The aim of this study was to investigate the impact of Process Oriented Guided Inquiry Learning (POGIL)-based instruction versus lecture-based instruction on Grade 12 students’ performance in circular motion unit. A quasi-experimental, pretest-posttest design, the impact of POGIL-based instruction versus lecture-based instruction on students’ performance as measured by three types of cognitive outcomes: Knowing, Applying and Reasoning (KAR). The total number of participants was approximately 110 students (N=110); 54 were assigned to treatment groups (25 girls and 29 boys) and 56 were assigned to control groups (27 girls and 29 boys). The treatment group was taught a unit of circular motion in physics using POGIL-based instruction while the control group was taught the unit using lecture-based instruction. The findings of the study showed statistically significant differences between students of the control group and the treatment group in favor of the later regarding their circular motion performance, suggesting the superiority of the POGIL in enhancing student understanding of the circular motion.

This article investigates the prospect of implementing multidisciplinary and multicultural student teamwork (MMT) involving Case-based Learning (CBL) and Problem-based Learning (PBL) as a sustainable teaching practice. Based on a mixed methods approach, which includes direct observation (both physical and virtual), questionnaire distribution and focus-group interviews the study reveals that MMT through CBL and PBL can both facilitate and hinder sustainable learning. Our findings show that while MMT enhances knowledge sharing, it also poses a wide range of challenges, raising questions about its social significance as a sustainable teaching practice. The study suggests the implementation of certain mechanisms, such as ‘Teamwork Training’ and ‘Pedagogical Mentors’, aiming to strengthen the sustainable orientation of MMT through CBL and PBL.

In MBSE there is yet no converged terminology. The term ’system model’ is used in different contexts in literature. In this study we elaborated the definitions and usages of the term ’system model’, to find a common definition. 104 publications have been analyzed in depth for their usage and definition as well as their meta-data e.g., the publication year and publication background to find some common patterns. While the term is gaining more interest in recent years it is used in a broad range of contexts for both analytical and synthetic use cases. Based on this three categories of system models have been defined and integrated into a more precise definition.

This article discusses the use of game design as a method for interdisciplinary project-based teaching in secondary school education to convey informatics and society topics. There is a lot of knowledge about learning games but little background on project-based teaching using game design as a method. We present the results of an analysis of student-created games and an evaluation of a student-authored database on learning contents found in commercial off-the-shelf games. We further contextualise these findings using a group discussion with teachers. Results underline the effectiveness of project-based teaching to raise awareness for informatics and society topics. We further outline informatics and society topics that are particularly interesting to students, genre preferences and potentially engaging game mechanics stemming from our analyses.

The ubiquity of mobile sensors (such as GPS, accelerometer and gyroscope) together with increasing computational power have enabled an easier access to contextual information, which proved its value in next generation of the recommender applications. The importance of contextual information has been recognized by researchers in many disciplines, such as ubiquitous and mobile computing, to filter the query results and provide recommendations based on different user status. A context-aware recommendation system (CoARS) provides a personalized service to each individual user, driven by his or her particular needs and interests at any location and anytime. Therefore, a contextual recommendation system changes in real time as a user’s circumstances changes. CoARS is one of the major applications that has been refined over the years due to the evolving geospatial techniques and big data management practices. In this paper, a CoARS is designed and implemented to combine the context information from smartphones’ sensors and user preferences to improve efficiency and usability of the recommendation. The proposed approach combines user’s context information (such as location, time, and transportation mode), personalized preferences (using individuals past behavior), and item-based recommendations (such as item’s ranking and type) to personally filter the item list. The context-aware methodology is based on preprocessing and filtering of raw data, context extraction and context reasoning. This study examined the application of such a system in recommending a suitable restaurant using both web-based and android platforms. The implemented system uses CoARS techniques to provide beneficial and accurate recommendations to the users. The capabilities of the system is evaluated successfully with recommendation experiment and usability test.

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using web-server tool PADLOC (Prokaryotic Antiviral Defense Locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring the resistance.

Antimicrobial resistance (AMR) is a growing public health issue worldwide that affects the world economy. The concern associated with this issue increased during the COVID-19 pandemic. The misuse of antibiotics during the COVID-19 pandemic will have catastrophic implications for the control of AMR. In 2019, the coronavirus illness COVID-19 first appeared in China. COVID-19 infection is a surface-to-surface communicable disease. It is considered the most vital global health disaster of the century. It has rapidly spread around the world and is the greatest challenge for humankind. This chapter discusses the origin, symptoms, transmission, treatment, and recommendations of the COVID-19 disease.

A novel group of conjugative plasmids of Pseudomonas is characterized. The prototype plasmid pPPUT-Tik1-1 (153663 bp), isolated from a permafrost strain of P. putida Tik1, carries a defective mercury transposon Tn501 and a streptomycin resistance transposon Tn5393. Ten plasmids and 34 contigs with backbone regions closely related to pPPUT-Tik1-1 have been found in Gene Bank. Two of these plasmids isolated from clinical strains of P. putida and P. fulva are almost identical to the ancient plasmid. A characteristic feature of this group of plasmids is the presence of two genes encoding the initiators of replication (repA1 and repA2). None of these genes has high similarity with plasmid replication genes belonging to known incompatibility groups. It has been demonstrated that while pPPUT-Tik1-1-like plasmids have homologous backbone regions they significantly differ by the molecular structure and the functional burden of their accessory regions. Some of the pPPUT-Tik1-1-related plasmids carry determinants of antibiotic resistance and/or heavy metal salts. Some plasmids are characterized by the ability to degrade xenobiotics. Plasmids related to pPPUT-Tik1-1 are characterized by a narrow host range and are found in various species of Pseudomonas genus. A group of shortened plasmids containing the same replication module, but without conjugation genes, were also found. These plasmids also contain other structural changes that strongly distinguish them from plasmids related to pPPUT-Tik1-1. The data obtained indicate the need for a complex approach to the classification of plasmids.

This paper presents a concise exploration of several analytical methods for extracting the parameters of the single-diode model (SDM) of a photovoltaic (PV) module under standard test conditions (STC). The paper investigates six methods and presents the detailed mathematical analysis leading to the development of each method. To evaluate the performance of these methods, MATLAB-based software has been developed and deployed to synthesize the results of each method when used to extract the SDM parameters of various PV test modules of different PV technologies. Similar software has also been developed to extract the same parameters using well-established numerical and iterative techniques. A comparison is subsequently made between the synthesized results and those obtained using numerical and iterative methods. The comparison indicates that in spite of the fact that analytical methods may involve fair amount of approximations, their accuracy can be comparable to that of their numerical and iterative counterparts, with the added advantage of significant reduction in computational complexity, and without the initialization and convergence difficulties, which are normally associated with numerical methods.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori (H. pylori) infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To meet the need to develop test systems for personalized drug selection, we conducted a study of H. pylori molecular resistance in Moscow using a self-developed Sanger sequencing test platform. We validated our test system on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100%, and to levofloxacin - 93% and 92%, respectively. Then we tested our platform on 112 H. pylori -positive patients who had not previously received proton pump inhibitors (PPI) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples, and to levofloxacin in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G, to levofloxacin resistance – 261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Modern fighter aircraft increasingly need to conjugate aerodynamic performance and low observability. In this paper we showcase a methodology for a gradient-based bidisciplinary aero-stealth optimization. The shape of the aircraft is parametrized with the help of a CAD modeler, and we optimize with the SLSQP algorithm. The drag, computed with the help of a RANS method, is used as the aerodynamic criterion. The stealth criterion, a function is derived from the radar cross section in a given cone of directions, weighed with a function whose goal is to cancel the electromagnetic intensity in a given direction. Stealth is achieved passively by scattering back the electromagnetic energy away from the radar antenna and no energy is absorbed by the aircraft, which is considered as a perfect conductor. A Pareto front is identified by varying the weights of the aerodynamic and stealth criteria. The Pareto front allows for an easy identification of the CAD model corresponding to a chosen aero-stealth trade-off.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

The correlations of seismic noise, recorded during 1997-2022 at 229 stations around the world are investigated. The property of waveforms, known as the Donoho-Johnston threshold, is analyzed, which separates the absolute values of the orthogonal wavelet coefficients into "small" and "large". Network of 50 reference points is considered. For each reference point, a time series with a time step of 1 day is calculated as the median of the values of the DJ index from the 5 nearest stations. For each reference point, the correlations between the values of the DJ index at other reference points are calculated in a sliding time window of 365 days. Average values of the DJ index decrease, which is interpreted as indicators of global seismic hazard increasing. The maximum distances between reference points with strong correlations show an explosive increase after 2011. Bursts in the mean coherences between the length of day (LOD) and the values of the DJ index at the reference points precede the release of seismic energy with a delay of about 530 days. High amplitude of the DJ index response to LOD for the times 2020-2022 was identified, which may forecast a strong earthquake in the second half of 2023.

Noise in requirements has been known to be a defect in software requirements specifications (SRS). Detecting defects at an early stage is crucial in the process of software development. Noise can be in the form of irrelevant requirements that are included within a SRS. A previous study had attempted to detect noise in SRS, in which noise was considered as an outlier. However, the resulting method only demonstrated a moderate reliability due to the overshadowing of unique actor words by unique action words in the topic-word distribution. In this study, we propose a framework to identify irrelevant requirements based on the MultiPhiLDA method. The proposed framework distinguishes the topic-word distribution of actor words and action words as two separate topic-word distributions with two multinomial probability functions. Weights are used to maintain a proportional contribution of actor and action words. We also explore the use of two outlier detection methods, namely Percentile-based Outlier Detection (PBOD) and Angle-based Outlier Detection (ABOD), to distinguish irrelevant requirements from relevant requirements. The experimental results show that the proposed framework was able to exhibit better performance than previous methods. Furthermore, the use of the combination of ABOD as the outlier detection method and topic coherence as the estimation approach to determine the optimal number of topics and iterations in the proposed framework outperformed the other combinations and obtained sensitivity, specificity, F1-score, and G-mean values of 0.59, 0.65, 0.62, and 0.62, respectively.

Animal-based measures are the measure of choice in animal welfare assessment protocols as they can often be applied completely independently to the housing or production system employed. Although there has been a small body of work on potential animal-based measures for farmed crocodilians [1-3], they have not been studied in the context of an animal welfare assessment protocol. Potential animal-based measures, that could be used to reflect the welfare state of farmed crocodilians, were identified and aligned with the Welfare Quality® principles of good housing, good health, good feeding and appropriate behaviour. A consultation process with a panel of experts was used to evaluate and score the potential measures in terms of validity and feasibility. This resulted in a toolbox of measures being identified for further development and integration into animal welfare assessment on the farm. Animal-based measures related to ‘good feeding’ and ‘good health’ received the highest scores for validity and feasibility by the experts. There was less agreement on the animal-based measures that could be used to reflect ‘appropriate behaviour’. Where no animal-based measures were deemed to reliably reflect a welfare criterion nor be useful as a measure on the farm, additional measures of resources or management were suggested as alternatives. Future work in this area should focus on the reliability of the proposed measures and involve further evaluation of their validity and feasibility as they relate to different species of crocodilian and farming system.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

Given the increase in consumers’ preferences for coffee, it is becoming important to understand their decision-making processes in the coffee chain context. To deepen the understanding of sustainable outcomes in this context, this study investigates the role of dedication- and constraint-based mechanisms in forming consumers’ repurchase and positive word-of-mouth (WOM) intentions, two critical sustainable outcomes. We examined the effects of coffee quality, the quality of the physical environment, and service quality in accelerating the formation of dedication-based factors. Moreover, this study offers an in-depth understanding of the enablers of perceived switching costs. Data collected from 238 university students that frequently visit coffee chains are empirically tested against the proposed theoretical framework by using structural equation modeling. The results confirm that both dedication- and constraint-based factors substantially predict consumers’ sustainable outcomes in the coffee chain context. Brand image and perceived switching costs play an important role in enhancing consumers’ repurchase and positive WOM intentions compared with customer satisfaction. Coffee quality is significantly associated with both customer satisfaction and brand image, whereas the quality of the physical environment and service quality are only significantly associated with brand image. Habit is found to be the key enabler of perceived switching costs, while loyalty programs have no significant impact on perceived switching costs.

Effectively mapping and monitoring rubber plantation is still changing. Previous studies have explored the potential of phenology features for rubber plantation mapping through a pixel-based approach (pixel-based phenology approach). However, in fragmented mountainous Xishuangbanna, it could lead to noises and low accuracy of resultant maps. In this study, we investigated the capability of an integrated approach by combining phenology information with an object-based approach (object-based phenology approach) to map rubber plantations in Xishuangbanna. Moderate Resolution Imaging Spectroradiometer (MODIS) data were firstly used to acquire the temporal profile and phenological features of rubber plantations and natural forests, which delineates the time windows of defoliation and foliation phases. Landsat images were then used to extract a phenology algorithm comparing three different approaches: pixel-based phenology, object-based phenology, and extended object-based phenology to separate rubber plantations and natural forests. The results showed that the two object-based approaches achieved higher accuracy than the pixel-based approach, having overall accuracies of 96.4%, 97.4%, and 95.5%, respectively. This study proved the reliability of a phenology-based rubber mapping in fragmented landscapes with a distinct dry/cool season using Landsat images. This study indicated that the object-based phenology approaches can effectively improve the accuracy of the resultant maps in fragmented landscapes.

Infections with multi-drug-resistant (MDR) pathogens in food-animals threaten public health and food security. However, the epidemiology and factors associated with MDR Escherichia coli on Ugandan farms are not well known. This study investigated the prevalence, resistance patterns and factors associated with MDR E. coli carriage on chicken farms. A total of 158 E. coli strains were isolated from 158 chicken farms. The disc diffusion method for susceptibility testing was performed. Clinical breakpoints were interpreted according to Clinical and Laboratory Standards Institute guidelines. MDR was defined as resistance to three or more classes of antimicrobials. MDR E. coli prevalence on chicken farms was 62.7% (95% CI: 55.0 – 70.3). High resistance was observed against ampicillin 79.8% (95% CI: 72.7–85.4), tetracycline 72.8% (95% CI: 65.2–79.2), cotrimoxazole 55.7% (95% CI: 47.8–63.3), and ciprofloxacin 38% (95% CI: 30.7–45.9). Farmers who were males (APR = 0.72, CI: 0.55, 0.93), and attained at least secondary education (APR=0.64, CI: 0.46, 0.88) and administration of recommended antibiotic doses (APR = 0.76, CI: 0.59–0.96) posed a lower risk of MDR E. coli carriage. Farms without footbaths posed a heighten risk (APR=1.48, CI: 1.16–1.88). MDR E. coli were highly prevalent on chicken farms. This study underscores the need for antimicrobial stewardship and improved infection prevention strategies on chicken farms.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Carbapenem resistant Enterobacteriaceae (CRE) has been public health risk in several countries and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of CRE E.coli from chicken. Routine bacteriology, PCR detection of E.coli species, multiplex PCR to detect carbapenemase encoding genes and phylogeny of CRE E. coli were conducted. The results show that 24.36 % (19/78) were identified as CRE based on the phenotypic identifications of which 17 were positive for the tested carabanemase genes. The majority, 57.99% (11/19) of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM blaOXA, blaIMP, five and two different isolates harbored blaNDM and blaOXA, and blaOXA and blaIMP respectively. The Meropenem, Imipenem and Ertapenem MIC values for the isolates ranged from 2g/mL to ≥256g/mL. Phylogenetic grouping showed that the CRE E.coli isolates belonged to five different groups; groups A, B1, C, D and unknown. The detection of carbapenem resistant E.coli in this study shows that CRE is has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

Rice blast, caused by Magnaporthe oryzae, poses significant threat to rice production. Rice blast susceptibility has been observed in Japanese rice varieties with excellent eating quality. Enhancing blast resistance is essential to ensure minimal use of agricultural chemicals. Two types of blast resistance are observed: true resistance, which is a type of qualitative resistance expressed by a major gene, and field resistance, which is a type of quantitative resistance expressed by multiple micro-acting genes. ‘Resistance collapse’, in which a variety with a true resistance gene becomes diseased by blast fungus races compatible with the resistance gene, has been observed. Varieties carrying blast-resistance genes, such as Pb1 (panicle blast resistance 1), have been developed through DNA marker-assisted selection. In this review, we focus on the Pb1, which expresses strong quantitative resistance to panicle blast and has been widely used in Japan without showing ‘resistance collapse’ for 40 years. Pb1 is an ‘adult plant resistance gene’ that does not exert strong selection pressure on the blast population during the leaf blast stage, thus preventing the selective multiplication of Pb1-compatible blast strains. This epidemiological mechanism prevents ‘resistance collapse’. Interdisciplinary research and breeding are required to sustainably use genes that induce high field resistance.

Saudi Arabia is an oil-reliant nation as a large percentage of its GDP comes from oil resources. Oil dependency leaves a county at the mercy of the international crude market, and a decrease in the price of crude can seriously destabilize the economy of such nations. An example is the case of Venezuela whose dependence on oil caused a national disaster (McCarthy, 2017). As such, the nation’s exports, GDP, and government revenue are primarily dependent on oil revenue, and the recent decrease in the oil prices has decreased Venezuela’s national revenue resulting in economic collapse as well as inflation. A shift from a resource based economy to a knowledge based economy will help Saudi Arabia become less reliant on its oil revenues for its economic stability and growth (Nurunnabi, 2017).

This paper is showing the results of a study focused on the occurrence of failures in heterogeneous structural materials, especially on the issue of modelling the formation and propagation of cracks. Attention is paid to the application of the finite element method to various types of materials in order to find critical parameters determining the behaviour of materials during the damage process. Application of damage mechanisms and approaches to modelling the origin of crack propagation by modifications in FEM systems are presented. Furthermore, some practical applications are tested. The main effort is devoted to composites and searching for procedures when using cohesion models for their more accurate modelling, especially near the stress concentrators, or before the crack tip. The use of the cohesive approach of elements that represent the physical nature of energy release in front of the crack front has proven to be promising not only in the direct use of cohesive elements, but also in combination with modified methods of standard finite elements. The authors of this article use their long-term experience in the given issue, which they consistently confront with developments in this area in recent years.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Medicinal activities carried out within hospitals lead to a high consumption of antibiotics and subsequently result in a high excretion rate of antibiotic residues. These antibiotics consumed in human medicine are not fully absorbed by the body and are often discharged into the environment as biological waste from infected human patients. The significant water consumption in hospitals and the pharmaceutical impact on wastewater from healthcare facilities facilitate the emergence and spread of antibiotic-resistant bacteria and antibiotic-resistant genes in the environment. Hospital effluents could be doubly involved in the dissemination of antibiotic molecules and multidrug-resistant bacteria in various ecosystems. The objective of this study is to characterize hospital effluents by assessing antibiotic concentrations and the diversity of antibiotic-resistant bacteria in these hospital wastewaters and within the environment (aquatic environments; rivers), as well as to inventory the bacteria present and those carrying antibiotic resistance in both hospital wastewater and the environment.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Available options to combat bacterial infections are getting scarce. We require innovative and imaginative approaches to enhance the identification and discovery of effective antimicrobials capable of combating bacteria resistant to multiple or all available drugs. These methods should either directly eliminate the resistant bacteria or influence their viability indirectly by inhibiting their virulence or reducing their resistance to antibacterial agents. One interesting approach is to analyze ancient remedies presumably used to treat bacterial infections, try formulating them, and test them against modern microbes. The field was recently named ancientbiotics. This approach allows us to take advantage of centuries of accumulated empirical knowledge, from several traditional medicines of various ancient cultures across the world. The strategy has already resulted in promising formulations to combat the ESKAPE group of nosocomial pathogens. Moreover, molecular de-extinction consists of genome analysis of extinct species in the search for useful antimicrobials, such as peptides. The de-extinction of simple organisms such as bacteriophages may eventually become a resource for novel tools to combat multidrug-resistant bacteria. In this review, we summarize and discuss the reported antimicrobial effects of ancient remedies and de-extinct molecules known to modern science, and discuss possible new strategies to further harness the potential of past remedies and molecules to help us fight the rise of superbugs.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Bananas, a staple food globally and a key agricultural commodity, face a severe threat from the fungus Fusarium oxysporum form specialis cubense (Foc), significantly impacting production. Genetic improvement to develop resistant cultivars stands out as a crucial strategy to mitigate this disease. This study focused on assessing and recommending enhanced diploid banana varieties for resistance against Foc subtropical race 4 (ST4) and Foc race 1 (R1). Twenty-five improved diploids developed by Embrapa, Brazil, underwent evaluation. Utilizing a scale for internal symptoms at 90 days post-inoculation, genotypes were categorized from highly resistant to highly susceptible based on the internal symptom index. The diploid M53 exhibited high resistance to R1 and resistance to Foc ST4, while only the diploid CNPMF 0534 demonstrated complete resistance to both R1 and ST4, with resistance to the latter likely associated with penetration. These findings provide valuable insights for banana and plantain breeding programs, offering selected diploids for crossbreeding with commercial cultivars to develop new, resistant genotypes against Foc.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple medi-ation analysis revealed that all three potential mediators played a role in mediating the associa-tion. However, in the parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43—0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31—0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003—0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

In this study, we aimed to determine the trend of antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU), in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. The resistance patterns were analyzed using Vitek 2 Compact system. Positive-bacterial culture data of 1695 samples from pre-COVID-19 period and 1562 from post-COVID-19 period were obtained. The most frequently isolated in both periods were Staphylococcus aureus and Klebsiella spp. Klebsiella spp. had a statistically significant increase in resistance rates in the post COVID-19 period, against colistin, gentamicin and aztreonam. For E. coli strains, it was registered a significant increase against colistin and a significant decrease against levofloxacin and imipenem. For Acinetobacter spp. strains it was observed a significant increase against colistin. More than 50% from the Staphylococcus aureus strains were MRSA with statistically significant increases in antimicrobial resistance rate in the post-COVID-19 period against doxycycline, linezolid, rifampicin and teicoplanin. The study revealed a significantly increasing trend of the antimicrobial resistance rate of Gram-negative pathogens (Klebsiella spp., Acinetobacter spp.) against certain antibiotics, including those used only in cases where there are no other therapeutic options.

Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the most destructive diseases in banana farming worldwide. Knowledge of the factors of genetic diversity and virulence of the pathogen contributes to the development of resistant cultivars and in management strategies based on exclusion. In this study, phenotypic traits such as virulence and aggressiveness in a sample of 52 Foc isolates, were analyzed and their relationship to the presence of putative effectors of gene SIX (Secreted in Xylem) pathogenicity homologues, verified. According to the dissimilarity matrix, there were three isolates closest to the standard Foc race 1 strain. Isolates 229A and 218A, were selected according to their aggressiveness profile in 'Grand Naine' and 'Prata-Anã', respectively, I order to replace the standard isolate of race 1 in the resistance screening process carried out by the breeding program. Two homologues of the SIX8 gene, SIX8a and SIX8b, are present in isolates of Foc from Brazil and the SIX8b gene correlates with avirulence in the cultivar ‘Grand Naine’ (Cavendish). These results are important to support the banana genetic breeding program by identification of sources of resistance to Foc and contribute in the establishment of the function of SIX effector proteins.

Antibiotic resistance currently considered as a global concern mostly impacting low- and middle-income nations and it can be accelerated by antibiotic abuse and other forms of excessive antibiotic use. There is little data on community practices and understanding in Somaliland on antibiotics and antibiotic resistance. To provide evidence-based communication intervention techniques for safer antibiotic use the qualitative study was done from November 1st to December 1st, 2023, and consisted of in-depth semi-structured interviews with adult heads of households in Hargeisa, Somaliland, using purposive and snowball sampling strategies. Participants were chosen from a variety of medical and educational backgrounds. Thematic analysis was used to investigate community knowledge and antibiotic use in the sampled population. To investigate the level of awareness on antibiotic use, 20 respondents (households) were questioned (Table 1). Of these, 17 (85%) became aware of the term antibiotic itself, with 7 (35%) being prescribed by a physician, 9 (45%) receiving laboratory diagnosis when using antibiotics, and 6 (30%) becoming aware of the potential risks associated with improper antibiotic use. This study highlighted the community's lack of understanding about antibiotic use. The majority of the study participants knew the phrase "antibiotic" but had no idea what it meant, the side effect of the antibiotics and other medical science related information regarding how to safely use antibiotics. According to the findings, initiatives for antibiotic stewardship should focus on community education to prevent antibiotic misuse or abuse.

Seawater has been proposed as a reservoir for antibiotic resistant bacteria and antibiotic resistance genes, thus representing a risk to public health. In this study, we evaluated the presence of antibiotic resistance determinants (bacteria and genes) in 77 seawater samples collected at different points along the coast of the Gulf of Valencia (Spain). Specifically, indicators of fecal contamination bacteria, Escherichia coli and Enterococcus sp. were isolated, and their antibiotic resistance profiles were analyzed by using the Sensititre® system, followed by the detection of main antibiotic resistance genes (blaTEM, qnrS, tetW, sulI, and ermB). The highest frequencies of resistance in E. coli isolates were detected against ampicillin (35.1%) and ciprofloxacin (17.5%), followed by sulfamethoxazole and trimethoprim (15.7%), while 23% of enterococci isolates showed resistance to a single antibiotic, 20% against tetracycline and 3% against daptomycin. By PCR, 93% of the E. coli strains showed the blaTEM and sulI resistance genes. Among the enterococci, the presence of the blaTEM gene was detected in 40% of the isolates, while the rest of the genes were present at very low rates. Among the water samples, 57% were positive for at least one of the tested genes, being blaTEM gene the most commonly found (47%), followed by qnrS (33%) and sulI (23%) genes. These results show that seawater, in addition to having a high rate of fecal contamination, can contribute to the spread of antibiotic resistance.

Antimicrobial resistance is one of the most important global health issues identified in recent decades. Different approaches have been used to establish the presence and abundance of antimicrobial resistance genes (ARGs) in the environment. In this study, we analyzed soil samples from Fildes Peninsula (King George Island, maritime Antarctica), exposed to different types of impact. The objective of the work was to identify ARGs in the samples, and evaluate if these genes were located in plasmids, using two different strategies. A metagenomic analysis was used to identify ARGs and if they were associated to plasmid sequences. The analysis showed that the site highly exposed to anthropogenic activity had a higher number of ARGs compared to other sites. A high percentage of those ARGs (19.4%), were located in plasmidic contigs. We also assessed replicon mobilization, using microbial communities from these soil samples as donors through an exogenous plasmid isolation method. In this case, we could recover plasmids with ARGs in a Tcr transconjugant clone. Although they could not be fully assembled, we could detect broad host range IncP1 and IncQ plasmid sequences. Our results indicate that sewage impacted soils could be a hotspot for ARGs spread into the Antarctic environment

Periodic assessment of bacterial contamination is necessary as it allows proper guidance in cases of eye infections through the use of appropriate antibiotics. Due to the extensive use of antibiotic treatment, most of the contamination flora is resistant to the usual ophthalmic antibiotics. The present study shows an updated picture of the susceptibility of Gram-positive and Gram-negative bacteria found on the ocular surface to the most commonly used antibiotic agents in patients undergoing cataract surgery. A total of 993 patients were included in the study with ages between 44 and 98 years old. Conjunctival culture was collected 7 days before cataract surgery. The response of Gram-positive and Gram-negative bacteria to various antibiotic classes like glycopeptides, cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, phenicols, tetracyclines, rifamycins, macrolides and penicillins was assessed. From the tested antibiotics, vancomycin had 97.8% efficacy on Gram-positive bacteria. In the cephalosporin category, we observed an increased resistance of the cefuroxime for both Gram-positive and negative bacteria. Antibiotics that have more than 90% efficacy on Gram-positive bacteria are: meropenem, imipenem, netilmicin, amikacin and rifampicin. On Gram-negative bacteria, we found 100% efficacy of all tested fluoroquinolones, aminoglycosides (except for tobramycin), doxycycline, azithromycin, clarithromycin and chloramphenicol. The current study illustrates patterns of increased resistance of certain bacteria present on ocular surface to some of the commonly used antibiotics in ophthalmological clinical practice. One such revealing example is cefuroxime, which has been highly used as an intracameral antibiotic for the prevention of bacterial endophthalmitis after cataract surgery.

Maize (Zea mays L.) stands as one of the most extensively cultivated crops globally, offering significant contributions to food, animal feed, and biofuel production. Maize yield is significantly impacted by diverse climate and soil variables, yet its productivity faces hindrances due to abiotic stresses, including drought, salinity, extreme temperatures, and cold conditions. In confronting these hurdles, the field of crop breeding has undergone a transformation thanks to high-throughput sequencing technologies (HSTs). These advancements have streamlined the identification of beneficial quantitative trait loci (QTL), associations between markers and traits (MTAs), as well as genes and alleles that contribute to crop improvement. Presently, well-established omics techniques such as genomics, transcriptomics, proteomics, and metabolomics are being amalgamated into maize breeding studies. These approaches have unveiled new biological markers that are being employed to bolster maize's capacity to withstand an array of challenges. In this chapter, we explore the current knowledge regarding the morpho-physiological and molecular mechanisms that underlie the resistance and tolerance of maize to biotic and abiotic stresses. The focus is on utilizing omics techniques to augment maize's ability to withstand these challenges. Moreover, it emphasizes the significant potential of integrating various omics techniques to tackle the challenges presented by biotic and abiotic stress in maize productivity, contrasting with singular approaches.

Inspired by the process of bone formation in living organisms, many studies have been conducted to develop organic-inorganic composite materials by generating calcium phosphate crystals within solutions or dispersions of polymers with appropriate functional groups. Bones are composite materials consisting of organic polymers (mainly Type I collagen), carbonated apatite, and water, with volume fractions 35-45%, 35-45%, 15-25%, respectively. Carbonated apatite in bone contributes to rigidity, while organic polymers and water contribute to toughness. The inorganic crystal, carbonated apatite, is a plate-shaped crystal with dimensions of 50 nm × 25 nm × 1-4 nm, generating a significant organic-inorganic interface due to its nanoscale size. This interface is believed to absorb externally applied forces to dissipate mechanical energy to thermal energy. Creating such nanometer-scale structures using top-down approaches is challenging, making bottom-up methods like co-precipitation of polymer and inorganic crystals more suitable. In this account, efforts to develop eco-friendly mechanical materials using biomass such as cellulose and starch based on the bottom-up approach to bone-like composites are described.

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance is polygenic and evolves from standing genetic variation. Using a CIDER-seq pipeline we show that herbicide resistant (HR) and herbicide sensitive (HS) F3 plants from these F2 seed families as well as the parent populations they were derived from carry extra-chromosomal circular DNA (eccDNA). We identify the similarities and differences in the coding structures within and between resistant and sensitive populations. Although the numbers and size of detected eccDNAs varied between the populations, comparisons between HR and HS blackgrass populations identified shared and unique coding content, predicted genes, and functional protein domains. These include genes related to herbicide detoxification such as Cytochrome P450s, ATP-binding cassette transporters and glutathione transferases including AmGSTF1. eccDNA content was mapped to the Alopecurus myosuroides reference genome, revealing genomic regions at distal end of chromosome 5 and the near center of chromosome 1 and 7 as regions with high number of mapped eccDNA gene density. Mapping to 15 known herbicide-resistant QTL regions showed the eccDNA coding sequences match 12 with four QLT matching HS coding sequences one region only contained HR coding sequences. These findings establish that like other pernicious weeds, blackgrass has eccDNAs that contain homologs of chromosomal genes, and these may contribute genetic heterogeneity and evolutionary innovation to rapidly adapt to abiotic stresses including herbicide treatment.

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

Background: Understanding the physicians’ knowledge, attitudes and antimicrobial prescribing behaviour is a crucial step towards designing strategies for optimal use of these agents. Methods: A cross-sectional online survey was conducted among clinicians across India between “May to July 2022” using a self-administered questionnaire in English comprising of 35 questions pertaining to demographic characteristics, knowledge, attitude and practices domains. Results. A total of 544 responses were received from 710 physicians contacted. 60 percent participants were males with mean age of 34.7 years. Mean ± SD scores for knowledge, attitude and practices domains were 8±1.6, 20.2±3.5 and 15.3±2.1, respectively. Higher scores were associated with basic [odds ratio (95% C.I.), P value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03] and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe classification of antibiotics, and role of infection prevention and control (IPC) measures in containment of antimicrobial resistance (AMR). Conclusions. There is a need to sensitize and educate clinicians on various issues related to antimicrobial use such as antibiograms, double anaerobic cover, IPC practices and guideline-based recommendations to curb the AMR pandemic.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled March 2019 to December 2020 from five facilities in Kisumu County, Kenya were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for VF (&gt; 1000 copies/ml)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; median age was 9 years (interquartile range (IQR) 7,12), 344 (49%) were female and median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associate with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual class resistance. A history of VF in prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

The rise of antibiotic-resistant strains of clinically important pathogens is a major threat to global health security. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the various suggested options with proven activity and a high potential to be developed into effective agents. Many AMPs are naturally produced by living organisms and protect the host against pathogens as a part of their innate immunity. Various mechanisms associated with their antimicrobial actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics that can induce apoptosis and necrosis. Acinetobacter baumannii is considered a critical pathogen, and severe clinical problems have appeared with isolates resistant to current antibiotic treatments and conventional control procedures such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing the primary candidates for new anti-A. baumannii drugs in a post-antibiotic era and present the use of computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.

SARS-CoV-2 pandemic caused an increase in Intensive Care Unit (ICU) hospitalizations with rise in morbidity and mortality; nevertheless, there is still little evidence of pandemic impact on antibiotic resistance in ICU. Retrospective monocentric epidemiological study. All microorganisms isolated from all patients admitted to E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. Aim of the study was to describe and analyze the impact of SARS-CoV-2 pandemic on ICU microorganisms resistance patterns. 1,771 microorganisms identified, 221 (12.47%) had resistant pattern (Resistant Organisms; ROs) isolated from 1,679 patients during 12,030 hospitalization days. The majority of ROs were Gram-negative (79.66% 2018, 77.29% 2019, 61.83% 2020, 62.56% 2021, 60.75% 2022), but increase of Gram-positive microorganisms was observed (20.34% to 39.25% between 2018-2022). Prevalence of AR was: 19.44% 2018, 11.54% 2019, 38.04% 2020, 34.15% 2021, 39.29% 2022 for Gram-positives; 19.86%, 13.56%, 18.12%, 12.41%, 12.31% for Gram-negatives. Incidence of Ros showed COVID-related rise in 2020-2021, followed by a lowering trend since 2021, with new rise in 2022. Possible explanations are antibiotic overtreatment and drop of containing measures. Interesting finding is the cumulative lowering trend of carbapenem resistant K. pneumoniae and P. aeruginosa probably due to different patient features.

Salvia hispanica (chia) is a highly nutritious food source and has gained popularity due to its high omega-3 fatty acid content. Red spider mites are a serious problem in the production of S. hispanica. However, no study has been conducted to analyse the defensive response to the infestation of red spider mites in S. hispanica. To elucidate the molecular mechanisms of the defensive response of S. hispanica to red spider mites, we performed a transcriptomic analysis of S. hispanica when infested by red spider mites. In the comparative assessment of leaf transcriptomes, a total of 1743 differentially expressed genes (DEGs) were identified between control and mite-infested S. hispanica. From these, 1208 (69%) transcripts were up-regulated and 535 (31%) were down-regulated. The DEGs included transcription factors, defense hormones, and secondary metabolites that were either suppressed or activated in response to spider mite herbivory. Gene Ontology (GO) enrichment analysis revealed that plant secondary metabolites such as glucosinolates, and signalling pathways, including the jasmonic acid signalling pathway, may play an important role in the defence against red spider mites. This study provides novel insights into the defence response of S. hispanica in response to insect herbivory and could be a resource for the improvement of pest resistance in the chia.

Background: Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are accurately detected late in the progressive form of the disease. Methods: Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. Results: In the apparently macroscopically unchanged tegument, photon microscopy revealed both progressive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. Conclusions: The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Insulin resistance, as a common pathological process of many metabolic diseases, including diabetes and obesity, has attracted much attention due to its relevant influencing factors. To date, studies have mainly focused on the mechanisms between mitochondrial stress and insulin resistance, and they are now pursued as a very attractive therapeutic target due to their extensive involvement in many human clinical settings. In view of the complex pathogenesis of diabetes, natural drugs have become new players in diabetes prevention and treatment because of their wide targets and few side effects. In particular, plant phenolics have been paid more attention because of their close relationship with oxidative stress. In this review, we briefly review the mechanisms by which mitochondrial stress leads to insulin resistance. Moreover, we list some cytokines and genes that have recently been found to play roles in mitochondrial stress and insulin resistance. Furthermore, we describe several natural drugs that are currently widely used and give a brief overview of their therapeutic mechanisms. Finally, we suggest possible ideas for future research related to the unique role that natural drugs play in the treatment of insulin resistance through the above targets.

Pneumonia kills over two million children under-age of five every year. Oral amoxicillin was recommended by WHO as the first drug of choice for treatment of non-severe pneumonia. The study aimed to determine the clinical failure rate of amoxycillin for the treatment of childhood non-severe pneumonia at Primary Health Care Centers (PHCCs). A randomized controlled multicenter-trial study was conducted in Sana’a. IMCI strategy was used to enrollments the cases where randomly allocated to receive amoxicillin or co-trimoxazole orally for five days. Multivariate logistic regression was used for identified risk factors associated with clinical failure. A total of 254 children were enrolled, of whom 128 cases were treated with amoxicillin while 126 with co-trimoxazole. The clinical failure for amoxicillin was significantly more than co-trimoxazole (30% vs 10%) p value > 0.001. the most risk factor which significantly associated to amoxicillin failure were pre-infection in the last 6 months, while abnormal CBC and literate mothers were associated with clinical failure of co-trimoxazole (p value > 0.05). The use of co-trimoxazole as an alternative to amoxicillin for the treatment of non-severe pneumonia in the PHCCs and conducting further studies to determine the appropriate antibiotic as the first line of defense are recommended.

Carbapenems have long been considered as treatment of choice for Gram-Negative Bacteria (GNB) infections, and today the clinical utility of this class is threatened by the emergence and spread of resistance favored by its increasing use. According to the WHO, Acinetobacter baumannii, nosocomial infection agent, tops the list of priority antibiotic-resistant pathogens, considered to be the most risky for humans. This study sought to determine the prevalence of Acinetobacter baumannii strains producing carbapenemases in four health facilities in the Center and Littoral regions of Cameroon and the associated risk factors. An analytical cross-sectional study was conducted over a six-month period from January to June 2022. All Acinetobacter baumanii or suspected strains isolated from pathological samples at the bacteriology laboratory of different health facilities were systematically collected and underwent a re-identification. After successfully subculturing and growing on nutrient agar, re-identification and antimicrobial susceptibility Testing (AST) were performed using the VITEK 2 System and the Kirby-Bauer method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Detection and phenotypic characterization of carbapenemases was performed according to adequate standard procedures. A total of 168/226 clinical isolates of Acinetobacter baumannii were confirmed after re-identification of which 52.69% came from male patients, and 55.09% from participants aged between 10-39 years old and 46.71% from pus samples. A very high resistance rates to all families of antibiotics was noted except to colistin (10.2%). About 40.12% of these strains produced carbapenemases with 62.69% of class B and 37.31% of class A. In addition, frequent hospitalisation was significantly associated to the production of carbapenemase among Acinetobacter baumanii (Ajusted-OR=16.53, P-value<0.0001). This study highlighted the emergence of carbapenemase-producing Acinetobacter baumannii which is increasingly growing. Continuous drug-resistant monitoring and preventive measures could help to prevent and curb the dissemination of A.baumanii resistance genes, especially in hospital settings.

Antibiotic resistance is a major public health issue that requires a multifaceted approach. One potential source of antibiotic-resistant bacteria is wastewater in developing countries, which often lacks proper treatment infrastructure and can release high levels of antibiotics and antibiotic-resistant bacteria into the environment. This review article summarizes current knowledge on strategies to combat antibiotic resistance in wastewater in developing countries. Our review highlights the importance of improving wastewater treatment infrastructure to effectively remove antibiotics and antibiotic-resistant bacteria, implementing measures to reduce the release of antibiotics into the environment, and monitoring and surveillance to track the presence and spread of antibiotic-resistant bacteria in wastewater. We also discuss the potential challenges and barriers to implementing these strategies and the need for further research to determine their effectiveness in real-world settings. Overall, this review highlights the need for a comprehensive approach to address antibiotic resistance in wastewater in developing countries and underscores the importance of addressing this issue to protect public health.

The cerebellum is an encephalic region classically known for its central role in the control of movement, although recent research has revealed its involvement in other cognitive and affective tasks. Several different pathologies are known to affect this structure, causing a wide range of behavioral and gait impairments. Intriguingly, although the neurodegenerative factors affect all Purkinje cells of the cerebellum uniformly, certain neurodegeneration patterns can be distinguished, in which some Purkinje cells persist longer than other cell types. Precisely, there is a cerebellar region, lobe X, which is more resistant to different types of neurodegeneration regardless of the injury. This work will review the main models of cerebellar degeneration, with special emphasis on this region, and aims to reveal a common origin for its resistance to neuronal death.

Bacteriophages have been recognized as potential biocontrol agents in the food industry. Bacteriophages have been proposed for a variety of applications within this industry including bio preservation, pathogen detection, and as an alternative treatment method to antibiotics in animal health. The potential applications of bacteriophages are widespread throughout the entire food production process and serve to enhance food quality, prevent foodborne illnesses, and enhance the efficiency of production. The ability of bacteriophages to lyse bacterial targets with high specificity and pose no threat to mammalian cells or natural microbiota is unique and relevant in terms of suitability for food safety. This review will outline potential and current applications of bacteriophages and their respective impacts on the field.

Background: Patients hospitalized in the intensive care unit (ICU) have a higher susceptibility to infections. Respiratory infections are the most common nosocomial infections. Rising antibiotic resistance due to indiscriminate use of antibiotics and poor adherence to standard precaution in healthcare facilities compounds the problem. The main aim of this study is to assess microbial patterns and antibiotic resistance from bronchoalveolar lavage specimens in severe pneumonia patients. Methods: This retrospective study was conducted in an Indonesian tertiary care hospital from January 2016-December 2020. Written and verbal informed consent was obtained prior to bronchoscopy procedures. Patients were enrolled if they had severe community-acquired pneumonia (CAP) according to American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) criteria, had high-risk hospital-acquired pneumonia (HAP), late-onset ventilator-associated pneumonia (VAP), or pneumonia caused by Coronavirus disease (COVID-19). Respiratory specimens via bronchoscopy were inoculated on general semi-sloid thioglycolate media. Testing for antibiotic susceptibility was done using the disk diffusion method. Results: Two hundred and one patients’ data were analyzed. The majority of patients were males (65,17%) and above 60 years of age. The most common type of pneumonia was CAP (39,3%). Neurologic/cerebrovascular disease was the most common comorbidity (35,32%). Acinetobacter baumannii was the most frequently isolated microorganism. Ampicillin/sulbactam and amikacin were found to yield lower microbial resistance. Conclusion: Combination of ampicillin/sulbactam and amikacin appeared effective as initial empirical therapy in severe pneumonia patients. Further studies are needed to evaluate the feasibility and effectiveness of this combined therapy.

Antimicrobial resistance (AMR) is one of the top 10 threats affecting global health. AMR defeats the effective prevention and treatment of infections caused by microbial pathogens including bacteria, parasites, viruses and fungi (WHO). Microbial pathogens have natural tendency to evolve and mutate over time resulting in AMR strains. The set of genes involved in antibiotic resistance also termed as “antibiotic resistance genes” (ARGs) spread through species by lateral gene transfer thereby causing global dissemination. While this biological mechanism is prevalent in the spread of AMR, human methods also augment through various mechanisms such as over prescription, incomplete treatment, environmental waste etc. A considerable portion of scientific community is engrossed in AMR related work trying to discover novel therapeutic solutions for tackling resistant pathogens. Comprehensive inspection of the literature shows that diverse therapeutic strategies have evolved over recent years. Collectively, these therapeutic strategies include novel small molecules, newly identified antimicrobial peptides, bacteriophages, phytochemicals, nanocomposites, novel phototherapy against bacteria, fungi and virus. In this work we have developed a comprehensive knowledgebase by collecting alternative antimicrobial therapeutic strategies from literature data. We have used subjective approach for datamining new strategies resulting in broad coverage of entities and subsequently add objective data like entity name, potency, safety information etc. The extracted data was organized KOMBAT (Knowledgebase Of Microbes’ Battling Agents for Therapeutics). A lot of these data are tested against AMR pathogens. We envision that this database will be noteworthy for developing future therapeutics against resistant pathogens. The database can be accessed through http://kombat.igib.res.in/.

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatment are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, the aim of this study was to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016 - February 2021). Our study identified positive predictive factors for TTF related to anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dl for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

Objective In this study, we aim to synthesize some evidence on the impacts that COVID-19 is having on the epidemiology of Antimicrobial Resistance (AMR) in Africa since it was declared global pandemic by WHO in March 2020. Methodology A scoping review was undertaken by collecting and curating relevant resources from peer-reviewed articles and also from the gray literature. Mixed approaches of extracting data (qualitative and quantitative) were employed in synthesizing evidence, as suggested by Health Evidence Network (HEN). Findings A model constructed based on the synthesis of early evidences available on the effects of factors linked to COVID-19 in impacting the evolution of AMR in Africa predicted that, in cumulative terms, those factors favoring the evolution of AMR outpace those disfavoring it by no less than three folds. Conclusion COVID-19 is fueling the evolution of AMR almost unhindered in Africa. Due recognition of this crisis, concerted efforts for resource mobilization and global cooperation are needed to tackle it.

Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

To examine the hydrophobicity of torrefied wood fuel, the water resistances of torrefied pellets prepared by two different methods were evaluated using exposure tests under indoor and outdoor conditions. Torrefied pellets from the xylem of Japanese cedar (Sugi, Cryptomeria japonica) and oak (Konara, Quercus serrata) were prepared by two methods: the torrefaction of wood chips followed by pelletization and the pelletization of wood chips followed by torrefaction. It was found that the pellets prepared by pelletization followed by torrefaction had much lower moisture levels than those prepared by the other method and they showed almost no change in diameter after an outdoor weathering test. These characteristics are unique and indicate that the pellets can be applied not only for industrial use but also for residential and commercial purposes.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant (MDR) or rifampin-resistant (RR) tuberculosis (TB) also play an important role in generating evidence to guide MDR/RR TB Generally, summary exposure classifications (e.g., ‘ever versus never’, ‘exposed at baseline’) have been used to characterize drug exposure, in the absence of detailed longitudinal data on MDR-TB regimen These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers’ ability to answer the most relevant questions while accounting for known This paper highlights the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens and offers an overview of the data and analytic strategies required to do

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. More the evolution of a character is probable more convergent evolution will be witnessed, consequently, convergent evolution could mean that the convergent character evolution result as a combination of these two factors. We investigate this phenomenon by studying the convergent evolution of biochemical functions. We use for the investigation the case of β-lactamases. β-lactamases hydrolyzes β-lactams which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase superfamily. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further show that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explaining the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part, by positive selection as the organisms having β-lactamase activity allows them to resist to organism secreting β-lactams. Indeed a mutation increasing the β-lactamases activity will be selected as the organisms having this activity will have an advantage over the others.

Background: Activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) play a key role in SCZ and treatment resistant SCZ. There are only few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ.Aim of the study: We examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls.Results: Serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions.Conclusion: The EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment.

Tomato is the highest-value fruit/vegetable crop worldwide. However, the quality and yield of tomatoes are severely affected by late blight. MicroRNA482s (miR482s) are involved in plant immune system. In this study, miR482c was transiently and stably overexpressed in tomatoes in transgenic plants to explore its mechanism in tomato resistance against late blight. Tomato in transgenic plants transiently overexpressed miR482c displayed larger lesion area than the control plants upon infection. Furthermore, compared with the WT tomato plants, the transgenic tomato plants stably overexpressing miR482c displayed decreased expression of target genes accompanied by lower POD, SOD, and PAL activity activities and higher MDA content, thereby leading to a decline in the ROS scavenging ability and aggravating the damage of lipid peroxidation product accumulation on the cell membrane, eventually enhancing plant susceptibility. This finding indicates that miR482c may act as a negative regulator in tomato resistance by regulating NBS-LRR expression levels and ROS levels.

Let G[F,Vk, Huv] be the graph with k pockets, where F is a simple graph of order n ≥ 1,Vk= {v1,v2,··· ,vk} is a subset of the vertex set of F and Hvis a simple graph of order m ≥ 2,v is a specified vertex of Hv. Also let G[F,Ek, Huv] be the graph with k edge pockets, where F is a simple graph of order n ≥ 2, Ek= {e1,e2,···ek} is a subset of the edge set of F and Huvis a simple graph of order m ≥ 3, uv is a specified edge of Huvsuch that Huv− u is isomorphic to Huv− v. In this paper, we derive closed-form formulas for resistance distance and Kirchhoff index of G[F,Vk, Hv] and G[F,Ek, Huv] in terms of the resistance distance and Kirchhoff index F, Hv and F, Huv, respectively.

The hydrodynamic results obtained from the permeability of porous materials not only affect the assessment of the stream of the gas flow through those materials but they also refer to the loss of pressure energy in that flow. The direct measure of that loss is flow resistances.The results of experimental research upon the assessment of the flow resistances of porous materials with respect to gas flow. The research conducted applied to natural materials with an anisotropic gap-porous structure. The tests were carried out on a gas permeability measuring system, adapted to different shapes of porous material samples. The process issue of the total pressure drop on a porous deposit was considered in the Reynolds number category. The coefficient of flow resistance for anisotropic materials was defined and the value of this coefficient was compared to the gas stream and the total pressure drop on the porous bed was experimentally evaluated.

Wastewater treatment plants (WWTPs) are thought to be potential incubators of antibiotic resistance. Persistence of commonly used antibiotics in wastewater may increase the potential for selection of resistance genes transferred between bacterial populations, some of which may pose a threat to human health. In this study, we measured the concentrations of ten antibiotics in wastewater plant influents and effluents, and in surface waters up- and downstream from two Charlotte area treatment facilities. We performed Illumina shotgun sequencing to assay the microbial community and resistome compositions at each site across four time points from late winter to mid-summer of 2016. Antibiotics are present throughout wastewater treatment, and elevated concentrations of multiple antibiotics are maintained in moving stream water downstream of effluent release. While some human gut and activated sludge associated taxa are detectable downstream, these seem to attenuate with distance while the core microbial community of the stream remains fairly consistent. We observe slight suppression of functional pathways in the downstream microbial communities, including amino acid, carbohydrate and nucleic acid metabolism as well as nucleotide and amino acid scavenging. Nearly all antibiotic resistance genes (ARGs) and potentially pathogenic taxa are removed in the treatment process, though a few ARG markers are elevated downstream of effluent release. Taken together, these results represent baseline measurements which future studies can utilize to help to determine which factors control the movement of antibiotics and resistance genes through aquatic urban ecosystems before, during and after wastewater treatment.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

The aim of our work was to check if one of the products of natural origin, namely honey bee propolis may be an alternative or supplement to currently used antifungal agents. The activity of 50 ethanolic extracts of propolis (EEPs), harvested in Polish apiaries, was tested on a group of 69 clinical isolates of C. albicans. Most of the EEPs showed satisfactory activity, with minimum fungicidal concentrations (MFC) mainly in the range of 0.08-1.25% (v/v). Eradication of biofilm from polystyrene microtitration plates in 50% (MBEC50) required concentrations in the range of 0.04% (v/v) to more than 1.25% (v/v). High activity was also observed in eradication of biofilm formed by C. glabrata and C. krusei on the surfaces of PVC and silicone catheters. EEPs at subinhibitory concentrations inhibited yeast-to-mycelia morphological transformation of C. albicans in liquid medium and mycelial growth on solid medium. A synergistic effect was observed for the action of EEPs in combination with fluconazole (FLU) and voriconazole (VOR) against C. albicans. In the presence of EEP at concentration as low as 0.02%, the MICs of FLU and VOR were 256 to 32 times lower in comparison to those of the drug alone. Evidences for the fungal cell membrane as the most probable target of EEPs are presented.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

In this study, graphite, the most stable form of carbon, was examined for its hexagonal crystalline structure with specific dimensions (ao=2.46 Ǻ; co=6.70 Ǻ). Its framework comprises parallel carbon atom planes forming regular hexagons (side length 1.415 Ǻ) and 120° angles between adjacent atoms. Two structural variations exist: hexagonal symmetry (1-2-1-2-1-2 planes) and rhomboidal symmetry (1-2-3-1-2-3 planes). The research aimed to produce high-density graphite utilizing carbonaceous raw materials. Graphite-based materials often exhibit high porosity, necessitating additional treatments. The study successfully obtained mesophase tar pitch (yield: 45%), a pivotal raw material, and high-density graphite. The resulting graphite underwent characterization for physical properties (apparent and real density, porosity and compression strength), demonstrating conformity with existing literature data.

After the great success of Mobile wallet, the Internet of Things (IoT) leaves the door wide open for consumers to use their connected devices to access their bank accounts and perform routine banking activities from anywhere, anytime and with any device. However, consumers need to feel safe when interacting with IoT-based payment systems, and their personal information should be protected as much as possible. Unlike as usually done in the literature, in this paper, we introduce two lightweight and secure IoT-based payment protocols based on an identity-based signature scheme. We adopt a server-aided verification technique to construct the first scheme. This technique allows to outsource the heavy computation overhead on the sensor node to a cloud server while maintaining the user's privacy. The second scheme is built upon a pairing-free ECC-based security protocol to avoid the heavy computational complexity of bilinear pairing operations. The security reduction results of both schemes are held in the Random Oracle Model (ROM) under the discrete logarithm and computational Diffie-Hellman assumptions. Finally, we experimentally compare the proposed schemes against each other and against the original scheme on the most commonly used IoT devices: a smartphone, a smartwatch and the embedded device Raspberry Pi. Compared with existing schemes, our proposed schemes achieve significant efficiency in the term of communication and computational overheads

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

This study examines the impact of the impregnation of fireclay-based conventional (CC) and medium cement castables (MCC) with liquid sodium silicate glass under vacuum conditions. The goal is to assess how this treatment affects physical, mechanical properties, and durability (alkali and thermal shock resistance) of these castables used in biomass combustion boilers, where they are exposed to temperatures up to 1100°C. The research work employs standard test methods to evaluate physical and mechanical properties. Additionally, advanced techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and specific tests for alkali resistance and thermal shock resistance are used. The research findings suggest that impregnation with sodium silicate glass under vacuum significantly enhances the alkali resistance of both CC and MCC castables. This improvement is primarily due to the reduction in porosity and the increase in density. SEM images reveal that impregnated samples are coated with a glassy layer and the pores are partially filled with sodium silicate. Tests for alkali resistance demonstrate the formation of a protective glassy layer (with a thickness of 0.9-1.5 mm) on the castables surfaces, thereby reducing further penetration of alkali into deeper layers of the samples. However, it is important to mention that impregnated refractory castables have reduced resistance to thermal shock cycles.

Patients receiving hemodialysis are at risk of vascular access infections (VAIs) and particularly vulnerable to the opportunistic pathogen Staphylococcus aureus. Hemodialysis patients were also at increased risk of infection during the COVID-19 pandemic. Therefore, this study determined the change in the molecular and antibiotic resistance profiles of S. aureus isolates from VAIs during the pandemic compared with before. 102 S. aureus isolates were collected from VAIs between November 2013 and December 2021. Before the pandemic, 69 isolates were collected, 58%, 39.1%, and 2.9% from arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs), respectively. The prevalence of AVG and TCC isolates changed to 39.4% and 60.6%, respectively, of 33 isolates during the pandemic. Sequence type (ST)59 was the predominant clone in TCC-methicillin-resistant S. aureus (MRSA) and AVG-MRSA before the pandemic, whereas the predominant clone was ST8 in AVG-MRSA during the pandemic. ST59 carrying the ermB gene was resistant to clindamycin and erythromycin. By contrast, ST8 carrying the msrA gene was exclusively resistant to erythromycin. The ST distribution for different VAIs changed from before to during the pandemic. The change in antibiotic resistance rate for different VAIs was closely related to the distribution of specific STs.

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens means requirement of harsh treatment methods such as medicinal drugs or antibiotics. However, such treatments impact the gut microbiome, and create dysbiosis, often leading to opportunistic pathogens, anti-microbial resistance, or functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). Recent studies have shown that these impacts do not remain confined to gut, and are reflected across the gut-brain, gut-liver, and gut-lung axes, among others. Therefore, apart from the medicinal treatment, nutritional supplementation is also a key aspect of providing the recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, the nutritional supplementation also helps to build a resilience against the opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterises the fundamental host-pathogen interaction biochemical pathways, at various infection and recovery stages. This same mechanism also allows to track the impact of abovementioned treatment methods of gut microbiome remediation. This manuscript is organised in sections delving into system biology approaches and upcoming developments to understand (1) Infection mechanism and current global status; (2) Cross-organ impacts of dysbiosis, particularly within gut-liver and gut-lung axes; (3) Nutritional interventions. It highlights the impact of antimicrobial resistance (AMR) and Multi-drug resistance (MDR) from a perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena.

This work aims to explore the impact of side loads, drill-pipe tool-joint (DP-TJ) speed (RPM), and mud type on the austenitic stainless steel SM2535-110 casing wear characteristics. Actual field drill pipe tool joints, casings, and drilling muds are used in this study. The results of the study show that under both types of lubrication, the wear volume increased with radial load and DP-TJ speed. SM2535-110 casing specimens tested under oil-based mud (OBM) lubrication had higher casing wear volumes than those obtained under water-based mud (WBM) lubrication. This unexpected behavior is mainly due to the increase in the surface hardness of the casing specimens tested under WBM. The results also show that the specific wear factor (K) values of specimens tested under WBM are in general 2 to 4 times higher than those obtained under OBM. While K values under WBM increase with both the side load and RPM, those under OBM show a sharp decrease with RPM. This behavior under OBM is due to this lubricant’s higher viscosity and the change of lubrication regime from thin film to thick film lubrication at higher RPM. Scanning electron microscopy (SEM) and the digital microscopic imaging (DMI) of SM235-110 casing specimens show that an aggressive combination of adhesive, abrasive, and plastic deformation was observed under WBM, while the dominant wear mechanism under OBM is abrasive wear.

Financial markets require a great deal of decision making from the investors and market makers. One metric that can help ease the process of decision making is investment risk which can be measured in two parts; systematic risk and idiosyncratic risk. Clear understanding of the volatilities in each risk component can be a powerful signal in recognizing the right assets to maximize the investment returns. In this paper, we focus on the idiosyncratic volatility values and pre-calculate the idiosyncratic volatility values for 31,198 members of NYSE, Amex and Nasdaq markets for the trades occurring between January 1963 and December 2019. Utilizing a subset of dataset, limited to Nasdaq100 index, we consider the application of machine learning techniques in predicting the idiosyncratic volatility values using the raw trade data to explore a data extension option for the future market trade records that have not yet occurred. We offer a deep learning based regression model and compare it with traditional tree-based methods on a small subset of our per-calculated idiosyncratic volatility dataset. Our analytical results show that the performance of the deep learning techniques is much more robust in comparison to that of the traditional tree-based baselines.

This study compares the effects of lecture-based instruction and process-oriented guided inquiry learning (POGIL)-based instruction on the self-efficacy performance of Grade 12 students. A quasi-experimental, pretest-posttest design was adopted to investigate and assess the impact of POGIL-based instruction versus lecture-based instruction on students’ performance as measured by three types of cognitive outcomes; Knowing, Applying and Reasoning (KAR). Two government high schools in Alain were selected as research sites, one for the boys and one for the girls. The total number of participants was approximately 110 students (N=110); 54 were assigned to treatment groups (25 girls and 29 boys), and 56 were assigned to control groups (27 girls and 29 boys). The treatment group was taught a circular motion unit in physics using POGIL-based instruction, while the control group was taught the unit using lecture-based instruction. The study's findings showed statistically significant differences between students of the control group and the treatment group in favour of the latter regarding their science performance, self-efficacy and science-related attitudes. Moreover, positive correlations were found between participants’ performance at the KAR test, self-efficacy and scientific attitudes towards scientific inquiry after the intervention. In conclusion, it is recommended to shift teaching towards POGIL-based instruction due to its positive impact on students’ performance and self-efficacy. It is also suggested to replicate the study to include government and private schools, elementary and high schools, teachers and advisors.

Management of urinary tract infection is challenged by increasing antimicrobial re-sistance (AMR) worldwide. In this study we describe the trends in antimicrobial re-sistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. Proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and car-bapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales were the commonest group of organisms, E. coli (70.6) being the commonest isolate and Enterococcus spp. the commonest gram positive (1.3%) organisms. Among oral antimicrobials the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2) %) and the least resistance to Fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem ( 0.3%). Highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). ESBL positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recom-mended antimicrobials

Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently pose a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carries mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n=586). mcr-1 genes were detected using a previously developed qPCR assay and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological background.

The production of public goods is a necessary condition for the survival of the species but it comes at the expense of individual growth. In a prototype bacterial colony, we model the role of quorum sensing as a resource redistribution mechanism. Two types of bacterial colonies are analyzed, one made up of a single strain and one made up of two different strains. Based on a recent series of experimental data present in the literature, we analyze two types of strains with different extinction times: strains that consume available resources very quickly, therefore becoming extinct quickly, and strains that consume resources slowly and die due to aging. We show that the proposed quorum sensing model describes the main experimental result, namely that coexistence favors the survival of both strains. Furthermore, the production of public goods is maximized when both types of individuals have the maximum proliferation output. Finally, we highlight the role played by so-called dormant cells in the duration of survival time. These cells are of particular interest, because their ability to counteract different types of stress (e.g. the use of antibiotics) still constitutes a challenge.

Background: Endometriosis is a female chronic inflammatory disease in which endometrial tissue develops outside the uterine cavity. It is a complex pathology, that significantly contributes to morbidity in premenopausal women, leading to chronic pain, infertility, and subfertility negatively impacting the physical, and emotional well-being and overall quality of life. The public health burden of endometriosis remains elusive and challenging to determine, and this uncertainty can lead to inadequate healthcare services and treatments. Objective: To estimate the incidence and prevalence of endometriosis in Italy using the hospital discharge records database. Population-based retrospective study. Nationwide between 2011 and 2020. Methods: From the National Hospital Discharge Database were selected all admissions with a diagnosis of endometriosis (ICD-9-CM, codes 617.x), supported by the presence of a procedure code of laparoscopy or any other surgical procedure allowing direct visualisation of the lesions. Main outcomes measures Incidence and prevalence of endometriosis were estimated for the entire 2010-2020 period and by individual year, analysing the time trend and variability in different geographical areas of Italy. Results: A total of 134,667,646 women aged 15–50 years with one or more hospitalisations for endometriosis in all Italian hospitals. The incidence of endometriosis in Italy during this period was 0.839 per 1000 women (CI95% 0.834-0.844), exhibiting a statistically significant decreasing trend over the years. A discernible north-south gradient was observed, with higher rates documented in the northern regions. The prevalence rate stood at 14.0 per 1000 during the same period, and a similar north-south geographical gradient was identifiable in the prevalence rates as well. Conclusions: The utilization of national-level hospital data enables the generation of incidence and prevalence data for endometriosis without variations in methods and definitions, facilitating the evaluation of temporal trends and regional comparisons. Understanding and quantifying this phenomenon is essential for appropriate healthcare planning in various Italian regions.

The potential advantages of plant-based interventions in decreasing the incidence and lessening the morbidity and mortality of COVID-19 are yet to be widely acknowledged. Nevertheless, recent publications propose that these interventions could be effective. Our cardiology center conducted an interventional study in which we incorporated plant-based foods and provided supplementation to 3470 elderly COVID-19 patients with multiple comorbidities. We pay close attention to the precise selection of food items, the application of appropriate processing methods, and the provision of nourishing meals to our patients. Our outcome was highly successful as we achieved a zero mortality rate, and none of our patients experienced worsening conditions or required hospitalization. In this review article we present the mechanisms how plant-based and supplement interventions can mitigate COVID-19 disease severity and mortality. And experts have validated our hypotheses very recently. The measures and methods used to address the ongoing SARS-CoV-2 pandemic through plant-based interventions and supplements are effective and may help prevent or manage future pandemics.

Abstract: This study aims to evaluate the effectiveness of plant-based diets and supplement interventions in mitigating the severity and mortality of COVID-19 patients. Observational research suggests that a diet high in plant-based foods may decrease the likelihood and severity of SARS-CoV-2 infection. However, several studies have faced criticism regarding the accuracy of obtaining dietary questionnaires and the insufficient intake of essential vitamins and minerals in such diets. To address these issues, this study employed a prospective interventional design that strictly controlled the quality, quantity, and processing of plant-based foods provided. Furthermore, the study incorporated supplementation, which enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a plant-based diet against the SARS-CoV-2 virus. Of the 3,470 COVID-19 elderly patients, half already followed a plant-based diet, and the other half new patients, both with various comorbidities, were intervened with a plant-based diet and supplementation. The results showed that the participants in the non-plant-based diet group were twice as likely to have experienced moderate disease (with 95% confidence limit: 1.42-3.12) and 2.4 times more likely to have experienced severe disease (with 95% confidence limit: 1.2-5.0) with a significant p-value of less than 0.0005 and 0.016 respectively, compared to those in the PBD group. During the interventions, none of the participants experienced disease progression or hospitalization, and there were no reported deaths by the end of the study. The outcome was highly favorable and aligned with the researchers' expectations, as COVID-19 morbidity and mortality rates in Indonesia were among the highest in Asia. This research may provide significant insights into the prevention and management of COVID-19 and aid in better preparation for future pandemics.

Chitosan is a copolymer of β-glucosamine and N-acetylglucosamine. Recent experiments showed that the degree and pattern of acetylation along the chitosan chain modulate the biological and physicochemical properties; however, the molecular mechanism is unknown. Here we apply the de novo all-atom molecular dynamics (MD) simulations to study chitosan’s self-assembly process at different degrees of acetylation and two different acetylation patterns. The simulations revealed that the 10-mer chitosan chains with 50% acetylation in either block or alternating patterns associate to form ordered nanofibrils comprised of mainly antiparallel chains in agreement with the fiber diffraction data of deacetylated chitosan. Surprisingly, regardless of the acetylation pattern, the same intermolecular hydrogen bonds mediate the fibril sheet formation while water-mediated interactions stabilize the sheet-sheet stacking. Moreover, the acetylated units are involved in forming the strong intermolecular hydrogen bonds (NH–O6 and O6H–O7), which offers an explanation for the experimental observation that increased acetylation lowers chitosan’s solubility. Taken together, the present study provides the atomic-level understanding the role of acetylation plays in modulating chitosan’s physiochemical properties, contributing to the rational design of chitosan-based materials with the ability to tune by its degree and pattern of acetylation. Additionally, we disseminate the improved molecular mechanics parameters that can be applied in MD studies to further understand chitosan-based materials.

The process of Targeted Opinion Word Extraction (TOWE), a critical component of aspect-based sentiment analysis (ABSA), revolves around identifying opinionated words linked to specific aspect-terms within sentences. Existing deep learning approaches, while effective, often overlook the syntactic structure of sentences, a factor that previous studies have identified as beneficial for TOWE. In this study, we introduce the Syntactic-Enhanced Deep Learning Model (SEDLM) that integrates syntactic structures into deep learning frameworks for TOWE. Our approach leverages syntax-driven opinion potential scores and syntactic inter-word connections, enhancing model performance. Additionally, we introduce an innovative regularization strategy aimed at distinguishing word representations in TOWE tasks. Our comprehensive analysis reveals that SEDLM sets new benchmarks in performance across multiple standard datasets.

The implementation of Boolean functions using Nano crossbar- based switching lattices has been suggested as a substitute for conventional CMOS-based approaches in digital circuits . This alternative may satisfy the needs of future electronic designs, con- sidering the expected end of Moore’s law. This study introduces CVM, a Crossbar-based circuit Verification through Modeling tech- nique

Castor oil may be differentiated from other non-edible vegetable oils because of its main composition of hydroxylated fatty acids. Ricinoleic acid comprises 80–90% wt. of fatty acids in castor oil (Ricinus communis). In this study, the thermo-oxidative stability and tribological behavior of bio-based lubricant samples synthesized from castor oil using isoamyl alcohol were evaluated. Initially, the compositional and physicochemical properties of the obtained samples were assessed using 1H NMR, FTIR, and ASTM methods. Oxidative stability of the samples was evaluated using Rancimat method at 110 °C under air flow. The final biolubricant sample (BL2), obtained after esterification, epoxidation, and oxirane rings opening reactions, presented an oxidation stability time (OST) of 14.3 h. The thermal stability was also evaluated by thermogravimetry (TG) from the mass variations under inert and oxidative atmosphere. BL2 showed higher thermal stability compared to the other samples, demonstrating higher decomposition temperatures in both inert (339.04 °C) and oxidative (338.47 °C) atmospheres, for a mass loss of 50%. The tribological properties of the samples were evaluated using a four-ball tribometer configuration. The BL1 and BL2 samples exhibited lower friction coefficients than the mineral oil sample (MOS) by 21.5% and 43.1%, respectively. Regarding wear, the observed wear scar diameter (WSD) was also lower in BL1 and BL2 compared to MOS by 5.2% and 40.4%, respectively. The results of the tribological evaluation suggest that both samples obtained in this study have promising potential for applications in lubricating machines and mechanical systems.

Waste management is a significant issue that Indonesia must face. The presence of waste will always exist as long as life continues. One of the main challenges in waste management is the proper separation of organic and inorganic waste. As a solution to address this issue, the Ministry of Environment has made efforts to develop Waste Banks. However, it also creates new problems related to manual data collection, lack of monitoring by the community in implementing waste management activities, and a lack of specific reports regarding waste management conducted by officers. We propose the creation of a website using the Agile Development SDLC method. This website involve several steps and incorporate functions for data digitalization and expedited data collection, such as the addition of QR Code functionality, Monthly Reporting Function, and enhanced data security. The method used in this research is Agile Development. The application has been developed with a user-friendly interface and the latest web development technologies to ensure smooth performance. Overall, the web-based application for organic and inorganic waste using Laravel is an important step to promoting sustainable waste management practices.

In this work, the inhibition properties of new bio-based lignine ILs on the corrosion of mild steel in an aqueous solution of 0.01 M NaCl were investigated by Potentiostatic Electrochemical Impedance Spectroscopy (PEIS), Cyclic Potentiodynamic Polarization (CPP). Moreover, the surface was characterized using SEM, EDS, and optical profilometry. The influence of cation and anion on the inhibitor properties and a possible synergistic effect were investigated. The IL choline syringate showed a promising performance, reducing the corrosion current after 24-hour immersion in 0.01 M sodium chloride, from 1.66 µA/cm2 for the control to 0.066 µA/cm2 with 10 mM of the IL present. In addition to the performance as a corrosion inhibitor, both components of this IL also meet or exceed current additional desired properties of such compounds, being readily available, economically efficient, and well tolerated in organisms and the environment.

Paper-based analytical devices have been substantially developed in recent decades. Many fabrication techniques for paper-based analytical devices have been demonstrated and reported. Herein we report a relatively rapid, simple, and inexpensive method for fabricating paper-based analytical devices using parafilm hot pressing. We studied and optimized the effect of the key fabrication parameters, namely pressure, temperature, and pressing time. We discerned the optimal conditions, including pressure of 3.8 MPa (3 tons), temperature of 80oC, and 3 minutes of pressing time, with the smallest hydrophobic barrier size (821 µm) being governed by laminate mask and parafilm dispersal from pressure and heat. Physical and biochemical properties were evaluated to substantiate the paper functionality for analytical devices. Wicking speed in the fabricated paper strips was slightly slower than that of non-processed paper, resulting from reducing paper pore size. A colorimetric immunological assay was performed to demonstrate the protein binding capacity of the paper-based device after exposure to pressure and heat from the fabrication. Moreover, mixing in two-dimensional paper-based device and flowing in a three-dimensional counterpart were thoroughly investigated, demonstrating that the paper device from this fabrication process is potentially applicable as analytical devices for biomolecule detection. Fast, easy, and inexpensive parafilm hot press fabrication presents an opportunity for researchers to develop paper-based analytical devices in resource-limited environments.

Abstract: Calcium-based catalysts are of a high interest for glycerol polymerization due to their high catalytic activity and large availability. However, their poor stability under reaction conditions is an issue. In the present study, we investigated the stability and catalytic activity of Ca-hydroxyapatites (HAps) as one of the most abundant Ca-source in nature. A stochiometric, a Ca-deficient and a Ca-rich HAps have been synthetized and tested as catalysts in the glycerol polymerization reaction. Deficient and stochiometric HAps exhibited a remarkable 100% selectivity to triglycerol at 15 % of glycerol conversion at 245 °C after 8 h of reaction in the presence 0.5 mol.% of catalyst. Moreover, under the same reaction conditions, Ca-rich HAp showed a high selectivity (88 %) to di- and triglycerol at a glycerol conversion of 27 %. Most importantly, these catalysts were unexpectedly stable towards leaching under the reaction conditions based on the ICP-OES results. However, based on the catalytic tests and characterization analysis performed by XRD, XPS, IR, TGA-DSC and ICP-OES, we found that HAps can be deactivated by the presence of the reaction products themselves, i.e., water and polymers.