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In this study, experimental research has been done to investigate and analyze the effects of fiber hybridization and stacking configurations on the impact performance of carbon/flax bio-hybrid composite laminates. A total of four composite laminates with pure carbon, sandwich, symmetric, and asymmetric stacking configurations were manufactured and investigated in terms of low-velocity impact test with varying energies between 30J and 75J. Both qualitative and quantitative analysis were performed to analyze the damage and failure patterns in the composite layups and were compared with the pure carbon-based layup to identify the effects stacking configuration. The experimental findings showed the symmetric layup having a consistent distribution of flax fiber layers, showed the most enhanced performance as compared to the carbon-based layup Moreover, damage and failure modes differed among layups and increased with varying impact energies. Furthermore, to enable the thorough comparison of the configurations, Composite Performance Index (CPI) was developed, which suggests that bio-hybrid configurations when designed optimally with a suitable number of evenly distributed flax layers, can equal or exceed the performance of a pure carbon fiber configuration.

Background:  In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care sector. In the context of the SALUS study, this approach is applied in practice in the form of electronic platforms to display and process disease-relevant data of glaucoma patients., Objectives:  The SALUS ECF is designed and implemented to support data acquisition and presentation, monitoring, and outcome control for patients suffering from glaucoma in a clinical setting. Its main aim is to provide a means for out- and inpatient exchange of information between various stakeholders with an intuitive user interface in ophthalmologic care. Instrument data, anamnestic data, and diagnostic assessments need to be accessible and historic data stored for patient monitoring. Quality control of the data is ensured by a reading center., Methods:  Based on an intensive requirement analysis, we implemented the ECF as a web-based application in React with a Datomic back-end exposing REST and GraphQL APIs for data access and import. A flexible role management was developed, which addresses the various tasks of multiple stakeholders in the SALUS study. Data security is ensured by a comprehensive encryption concept. We evaluated the usability and efficiency of the ECF by measuring the durations medical doctors need to enter and work with the data., Results:  The evaluation showed that the ECF is time-saving in comparison to paper-based assessments and offers supportive monitoring and outcome control for numerical and imaging-related data. By allowing patients and physicians to access the digital ECF, data connectivity as well as patient autonomy were enhanced., Conclusion:  ECFs have a great potential to efficiently support all patients and stakeholders involved in the care of glaucoma patients. They benefit from the efficient management and view of the data tailored to their specific role., Competing Interests: None declared., (Thieme. All rights reserved.)

Adaptive therapy (AT) is an evolution-based treatment strategy that exploits cell-cell competition. Acquired resistance can change the competitive nature of cancer cells in a tumor, impacting AT outcomes. We aimed to determine if adaptive therapy can still be effective with cell's acquiring resistance. We developed an agent-based model for spatial tumor growth considering three different types of acquired resistance: random genetic mutations during cell division, drug-induced reversible (plastic) phenotypic changes, and drug-induced irreversible phenotypic changes. These three resistance mechanisms lead to different spatial distributions of resistant cells. To quantify the spatial distribution, we propose an extension of Ripley's K-function, Sampled Ripley's K-function (SRKF), which calculates the non-randomness of the resistance distribution over the tumor domain. Our model predicts that the emergent spatial distribution of resistance can determine the time to progression under both adaptive and continuous therapy (CT). Notably, a high rate of random genetic mutations leads to quicker progression under AT than CT due to the emergence of many small clumps of resistant cells. Drug-induced phenotypic changes accelerate tumor progression irrespective of the treatment strategy. Low-rate switching to a sensitive state reduces the benefits of AT compared to CT. Furthermore, we also demonstrated that drug-induced resistance necessitates aggressive treatment under CT, regardless of the presence of cancer-associated fibroblasts. However, there is an optimal dose that can most effectively delay tumor relapse under AT by suppressing resistance. In conclusion, this study demonstrates that diverse resistance mechanisms can shape the distribution of resistance and thus determine the efficacy of adaptive therapy., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare. All authors have approved the manuscript and agree with its submission to this journal., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A maximum-tolerated dose (MTD) reduces the drug-sensitive cell population, though it may result in the competitive release of drug resistance. Alternative treatment strategies such as adaptive therapy (AT) or dose modulation aim to impose competitive stress on drug-resistant cell populations by maintaining a sufficient number of drug-sensitive cells. However, given the heterogeneous treatment response and tolerable tumor burden level of individual patients, determining an effective dose that can fine-tune competitive stress remains challenging. This study presents a mathematical model-driven approach that determines the plausible existence of an effective dose window (EDW) as a range of doses that conserve sufficient sensitive cells while maintaining the tumor volume below a threshold tolerable tumor volume (TTV). We use a mathematical model that explains intratumor cell competition. Analyzing the model, we derive an EDW determined by TTV and the competitive strength. By applying a fixed endpoint optimal control model, we determine the minimal dose to contain cancer at a TTV. As a proof of concept, we study the existence of EDW for a small cohort of melanoma patients by fitting the model to longitudinal tumor response data. We performed identifiability analysis, and for the patients with uniquely identifiable parameters, we deduced patient-specific EDW and minimal dose. The tumor volume for a patient could be theoretically contained at the TTV either using continuous dose or AT strategy with doses belonging to EDW. Further, we conclude that the lower bound of the EDW approximates the minimum effective dose (MED) for containing tumor volume at the TTV., (© 2023. The Author(s).)

COVID-19 is caused by the SARS-CoV-2 virus, which is mainly transmitted directly between humans. However, it is observed that this disease can also be transmitted through an indirect route via environmental fomites. The development of appropriate and effective vaccines has allowed us to target and anticipate herd immunity. Understanding of the transmission dynamics and the persistence of the virus on environmental fomites and their resistive role on indirect transmission of the virus is an important scientific and public health challenge because it is essential to consider all possible transmission routes and route specific transmission strength to accurately quantify the herd immunity threshold. In this paper, we present a mathematical model that considers both direct and indirect transmission modes. Our analysis focuses on establishing the disease invasion threshold, investigating its sensitivity to both transmission routes and isolate route-specific transmission rate. Using the tau-leap algorithm, we perform a stochastic model simulation to address the invasion potential of both transmission routes. Our analysis shows that direct transmission has a higher invasion potential than that of the indirect transmission. As a proof of this concept, we fitted our model with early epidemic data from several countries to uniquely estimate the reproduction numbers associated with direct and indirect transmission upon confirming the identifiability of the parameters. As the indirect transmission possess lower invasion potential than direct transmission, proper estimation and necessary steps toward mitigating it would help reduce vaccination requirement., (© 2022. The Author(s).)

The COVID-19 pandemic has caused a global crisis with 47,209,305 confirmed cases and 1,209,505 confirmed deaths worldwide as of November 2, 2020. Forecasting confirmed cases and understanding the virus dynamics is necessary to provide valuable insights into the growth of the outbreak and facilitate policy-making regarding virus containment and utilization of medical resources. In this study, we applied a mathematical epidemic model (MEM), statistical model, and recurrent neural network (RNN) variants to forecast the cumulative confirmed cases. We proposed a reproducible framework for RNN variants that addressed the stochastic nature of RNN variants leveraging z-score outlier detection. We incorporated heterogeneity in susceptibility into the MEM considering lockdowns and the dynamic dependency of the transmission and identification rates which were estimated using Poisson likelihood fitting. While the experimental results demonstrated the superiority of RNN variants in forecasting accuracy, the MEM presented comprehensive insights into the virus spread and potential control strategies., Competing Interests: The authors declare no conflict of interest., (© 2022 Elsevier Ltd. All rights reserved.)

Nigella sativa L. is one of the most extensively used traditional medicinal plants. This widely studied plant is known to display diverse pharmacological actions, including antimicrobial activities. Current literature has documented its multi-target mode of antimicrobial actions. N. sativa or its bioactive compounds, such as thymoquinone, can induce oxidative stress, cell apoptosis (by producing reactive oxygen species), increase membrane permeability, inhibit efflux pumps, and impose strong biocidal actions. Despite its well-documented antimicrobial efficacy in the experimental model, to the best of our knowledge its antimicrobial mechanisms highlighting the multi-targeting properties have yet to be well discussed. Is N. sativa or thymoquinone a valuable lead compound for therapeutic development for infectious diseases? Are N. sativa's bioactive compounds potential antimicrobial agents or able to overcome antimicrobial resistance? This review aims to discuss the antimicrobial pharmacology of N. sativa-based treatments. Additionally, it provides a holistic overview of the ethnobotany, ethnopharmacology, and phytochemistry of N. sativa., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The green synthesis strategy of metallic nanoparticles (NPs) has become popular due to being environmentally friendly. Stable silver nanoparticles (AgNPs) have been synthesized by natural products such as starch, soy protein, various extract of leaves, barks, and roots functioning both as reducing and stabilizing agents. Likewise, silk sericin (SS) is a globular protein discarded in the silk factory might be used for NP synthesis. In this research, we focus on the green synthesis and stabilization of AgNPs by SS as well as assessment of their antibacterial activities against some drug-resistant pathogen., Results: SS was extracted from Bombyx mori silkworm cocoons in an aqueous medium. 17 w/w% of dry sericin powder with respect to the cocoon's weight was obtained by freeze-drying. Furthermore, AgNPs conjugated to sericin, i.e., SS-capped silver nanoparticles (SS-AgNPs) were synthesized by easy, cost-effective, and environment-friendly methods. The synthesized SS-AgNPs were characterized by UV-visible spectroscopy, Fourier-transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, transmission electron microscopy (TEM), and X-ray diffraction measurement. It has been found from the absorbance of UV-visible spectroscopy that a higher percent of SS-AgNPs was obtained at a higher concentration of silver nitrate solution. FTIR-ATR spectra showed that the carboxylate groups obtained from silk sericin act as a reducing agent for the synthesis of silver nanoparticles, while NH 2 + and COO- act as a stabilizer of AgNPs. The X-ray diffractogram of SS-AgNPs was quite different from AgNO 3 and sericin due to a change in the crystal structure. The diameter of AgNPs was around 20-70 nm observed using TEM. The synthesized SS-AgNPs exhibited strong antibacterial activity against multidrug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 20μg/mL., Conclusions: This study encourages the use of Bombyx mori for the ecofriendly synthesis of SS-AgNPs to control multidrug-resistant microorganisms.

Introduction: Ponseti technique is the treatment of choice for idiopathic congential talipes equino varus (ICTEV) since 1950s with excellent treatment outcomes reported worldwide. However, despite the popularity of this technique, Uganda adapted it as a treatment modality for ICTEV in May 2005. Since then, the effectiveness of delivered Ponseti care to children with this very common orthopaedic deformity under the supervision of an orthopaedic surgeon was unknown. The implication of this undertaking was that, satisfactory outcomes would then support the Ministry of Health (MOH)-Uganda´s decision to embrace this mode of treatment and if the outcomes were unsatisfactory, MOH would then consider a policy revision in this regard. To assess the midterm treatment outcomes of children with ICTEV who had been enrolled for treatment at Mulago National Referral Hospital in the period of 2006-2009., Methods: in November/December 2013, a cross-sectional study was conducted to assess the treatment outcomes of 68 feet of 45 children using the designed questionnaire and the PBS score; a pilot study of 10 neonates was performed prior to research. A good treatment outcome meant having a foot or feet that did not require any major or minor surgery., Results: forty-five (45) children with 68 ICTEV feet were evaluated; males 29 (64.4%) and 16 (35.6%) females with a mean age of 73.22 months (SD 11.364, range 48-96 months). Among the feet assessed, 46 (68%) had good to excellent outcomes while 22 (32%) had a relapse of moderate and severe deformity. Good functionality was seen in 61.8% out of which, 69% and 55.9% had no limitation in walking or running respectively., Conclusion: Ponseti treatment technique in children with ICTEV under the care of predominantly orthopaedic officers with some supervision from orthopaedic surgeons had fair to good midterm outcomes even in low resource settings like Uganda. Public health approach should be embraced in the management of clubfoot in Uganda by enhancing adequate comprehensive support supervision and establishment of reliable institutionalized systems for patient follow up which will lead to early detection and treatment of relapsed ICTEV cases or neglected clubfeet in the communities., Competing Interests: The authors declare no competing interests., (Copyright: Raymond Joseph Malinga et al.)

Background: G-lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, is called lipopolysaccharide. The detection of G-lipopolysaccharide can be used for the early diagnosis of infectious diseases, but some-times G-lipopolysaccharide provides limited help. We report a case of a patient with hemoptysis and high-density shadow of both lungs combined with elevated serum G-lipopolysaccharide which mimicked bronchiectasis with Gram-negative bacterium infection. It was ultimately confirmed as Mycobacterium iranicum infection by CT-guided percutaneous lung biopsy and next generation sequencing., Methods: The chest computed tomography (CT) scan, CT-guided percutaneous lung biopsy, and NGS were performed for diagnosis and blood tests explored for the latent etiology., Results: The chest CT scan showed a high-density shadow of both lungs, atelectasis of right middle lobe, multiple enlarged lymph nodes in mediastinum and right hilum. Pathology of CT-guided percutaneous lung biopsy indicated fibrous tissue proliferation and granulation tissue formation and some alveolar epithelial cells slightly proliferated with focal carbon powder deposition in alveolar sacs and spaces. The lung tissue NGS confirmed Mycobacterium iranicum infection., Conclusions: Elevated serum G-lipopolysaccharide is not a specific index for infectious diseases. CT-guided percutaneous lung biopsy and lung tissue NGS has high specificity in pathogen detection of infectious diseases.

Background: Detection of carcinoembryonic Antigen (CEA) in pleural effusion has good clinical application value in differentiating benign and malignant pleural effusion, but sometimes CEA provides limited help. We report a case of a patient with left lung neoplasms combined with bilateral pleural effusion with increased CEA in the pleural effusion whose thoracoscopy pleural biopsy pathology was negative, mimicking lung carcinoma and ultimately confirmed as pulmonary sarcomatoid carcinoma by CT-guided percutaneous lung biopsy., Methods: The chest computed tomography (CT) scan, thoracoscopy pleural biopsy, and CT-guided percutaneous lung biopsy were arranged to explore the etiology of pleural effusion., Results: The chest CT scan showed bilateral pleural effusion with left lung neoplasms, pulmonary atelectasis, and left hilar enlargement. Pathology of thoracoscopy biopsy showed pleural inflammation with infiltration of inflammatory cells. Pathology of CT-guided percutaneous lung biopsy confirmed pulmonary sarcomatoid carcinoma., Conclusions: Elevated pleural effusion CEA is not a specific index of lung cancer. CT-guided percutaneous lung biopsy is appropriate for patients presenting with pleural diseases with lung neoplasms, especially when thoracoscopy pleural biopsy result was negative.

Background: Scoring systems including CURB-65 and Pneumonia Severity Index (PSI) and novel or traditional biomarkers including procalcitonin (PCT) and c-reactive protein (CRP) are very significant for understanding the severity and prognosis in community-acquired pneumonia (CAP) patients, while prognostic items are useful for CAP prognostication and point-of-care decisions. The aim of this study was to investigate the usefulness of peripheral blood routine items in predicting ICU admission and 30-day mortality in CAP patients.

Methods: A retrospective study was conducted. All adult patients with a primary diagnosis of CAP were included and peripheral blood routine tests were evaluated. Univariate analysis and multivariate logistic regression analysis were used to explore association of risk factors with 30-day mortality among CAP patients. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of peripheral blood routine items and compared with CURB-65 scores in predicting ICU admission and/or 30-day mortality.

Results: One hundred fifty patients were included and compared with non-ICU admission patients. There was a statistically significant difference in age, co-existing illness, RDW, WBC, and CURB-65 scores ranking in ICU admission patients (p < 0.05). In multivariate logistic regression analysis, we found RDW, WBC, and CURB-65 ≥ 3 scores increased the risk of 30-day mortality by 4.01, 1.65, and 3.43 times, respectively. The area under the curve (AUC) of ROC curves of RDW combined with WBC and CURB-65 was 0.786 (95% CI 0.701 to 0.876) and 0.836 (95% CI 0.764 to 0.908), respectively and the sensitivity was 84.0% and 60.0%, respectively, and the specificity 66.7% and 93.7%, respectively.

Conclusions: Elevated RDW and WBC increased mortality in adult CAP patients, RDW combined with WBC had a better sensitivity than CURB-65 scores in predicting ICU admission and/or mortality in CAP patients.

Dengue viruses (DENV) are transmitted to humans by the bite of Aedes mosquitoes. It is known that dengue virus infection in Aedes aegypti female mosquitoes makes a change in the feeding behavior of the infected mosquitoes. In this study, using the forces of infection, we incorporated the effect of changes in the feeding behavior of mosquitoes into the standard vector-borne SIR-SI model. It has been proved that both a single-strain model and a two-strain model exhibit forward bifurcations. Moreover, optimal implementations of control with specific prevention measures for dengue transmission are analyzed. As a result we found that more implementation of controls on the secondary infection of humans should be considered for the behavioral changes in feeding of the infected mosquitoes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In 2005, Lacroix et al. demonstrated that infected humans are more attractive to mosquitoes, a phenomenon known as the vector-bias effect. The aim of this study was to determine how a vector-bias effect affects the changes in the dynamics of malaria transmission, and the changes in control strategies and cost-effectiveness for optimal control considering the regional characteristics or force of infections for different transmission rates. We used a vector-bias mathematical model and considered two different incidence areas: a high transmission area and a low transmission area. Our results showed that the dynamics in the two areas differed; as bias exists and the strategy for optimal control could be changed in the different areas. Thus, this work may give that considering the vector-bias effect in different areas facilitates prediction of the future dynamics and make decisions for establishing controls. We also mention the evolution of malaria parasites in this study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Deliberate self-harm (DSH) of a young person has been a matter of growing concern to parents and policymakers. Prevention and early eradication are the main interventional techniques among which prevention through reducing peer pressure has a major role in reducing the DSH epidemic. Our aim is to develop an optimal control strategy for minimizing the DSH epidemic and to assess the efficacy of the controls., Methods: We considered a deterministic compartmental model of the DSH epidemic and two interventional techniques as the control measures. Pontryagin's Maximum Principle was used to mathematically derive the optimal controls. We also simulated the model using the forward-backward sweep method., Results: Simulation results showed that the controls needed to be used simultaneously to reduce DSH successfully. An optimal control strategy should be adopted, depending on implementation costs for the controls., Conclusion: The long-term success of the optimum control depends on the implementation cost. If the cost is very high, the control could be used for a short term, even though it fails in the long run. The control strategy, most importantly, should be implemented as early as possible to attack a comparatively fewer number of addicted individuals.

Objectives: Now-a-days gambling is growing especially fast among older adults. To control the gratuitous growth of gambling, well-analyzed scientific strategies are necessary. We tried to analyze the adequacy of the health of society mathematically through immediate treatment of patients with early prevention., Methods: The model from Lee and Do was modified and control parameters were introduced. Pontryagin's Maximum Principle was used to obtain an optimal control strategy., Results: Optimal control can be achieved through simultaneous use of the control parameters, though it varies from society to society. The control corresponding to prevention needed to be implemented in full almost all the time for all types of societies. In the case of the other two controls, the scenario was greatly affected depending on the types of societies., Conclusion: Prevention and treatment for elderly people with ludomania are the main intervention strategies. We found that optimal timely implementation of the intervention strategies was more effective. The optimal control strategy varied with the initial number of gamblers. However, three intervention strategies were considered, among which, preventing people from engaging in all types of gambling proved to be the most crucial.

Background/aims: Although irritable bowel syndrome (IBS) is a common gastrointestinal disorder, its prevalence is unknown, especially in the urban population of Bangladesh. This community-based study aimed to find out the prevalence of IBS and healthcare-seeking patterns using the Rome-II definition., Materials and Methods: A population-based cross-sectional survey of 1503 persons aged 15 years and above was carried out in an urban community of Bangladesh. The subjects were interviewed using a valid questionnaire based on Rome-II criteria in a home setting. Statistical analysis was performed with Statistical Package for Social Science (SPSS) Programmers and the level of significance was set at P

Bacterial spot of tomato is caused by four species of Xanthomonas. The accession PI 128216 (Solanum pimpinellifolium) displays a hypersensitive reaction (HR) to race T3 strains (predominantely Xanthomonas perforans). We developed an inbred backcross (IBC) population (BC(2)S(5), 178 families) derived from PI 128216 and OH88119 (S. lycopersicum) as the susceptible recurrent parent for simultaneous introgression and genetic analysis of the HR response. These IBC families were evaluated in the greenhouse for HR to race T3 strain Xcv761. The IBC population was genotyped with molecular markers distributed throughout the genome in order to identify candidate loci conferring resistance. We treated the IBC population as a hypothesis forming generation to guide validation in subsequent crosses. Nonparametric analysis identified an association between HR and markers clustered on chromosome 11 (P < 0.05 to 0.0001) and chromosome 6 (0.04 > P > 0.002). Further analysis of the IBC population suggested that markers on chromosome 6 and 11 failed to assort independently, a phenomenon known as gametic phase disequilibrium. Therefore, to validate marker-trait linkages, resistant IBC plants were crossed with OH88119 and BC(3)F(2) progeny were evaluated for HR in the greenhouse. In these subsequent populations, the HR response was associated with the chromosome 11 markers (P < 0.0002) but not with the markers on chromosome 6 (P > 0.25). Independent F(2) families were developed by crossing resistant IBC lines to OH8245, OH88119, and OH7530. These populations were genotyped, organized into classes based on chromosome 11 markers, and evaluated for resistance in the field. The PI 128216 locus on chromosome 11 provided resistance that was dependent on gene dosage and genetic background. These results define a single locus, Rx-4, from PI 128216, which provides resistance to bacterial spot race T3, has additive gene action, and is located on chromosome 11.

Objective: The aim of this study was to investigate the prevalence of irritable bowel syndrome (IBS) and the pattern of symptoms and health care seeking behavior of IBS subjects in the rural population in Bangladesh., Methods: This was an observational study to do a positive diagnosis of IBS. A total of 2426 persons > or =15 yr old were interviewed by a predesigned questionnaire based on the Rome criteria. Two villages of a northern district in Bangladesh were included., Results: A response of 95.4% yielded 2426 questionnaires for analysis. Mean age of the surveyed sample was 32.3+/-14.2 yr. In total, 1113 (45.9%) were men, and 1313 (54.1%) were women. Farmers and housewives comprised 2058 (84.8%) persons. The apparent prevalence of IBS was 24.4% with a prevalence of 20.6% in men and 27.7% in women. With strict Rome criteria, the overall prevalence was 8.5% (10.7% in women and 5.8% in men). Age was not found to influence the prevalence in either sex. Other than abdominal pain, the most common IBS symptom was altered stool passage (81.1%). Others in order of frequency were passage of mucus with stool (56.8%), abdominal distension (46.2%), altered stool form (46%), and altered stool frequency (18.2%). Spastic colon pain was noted in 339 (57.2%). IBS subjects with more prevalence of colonic symptoms in the nonspastic group. Drinking milk was found to have a little impact on IBS. A total of 35% IBS subjects consulted doctors for symptoms. Age, sex, and number of symptoms did not influence health care seeking behavior., Conclusions: IBS is also a problem in rural people in Bangladesh with a prevalence almost identical to most other countries, and only a minority of them seeks health care. Positive diagnosis of IBS can be done by precisely enquiring colonic symptoms in apparently healthy people.