For marine vessels, a propeller shaft system, also known as a propulsion shaft system, is an essential changer in engine torque and propeller thrust. The propeller shaft system is subjected to transverse, longitudinal, and torsional excitations during operation. These sources of excitations originate from alternating thrust generated by the propeller, operation of a propeller in a stern flow field which is non-uniform in time and space, misalignment of components such as shafts, bearings, and keyholes in the assembly, excitations in the form of rotational motion, and the whirling motion of the shafts. These dynamic excitations posed a challenging issue for the integrity and reliability of a marine vehicle. Thus, it is crucial to analyze the dynamic response of the propulsion shaft system. The dynamic analysis of the propulsion shaft system is typically conducted using numerical /analytical models. At present, Finite Element Model (FEM) as a numerical model plays a vital role in analyzing the dynamic response of the structure. The computed response and the modal parameters from the FE model are reliable only if accurate boundary conditions, such as stiffness, can be imposed on the model. However, the numerical FE model deviates from the experimental results because of uncertainties in the stiffness values of the bearings and other connectors. This paper uses the Response Surface Optimization (RSO) technique to estimate the unknown stiffness of the bearings used in the propulsion shaft system. The experimental model of the propeller shaft system is constructed from the steady-state response of the system using the step sine excitation. The natural frequencies and the amplitude of vibrations in the FE model are updated using the parametric RSO technique. The updated model shows that the difference in natural frequencies and vibration amplitude is less than 10% between the optimized and experimental models. Propeller Shaft, Vibrations, Optimization, Response Surface

The recent outbreak of Nipah virus in India in 2023 had affected the Kozhikode district in Kerala, with a total of 6 confirmed cases and 2 deaths. The source of the outbreak was traced to fruit bats that contaminated date palm sap, a common drink in the region. The outbreak was contained by rapid detection, isolation, and contact tracing of the cases, as well as public health education and social distancing measures. It also highlighted the need for improved surveillance, diagnostics, and therapeutics for Nipah virus. This letter highlights the latest insights gained from the epidemiological, clinical, and laboratory investigations of the outbreak.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Salmonella is the intracellular pathogen and etiological known for the cause of asymptomatic carriage, gastroenteritis, systemic disease (typhoid fever), in severe cases death may also occur. Altered function of mitochondria due to Salmonella infection impacts the immune response. Mitochondria which are recognized as the “powerhouse” of the cells are also know to play central role in the immune metabolism. Mitochondrial dynamics such as fusion, fission, signaling, transport and mitophagy influences the immune system and also maintains the cellular integrity. Mitochondrial DNA and Reactive oxygen species formation also elicits the inflammatory responses. This review discusses the immune metabolism and effect of altered mitochondrial dynamics in case of Salmonella infection.

The influence of four levels of dietary supplementation on the development of the immune response and on the biology of Haemonchus contortus and Trichostrongylus colubriformis was evaluated in Dorper lambs under serial artificial mixed-infections with 1000 infective larvae (L3) of each species, given every three days for 12 weeks. For each of the four diets formulated, one infected group (n=7) and one control group (n=4) were set up. Diets 1, 2, 3 and 4 contained 0%, 25%, 50% and 75% of concentrate, respectively. There was an evident immune response to infection in all groups, manifested through eosinophilia and production of anti-L3 immunoglobulins. There was a significant inverse relationship between the levels of nutrients in the diets and the numbers of late fourth-stage larvae, early fifth-stage larvae and adults of H. contortus. Most of the H. contortus parasite population was in hypobiosis at the early-fourth stage, representing 59.5%, 75.8%, 83.3% and 86.3% of the total Haemonchus worm burden, respectively, in the Diets 1, 2, 3 and 4. In the case of T. colubriformis, hypobiosis was not observed and the diet had no influence on establishment of the parasite.

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

In Μay 2022, for the first time, multiple cases of mpox were reported in several non-endemic countries. The first ever case of the disease in Greece was confirmed on 8 June 2022 and a total of 88 cases were reported in the country until the end of April 2023. A multidisciplinary response team was established by the Greek National Public Health Organization (EODY) to monitor and manage the situation. EODY’s emergency response focused on enhanced surveillance, laboratory testing, contact tracing, medical countermeasures, and education of health care providers and the public. Even though management of cases was considered successful and the risk from the disease was down-graded, sporadic cases continue to occur. Here, we provide epidemiological and laboratory features of the reported cases to depict the course of the disease notification rate, that suggests measures for raising awareness as well as vaccination of high-risk groups of the population should be continued.

One of the significant challenges today in the brain-machine interface using invasive methods is the stability of the chronic record. In recent years, polymer-based electrodes have gained notoriety for achieving mechanical strength values close to that of brain tissue, promoting a lower immune response to the implant. In this work, we fabricated fully polymeric electrodes based on PEDOT:PSS for neural recording in Wistar rats. We characterized the electrical properties and both in-vitro and in-vivo functionality of the electrodes. Also, we employed histological processing and microscopical visualization to evaluate tecidual immune response in 7, 14, and 21 days post-implant days. Electrodes with 400-micrometer channels showed a 12dB signal-to-noise ratio. Local field potentials were characterized under two conditions: anesthetized and free-moving. There was a proliferation of microglia to the tissue-electrode interface in the first days, with a decrease after 14 days. Astrocytes also migrated to the interface, but there was no continuous recruitment of these cells in the tissue, showing inflammatory stability at 21 days. The signal was not affected by this inflammatory action, demonstrating that fully polymeric electrodes can be an alternative to prolong the valuable time of neural recordings.

Bunyaviruses represent the largest group of RNA viruses, and are the causative agent of a variety of febrile and hemorrhagic illnesses. Originally characterized as a single serotype in Africa, the number of described bunyaviruses now exceeds over 500, with its presence detected around the world. These predominantly tri-segmented, single-stranded RNA viruses are transmitted primarily through arthropod and rodent vectors, and can infect a wide variety of animal and plants. Although encoding for a small number of proteins, these viruses can inflict potentially fatal disease outcomes, and have even developed strategies to suppress the innate antiviral immune mechanisms of the infected host. This short review will attempt to provide an overall description of the order Bunyavirales, describing the mechanisms behind their infection, replication and their evasion of the host immune response. Furthermore, the historical context of these virus will be presented, starting from their original discovery almost 80 years ago, to the most recent research pertaining to viral replication and host immune response.

Deaths and property damage from the flood have increased drastically in the past two decades due to various reasons such as increased population, unplanned development and climate change. Losses from floods can be reduced by having accurate intelligence of an emerging flood situation in order to make timely decisions for issuing early warnings and responding efficiently. This paper presents a thorough analysis of the types and sources of intelligence required for flood warning and response processes and technology solutions that can be used for capturing such intelligence. A structured review, covering a more comprehensive range of published literature on Flood Early Warning and Response Systems (FEWRS), was conducted to identify the necessary intelligence and the technology that can be used to capture intelligence required for various phases of a flood hazard as it develops. Twenty-seven different types of key intelligence required in the flood cycle were identified. A conceptual architecture was identified that illustrates how relevant technology solutions can be used to extract intelligence at various stages of a flood event for decision making for early warnings and response.

Background: We aimed to identify overexpressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant therapy with trastuzumab in HER2-positive breast cancer patients. Methods: We recruited 64 women with breast cancer and categorized them into three groups according to anti-HER2 therapy response. RNA from twenty core needle biopsy paraffin-embedded tissues and four cultured cell was extracted, reverse transcribed, and subjected to microarray. The obtained data were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and database for annotation, visualization, and integrated discovery. Results: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines (3,224 upregulated and 3,432 downregulated). Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in complete response group. Conclusions: This multigene assay-based study provides insights into breast cancer signal transduction and the possible prediction of treatment response to targeted therapies such as trastuzumab.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the im-mune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049); whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

A highly efficient reduction process of Cr (VI) with biochar was conducted in this paper. The results showed that nearly 100% Cr (VI) was reduced at selected reaction conditions: the dosage of biochar at m (C)/m(Cr) = 3.0, reaction temperature of 90 ℃, reaction time at 60 min and concentration of H2SO4 of 20 g/L, respectively. The reduction kinetics analysis demonstrated that the reduction of Cr (VI) fitted well with the pseudo-first-order model and the apparent activation energy was calculated to 40.24 kJ/mol. Response surface methodology confirmed that all the experimental parameters had positive effect on the reduction of Cr (VI). The influence of each parameter on the reduction process followed the order: dosage of biochar> Concentration of H2SO4 > Reaction Temperature > Reaction Time. This paper provided a versatile strategy for treatment of wastewater containing Cr (VI) and showed a bright tomorrow for wastewater treatment.

Purpose: This study aimed to determine the efficacy and safety of Oncoxin as an antitumoral supplement, and to describe its mechanism of action. Methods: We performed this scoping review according to the recommendations of the Joanna Briggs Institute and included patients older than 18 years-old who have any kind of tumor and receive Oncoxin as a supplement. We focused on the efficacy in terms of antitumoral properties, quality of life and survival, safety in terms of adverse events, and the mechanism of action. We did not limit for language or setting. We searched MEDLINE (Pubmed), EMBASE (Scopus), LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. Results: We found a promising increment of survival when taking Oncoxin as a supplementary treatment. Additionally, the quality of life increased in terms of Karnofsky and EORTC scales. Regarding the mechanism of action, studies suggest it modifies inflammatory mediators’ expression, as evidenced by the reduction of COX-2, IL-1β, IL-6, TNF-α, IL-1β, IL-12, and IFN-γ. Besides, it promotes an arrest in the progression of cells from G1 into S, along with an increase in p27 and a decrease in cyclin D1 and pRb. Conclusions: We found promising complementary effects of Oncoxin to the standard treatment of cancer patients in diverse scenarios, with putative robust mechanisms of action. In addition to clinically relevant impacts verified in clinical trials, as well as it decreases the levels of pro-inflammatory cytokines, it can also decrease cytokines with antitumor activity such as IFN-γ, which should be further explored in larger trials and the long term.

Background: The COVID-19 has put global health institutions on alert. Organizations such as the CDC and WHO have developed preparedness and prevention checklist of 2019-nCoV infection to be used by public and healthcare professionals. Since COVID 19 pandemic is unexpected and no country aware of it prior to outbreak, there is limited information on the overall preparations of healthcare providers in Ethiopia. Therefore, the aim of this study was to assess early healthcare professionals’ preparedness and response to COVID 19 Pandemic in Oromia regional state, Ethiopia. Methods: The study was conducted on healthcare professionals working in public hospitals of Oromia regional state. The study was carried out by online questionnaire prepared using SurveyMonkey©. The collected data was analyzed and One-way ANOVA was used to determine the significant differences between health professionals working in different hospitals. The statistical significance associations of variables of interest was determined at 95% confidence intervals. Results: Healthcare professionals in the public hospitals of Oromia regional state, Ethiopia perceived that they are not yet well prepared and may not respond to the pandemic quickly and efficiently. Even though, they have positive response towards identifying signs and symptoms, provide education and utilization of PPE, they are still lacking in practical responses like managing cases, implementing emergency plans and isolation procedures from many others. Conclusion: As the Federal Ministry of Health, Ethiopia Public health institute and Oromia health bureau are vigilant and continually conducting preventive measures programs, extensive and maximum effort should be done to improve healthcare providers’ preparedness and response towards any emergency related to COVID-19 pandemic.

Optical conductivity of an interacting polaron gas is calculated within an extended random phase approximation which takes into account mixing of collective excitations of the electron gas with LO phonons. This mixing is important for the optical response of strongly polar crystals where the static dielectric constant is rather high, as in the case of strontium titanate. The present calculation sheds light on unexplained features of experimentally observed optical conductivity spectra in $n$-doped SrTiO$_{3}$. These features appear to be due to dynamic screening of the electron-electron interaction by polar optical phonons and hence do not require additional mechanisms for their explanation.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

To date, radiation adaptation response has been reported as a low-dose related phenomenon and has been associated with radiation hormesis. Well-known cancers are caused by non-radiation active reactants, in addition to radiation. A model of suppression for radiation-specific cancers was previously reported, but the model did not target radiation-nonspecific cancers. In this paper, we describe kinetic models of radiation-induced suppressors for general radiation non-specific cancers, estimating the dose that induces the maximum hormesis effect while satisfying the condition that the risk is approximately proportional to dose above 100 mSv. It was found that the radiation hormesis effect is maximal at about 20 mSv when the rate constant for generation is the same as the rate constant for decomposition. When the two rate constants are different, the dose at which the radiation hormesis effect is maximized depends on both rate constants, but the dose increases as the two rate constants approach each other, reaching a maximum of about 20 mSv. This conclusion may lead to the discovery of unknown cancer suppressors at low doses and the development of cancer suppression methods in the future.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

Background: In March 2020, a COVID-19 outbreak associated with the Falles Festival in Borriana, Spain, led to significant infections. Methods: In June 2022, we conducted a cross-sectional follow-up study of 473 socially engaged adults aged 18 to 64, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse weighted probability analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count. Results: 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Not complying with long COVID criteria associated with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ‐producing‐CD8+ response, and infection during the Omicron period. Conversely, increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56.4% to 91.7%) and symptom count by 55.2% (95% CI: 31.6% to 78.7%). Conclusion: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination’s role in mitigating SARS-CoV-2 infection consequences.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Effects of the convection flow, atmospheric diffusivity and humidity on evolution and travel distances of exhaled aerosol clouds by an infected person are considered. The aim of this work is to evaluate the importance of aerosol transmission routes and the effectiveness of the 2-metre separation distance policy. A potential impact of use of face masks on the infection transmission rate, and an opportunity to reduce infection in hospitals, care homes and other public spaces by appropriate monitoring and filtering of air are also considered. The results obtained demonstrate that aerosol particles generated by coughing and sneezing can travel over 30 m. Modelling of the evolution of aerosol clouds generated by coughing and sneezing enables us to evaluate the deposition dose of aerosol particles in healthy individuals. For example, a person in a public place (e.g. supermarket or car park) can accumulate in the respiratory system up to 200 virus copies in 2 min time by breathing in virus laden aerosols. Wearing face mask considerably reduces the deposited load down to 2 virus copies per 2 min. The modelling also suggests that it should be possible to measure virus causing COVID-19 (SARS-CoV-2) within aerosol particles in hospitals and public places, e.g. care homes and supermarkets.

The response of plasmonic metal particles to an electromagnetic wave undergoes significant features at the nanoscale level. Different properties of the internal composition of a metal, such as its ionic background and the free electron gas, begin to manifest more prominently. As the dimensions of the nanostructures decrease, the classical local theory gradually becomes inadequate. Therefore, Maxwellʹs equations need to be supplemented with a relationship determining the dynamics of current density which is the essence of nonlocal plasmonic models. In this field of physics, the standard (linearized) hydrodynamic model (HDM) has been widely adopted with great success, serving as the basis for a variety of simulation methods. However, ongoing efforts are also being made to expand and refine it. Recently, the GNOR (general nonlocal optical response) modification of the HDM has been used, with the intention of incorporating the influence of electron gas diffusion. Clearly, from the classical description of fluid dynamics, a close relationship between viscosive damping and diffusion arises. This offers a relevant motivation for introducing the GNOR modification in an alternative manner. The standard HDM and its existing GNOR modification also do not include the influence of interband electron transitions in the conduction band and other phenomena that are part of many refining modifications of the Drude‐Lorentz and other models of metal permittivity. In this article, we present a modified version of GNOR‐HDM that incorporates the viscosive damping of the electron gas and a generalized Drude‐Lorentz term. In the selected simulations, we also introduce Landau damping which corrects the magnitude of the standard damping constant of the electron gas based on the size of the nanoparticle. We have chosen a spherical particle as a suitable object for testing and comparing HD models and their modifications because it allows finding precise analytical solutions for the interaction and, simultaneously, it is a relatively easily fabricable nanostructure in practice. Our contribution also includes our own analytical method for solving the HDM interaction of a plane wave with a spherical particle. This method forms the core of calculations of the characteristic quantities, such as the extinction cross‐sections and the corresponding components of electric fields and current densities.

IMPORTANCE: On December 10, 2021, the FDA published a Determination Letter, along with a Statistical Review and Evaluation Report, and concluded that under the non-informative prior, the local Bayesian optimal interval design (BOIN) design, in its revised form, can be designated fit-for-purpose for identifying the maximum tolerated dose of a new drug, assuming that dose-toxicity relationship is monotonically increasing. Although setting the BOIN design parameter p.tox = 1.4 * target.DLT.rate is recommended in almost all BOIN methodology articles and is the default value in the R package BOIN, it's unclear if the choice of p.tox should only depend on the target DLT rate and if certain range of p.tox could produce the same BOIN boundary table. DESIGN: In this simulation study, following parameters were varied one at a time, using R package BOIN, to explore their effects on the equivalence intervals of p.saf and p.tox: 1) target DLT rate, 2) n.earlystop, 3) cutoff.eli, 4) cohortsize, and 5) ncohort. And a simple 3+3 design was used as an example to explore equivalent sets of BOIN design parameters that can generate the same boundary table. RESULTS: When the early stopping parameter n.earlystop is relatively small or the cohortsize value is not optimized via simulation, it might be better to use p.tox < 1.4 * target.DLT.rate, or try out different cohort sizes, or increase n.earlystop, whichever is both feasible and provides better operating characteristics. This is because if the cohortsize was not optimized via simulation, even when n.earlystop = 12 and cohortsize > 3, the BOIN escalation/de-escalation rules generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as those calculated using p.tox > 3 * target.DLT.rate, which might not be acceptable for some pediatric trials targeting 10% DLT rate. The traditional 3+3 design stops the dose finding process when 3 patients have been treated at the current dose level, 0 DLT has been observed, and the next higher dose has already been eliminated. If additional 3 patients were required to be treated at the current dose in the situation described above, the decision rules of this commonly used 3+3 design could be generated using BOIN design with target DLT rates ranging from 18% to 29%, p.saf ranging from 8% to 26%, and different p.tox values ranging from 39% to 99%. These BOIN parameters also need to satisfy a set of conditions. Meaning: This study demonstrates the importance of interpreting BOIN design parameter p.tox as an interval of toxicity rates that are considered too toxic, rather than one prespecified value that corresponds to the lowest toxicity probability that is deemed overly toxic. When designing a dose-finding trial using BOIN, it is important to perform simulation studies to identify equivalent sets of BOIN design parameters that can generate the same boundary table so that we can better compare the safety properties of different boundary tables.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Radiological imaging is essential for acute patient management in Intensive Care Units (ICUs); however, it introduces the risk of exposure to ionizing radiation. This review synthesizes research on radiation exposure in intensive care unit (ICU) settings, highlighting its rise during the COVID-19 pandemic and repetitive imaging. Our analysis extends to radiation safety thresholds, revealing that some ICU patients exceed annual occupational limits, emphasizing the need to balance diagnostic utility against potential long-term risks, such as cancer. Prospective studies have demonstrated an increase in the median Cumulative Effective Dose (CED) in patients with trauma over time, prompting calls for improved awareness and monitoring. Moreover, innovative dose-reduction strategies and optimized protocols, especially in neuro-ICU units, promise to mitigate these risks. This review highlights the essential but risky role of radiological imaging in critical care. It advocates rigorous radiation management protocols to safeguard patient health, while ensuring the continuity of high-quality medical care.

FLASH-RT represents a novel therapeutic radiation modality that holds remarkable potential for mitigating radiation therapy’s adverse side effects. This cutting-edge technology allows for the sparing of healthy tissue while precisely targeting cancerous cells by administering an ultra-high dose-rates of typically between 10 and 30 Gy in less than a few hundred milliseconds. FLASH-RT has demonstrated impressive results in small-animal models, prompting scientists to adapt and advance existing technologies to make it a viable treatment option for humans. However, producing the ultra-high-dose-rate radiation required for the therapy remains a significant challenge. Several radiation sources, such as very high energy electrons (VHEEs), low energy electrons, x-rays, and protons, have been studied for their ability to deliver the necessary dose. Among them, FLASH-x-ray has gained the most attention owing to its capacity to penetrate deeply seated tumours. Despite the complexity of the process, the potential advantages of FLASH-RT make it an exciting area of research. To achieve the FLASH effect, high-frequency, pulsed irradiated accelerator technology can be employed. Sparing healthy tissue, it may allow for more aggressive and effective cancer treatments, leading to a better quality of life for patients. Ongoing research and development will be necessary to refine and optimize this approach to radiation therapy.

Purpose: The purpose of this study was to evaluate the dosimetric impact of multiple channels compared to a single channel in high dose rate (HDR) vaginal cuff brachytherapy (VCBT). Methods and materials: Sample plans of HDR VCBT from both single and multiple channel cylinders at 2.5, 3.0 and 3.5 cm in diameter were created and analyzed. The doses were prescribed either at the 0.5 cm depth with 5.5 Gy for 4 fractions or at the cylinder surface with 8.8 Gy for 4 frac¬tions, in various treatment lengths ranging from 3 to 8 cm. A 0.5 cm ring target volume called PTV_Eval was contoured for each plan and served as the target volume for dosimetric evaluation. Mean doses and the doses covering 90% (D90), 10% (D10), and 5% (D5) of PTV_Eval were calculated and compared. The same treatment lengths, same prescription regimens, same target volume contouring and same plan evaluation methods were repeated for the similar size single channel and multiple channel cylinders. Results: The mean doses of both regimens with the multi-channel cases (6.3 to 7.1 Gy) were comparable to single channel ones (6.4 and 7.5 Gy). The ranges of D90, D10 and D5 were from 3.654 to 5.04 Gy, 8.44 to 10.08 Gy and 8.84 to 10.86 Gy in the multi-channel cases, but from 5.36 to 5.76 Gy, 7.40 to 9.97 Gy and 8.16 to 11.93 Gy in the single channel cases, respectively. Conclusion: The single channel and multiple-channel cylinder deliver a similar mean dose, but with marked heterogeneity in D90, D5 and D10 for the same prescription dose and target volume. Multi-channel cylinders adequately cover the target volume, but given the heterogeneity, increased treatment time and cost are best suited for asymmetric target volumes.

Due to the long duration and high cost of traditional pumping tests, the response of well water level to seismic wave, earth tide, and barometric pressure provides a feasible method for determining continuous changes in aquifer hydraulic parameters. Aiming at the problem that the response phase shift of well BB water level to tidal tide M2 is greater than that of tide O1, this paper preferentially calculated the time series changes of S, Be, n and BKu based on the response mechanism of well water level to barometric pressure and earth tide and with the help of smooth moving method. Then by using the mixed flow model, the variation of transmissivity and leakage coefficient over time were simultaneously obtained, and the evolution process and characteristics of aquifer parameters near well BB caused by the Wenchuan earthquake were ultimately discussed. The calculation results are basically consistent with the previous pumping test, and have been verified and compared by using other scholars' methods. This solving process avoids the problems such as excessive dependence on initial values, multiple solutions, and unstable tide O1, which has a promoting effect on the study of the impact of seismic activity on aquifer systems.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

This study examined infants' neural responses to emotional prosody in natural speech. A multi-feature oddball paradigm was used with 34 3~11 month-old infants. Results showed distinct early (100-200 ms) and late (300-500 ms) mismatch responses to different emotional prosodies. Older infants had more negative early responses with happy and angry prosodies evoking stronger responses compared to sad prosody while younger infants showed a clearer distinction between angry and sad prosodies. In the late time window, angry prosody elicited more negative responses than sad prosody with younger infants showing more distinct responses between these two prosodies. Males exhibited stronger early mismatch responses than females. These findings call for further research on the implications for socio-emotional and language development.

Food and drinks can be contaminated with pollutants such as lead and strontium and this poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest -thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article we produce an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that the TBA should perform better as a detector of strontium rather than lead.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. The treatment target is slowing down the disease course and mitigating the symptoms. Approximately 30 to 50% of patients do not respond optimally to Disease Modifying Therapies (DMTs), in which therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of HLA DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3), was used to classify therapeutic response. Patients were classified as follows: a) control: patients who achieved NEDA-3 b) case: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were: GG 50.5%, GA 34.3% and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p=0.6). We concluded that in Mexican patients with MS, HLA DRB1*0403 was not associated with therapeutic response to DMTs.

The noncoding RNAs (ncRNAs) are small transcript sequences that do not encode proteins but participate in the regulation of gene expression at the post-transcriptional level playing important biological roles such as proliferation and differentiation. In the tumor microenvironment, the dysregulated immunological response can participate in the progression and negative phenotype of cancer, the variability of switch cell differentiation and activation of the different immune cell lineages showed differential regulation by the type of cancer. Recent evidence showed that the upregulation of lncRNA can be used as a biomarker and predictive indicator for cancer progression. The use of lncRNA to turn off the tumor immune response and activate the anti-tumoral immune response is day by day a promising reality for the control of cancer. However, is imperatively elucidated the role of each ncRNA identified as well as its respective molecular pathways regulated, including the immune checkpoints, before its application at the clinical level. The correct delivery of lncRNA or mimics to inhibit its expression using the most efficient carriers to the cell or cellular organelle is a science that should continue to be developed.

Ransomware is continually evolving. The most recent tactic is to combine crypto-ransomware with data exfiltration, mandate fraud, and other such schemes to steal from victims and attempt to blackmail them. This paper examines the new trend, its underlying motives, and proposes practical recommendations to help organizations defend against this menace

We select four important waves of new entrants that knocked on the door of European electricity markets to illustrate how market rules need to be continuously adapted to allow new entrants to come in and push innovation forward. The new entrants that we selected are utilities venturing into neighbouring markets after establishing a strong position in their home market, utility-scale renewables project developers, asset-light software companies aggregating the assets of smaller consumers and producers, and different types of communities. We show that well-intentioned rules designed for certain types of market participants can (unintentionally) become obstacles for new entrants. We conclude that the evolution of market rules illustrates the importance of dynamic regulation. At the start of the liberalisation process the view was that we would deregulate or re-regulate the sector after which the role of regulators could be reduced. But their role has only increased. New players might also present new risks that require intervention by regulators.

Background: Twitter is a major tool for communication in emergencies such as natural disasters. This online social network allows the user to produce content, and it is not designed exclusively for news releases, as opposed to other service providers. Aim: The aim of this study is to investigate Twitter uses in natural disasters and pandemics. Methods: The included studies reported the role of Twitter in natural disasters. The studies that report in settings other than the natural disasters (such as man-made disasters) and other social media were excluded. Electronic databases for a comprehensive literature search including MEDLINE, Web of Science, CINAHL, PsycINFO, Cochrane Register of Controlled Trials (CENTRAL) and EMBASE were used to identify the records that match the mentioned inclusion criteria published till May 2020. The study characteristics were extracted from the qualified studies including year of publication, findings, and geographical location of the study conduct. A narrative synthesis for this literature review was used. Results: The search identified 822 articles of which 780 articles were removed, 256 were not available, 311 papers were not relevant, 16 were duplicated articles, and 197 were non-related to the emergencies. 45 articles met the selection criteria and were included in the review. eleven themes were found in the narrative synthesis including early warning, disseminating information and misinformation, advocacy, personal gains, assessment, various roles of organizations, public mood, geographical analysis, charity, using influencers, and trust. Conclusions: It is recommended that influential individuals be identified in each country and community before disasters occur so that the necessary information can be disseminated in response to disasters. Preventing the spread of misinformation is one of the most important issues in times of disaster, especially pandemics. Disseminating accurate, transparent, and prompt information from relief organizations and governments can help. Also, analyzing Twitter data can be a good source for understanding the mental state of the community, estimating the number of injured people, estimating the points affected by natural disasters, and modeling the prevalence of epidemics. Therefore, various groups such as politicians, the government, non-governmental organizations, aid workers, and the health system can use this information to plan and implement interventions.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim of this study was to estimate the correlated response in kits’ weight and its survival, and weight distance from birth to weaning. Weight distance was calculated as the absolute values of the differences between the individual value and the mean value of its litter. Also, relationship between probability of survival at 4 d of age and weight at birth was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does of the low line (selected for reducing litter size variability) and 1916 kits of 114 does of the high line (selected for increasing litter size variability) of the 12th generation were weighed. Bayesian methodology was used to estimate the correlated response to selection, and LOGISTIC procedure of SAS was used to estimate the relationship between weight and probability of survival. Both lines showed similar individual weight at birth and at weaning, and similar survival at birth and at 4 d of age. Survival at weaning was higher in the low line than in the high line (0.67 and 0.62; P= 0.93). Weight distance was higher at birth but lower at weaning in the low line (47.8 g and 54.1 g; P=0.98). Kit’s weight at birth affected its survival. In conclusion, selection for environmental sensitivity showed correlated response in kits survival and in homogeneity of litter weight at weaning.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

The present work aims at the comprehensive application of stochastic and optimization tools with the support of Information and Communication Technologies (ICT) through a case study in a logistics process for electronic goods; simulation and Response Surface Methodology (RSM) are applied for this purpose. The problem to be evaluated is to define an optimal distribution cost for products shipped to wholesale customers located in different cities in Mexico from a manufacturing plant in Tijuana, Mexico. The factors under study are the product allocation for each distribution center, finished good inventory level and on time deliveries, which are supposed to be significant to get the objective. The methodology applied for this problem considers the design of a discrete event simulation model to represent virtually the real life of logistics process, which is considered a complex system due to different activities are interrelated to carry it out. This model is used to execute the different experiments proposed by the RSM. The results obtained from simulation model were analyzed with the RSM to define the mathematical model that allows identifying the parameters of the factors in order to optimize the process. The findings prove how the ICT facilitate the application of stochastic tools with the purpose of process optimization.

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

Phononic crystals are periodic composite structures with specific resonant features that are gaining strength in the field as liquid sensors. The introduction of a structural defect in an otherwise periodic regular arrangement can generate a resonant mode, also called defect mode, inside the characteristic band gaps of phononic crystals. The morphology, as well as the frequency in which these defect modes appear, can give useful information on the composition and properties of an analyte. Currently, only gain, and frequency measurements are performed using phononic crystal sensors. Other measurements like the transient response have been implemented in resonant sensors such as quartz microbalances showing great results and proving to be a great complimentary measure to the gain and frequency measurements. In the present paper, a study of the feasibility of using the transient response as a measure to acquire additional information about the analyte is presented. Theoretical studies using the transmission line model were realized to show the impact of variations in the concentration of an analyte, in this case, lithium carbonate solutions, in the transient time of the system. Experimental realizations were also performed showing that the proposed measurement scheme presents significant changes in the resulting data, indicating the potential use of this measure in phononic crystal sensors. This proposed measure could be implemented as a stand-alone measure or as a compliment to current sensing modalities.

Improved understanding of climate-growth relationships of multi-species is fundamental to understand and predict response of forest growth to future climate change. Forests are mainly composed of conifers in Northwestern Yunnan Plateau, but variations of growth response to climates among the species are not well understood. To detect growth response of multiple species to climate change, we developed residual chronologies of four major conifers, i.e. Abies georgei, Picea likiangensis, Pinus densata and Larix potaninii at upper distributional limits in Shika Snow Mountain. By using dendroclimatology method, we analyzed correlations between the residual chronologies and climate variables. The results showed that conifer radial growth was influenced by both temperature and precipitation in Shika Snow Mountain. Previous November temperature, previous July mean maximum temperature (T_max) and current June precipitation were the common climatic factors, which had consistent influences on radial growth of four species. Temperature in previous post growing season (September–October) and current growing season (June-August), and precipitation in previous August were the common climatic factors, which had divergent impacts on four species radial growth. Current May T_max and early growing season (April-May) precipitation showed positive and negative influences on growth of P. likiangensis, respectively. Temperature in current post growing season positively affected growth of A. georgei. According to the prediction of climate models and our understanding in growth response of four species to climate variables, we may understand growth response to climate change at species level. It is difficult to predict future forest growth in the study area, since future climate change might cause both increases or decreases for four species and indirect effects of climate change on forest should be considered.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

Antimicrobial use (AMU) is one of the major drivers of emerging antimicrobial resistance (AMR). Surveillance of AMU, a pillar of AMR stewardship (AMS), helps devise strategies to mitigate AMR. This descriptive, longitudinal retrospective study quantified the trends in human antibiotic utilization between 2010 and 2016 using data on all antibiotics imported for systemic human use into Tanzania's mainland. Regression and time series analyses were used to establish trends in antibiotics use. A total of 12,073 records for antibiotics were retrieved, totaling 154.51Daily Defined Doses per 1,000 inhabitants per day (DID) with a mean (± standard deviation) of 22.07 (±48.85) DID. The private sector contributed 93.76%% of utilized antibiotics. The top-ranking antibiotics were amoxicillin, metronidazole, tetracycline, ciprofloxacin and cefalexin. The DDIs and percentage contribution of these antibiotics were 53.78 (34.81%), 23.86 (15.44), 20.53 (13.29), 9.27 (6.0) and 6.94 (4.49), respectively. The time series model predicted significant increase in utilization(p-value =0.002). The model forecasted that by 2022, the total antibiotics consumed would reach 89.6 DIDs, corresponding to a 13-fold increase compared to 2010. Government intervention to curb inappropriate antibiotic utilization to mitigate the rising threat of antibiotic resistance should focus on implementing AMS programs in pharmacies and hospitals in Tanzania.

The focus of recent research shifts towards complex ‘whole organism’ responses (i.e., in multiple functional traits) in adaptation to or to defend against stressors under complex environmental conditions. This increasing complexity is challenging to analyse and demands sophisticated tools to drive meaningful conclusions from those data. Trait-based regression models, multivariate analyses, like principal component analyses, and plasticity indices can be used to tackle challenges with those complex investigations. But those methods have substantial limitations, like the need for high sample size, multi-dimensionality of results or the need for trait coordination in high-dimensional space, or the calculation on the population level, which might buffer or cover the de facto occurring individual effects. To improve and simplify studies on ‘whole organism’ responses, analyses, and their interpretation, we developed the Index for Adaptive Responses. This straightforward framework can unite all traits of an organism in one number. A newly developed transformation method, included in this framework, comprises a normalisation and standardisation to a baseline or control without changing the data or variance structure of the original data. We assessed the performance and accuracy of the framework with an application in an extensive predator-prey case study, with simulations and application examples using literature data. We show that the Index for Adaptive Responses respects adaptations as well as maladaptations and outperforms established approaches. The framework is robust against outliers and non-gaussian distribution. We further show that the qualitative prediction of the adaptiveness of included traits is highly accurate, even under challenging conditions, e.g., low replicate numbers. Functions and algorithms of the framework are provided with an R package but can easily be translated into other programming languages. The Index for Adaptive Responses will simplify future research on complex adaptive responses and improves our understanding of these responses’ ecological as well as evolutionary implications.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

Trichoderma atroviride is a strong necrotrophic mycoparasite antagonizing and feeding on a broad range of fungal phytopathogens. It further beneficially acts on plants by enhancing growth in root and shoot and inducing systemic resistance. Volatile organic compounds (VOCs) are playing a major role in all those processes. To date, T. atroviride IMI 206040 and T. atroviride P1 are among the most frequently studied T. atroviride strains and hence are used as model organisms to study mycoparasitism and photoconidiation. However, there are no studies available, which systematically and comparatively analyzed putative differences between these strains regarding their light-dependent behavior. We therefore explored the influence of light on conidiation and the mycoparasitic interaction as well as the light-dependent production of VOCs in both strains. Our data show that in contrast to T. atroviride IMI 206040 conidiation in strain P1 is independent of light. Furthermore, significant strain-and light-dependent differences in the production of several VOCs between the two strains became evident, indicating that T. atroviride P1 could be a better candidate for plant protection than IMI 206040.

The prevailing challenge in our current era is climate change, a crisis recognized by the global community that has prompted immediate actions to confront and mitigate its consequences. There is a consensus among scientists that human activities, driven by developmental ambitions, are the driving force behind the ongoing climate crisis. “The well-documented aftermath, including the rise in sea levels, coastal erosion, reduced agricultural yields, compromised access to clean water, and health implications, emphasizes the intricate and wide-ranging effects of climate change.” Furthermore, there is an increasing recognition that climate change gives rise to distinct social, economic, and divergent consequences. “Although all countries worldwide will undergo the impacts of climate change, the distribution of these effects will differ among regions, generations, age groups, income levels, occupations, and genders.” Notably, the adverse consequences will disproportionately impact the impoverished, predominantly situated in developing nations. “This paper explores the effects of climate change on displacement and the ensuing refugee dilemma.” It aims to scrutinize the inclusion of climate-induced displacement in the present international framework, encompassing both climate change and refugee regimes. The paper promotes a human rights-centred approach to tackling displacement stemming from climate change.

Glioblastoma, a deadly brain tumor, shows limited response to standard therapies like te-mozolomide (TMZ). Recent findings from the REGOMA trial underscore a significant survival improvement offered by regorafenib (REGO) in recurrent glioblastoma. Our study aimed to propose a 3D ex vivo drug response precision medicine approach to investigate recurrent glio-blastoma sensitivity to REGO and elucidate the underlying molecular mechanisms involved in tumor resistance or responsiveness to treatment. 3D glioblastoma organoids (GB-EXPs) obtained from 18 patients’ resected recurrent glioblastoma tumors were treated with TMZ and REGO. Drug responses were evaluated using NAD(P)H FLIM, stratifying tumors as responders (Resp) or non-responders (NR). Whole-exome sequencing was performed on 16 tissue samples, and whole-transcriptome analysis on 13 GB-EXPs treated and untreated. We found 35% (n=9) and 77% (n=20) of tumors responded to TMZ and REGO, respectively, with no instances of TMZ-Resp be-ing REGO-NR. Exome analysis revealed a unique mutational profile in REGO-Resp tumors compared to NR tumors. Transcriptome analysis identified distinct expression patterns in Resp and NR tumors, impacting Rho GTPase and NOTCH signaling, known to be involved in drug response. In conclusion, recurrent glioblastoma tumors were more responsive to REGO com-pared to TMZ treatment. Importantly, our approach enables a comprehensive longitudinal ex-ploration of the molecular changes induced by treatment, unveiling promising biomarkers in-dicative of drug response.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 hours resulted in increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx), but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune-response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, providing insights into the molecular and functional diversity of the immune response in chordates.

Micro/Nano Robot is an intelligent and efficient microrobot that can perform specific tasks under the influence of external stimuli. Depending on the application scenarios, the microrobot can adaptively transform into appropriate functional forms under different external stimuli, thus perfectly matching the needs. To date, microbots have been widely used in targeted therapy, drug delivery, tissue engineering, environmental remediation, and other fields. Although the applications of microrobots are promising, there are only a few reviews that can focus on the preparation methods and driving mechanisms. Therefore, it is necessary to outline the current status of the development of these microrobots in order to provide some new insights for the further development of the field. Therefore, this paper reviews the research progress of microrobots in terms of preparation methods, stimulus response mechanisms and applications, and highlights the applicability of different preparation methods and stimulus types. Finally, the current challenges faced by microrobots are highlighted and possible solutions are proposed to facilitate the practical application of microrobots.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

Atopic dermatitis (AD), a T2 inflammatory skin condition, is widely recognized as one of the most prevalent chronic and recurrent skin disorders. One of the most effective therapy for treating moderate-to-severe AD is Dupilumab, a monoclonal antibody that blocks both IL-4 and IL-13 signaling. At the same time, no comprehensive analysis of cytokines profile was made in AD patients undergoing Dupilumab therapy. The primary objective of our research was to examine the levels of main cytokines to better understanding systemic immune response in AD and to identify potential biomarkers of the effectiveness of Dupilumab treatment. AD patients demonstrated significant clinical improvements one year after initializing of Dupilumab therapy. We identified 16 cytokines that showed major difference between Dupilumab-treated patients and patients without Dupilumab therapy. Six cytokines showed correlation with AD severity and the efficacy of Dupilumab therapy. Jointly revealed cytokines could potentially predict the effectiveness of Dupilumab treatment and help to choose the precision target therapy in AD patients as well.

In the dairy cattle sector, the evaluation of the effects induced by heat stress is still one of the most impactful and investigated aspects as it is strongly connected to both sustainability of the production and animal welfare. On the other hand, more recently, the possibility of collecting large dataset made available by the increasing technology diffusion is paving the way for the application of advanced numerical techniques based on machine learning or big data approaches. In this scenario driven by rapid change there could be the risk of dispersing the relevant information represented by the physiological animal component, which should maintain the central role in the development of numerical models and tools. In the light of this, the present literature review aims to consolidate and synthesize existing research on the physiological consequences of heat stress in dairy cattle. The present review provides, in a single document, an overview as complete as possible of the heat stress-induced responses in dairy cattle with the intent of filling the existing research gap for extracting the veterinary knowledge present in the literature and make it available to those who are developing numerical models and tools.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TNM-stages. Locoregional control rates have been impressive even from the 2D-radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there had been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally-advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

This paper presents a novel approach for individual design perception modeling using the YUKI-trained Fuzzy Inference System. The study focuses on understanding how individuals perceive design based on personality traits, particularly openness to experience. The proposed YUKI algorithm optimizes the FCM clustering algorithm, enhancing its ability to handle uncertain and imprecise data. The YUKI-trained FIS generates several Sugeno-type FIS models to predict design perception, to minimize the Root Mean Squared Error between the model prediction and the actual design perception of participants. The results demonstrate that the YUKI-trained FIS offers more accurate predictions compared to the traditional FCM-trained FIS, and the RMSE values for individual design perceptions fall within a satisfactory range of 0.84 to 1.32. The YUKI-trained FIS proves effective in clustering individuals based on their level of openness, providing insights into how personality traits influence design perception.

In their natural environment, bacteria are exposed to various stresses. The stress-response sigma factor SigB of gram-positive Bacillus subtilis is the best-characterized example. Unlike Bacillus subtilis, the gram-positive bacterium Streptomyces coelicolor A3(2) contains nine SigB homologues (SigBFGHIKLMN) with a major role in differentiation and response to osmotic stress. We previously constructed a two-plasmid system to identify promoters recognized by these sigma factors. Interestingly, almost all identified promoters were recognized by two or more SigB homologues. However, no specific sequences characteristic for these recognition groups were found. To examine this cross-recognition in vivo in S. coelicolor A3 (2), one of these promoters was cho-sen, which drives the expression of the sporulation-specific gene ssgB. The ssgBp promoter was inserted into a luciferase reporter plasmid and conjugated to S. coelicolor M145 and nine mutant strains containing deleted individual sigB homologous genes. Luciferase reporter activity indi-cated differential activity of this promoter in these mutant strains, suggesting overlapping pro-moter recognition by these SigB homologues. To determine which nucleotides in the ̶ 10 re-gion are responsible for the selection of a specific SigB homologue, several mutant promoters with altered last three nucleotides in this region were prepared and tested in the two-plasmid system. Some mutant promoters were specifically recognized by some SigB homologues. Mutant promoters were inserted into a luciferase reporter plasmid and conjugated to S. coelicolor A3(2) and these nine mutant strains. Luciferase reporter activity indicated differential activity of these ssgBp mutant promoters, indicating overlapping promoter recognition by these SigB homologues in S. coelicolor A3(2).

Studies evaluating candidate tick-derived proteins as anti-tick vaccines in natural hosts have been limited due to high costs. To overcome this problem, animal models are used in immunization tests. The aim of this article was to review the use of rabbits as an experimental model for the evaluation of tick-derived proteins as vaccines. A total of 57 tick proteins have been tested for their immunogenic potential using rabbit as model for vaccination. The most commonly used rabbit breeds were New Zealand (73.8%), Japanese white (19%), Californians (4.8%) and Flemish lop-eared rabbit (2.4%). Anti-tick vaccines efficacy resulted in up to 99.9%. Haemaphysalis longicornis (17.9%) and Ornithodoros moubata (12.8%) were the most common tick model in vaccination trials. Experiments in rabbits have revealed that some proteins (CoAQP, OeAQP, OeAQP1, Bm86, GST-Hl, 64TRP, serpins and voraxin) can induce immune responses against various tick species. In addition, in some cases it was possible to determine that the vaccine efficacy in rabbits was similar to experiments performed in natural hosts (e.g. Bm86, IrFER2, RmFER2, serpins and serine protease inhibitor). In conclusion, results have shown that prior to performing anti-tick vaccination trials using natural hosts, rabbits can be used as suitable experimental models for these studies

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

The objective of this study was to evaluate the glycemic index and the satiety response of three Mexican kinds of honey. The values of fructose ranged from 272.40-395.10 g/kg, while the glucose value ringed 232.20-355.50 g/kg. The ratio F/G of sample honey was 1.45, 1.00, and 1.17 for Highland, Multifloral, and Avocado honey, respectively. Twenty-six participants completed this study, which was previously approved by the ethics committee of the Facultad de Salud Pública y Nutrición (CE 2/2018-19). Highland and Avocado honey is classified as medium-GI (69.204.07 and 66.365.74, respectively), while Multifloral honey is classified as high-GI (74.245.98). The Highland honey presented the best satiety response. The difference in IG values and the effect of the satiety response of Highland honey could be explained by the different fractions of carbohydrates in samples and other components such as phytochemicals.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wildtype females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), by confocal immunofluorescence microscopy. The comparison between both insecticides’ revels that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AX in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AX in the germarium.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

Electricity generation from renewable energy sources is emerging as a result of global carbon emission reduction policies. However, most renewable energy sources are non-dispatchable and cannot be adjusted to meet the fluctuating electricity demands of society. A flexible operation process has been proposed as an effective solution to compensate for the unstable nature of renewable energy sources. Thermal load fluctuations during flexible operation may cause creep-fatigue damage to the high-temperature components of thermal power plants, as they are designed with a focus on creep damage under a constant power level. This study investigated the residual life of high-temperature components, such as a superheater tube and a reheater header, to failure under flexible operation conditions using finite element analysis and empirical models. First, we determine an analytical solution for the straightened superheater tube under thermal conditions and compare it with the numerical solution to verify the numerical models. Through the verified finite element model, the creep-fatigue life of the reheater header is estimated by considering flexible operation factors and employing the Coffin-Manson and Larson-Miller models. Although fatigue damage increases with decreasing minimum load and ramp rate, we confirmed that creep damage significantly affects the residual life during flexible operation. In addition, a surrogate model was proposed to evaluate the residual life of the reheater as a function of the flexible operation factors using the machine learning methodology, based on the results of finite element methods. It can be used to predict its residual life without performing complex thermal-structure analysis and relying on empirical models for fatigue and creep life. We expect our findings to contribute to the efficient operation of thermal power plants by optimizing the flexible operation factors.

Minute Virus of Mice (MVM) is an autonomous parvovirus of the Parvovirus family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 locallization to cellular DDR sites is independent of ATM or DNA-PK signaling, but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.

Background: Different investigations have shown an association between the eating behavior of children and adolescents, and their nutritional status. The objective is to identify eating behavior patterns associated with nutritional status diagnosed by anthropometry in a sample of Spanish schoolchildren. Methods: A cross-sectional study in 283 Spanish schoolchildren (6 to 16 years old). Methods: The sample was assessed anthropometrically by Body Mass Index (BMI), Waist-to height ratio (WHtR) and body fat percentage (%BF). Eating behavior was analyzed using the CEBQ "Children's Eating Behavior Questionnaire" answered by parents or guardians. Results: A positive association was found between excess weight, abdominal obesity, high adiposity, lower scores in anti-intake subscales and higher scores in pro-intake subscales. These were mainly associated with lower satiety response, higher food intake, higher food enjoyment, higher eating speed, and emotional overeating. Conclusion: Our results support the usefulness of the CEBQ as an easy-to-use tool to identify eating behaviors associated with the development of childhood and adolescent obesity. Its use in future research could help to understand behavioral phenotypes in schoolchildren and guide nutrition education and obesity prevention initiatives

Human trafficking is the third most lucrative form of trafficking in the world (just behind drugs and counterfeit goods). Multiple outbreaks of unrest between October 2016 and August 2017 in the Rakhine State of Myanmar triggered around 745,000 influxes of Rohingyas crossing into Bangladesh through the border boundaries at Teknaf and Ukhiya sub-districts of Cox’s Bazar. In this regard the media confirmed that over a thousand Rohingya people particularly women and girls were victims of human traffickers. This research aims to explore the underlying cause of human trafficking (HT) during emergency response and seeks how the knowledge and capacity of the refugee, local administration and law enforcement agencies in Bangladesh can be improved in promoting counter trafficking (CT) and safe migration processes. In order to achieve the objectives, this research starts with reviewing acts, rules, policies and action plans of the Government of Bangladesh on the HT, CT and safe migration processes. Then, a case study method has been applied to present ongoing the CT and safe migration programs of a NGO called Young Power in Social Action (YPSA) that received funding and technical support from the International Organization of Migration (IOM) for this purpose, the research in this paper will later evaluate the effectiveness of the program through conducting key informant interviews (KII) and focus group discussion (FGDs) with beneficiary and non-beneficiary participants from refugees, law-enforcing agencies (LEA) and non-governmental organizations’ (NGOs) in Teknaf, and Ukhyia sub-districts in Bangladesh. Thus, this research identified program level strengths and weaknesses in relation to the CT, and safe migration process and provide key directions how they can be improved.

When exposed to a viral infection, the attacked cells promptly set up defence mechanisms. Part of antiviral responses, the innate immune interferon pathway and associated interferon stimulated genes are notably allowing the production of proteins bearing an antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides and lipids. They then benefit from a reprogramming of the metabolism that favours glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following poly:IC stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.

Since the process of waste recycling generates dust and flammable gas during fragmentation, there is always a risk of fire resulting therefrom, and fire does, in fact, frequently occur. However, research on disaster management at recycling facilities deals only with the problem of processing systems from a technical point of view, but it does not suggest concrete alternatives from a management point of view. Therefore, in this study, we analyzed the influence of the disaster response network of a waste recycling center at the organizational level based on the concept of the cognitive accuracy of a network when considering administrative aspects. Through this analysis, we confirmed that factors affecting the influence of the network exist, such that the entire network and the networks of different levels of position are different. We suggest that this can be improved by deploying members who perform formal tasks at the center of the network so that everyone can agree political approach.

Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp to Staphylococcus sp as the primary organism of interest. This has significant consequences given the virulence of Staphylococcus and its propensity to form a biofilm, rendering non-surgical therapy ineffective. In addition, antibiotic resistance has affected treatment of this organism. The cohorts at most risk for Staphylococcal endocarditis are the elderly patients with multiple comorbidities. The innovation of transcatheter technologies alongside other cardiac interventions such as implantable devices have contributed to the increased risk attributable to this cohort. We examine the role of the heart team for diagnosis and treatment of this condition. In addition, we examine the determinants of virulence of Staphylococcus aureus, the interaction with hosts immunity and the discovery and emergence of a potential vaccine. We also examine the potential role of prophylactic antibiotics during dental procedures. With increasing rates of transcatheter device implantations, there is a projected increment of endocarditis especially in this high-risk group. A high index of suspicion is needed alongside early initiation of therapy and referral to the heart time to improve outcomes.

Background: In long-term care facilities, there are many residents who do not have the ability to seek shelter by themselves in the case of an emergency. Thus, it is extremely important that the staff of nursing homes are equipped with correct disaster prevention concepts, emergency survival responses, and hazard mitigation measures. Purpose: Discuss the intervention effectiveness of different fire prevention and emergency response trainings at nursing homes and the relationship and predictivity of awareness to self-efficacy. Method: Recruit staff from two nursing homes through purposive sampling, using a two-team pre-and post-test design to collect results from 41 individuals in the experiment group and 40 individuals in the control group. The research tool is the “Nursing Home Fire Prevention and Emergency Response Awareness and Self-Efficacy Scale,” to compare the effectiveness of advanced and general fire safety trainings. Result: After receiving improved advanced fire safety training, the total score and the result of the experiment group on fire prevention and emergency response awareness and self-efficacy had both performed better than the control group who received general fire safety training (p < .001); fire prevention and emergency response awareness has significant and positive correlation with self-efficacy (r=.601, p < .001), and awareness is a significant predictor variable to self-efficacy (p < .001). Conclusion/Practical Application: This study finds that the key to improving learning effectiveness includes adding fire science concept chapter when creating fire safety training material in order to strengthen basic awareness; fire safety training should comprehensively introduce all related duty responsibilities of staff fire defense formation, in turn enabling mutual responsive support for the needs of the site; also, to become familiarized with the knowledge requires appropriate frequency of training and enhancing the staff’s awareness to fire prevention and emergency response, which is the most important key of learning effectiveness.

Based on the textured controllable interface effect, the dynamic performances of the textured and ordinary pilot valve are analyzed experimentally, and the influence of the textured controllable interface on the response of pilot valve is studied. Results show that when Pin is small, the textured surface shortens the reciprocating time of valve core, increasing the flow rate, and speeds up the piston stroke of oil cylinder. The valve core actions much more stable and sensitivity. Meanwhile, combined with the theoretical calculation, the operation mechanism of texturing the pilot valve is analyzed. It is concluded that the stress of textured valve core sealing surface is greater than that of ordinary one, and the pressure difference gradually decreases with the increase of Pin, and the flow difference is basically the same as the force on the sealing surface. This indicates that the textured surface improves lubrication characteristics, reduces the friction between components. The textured valve makes the velocity changes gently, and enhances the responsiveness and stability of the valve. Those related results provide a new idea for enhancing the response design of the pilot valve.

Here we draw insights from the latest serendipitous findings made on the opposing roles of a validated drug-target protein Keap1. We weigh up how natural reactive electrophiles and electrophilic small-molecule drugs in clinical use directly impinge on seemingly conflicting, yet both Keap1-electrophile-modification-dependent, cell-survival- vs. cell-death-promoting behaviors. In the process, we convey how understanding reactive chemical-signal regulation at a single-protein-specific level is an enabling necessity in deconstructing otherwise intricate reactive-small-molecule-responsive cellular pathways. We hope this opinion piece further spurs the broader interests of basic and pharmaceutical research communities toward better understanding of molecular mechanisms underpinning reactive small-molecule-regulated signaling subsystems.

Featured Application: Bio-electronic devices take advantages of some specific duties of biological matter. The specific ability of some proteins to use sunlight is considered for the realization of photo-electronic devices . Here the focus is on the role of the pH, whose variations seem to affect the protein conductance

Emergency Management has not developed in a cohesive or comprehensive manner. Differing terms are used to name identical concepts. A standard comprehensive doctrine for the important development of emergency management is needed. In this paper I explain a doctrinal framework for emergency management. The paper states a clear identification of the five dimensions, and each of their components, necessary to the informed practice of Emergency Management. Although emergencies vary in cause and severity, the process of Emergency Management necessary for optimal handling of these emergencies varies little. The “All Hazards Approach” to emergency management establishes and reinforces commonality in processes, procedures, planning templates and organizational structure. The three types of agencies associated with emergency management activities are discussed, including the subject matter agency, coordinating agency, and supporting agency. The four critical functions of emergency management are detailed, and include mitigation, preparedness, response, and recovery, often all carried out concurrently. The ten activities, and seven resources of emergency management are highlighted. There are many ways to represent the integration of these five dimensions, to ensure completeness, while ensuring clarity; the two most common are described. When experts in Emergency Management follow the doctrine, they can coordinate all those involved to be sure that all aspects of any hazard are considered, and that all organizations/agencies, functions, activities, and resources of Emergency Management are coordinated and optimally active. Following this process is the only way to ensure the best outcomes from any emergency.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

The Tsunami disaster was the first and the biggest in Banten Province. However, in response to the health crisis, the preparedness was still lacking, even though in an emergency response situation, the management of disaster management carried out was quite good. The method of research is based on data reports that include quantitative and qualitative methods. Analyzing health facilities and the impacts that occurred in the field during the tsunami period is the basis for this article and, at the same time, a discussion of describing problems that can be anticipated in the future.

Seroprevalence studies suggest that the number of PCR-confirmed COVID-19 cases is significantly smaller than the true number of infections. I study logintidual seroprevalence data from 7 sites across the US, from early April 2020 to June 27. I show that not only COVID-19 seroprevalence does not seem to increase over time, there is no clear association between the number of cases reported during a period and the change in seroprevalence during the same time. I conclude that as they are, seroprevalence studies can only be used in the qualitative sense and distinguish between populations with no COVID-19 exposure, to those populations where the virus had already started spreading.

SARS-CoV-2 is a novel coronavirus that is the causative agent of Coronavirus infectious disease 2019 (COVD-19). As of the 17^th April 2020, it has infected 2 114 269 people resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

Boiler efficiency is called to some extent of total thermal energy which can be recovered from the fuel. Boiler efficiency losses are due to four major factors: the dry gas flux, the latent heat of steam in the flue gas, the combustion loss or the loss of unburned fuel, radiation and convection losses. In this research, the thermal behavior of boilers in gas refinery facilities is studied and their efficiency and their losses are calculated. The main part of this research is comprised of analyzing the effect of various parameters on efficiency such as excess air, fuel moisture, air humidity, fuel and air temperature, the temperature of combustion gases, and thermal value of the fuel. Based on the obtained results, it is possible to analyze and make recommendations for optimizing boilers in the gas refinery complex using response-surface method (RSM).

This study examines the matrix metalloproteinase (MMP) activity in the healing of liver injuries treated with biological adhesives Tachosil^® and GelitaSpon^® and the elastic cyanoacrylate Adhflex^®. Hepatic lesions were induced in male rats using a Stiefel biopsy punch. Healing was assessed 2, 6, and 18 days after injury by quantifying tissue levels of MMP1, 2, 8, 9, and 13. Histopathological repair was evaluated using hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and immunohistochemical markers CD31 and CD68. The sealants contributed to complete healing. Histopathology and MMP findings indicate that Adhflex^® has slower degradation and a strong inflammatory reaction at the onset of healing. Early on, all MMPs showed higher levels in Adhflex^® and Tachosil^®-treated animals, and MMP2 and MMP9 expressions were significantly higher in the Adhflex-treated group at 18 days post-injury (T3). The Adhflex^® group had significantly higher MMP8 and MPP13 levels than other treated groups and showed a sustained overexpression of all MMPs, even in the latest healing stages. Notably, the overexpression did not negatively influence the histological healing process. All hepatic trauma injuries should be treated as emergencies, and any easy-to-use and rapid sealant like Adhflex^® could be considered as an option for treating liver trauma.

Novel multifunctional fluorescent chemosensors composed of electrospun (ES) nanofibers with high sensitivity toward pH, mercury ions (Hg²⁺), and temperature were prepared from poly(N-Isopropylacrylamide-co-N-methylolacrylamide-co-rhodamine derivative) (poly(NIPAAm-co-NMA-co-RhBN2AM)) by employing electrospinning process. NIPAAm and NMA moieties provide hydrophilic and thermo-responsive properties (absorption of Hg²⁺ in aqueous solutions), and chemical cross-linking sites (stabilization of the fibrous structure in aqueous solutions), respectively. The fluorescent probe, RhBN2AM is highly sensitive toward pH and Hg²⁺. Synthesis of poly(NIPAAm-co-NMA-co-RhBN2AM) with different compositions were carried on via free-radical polymerization. ES nanofibers prepared from sensory copolymers with a 71.1:28.4:0.5 NIPAAm: NMA: RhBN2AM ratio (P3 ES nanofibers) exhibited significant color change from nonfluorescent to red fluorescence while sensing pH or Hg²⁺, and high reversibility of on/off switchable fluorescence emission when Hg²⁺ and ethylenediaminetetraacetic acid (EDTA) were sequentially added. The P3 ES nanofibrous membranes had a higher surface-to-volume ratio to enhance their performance than did the corresponding thin films. In addition, the fluorescence emission of P3 ES nanofibrous membranes exhibited second enhancement above the lower critical solution temperature. Thus, the ES nanofibrous membranes prepared from P3 with on/off switchable capacity and thermo-responsive characteristics can be used as multifunctional sensory devise for specific heavy transition metal (HTM) in aqueous solutions.

This paper presents performed Ansys numerical simulation on WindFloat structures. It contributes to the methodology of calculation based on CFD instruments to study the movements of the waves on semi-submersible stationary structures and highlights the importance of using RAO functions. RAO numerical approach developed can be applied to design semisubmersible WindFloat structures in order to fulfill essential requirements regarding operational safety and design. Numerical methodology was designed in accordance marine loads and the I.T.T.C. recommendations. The numerical RAO results for regular wave movements include many elements for the semi-submergible structure. Close results to open sea operation can be achieved by constant improvement in numerical simulation methodologies. The work opens the way for further hydrodynamic development on irregular waves for realistic hydrodynamic and structural response of the actual semi-submersibles at sea. The results demonstrate the accuracy of RAO function approach for specific WindFloat in Jonswap spectrum.

Background: Recent infectious disease outbreaks have brought increased attention to strengthening the capacity to prevent, detect, and respond to natural biological threats. However, deliberate biological events also represent a significant global threat that have received relatively little attention. The Biological Weapons Convention provides a foundation for the response to deliberate biological events, but the political mechanisms to respond to and recover from such an event are poorly defined. Methods: We performed an analysis of the epidemiological timeline, the international policies triggered as a notional deliberate biological event unfolds, and the corresponding stakeholders and mandates assigned by each mandate. Findings: The results of this analysis identify a significant gap in both policy and stakeholder mandates: there is no single policy nor stakeholder mandate for leading and coordinating the response activities associated with a deliberate biological event. These results were visualized using an open source web-based tool published at https://dbe.talusanalytics.com. Interpretation: While there are organizations and stakeholders responsible for roles in leading security or public health response, these roles are non-overlapping and are led by organizations not with limited interaction outside such events. The lack of mandates highlights a gap in the mechanisms available to coordinate response and a gap in guidance for managing the response. The results of the analysis corroborate anecdotal evidence from stakeholder meetings and highlight a critical need and gap in deliberate biological response policy.

LncRNA are involved in multiple regulatory pathways, its versatile mode of action has disclosed a new layer in gene regulation. They are reportedly modulated during plant development, with specific tissue functions and in response to stresses. In this study, we analyzed LncRNA from leave samples collected from the legume Copaifera langsdorffii (copaiba) from two divergent ecosystems: Cerrado (CER) and Atlantic Rain Forest (ARF). We identified 8020 novel lncRNAs, from which 2893 transcripts were regulated above 2-fold and 566 above 5-folds in either condition. This putative lncRNA set was compared with seven Fabaceae genomes, of which 1747 and 1879 transcripts (from ARF and CER, respectively) aligned to at least two genomes. Further, 2194 copaiba lncRNAs were successfully mapped to at least one of six Fabaceae transcriptomes. The secondary structures of the lncRNAs that were conserved and differentially expressed between the populations were predicted using in silico methods. Our results indicate the potential involvement of lncRNAs in the adaptation of C. langsdorffii to two different biomes.

. Sealants and adhesives are used in the repair and preservation of damaged solid organs. This study examines the matrix metalloproteinases (MMP) activity in the healing of liver injuries treated with two biological adhesives (Tachosil® and GelitaSpon®) as well as that of a new elastic cyanoacrylate (Adhflex®). Methods. We induced in 90 male rats hepatic lesions using a Stiefel biopsy punch in the liver. Wound healing was assessed 2, 6, and 18 days after injury by quantifying MMP1, 2, 8, 9, and 13 tissue levels. The histopathological repair was evaluated by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and CD31, CD68 immunohistochemical marker. The three sealants used contributed to the complete healing of hepatic lesions. Both histopathology and MMP findings point to the fact that degradation with Adhflex® is slower and causes a strong inflammatory reaction at the onset of healing. Results. All the MMPs measured showed higher values early in the healing process in animals treated with Adhflex® and Tachosil, expression for MMP2 and MMP9 being significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant greater values of MMP8 and MPP13 than the Adhflex group. Animals treated with Adhflex® showed a sustained overexpression in all MMPs even at the latest wound healing stages. Conclusion. Notably, the overexpression of the MMPs did not negatively influence the histological healing process of liver injuries. Since all hepatic trauma injuries should be treated as emergencies, any easy-to-use and rapid sealant, like Adhflex®, could be considered an adequate treatment option.

Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.

With the rapid development of wind power generations, the inertial response of wind turbines (WTs) are widely concerned recently, which is important for grid frequency dynamic and stability. This paper recognizes and understands the inertial response of type-3 and type-4 WTs from the view of equivalent internal voltage, in analogy with typical synchronous generators (SGs). Due to the dynamic of the equivalent inertial voltage different from SGs, the electromechanical inertia of WTs is completely hidden. The rapid power control loop and synchronization control loop is the main reasons that the WT's inertial response is disenabled. On the basis of the equivalent internal voltage's dynamic, the existing inertia control method for WTs are reviewed and summarized as three approaches from the view of WT's control, i.e. optimizing the power control or synchronization control or both. At last, the main challenges and issues of these inertia controls are attempted to explain and address.

A steel damper column is an energy-dissipating member that is suitable for reinforced concrete (RC) buildings and multistory housing. To assess the seismic performance of buildings with steel damper columns, the peak displacement of the whole building and the energy dissipation demand of the dampers must be evaluated. This article proposes an energy-based prediction procedure for the peak and cumulative response of an RC frame building with steel damper columns. The proposed procedure considers two energy-related seismic intensity parameters, namely the maximum momentary input energy and the total input energy. The peak displacement is predicted considering the energy balance during a half cycle of the structural response, using the maximum momentary input energy. The energy dissipation demand of the dampers is then predicted considering the energy balance during a whole response cycle using the total input energy. The local responses (e.g., peak drift, maximum plastic rotation of beams, maximum shear strain, and energy dissipation demand of dampers) are predicted using pushover analysis. Numerical analysis results for 8- and 16-story RC buildings show that the proposed prediction method achieves satisfactory accuracy.

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the OXPHOS system for ATP production. It requires, in addition, the import of thousands of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPR^mt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial PHB (prohibitin) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

Deep neural networks (DNNs) have gained prominence in addressing regression problems, offering versatile architectural designs that cater to various applications. In the field of earthquake engineering, seismic response prediction is a critical area of study. Simplified models such as single-degree-of-freedom (SDOF) and multi-degree-of-freedom (MDOF) systems have traditionally provided valuable insights into structural behavior, known for their computational efficiency facilitating faster simulations. However, these models have notable limitations in capturing the nuanced nonlinear behavior of structures and the spatial variability of ground motions. This study focuses on leveraging ambient vibration (AV) measurements of buildings, combined with earthquake (EQ) time-history data, to create a predictive model using a neural network (NN) in image format. The primary objective is to predict a specific building's earthquake response accurately. The training dataset consists of 1,197 MDOF 2D shear models, generating a total of 32,319 training samples. To evaluate the performance of the proposed model, termed MLPER (Machine Learning based Prediction of building structures' Earthquake Response), several metrics are employed. These include mean absolute percentage error (MAPE) and mean deviation angle (MDA) for comparisons in the time domain. Additionally, we assess magnitude-squared coherence values and phase differences (Δφ) for comparisons in the frequency domain. This study underscores the potential of MLPER as a reliable tool for predicting building earthquake response, addressing the limitations of simplified models. By integrating AV measurements and EQ time-history data into a neural network framework, MLPER offers a promising avenue for enhancing our understanding of structural behavior during seismic events, ultimately contributing to improved earthquake resilience in building design and engineering.

(1) Background: CTA has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation and plays a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution; (2) Methods: Our prospective observational study included 52 patients (mean age 60.43) with typical chest pain, a low-to-intermediate likelihood of CAD, and documented atheromatous plaque through CCT. We utilized advanced features of the CaRi-Heart® and syngo.via Frontier® systems to assess coronary plaques and changes in PCAT attenuation; (3) Results: Changes in plaque morphology were investigated, revealing significant alterations. Notably, in mixed plaques, calcified portions increased (p &lt; 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: LAD (p = 0.0142), LCX (p = 0.0513), and RCA (p = 0.1249). The CaRi-Heart® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p &lt; 0.0001, r = 0.3032) and lipid-rich plaque volume (p &lt; 0.0001, r = 0.3281); (4) Conclusions: Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression.

A new approach to the treatment of wound lesions, which are complicated by the presence of polyresistant microflora and a possible immunodeficiency background has been proposed. It involves treating the wound surface with high-intensity pulsed optical radiation of a continuous spectrum, continuously covering the entire UV range (from 200 to 400 nm), visible and near infrared region of the spectrum. A pulsed xenon lamp is used as a radiation source. A description of the design and technical characteristics of the developed device for high-intensity optical irradiation "Zarnitsa-A", which implements the proposed medical technology for wound therapy, is represented. The results of preclinical studies of the apparatus in vitro and in vivo are represented hereinafter. The article shows that the apparatus exposure has pronounced bactericidal and wound-healing properties. The apparatus action reliably provides higher rates of wound healing compared to the use of only a typical antibacterial and wound healing agent – “Levomekol” ointment.