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Background: Extensive research on Lupeol's potential in cancer prevention highlights its ability to target various cancer-related factors. It regulates proliferative markers, modulates signaling pathways, including PI3K/AKT/mTOR, and influences inflammatory and apoptotic mechanisms. Additionally, Lupeol demonstrates selectivity in killing cancer cells while sparing normal cells, thus minimizing the risk of toxic effects on healthy tissues., Hypothesis: Therefore, we aimed to explore Lupeol's potential roles as a chemotherapeutic agent and as a sensitizer to chemotherapy by reviewing various animal-based studies published on its effects., Study Design: We conducted a comprehensive search across databases, including PubMed, PMC, Cochrane, EuroPMC, and ctri.gov.in to identify pertinent articles. Our focus was solely on published animal studies examining Lupeol's anti-cancer effects, with reviewers independently assessing bias risk and resolving discrepancies through consensus., Result: 20 studies were shortlisted. The results demonstrated that Lupeol brings changes in the tumor volume by [Hedges's g: -6.62; 95 % CI: -8.68, -4.56; τ 2 : 24.36, I 2 : 96.50 %; p < 0.05] and tumor weight by [Hedges's g: -3.97; 95 % CI: -5.20, -2.49; τ 2 : 2.70, I 2 : 79.27 %; p <0.05]. The high I 2 , negative Egger's value, and asymmetrical funnel plot show the publication bias among the studies. Further, Lupeol in combination with other chemotherapeutic agents showed better outcomes as compared to them alone [Hedges's g: -6.38; 95 % CI: -11.82, -0.94; τ 2 : 46.91; I 2 : 98.68 %; p <0.05]. Lupeol also targets various signaling molecules and pathways to exert an anti-cancer effect., Conclusion: In conclusion, Lupeol significantly reduces tumor volume and weight. Combining Lupeol with other chemotherapy agents shows promise for enhancing anti-cancer effects. However, high variability among studies and evidence of publication bias suggest caution in interpreting results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The biological synthesis of zinc oxide nanoparticles (ZnO NPs) from plant extracts has emerged as a novel method for producing NPs with great scalability and biocompatibility. The present study is focused on bio-fabricated zinc oxide nanomaterial characterization and investigation of its photocatalytic and antifungal activities. ZnO NPs were biosynthesized using the leaf extract of Polyalthia longifolia without using harmful reducing or capping chemicals, which demonstrated fungicidal activity against Fusarium oxysporum f. sp. ciceris . The results showed that the inhibition of the radial growth of F . oxysporum f. sp. ciceris was enhanced as the concentration increased from 100 ppm to 300 ppm. The effectiveness of the photocatalytic activity of biosynthesized ZnO NPs was analyzed using MB dye degradation in aqueous medium under ultraviolet (UV) radiation and natural sunlight. After four consecutive cycles, the photocatalytic degradation of MB was stable and was 84%, 83%, 83%, and 83%, respectively, during natural sunlight exposure. Under the UV sources, degradation reached 92%, 89%, 88%, and 87%, respectively, in 90 minutes. This study suggests that the ZnO NPs obtained from plant extract have outstanding photocatalytic and antifungal activities against F. oxysporum f. sp. ciceris and have the potential for application as a natural pest control agent to reduce pathogenesis., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (This journal is © The Royal Society of Chemistry.)

Reactive oxygen species at supra-physiological levels trigger oxidative stress during cryopreservation, which can be neutralised by incorporating suitable antioxidants into the semen extender medium. This study was intended to explore the effect of asiatic acid (AA) as an antioxidant in semen extender on frozen-thawed sperm quality and in vivo fertility of bull sperm. Semen was collected from Holstein Friesian bulls for 10 consecutive weeks (total ejaculates = 60). Semen was cryopreserved with a Tris citric acid egg yolk-based extender supplemented with 0 (control), 20, 40, 60, and 100 μM AA. The supplementation of the extender with 40 and 60 μM AA improved ( p < 0.05) post-thaw motility kinematics, plasma membrane integrity, acrosome integrity, sperm viability, and DNA integrity of bull sperm. Mitochondrial membrane potential was high ( p < 0.05) with 60 μM of AA concentration in extender media. The catalase activity in seminal plasma was maintained ( p < 0.05) when semen was added with 20, 40, and 60 μM of AA. The in vivo fertility was found to be significantly high with the semen extended with 60 μM AA. Conclusively, this study showed that AA supplementation in semen extender significantly improved sperm motility kinematics and cell integrity, conserved antioxidant enzyme activity, and improved in vivo fertility.

Enzalutamide is an androgen receptor (AR) antagonist commonly used in the treatment of prostate cancer (CaP). However, due to the potential toxicity and development of resistance associated with Enzalutamide-based therapy, there is a need to explore additional compounds that can enhance its therapeutic effectiveness while minimizing toxicity. Lupeol is a pharmacologically active triterpene having anticancer effects. The objective of this study was to explore Lupeol's potential in enhancing the chemosensitivity of chemoresistant CaP cells to Enzalutamide in vitro and in a mouse model. To test our hypothesis, we performed cell viability and luciferase reporter gene assay, flow cytometry, animal studies, and histopathological analysis. Finally, we analyzed the change in selective metabolites in the prostate tissue by LCMS. Results demonstrated that a combination of Lupeol and Enzalutamide could better (i) suppress the Cancer Stem Cells (CSCs) and chemoresistant cells (PTEN-CaP8 and PC3) viability and migration, (ii) increase cell cycle arrest, (iii) inhibit the transcriptional activity of AR, c-MYC, c-FLIP, and TCF (iv) inhibit tumor growth in a mouse model (v) protect Enzalutamide-induced adverse effects in prostate glands and gut tissue (vi) decrease levels of testosterone and methionine metabolites. In conclusion, Lupeol enhances the pharmacological efficacy of Enzalutamide and reduces the adverse effects. Thus, Lupeol could be a promising adjuvant for improving Enzalutamide-based treatment outcomes and warrant further research., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

The intrathecal baclofen pump (ITB) is one of the advanced treatment options in the management of spasticity. This retrospective cohort study was conducted to identify the complications of ITB treatment at a tertiary care rehabilitation facility. Various demographic and technical factors were analyzed, which are less often reported in the literature. All patients with ITB who had their refill at the ITB clinic between November 2019 and March 2020 were included. Of 48 patients, 17 patients had 18 (37.5%) ITB-related complications. Catheter-related complications were most common, whereas loss of efficacy (16.7%) and baclofen withdrawal (14.5%) were the most common outcomes of complications. Only catheter occlusion had a significant relationship with the pattern of spastic quadriparesis ( p = 0.001). Gender, rehabilitation diagnosis, patients' residence, and facility of ITB placement did not have significant association. Similarly, age, distance from hospital, disease onset, ITB therapy duration, and baclofen dose were not statistically significant in relation to ITB-related complications.

Background: Lymphomatoid granulomatosis (LYG) is a rare pediatric disorder driven by the Epstein-Barr virus and is considered as a part of the lymphoma spectrum. It is mostly associated with immune deficiency and patients on immunosuppressive therapy, especially with acute leukemia. It can present as a multisystemic disease, diagnosed on biopsy as atypical lymphocytes with an angiocentric pattern against a background composed of histiocytes, neutrophils, and extensive T-cell infiltration., Observation: We report 3 cases of children with Lymphomatoid granulomatosis, one with Langerhans cell histiocytosis., Conclusion: Combination chemotherapy was used for the treatment of Lymphomatoid granulomatosis; however, the prognosis is guarded. One of 3 patients is alive and in remission on the last follow-up visit at 15 months., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Prostate cancer (CaP) is one of the most prevalent male malignancies, accounting for a considerable number of annual mortalities. However, the prompt identification of early-stage CaP often faces delays due to diverse factors, including socioeconomic inequalities. The androgen receptor (AR), in conjunction with various other signaling pathways, exerts a central influence on the genesis, progression, and metastasis of CaP, with androgen deprivation therapy (ADT) serving as the primary therapeutic strategy. Therapeutic modalities encompassing surgery, chemotherapy, hormonal intervention, and radiotherapy have been formulated for addressing early and metastatic CaP. Nonetheless, the heterogeneous tumor microenvironment frequently triggers the activation of signaling pathways, culminating in the emergence of chemoresistance, an aspect to which cancer stem cells (CSCs) notably contribute. Phytochemicals emerge as reservoirs of bioactive agents conferring manifold advantages against human morbidity. Several of these phytochemicals demonstrate potential chemoprotective and chemosensitizing properties against CaP, with selectivity exhibited towards malignant cells while sparing their normal counterparts. In this context, the present review aims to elucidate the intricate molecular underpinnings associated with metastatic CaP development and the acquisition of chemoresistance. Moreover, the contributions of phytochemicals to ameliorating CaP initiation, progression, and chemoresistance are also discussed., Competing Interests: The authors declare no conflicts of interest.

Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS, OMIM#619150) is an ultra-rare childhood-onset autosomal recessive movement disorder manifesting paroxysmal dyskinesia, global developmental delay, impaired cognition, progressive psychomotor deterioration and/or drug-refractory seizures. We investigated three consanguineous Pakistani families with six affected individuals presenting overlapping phenotypes partially consistent with the reported characteristics of IDDPADS. Whole exome sequencing identified a novel missense variant in Phosphodiesterase 2A (PDE2A): NM&#95;002599.4: c.1514T > C p.(Phe505Ser) that segregated with the disease status of individuals in these families. Retrospectively, we performed haplotype analysis that revealed a 3.16 Mb shared haplotype at 11q13.4 among three families suggesting a founder effect in this region. Moreover, we also observed abnormal mitochondrial morphology in patient fibroblasts compared to controls. Belonging to diverse age groups (13 years-60 years), patients presented paroxysmal dyskinesia, developmental delay, cognitive abnormalities, speech impairment, and drug-refractory seizures with variable onset of disease (as early as 3 months of age to 7 years). Together with the previous reports, we observed that intellectual disability, progressive psychomotor deterioration, and drug-refractory seizures are consistent outcomes of the disease. However, permanent choreodystonia showed variability. We also noticed that the later onset of paroxysmal dyskinesia manifests severe attacks in terms of duration. Being the first report from Pakistan, we add to the clinical and mutation spectrum of PDE2A-related recessive disease raising the total number of patients from six to 12 and variants from five to six. Together, with our findings, the role of PDE2A is strengthened in critical physio-neurological processes., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Wind turbine power curve (WTPC) serves as an important tool for wind turbine condition monitoring and wind power forecasting. Due to complex environmental factors and technical issues of the wind turbines, there are many outliers and inconsistencies present in the recorded data, which cannot be removed through any pre-processing technique. However, the current WTPC models have limited ability to understand such complex relation between wind speed and wind power and have limited non-linear fitting ability, which limit their modelling accuracy. In this paper, the accuracy of the WTPC models is improved in two ways: first is by developing multivariate models and second is by proposing MARS as WTPC modeling technique. MARS is a regression-based flexible modeling technique that automatically models complex the nonlinearities in the data using spline functions. Experimental results show that by incorporating additional inputs the accuracy of the power curve estimation is significantly improved. Also by studying the error distribution it is proved that multivariate models successfully mitigate the adverse effect of hidden outliers, as their distribution has higher peaks and lesser standard deviation, which proves that the errors, are more converged to zero compared to the univariate models. Additionally, MARS with its superior non-linear fitting ability outperforms the compared methods in terms of the error metrics and ranks higher than regression trees and several other popular parametric and non-parametric methods. Finally, an outlier detection method is developed to remove the hidden outliers from the data using the error distribution of the modeled power curves., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mushtaq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Craniosynostosis is characterized by the premature fusion and ossification of one or more of the sutures of the calvaria, often resulting in abnormal features of the face and the skull. In cases in which growth of the brain supersedes available space within the skull, developmental delay or cognitive impairment can occur. A complex interplay of different cell types and multiple signaling pathways are required for correct craniofacial development. In this study, we report on two siblings with craniosynostosis and a homozygous missense pathogenic variant within the IL11RA gene (c.919 T > C; p.W307R). The patients present with craniosynostosis, exophthalmos, delayed tooth eruption, mild platybasia, and a basilar invagination. The p.W307R variant is located within the arginine-tryptophan-zipper within the D3 domain of the IL-11R, a structural element known to be important for the stability of the cytokine receptor. Expression of IL-11R-W307R in cells shows impaired maturation of the IL-11R, no transport to the cell surface and intracellular retention. Accordingly, cells stably expressing IL-11R-W307R do not respond when stimulated with IL-11, arguing for a loss-of-function mutation. In summary, the IL-11R-W307R variant, reported here for the first time to our knowledge, is most likely the causative variant underlying craniosynostosis in these patients., (© 2023. Springer Nature Limited.)

Soil fertilizers have the potential to significantly increase crop yields and improve plant health by providing essential nutrients to the soil. The use of fertilizers can also help to improve soil structure and fertility, leading to more resilient and sustainable agricultural systems. However, overuse or improper use of fertilizers can lead to soil degradation, which can reduce soil fertility, decrease crop yields, and damage ecosystems. Thus, several attempts have been made to overcome the issues related to the drawbacks of fertilizers, including the development of an advanced fertilizer delivery system. Biopolymer aerogels show promise as an innovative solution to improve the efficiency and effectiveness of soil-fertilizer delivery systems. Further research and development in this area could lead to the widespread adoption of biopolymer aerogels in agriculture, promoting sustainable farming practices and helping to address global food-security challenges. This review discusses for the first time the potential of biopolymer-based aerogels in soil-fertilizer delivery, going through the types of soil fertilizer and the advert health and environmental effects of overuse or misuse of soil fertilizers. Different types of biopolymer-based aerogels were discussed in terms of their potential in fertilizer delivery and, finally, the review addresses the challenges and future directions of biopolymer aerogels in soil-fertilizer delivery.

Exosomes are nanoscale extracellular vesicles which regulate intercellular communication. They have great potential for application in nanomedicine. However, techniques for their isolation are limited by requirements for advanced instruments and costly reagents. In this study, we developed a lyophilization-based method for isolating exosomes from cultured cells. The isolated exosomes were characterized for protein content using Bradford assay, and for size distribution and shape using scanning electron microscopy (SEM) and nanoparticles tracking analysis (NTA). In addition, CD63, CD9, CD81, HSP70 and TSG101 were evaluated as essential exosomal surface markers using Western blot. Drug loading and release studies were performed to confirm their drug delivery properties using an in vitro model. Exosomes were also loaded with commercial dyes (Cy5, Eosin) for the evaluation of their drug delivery properties. All these characterizations confirmed successful exosome isolation with measurements of less than 150 nm, having a typical shape, and by expressing the known exosome surface protein markers. Finally, tyrosine kinase inhibitors (dasatinib and ponatinib) were loaded on the exosomes to evaluate their anticancer effects on leukemia cells (K562 and engineered Ba/F3-BCR-ABL) using MTT and Annexin-PI assays. The expression of MUC1 protein on the exosomes isolated from MCF-7 cells also indicated that their potential diagnostic properties were intact. In conclusion, we developed a new method for exosome isolation from cultured cells. These exosomes met all the essential requirements in terms of characterization, drug loading and release ability, and inhibition of proliferation and apoptosis induction in Ph+ leukemia cells. Based on these results, we are confident in presenting the lyophilization-based exosome isolation method as an alternative to traditional techniques for exosome isolation from cultured cells.

Indiscriminate uses of insecticide greatly damage the environment as well as non-target organisms. Thus, multiple levels of bioassays can help better management of our environment. Flubendiamide is a phthalic acid diamide insecticide that ceases the function of insect muscle leading to paralysis and death. Here, we aimed to explore the effects of Flubendiamide on the life cycle of Spodoptera litura vis-a-vis the mode of action. Fourth instar larvae of the same age (120 ± 2 h) and size were fed with different concentrations (20-80 μg/mL) of Flubendiamide for 12-72 h. We performed a pharmacokinetics study, different biochemical assays, p450, Ecdysone receptor (EcR) and other genes expression analyses by Real-Time PCR and gross damages by Dye exclusion assay and histopathology. Our results demonstrate that the mean concentration of Flubendiamide after 48 h is 9.907 μg/mL and (i) altered the molting, metamorphosis, and reproduction at 80 μg/mL (24 h) (ii) increases all oxidative stress parameters (ROS/RNS, MDA, 8OHdG), decreases oxidative defense mechanisms (SOD, CAT, GST) at 80 μg/mL (48 h) and p450 in a time and concentration-dependent manner, (iii) activates CncC/Maf apoptotic pathways at 80 μg/mL concentration at 24 h while the expression declined from 48 h onwards, (iii) downregulates the EcR expression in a time and concentration-dependent manner, which might be responsible for disturbed molting, metamorphosis, and reproduction, and (iv) increase the expression of apoptotic genes (Caspase 1, -3, and - 5), in time and concentration-dependent manner causing gross morphological and histological damages. In conclusion, indiscriminate use of this insecticide can affect the ecosystem and have the capacity to cause multiple hazardous effects on experimental organisms. Thus, it warrants further investigations to improve and optimize the integrated pest management packages, including Flubendiamide for better management., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Cancer chemotherapeutic drugs can potentially cause several adverse effects that influence a patient's general well-being. Sorafenib, an approved drug used in clinics against multiple cancers whose overall efficacy suffered a serious setback due to various side effects, leading to its frequent discontinuation. Lupeol has recently been considered an important prospective therapeutic agent due to its low toxicity and enhanced biological efficacy. Hence, our study aimed to evaluate whether Lupeol can perturb the Sorafenib-induced toxicity., Main Methods: To test our hypothesis, we studied DNA interaction, level of cytokines, LFT/RFT, oxidant/antioxidant status, and their influences on genetic, cellular, and histopathological changes using both in vitro and in vivo models., Key Findings: The Sorafenib-treated group showed a marked increase in reactive oxygen and nitrogen species (ROS/RNS), an increase in liver and renal function marker enzymes, serum cytokines (IL-6, TNF-α, IL-1β) macromolecular damages (protein, lipid, and DNA), and a decrease in antioxidant enzymes (SOD, CAT, TrxR, GPx, GST). Moreover, Sorafenib-induced oxidative stress caused marked cytoarchitectural damage in the liver and kidney and increased p53 and BAX expression. Interestingly, combining Lupeol with Sorafenib improves all the examined toxic insults caused by Sorafenib. In conclusion, our findings suggest that Lupeol can be used in combination with Sorafenib to reduce ROS/RNS-induced macromolecule damage, which might result in hepato-renal toxicity., Significance: This study presents the possible protective effect of Lupeol against Sorafenib-induced adverse effects by perturbing redox homeostasis imbalance and apoptosis leading to tissue damage. This study is a fascinating finding that warrants further in-depth preclinical and clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The presence of Meloidogyne spp., also known as root-knot nematodes, presents a significant danger to global agricultural progress. Since chemical nematicides have high levels of toxicity, it is imperative to develop environmentally friendly methods to manage root-knot nematodes. Nanotechnology is now the most progressive way to attract researchers due to its innovative quality in combating plant diseases. Our study focused on the sol-gel process to synthesize grass-shaped zinc oxide nanoparticles (G-ZnO NPs) and assess its nematicidal behavior against Meloidogyne incognita . Various concentrations (250, 500, 750, and 1000 ppm) of G-ZnO NPs were utilized to expose both the infectious stage (J2s) and egg masses of M. incognita . Laboratory results revealed that G-ZnO NPs showed toxicity to J2s with LC50 values of 1352.96, 969.64, and 621.53 ppm at 12, 24, and 36 hours, respectively, and the result was the inhibition of egg hatching in M. incognita . All three exposure periods were reported linked with the concentration strength of G-ZnO NPs. The pot experiment results exhibited that G-ZnO NPs significantly reduced the root-gall infection of chickpea plants under M. incognita attack. Compared with the untreated control, there was a significant improvement in plant growth attributes and physiological parameters as well, when distinct G-ZnO NP doses (250, 500, 750, and 1000 ppm) were applied. In the pot study, we noticed a reduction in the root-gall index with an increase in the concentration of G-ZnO NPs. The results confirmed that G-ZnO NPs have enormous potential in sustainable agriculture for controlling the root-knot nematode, M. incognita , in chickpea production., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Amir Khan et al.)

The current study investigated the multifunctional properties of Cadmium Sulphide Nanoparticles synthesized using a green synthesis method (CdS NPs) using a green feedstock, Nopal Cactus fruit extract. The biological activities of the CdS NPs were thoroughly investigated, including their insecticidal, antibacterial, and anticancer activities. The different concentrations (0.005-0.04%) of CdS NPs were fed to the larvae of Spodoptera litura, and their ingestion effects were observed on the different biological, biochemical, and oxidative stress markers. There are significant dose-dependent changes in the biochemical parameters like superoxide dismutase (SOD), Catalase (CAT), Glutathione-S-transferase (GST), and MDA level as a marker of lipid peroxidation in the treated larvae were studied. In the highest concentration (0.04%), significant larval mortality (46.66%), malformation (pupae and adult) (27.78%), inhibition of adult emergence (43.87%), as well as reduced fecundity (25.28%), and fertility (22.74%) as compared to control was observed. CdS NPs have been investigated for antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus bacterial strains. In vitro anticancer activities were carried out to decrease the viability of the Pancreatic cancer cell line. The cells showed 18% and 12% viability at a 200 μg/ml concentration when incubated with CdS NPs for 24 and 48 h, respectively, confirming its potent anticancer property. The lack of cytotoxicity against the (RBC) endorses the biocompatible nature of synthesized CdS NPs. It was observed that green synthesized CdS NPs could be used as a promising insecticidal, antibacterial, and anticancer agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The integration of a decision maker's preferences in evolutionary multi-objective optimization (EMO) has been a common research scope over the last decade. In the published literature, several preference-based evolutionary approaches have been proposed. The reference point-based non-dominated sorting genetic (R-NSGA-II) algorithm represents one of the well-known preference-based evolutionary approaches. This method mainly aims to find a set of the Pareto-optimal solutions in the region of interest (ROI) rather than obtaining the entire Pareto-optimal set. This approach uses Euclidean distance as a metric to calculate the distance between each candidate solution and the reference point. However, this metric may not produce desired solutions because the final minimal Euclidean distance value is unknown. Thus, determining whether the true Pareto-optimal solution is achieved at the end of optimization run becomes difficult. In this study, R-NSGA-II method is modified using the recently proposed simplified Karush-Kuhn-Tucker proximity measure (S-KKTPM) metric instead of the Euclidean distance metric, where S-KKTPM-based distance measure can predict the convergence behavior of a point from the Pareto-optimal front without prior knowledge of the optimum solution. Experimental results show that the algorithm proposed herein is highly competitive compared with several state-of-the-art preference-based EMO methods. Extensive experiments were conducted with 2 to 10 objectives on various standard problems. Results show the effectiveness of our algorithm in obtaining the preferred solutions in the ROI and its ability to control the size of each preferred region separately at the same time., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Mohammed Jameel and Mohamed Abouhawwash.)

For the creation of healable cement concrete matrix, microbial self-healing solutions are significantly more creative and potentially successful. The current study investigates whether gram-positive " Bacillus subtilis " ( B. subtilis ) microorganisms can effectively repair structural and non-structural cracks caused at the nano- and microscale. By creating an effective immobilization strategy in a coherent manner, the primary challenge regarding the viability of such microbes in a concrete mixture atmosphere has been successfully fulfilled. The iron oxide nanoparticles were synthesized. The examined immobilizing medium was the iron oxide nanoparticles, confirmed using different techniques (XRD, SEM, EDX, TGA, and FTIR). By measuring the average compressive strength of the samples (ASTM C109) and evaluating healing, the impact of triggered B. subtilis bacteria immobilized on iron oxide nanoparticles was examined. The compressive strength recovery of cracked samples following a therapeutic interval of 28 days served as a mechanical indicator of the healing process. In order to accurately correlate the recovery performance as a measure of crack healing duration, the pre-cracking load was set at 80% of the ultimate compressive stress, or "f c," and the period of crack healing was maintained at 28 days. According to the findings, B. subtilis bacteria greatly enhanced the compressive strength and speed up the healing process in cracked cement concrete mixture. The iron oxide nanoparticles were proven to be the best immobilizer for keeping B. subtilis germs alive until the formation of fractures. The bacterial activity-driven calcite deposition in the generated nano-/micro-cracks was supported by micrographic and chemical investigations (XRD, FTIR, SEM, and EDX).

Background: To contribute to the World Health Organization's End TBStrategy, the active tuberculosis (TB) case-finding approach has been proven effective., Methods: A total of 66 chest camps were organised for patients in 15 selected districts in Punjab, Pakistan, in 2017. A mixed-method process evaluation was conducted in four randomly selected districts to evaluate the use of chest camps for active TB case finding to reach the maximum number of people with TB and to assess the implementation outcomes, such as effectiveness, feasibility, fidelity, and costs., Results: Results indicated that 1458 attendees visited 24 chest camps in four selected districts. Among attendees, 297 presumptive cases were found and smear-tested; and 34 of the smear-tested were diagnosed as smear-positive TB patients. The prevalence of smear-positive TB patients among the chest camp participants was found to be 2.3%. The findings from interviews showed that preparation of chest camp activities, especially the involvement of community leaders, was found to be effective in achieving the desired level of attendance. The respondents found attending the chest camps for TB symptoms feasible and acceptable. The chest camp costs approximately US$280, including the pre-camp mobilisation events, whereas the cost per TB-positive patient was found to be US$197.64., Conclusions: The higher number of attendees without TB symptoms, the low proportion of smear-negative case registrations; and relatively high unit cost (per patient detected) were the areas identified for further attention. The study supports the continuation of chest camp activity, with further attention required for quality and efficiency concerns.

Nanotechnology is a rapidly evolving discipline as it has a wide variety of applications in several fields. They have been synthesized in a variety of ways. Traditional processes such as chemical and physical synthesis have limits, whether in the form of chemical contamination during synthesis operations or in subsequent applications and usage of more energy. Over the last decade, research has focused on establishing easy, nontoxic, clean, cost-effective, and environmentally friendly techniques for nanoparticle production. To achieve this goal, biological synthesis was created to close this gap. Biosynthesis of nanoparticles is a one-step process, and it is ecofriendly in nature. The metabolic activities of biological agents convert dissolved metal ions into nanometals. For biosynthesis of metal nanoparticles, various biological agents like plants, fungus, and bacteria are utilized. In this review paper, the aim is to provide a summary of contemporary research on the biosynthesis of gold nanoparticles and their applications in various domains have been discussed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Arpita Roy et al.)

The linear complementarity approach has been utilized as a systematic and unified numerical process for determining the response of a rigid-plastic structure subjected to impulsive loading. However, the popular Lemke Algorithm for solving linear complementarity problems (LCP) encounters numerical instability issues whilst tracing the response of structures under extreme dynamic loading. This paper presents an efficient LCP approach with an enhanced initiation subroutine for resolving the numerical difficulties of the solver. The numerical response of the impulsively loaded structures is affected by the initial velocity profile, which if not found correctly can undermine the overall response. In the current study, the initial velocity profile is determined by a Linear Programming (LP) subroutine minimizing the energy function. An example of a uniform impulsively loaded simply supported beam is adduced to show the validity and accuracy of the proposed approach. The beam is approximated with bending hinges having infinite resistance to shear. Comparison of the numerical results to the available closed-form solution confirms the excellent performance of the approach. However, a subsequent investigation into a beam having the same support conditions and the applied loading, but with bending and shear deformation, results in numerical instability despite optimizing the initial velocity profile. Thus a more generic description of kinetics and kinematics is proposed that can further enhance the numerical efficiency of the LCP formulation. The ensuing numerical results are compared with the available close form solution to assess the accuracy and efficiency of the developed approach., (© 2022. The Author(s).)

Breath sensor technology can be used in medical diagnostics. This study aimed to build a device to measure the level of hydrogen sulfide, ammonia, acetone and alcohol in exhaled breath of patients as well as healthy individuals. The purpose was to determine the efficacy of these gases for detection of obstructive lung disease. This study was conducted on a total of 105 subjects, where 60 subjects were patients of obstructive lung disease and 45 subjects were healthy individuals. Patients were screened by means of the Pulmonary Function Test (PFT) by a pulmonologist. The gases present in the exhaled breath of all subjects were measured. The level of ammonia (32.29 ± 20.83 ppb), (68.83 ± 35.25 ppb), hydrogen sulfide (0.50 ± 0.26 ppm), (62.71 ± 22.20 ppb), and acetone (103.49 ± 35.01 ppb), (0.66 ± 0.31 ppm) in exhaled breath were significantly different (p < 0.05) between obstructive lung disease patients and healthy individuals, except alcohol, with a p-value greater than 0.05. Positive correlation was found between ammonia w.r.t Forced Expiratory Volume in 1 s (FEV1) (r = 0.74), Forced Vital Capacity (FVC) (r = 0.61) and Forced Expiratory Flow (FEF) (r = 0.63) and hydrogen sulfide w.r.t FEV1 (r = 0.54), FVC (r = 0.41) and FEF (r = 0.37). Whereas, weak correlation was found for acetone and alcohol w.r.t FEV1, FVC and PEF. Therefore, the level of ammonia and hydrogen sulfide are useful breath markers for detection of obstructive lung disease.

Flow around circular cylinder has been extensively studied by researchers for several decades due to its wide range of engineering applications such as in heat exchangers, marine cables, high rise building, chimneys, and offshore structures. The lack of clear understanding of the unsteady flow dynamics in the wake of circular cylinder and high computational cost are still an area of high interest amongst the researchers. The aim of the current study is to investigate the effect of variation in spanwise length and grid resolution in the spanwise direction on the recirculation length, separation angle of wake flow by performing large eddy simulations (LES). This study is an extension to previous work by Khan, NB et al, 2019 in which the spanwise length is restricted to 4D only. In current study, the spanwise length is changed from 0.5D to 8D where D is diameter of cylinder and mesh resolution in the spanwise direction is changed from 1 to 80 elements in the present study. The recirculation length, separation angle and wake characteristics are analyzed in detail. It is concluded that after getting optimize spanwise length, mesh resolution in the spanwise direction is the only parameter contributing toward better result., Competing Interests: The authors have declared that no competing interests exist.

Autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1) is an autosomal recessive disorder characterized by progressive weakness of the proximal limb and girdle muscles. Biallelic mutations in CAPN3 are reported frequently to cause LGMDR1. Here, we describe 11 individuals from three unrelated consanguineous families that present with typical features of LGMDR1 that include proximal muscle wasting, weakness of the upper and lower limbs, and elevated serum creatine kinase. Whole-exome sequencing identified a rare homozygous CAPN3 variant near the exon 2 splice donor site that segregates with disease in all three families. mRNA splicing studies showed partial retention of intronic sequence and subsequent introduction of a premature stop codon (NM&#95;000070.3: c.379 + 3A>G; p.Asp128Glyfs*15). Furthermore, we observe reduced CAPN3 expression in primary dermal fibroblasts derived from an affected individual, suggesting instability and/or nonsense-mediated decay of mutation-bearing mRNA. Genome-wide homozygosity mapping and single-nucleotide polymorphism analysis identified a shared haplotype and supports a possible founder effect for the CAPN3 variant. Together, our data extend the mutational spectrum of LGMDR1 and have implications for improved diagnostics for individuals of Pakistani origin., (© 2021 Wiley Periodicals LLC.)

Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition., Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable., Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca 2+ -binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4., Conclusion: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans., (© 2021. The Author(s).)

Background: In living donor renal transplantation, surgeons traditionally prefer the left kidney for donation. The aim of this study was to assess the effects of the choice of laterality of donor nephrectomy on donor and recipient outcomes., Methods: The data was obtained from the UK National Health Service Blood and Transplant (NHSBT). During the study period, 7919 donor nephrectomy and transplantation were carried out in 24 transplant centers. Of these procedures, 6407 (80.9%) were left and 1512 (19.1%) were right kidney donors., Results: Right kidney donation was associated with higher incidence of surgical site infection in the donor. Recipient outcome was superior for left-sided kidneys in terms of immediate graft function, delayed graft function, graft loss within 30 days, and graft survival at 3 years, but not at 1 and 5 years. Open donor nephrectomy (n = 2396, 30.2%) was associated with higher rates of pneumothorax and hemorrhage, longer hospital stay, and inferior graft survival at 3 and 5 years compared with laparoscopic donor nephrectomy (n = 5523, 69.8%)., Conclusions: A right donor nephrectomy is associated with higher rate of wound infection in the donor and similar long-term graft outcomes in the recipients. Laparoscopic donor nephrectomy offers lower rate of major complications in the donor and a better overall graft survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic-microcephaly primary hereditary (MCPH)-and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH ( n = 3) or Seckel syndrome ( n = 2). In addition to homozygous causal variants in ASPM or CENPJ , we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT -genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression. We also observed centrosome amplification errors in patient cells, which were twofold higher in MOPDII as compared to Seckel cells. Taken together, these observations advocate for consideration of additional variants in related genes for their role in modifying the expressivity of the phenotype and need to be considered in genetic counseling and risk assessment.

Purpose: The COVID-19 pandemic has resulted in mandatory isolation and quarantine. The objective of this study was to describe and compare the psychological impacts of COVID-19 isolation and quarantine., Methods: This was a cross-sectional retrospective study. Participants were Bahrainis aged >18 years who had undergone either isolation or quarantine. Eligible participants were identified from the COVID-19 contacts (quarantine) and cases (isolation) database of Bahrain. Validated questionnaires for self-reported depression (Center for Epidemiological Studies - depression [CES-D]), posttraumatic stress (Impact of Event Scale - revised [IES-R]), and perceived stigma (Stigma Scale [SS]) were administered., Results: Mean CES-D, IES-R, and SS scores were 16.76±5.65, 13.50±14.67, and 25.29±7.99, respectively. In sum, 40% (205 of 502) of participants showed clinically significant depression, and <20% (98 of 502) had indications of some posttraumatic distress, with greater depression and distress in those isolated than those quarantined. Perceived stigma was reported by 53.4% (268 of 502) of participants, more prominent among those quarantined. Depression and posttraumatic stress scores were significantly higher in females, college students, those with a history of mental health conditions, knowing a COVID-19 fatality, and experiencing social conflict. Age was a significant variable correlated with all three scales, with younger participants indicating more distress, depression, and stigma. Duration of segregation was significantly correlated with CES-D, score showing more depressive symptoms as the duration of isolation increased. Significant predictors were age, sex, history of mental illness, and COVID-19 status., Conclusion: Isolated and quarantined individuals reported depression, perceived stigma, and to a lesser extent distress. Psychological interventions identifying and targeting people with different-severity psychological burdens are in urgent need., Competing Interests: The authors declare that they have no competing interests., (© 2021 Jassim et al.)

Aim: The aim of this study is to present the outcome of kidney transplantation after laparoendoscopic single-site donor nephrectomy (LESS DN) compared with conventional laparoscopic donor nephrectomy (LDN) in a single-center experience., Methods: This retrospective study compares data from the initial experience with 110 consecutive LESS DN donors and their recipients (group A) with 205 consecutive conventional LDN donors and their recipients (group B)., Results: This study compared 110 LESS DNs completed in an 18-month period with 205 LDNs completed in the immediately preceding 42-month period. All procedures were performed by the same surgeon. In groups A and B, respectively, the incidence of immediate graft function was 90% vs 91.2%, slow graft function was 9% vs 5.3%, delayed graft function was 0.9% vs 2.9%, graft loss was 0.9% vs 2.9%, and death with a functioning graft was 0.9% vs 1.5%. The mean serum creatinine levels were 1.3 ± 0.93 mg/dL vs 1.4 ± 1.2 mg/dL (P = .447), 1.1 ± 0.33 mg/dL vs 1.2 ± 0.75 mg/dL (P = .184), and 1.05 ± 0.25 mg/dL vs 1.1 ± 0.39 mg/dL (P = .224) at 7, 30, and 365 days after transplantation. The estimated glomerular filtration rate at 1 year was 88 ± 18.2 vs 83 ± 12.2 mL/min/1.73 m 2 (P = .004). The mean donor operative times in groups A and B were 175.9 ± 24.9 minutes vs 199.88 ± 37.06 minutes (P = .0001), respectively, and the mean warm ischemia time was 5.2 ± 1.02 minutes vs 3.64 ± 1.38 minutes, respectively (P = .0001). The mean body mass index, the incidence of complex vascular anatomy, and the rate of complications were the same in the 2 donor groups., Conclusions: The outcome of kidney transplantation after LESS DN is comparable to conventional LDN. LESS DN can be employed as the primary approach for kidney donation with low donor risk and without compromising recipient outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Studies of intermittent claudication gait report inconsistent outcomes. Changes in gait are often attributed to degradation of calf muscles, but causation has not been proven through real-time electromyographic data. Neither have effects of walking speed been fully considered. This study aimed to investigate the effect of intermittent claudication on kinematics, kinetics and muscle activity during pain-free gait., Methods: 18 able bodied individuals and 18 with intermittent claudication walked at their preferred speed while lower limb kinematic, kinetic and electromyography data were collected., Findings: People with intermittent claudication walk slower and with reduced step length. Internal ankle plantarflexion moment (P = 0.004, effect size = 0.96) and ankle power generation (P < 0.001, effect size = 1.36) in late stance were significantly reduced for individuals with intermittent claudication. Significant moment and power reductions at the knee and power reduction at hip occurred in early stance, with similar reductions in early and late stance for ground reaction forces. Peak electromyography of soleus activity was significantly reduced in late stance (P = 0.01, effect size = 1.1, n = 13). Effects were independent of walking speed., Interpretation: Reductions in ankle plantarflexion moments and power generation were consistent with reduced soleus electromyography activity and reduced peak vertical ground reaction forces during late stance. These effects are not due to a reduced walking speed. Changes in knee and hip function are also unrelated to walking speed. These outcomes provide a platform for the design and evaluation of interventions that seek to restore normal walking and improve pain-free walking distances for people with intermittent claudication., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study evaluates the impact of two separate incubation periods (4 and 6 weeks) on the morphology of sol-gel-fabricated ZnO nanospikes (ZNs), that is, ZN1 and ZN2, respectively. We further analyzed the inhibitory effects of ZN1 and ZN2 on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa (PAO1) and Chromobacterium violaceum (strains 12472 and CVO26). The size of the synthesized ZNs was in the range of 40-130 nm, and finer nanoparticles were synthesized after an incubation period of 6 weeks. Treatment with ZNs decreased the production of violacein in the pathogen without affecting the bacterial growth, which indicated that ZNs inhibited the QS signaling regulated by N -acyl homoserine lactone. ZN2 had a higher inhibitory action on the virulence factor productivity than ZN1. Furthermore, ZN2-treated cells displayed a substantial decrease in azocasein-degrading protease activity (80%), elastase activity (83%), and pyocyanin production (85%) relative to untreated P. aeruginosa PAO1 cells. Treatment with ZN2 decreased swarming motility and exopolysaccharide production by 89 and 85%, respectively. ZN2 was effective against both the las & pqs systems of P. aeruginosa and exhibited broad-spectrum activity. Additionally, ZN2 was more efficient in inhibiting the biofilm formation at the attachment stage than ZN1. These findings revealed that in P. aeruginosa , ZN2 demonstrated inhibitory effects on QS as well as on the development of biofilms. Thus, ZN2 can be potentially used to treat drug-resistant P. aeruginosa infections., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Extensive research on functionalized graphene, graphene oxide, and carbon nanotube based cement composites has been carried out to strengthen and overcome the shortcomings of construction materials. However, less literature is available on the pure graphene based cement composite. In this review paper, an in-depth study on a graphene-based cement composite was performed. Various structural forms of graphene and classifications of graphene-based nanomaterial have been presented. The dispersion mechanism and techniques, which are important for effective utilization in the construction industry, are reviewed critically. Micro-scale characterization of carbon-based cement composite using thermogravimetric analysis (TGA), infrared (IR) spectroscopic analysis, x-ray diffractometric (XRD) analysis, and morphological analysis has also been reviewed. As per the authors' knowledge, for the first time, a review of flow, energy harvesting, thermoelectrical, and self-sensing properties of graphene and its derivatives as the bases of cement composite are presented. The self-sensing properties of the composite material are reported by exploring physical applications by reinforcing graphene nanoplatelets (GNPs) into concrete beams.

Background Upper gastrointestinal bleeding is a life-threatening emergency. Endoscopy is the therapeutic and diagnostic procedure of choice after initial stabilization of the patient. But the presence of retained blood, blood products, and other residual material in the stomach is a big challenge for endoscopists during urgent endoscopy after acute upper gastrointestinal bleeding. Intravenous erythromycin before endoscopy improves the visualization of gastric and duodenal mucosa in these patients. Use of oral erythromycin is more easy and convenient, so the objective of our study was to assess the effects of oral erythromycin on quality of endoscopy in upper gastrointestinal bleeding patients. Methods This interventional study was conducted at the Department of Medicine, POF Hospital Wah Cantt, Pakistan from January 2019 to December 2019. Patients with clinical evidence of acute upper gastrointestinal bleeding within 12 hours were inducted consecutively. Patients were randomly assigned to erythromycin (500 mg) suspension or placebo, orally three hours before endoscopy. One endoscopist performed all the procedures with the same double-channel video endoscope. The primary endpoint was endoscopic quality. The secondary endpoints were the need for second-look endoscopy within 48 hours, endoscopy related complications, therapeutic procedure performed or not during endoscopy, number of blood transfusions, and length of hospital stay. Results A total of 60 patients were included in the study; 30 received erythromycin and 30 received placebo. Out of these, 60% were male and 40% were female. The mean age was 53.68 ± 16.64. Quality of endoscopy was much better in the erythromycin group (83.3%) as compared to placebo (40%). Erythromycin did not shorten the endoscopic duration (15.53 vs. 14.33 minutes in the placebo group; p=0.216) and length of hospital stay (5.23 in erythromycin vs. 5.40 days in placebo group; p=0.807). Statistically no significant association was found between use of erythromycin and establishment of cause of bleed, need for second-look endoscopy, number of blood transfusions and number of endoscopic therapeutic procedures. Conclusion Erythromycin oral suspension before endoscopy in patients with acute upper gastrointestinal bleeding produced good quality of endoscopy in our study. It improved the visualization of gastric and duodenal mucosa significantly. However, it did not shorten the duration of endoscopy or hospital stay. There was no significant difference in number of second-look endoscopies and blood transfusions as well., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Ali Shah et al.)

In the present scenario, insecticides/pesticides are used intensively to control the various insect pests. Indiscriminate use of these insecticides/pesticides affects the structure and function of the ecosystem. In this context, a thorough toxicological study of each insecticide/pesticide is a must to understand the hazardous effect of these chemicals on the target and non-target organisms. The present study was aimed to understand the hazardous effect of thiamethoxam against the Spodoptera litura. Different concentrations (20-80 μg/mL) of thiamethoxam were prepared, and fourth instar larvae of S. litura were allowed to feed for 12-72 h. We first examined the interaction of thiamethoxam with DNA. Next, treated and non-treated larvae were assessed for different biological parameters such as mortality, emergence, fecundity, fertility, longevities, and biochemical parameters. Our result showed that thiamethoxam directly interacts with the DNA and significantly influenced the different biological and biochemical parameters of exposed the organisms. We observed a significant change in stress enzymes such as SOD, CAT, and GST. A similar observation was also made with the oxidative marker for lipid damage, MDA and DNA damage, 8-OHdG, respectively. In conclusion, our results suggest that improper use of synthetic chemical insecticides influenced both biological and biochemical parameters through oxidative stress and probably damage the genetic material., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Magnetohydrodynamics or hydro-magnetics (MHD) is the study of dynamics in the presence of magnetic characteristics and impact of electrically conducting liquids which has a significant applications in engineering and biomedical sciences. Liquid metals, plasma, electrolytes and salt water are the examples of such magneto-fluids. MHD liquid flow in various geometries significant to engineering sciences is an interesting and noteworthy scientific area because of applications. The above applications of magnetohydrodynamics insist the engineers and analyst to develop new mathematical modeling in the field of fluid mechanics. Therefore, we considered electrical conducting viscous fluid flow over a curved surface with second order slip. The Buongiorno model is utilized in the modeling of flow problem with thermophoretic and Brownian diffusions. The effects of viscous dissipation, thermal radiation and Joule heating (Ohmic heating) is used in the modeling of energy equation. Homogeneous-heterogeneous reactions are further considered. The energy equation is modeled., Method: The nonlinear ODE's are obtained through utilization of appropriate transformations and numerical results are computed via NDSolve MATHEMATICA., Results: Velocity field is decreasing function of first order slip parameter. Both Bejan number and entropy generation is upsurged versus heterogeneous reaction parameter., (Copyright © 2019. Published by Elsevier B.V.)

Background: Mixed convection (forced+natural convection) is frequently observed in exceptionally high output devices where the forced convection isn't sufficient to dissipate all of the heat essential. At this point, consolidating natural convection with forced convection will frequently convey the ideal outcomes. Nuclear reactor technology and a few features of electronic cooling are the examples of these processes. Mixed convection problems are categorized by Richardson number (Ri), which is the ratio of Grashof number (for natural convection) and Reynolds number (for forced convection). For buoyancy or mixed convection the relative effect can be addressed by Richardson number. Typically, the natural convection is negligible when Richardson number is less than 0.1 (Ri < 0.1), forced convection is negligible when Richardson number is greater than 10 (Ri > 10) and neither is negligible when (0.1 < Ri < 10). It might be noticed that generally the forced convection is large comparative with natural convection except in case of remarkably low forced flow velocities. The current work gives significant insights regarding dissipative mixed convective Darcy-Forchheimer flow with entropy generation over a stretched curved surface. The energy equation is developed with respect to nonlinear radiation, dissipation and Ohmic heating (Joule heating). Binary reaction via activation energy is accounted., Method: Curvilinear transformations are utilized to change the nonlinear PDE's into ordinary ones. Computational outcomes are obtained via NDSolve MATHEMATICA. The results are computed and discussed graphically., Results: Velocity decays for Forchheimer number. Entropy generation enhances for diffusion parameter and chemical reaction parameter. Concentration profile reduces chemical reaction parameter and enhances for activation parameter., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflict of interest and the paper presents their own work which does not been infringe any third-party rights, especially authorship of any part of the article is an original contribution, not published before and not being under consideration for publication elsewhere., (Copyright © 2019. Published by Elsevier B.V.)

Indiscriminate and unregulated application of pesticides produces deleterious effect in various groups of organisms including humans and the environment. To solve these issues, it has been reported that the residue-free green nanocomposite synergistically enhances the pesticide efficacy. In this study, ZnO nanoparticles (NPs) with a thiamethoxam nanocomposite were synthesized and we investigated their synergistic effect on 4th instar larvae of Spodoptera litura (Lepidoptera: Noctuidae). These larvae were allowed to feed on the composite of ZnO NPs with thiamethoxam (10-90 mg/L) and thiamethoxam-impregnated castor leaves. Observations showed an increased larval mortality (27% increased mortality), a malformation in pupae and adults, overdue emergence, and reduced fecundity and fertility. A significant dose-dependent variation in the biochemical parameters such as superoxide dismutase (SOD), glutathione- S -transferase (GST), and thiobarbituric acid-reactive substances (TBARS) in the treated larvae was also observed. A decline of 72.42 and 33.82% in SOD and GST activity ,respectively, was observed at higher concentration as compared to the control. On the contrary, it enhanced the TBARS level up to 56.7%. The synthesized nanocomposite was characterized by different biophysical techniques such as X-ray diffraction (average crystalline size 34 nm), scanning electron microscopy, transmission electron microscopy (average particle size 30 nm), and Fourier transform infrared spectroscopy (Zn-O stretching peaks at 432 cm -1 and 503 cm -1 ). The observation of the present study suggests that ZnO NPs pave the way for developing cost-effective, eco-friendly, and capable nanomaterial for its applications in the field of biological sciences., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Introduction: The CDC and Illinois Department of Public Health disseminated risk factor criteria for COVID-19 testing early in the pandemic. The objective of this study is to assess the effectiveness of risk stratifying patients for COVID-19 testing and to identify which risk factors and which other clinical variables were associated with SARS-CoV-2 PCR test positivity., Methods: We conducted an observational cohort study on a sample of symptomatic patients evaluated at an immediate care setting. A risk assessment questionnaire was administered to every patient before clinician evaluation. High-risk patients received SARS-CoV-2 test and low-risk patients were evaluated by a clinician and selectively tested based on clinician judgment. Multivariate analyses tested whether risk factors and additional variables were associated with test positivity., Results: The adjusted odds ratio of testing positive was associated with COVID-19-positive or suspect close contact (aOR 1.56, 95% CI 1.15-2.10), large gathering attendance with a COVID-19-positive individual (aOR 1.92, 95% CI 1.10-3.34), and, with the largest effect size, decreased taste/smell (aOR 2.83, 95% CI 2.01-3.99). Testing positive was associated with ages 45-64 and ≥65 (aOR 1.75, 95% CI 1.25-2.44, and aOR 2.78, 95% CI 1.49-5.16), systolic blood pressures ≤120 (aOR 1.64, 95% CI 1.20-2.24), and, with the largest effect size, temperatures ≥99.0°F (aOR 3.06, 95% CI 2.23-4.20). The rate of positive SARS-CoV-2 test was similar between high-risk and low risk patients (225 [22.2%] vs 50 [19.8%]; P  = .41)., Discussion: The risk assessment questionnaire was not effective at stratifying patients for testing. Although individual risk factors were associated with SARS-CoV-2 test positivity, the low-risk group had similar positivity rates to the high-risk group. Our observations underscore the need for clinicians to develop clinical experience and share best practices and for systems and payors to support policies, funding, and resources to test all symptomatic patients.

With the wave of artificial intelligence sweeping the world in recent years, UAVs is widely used in various fields. UAV path planning has attracted much attention from scientists as an essential part of UAV work. In order to design an efficient and reasonable 3D UAV path planning program, recent researchers have invented and improved many algorithms. This paper proposes an elite RIME algorithm for 3D UAV path planning. First, we propose an elite reverse learning population selection strategy based on piecewise mapping to enhance the population diversity of the algorithm for better exploration. Second, this paper proposes a stochastic factor-controlled elite pool exploration strategy so that the algorithm is difficult to enter the local optimum and can better explore the global optimum. Then, this paper proposes a hard frost puncture exploitation strategy based on the sine-cosine function so that the algorithm can find the global optimum faster during the exploitation process. Meanwhile, in order to test the performance of the algorithm proposed in this paper, we compare it with 13 other intelligent optimization algorithms that are classical and popular nowadays on 52 test functions in three test sets, CEC2017, CEC2020, and CEC2022, and obtain competitive results. Finally, we applied it to the 3D UAV path planning problem in three different terrain scenarios, and the ELRIME algorithm achieved good results in all of them. Especially in the 7-peak model, the ELRIME algorithm improves the performance of the RIME algorithm by a factor of two. In the 9-peak model, the average value aspect also reduce the cost by 91 compared to the RIME algorithm, and more importantly, it has the smallest fluctuation in 30 runs, which is among the most stable of all the compared algorithms. In the 12-peak model, its stability is also significantly enhanced, and in terms of worst-case cost, it improves the cost by 340 compared to RIME., (© 2024. The Author(s).)

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C 2 H 2 domain-containing transcription factor., Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals., Results: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia., Conclusion: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

Indiscriminate use of insecticides/pesticides affects the structure and function of the ecosystems. The present study was aimed to investigate the toxic potential of Fipronil (a second generation phenylpyrazole) using Spodoptera litura larvae (Lepidoptera: Noctuidae) as an experimental model. Commercial grade of Fipronil, an insecticide was fed (20-80 mg/L) to the 4th instar larvae of S. litura for 12-72 h and examined different molecular, biochemical and organismal parameters. We observed a significant dose- and time-dependent changes in the biochemical parameters such as Superoxide dismutase (SOD), Glutathione-S-transferase (GST), Catalase (CAT), level of 8-hydroxy 2'-deoxyguanosine (8-OHdG) and Thiobarbituric Acid Reactive Substances (TBARS) [Malondialdehyde (MDA) equivalent] in the exposed larvae. We also observed that Fipronil interacts with DNA. Next, we examined the influence of sub-cellular damages at the organismal level. The alterations in the parameter such as the delayed emergence of larvae, reduced fecundity, fertility and increased rate of malformation in pupae and adults indicate the sub-organismal damages influence at the organismal level. The findings of the present study suggest that discriminatory non-scientific use of insecticide/pesticide might influence the population dynamics of insects and in large ecosystem too and needs further thorough investigations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Angiosarcomas are highly aggressive tumors of endothelial origin, which carry a poor prognosis. Fenofibrate is a hypolipidemic drug, which acts by activating the transcription factor PPARα. It has also been widely reported to have 'anti-cancer' activity. The current study investigated its effect in a murine VEGF-dependent angiosarcoma cell-line, MS1 VEGF. The study utilised assays to monitor cell proliferation and viability, apoptosis, cell cycle progression, mitochondrial membrane potential, changes in protein expression, and changes in miRNA expression using microarrays. Fenofibrate showed potent anti-proliferative action in MS1 VEGF angiosarcoma cells, without inducing apoptosis. It enriched cells in G2/M cell cycle phase and hyperpolarised mitochondria. Other PPARα activators failed to mimic fenofibrate action. Inhibitors of PPARα and NFκB failed to reverse the inhibitory effect of fenofibrate and their combination with fenofibrate was cytotoxic. Fenofibrate downregulated the expression of key VEGF-effector proteins, including Akt, ERK, Bcl-2 and survivin, and a chemical inhibitor screen discovered relevance of these proteins to cell proliferation. A miRNA microarray revealed that fenofibrate differentially regulated cellular miRNAs with known roles in cancer and angiogenesis. The data raise the possibility that fenofibrate could be useful in angiosarcoma therapy, especially considering its well-established clinical safety and tolerability profile.

The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients., Methods: Patients 60 years or older who received transplants from DCD donors 60 years or older, between February 2010 and January 2014, were identified from a prospectively maintained database., Results: Over a 4-year period, 88 patients 60 years or older received DCD kidney transplants from donors 60 years or older. Of these 44 (55%) were 60 to 69 years old and 40 (45%) were 70 years or older. Median follow up was 63 months. Patient survival was 95% and 79% at 1 and 5 years, respectively, with a survival in those 70 years and older (69%) compared with those aged 60 to 69 (88%) years (P = .01). Censored for death graft survival was 94% and 80% at 1 and 5 years, respectively. Median estimated glomerular filtration rate at 12 months and 36 months was 36 mL/min (range, 11-70 mL/min) and 39.5 mL/min (range, 11-77 mL/min), respectively., Conclusions: Older DCD kidneys, when transplanted into older recipients, result in good patient and graft survival and an acceptable graft function, especially considering their age. This represents a good use of this organ resource., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Kidney transplants from young pediatric donors are uncommonly performed in the UK. Published literature of kidney transplant from donors weighing less than 5 kg is sparse. We present our initial experience of en bloc kidney transplantation (EKT) from donors weighing less than 20 kg, including neonatal donors. All recipients undergoing EKT from donors under 20 kg at our center from January 2005 to October 2016 were included. Donor and recipient details were recorded from a prospective database. Electronic patient records were examined for follow-up data. Of 30 EKTs included, 15 were from ≤5 kg donors and 15 from >5 kg donors (median weight 3.4 and 12.7 kg, respectively). One-year graft survival for ≤5 kg and >5 kg donors for EKT was 86.7% and 93.3% (P = 0.85), respectively. Progressive improvement in estimated GFR (eGFR) was noted in both donor categories through first-year posttransplant but in the ≤5 kg donor category significant improvement was seen at 12 months compared to 3 months after transplantation (median eGFR 37.3 vs 70.0 mL/min/1.73 m 2 , P = 0.03). Two early graft losses were attributable to early vascular complications and one graft loss due to primary nonfunction. Our data show that kidney transplantation from such donors is a feasible option at centers with experience of EKT, albeit with increased risk of early graft loss., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Breast cancer is one of the most common malignancies in women worldwide. In breast cancer, the cell proliferation rate is known to influence the cancer malignancy. Recent studies have shown that DNA replication initiation/licensing factors are involved in cancer cell proliferation as well as cancer cell migration and invasion. Licensing factors have also been reported as important prognostic markers in lung, prostrate, and bladder cancers. Here, we studied the role of MCM10, a novel licensing factor, in breast cancer progression. From the public database, NCBI, we investigated six independent breast cancer patient cohorts, totaling 1283 patients. We observed a significant association between high MCM10 mRNA expression with tumor grading and patients' survival time. Most importantly, using breast cancer cohorts with available treatment information, we also demonstrated that a high level of MCM10 is associated with a better response to conventional treatment. Similarly, in in vitro studies, the expression level of MCM10 in breast cancer cell lines is significantly higher compared to paired normal breast epithelium cells. Knockdown of MCM10 expression in the cancer cell line showed significantly decreased tumorigenic properties such as cell proliferation, migration and anchorage independence. The MCF7 breast cancer cell line, after MCM10 expression knockdown, showed significantly decreased tumorigenic properties such as cell proliferation, migration, and anchorage independent growth. Mechanistically, MCM10 expression is observed to be regulated by an Estrogen Receptor (ER) signaling pathway, where its expression is suppressed by the inhibition of the ER or serum withdrawal. Our results suggest that MCM10 plays an important role in breast cancer progression and is a potential prognostic/predictive biomarker and therapeutic target for breast cancer patients.

The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP) range from a mild form of multiple epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the phenotypic effect from biallelic COMP variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH in 2 individuals. Another 14 family members presented with a mild PSACH phenotype similar to MED. Using exome sequencing and subsequent segregation analysis, we identified homozygosity for a COMP missense variant [c.1423G>A; p.(D475N)] in the 2 severely affected individuals, whereas family members with the mild PSACH phenotype were heterozygous. Our observations show for the first time that a biallelic COMP variant may be associated with pronounced and widespread skeletal malformations suggesting an additive effect of the 2 mutated alleles., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study numerically investigates the vortex-induced vibration (VIV) of an elastically mounted rigid cylinder by using Reynolds-averaged Navier-Stokes (RANS) equations with computational fluid dynamic (CFD) tools. CFD analysis is performed for a fixed-cylinder case with Reynolds number (Re) = 104 and for a cylinder that is free to oscillate in the transverse direction and possesses a low mass-damping ratio and Re = 104. Previously, similar studies have been performed with 3-dimensional and comparatively expensive turbulent models. In the current study, the capability and accuracy of the RANS model are validated, and the results of this model are compared with those of detached eddy simulation, direct numerical simulation, and large eddy simulation models. All three response branches and the maximum amplitude are well captured. The 2-dimensional case with the RANS shear-stress transport k-w model, which involves minimal computational cost, is reliable and appropriate for analyzing the characteristics of VIV.

Objective: Autosomal recessive primary microcephaly (MCPH) is a rare condition characterized by a reduced cerebral cortex accompanied with intellectual disability. Mutations in 17 genes have been shown to cause this phenotype. Recently, mutations in CIT, encoding CRIK (citron rho-interacting kinase)-a component of the central spindle matrix-were added. We aimed at identifying novel MCPH-associated genes and exploring their functional role in pathogenesis., Methods: Linkage analysis and whole exome sequencing were performed in consanguineous and nonconsanguineous MCPH families to identify disease-causing variants. Functional consequences were investigated by RNA studies and on the cellular level using immunofluorescence and microscopy., Results: We identified homozygous mutations in KIF14 (NM&#95;014875.2;c.263T>A;pLeu88*, c.2480&#95;2482delTTG; p.Val827del, and c.4071G>A;p.Gln1357=) as the likely cause in 3 MCPH families. Furthermore, in a patient presenting with a severe form of primary microcephaly and short stature, we identified compound heterozygous missense mutations in KIF14 (NM&#95;014875.2;c.2545C>G;p.His849Asp and c.3662G>T;p.Gly1221Val). Three of the 5 identified mutations impaired splicing, and 2 resulted in a truncated protein. Intriguingly, Kif14 knockout mice also showed primary microcephaly. Human kinesin-like protein KIF14, a microtubule motor protein, localizes at the midbody to finalize cytokinesis by interacting with CRIK. We found impaired localization of both KIF14 and CRIK at the midbody in patient-derived fibroblasts. Furthermore, we observed a large number of binucleated and apoptotic cells-signs of failed cytokinesis that we also observed in experimentally KIF14-depleted cells., Interpretation: Our data corroborate the role of an impaired cytokinesis in the etiology of primary and syndromic microcephaly, as has been proposed by recent findings on CIT mutations. Ann Neurol 2017;82:562-577., (© 2017 American Neurological Association.)