The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

In this paper, we propose an imagined speech-based brain wave pattern recognition using deep learning. Multiple features were extracted concurrently from eight-channel Electroencephalography (EEG) signals. To obtain classifiable EEG data with fewer number of sensors, we placed the EEG sensors on carefully selected spots on the scalp. To decrease the dimensions and complexity of the EEG dataset and to avoid overfitting during the deep learning algorithm, we utilized the wavelet scattering transformation. A low-cost 8-channel EEG headset was used with MATLAB 2023a to acquire the EEG data. The Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) was used to decode the identified EEG signals into four audio commands: Up, Down, Left, and Right. Wavelet scattering transformation was applied to extract the most stable features by passing the EEG dataset through a series of filtration processes. Filtration has been implemented for each individual command in the EEG datasets. The proposed imagined speech-based brain wave pattern recognition approach achieved a 92.50% overall classification accuracy. This accuracy is promising for designing a trustworthy imagined speech-based Brain-Computer Interface (BCI) future real-time systems. For better evaluation of the classification performance, other metrics were considered, and we obtained 92.74%, 92.50% and 92.62% for precision, recall, and F1-score, respectively.

Cancer patients and their family caregivers experience various losses when patients become terminally ill, yet little is known about the grief experienced by patients and caregivers and factors that influence grief as patients approach death. Additionally, few, if any, studies have explored associations between advance care planning (ACP) and grief resolution among cancer patients and caregivers. To fill this knowledge gap, the current study examined changes in grief over time in patients and their family caregivers and whether changes in patient grief are associated with changes in caregiver grief. We also sought to determine how grief changed following completion of advance directives. The sample included advanced cancer patients and caregivers (n=98 dyads) from Coping with Cancer III, a federally funded, multi-site prospective longitudinal study of end-stage cancer care. Participants were interviewed at baseline and at follow-up roughly 2 months later. Results suggest synchrony, whereby changes in patient grief were associated with changes in caregiver grief. We also found that patients who completed a living will (LW) experienced increases in grief, while caregivers of patients who completed a do-not-resuscitate (DNR) order experienced reductions in grief, suggesting that ACP may prompt “grief work” in patients while promoting grief resolution in caregivers.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

This paper proposes a Mixed Integer Conic Programming (MICP) model for community microgrids considering the network operational constraints and building thermal dynamics. The proposed multi-objective optimization model optimizes not only the operating cost, including fuel cost, purchasing cost, battery degradation cost, voluntary load shedding cost and the cost associated with customer discomfort due to room temperature deviation from the set point, but also several performance indices, including voltage deviation, network power loss and power factor at the Point of Common Coupling (PCC). In particular, the detailed thermal dynamic model of buildings is integrated into the distribution optimal power flow (D-OPF) model for the optimal operation. The heating, ventilation and air-conditioning (HVAC) systems can be scheduled intelligently to reduce the electricity cost while maintaining the indoor temperature in the comfort range set by customers. Numerical simulation results show the effectiveness of the proposed model and significant savings in electricity cost with network operational constraints satisfied.

Aims: Anxiety, major depressive disorder and accelerated cognitive decline frequently complicate traumatic brain injury. Obesity and type 2 diabetes mellitus drive peripheral inflammation which can accelerate traumatic brain injury-associated neurodegeneration. The Zucker rat harbors G-protein coupled receptor agonist IgG autoantibodies and in vitro neurotoxicity caused by these autoantibodies was prevented by a novel synthetic fragment of the serotonin 2A receptor. The aim of the present study was to test whether genetic obesity manifested in Zucker diabetic fatty rat is associated with anxiety, depression and spatial memory impairment induced by mild traumatic brain injury. Furthermore, we investigated whether these neurobehavioral or neurodegenerative complications can be lessened by administration of a novel putative neuroprotective peptide. Methods: Age-matched lean and fatty diabetic Zucker rats were tested in the sucrose preference test (anhedonia), open field test in bright light (anxiety measure) and the Morris water maze (spatial memory) prior to receiving a sham-injury or lateral fluid percussion (LFP) mild traumatic brain injury. Behavioral testing was repeated at 1-week, 1-month, and 3-month intervals following injury. A synthetic peptide consisting of a portion of the 5- hydroxytryptamine (serotonin) 2A receptor (2 mg/kg) (or vehicle) was administered via intraperitoneal route every other day for 7 days after sham or LFP injury to lean rats or 7 days before and after sham or LFP injury to fatty rats. Results: Sucrose preference decreased transiently (one week after mild traumatic brain injury) in Zucker lean rats indicative of anhedonia. Baseline anxiety-like behavior (bright light, open field test) was lower in fatty vs. lean Zucker rats, and anxiety behavior increased significantly in fatty rats but not lean rats following mild traumatic brain injury. Mild traumatic brain injury impaired recall of spatial memory in fatty and lean rats, and the effect was longer-lasting in fatty rats. A synthetic peptide fragment of the 5-hydroxytryptamine 2A receptor enhanced recall of spatial learning one-week after sham injury in Zucker rats and it may have prevented ‘anhedonia’ one-week after TBI (LFP) in a subset of Zucker fatty and lean rats expressing near-normal baseline sucrose preference. Mean plasma 5-hydroxytryptamine 2A receptor autoantibody level (determined 2 weeks after injury) was 2.5-fold higher than background, but did not differ significantly in (sham- vs TBI) Zucker lean rats. Conclusions: These are the first data to suggest reduced baseline anxiety-like behavior in Zucker fatty (vs. lean) rats. The pronounced increases in anxiety , and spatial memory impairment experienced by Zucker fatty (vs lean) rats following mild traumatic brain injury may have accounted in part for absence of a 5-hydroxytryptamine 2A receptor peptide neuroprotective effect in brain- injured Zucker fatty rats.

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

Background/Purpose: Over the last two decades, malaria has remained a major worldwide public health concern, especially in the developing countries leading to high morbidity and mortality among children. Nigeria is the world most burdened malaria endemic nation, contributing more than a quarter of global malaria cases. This study determined the prevalence of malaria among children 6-59 months in Nigeria, and the effects of individual and contextual factors. Methods: The study utilized data from 2018 Nigeria Demographic and Health Survey (NDHS) involving a weighted sample size of 10,185 children who were tested for malaria using rapid diagnostic test (RDT). Given the hierarchical structure of the data set, such that children at level-1 are nested in community at level-2, and nested in states and Federal Capital Territory (FCT) at level-3, multilevel mixed effect logistic regression models were used for the analysis. Results: The proportion of children 6-59 months of age in Nigeria that had malaria fever positive as assessed by RDTs was 35.5% (3,418/10185), (CI: 33.9-37.1). Kebbi State had the highest proportion of children 6-59 months who were malaria positive, 77.6%, (CI: 70.2-83.5), followed by Katsina State, 55.5%, (CI: 47.7-63.1). The Federal Capital Territory (FCT), Abuja had the proportion of 29.6%, (CI: 21.6-39.0), malaria positive children of 6-59 months of age. Children between the age of 48 and 59 months were 2.68 times more likely to have malaria fever than children 6-11 months of age (AOR=2.68, 95% CI: 2.03-3.54). Also, children from the rural area (AOR= 2.12, 95% CI: 1.75-2.57), were more likely to suffer from malaria infection compare with children from urban area. Conclusion: The study identified some individual and contextual predictors of malaria among children in Nigeria. These factors are areas that need to be considered for policy designs and implementations toward control and total elimination of malaria-related morbidity and mortality among children in Nigeria.

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

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Chronic pain is a serious health concern and potentially debilitating condition, leading to anxiety, depression, reduced productivity and functionality, and poor quality of life. This condition can be even more detrimental and incapacitating in the pediatric patient population. In low and middle income countries (LMICs), pain services are inadequate or unavailable, leaving most of the world's pediatric population with chronic pain untreated. Many of these children in LMICs are suffering without treatment, and often die in pain. Awareness and advocacy for this population must be prioritized. We reviewed the available literature on the chronic pediatric pain burden in LMICs, barriers to treatments, and current efforts to treat these patients.

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

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

The formation and propagation of cracks occurs through irreversible dislocation movements at notches, material defects and grain boundaries. Since this process is partly thermally controlled, the resistance to dislocation movements at low temperatures increases. This slows both fatigue initiation and fatigue crack propagation. From recent experimental data, it can be seen that fatigue crack growth is accelerated below the fatigue transition temperature (FTT) that correlates with the ductile-brittle transition temperature (DBTT) found by well-known fracture mechanics tests, i.e., Charpy impact, fracture toughness, and CTOD. Hence, this study investigates the relation between FTT and DBTT in S500 high-strength steel base material and welded joints at low temperatures using fatigue crack growth, fracture toughness tests as well as scanning electron microscopy. From the tests, an almost constant decrease in fatigue crack propagation rate is determined with decreasing test temperature even below the DBTT.

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Background: Only few studies have studied the link between risk perception and sleep in the context of the COVID-19 pandemic. This study investigates the effect of two distinct risk appraisals—risk perception and perception of collective coordinated defense (PCCD) on Chinese adults’ sleep quality during the COVID-19 pandemic, and tested COVID-19-related fear and rumination as potential mediators of the relationships. Methods: Data were collected using a self-report online questionnaire from a sample of 224 Chinese adults during the fourth wave of the COVID-19 pandemic in Hong Kong. Results: COVID-19 risk perception and PCCD were related to poor sleep quality. Mediation analysis showed that both fear and rumination mediated the relationship between risk perception and sleep quality, whereas only fear mediated the relationship between PCCD and sleep quality. The model showed an excellent fit to the data and accounted for 44% of the variance in sleep quality in Chinese adults. Conclusions: This study demonstrates the distinct perceptual processes—risk appraisals in particular—contributed to poor sleep quality in Chinese adults during the COVID-19 public emergencies. These findings would be helpful for policy makers to address the sleep problems induced by psychological consequences of the pandemic.

Many lifestyle and occupational habits negatively impact on physical and mental health, increasing the risk of cardiovascular and other diseases. While larger institutions fulfill occupational health requirements to ensure their employees’ wellbeing at work, smaller business workers and entrepreneurs may neglect initial signs of stress or physical decline, putting themselves at increased risk. Early detection of compromised cardiopulmonary health or fitness has the potential to flag up indications for early interventions and reduce the risk of disease onset and progression. This case study highlights the usefulness of respiratory muscle training (RMT) in improving pulmonary and cardiovascular parameters as an early countermeasure to cardiopulmonary decline. We suggest RMT as an easily accessible, cost- and time effective opportunity to support a healthy lifestyle.

The aim of this study was to evaluate the Hapo ms, a passive upper limbs exoskeleton developed to assist workers for tasks with arms in front of the body. Twelve participants had to perform a static task, a manual handling task and a load carrying task two times: with and without the exoskeleton. In all cases subjective (perceived effort in arm and back areas, comfort) and objective (muscular activity, postural balance) criteria were evaluated. Results have shown a decrease in anterior deltoid (-12 to -18% depending of the task) and in biceps brachii (-19% to -33% depending of the task) muscular activity. No significant difference was pointed out in back muscle and postural balance was not significantly perturbed due to the wear of the exoskeleton. Finally, perceived effort reduction was observed during the three tasks (except in back area for task 1). To conclude, the Hapo ms seems well adapted to assist upper arms during tasks with arms in front of the body.

Background/Purpose: In recent times, Sub-Sahara Africa (SSA) had been rated by the World Health Organization, (WHO), as the most malaria endemic region in the world. Evidence synthesis of the risk factors associated with malaria among children aged under-five in SSA is urgently needed. This would help to inform decisions that policy makers and executors in the region need to make for the effective distribution of scare palliative resources to curb the spread of the illness. This scoping review is aimed to identify studies that have used multivariate classical regression analysis to determine risk factors associated with malaria among children under-five years old in SSA. Methods/Design: The search terms followed PICOTS, (Population, Intervention, Comparator, Outcome, Timing, Setting), and were used in searching through the following databases: PubMed, MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and MeasureDHS. The databases were searched for published articles from January 1990 to December 2020. Results: Among the 1154 studies identified, only thirteen (13) studies met the study’s inclusion/exclusion criteria. Narrative syntheses were performed on the selected papers to synchronise the various risk factors identified. Factors ranging from child-related, (age, birth order and use of bed net), parental/household-related, (maternal age and education status, household wealth index) and community-related variables, (community wealth status, free bed net distribution), were some of the identified significant risk factors. Conclusion: It is timely to have a synthesis of risk factors that influence the malaria status of children under-five in SSA. The outcome of the review will increase the knowledge of the epidemiology of morbidity that will form the basis for designing efficient and cost-effective distribution of palliatives and controls of malaria in SSA.

Alloy 800H stands as one of the few code qualified materials for fabricating in core and out of core components operating in high temperature reactors (HTRs). Welding is a common practice for assembling these components, however, the election of a suitable filler material is essential to enhance the high-temperature creep resistance of Alloy 800H weldments in high temperature applications. In this study, Inconel 625 and Haynes 230 filler material were used to weld the Alloy 800H plates employing the Gas Tungsten Arc Welding (GTAW) technique. The high temperature tensile, creep rupture property, microstructural stability and evolution of the weldments after high temperature exposure were investigated and compared with Alloy 800H. The results showed that the both weldments exhibited enhanced tensile and creep behavior at 760 oC. The creep rupture time of the weldments with Inconel 625 filler and Haynes 230 filler materials was about two and three time longer than that of Alloy 800H base metal when tested at 80 MPa and 760 oC, respectively. Carbides (MC and M23C6) were commonly observed in the microstructure of both the weld and base metals in the two weldments after high temperature creep tests. However, the Inconel 625 filler weldment displayed detrimental δ and Laves phase in the fusion zone and these precipitates could be potential sites for initiating cracks following prolonged high temperature exposure. The study showed that the weldment with Haynes 230 exhibited better phase stability and creep rupture property than the one with Inconel 625 filler material, suggesting its potential as a candidate filler material for Alloy 800H for further investigation. The finding also emphasizes the critical consideration of microstructural evolutions and phase stability in evaluating high temperature materials and their weldments in high temperature reactor applications.

Brain-Computer Interface (BCI) systems can assist physically challenged people to interact with their surroundings and improve the quality of their lives. Decoding human thoughts is a powerful technique that can assist paralyzed people who have lost their speech production ability. Speaking is a combined process involving synchronizing the brain and the oral articulators. This paper proposed a high-accuracy brain wave pattern recognition based on inner speech using a novel feature extraction method. Only eight EEG electrodes were used in this study, and they were set on selected spots on the scalp. Support Vector Machine (SVM) was employed to decode the recorded EEG dataset into four internally spoken words which are: Up, Down, Left, and Right. The proposed approach achieved overall classification accuracy that ranges between 96.20% to 97.5%. In addition, more performance evaluation metrics were estimated to test the reliability of classifying the EEG-based inner speech data, and we obtained 97.61%, 97.50%, and 97.73% for F1-score, recall, and precision respectively. Furthermore, the Area Under Curve of the Receiver Operating Characteristic (AUC-ROC) proved the strength of the proposed approach for classifying the specified inner speech commands by achieving a macro-average amount of 99.32%. The inner speech classification method using electroencephalography proposed in this work can clinically help improve communication for patients with problems including speech disorder, mutism, cognitive development, executive function, and psychopathology.

We find that the standard relative entropy and the Umegaki entropy are designed for the purpose of inferentially updating probability and density matrices respectively. From the same set of inferentially guided design criteria, both of the previously stated entropies are derived in parallel. This formulates a quantum maximum entropy method for the purpose of inferring density matrices in the absence of complete information.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

: Extra- and intra-cellular activity occurs under the direction of numerous inter-molecular interactions, and in any tissue or cell, molecules are densely packed, thus promoting those molecular interactions. Galectins and chemokines, the focus of this review, are small, protein effector molecules that mediate various cellular functions, in particular cell adhesion and migration, as well as cell signaling/activation. In the past, researchers have reported that combinations of these (and other) effector molecules act separately, yet sometimes in concert, but nevertheless physically apart and via their individual cell receptors. This view that each effector molecule functions independently of the other limits our thinking about functional versatility and cooperation, and, in turn, ignores the prospect of physiologically important inter-molecular interactions, especially when both molecules are present or co-expressed in the same cellular environment. This review is focused on such protein-protein interactions with chemokines and galectins, their homo- and hetero-oligomeric structures that they can form, and the functional consequences of those paired interactions.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel Salmonella typhimurium (ST) vector expressing the bacterial collagenase Streptomyces omiyaensis trypsin (SOT), a serine protease known to hydrolyze collagens I and IV, which are predominantly found in PDAC. Utilizing aggressive models of PDAC, we show that ST-SOT selectively degrades intratumoral collagen leading to enhancement of immune checkpoint blockade (ICB) therapy in tumor-bearing mice. Ultimately, we found that ST-SOT treatment significantly modifies the intratumoral immune landscape to generate a microenvironment more conducive to ICB.

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Two new zoanthamine alkaloids, namely 3-acetoxynorzoanthamine (1) and 3-acetoxyzoanthamine (2), have been isolated from the zoantharian Zoanthus cf. pulchellus collected off the coast of the Peninsula of Santa Elena – Ecuador, together with three known alkaloids zoanthamine, norzoanthamine and 3-hydroxynorzoanthamine. The chemical structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR data and comparison with literature data. This is the first report of zoanthamine-type alkaloids from Zoanthus cf. pulchellus collected in the Tropical Eastern Pacific. The neuroinflammatory activity of all the isolated compounds were evaluated in microglia BV-2 cells and high inhibitory effects were observed in ROS and NO generation.

Human-Computer Interaction, including technology-aided instruction, is beginning to focus on virtual reality (VR) technology due to its ability to support immersive learning, teaching through simulation, and gamification of learning. These systems can deliver high-level multisensory learning experiences that are important in the teaching of many subjects, especially those involving abstract concepts or requiring spatial skills, such as organic chemistry. Haptic experiences with VR, however, remain a challenge. In addition, development have focused on general entertainment/gaming; VR systems in chemistry implement simulations of the chemistry laboratory and other advanced systems whereas those that support safe, game-like, immersive and multisensory learning of organic chemistry with haptics at pre-university education levels are scarce. We developed the VR Multisensory Classroom (VRMC) as an immersive learning environment within a VR head-mounted display, where learners employ hand movements to build hydrocarbon molecules and experience haptic feedback through gloves with built-in sensors and hand-tracking with the Leap Motion system. We report here the evaluation of the first prototype by learners from diverse backgrounds who reported on the ability of the VRMC to support high engagement, motivation, interest and organic chemistry learning as well as diverse learning styles. The VRMC is a novel VR classroom that supports immersive learning in molecular organic chemistry with haptics for multisensory learning.

This paper defines the two main causes of global warming in the UK and seeks to cut climate change using green hydrogen made from renewable electricity sources. Combustion vehicles powered by fossil gasoline and diesel emit a third of UK climate-warming CO2 while buildings heated by natural gas provide a quarter. First, current UK grid problems are defined: Electricity grid, gas grid and petroleum grid. Then experiments on the private energy community of Keele University allow electrolysis demonstrations producing green hydrogen for buildings and vehicle refueling. Next, the model supply chain is planned and tested. Finally, experiments and calculations are outlined, analyzing the optimum system design criteria proposed. We conclude that economic green hydrogen can displace diesel and gasoline in vehicle transport, while also displacing natural gas for combined heat and power in buildings. In addition, the prospect in 2023 is that profits can now be made all along the green hydrogen supply chain, such that new businesses involved in clean communities can beat the National Grid monopoly and other large dominant fossil grid companies.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

Iron oxide nanozymes are a form of nanomaterial with both superparamagnetic and enzyme-mimicking properties. Given the multifunctional nature of iron oxide nanozymes, it is attractive for creating iron oxide hybrid nanozymes through biomolecular modifications to imbue with auxillary properties. Such iron oxide hybrid nanozymes can be useful for rapid and cost-effective analysis of circulating tumor nucleic acids (ctNAs) in patient liquid biopsies during minimal residual disease (MRD) monitoring of cancer recurrence. Herein, the use of streptavidin-modified iron oxide hybrid nanozymes is reported for magnetic enrichment and bioelectrocatalytic sensing of three prostate cancer (PCa) ctRNA biomarkers with high detection specificity and sensitivity (10 copies) over an ultrabroad dynamic range (five orders of magnitude). Furthermore, the feasibility of ctRNA analysis for pre- and post-cancer treatment MRD monitoring is demonstrated using PCa urinary liquid biopsy samples.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We asses s the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.

Low-cost particulate matter (PM) sensors offer an excellent opportunity to improve our knowledge about this type of pollution. Their size and their cost, which support multi-node network deployment, along with their temporal resolution, enable them to report fine spatio-temporal resolution for a given area. These sensors have known issues across performance metrics. Generally, the literature focuses on the PM mass concentration reported by these sensors but some models of sensors also report particle number concentrations (PNC) segregated into different PM size bins. In this study, 8 units of each Alphasense OPC-R1, Plantower PMS5003 and Sensirion SPS30 have been exposed, under controlled conditions, to short-lived peaks of PM generated using two different combustion sources of PM, exposing the sensors to different particle size distributions to quantify and better understand the low cost sensors performance across a range of relevant environmental ranges. The PNC reported by the sensors were analysed. This study showed that there is added value in directly using the PNC reported by the sensors instead of the mass concentrations, which could aid the efforts to calibrate these sensors to a known accuracy. It demonstrated that all sensors tested here could track the fine temporal variation of PNC, that the Alphasense OPC-R1 could closely follow the variations of size distribution between the two sources of PM, and it showed that particle size distribution and composition are more impactful on the sensors measurement than relative humidity.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

The theories of quantum mechanics and relativity dramatically altered our understanding of the universe ushering in the era of modern physics. Quantum theory deals with objects probabilistically at small scales, whereas relativity deals classically with motion in space and time. We show here that the mathematical structures of quantum theory and of relativity follow together from pure thought, defined and uniquely constrained by the same elementary ``combining and sequencing'' symmetries that underlie standard arithmetic and probability. The key is uncertainty, which inevitably accompanies observation of quantity and imposes the use of pairs of numbers. The symmetries then lead directly to the use of complex \sqrt{-1} arithmetic, the standard calculus of quantum mechanics, and the Lorentz transformations of relativistic spacetime. One dimension of time and three dimensions of space are thus derived as the profound and inevitable framework of physics.

Background/Purpose: Multimorbidity of malaria, anaemia, and malnutrition (MAMM) is a condition in which an individual cohabits with two or more of these health outcomes and is becoming an emergent public health concern in sub-Saharan African countries. The independent associations of a child’s demographic variables and socioeconomic disparities with a child’s health outcomes have been established in literature. However, the effects of the intersection of these factors on MAMM, while accounting for other covariates have not been studied. Therefore, this study aimed to determine how children’s sex, age and socioeconomic status interact to explain the variations in MAMM among children aged 6-59 months in Nigeria. Methods: Data from the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report (NHDR) were used. The study includes weighted samples of 10,184 children aged 6-59 months in Nigeria. A three-level multilevel mixed effect ordinal logistic regression model such that individual characteristics at level 1 are nested in communities at level 2 and nested in states at level 3 was used. Subsequently, predictive probability charts and average adjusted probability tables were used to interpret the intersectional effects. Five models were created in this scenario. Model 1 is the interaction between the child's sex and wealth status; model 2, child's sex and age; model 3 is between child's age and wealth status; model 4 has the three 2-way interactions of child's sex, age, and household wealth status, and model 5 includes model 4 and the 3-way interactions between a child's sex, age, and wealth quintiles. Results: The prevalence of children with ‘none of the three diseases’ outcomes was 17.3% (1767/10,184), while, 34.4% (3499/10,184) had ‘only one of the diseases’, and 48.3% (4,918/10,184) cohabit with ‘two or more’ of MAMM. However, in the multivariate analyses, model 3 was the best fit compared with other models, so, that the two-way interaction effects of a child's age and wealth status are significant predictors in the model. Children aged 36-47 months living in the poorest households have the probability of 0.11, 0.18, and 0.32 of contracting MAMM above the probability of children of the same age and live in the middle, more prosperous and richest households, respectively, while all other covariates are held constant. Thus, the variation in MAMM over a child's age differs depending on the household wealth quintile. In other words, as the children grow older, variations in MAMM become more evident between the rich and the poor household. Conclusion: Therefore, it is recommended that policies that are geared toward economic redistribution will help bridged the disparities observed in multiple diseases among children aged 6-59 months in Nigeria

The extracellular matrix (ECM) is a ubiquitous member of the body and is key to the maintenance of tissues and organs integrity. Initially thought to be a by-stander in many cellular processes, the extracellular matrix has been shown to have diverse components that regulate and activate many cellular processes and ultimately influence cell phenotype. Importantly, the ECM composition, architecture, and stiffness/elasticity influence cellular phenotypes. Under normal conditions and during development, the synthesized ECM is constantly undergoing degradation and remodeling processes via the action of matrix proteases that maintain tissue homeostasis. In many pathological conditions including fibrosis and cancer, the ECM synthesis, remodeling, and degradation is dysregulated causing its integrity to be altered. Both physical and chemical cues from the ECM are sensed via receptors including integrins and play key roles in driving cellular proliferation and differentiation and in various disease progression such as cancers. Advances in ‘omics’ technologies have seen an increase in studies focussing on bi-directional cell-matrix interactions and here we highlight emerging knowledge on the role played by the ECM during normal development and in pathological conditions. This review summarizes current ECM-targeted-therapies that can modify tumor ECM to overcome drug resistance and better cancer treatment.

Highly diverse agroecosystems are increasingly of interest as the realization of farms' invaluable ecosystem services grows. Simultaneously there has been an increased use of uncrewed aerial systems (UAS) in remote sensing as drones offer a finer spatial resolution and faster revisit rate than traditional satellites. With the combined utility of UAS and the attention on agroecosystems, there exists an opportunity to assess UAS practicality in highly biodiverse settings.  In this study, we utilized UAS to collect fine-resolution 10-band multispectral imagery of coffee agroecosystems in Puerto Rico. We created land cover maps through a pixel-based supervised classification of each farm and assembled accuracy assessments for each classification. To bolster our understanding of the classifications, we interviewed farmers to understand their thoughts on how these maps may be best used to support their land management. The average overall accuracy (53.9%), though relatively low, was expected for such a diverse landscape with fine-resolution data. After sharing imagery and land cover classifications with farmers, we found that while the prints were often a point of pride or curiosity for farmers, integrating the maps into farm management was perceived as impractical. These findings highlight that while remote sensing of diverse agroecosystems may provide a detailed way of estimating land cover classes and ecosystem services for researchers and government agencies for example these maps may be of limited use to land managers without additional interpretation.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Based on its large surface area and covering the whole human body, the skin body’s largest organ and its main function is protection. Injuries and wound healing involving the skin offer valuable lessons shared with and of relevance to other organ systems and the diseases that impact them. Arguably the most complex human body process, wound healing is a multifaceted process that involves multiple cells and the extracellular matrix (ECM), with each component playing a specific role in the different stages of the healing process. Importantly, studies indicate that cells with stem cell-like properties are present within many of the human tissues and play key roles in case of tissue and cellular injury. Cell-to-cell and cell-to-ECM interactions are salient in wound healing subsequent to an injury. Microenvironment related factors and the variations therein including hypoxia or the abundance of oxygen, the presence/absence of growth factors and cytokines add to the complexity of the wound healing process and impact cell function and result in compromised or enhanced wound healing. This expert review critically examines the advances in biochemical and analytical tools that are enable the analysis of numerous cells and molecules within the wound microenvironment, revealing great cellular heterogeneity as well as novel molecular targets of importance to enhance wound healing. In a broader angle, we emphasize the ways in which wound healing is significant in the search for perfect skin after injury and in many common complex human diseases including cancer. In all, wound healing is a centrepiece of integrative biology research and applications in medicine as well as dermatology as discussed in this review.

More people around the world now have obesity than suffer from starvation thanks to our modern food system. Agriculture was transformed over the 20^th century by a variety of technological advancements that relied heavily on fossil fuels. In the United States of America, government policies and economic incentives led to surplus production of cheap inputs to processed food industries that produced a wide variety of heavily marketed, convenient, rewarding, timesaving, and relatively inexpensive ultra-processed foods. The energy available in the United States food supply increased much more than population needs, albeit with large inequities in food distribution and nutrition security. While most of the rise in per capita food availability during the late 20^th and early 21^st centuries in the United States resulted in increased food waste, a variety of mechanisms have been proposed by which changes in the increasingly ultra-processed food environment resulted in excess energy intake disproportionately in people genetically susceptible to obesity. As populations continue to grow, substantial investments in coordinated nutrition and agricultural research are needed to transform our current food system to one that relies less on fossil fuels, preserves biodiversity, ensures environmental health, and provides equitable access to affordable, safe, and nutritious food that reduces the prevalence of chronic diseases like obesity.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

Fractional differential equations have become a fundamental modelling approach for understanding and simulating the many aspects of nonlocality and spatial heterogeneity of complex materials and systems. Yet, while real-order fractional operators are nowadays widely adopted, little progress has been made in extending such operators to complex-order counterparts. In this work, we introduce new definitions for the complex-order fractional Laplacian, fully consistent with the theory of averaging of smooth functions over fractal sets, and present tailored spectral methods for their numerical treatment. The proposed complex-order operators exhibit a dual particle-wave behaviour, with solutions manifesting wave-like features depending on the magnitude of the imaginary part of the fractional order. Reaction-diffusion systems driven by the complex-order fractional Laplacian exhibit unique spatio-temporal dynamics, such as equilibrium of diffusion in random materials by interference of scattered waves, conduction block and highly fractionated propagation, or the generation of completely novel Turing patterns. Taken together, our results support that the proposed complex-order operators hold unparalleled capabilities to advance the description of multiscale transport phenomena in physical and biological processes highly influenced by the heterogeneity of complex media.

Measuring the impact of land use regulation on the land market involves identifying and classifying relevant impact factors related to the land market. The objective of this study was to identify land market impact factors in the context of the introduction of land use regulation in Nepal. A desktop review was carried out to identify preliminary set of impact factors, which were reclassified through intuitive analysis based on the degree of thematic closeness. Perspective-based impact factors were identified through the qualitative analysis of primary data collected through semi-structured interviews with the Nepalese land market stakeholders. These independently derived impact factors were compared with the desktop literature review impact factors resulting in fourteen land market impact factors across four dimensions, including transaction cost, valuation, mortgage availability, taxation, and compensation across the economic dimension; lot size, subdivision restrictions, and coordination across the institutional dimension; awareness, expectation and proximity across the social dimension; and risk reduction, quality of residential land, and suitability of zoning classification across the environmental dimension. There was significant overlap and commonality across factors identified from both the literature review and semi-structured interviews. The land market impact factors determined in the study may be adapted and generalized across other countries and could be utilized to better understand the impacts of land policy decisions on urban planning and development. Further research is recommended on the process to operationalize the use of these factors to quantify the impact of land use regulation on different land markets.

10% copper substituted (BiCUVOX/Bi₂V_0.9Cu_0.1O_5.5−δ) and 5% copper/titanium double-substituted bismuth vanadate (BiCUTIVOX/Bi₂V_0.9(Cu_0.05Ti_0.05)O_5.5−δ) platelets were formed by molten salt synthesis (MSS) using a eutectic KCl/NaCl salt mixture. The product was phase pure within the limits of X-ray diffraction. The size and form of the platelets could be controlled by changing the heating temperature and time. The crystallite growth rate at a synthesis temperature of 650 °C, and activation energy for grain growth were determined for BICUTIVOX, which experienced inhibited growth compared to BICUVOX. Quasi-equilibrium, multi-foil shapes consisting of lobes around the perimeter of the platelets were observed and explained in the context of relative two-dimensional nucleation and edge growth rates.

‘‘Sustainable Supply Chain Management’’ (SSCM) has become a hot topic on which eminent researchers are working on every day. However, it is clear that we still observe in this field of research, an artistic vagueness on the fundamental differences between Sustainable Supply Chain Management and Green Supply Chain Management (GSCM) Moreover, it is regrettable to note that previous researchers haven't yet thought about having a specific theory which can be applied to SSCM, the use of macro theories still being observed. In addition, we observe a lack of research in the oil and gas industry especially in Developing Countries when we know that this industry is the most lucrative and polluting. Therefore, this paper’s purpose consists to make a Systematic Literature Review (SLR) of 38 papers published from 2005 to 2023 especially in oil and gas industry and in Developing Countries, in order to make a clear distinction between SSCM and GSCM while highlighting the practices related to them and at the same time, generating a united theory which will bring together the triple bottom line of the SSCM. As findings, the authors built a Conceptual Framework that applies the triple bottom line of the SSCM in oil and gas industry by demonstrating that GSCM which is more related to environmental issues and is a part of the SSCM. Therefore, in order to be more efficient and to have a great impact on their performances, Oil and gas companies should apply SSCM practices rather than GSCM practices which are very different from what is applied in Developed Countries because of certain barriers and pressures.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

Background: Positive person-centered attributes of inpatient rehabilitation need to be identified from the patient perspective to be further developed and sustained. Purpose: To identify which attributes patients openly evoke as being great care experiences, using an open appreciative inquiry during the inpatient rehabilitation stay. Methods: Qualitative secondary analysis of appreciative patient comments during a bedside patient experience rounding, facilitated by a neutral party. Two independent analysts employed an inductive, summative form of content analysis. Results: Among 150 patients rounded, 122 provided categorizable appreciative accounts. Over two thirds of the patients (67.2%) focused on “staff attributes” in their great-experience accounts. Those attributes were mostly interpersonal such as being “attentive & caring - beyond clinical duty” and being “encouraging (but not too hard) & reassuring”. These interpersonal staff attributes were reported with words showing deep levels of personal significance or patient appreciation. Beyond staff attributes, the perceived quality of the “patient care” (31.1%) and opportunities for “leisure and social activities” (9.0%) were also frequently evoked. Amenities like food or costumer service were the least evoked, rarely so as an exclusive attribute (0.8% for each). Conclusions: The human(e) factor, especially the interpersonal qualities of staff, emerged as greatly appreciated from the patient experience perspective during inpatient rehabilitation. These experiences help identify which person-centered attributes of care might be further developed and sustained.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Translation of basic animal research to find effective methods of diagnosing and treating human neurological disorders requires parallel analysis infrastructures. Small animals such as mice provide exploratory animal disease models. However, many interventions developed using small animal models fail to translate to human use due to physical or biological differences. Recently, large-animal minipigs have emerged in neuroscience due to both brain similarity and economic advantages. Medical image processing is a crucial part of research as it allows researchers to monitor their experiments and understand disease development. However, although many algorithms are created and optimized for MR analysis of human data, those tools are not directly applicable or sufficiently sensitive to measure minipig data. In this work, we propose PigSNIPE - a pipeline for the automated handling, processing, and analyzing of large-scale data sets of minipig MR images. The pipeline allows for image registration, AC-PC alignment, landmark detection, skull stripping, brainmasks and intracranial volume segmentation (DICE 0.98), tissue segmentation (DICE 0.82), and caudate-putamen brain segmentation (DICE 0.8) in under two minutes. To the best of our knowledge, this is the first automated pipeline tool aimed at large animal images.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

In the present manuscript, we report new insights into the concept of (a)synchronicity in Diels-Alder (DA) reactions in the framework of the reaction force analysis, in conjunction with natural population calculations and atomic resolution of energy derivatives along the intrinsic reaction coordinate (IRC) path. Our findings suggest that the DA reaction transitions between a preferentially concerted mechanism to a stepwise one in a 0.10 Å window of synchronicity indices, ranging from 0.90 to 1.00 Å. We have also shown that the relative position of the global minimum of the reaction force constant with respect to the TS is an alternative and quantifiable indicator of the (a)synchronicity in DA reactions. Moreover, the atomic resolution of energy derivatives reveals that the mechanism of the DA reaction involves two inner elementary processes associated with the formation of each of the two C-C bonds. This resolution goes on to indicate that, in asynchronous reactions, the driving and retarding components of the reaction force are mostly due the fast and slow-forming C-C bonds (elementary process) respectively, while in synchronous ones both elementary processes retard and drive the process concomitantly and equivalently.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

In the U.S. 44% of low-income households struggle to pay their utility bills, affecting their ability to afford necessities such as food and health expenses. Several government and utility funded energy efficiency programs exist to assist those experiencing energy insecurity. In Salt Lake City, Utah, there is a high demand for, but low availability of, energy efficiency services in underserved neighborhoods creating an opportunity for creative community-based programs to fill this inherent gap. This pilot project, involving the exchanging of LED bulbs in Salt Lake City, highlights the development of a community-based energy efficiency program that aims to bring energy savings to a uniquely targeted portion of the city and determines its feasibility in addressing energy insecurity at a larger scale. Through the 8-month project duration, 1,432 bulbs were exchanged at 23 events reaching 181 households in low-income areas. Through a year of use, these bulbs are estimated to save residents approximately 18,219 USD in electricity bills and reduce CO2 emissions from power plants by 122.23 metric tons, in addition to a savings of 4,400 USD in social cost of carbon as defined by the U.S. Environmental Protection Agency. Since this pilot reached less than 1% of households, we extrapolated a reach of 2%, 5%, and 7.5% and found substantial potential decreases in power plant emissions and financial savings. As this project is ongoing and being expanded, we discuss relevant findings that will help shape future community-based models so that they are appropriately deployed and more effective in alleviating local energy insecurity.

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

Eating and drinking difficulties are common in dementia, but little is known about the experiences of ethnic minority groups managing these difficulties at home. We undertook qualitative semi-structured interviews, exploring the meaning of food, the impact of dementia on eating and drinking and carers’ experiences of support. Interviews were audio-recorded and transcribed verbatim. We interviewed 17 carers and people with dementia from ethnic minority backgrounds, using reflexive thematic analysis to analyse data. Food/drink had strong links to identity, culture and emotions. Providing culturally familiar foods, celebrating traditional festivals and supporting previous food-related roles promoted reminiscence, which encouraged people with dementia to eat and drink, as did social interactions. However, these strategies sometimes led to distress in those with more advanced dementia. Food choices were also influenced by carer strain, generational differences and the impact of health conditions. Despite a strong sense of duty to care for relatives at home, there was low awareness of community support services. Carers expressed a need for culturally tailored support for managing dementia-related eating and drinking difficulties at home. Healthcare professionals must provide contextually relevant advice to carers, being mindful of how cultural backgrounds can affect dietary choices.

Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis and highlight various ways through which tumor cells reprogram normal cells including into phenotypes that are pro-tumorigenic including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to formation of new vascular networks in order to actively promote and sustain tumor growth via supply of oxygen and nutrients whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to targeting of tumor cells. Re-programming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centred therapies under investigations.

Text fields in electronic medical records (EMR) contain information on important factors that influence health outcomes, however, they are underutilized in clinical decision making due to their unstructured nature. We analyzed 6,497 inpatient surgical cases with 719,308 free text notes from Le Bonheur Children’s Hospital EMR. We used a text mining approach on preoperative notes to obtain the text-based risk score algorithm as predictive of death within 30 days of surgery. We studied the additional performance obtained by including text-based risk score as a predictor of death along with other structured data based clinical risk factors. The C-statistic of a logistic regression model with 5-fold cross-validation significantly improved from 0.76 to 0.92 when text-based risk scores were included in addition to structured data. We conclude that preoperative free text notes in EMR include significant information that can predict adverse surgery outcomes.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Consumer preference not only dictates what food is consumed but how that food is produced. Ingredients in livestock feed that are not antibiotics, not genetically modified, not of animal origin, and that are nutrient-like, tend to be more acceptable to consumers, retailers, and producers. Mono- and diglycerides (MDG) fit these criteria, are commonly used in food, and are generally recognized as safe. But beyond being emulsifiers and a source of energy, MDG are also known to have antimicrobial, immune and microbiome modulation, and angiogenic activity. MDG in broiler diets have been shown to impact a variety of immune-related functions such as regulation of circulating antibodies, as well as decreased gene expression or protein concentration of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IFN-γ. In addition, MDG can affect metabolic function and intestinal integrity. Results of this review show that MDG can serve as antimicrobial and growth-supporting alternatives for reducing poultry production losses, improving resource utilization, and meeting consumer demand for sustainably produced and safe animal protein.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

In this work, zinc oxide (ZnO)/ granular activated carbon (GAC) composites at different ZnO concentration (0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC) were prepared by an in-situ hydrothermal method and demonstrated synergistic photocatalytic degradation and ad-sorption of Rhodamine B (RhB). The thermal stability, morphological structure, elemental com-position, crystallographic structure, and textural properties of developed catalysts were charac-terized by thermal gravimetric analysis (TGA/DTG), scanning electron microscopy equipped with energy dispersive-x-ray (SEM-EDS), x-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) analysis. Successful loading of ZnO onto GAC was confirmed by SEM-EDS and XRD analysis. The BET surface areas of GAC, 0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC were 474 m2/g, 450 m2/g, 453 m2/g, and 421 m2/g, respectively. The decrease in GAC could be attributed to the successful loading of ZnO on the GAC surface. Notably, 0.5M-ZnO@GAC exhibited the best photocatalytic degradation efficiency of 82% and 97% under UV-A and UV-C light over 120 min, attributed to improved crystallinity and visible light absorption. The photocatalytic degradation parameters revealed that lowering the RhB concentration, raising the catalyst dosage and pH be-yond the point of zero charge (PZC) would favor the RhB degradation. Photocatalytic reusability was demonstrated over 5 cycles. Scavenger tests revealed that the hydroxyl radicals (•OH), su-peroxide radicals (O2−•), and photoinduced hole (h+) radicals play a major role during the RhB degradation process. Based on the TOC results, the RhB mineralization efficiency of 79.1% was achieved by 0.5M-ZnO@GAC. Additionally, GAC exhibited a strong adsorptive performance towards RhB with adsorption capacity and RhB removal of 487.1 mg/g and 99.5% achieved within 90 min equilibrium time. The adsorption characteristics were best described by pseu-do-second-order kinetics, suggesting chemical adsorption. This research offers a new strategy for the development of effective photocatalyst materials with potential for wider wastewater treat-ment applications.

Fractional calculus gained a lot of attention in the last couple of years. Researchers discovered that processes in various fields follow rather fractional dynamics than ordinary integer-ordered dynamics, meaning the corresponding differential equations feature non-integer valued derivatives. There are several arguments for why this is the case, one of them being that fractional derivatives’ inherit spatiotemporal memory and/or the ability to express complex naturally occurring phenomena. Another popular topic nowadays is machine learning, i.e., learning behavior and patterns from historical data. In our ever-changing world with ever-increasing amounts of data, machine learning is a powerful tool for data analysis, problem-solving, modeling, and prediction. It further provides many insights and discoveries in various scientific disciplines. As these two modern-day topics provide a lot of potential for combined approaches to describe complex dynamics, this article reviews combined approaches of fractional derivatives and machine learning from the past, puts them into context, and thus provides a list of possible combined approaches and the corresponding techniques. Note, however, that this article does not deal with neural networks, as there already is profound literature on neural networks and fractional calculus. We sorted past combined approaches from the literature into three categories, i.e., preprocessing, machine learning & fractional dynamics, and optimization. The contributions of fractional derivatives to machine learning are manifold as they provide powerful preprocessing and feature augmentation techniques, can improve physically informed machine learning, and are capable of improving hyperparameter optimization. Thus, this article serves to motivate researchers dealing with data-based problems, to be specific machine learning practitioners, to adopt new tools and enhance their existing approaches.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

The increasing spatial and spectral resolution of hyperspectral imagers yields detailed spectroscopy measurements from both space-based and airborne platforms. Machine learning algorithms have achieved state-of-the-art material classification performance on benchmark hyperspectral data sets; however, these techniques often do not consider varying atmospheric conditions experienced in a real-world detection scenario. To reduce the impact of atmospheric effects in the at-sensor signal, atmospheric compensation must be performed. Radiative Transfer (RT) modeling can generate high-fidelity atmospheric estimates at detailed spectral resolutions, but is often too time-consuming for real-time detection scenarios. This research utilizes machine learning methods to perform dimension reduction on the transmittance, upwelling radiance, and downwelling radiance (TUD) data to create high accuracy atmospheric estimates with lower computational cost than RT modeling. The utility of this approach is investigated using the instrument line shape for the Mako long-wave infrared hyperspectral sensor. This study employs physics-based metrics and loss functions to identify promising dimension reduction techniques. As a result, TUD vectors can be produced in real-time allowing for atmospheric compensation across diverse remote sensing scenarios.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Crowdsourced Data (CSD) generated by citizens is becoming more popular as its potential utilisation in many applications is increasing due to its currency and availability. However, the quality of CSD, including its relevance, is often questioned as the data is not generated by professionals nor follows standard data collection procedures. The quality of CSD can be assessed according to a range of attributes including its relevance. Information relevance has been explored through using in Geographic Information Retrieval (GIR) techniques to identify relevant information. This research tested a relevance assessment approach for CSD by adapting relevance assessment techniques available in the GIR domain. The thematic and geographic relevance were assessed using the Term Frequency-Inverse Document Frequency (TF-IDF), Vector Space Model (VSM) and Natural Language Processing (NLP) techniques. The thematic and geographic specificities of the queries were calculated as 0.44 and 0.67 respectively, which indicates the queries used were more geographically specific than thematically specific. The Spearman's rho value of 0.62 indicated that the final ranked relevance lists showed reasonable agreement with a manually classified list and confirmed the potential of the approach for CSD relevance assessment for other possible crowdsourced data analysis.

Climate warming is expected to have pronounced effects on Arctic and Subarctic ecosystems, especially regions underlain by discontinuous and relatively warm permafrost. The main goal of this research is to evaluate the vulnerability and dynamics of permafrost under climate warming across the various ecotypes in respect of ecosystem stability, socioeconomic impact, and for better understanding possible future environmental changes. We suggested the new version of the spatially distributed permafrost dynamics model (GIPL2-MPI), which is developed in the Geophysical Institute, University of Alaska Fairbanks. This model is based on the ecosystem approach to simulate the permafrost dynamics, which we are discussing in this paper. We combined ground-based observations and numerical freeze/thaw modeling using climate-ecosystem-permafrost interactions to understand the physical processes and mechanisms controlling permafrost physical state. We predict the changes in permafrost conditions using output from two GCMs (NCAR-CCSM4 and GFDL-CM3) and Five-Model Average Ensemble for the RCP-4.5 and RCP-8.5 scaled down to 1 by 1 km spatial resolution (https://uaf-snap.org/) across entire Alaska. Our result shows that by the end of the current century widespread near-surface permafrost degradation could begin everywhere in Alaska southward of the Brooks Range as well as across some spots at the North Slope Alaska.

We provide quantitative results from GIS-based modelling of urban emission functions for a range of representative low- and mid-rise locations, ranging from individual streets to residential communities within cities as well as entire towns and city regions with the aim of whether lantern photometry or built environment has the dominant effect on light pollution. We demonstrate the scalability of our work by providing results for the largest urban area modelled to date, comprising the central 117 km2 area of Dublin City and containing nearly 42,000 public lights. Our results show a general similarity in the shape of the azimuthally-averaged emission function for all areas examined, with differences in total light output distribution depending primarily on the nature of the lighting and, to a smaller extent, on the obscuring environment including seasonal foliage effects. A comparison with global satellite observations shows that they are consistent with the deduced angular emission function for other low-rise areas worldwide. We further validate our approach by comparing results for a range of urban locations by the close agreement observed in a detailed comparison of with calibrated imagery from the International Space Station. To our knowledge, this is the first such detailed quantitative verification of light loss calculations.

We examine the relation between environmental, social, and governance commitment levels (ESG) and firm dividend payer status. Given that larger and more profitable firms are positively associated with both payer status and ESG, it could be that ESG and dividends are complements. However, given that both dividends and ESG relate to firm spending decisions, it may be that the choice is “either/or” and that ESG and dividends are substitutes. We document a positive relation between ESG and dividend payer status in U.S. firms over the period 1991-2016. In particular we find that the proportion of dividend payers is roughly 13% higher for firms with positive ESG compared to those with negative ESG. Including ESG in the models used to predict payer status provides, on average, a nearly 26% improvement in relative forecast accuracy. Our results are robust to estimation techniques and the inclusion of variables known to be determinants of payer status.

Majority of the studied MADS box members are linked with flowering and fruit traits. However, higher volumes of studies on the type II of their two types so far suggest that florigenic effect of the gene members could just be tip of the iceberg. In current study we used a systematic approach to have general overview on the MADS box members their cross-trait and multifactor associations as well as their pleiotropic potentials based on local reference database curated for MADS box members. While doing so, we screened for the co-occurrence of the terms of interest within the title or abstract of each reference with threshold of 3 hits. Analysis results showed that our approach can retrieve multi-faceted information on the subject of study (MADS box gene members in current case) which could otherwise have been skewed depending on the authors’ expertise and/or volume of literature reference base. Overall, our study discusses on the roles of MADS box members in association with plant organs and traits-linked factors among plant species. Our assessment showed that plants with majority of the MADS box member studies include tomato, apple, rice etc., after Arabidopsis. Furthermore, based on the degree of their multi-trait associations, FLC, SVP, SOC1, etc. are suggested to have relatively higher pleiotropic potential among others in plant growth, development and flowering process. The approach devised in this study is expected applicable for having basic understanding on any study subject of interest regardless of depth prior knowledge.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

Ovarian cancer is among the most common causes of female mortality. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1) was examined. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both on cancer stem cells (CSCs), marked as CD49f+ and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (P &lt; 0.001). The expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P&lt;0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P &lt; 0.001)

The main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

Dementia education and training for workforce development is becoming increasingly important in bridging knowledge gaps among health and social care practitioners in the UK and internationally. Dementia Education for Workforce Excellence (DEWE) was developed during the COVID-19 pandemic blending both synchronous and asynchronous instruction and delivered across three different contexts: care homes, home care, and nurse education within the UK and India. This study aimed to evaluate DEWE using mixed methods with online survey data analyzed descriptively and interview data analyzed thematically. Integration of survey and interview data aimed toward a comprehensive evaluation of this novel approach for dementia workforce development. Thirty-four social care practitioners and nurse educators completed the online survey demonstrating high-level learner satisfaction; learning gains; behavioral change, and motivation to share new knowledge. Four key themes developed from the analysis of interviews (n=9) around participants’ pursuit of new knowledge; delivery modes in DEWE; learning gains and impact of DEWE; and adaptations for future program implementation. Findings suggest DEWE is an innovative resource that promotes person- and relationship-centered dementia care across all stages of one’s dementia journey. Cultural adaptations are recommended for international delivery to ensure contextual alignment and maximum impact.

The terms 'open' and 'openness' are widely used across the current higher education environment particularly in the areas of repository services and scholarly communications. Open-access licensing and open-source licensing are two prevalent manifestations of open culture within higher education research environments. As theoretical ideals, open-licensing models aim at openness and academic freedom. But operating as they do within the context of global neoliberalism, to what extent are these models constructed by, sustained by, and co-opted by neoliberalism? In this paper, we interrogate the use of open-licensing within scholarly communications and within the larger societal context of neoliberalism. Through synthesis of various sources, we will examine how open access licensing models have been constrained by neoliberal or otherwise corporate agendas, how open access and open scholarship have been reframed within discourses of compliance, how open-source software models and software are co-opted by politico-economic forces, and how the language of 'openness' is widely misused in higher education and repository services circles to drive agendas that run counter to actually increasing openness. We will finish by suggesting ways to resist this trend and use open-licensing models to resist neoliberal agendas in open scholarship.

In the power plant industry, the turbine inlet temperature (TIT) plays a key role in the efficiency of the gas turbine and, therefore, the overall—in most cases combined—thermal power cycle efficiency. Gas turbine efficiency increases by increasing TIT. However, an increase of TIT would increase the turbine component temperature which can be critical (e.g., hot gas attack). Thermal barrier coatings (TBCs)—porous media coatings—can avoid this case and protect the surface of the turbine blade. This combination of TBC and film cooling produces a better cooling performance than conventional cooling processes. The effective thermal conductivity of this composite is highly important in design and other thermal/structural assessments. In this article, the effective thermal conductivity of a simplified model of TBC is evaluated. This work details a numerical study on the steady-state thermal response of two-phase porous media in two dimensions using personal finite element analysis (FEA) code. Specifically, the system response quantity (SRQ) under investigation is the dimensionless effective thermal conductivity of the domain. A thermally conductive matrix domain is modeled with a thermally conductive circular pore arranged in a uniform packing configuration. Both the pore size and the pore thermal conductivity are varied over a range of values to investigate the relative effects on the SRQ. In this investigation, an emphasis is placed on using code and solution verification techniques to evaluate the obtained results. The method of manufactured solutions (MMS) was used to perform code verification for the study, showing the FEA code to be second-order accurate. Solution verification was performed using the grid convergence index (GCI) approach with the global deviation uncertainty estimator on a series of five systematically refined meshes for each porosity and thermal conductivity model configuration. A comparison of the SRQs across all domain configurations is made, including uncertainty derived through the GCI analysis.

Objectives Asylum seekers in Germany represent a highly vulnerable group from a health perspective due to a variety of risk factors. At the same time their access to healthcare is restricted. While the introduction of the Electronic Health Insurance Card (EHIC) for asylum seekers instead of healthcare-vouchers is discussed controversially using politico-economic reasons, there is hardly any empirical evidence on its actual impact on the use of medical services Study design Thus, the aim of this study is to examine the influence of the possession of the EHIC on the use of medical services by asylum seekers as measured by their consultation rate of ambulant physicians (CR). For this purpose, a standardized survey was carried out to 260 asylum seekers in different municipalities of which some have introduced the EHIC for asylum seekers, while others have not. Methods Various CR were differentiated considering possible third variables as well as confounding factors. The period prevalence was compared between the groups "with EHIC" and "without EHIC" using a two-sided t-test. Multivariate analysis was done using a linear OLS regression model. Results Asylum seekers who are in possession of the EHIC are significantly more likely to seek ambulant medical care than those receiving healthcare-vouchers. Their CR, however, does not differ significantly from the age-corrected CR of the autochtonous population. Taking into account relevant covariables, the possession of the EHIC can be viewed as an independent influencing factor on the asylum seekers' use of medical care. Conclusions The results of this study suggest that having to ask for healthcare-vouchers at the social security office could be a relevant barrier for asylum seekers. Nevertheless, the ownership of the EHIC does not seem to lead to an overuse of medical services.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

The ability to detect the presence as well as classify the activities of individuals behind visually obscuring structures is of significant benefit to police, security and emergency services in many situations. This paper presents the analysis from a series of experimental results generated using a through-the-wall (TTW) Frequency Modulated Continuous Wave (FMCW) C-Band radar system named Soprano. The objective of this analysis was to classify whether an individual was carrying an item in both hands or not using micro-Doppler information from a FMCW sensor. The radar was deployed at a standoff distance, of approximately 0.5 m, outside a residential building and used to detect multiple people walking within a room. Through the application of digital filtering, it was shown that significant suppression of the primary wall reflection is possible, significantly enhancing the target signal to clutter ratio. Singular Value Decomposition (SVD) signal processing techniques were then applied to the micro-Doppler signatures from different individuals. Features from the SVD information have been used to classify whether the person was carrying an item or walking free handed. Excellent performance of the classifier was achieved in this challenging scenario with accuracies up to 94%, suggesting that future through wall radar sensors may have the ability to reliably recognize many different types of activities in TTW scenarios using these techniques.

Electromagnetic interference (EMI) generated by switching operations within high voltage DC (HVDC) converter stations is an issue that has been addressed by CIGRE and methods to manage EMI should be considered in the design phase using electromagnetic modeling techniques. It is shown that method of moments-based techniques that have been used in many previous studies may not be sufficient. Here, the finite-difference time-domain method is used to study the properties of single switching events using a realistic model of an HVDC converter station with special emphasis on determining the impact of the valve hall on shielding EMI. It is shown that the valve hall does not confine high frequency electromagnetic fields to the valve hall; rather it delays them from exiting through bushings in the wall. Further, it is shown that incorporating electromagnetic absorbing material into the valve hall design can significantly reduce EMI outside the converter station.