaves and roots under combined SDZ + TWW (30 mg kg-1+100%), compared without foliar application. Considerably GA (10 mM) reduced total Cr 18, CrIII 20, and CrVI 50% in roots and shoots 19, 41, and 48%, and grains 15, 27, and 29% respectively, under combined SDZ + TWW (30 mg kg-1+100%) stress, compared without foliar. Overall, GA boosted the wheat growth, physiology, and defence system by inhibiting the combined SDZ + Cr toxicity.

Seroepidemiology and associated risk factors of brucellosis in small ruminants of district Khanewal, Pakistan.

Objectives: Keeping in view the economic and veterinary public health importance of brucellosis, this research was conducted to determine its seroprevalence and associated risk determinants in small ruminants in district Khanewal, Southern Punjab, Pakistan. Materials and Methods: Two-stage cluster sampling technique was used for sampling, and the sample size was calculated using C-survey 2.0. Accordingly, sera samples (n = 392) were collected from small ruminants in the study area from October 2022 to July 2023. All the samples were tested for the presence of anti-Brucella antibodies by Rose Bengal Plate Test (RBPT), followed by confirmation of all the samples using an enzyme linked immunosorbent assay (ELISA) kit (ID.vet®, France; sensitivity and specificity=100%, each). Results: The seropositivity rate of brucellosis was 7.14% [n = 28/392; 95% confidence interval (CI) = 4.87%-10.12%] by RBPT, whereas the results of ELISA showed an overall seroprevalence rate of 7.40% (n = 29/392; 95% CI = 5.11%-10.37%) in the study population. Univariate analysis of risk factors revealed that abortion history (AH), retained fetal membranes (RFMs), repeat breeding, flock size (FS), educational status of farmers (ESFs), awareness about brucellosis (AB), and farm hygiene had a significant association with the seroprevalence of brucellosis (p < 0.05). The multivariate analysis using a binary logistic regression model revealed that variables including tehsil, FS, AH, RFM, ESF, AB, and farming system were significant factors (p < 0.05) associated with brucellosis in the target population. Conclusion: Brucellosis is prevalent in small ruminants in Khanewal, Pakistan. The disease burden can be reduced by improving the reproductive health of animals, farm hygiene, and farmers' awareness about the diseases. Further studies are needed on a larger scale to devise stringent disease control strategies to avoid losses associated with brucellosis at regional, national, and global levels.

Does green investment affect environment pollution: Evidence from asymmetric ARDL approach?

Pollution in the environment is today the biggest issue facing the globe and the main factor in the development of many fatal diseases. The main objective of the study to investigate green investments, economic growth and financial development on environmental pollution in the G-7 countries. This study used annual penal data from 1997 to 2021. The panel NARDL (Non-linear autoregressive distributed lag) results affirm that the positive change of green investment and negative shock in green investment have a significant and positive association with environment pollution in G-7 nations. Our findings provide more evidence for the long-term asymmetry between financial development and environmental performance. However, the findings confirm that a positive modification in financial development has a positive and significant effect on environment pollution. Whereas negative shock in financial development is negative and insignificant relationship with environment pollution. Moreover, the outcomes of the study reveal that both positive shock in gross domestic product growth and negative shock of economic growth have a significant and positive link with environment pollution in G-7 countries. According to the findings, by lowering carbon dioxide emissions, green investments reduced environmental pollution in the G-7 nations over the long and short term. Moreover, it is an innovative research effort that provides light on the connection between green investments, financial development, and the environment while making mention to the EKC in G-7 countries. After all these, our recommendation is to increases green investment expenditures to reduce environmental pollution in the G-7 nations based on our findings. Additionally, one important way for the nation to achieve its sustainable development goals is to improve advancements in the financial sector.

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition.

The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4+ immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein. In vitro experiments showed that GINPs have strong affinity toward HIV-1 (Kd = 36.7 ± 2.2 nM) and possess high anti-interference and specificity. GINPs demonstrate broad inhibition activity against both tier 1 and tier 2 HIV-1 strains with a pM-level IC50 and exhibit a significant inhibitory effect on long-term viral replication by more than 95%. The strategy provides a promising method for the inhibition and therapy of HIV-1 infection.

CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer's disease.

In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.05). These sex-specific proteins strongly predicted amyloid/tau positivity (AUC=0.98 in males; 0.99 in females), significantly higher than those with age, sex, and APOE-ε4 (AUC=0.85). The identified sex-specific proteins were well validated (r≥0.5) in the Stanford study (N=108) and Emory study (N=148). Biological follow-up of these proteins led to sex differences in cell-type specificity, pathways, interaction networks, and drug targets. Male-specific proteins, enriched in astrocytes and oligodendrocytes, were involved in postsynaptic and axon-genesis. The male network exhibited direct connections among 152 proteins and highlighted PTEN, NOTCH1, FYN, and MAPK8 as hubs. Drug target suggested melatonin (used for sleep-wake cycle regulation), nabumetone (used for pain), daunorubicin, and verteporfin for treating AD males. In contrast, female-specific proteins, enriched in neurons, were involved in phosphoserine residue binding including cytokine activities. The female network exhibits strong connections among 51 proteins and highlighted JUN and 14-3-3 proteins (YWHAG and YWHAZ) as hubs. Drug target suggested biperiden (for muscle control of Parkinson's disease), nimodipine (for cerebral vasospasm), quinostatin and ethaverine for treating AD females. Together, our findings provide mechanistic understanding of sex differences for AD risk and insights into clinically translatable interventions.

Deep learning based buck-boost converter for PV modules.

Over the past few years, the use of DC-DC buck-boost converters for Photovoltaic (PV) in renewable energy applications has increased for better results. One of the main issues with this type of converter is that output voltage is achieved with the undesired ripples. Many models are available in the literature to address this issue, but very limited work is available that achieves the desired goal using deep learning-based models. Whenever it comes to the PV, then it is further limited. Here, a deep learning-based model is proposed to reduce the steady-state time and achieve the desired buck- or boost mode for PV modules. The deep learning-based model is trained using data collected from the conventional PID controller. The output voltage of the experimental setup is 12V while the input voltage from the PV modules is 10V (when the sunlight decreases) to 24V (for 3.6 kVA) to 48V (for more than 5 kVA). It is among the few models using a single big battery (12V) for off-grid and on-grid for a single building. Experimental results are validated using objective measures. The proposed model outperforms the conventional PID controller-based buck-boost converters. The results clearly show improved performance in terms of steady-state and less overshoot.

Tumor size impact on TNM staging which define post-operative complications in rectal cancer.

The purpose of this study was to see how accurate tumor size was at predicting T and N stages in rectal malignancies. Tumor sizes of 40 mm and greater than 40 mm were used to assess post-operative challenges in related to T1-T2 and T3-T4 stages, as well as between node N0 and node N1 and N2 patients. A total of 131 patients were treated for colorectal cancer, with 54 patients < 40 mm and 77 patients > 40 mm receiving Da Vinci colorectal surgery. Conferring to the Clavien-Dindo classification grade III, there's an increase in the percentage of tumors > 40 mm, which also impacts the percentage of intestinal obstruction, anastomotic leakage, GERD, and sepsis with a P < 0.05. A tumor size of more than 40 mm is strongly associated with advanced pT stages. Tumor size may serve in addition to clinical staging and improve the management of rectal cancer.

Spatial variations and determinants of timely completion of vaccination in Ethiopia using further analysis of EDHS 2019 data: Spatial and multilevel analysis.

BACKGROUND: Timely vaccination is the practice of administering the vaccine within the first birthday of the child. Not vaccinating the child at the appropriate age is the cause of improper protection of diseases and can be a possible factor in death. The problem of not completing the vaccine in the scheduled period is a globally distributed problem, but especially in sub-Saharan African countries, it is a bottleneck to child health. Even if timely vaccination is crucial for reducing the impact of VPDs, there are no current national-level studies to generate conclusive and tangible evidence in Ethiopia. OBJECTIVE: To assess spatial variations and determinants of timely completion of vaccination in Ethiopia using further analysis of EDHS 2019 data. METHOD: The secondary data analysis of a community-based cross-sectional study design was employed among 3094 participants. Stata-14 software was used for data cleaning, recording, and analysis. Arc GIS version 10.3 and Kuldorff SAT scan version 9.6 software are used for spatial and SAT scan statistics. A multilevel mixed-effect binary logistic regression analysis was used to identify the predictors of timely vaccination. The clustering effect was also evaluated by Moran's I statistics and intra class correlation. RESULTS: The timely completion of vaccination among Ethiopian women who had a child aged 12-35 months was 19.5% (95%CI: 18.2-20.8), and the spatial distribution of timely completion of vaccinations in Ethiopia was non-randomly distributed. A statistically significant high proportion of timely completion areas were clustered in the eastern part of Amhara, the south part of Afar, Addis Ababa, and Oromia. The primary cluster was located at a 13.11 km radius in Diredawa, which was 3.68 times higher than outside the window (RR = 3.68, LLR = 68.76, p-value < 0.001). History of antenatal care follow-up (AOR = 1.63, 95% CI: 1.3-2.04), giving birth at health facilities (AOR = 1.63, 95% CI: 1.25-2.13), age ≥ 35 years (AOR = 186, 95% CI: 1.35-2.63), age 25-34 years (AOR = 1.72, 95% CI: 1.33-2.21), and being richest (AOR = 2.71, 95% CI: 1.86-3.94) were the factors contributing to the timely completion of vaccination. CONCLUSION: The prevalence of timely completion of vaccination was low in Ethiopia, and the spatial distribution of timely completion of vaccination in Ethiopia was non-randomly distributed across the regions. The factors associated with the timely completion of vaccinations were ANC follow-up, place of delivery, age of the participant, and wealth index. We recommend expanding facility delivery, antenatal care services, and empowering women to scale up timely vaccination in Ethiopia.