Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved vaccines or treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their combinations may have fewer side effects in vivo and therefore should be further studied in pre- and clinical trials.

The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to significant enhancement of what is still arguably a novel technology. Yet the major applications of photodynamic therapy still remain firmly located in neoplasms, from where most of the new innovations appear to launch to other areas, such as microbial, fungal, viral, acne, wet age-related macular degeneration, atherosclerosis, psoriasis, environmental sanitization, pest control, and dermatology. The core value proposition of combinations of photodynamic therapy is that they enhance the leading alternative and are proposed to overcome challenges of the leading clinical anticancer and antibacterial methods, mainly due to its inherent barriers against the emergence of resistance and its rapid development of targeted and high precision therapy. Combinations with chemotherapy and radiotherapy and demonstrated applications in mop-up surgery adventitiously promise to repurpose these top three clinical tools. This review will navigate the vast and increasing innovations that have been created so as to obviate novel areas of further innovation.

Based on the dynamic strength variation mechanism of concrete under complex loading conditions, two approaches were devised: numerical testing and CT scanning, guided by the principle of minimizing energy dissipation. A methodology for calculating concrete's failure area and measuring its strength was developed. The analysis delves into the mechanisms behind failure patterns and variations in concrete specimen strength, focusing on crack initiation, development, and the resultant failure surface formed by crack propagation, along with the stress distribution in concrete specimens subjected to diverse loading conditions. Through evaluating the strength and computed failure area of concrete specimens, it is evident that the loading method influences both the strength and failure area of concrete specimens. In general, a larger failure area correlates with a higher measured strength.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

In this paper, a continuous power management for a decentralized DC microgrid (DCMG) is proposed to achieve voltage regulation and power balance even under system uncertainty and voltage sensor failure. The DCMG system achieves a continuous power management through only the primary controller to reduce the computational burden of each power agent. To enhance the reliability and resilience of the DCMG system under voltage sensor failure, a DC bus voltage (DCV) sensor fault detection algorithm is proposed. In this algorithm, the DCV sensor failure is detected by comparing the measured DCV with the estimated DCV. When the power agent identifies the DCV sensor failure, it changes the operation properly according to the proposed control mode decision algorithm to maintain the stability of the DCMG system. When uncertain conditions such as the power variation of the distributed generations, sudden grid disconnection, DCV sensor failure, electricity price change, and critical battery status occur, the DCMG system is changed to transitional operation modes. These transitional operation modes are employed to transmit the power agent information to other agents without digital communication links (DCLs) and to accomplish power sharing even under such uncertain conditions. In the transitional operation modes of the DCMG system, the DCV levels are temporarily shifted to an appropriate level, enabling each power agent to detect the uncertainty conditions, and subsequently to determine its operation modes based on the DCV levels. Simulation and experimental results under different test conditions confirm the reliability and effectiveness of the proposed control scheme.

Several mathematicians and physicists are working all over the globe to get a unified theory. However, most of them are discarding Einstein’s view at the very first step of their theories. This article provides a brief description about this. Also, on the basis of Koga’s theory we point out two reasons which might have caused Einstein’s failure to get a unified theory.

This paper discusses a possible approach to validate the Goldbach conjucture which states that all even numbers can be expressed as a summation of two prime numbers. For this purpose the paper begins with the concept of successive-addition-of-digits-of-an-integer-number (SADN) and its properties in terms of basic algebraic functions like addition, multiplication and subtraction. This concept of SADN forms the basis for classifying all odd numbers into 3 series- the S1, S3 and S5 series- which comprise of odd numbers of SADN(7,4,1), SADN(3,9,6) and SADN(5,2,8) respectively and follow a cyclical order. The S1 and S5 series are of interest in the analysis since they include both prime and composite numbers while the S3 series exclusively consists of composite numbers. Furthermore, the multiplicative property of SADN shows why composites on the S1 series are derived as products of intra-series elements of the S1 and S5 series while composites on the S5 series are derived as products of inter-series elements of the S1 and S5 series. The role of SADN is also important in determining the relevant series for identifying the combination of primes for a given even number since it shows why such combinations for even numbers of SADN(1,4,7) will be found on the S5 series while those for even numbers of SADN(2,5,8) will lie on the S1 series and both the series have a role to play in identifying the prime number combinations for even numbers with SADN(3,6,9). Thereafter, the analysis moves to calculating the total number of acceptable combinations for a given even number that would include combinations in the nature of two composites (c1+c2), one prime and one composite (p+c) and two primes (p1+p2). A cyclical pattern followed by even numbers is also discussed in this context. Identifying the c1+c2 and p+c combinations and thereafter subtracting them from the total number of combinations will yield the number of p1+p2 combinations. For this purpose the paper discusses a general method to calculate the number of composites on the S1 and S5 series for a given number and provides a detailed method for deriving the number of c1+c2 combinations. The paper presents this analysis as a proof to validate the Goldbach conjecture. Since even numbers can be of SADN 1 to 9 and the relation between nTc (i.e. total number of acceptable combinations) and nc(i.e. number of composites) for all even numbers can either be of nTc > nc or nTc ≤ nc, the paper shows that the Goldbach conjecture is true for both these categories of even numbers. In this manner this analysis is totally inclusive of all even numbers in general terms and since the analysis of every even number is common in methodology but unique in compilation, apart from being totally inclusive, it is also mutually exclusive in nature. This proves that the Goldbach conjecture which states that all even numbers can be expressed as atleast one combination of two prime numbers holds true for all even numbers, across all categories possible. Additionally this approach proves that the identification of p1+p2 combinations which would validate the Goldbach conjecture lies in the identification of c1+c2 combinations.

Texture has long been considered an important attribute for food acceptance. However, which specific textural characteristics contribute to overall acceptance of a food is not well understood. It has been suggested that texture contrasts and combinations are a universal feature in giving foods a desirable texture, yet this notion is largely based upon anecdotal data. This study uses multiple survey research methods to assess the importance of texture contrast and combinations across cultures (Poland, U.S.A., and Singapore). Participants (n = 288) completed a survey that included overt measures of food texture contrast importance as well as free response questions regarding texture. The overall importance of texture for food liking was not different across the populations. However, the participants from Singapore and Poland gave more importance to a desirable food having multiple textures than the U.S.A. cohort. When looking at free responses, participants were twice as likely to mention combinations (multiple textures) with a texture contrast when describing foods they liked, in comparison to foods they disliked. This was observed across all 3 cultures. However, the type and quantity of texture terms used within combinations were different among cultures. For instance, Asians enjoyed more texturally diverse food combinations than the other two cultures. These findings highlight the importance of texture contrasts and combinations in three distinct cultures.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Cisplatin is an election chemotherapeutic agent for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. In this paper we report that a combination of vitamins A, C, E and Mg++ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in the rat. The addition of 500 mg N-acetylcysteine (NAC), which administered individually also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation, results in degradation of ACEMg otoprotection. Mg++ administered alone, as MgSO4, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection also is greatly degraded. Increasing the dose of NAC to 1000 mg, also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet to be defined “antioxidation threshold”, results in unrecoverable redox imbalance with loss of otoprotectant activity.

Bayesian analysis for masked data under competing risk frameworks is studied for the purpose of assessing the impact of covariates on the hazard functions when the failure time is exactly observed for some subjects but only known to lie in an interval of time for the remaining subjects. Such data, known as partly interval-censored data, usually result from periodic inspection. Dirichlet and Gamma processes are assumed as priors for masking probabilities and baseline hazards. The Markov Chain Monte Carlo (MCMC) technique is employed for the implementation of the Bayesian approach. The effectiveness of the proposed model is tested through numerical studies, including simulated and real data sets.

Rubber compounds based on styrene-butadiene rubber, ethylene-propylene-diene-monomer rubber and the combinations of both rubbers were cured with different sulfur and peroxide curing systems. In sulfur curing systems, two type of accelerators, namely N-cyclohexyl-2-benzothiazole sulfenamide, tetramethylthiuram disulfide and combinations of both accelerators were used. In peroxide curing systems, dicumyl peroxide, and combination of dicumyl peroxide with zinc diacrylate or zinc dimethacrylate, respectively were applied. The work was focused on investigation of the curing system composition as well as type of the rubber or rubbers combinations on curing process, cross-link density and physical-mechanical properties of vulcanizates. The dynamic-mechanical properties on the selected vulcanizates were examined, too. The result revealed correlation between the cross-link density and physical-mechanical properties. Similarly, there was recorded certain correlation between cross-linking degree and glass transition temperature. The tensile strength of vulcanizates based on rubbers combinations was higher when compared to that based on pure rubbers, which points out the fact that by rubbers combination, not only the features of both elastomers can be combined, but also improved tensile characteristics can be achieved. When compared to vulcanizates cured with dicumyl peroxide, materials cured with sulfur system exhibited higher tensile strength. By application of co-agents in peroxide vulcanization, the tensile strength overcame the tensile behavior of sulfur cured vulcanizates.

In the semi-arid region of Brazil, it is common to use saline or brackish water for crop production. However, this practice can negatively affect the soil, nutrient balance, and fruit quality and production. From this perspective, this study aimed to evaluate the effect of fertilization combinations with nitrogen (N), phosphorus (P), and potassium (K) on the production and quality of West Indian cherry grown under salt stress in the second year of production. The study was conducted in a protected environment following a randomized block design with treatments distributed in a 2 x 10 factorial arrangement referring to two levels of electrical conductivity of irrigation water (ECw) (0.6 and 4.0 dS m-1) and 10 NPK fertilization combinations (80-100-100; 100-100-100; 120-100-100; 140-100-100; 100-80-100; 100-120-100; 100-140-100; 100-100-80; 100-100-120 e 100-100-140% of the recommendation in the second year of production), with three replicates and one plant per lysimeter. The results indicate that irrigation of West Indian cherry crop irrigation at the water salinity of 4.0 dS m-1 negatively affected all fruit production variables. The interaction between the ECw of 0.6 dS m-1 and the 100-80-120 NPK fertilization combination increased the total number of fruits and the total fruit weight of West Indian cherry.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

During composting process, soils undergo many changes in their physical, chemical and biological properties. Composting has been widely known as an aerobic process during which organic matter is decomposed to humus like substances broken into many organic materials or compounds. The project aims to compare and analyze different combination of composting that yield different properties and nature of soils, and testing their soil physical properties. Dug three compost pits each 1.5 m in depth, labeled compost pit A consisting of potato peels – the only kitchen waste most common around the college hostels, compost pit B consisting of leaf litter and other garden trimmings and compost pit C consisting of cow dung and the other as a controlled experiment with no composting practices.

The unusual occurrence and developmental diversity of asexual eukaryotes still remain a puzzle. Despite asexual organisms have a theorized two-fold reproductive advantage over sexuals, asexual lineages are rare among multicellular eukaryotes. Justification of such disparity relies on the consequences of a lack of meiosis, which restricts genotype diversity and adaptation to novel conditions while accelerating the genetic degeneration that drives asexual lineages to an early demise. However, evidence indicates asexuals use different strategies to limit negative consequences of ameiosis, and age estimates show some asexual vertebrates and plants are much older than expected. If rapid extinction is not a factor influencing asexuals lifespan, then why asexuals are not more frequent? Here we review traditional ideas and new data and provide a novel unified evolutionary frame to understand the intriguing nature, developmental diversity and maintenance of asexual lineages. As a rule, de novo formation of a functioning asexual genome requires a unique assemblage combining particular sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and affect discrete components of sexuality to produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, i.e. a non-recombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.

Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. In our previous work, it had been concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here three aspects were further explored. First, the power function (y=ax^b, a > 0) correlation between the SI (y) of one agent and the ratio value (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations show greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These results together of above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.

Pseudomonas aeruginosa infections are the focus of new treatment alternatives due to their frequent development of resistance to antibiotics and formation of biofilms. Recently, emphasis has been placed on combinations of antibiotics with drugs used for different indications. In this study the combined effects of metformin with imipenem, ceftazidime, cefepime, ciprofloxacin and levofloxacin has been investigated. 50 P. aeruginosa isolates isolated from patients with cystic fibrosis come to Gaziantep University Microbiology Laboratory were included in the study. The susceptibilities of the isolates to antibiotics were investigated by the liquid microdilution method and the combined effect of metformin and antibiotics by the chequerboard synergy test. In our study, as a result of the chequerboard synergy test; synergy between ceftazidime and metformin 6%, partial synergistic 22% isolates; while no synergistic effect was detected between cefepime and metformin in any isolate, partially synergy 46%; synergy between imipenem and metformin 4%, partial synergy 10%; synergy between ciprofloxacin and metformin 6%, partial synergy 6%, antagonist effect 2%; synergy was detected between levofloxacin and metformin 2% and a partial synergy was detected 12%. This study shows that metformin could be a potential antibiotic in its current form or in different chemical forms to be produced synthetically.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them, and moreover, their combinations have been studied wide enough in terms of their in-fluence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′ end lipophilic (single cholesteryl or pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combi-nation of used lipophilic groups with phosphate modifications of various nature and different position on the efficiency of cell penetration was evaluated. Obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the ra-tional design of oligonucleotide structures with desired predefined properties.

The athletic performance and safety of racehorses is influenced by hoof-surface interactions. This intervention study assessed the effect of eight horseshoe-surface combinations on hoof acceleration patterns at impact and foot-off in 14 galloping Thoroughbred racehorses retired from racing. Aluminium, barefoot, GluShu (aluminium-rubber composite) and steel shoeing conditions were trialled on turf and artificial (Martin Collins Activ-Track) surfaces. Shod conditions were applied across all four hooves. Tri-axial accelerometers (SlamStickX, range ±500 g, sampling rate 5000 Hz) were attached to the dorsal hoof wall (x: medio-lateral, medial=positive; y: along dorsal hoof wall, proximal=positive; z: perpendicular to hoof wall, dorsal=positive). Linear mixed models assessed whether surface, shoeing condition or stride time influenced maximum (most positive) or minimum (most negative) accelerations in x, y and z directions, using ≥40,691 strides (significance at p&lt;0.05). Day and horse-rider pair were included as random factors and stride time as a covariate. Collective mean accelerations across x, y and z axes were 22–98 g at impact and 17–89 g at foot-off. Mean stride time was 0.48 ± 0.07 s (mean ± 2 s.d.). Impact accelerations were larger on turf in all directions for forelimbs and hindlimbs (p≤0.015), with the exception of forelimb z-minimum, and in absolute terms maximum values were typically double minimum values. Surface-type affected all foot-off accelerations (p≤0.022), with the exception of hindlimb x-maximum; for example, there was an average increase of 17% in z-maximum across limbs on the artificial track. Shoe-type influenced all impact and foot-off accelerations in forelimb and hindlimb datasets (p≤0.024), with the exception of hindlimb impact y-maximum. Barefoot hooves generally experienced the lowest accelerations. Stride time affected all impact and foot-off accelerations (p<0.001). Identifying factors influencing hoof vibrations on landing and hoof motion during propulsion bears implication for injury risk and racing outcomes.

Climate change is the long-term shift in global weather patterns, largely caused by anthropogenic activity of greenhouse gas emissions. Global climate temperatures have unmistakably risen and naturally-occurring climate variability alone cannot account for this trend. Human activities are estimated to have caused about 1.0 °C of global warming above the pre-industrial baseline and if left unchecked, will continue to drastically damage the Earth and its inhabitants. Globally, natural disasters and subsequent economic losses have become increasingly impactful as a result of climate change. Both wildlife ecosystems and human habitats have been negatively impacted, from rising sea levels to alarming frequency of severe weather events around the world. Attempts towards alleviating the effects of global warming have often been at odds and remain divided among a multitude of strategies, reducing the overall effectiveness of these efforts. It is evident that collaborative action is required for avoiding the most severe consequences of climate change. This paper evaluates the main strategies (industrial/energy, political, economic, agricultural, atmospheric, geological, coastal, and social) towards both mitigating and adapting to climate change. As well, it provides an optimal combination of seven solutions which can be implemented simultaneously, working in tandem to limit and otherwise accommodate the harmful effects of climate change. Previous legislation and deployment techniques are also discussed as guides for future endeavors.

Background: In the present study, cisplatin, artemisinin and oleanolic acid were evaluated alone and in combination, on human ovarian A2780, A2780ZD0473R and A2780cisR cancer cell lines with aim of overcoming cisplatin resistance and side effects. Methods: Cytotoxicity was assessed by MTT reduction assay. CI values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Results: Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism and biosynthetic processes and drug resistance and detoxification. Conclusion: Results indicate that appropriately sequenced combinations of cisplatin with ART and OA may provide a means to reduce side effects and circumvent platinum resistance.

With the global increase of photovoltaic (PV) modules deployment in recent years, the need to explore and realize their reported failure mechanisms has become crucial. Despite PV modules being considered reliable devices, failures and extreme degradations often occur. Some degradations and failures can be minor and cause no critical harm if within the expected range. Others, may start mildly and then deteriorate faster to become catastrophic, especially in harsh environments. This paper conducts a state-of-the-art literature review to scan PV failures, types, and their root cause based on PV’s constructed components (from protective glass to junction-box). It outlines the hazardous consequences beyond PV module failures, describing what harm they can bring to the PV system. As we delve into the literature, it becomes clear that every component is vulnerable to certain types of failures; some can deteriorate within themselves, and others infect further PV components resulting in emerging more severe failures. In the end, the review briefly summarises PV failure detection techniques, emphasising electrical characterization techniques, and disclosing the need to engage more electrical parameters. Most importantly, this review can prepare the stage for the PV research community to identify the most prevalent degradation processes. This, in turn, encourages researchers to investigate them throughout modelling and experimental studies to forecast them at the early onset in order to protect the PV systems from hazardous malfunctions.

Veratrum californicum is a rich source of steroidal alkaloids such as cyclopamine, a known inhibitor of the Hedgehog (Hh) signaling pathway. Here we provide a detailed analysis of the alkaloid composition of V. californicum by plant part through quantitative analysis of cyclopamine, veratramine, muldamine and isorubijervine in the leaf, stem and root/rhizome of the plant. To determine if additional alkaloids in the extracts contribute to Hh signaling inhibition, we replicated the concentrations of these alkaloids observed in extracts using commercially available standards and compared the inhibitory potential of the extracts to alkaloid standard mixtures using Shh-Light II cells. Alkaloid combinations enhanced Hh signaling pathway antagonism compared to cyclopamine alone, and significant differences were observed in the Hh pathway inhibition between the stem and root/rhizome extracts and their corresponding alkaloid standard mixtures, indicating that additional alkaloids present in these extracts contribute to Hh signaling inhibition.

Background: The adoption of self-care behaviors among patients with congestive heart failure (CHF) is essential for the management of their health condition. However, there is a lack of tools for estimating self-care in CHF patients. We aim to develop and validate the Hippocratic heart failure self-care scale (HHFSCS). Methods: the scale includes 22 items which are reviewed by a committee of experts. Individuals indicate the frequency at which they follow each self-behavior on a five-point Likert scale. Adult patients with CHF (n=250) from a General Hospital, in Athens, were participated in the study from June 2020 to March 2021. Reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and the Principal Components Method were used to assess the psychometric measurements. Results: The Cronbach’s alpha coefficient of the HHFSCS was 0.807. The exploratory factor analysis identified two domains that accounted for 88.44% of the variance of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test-retest showed a significant strong correlation (r=0.973, p&lt;0.001). Conclusions: The HHFSCS is a reliable and valid tool for assessing self-behaviors in CHF patients. Health professionals can use it in their clinical practice to improve the management of patient’s health conditions.

Phage, which is often used therapeutically, has begun to receive interest as an alternative to antibiotic growth promoters (AGPs) to enhance chicken growth. Another option that has been extensively studied as a growth promoter in chicken is probiotics. However, there are no studies using phages and probiotics as prospective feed additives for broiler chickens. Therefore, this study demonstrated the effects of phage cocktail, probiotics and their combinations on growth performance and gut microbiota of broiler chickens. A total of 288 one-day-old male Cobb 500 broilers were randomly allotted to 1 of 6 treatments in a completely randomised design. The treatments were: (i) C (basal diet (BD) only), (ii) 1ɸ (BD + 0.1% phage cocktail), (iii) 2ɸ (BD + 0.2% phage cocktail), (iv) P (BD + 0.1% probiotic), (v) 1ɸP (BD + 0.1% phage cocktail + 0.1% probiotic), (vi) 2ɸP (BD + 0.2% phage cocktail + 0.1% probiotic). The 1ɸP treatment had significantly (P < 0.05) better BW (35 d), BWG (22 – 35 d, 1 – 35d), and FCR (1-21 d. 22-35 d, 1-35 d) compared to C. Unique gut microbiota diversity was also found between the ɸP (1ɸP and 2ɸP) and non-ɸP groups (C, 1ɸ, 2ɸ and P) in ilea, particularly in the 35 d chickens. Microorganisms associated with short-chain fatty acid (SCFA) producers were significantly (P <0.05) present in the ɸP group than in the non- ɸP group. The carbohydrate and amino acid metabolism predicted genes were significantly upregulated in ɸP groups compared to non- ɸP groups. These genes were involved in the digestion and absorption of nutrients as well as the production of energy. Our findings showed that 1ɸP treatment could be a potential alternative to AGPs for poultry where growth performance was enhanced, and gut microbiota was positively modulated.

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by ROS production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. It was discussed how these differences may explain different levels of ROS production and cytotoxicity induced by combinations of thiols with HOCbl and CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved and might be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component. In addition, these data may be useful for a better understanding of mechanisms underlying induction of different types of death of cancer cells and in a search for new targets for anticancer therapy.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year [the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting]. Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecologic malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

With the global warming and the frequent occurrences of harsh environments, mooring line failures are frequent. Response analysis of the platform structure and its residual mooring system under multiple mooring line failures is needed. Therefore, it is necessary to investigate the change law of platform motion response after mooring line failure to find out the reasons for the change. Studies for different failure combinations of mooring lines show that the variation of the steady-state equilibrium position of the platform is closely related to the stiffness, with a clear functional. The duration and amplitude of the transient response are mainly influenced by the Morison drag force. And it was found that the suspended mooring line reduced the motion responses. It is also found that the mooring line failure increased the effective tension and suspension length of the riser. Based on the improved Dezert-Smarandache theory (DSmT), it is calculated that mooring line failure has little effect on the failure probability in different zones of the riser.

This paper examines a persuasion game between two agents with one-sided asymmetric information, where the informed agent can reveal her private information prior to playing a Battle-of-the-Sexes coordination game. We find that in the presence of strategic uncertainty in coordination there exists an equilibrium where there is no 'unraveling' of information. We provide a purification argument for this mixed strategy equilibrium to strengthen the central result, which is robust to several extensions, including both-sided asymmetric information and imprecise information revelation.

The biofilm is a conglomerate of cells surrounded by an extracellular matrix, which contributes to the persistence of infections. The difficulty in removing the biofilm drives the research for new therapeutic options. In this work, the effect of terpenes (-)-trans-Caryophyllene, (S)-cis-Verbenol, (S)-(-)-Limonene, (R)-(+)-Limonene, and linalool was evaluated, individually and in combinations on bacterial growth, by assay with resazurin; the formation of biofilm, by assay with violet crystal; and the expression of associated genes, by real-time PCR, in two clinical isolates of S. aureus, ST30-t019 and ST5-t311, responsible for more than 90% of pediatric infections by this pathogen in Paraguay. All combinations of terpenes can inhibit biofilm formation in more than 50% without affecting bacterial growth. The most effective combination was (-)-trans-Caryophyllene and linalool at a 500 μg/mL concentration for each, with an inhibition percentage of 88%. This combination decreased the expression levels of the sdrD, spa, agr, and hld genes associated with the initial cell adhesion stage and quorum sensing. At the same time, it increased the expression levels of the cap5B and cap5C genes related to the production of capsular polysaccharides. The combinations of compounds tested are promising alternatives to inhibit biofilm formation in S. aureus.

WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stem- ness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2^nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1, we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2^nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline’s efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (ra- dial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3^rd order biological hypotheses emerge some of which are con- firmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest.

The inherent value and use of hydrocarbon from waste plastics and solvents can be extended through open-loop chemical recycling as this process converts plastic to range of non-plastic materials. This process is enhanced by first creating plastic-solvent-combinations from multiple sources which are then streamlined through single process stream. We report on the relevant mechanics for streamlining industrially relevant polymers such as polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE) and acrylonitrile butadiene styrene (ABS) into chemical slurries mixed with various organic solvents such as toluene, xylene and cyclohexane. The miscibility of the polymer feedstock within the solvent was evaluated using the Relative Energy Difference method, and the dissolution process was evaluated using the “Molecular theories in a continuum framework” model. These models were used to design a batch process yielding 1 tonne/h slurry by setting appropriate assumptions including constant viscosity of solvents, disentanglement-controlled dissolution mechanism and linear increase of the dissolved polymer’s mass fraction over time. Solvent selection was found to be the most critical parameter for the dissolution process. The characteristics of the ideal solvent are high affinity to the desired polymer and low viscosity. This work serves as a universal technical guideline for open-loop chemical recycling of plastics avoiding the growth of waste plastic in a circular economy framework.

Based on the nonlinear failure criterion and modified tangential technique, the upper bound solutions of supporting pressure on the deep tunnel face were obtained under pore water pressure conditions. The influence of parameters on the supporting pressure and collapse range was investigated according to the unlimited block failure mechanism. It is found that the upper bound solutions of supporting pressure increase with the growth of the nonlinear coefficient and pore water pressure coefficient. The collapse range of the tunnel face scales out with the increase of the nonlinear coefficient and shrinks when increasing the pore water pressure coefficient. Moreover, with the increase of the nonlinear coefficient, the impact strength on supporting pressure and collapse range declines gradually. According to the calculating results, it is manifest that both the pore water pressure and nonlinear criterion factors have negative impacts on the stability of the tunnel face. Thus, more attention should be paid to these parameters to ensure face stability in deep tunnel construction.

We examined how combinations of corporate social responsibility (CSR) activities lead to high performance in Korean companies. This study addressed two related questions to expand our limited knowledge in this area. The first was what combinations of CSR activities achieve high performance. The second was to identify how CSR activities form an interdependent system, depending on different corporate situations. Korean Economic Justice Institute index data, from 2012 to 2018, were used with fuzzy set qualitative comparative analysis, and the results revealed several effective CSR activity factor combinations under given strategies and management environments. Companies with high performance exhibit complementarity between social contribution, environmental management, fairness, and employee satisfaction. By contrast, companies with low corporate performance show no complementarity between relatively unrelated activity factors. For companies whose CSR activities lead to low financial performance, most of the causal pathways focused only on activities at the primary stakeholder level, with weak diversity of CSR activities’ combinations at the primary and secondary stakeholder levels. These results indicate not only the appropriateness of CSR activity factor combinations for companies’ strategy and management environment contexts, but also their effectiveness, and are expected to provide companies with significant implications for CSR activities.

In the case of solid slabs made of reinforced concrete that are usually subjected to bending, large areas of the structure are stressed well below their load-bearing capacity. Contrary to this are shell structures, which can bridge large spans with little material if designed according to the force flow. To improve the efficiency of ceiling slabs, we want to utilize the shell load-bearing behavior on a smaller scale by resolving the solid interior accordingly. In order to be able to study a wide range of such constructions virtually, a parametric multiobjective simulation environment is being developed in an ongoing research project. The basic analysis approaches which were implemented are presented in this paper. The basic workflow, the used programs and material models and their calibration on the tests on textile-reinforced concrete (TRC) samples are described.

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, complicating treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is in-volved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. However, the generation of reactive oxygen species (ROS) results in the dysregulation of antioxidant defenses in GBM cells, creating a vulnerability that can be thera-peutically exploited. Evaluating pro-oxidant therapies in brain tumors is crucial due to their po-tential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were ana-lyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Cisplatin (CDDP) is widely used to treat several types of cancer. However, CDDP induces nephrotoxicity. This toxicity could be avoided, applying a lower cisplatin dose; however, it could induce a lesser therapeutic activity. In this paper, we present the cytotoxic activity against prostate human cancer cell line (PC-3) of the combination of CDDP with masticadienonic acid (MDA), a triterpene isolated from Amphypterygium adstringens.The combinations A (half of the IC₅₀), B (IC₅₀) and C (twice IC₅₀ of the compounds) in a radio 1:1 were evaluated. Our results showed that the B and C combinations presented synergism effect. However, B combination showed almost 100% inhibition of cell proliferative activity and increased apoptosis compared with those presented by each compound apart. A pretreatment of MDA 24 h to cells before the CDDP, AMD or B combination administration result in a resistance to the treatments. A xenograft study using PC-3 cells showed that the combination of 47.5 mM/kg (AMD) plus 4 mM/kg (CDDP) administered weekly for 3 weeks reducing the tumor volume in approximately 47 %. However, the combination of 47.5 mg/kg (AMD) plus 2 mg/kg (CDDP) administered every third day for 21 days reduce, approximately 82% of tumor compared with mice no treated.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Studies have found critical software malfunctions responsible for some of the worst accidents in recent times. These malfunctions are often only minor defects that snowball into large problems; a few lines of code is all it takes. Complexity, safety, quality, and resilience are among the key attributes defining a software’s operational success. There are many leading factors for complexity, such as increases in the product size, the rate of requirement changes, and the number and type of stakeholders, and failure to manage these issues efficiently always has the same consequence, i.e., massive failure and sometimes technological catastrophe. This work analyzes some of the architecture, design, and implementation guidelines used as detection and mitigation techniques. It also discusses the safety considerations, as considering how the steam industry has handled safety issues could offer some guidance for ensuring safety. Complexity in such systems also causes some of the worst side effects from the quality auditor's perspective. While failures in the software are hard to predict, one of the most significant ways of showing preparedness is practicing software resilience. New mitigation areas, such as the fragility spectrum and failure obviation, and their usage for building a safer system are analyzed. Also discussed are various architecture styles in practice and the dramatic effect human factors can have on the success of the software being developed.

In the food industry, Listeria is a standard control microorganism in ready-to-eat food since it may be pathogenic and cause a disease called listeriosis. The objective of the present study was to carry out a challenge test to verify the efficiency of different combinations of natural antimicrobial ingredients, against Listeria monocytogenes, to be used in ready-to-eat foods. Six different formulations of cooked ham were elaborated: a control, and five different formulations. An initial inoculation of 2 log cycles was used in the different products and the growth of Listeria was monitored at different temperatures and times (4° C for 17 w; 7ºC for 12 w). Control samples showed a progressive growth, reaching 5-6 log after 3 or 4 weeks. The rest of samples showed constant counts of Listeria during the all study. Only samples containing: 100 ppm nitrite + 250 PPM ascorbic acid+0,7% PRS DV-5 did not control the growth of Listeria at 7 ° C after 7 w of storage. The results obtained allowed to classified the cooked ham elaborated using any natural ingredients combinations as a “Ready-to-eat food unable to support the growth of L. monocytogenes other than those intended for infants and for special medical purposes”.

Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. One of the reasons for the severe course of leptospirosis is a cytokine storm, which develops as a result of an excessive immune response. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis and a bidirectional relationship with many internal organs. A change in the gut microbiota can be caused not only by antibiotics, but also by infectious agents such as the coronavirus or the flu virus. It is known that L. interrogans can change the microbiota of mice. Thus, gut dysbiosis in leptospirosis can affect the clinical course of the disease, through the gut–organ axis. Modulation of intestinal microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

In the development of the safety-critical systems, it is important to perform Failure Modes and Effects Analysis (FMEA) process to identify potential failures. However, traditional FMEA activities tend to be considered difficult and time-consuming tasks. To compensate for the difficulty of the FMEA task, various types of tools are used to increase the quality and the effectiveness of the FMEA reports. This paper explains an Automatic FMEA tool which integrates the Model-based Design (MBD), FMEA, and Simulated Fault Injection techniques in a single environment. The Automatic FMEA tool has the following advantages compared to the existing FMEA analysis tool. First, the Automatic FMEA tool automatically generates FMEA reports compared to the traditional spreadsheet-based FMEA tools. Second, the Automatic FMEA tool analyzes the causality between the failure modes and the failure effects by performing model-based fault injection simulation. In order to demonstrate the applicability of the Automatic FMEA, we used the electronic fuel injection system (EFI) Simulink model. The results of the Automatic FMEA were compared to that of the legacy FMEA.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

The polymer cures as it enters the ballast, forming a three-dimensional geo-composite reinforcing cage. Although there will be some adherence to the ballast in dry conditions, the polymer's primary job is to construct this reinforcing cage. Polymer penetration is controlled by altering the rheology of the polymer. The method is also said to include a built-in safety system, with the track reverting to a ballast state in the event of a polymer or geo-composite failure. Many of the sites were considered unmaintainable before the polymer was put. The design method was utilized to forecast track behaviour before and after treatment, allowing the most appropriate polymer rheology, polymer distribution, and loading levels to be designed in order to achieve optimum performance and confirm that the procedure worked. This method can be utilized to tackle these types of long-standing problems by displaying actual polymer application profiles at a typical important location.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review the relationship between smoking and sleep is investigated, based on the existing literature. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnoea-hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, restless legs but also non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric. This review aims to consolidate all the existing knowledge about the relationship between smoking and sleep.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction of antiviral effective concentration of drugs already approved by the FDA, such as ivermectin  (IVM), ribavirin (RIBA) and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV) and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecule with broad-spectrum antiviral activity, the ferruginol analogue 18-(phthalimid-2-yl)ferruginol (phthFGL). In general, the combination of IVM, phthFGL and Oregano EO showed the greatest synergism potential against CHIKV, ZIKV and HHV-2, obtaining a reduction in the EC99 value of up to ~8, and ~27, and ~12-fold for CHIKV, in example, respectively. The ternary combination RIBA, phthFGL, Oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, Oregano EO which indicates that IVM could contribute more to the differentiations of cell targets (for example by inhibition of host heterodimeric importin IMP α/β1 complex) than ribavirin. PhthFGL showed a good pharmacokinetic profile.

Congestion not only represents a cardinal sign of heart failure but is also now recognized as the primary cause for hospital admissions, rehospitalizations, and mortality among patients with acute heart failure. Congestion can manifest through various heart failure phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Complete decongestion is hardly achieved among patients with acute heart failure, as more than half still have residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with acute heart failure by highlighting insights into the pathophysiology mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.

In the current study, the failure behavior of retrofitted steel structures was studied experimentally and theoretically with steel/CFRP double strap joints (DSJs) under quasi-static tensile loading. A series of DSJs with different bonding lengths are also considered and examined to experimentally assess the effective bond length. To predict the failure load values of the tested specimens, a new stress-based criterion, namely the point stress (PS) criterion is proposed. Although some theoretical predictive modelling for the strength between steel/CFRP joints under various loading conditions has been presented, in this work by using the new proposed approach, one can calculate rapidly and conveniently the failure loads of the steel/CFRP specimens. Furthermore, to assess the validity of the new proposed criterion, further experimental data on steel/CFRP DSJs available in the open literature are predicted using the PS criterion. Finally, it was found that a good agreement exists between the experimental results and the theoretical predictions based on the PS criterion.

The present study investigates the failure mechanisms of industrial fiber materials, using a custom designed fiber cutting performance test bench. The fracture morphologies of single PA6 fibers are examined by scanning electron microscopy. The analysis reveals that fiber cutting can be distinguished according to four distinct stages of fiber failure represented by shearing, cutting, brittle fracture, and tensile failure, which are the result of different mechanisms active during the processes of crack initiation, extension and fracture. The results of fractographic analysis are further verified by an analysis of the blade assembly speed with respect to time over the entire fracture failure process based on high-speed camera data. The results of fractographic analysis and blade assembly speed are fully consistent.

Background: Bangladeshi students from science, technology, engineering, and mathematics (STEM) often struggle with solving many mathematical problems in different pedagogic contexts. They mostly lack the considerable prior learning or strong basics required to cope with the teaching and learning materials used at the undergraduate levels, which leads many students to take readmissions every year. Objective: This research aims at investigating the factors affecting the success and deficit of university undergraduate mathematics students in Bangladesh. The mixed-method research incorporates quantitative and qualitative data analysis on the students' and teachers’ perspectives regarding the issues. The authors focus more on categorizing the reasons influencing effective mathematics pedagogies than on identifying new or unknown causes. Methodology: This study is outlined in three phases. The phases include i. Exploratory qualitative survey ii. Quantitative triangulation survey, iii. Explanatory semi-structured interviews. Findings: First, the qualitative survey exposes the important factors that highlight the student’s success and failure in mathematics. Next, the quantitative data confirm that there are some similarities and dissimilarities between students’ and teachers’ perceptions. Also, the coefficient correlation analysis shows male students lack consistency and passion for study resulting in poor performances. Conversely, female students emphasize the inability to connect mathematical theories to real-life usages, curriculum loads, and unavailable resources as the reasons for underperformance. Finally, the interview data demonstrate the students attribute their failure to inadequate practices, memorizing habits, poor teaching, low motivation, and external distractions. Also, students acknowledge the necessity of steady practice, clear understanding, regular study, and working strategies for successful mathematics education. Teachers emphasize students’ clear concepts, aptitude, motivation, and curiosity for successful learning. Conclusion: This conclusion proposes a fresh start with the local mathematics pedagogic practices by analyzing teacher-student feedback on the success and failure factors impacted by varied individual and contextual elements. The study offers inclusive feedback on the part of both stakeholders. However, an open discussion or interaction between students and teachers might be needed to enhance mutual trust and understanding between them.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. Results: HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p&lt;0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

Current methodologies for developing patient-derived xenografts (PDX) in humanized mice in preclinical trials to test response to immune-based therapies are limited by graft versus host disease. Here we compared two approaches for establishing PDX tumors in humanized mice: 1) PDX are first established in immune-deficient mice; 2) PDX are initially established in humanized mice, before transplanting established PDX’s to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Pre-clinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with limited infiltration of CD8+ T cell into the tumor. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in the presence of human immune cells before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. Standard treatment of HF includes angioten-sin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorti-coid-receptor antagonists, beta-blockers, and sodium-glucose co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with de-creased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of HFrEF therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater num-ber of medications for the management of these patients. This review covers vericiguat's metab-olism, molecular mechanisms, and drug-drug interactions.

Extracorporeal membrane oxygenation (ECMO) support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, ECMO may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous (V-V) ECMO, however in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary (V-P) ECMO or veno-venoarterial (V-VA) ECMO. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of ECMO, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and ECMO weaning in patients with respiratory failure. As the footprint of ECMO continues to expand it is essential that clinicians understand the underlying physiology and management of these complex patients.

Heart failure is a leading cause of death among people worldwide. The cost of treatment can be prohibitive, and early prediction of heart failure would reduce treatment costs to patients and hospitals. Improved prediction of readmission would also be of great help hospital, allowing them to better manage their treatment programs and budgets. This systematic review aims to summarize recent studies of predictive analytics models that have been constructed to predict heart failure and readmission. Some of these models use a statistical approach and others a machine learning approach. Electronic patient health records, including demography, physical and clinical values, and laboratory findings are used to design and build predictive models. Predictive analytics with good performance have become essential for clinicians and specialists. Choosing a suitable machine learning algorithm and data preprocessing technique will improve predictive model performance, including data imputation and class imbalance.

BackgroundHeart failure is a life-threatening disease affecting millions worldwide. Tolvaptan is the first FDA-approved orally active nonpeptide vasopressin 2 receptor antagonist to be used in hypervolemic hyponatremia, heart failure, cirrhosis, etc. In clinical trials, tolvaptan impacts short-term in increasing water excretion, and restoring Na+ and dyspnoea. Aims & ObjectivesThe objective is to analyze the outcomes of tolvaptan in existing cases of heart failure. MethodologyWe conducted a database search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and RCTs till 1st September 2019 were included following PRISMA guidelines after being matched with inclusion and exclusion criteria. 21 RCTs were included with 7,357 patients receiving tolvaptan and 7,273 patients being the control group. We used the MESH strings such as 'tolvaptan', 'vasopressin V2 receptor blocker', 'acute heart failure', and 'acute decompensated heart failure'. ResultsMeta-analysis showed that Tolvaptan was associated with a significant reduction in edema (RR = 1.05, 95% CI = 1.019-1.081, p=0.001) and significant body weight reduction (Control-SMD = -0.489, 95% CI =-0.637 to -0.342, p<0.001)&(Placebo-SMD = -0.425, 95% CI = -0.425 to -0.382, p<0.001) It shows significant decrease in serum sodium levels (SMD = 0.678, 95% CI = 0.609 to 0.748, p<0.001). There was no significant decrease in all-cause mortality (Control-RR = 0.855, 95% CI 0.470 to 1.555, p=0.607)(Placebo-RR= 0.972, 95% CI = 0.879-1.074, p=0.575). Results for Worsening renal function in heart failure (Placebo-RR = 0.798 95% CI 0.619 to 1.028, p=0.081)(Control-RR = 1.349, 95% CI=0.927-1.964, p=0.118). ConclusionAlthough tolvaptan may significantly reduce edema, congestive symptoms and decreased body weight, it has no impact on all-cause mortality and worsening renal function in heart failure.

Globally 30% of landslides occur in the northeastern part of India [1]. One of the major earthquake events in Sikkim, India occurred on 18th September 2011 (Mw 6.9) led to over 300 landslides and 122 human deaths [2]. These landslides not only controlled by natural disasters but initiated due to human activities. The present study considered Lungchok landslide occurred in south district of Sikkim due to 2011 seismic event. The study focused on the failure mechanism of the landslide based on finite element analysis by adopting eight different cases. The deformation characteristic was investigated for dry and saturated slope conditions under static and dynamic behavior considering vehicle loads using GeoStudio software. The FEM analysis has been carried out using load deformation and linear elastic. The analysis shows that the failure of the slope was not sudden due to the 2011 earthquake event, but progressive failure was observed with time and construction activity. The paper demonstrates that, an increase in infrastructure development including construction by hill cutting increased the initiation of landslide with soil erosion. The cracks developed after 2011 earthquake event led to further deformations during future disasters required effective stabilization measures.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

(1) Objectives. Patients with heart failure (HF) who experience hospitalizations for worsening HF (HFH) are at high risk of subsequent events. We aimed to evaluate the impact of an outpatient care management program that includes a clinician-to-clinician e-consultation using an integrated electronic medical record in a healthcare area with a widely dispersed population on delay time in care, hospital admissions, and mortality in a high-risk group of patients with HF and previous episodes of HFH. (2) Methods. We selected 6,444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4,851 were attended in e-consult, and 2,008 in one-time in-person consultations. In 2,230 HF patients, there was documentation of a previous episode of HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the health care model in the group of patients with HFH and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). (3) Results. In the group of patients with previous HF hospitalizations, the introduction of e-consult substantially decreased waiting times to cardiology care. The time elapsed to care after e-consult implementation was significantly reduced compared with the previous in-person period (8.6 [8.7] vs 55.4 [79.9] days, p&lt;0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [CI95%]: 0,837 [0,840-0,833]), 0,900 [0,862-0,949] for CV and 0,699 [0,678-0,726] for all-cause hospitalizations. There was also lower mortality (iRR [CI95%]: 0.715 [0.657-0.798] due to HF, 0,737 [0.764-0.706] for CV and 0,687 [0.652-0,718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH and were independent of the patient’s clinical characteristics managed during the in-person or e-consultation periods. (4) Conclusions. In HF patients with previous HFH, an outpatient care program that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.

Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

We propose a new statistical analysis of the Acoustic Emissions (AE) produced in a series of triaxial deformation experiments leading to fractures and failure of two different rocks, namely, Darley Dale Sandstone (DDS) and AG Granite (AG). By means of q-statistical formalism, we are able to characterize the pre-failure processes in both types of rocks. In particular, we study AE inter-event time and AE inter-event distance distributions. Both of them can be reproduced with q-exponential curves, showing universal features which are observed here for the first time and could be important in order to understand more in detail rock fractures dynamics.

In this paper, we introduce the application of Type-I fuzzy inference systems (FIS) as an alternative to improve the prioritization in the FMECA analysis applied in cyber-power grids. Classical FMECA assesses the risk level through the Risk Priority Number (RPN). The multiplication between three integer numbers computes this, called risk factors, representing the severity, occurrence, and detectability of each failure mode and are defined by a team of experts. The RPN does not consider any relative importance between the risk factors and may not necessarily represent the real risk perception of the FMECA team members, usually expressed by natural language; this is the main FMECA shortcoming criticized in the literature. Our approach considers fuzzy variables defined by FMECA experts to represent the uncertainty associated with the human language and a rule base consisting of 125 fuzzy rules to represent the risk perception of the experts. To test our approach, we select a cyber-power grid previously analyzed by the authors using the classical FMECA. The results reveal our proposed fuzzy approach as promissory to represent the uncertainty associated with expert knowledge and to perform an accurate prioritization of failure modes in the context of electrical power systems.

Large power transformers are generally associated with a maximum capacity rating of 100 MVA or higher. These large liquid dielectric power transformers are a custom-built piece of equipment, thus very expensive, and a backbone element of the power grid. In extreme cases as, for example, severe geomagnetic disturbances, permanently monitoring their condition will enhance their electrical reliability and resilience to guarantee efficient management of its life cycle. However, some traditional monitoring/diagnosis techniques have singular features when applied to large power transformers and their interlinked subsystems. In this context, and since that information is hardly put in evidence and compiled in the literature, this paper reviews the particularities of monitoring and diagnosing those assets.

The bioactive compound, thymoquinone (TQ), found in Nigella sativa seeds is known for its various therapeutic properties. Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, is known for its various therapeutic properties. However, TQ as a compound is challenging for a pharmaceutical formulator due to its hydrophobic nature and chemical instability, limiting its skin penetration. Transethosomes, as a formulation, provide an environment that enhances the solubility of TQ, stability, as well as skin permeation. To optimize TQ transethosomal formulations, we introduced a combination of surfactants namely nonionic Tween 20 and ionic sodium lauryl sulfate (SLS) or sodium lauroyl glutamate (SLG). These surfactants stabilize the formulation, reduce aggregation, and improve biocompatibility, as well as minimizing potential toxicity. Using the Langmuir monolayer technique, we fine-tuned the formulation composition and gained insights into its interfacial behavior. We conducted skin penetration studies using Rhodamine B as a model lipophilic compound to understand the skin penetration mechanisms. Our findings revealed that the transethosomes formulation, a combination of ionic and nonionic surfactants in the F2 formulation, resulted in the smallest particle sizes (115.4 nm) and demonstrated the highest skin permeation after 24 hours (267.13 μg/cm²), surpassing the control and ethosomal formulations. Additionally, this transethosomal formulation exhibited antimicrobial activity against S. aureus, with a zone of inhibition of 26.4 ± 0.3 mm. Importantly, we assessed the cytotoxicity of both ethosomes and transethosomes at concentrations ranging from 3.5 μM to 50 μM on HaCaT cell lines and found no cytotoxic effects in comparison to TQ solution controls. These results suggest the potential safety and efficacy of these TQ formulations and their further development in skin delivery.

DNA repair helps in maintaining the proper and healthy functioning for the cells in the human body. Failure in DNA repair process can lead to aberrations as well as tumorous stages. There are various types of damages that a DNA can go through, one of which is the DNA double strand breaks (DSB) that can be repaired via homologous recombination (HR). RAD51 plays a central role in HR and has been implicated as a negative/poor prognostic marker for colorectal adenocarcinoma, with high expression in colorectal cancer. Mechanistically, RAD51AP1 facilitates RAD51 during the repairing process by binding with RAD51 via two DNA binding sites, thus helping in the D-loop formation in the HR process. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, RAD51AP1-XRCC2 is one such 2^nd order combination whose relation needs to be tested under the influence recently developed Porcupine-WNT inhibitor ETC-1922159. The x-ray repair cross complementing XRCC family is known to work as a mediator or stabilizer for RAD51 during the HR process. The inhibitor is known to suppress Porcupine and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2^nd order level after the drug was administered. The in silico observations showed that the combination of RAD51AP1-XRCC2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both RAD51AP1 and XRCC2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3^rd order combinations of RAD51-X-X & RAD51AP1-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hibert Schmidth Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested RAD51/RAD51AP1 related 3^rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested.

Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.

A study was conducted to predict failure stresses, failure locations, and their paths of initiation of perforated polymethyl methacrylate (PMMA) specimens as they were loaded using pins inserted into the holes. First, a series of experiments were conducted for perforated PMMA coupons. There were six different types of coupons. The test specimens had three different widths with a circular hole of a diameter of 8 mm, which was placed at two different locations along the specimen length. All the specimens were loaded using a pin inserted into the hole with three different pins of nominal diameters of 8 mm, 6 mm, and 5 mm, respectively. To predict the failure and compare the results against the experimental data, the recently proposed universal failure criterion was used in the study using finite element analyses. The failure criteria gave acceptable results as compared to the experimental data.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

Background: The increase in the prevalence of obesity in South Africa is a problem and weight management play an important role in the treatment of the high prevalence. For this purpose, a quantitative study was carried out using a structured questionnaire to assess predictors of attempt and failure to lose weight. Methods: One thousand and fifty adults were enrolled in the study and 54% (n=562) were overweight and obese (BMI &gt;/25kg/m2). Descriptive statistics were analysed. Inferential statistical tests (chi-square tests, logistic regression, and Pearson’s correlation coefficients) were used to determine the relationship between variables. Results: The results revealed that age, sex, marital status, educational level, employment status, income level, area of residence, ethnic groups, and self-perceived BMI (normal weight, overweight, and obese) were predictors of attempt and failure to lose weight. There was a positive correlation between self-perceived BMI and the attempt and failure to lose weight. Conclusion: Weight management is important in the realm of public health and can be regarded as an investment in the population, as it leads people toward weight control strategies grounded in empirical evidence. Additionally, the findings can inform public health policies and interventions to improve weight management strategies at the population level.

Serine/arginine-rich splicing factors (SRSF) are a family of proteins involved in RNA metabolism, including pre-mRNA constitutive and alternative splicing. The role of SRSF proteins on mitochondria activity has already been shown for SRSF6 but SRSF4 altered expression has never been reported as disease causing. An 8-year-old patient admitted to the Hematology Unit because of leukopenia, lymphopenia, and neutropenia showed a missense variant of unknown significance on the SRSF4 gene (p.R235W) found by Whole Genome Sequencing analysis and inherited by the mother who suffered from mild leuko-neutropenia. Both patients showed lower SRSF4 protein expression compared to HD and altered mitochondrial function and energetic metabolism, which appeared associated with low mTOR phosphorylation and an imbalance in proteins regulating biogenesis (i.e., CLUH) and mitochondrial dynamics (i.e., DRP1, OPA1). Transfection with the wt-SRSF4 gene restored the mitochondrial function. In conclusion, this study shows that the de-scribed variant of the SRSF4 gene is pathogenetic and causes reduced SRSF4 protein expression, which leads to cells’ mitochondrial function impairment. Since mitochondrial function is crucial for hematopoietic stem cells maintenance and some genetic bone marrow failure syndromes display mitochondrial defects, SRSF4 mutation could have substantially contribute to the clinical phenotype of our patient.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.

An experimental series of shearing tests with water infiltration were performed on compacted unsaturated soil to simulate the behavior of shallow slope failures. Soil samples were compacted at moisture contents from dry to wet of optimum moisture content with the degree of saturation varying from 24.0% to 59.5% while maintaining the degree of compaction at 80%. Two series of shearing with infiltration tests were performed in this study. In Series-I, just before the start of shearing, matric suction was decreased by increasing pore water pressure to start water infiltration i.e. shearing is carried simultaneously with water infiltration. In Series-II, the soil was first sheared with drained pore air and undrained pore water to pre-defined value of deviatoric stress, after which matric suction was decreased by increasing pore water pressure to start water infiltration and shearing is performed by keeping deviatoric stress constant on the specimen. The test results showed that the decrease in matric suction has an effect on the volume of infiltrated water and degree of saturation. The soil slopes compacted on the dry side of optimum moisture content showed better performance than other soils, they require more decrease in matric suction to start water infiltration and showed higher deviatoric stress. In addition to this, water infiltration alone can cause the failure of shallow slopes without having to have any further loading.

We asked whether the level of peripheral fatigue would differ when three consecutive exercise trials were completed to task failure, and whether there would be delayed recovery in maximal voluntary contraction (MVC) force, neuromuscular activation and peripheral fatigue following task failure. Ten trained sport students performed three consecutive knee extension isometric trials (T1, T2, T3) to task failure without breaks between trials. T1 and T2 consisted of repeated 5-s contractions followed by 5-s rest. In T1, contractions were performed at a target force at 60% pre-exercise MVC. In T2, all contractions were MVCs, and task failure occurred at 50% MVC. T3 was a sustained MVC performed until force fell below 15% MVC. Evoked force responses to supramaximal electrical femoral nerve stimulation were recorded to assess peripheral fatigue. Electromyography signals were normalized to M-wave amplitude to assess neuromuscular activation. Lower levels of evoked peak forces were observed at T3 compared to T2 and T1. Within 5 s of task failure in T3, MVC force and neuromuscular activation recovered substantially without any recovery in evoked peak force. Neuromuscular activation 5-10 s after T3 was unchanged from pre-exercise values, but evoked peak forces were substantially reduced. These results challenge the existence of a critical peripheral fatigue threshold that reduces neuromuscular activation. Since neuromuscular activation changed independently of any change in evoked peak force, immediate recovery in force production after exercise is due to increased central recruitment and not to peripheral mechanisms.

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

The damage evolution rules of coal under true triaxial combined static-dynamic loads are important to understand and reveal the mechanism of rockburst in coal mines. The numerical simulation was carried out using FLAC3D to explore the coupling effect of static and dynamic stress, especially the influence of dynamic load parameters. The results show that the increase of dynamic load amplitude not only makes the plastic zone grow exponentially and shorten the damage development time, but also decreases the residual strength of the coal sample, which leads to a much more violent of the dynamic failure. The stress wave can propagate more stable in the coal sample with the increase of dynamic load frequency and the development time of the plastic zone also show synchronous fluctuating features, and when the frequency is like the intrinsic frequency of the coal sample, the dynamic load has a significant stimulate effect. The static and dynamic loads have different damage effect to the coal sample under true triaxial stress path, the weight decreases in order of the minimum principal stress, the maximum principal, the amplitude of the dynamic load and at last the dynamic stress frequency by the entropy weight method analysis.

The early failure of glaucoma surgery is mainly caused by an overly fibrosis at the subconjunctival space causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signature with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGF-A, IL-8, C-MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGF-A and IL-8 protein levels were also increased in fibroblast supernatants. We propose that these proteins may act as biomarkers of conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery leading to more optimal and personalized treatments.

Reliability assessment in traditional power distribution systems has played a key role in power system planning, design, and operation. Recently, new information and communication technologies have been introduced in power systems automation and asset management, making the distribution network even more complex. In order to achieve efficient energy management, the distribution grid has to adopt a new configuration and operational conditions that are changing the paradigm of the actual electrical system. Therefore, the emergence of the cyber-physical systems concept to face future energetic needs requires alternative approaches for evaluating the reliability of modern distribution systems, especially in the smart grids environment. In this paper, a reliability approach that makes use of failure modes of power and cyber network main components is proposed to evaluate risk analysis in smart electrical distribution systems. We introduce the application of Failure Modes and Effects Analysis (FMEA) method in future smart grid systems in order to establish the impact of different failure modes on their performance. A smart grid test system is defined and failure modes and their effects for both power and the cyber components are presented. Preventive maintenance tasks are proposed and systematized to minimize the impact of high-risk failures and increase reliability.

: The cyber-physical gap (CPG) is the difference between the 'real' state of the world and the way the system perceives it. This discrepancy often stems from the limitations of sensing and data collection technologies and capabilities, and is an inevitable issue in any cyber-physical system (CPS). Ignoring or misrepresenting such limitations during system modeling, specification, design, and analysis can potentially result in systemic misconceptions, disrupted functionality and performance, system failure, severe damage, and potential detrimental impacts on the system and its environment. We propose CPG-Aware Modeling & Engineering (CPGAME), a conceptual model-based approach for capturing, explaining, and mitigating the CPG, on top of and in sync with the conventional system model, and as an inherent systems engineering activity. This approach enhances the systems engineer’s ability to cope with CPGs, mitigate them by design, and prevent erroneous decisions, actions, and hazardous implications. CPGAME is a generic, conceptual approach, specified and demonstrated with Object Process Methodology (OPM). OPM is a holistic conceptual modeling paradigm for multidisciplinary, complex, dynamic systems, which is also ISO-19450. We analyze the 1979 Three Miles Island 2 nuclear accident as a prime example of the disastrous consequences of unmitigated CPGs in complex systems.

The construction of a house with a stage structure is the uniqueness of Banjarmasin's swampland. Particularly, foundations for swampy terrain necessitate special handling. Building material defects and the basic inability to modify the use and design of wood pillar foundations are the main causes of house building problems. The very limited capacity of a wooden pillar foundation makes house buildings collapse frequently. The aim of the study is to determine the weaknesses of the wooden pillar foundations by examining the indications of damage to the house structure. Field observation investigations, including housing and individual object observations, will be carried out at multiple construction sites in Banjarmasin (Indonesia) as part of this study. The way the data is presented is descriptive. A wooden pillar foundation, which is a frequently used foundation, has a limited load bearing capacity. Because that, there has been no related research that addresses the issue of how this foundation damage. The aim of the study is to determine the early signs of swamp building collapse in the wooden pillar foundations weaknesses by examining the indications of damage to the house structure. The weak construction of a wooden pillar foundation explains some indications of house building damage, such as broken wooden pillars and floor settlement. The existence of evidence that there is a broken 'sunduk’ element is one of the causes of damage to this foundation

In this study, experimental work was carried out on reinforced concrete (RC) beams strengthened with carbon fiber reinforced polymers (CFRP) plates. This study aims to examine the effect of the reinforcement ratio on the flexural behavior of these beams and propose a new model for predicting the debonding moment. Six RC beams consisting of three control beams and three beams strengthened with CFRP plates were tested. The beams were simply supported and loaded with four-point bending. The test variable was the tensile reinforcement ratio (1%, 1.5%, and 2.5%). Analytical prediction using the fiber element method was also carried out to obtain the complete theoretical response of the beam due to flexural loads. The test results show that the reinforcement ratio affected the bending performance of RC beams with CFRP plates. Following this, the experimental data from 60 beam test results from published literature and this study were analyzed. From these data, it was found that the ratio of tensile reinforcement, the ratio of modulus of elasticity of concrete, the modulus of elasticity of the plate, and plate thickness all affect the value of debonding moment. A parametric study using fiber element and two-dimensional finite element method was also carried out to confirm the effect of these parameters on debonding failure. These parameters were then used to develop an equation to predict the debonding moment of RC beams strengthened with CFRP plates using simple statistical analysis. This analysis resulted in a simple model for predicting the debonding moment. Then the model is entered into a computer program, and the complete response of the cross-section due to debonding failure can be obtained.

Heart failure (HF) is a disease state which has been shown to affect 1-2% of the global population, being often associated with comorbidities such as diabetes, hypertension, obesity or hyperlipidaemia which increase the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non pharmacological approaches have led to significant improvements in clinical outcomes in patients affected by HF, residual unmet needs remain. Treatment of the disease remains unclear particularly related to poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to may contribute in the protection of the failing myocardium, though their place in the treatment of HF still needs to be better clarified. In this context, the ONUS-HF working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease in order to counteract selected pathways which are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring druing the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, cardiac stem cell mobilization and imbalanced regulation of metalloproteinases. Several candidates for nutraceutical supplementation in HF, such as CoQ10, grape seed extract, Olea Europea L- related antioxidants, SGLT2 inhibitors-rich apple extract and bergamot polyphenolic fraction have been assessed for their potential contribution to cardiomyocyte prottection. This approach should define the optimal approach for more targeted and successful strategies based on the use of nutraceuticals in HF to be confirmed by means of clinical trials exploring efficacy and safety of these compounds.