Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.

Social distancing, washing hands and good hygiene are essential and currently the most potent methods available to curb down the unprecedented speed by which the new coronavirus is spreading across the globe. Even under lockdown, which is necessary to significantly reduce the number of people that get infected by an ill person, are there additional measures that each of us can embrace to even further reduce the risk of infection and the severity of the COVID-19 disease? Given the lack of licensed drugs that target SARS-CoV-2 specifically, we have to look into additional non-specific defense mechanisms that animals and humans evolved to protect themselves from pathogen invasions. The goal of this article is to describe how various of our non-specific defense mechanisms work, which actually precede the inflammatory response, and to discuss whether we can exploit the unique features of the coronavirus envelope and the self-cleaning machinery of the human respiratory tract to strengthen our self-defense. The challenge is to actively interfere with supportive measures during the short time window between getting exposed and before an inflammatory response gets initiated.

In this paper, we revisit the q-states clock model for small systems. We present results for the thermodynamics of the q-states clock model from $q=2$ to $q=20$ for small square lattices $L \times L$, with L ranging from $L=3$ to $L=64$ with free-boundary conditions. Energy, specific heat, entropy and magnetization are measured. We found that the Berezinskii-Kosterlitz-Thouless (BKT)-like transition appears for $q>5$ regardless of lattice size, while the transition at $q=5$ is lost for $L<10$; for $q\leq 4$ the BKT transition is never present. We report the phase diagram in terms of $q$ showing the transition from the ferromagnetic (FM) to the paramagnetic (PM) phases at a critical temperature T$_1$ for small systems which turns into a transition from the FM to the BKT phase for larger systems, while a second phase transition between the BKT and the PM phases occurs at T$_2$. We also show that the magnetic phases are well characterized by the two dimensional (2D) distribution of the magnetization values. We make use of this opportunity to do an information theory analysis of the time series obtained from the Monte Carlo simulations. In particular, we calculate the phenomenological mutability and diversity functions. Diversity characterizes the phase transitions, but the phases are less detectable as $q$ increases. Free boundary conditions are used to better mimic the reality of small systems (far from any thermodynamic limit). The role of size is discussed.

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signalling pathways and transcription programs. Forkhead Box G1 (FOXG1) is one of the master regulators that plays fundamental roles in forebrain development, from the timing of neurogenesis to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as increased yield of information from high throughput omics opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems to highlight prospects of research and possible clinical interventions.

Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. However, the positive feedback mechanisms by which spontaneous contractions can be amplified towards large-scale directed flows remain mostly speculative. To investigate such a process on spherical surfaces, we reconstituted and confined initially isotropic minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced local contractions that self-organize and amplify into directed, large-scale actomyosin flows. By combining our experiments with theory, we found that the feedback mechanism leading to a coordinated, directional motion of actomyosin clusters can be described as asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spatial confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinement in vitro and in living systems.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

Cacipacoré virus (CPCV) was discovered in 1977 deep in the Amazon rainforest, from the blood of a black-faced ant thrush (Formicarius analis). As a member of the family Flaviviridae, genus orthoflavivirus, CPCV's intricate ecological association with vectors and hosts raises profound questions. CPCV’s transmission cycle may involve birds, rodents, equids, bovines, marsupials, non-human primates and bats as potential vertebrate hosts, whereas Culex and Aedes spp mosquitoes, have been implicated as potential vectors of transmission. The virus' isolation across diverse biomes, including urban settings suggests its adaptability as well as presents challenges for its accurate diagnosis and thus its impact on veterinary and human health. With no specific treatment or vaccine, prevention hinges on traditional arbovirus control measures. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis and prevention, aiming in improving our ability to better understand this neglected arbovirus.

Clean, fresh, and safe drinking water is essential to human health and well-being. Occasionally, chemical pollutants taint surface water quality used for consumption. Microcystins (MCs) are toxic heptapeptides produced by freshwater cyanobacteria. These secondary metabolites can reach hazardous concentrations, impairing surface drinking water supplies. Inconsistent screening of MCs is not uncommon in Florida waters as no provisional guidance value is established to protect public health. The occurrence of MCs in Lake Manatee and Lake Washington was monitored over the potential peak algae bloom season (June-August). An indirect competitive enzyme-linked immunosorbent assay (icELISA) quantified total MCs in two drinking water systems. Varied concentrations occurred between June and July, whereas concentrations peaked in August. Overall, MC prevalence was higher in Lake Manatee than Lake Washington. Colorimetric assays measured phosphate and nitrite in environmental water samples. Phosphate and nitrite concentrations strongly correlated with total MCs (p < 0.01). The results indicate the intrinsic nature of environmental MCs in surface drinking water supplies and the need to examine hepatotoxin dynamics to preserve drinking water quality in community served areas.

Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash processes. Some of these systems have very limited flexibility due to their rigid structures and require considerable investment in hardware. As such, there is a need for an autonomous low-cost system (~€500) that can be rapidly deployed in the field, while still producing the outcomes required for coastal monitoring. This research presents a sensitivity analysis of time-lapse intervals for two low-cost cameras located in a remote coastal area, overlooking a dissipative beach-dune system. The analysis shows that RMSD in the detected shoreline is similar to other studies for intervals ranging between 1 second and 30 seconds (i.e., RMSDmax for Camera 1 = 2.8 m and Camera 2 = 1.3 m). The increase of the sampling interval from 1 s to 30 s is shown to have no significant adverse effect on the precision of shoreline detection. The research found that the limitations of battery life and memory storage substantially decrease when sampling intervals increase without an effect on the data quality. This also has a positive effect for low-cost systems and removes the requirement for external battery and memory storage. On the systems used, the battery life increased from ~10 days to ~100 days when the sampling interval was increased from 1 to 5 s., As such, the current standard of producing Timex images from 1 s sampling intervals over 10 minutes can be changed depending on the application and requirements needed for analysis.

The Fruit Harvest Helper, a mobile application developed by Northwest Nazarene University’s (NNU) Robotics Vision Lab, aims to assist farmers in estimating fruit yield for apple orchards. Currently, farmers manually estimate the fruit yield for an orchard, which is a laborious task. Fruit Harvest Helper seeks to simplify their process. While prior research efforts at NNU concentrated on developing an iOS app for blossom detection, this current research aims to adapt that smart farming application for apple detection across multiple platforms, iOS and Android. The old and new applications were designed with an intuitive user interface that is easy for farmers to use, allowing for quick image selection and processing. Unlike before, the adapted app utilizes a color ratio-based image segmentation algorithm implemented in OpenCV C++ to detect apples in apple tree images selected for processing. The results of testing the algorithm with a dataset of images indicate an 8.52% Mean Absolute Percentage Error (MAPE) and a Pearson correlation coefficient of 0.6 between detected and actual apples on the trees. These findings were obtained by evaluating the images from both the east and west sides of the trees, which was the best method to reduce the error of this algorithm. Although the Fruit Harvest Helper shows promise, there are many opportunities for improvement. These opportunities include exploring alternative machine-learning approaches for apple detection, conducting real-world testing without any human assistance, and expanding the app to detect various types of fruit. The Fruit Harvest Helper mobile application is among the many mobile applications contributing to precision agriculture, nearing readiness for farmers to use in yield monitoring and farm management.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

Even though hard, low friction coatings such as diamond like carbon (DLC) would be beneficial for the per-formance and longevity of rubber seals, a crucial challenge – as graphically illustrated in Figure 1.a – remains. The elastic mismatch of rubber substrate and DLC coating prevents a fracture free coating application. In this work a nature inspired approach (Figure 1.b) is applied to render the stiff coating flexible and resilient to delamination at the same time by direct patterning. Rubber substrates were laser structured with tile patterns and subsequently DLC-coated. Tensile and tribology tests were performed on structured and unstructured samples. Unstructured DLC-coatings showed a crack pattern induced by the coating process, which was further fragmented by tensile stress. Coatings with tile patterns did not experience a further fragmentation under load. During continuous tribological loading, less heterogenous damage is produced for tile structured samples. The findings are ascribed to the relief of induced coating stress by the tile structure, meaning a more resilient coating.

Conditional generative adversarial networks (CGANs) learn a mapping from conditional input to observed image and perform tasks in image generation, manipulation and translation. In-situ monitoring uses sensors to obtain real-time information of additive manufacturing (AM) processes that relate to process stability and part quality. Understanding the correlations between process inputs and in-situ process signatures through machine learning can enable experimental-driven predictions of future process inputs. In this research, in-situ data obtained during a metallic powder bed fusion AM process is mapped with a CGAN. A single build of two turbine blades is monitored using EOSTATE Exposure OT, a near-infrared optical tomography system of the EOS M290 system. Layerwise images generated from the in-situ monitoring system were paired with a conditional image that labeled the specimen cross-section, laser-scan stripe overlap and z-distance to part surfaces. A CGAN was trained using the turbine blade data set and employed to generate new in-situ layerwise images for unseen conditional inputs.

This study evaluated the impact of didactic videos and service user testimonial videos on mental illness stigma among medical students. Two randomized controlled trials were conducted in Nepal. Study 1 examined stigma reduction for depression. Study 2 examined depression and psychosis. Participants were Nepali medical students (Study 1:n=94, Study 2:¬n=213) randomized to three conditions: a didactic video based on the mental health Gap Action Programme (mhGAP), a service user video about living with mental illness, or a control condition with no videos. In Study 1, videos only addressed depression. In Study 2, videos addressed depression and psychosis. In Study 1, both didactic and service user videos reduced stigma compared to the control (F2,91=6.37, p=0.003). In Study 2 (depression and psychosis), there were no differences among the three arms (F2,210=2.07, p=0.13). When comparing Study 1 and 2, there was greater stigma reduction in the service user video arm with only depression versus service user videos with depression and psychosis (t(31)=-3.04, p=0.005). In summary, didactic and service user videos were associated with decreased stigma when content addressed only depression. However, no stigma reduction was seen when including depression and psychosis. This calls for different strategies based on types of mental illnesses. ClinicalTrials.gov identifier: NCT03231761

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

The aim of this review was to summarize the available literature regarding resident and medical student education utilizing the spaced repetition program Anki. This review enables current residents and medical students to recognize and utilize evidence-proven study techniques to increase learning efficacy. A systemic review of papers across all medical journals available on Pubmed was conducted to identify studies published without time constraints. The search was for (Anki) and (spaced repetition residency). Available outcome data was collected and discussed independently for students and residents. Many studies showed a statistically significant increase in exam performance associated with Anki use and high levels of satisfaction among residents and medical students. Further research is warranted to provide high-quality evidence of Anki’s applications and there is a need for exploration in additional residency specialties. Anki use has steadily increased with both medical students and residents. The application demonstrated consistent improvement on exam-based performance and was regarded highly by users. As burnout and time constrictions threaten educational workflow, Anki may serve as a powerful tool to improve the quality of learning. Further data needs to be collected and analyzed in specialties where Anki use may already exist.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Beyond the usual ferromagnetic and paramagnetic phases present in spin systems, the usual q-state clock model, presents an intermediate vortex state when the number of possible orientations q for the system is equal to 5 or larger. Such vortex states give rise to the Berezinskii-Kosterlitz-Thouless (BKT) phase present up to the XY model in the limit q→∞. Based on information theory, we present here an analysis of the classical order parameters plus new short-range parameters defined here. Thus, we show that even using the first nearest neighbors spin-spin correlations only, it is possible to distinguish the two transitions presented by this system for q greater than or equal to 5. Moreover, the appearance at relatively low temperature and disappearance of the BKT phase at a rather fix higher temperature is univocally determined by the short-range interactions recognized by the information content of classical and new parameters.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

We introduce a magnetic bead-based sample preparation scheme for enabling a Raman spectroscopic differentiation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positive and negative samples. The beads were functionalized with the angiotensin-converting enzyme 2 (ACE2) receptor protein, which is used as recognition element to selectively enrich SARS-CoV-2 on the surface of the magnetic beads. Subsequent Raman measurements directly enable discriminating SARS-CoV-2 positive and negative samples. The proposed approach is applicable for other virus species, too, when the specific recognition element is exchanged. Series of Raman spectra were measured on three types of samples, namely SARS-CoV-2, Influenza A H1N1 virus and a negative control. For each sample type, eight independent replicates were considered. All spectra are dominated by the magnetic bead substrate and no obvious differences between sample types are apparent. In order to address the subtle differences in the spectra, we calculated different correlation coefficients, namely the Pearson coefficient and the Normalized Cross Correlation coefficient. By comparing the correlation with the negative control differentiating between SARS-CoV-2 and Influenza A virus is possible. This study provides a first step towards the detection and potential classification of different viruses with the use of conventional Raman spectroscopy.

Background: Physiological changes of blood amino acids and acylcarnitines during healthy child development are not well studied. The LIFE Child study offers a platform with a large cohort of healthy children to investigate these dynamics. We aimed to assess the intra-person variability of these blood metabolites and associations with anthropometric parameters related to excess body fat and IGF1 serum levels. Methods: Concentrations of 23 amino acids, 5 acylcarnitines and free carnitine of 2213 children aged between 3 months and 19 years were analyzed using liquid chromatography/tandem mass spectrometry. Standard deviation score values were used to account for physiological sex- and age-related differences. The stability of metabolites was assessed through the coefficient of determination. Associations with parameters for body composition and IGF1 serum levels were determined by Pearson correlation and linear regression. Results: Our research reveals substantial fluctuations in metabolite concentrations in the same person during childhood and adolescence. Most metabolites had a positive correlation with parameters of body composition with notable influence of sex, pubertal status and weight group specific differences. Glycine exhibited negative associations with parameters of body fat distribution especially in normal weight girls, overweight/obese boys and during puberty. Conclusions: The observed alterations in metabolite concentrations contribute to our knowledge on the complex interplay between blood amino acid and acylcarnitine levels and metabolic health in children and adolescents.

While maintenance dredging of port access channels is often required to maintain navigability, it can result in increased turbidity, sediment plumes, and associated reductions in water quality. Unoccupied aircraft systems (UAS, or drones) are increasingly applied to study water quality due to their high spatial and temporal resolutions. In this study, we investigated the use of drone imagery to monitor turbidity in the Morehead City Harbor, North Carolina, USA, during channel maintenance by hopper dredge. Drone flights were conducted concurrently with in-situ sampling during active dredging and post-dredging. Multispectral drone images were radiometrically calibrated, converted to reflectance and then turbidity using two separate processing methods and a single-band (red; 620nm-700nm) generic turbidity retrieval algorithm, and then compared to in-situ measurements. The method of using average reflectance to retrieve a single turbidity measurement per drone image produced agreeable results when compared to the in-situ measurements (R² = 0.84). This method was then used to generate turbidity maps and extract surface plumes. While this could be considered a limited validation, the results indicate that realistic values can be obtained from drone imagery for low and high turbidity concentrations (1-72 FNU), making drones a viable option for monitoring surface turbidity associated with dredging.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Abstract: Our research analyzed the characteristics of phase IV clinical trials in oncology using data from the ClinicalTrials.gov registry. The included trials were conducted between January 2013 and December 2022 and were examined for key characteristics, including outcome measures, interventions, sample sizes, and study design, different cancer types, and geographic regions. Our analysis included 368 phase IV oncology studies. We found that 50% of these studies aimed to examine both safety and efficacy, while 43.5% only reported efficacy outcome measures, and 6.5% only described safety outcome measures. Only 16.9% of studies were powered to detect adverse events with a frequency of 1 in 100. Targeted therapies accounted for the majority of included studies (53.5%), with breast (32.91%) and hematological cancers (25.82%) being the most frequently investigated malignancies. Most phase IV oncology studies lacked sufficient power to detect rare adverse events due to their small sample sizes and instead focused on effectiveness. To ensure that there is no gap in drug safety data collection and detection of rare adverse events due to limited phase IV clinical trials, there is a significant need for additional education and participations by both health care providers and patients in spontaneous reporting processes.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

In the upgrading of biomass pyrolysis vapors to hydrocarbons, dehydration accomplishes a primary objective of removing oxygen and acidic zeolites represent promising catalysts for dehydration reaction. Here, we utilize density functional theory calculations to estimate adsorption energetics and intrinsic kinetics of alcohol dehydration over H-ZSM-5, H-BEA, and H-AEL zeolites. ONIOM calculations of adsorption energies were observed to be inconsistent when benchmarked against QM/Hartree-Fock and periodic boundary condition calculations. However, reaction coordinate calculations of adsorbed species and transition states were consistent across all levels considered. Comparison of ethanol, iso-propanol (IPA), and tert-amyl alcohol (TAA) over these three zeolites allowed for a detailed examination of how confinement impacts reaction mechanisms and kinetics. TAA, seen to proceed via a carbocationic mechanism, was found to have the lowest activation barrier, followed by IPA and then ethanol, both of which dehydrate via a concerted mechanism. Barriers in H-BEA were consistently found to be lower than in H-ZSM-5 and H-AEL, attributed to late transition states and either elevated strain or inaccurately estimating long-range electrostatic interactions in H-AEL, respectively. Molecular dynamics simulations revealed that the diffusivity of these three alcohols in H-ZSM-5 are significantly overestimated by Knudsen diffusion, which will complicate experimental efforts to develop a kinetic model for catalytic fast pyrolysis.

The integration of diverse distributed generation (DG) units, encompassing both Renewable Energy Sources (RES) and non-RES technologies delves into voltage levels, current distributions, and power flows, aiming to optimize and effectively manage the distribution network. An RES-based DGs such as photovoltaic systems and wind turbines, alongside non-RES units like fuel cells and micro turbines. This study proposes a hybrid approach the Multi-Objective Genetic Algorithm - Grey Wolf Optimizer (MOGA-GWO). By merging the strengths of multi-objective genetic algorithms with the efficiency of the Grey Wolf Optimizer, this advanced algorithm seeks semi-optimal solutions for multi-objective optimization problems. The algorithm aims to improve convergence speed without compromising solution quality, offering a promising solution for optimizing the characteristics of DG and RES integration in distribution networks compared to Cuckoo Search and Simulation Annealing Techniques. Key algorithmic operations include individual representation, initialization, fitness function computation, selection, crossover, mutation, and ending conditions. The DG optimal power flow problem is explored with a focus on minimizing generation costs, improving voltage profiles, minimizing losses, enhancing reliability, integrating renewable energy, reducing environmental impact, managing congestion, and ensuring compliance with operational constraints. Beyond traditional considerations, the study emphasizes neglected objectives and constraints, such as cyber-security concerns, real-time operation, regulatory frameworks, social acceptance, lifecycle environmental impact, grid resilience, data privacy, aging infrastructure compatibility, and economic viability.

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive creating immunocompromised conditions or hyperactive causing autoimmune tissue destruction. Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Abstract: Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to hospital-based settings. Updated Dutch PPSA guidelines recommending two anesthesiologists and a ventilator during out-of-hospital PPSA have increased costs and raised concerns about the accessibility to specialized high quality dental care for children in the Netherlands. Aim: This study aims to investigate the impact of the updated 2017 guideline on the occurrence rate of adverse events during PPSA, as recorded in the anesthesia complication database of twelve participating Dutch dental clinics, with adjustments made for age, weight, and duration of treatment. Method: Data of 25,872 children treated at 12 dental clinics performing out-of-hospital PPSA between 1997 and 2019 were analyzed. Eligible children were aged 2-18 with ASA classification I and II. A logistic two-level mixed-effects model is used to estimate the updated guideline’s impact on adverse events. Results: In the final model we analyzed the data of 21,759 children in nine dental clinics. The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64 – 0.89) after the implementation of the updated guideline, compared to before the updated guideline. This outcome was significant with a P=0.001, indicating a protective effect. The average odds per clinic of having an adverse event was 0.04 with a 3.81% chance. Conclusion: Our findings demonstrate a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adherence to evidence-based guidelines in improving patient safety and the quality of care provided during pediatric procedural sedation and analgesia in out-of-hospital dental clinics. Our study underlines the necessity of considering the complex underlying mechanisms that play a role in the development and implementation of evidence-based practice and safety initiatives on the occurrence of adverse events.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Background: Glioblastoma (GBM) is a highly aggressive, invasive, and growth-factor-independent grade IV glioma. Survival following the diagnosis is generally poor, with a median survival of approximately 15 months, and it is considered the most aggressive and lethal central nervous system tumor. Conventional treatments based on surgery, chemotherapy, and radiation therapy only delay progression, and death is inevitable. Malignant glioma cells are resistant to traditional therapies, potentially due to a subpopulation of glioma stem cells that are invasive and capable of rapid regrowth. Methods: Systematic retrieval of information was performed on PubMed. Specified keywords were used in PubMed and the articles published in peer-reviewed scientific journals were associated with brain GBM cancer, sodium iodide symporter (NIS). Additionally, the words 'radionuclide therapy', 'radioiodine', 'iodine-131', 'molecular imaging', 'gene therapy', and 'translational imaging' were used. Other keywords such as ‘glioblastoma', 'targeted', 'theranostic', 'symporter', 'virus', 'solid tumor', 'combined therapy', 'pituitary', or 'plasmid' were also used in appropriate literature databases and search engines. 19 articles were found in this search on Mesenchymal Stem Cell Sodium Iodide Symporter and GBM. \ These articles were from the years 2000 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. Results: For as long as they express functional NIS, mesenchymal stem cells systemically repress T and B cells; however, after that, they are largely replaced by mesenchymal stem cells generated from embryonic stem cells that are functionally competent. As a result of their natural capacity to identify malignancies, MSC are employed as tumor therapy vehicles. Because MSCs may be transplanted in several methods, they have been proposed as ideal vehicles for NIS gene transfer. Conclusion: Non-invasive imaging-based detection of glioma stem cells presents an alternate means to monitor the tumor and diagnose and evaluate recurrence. The sodium iodine symporter gene is a specific gene in a variety of human thyroid disease that functions to move iodine into the cell. In recent years, an increasing number of studies related to the sodium iodide symporter gene have been reported in a variety of tumors and as therapeutic vectors for imaging and therapy. Gene therapy and nuclear medicine therapy for GBM provide a new direction.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

Rare Earth Elements (REE), also known as Lanthanides (Ln3+), are a group of 17 elements showing peculiar physical and chemical properties. Unlike technological applications, very little is known about the physiological role and toxicity of Ln3+ on biological systems, in particular on microorganisms (e.g., bacteria), which represent the most abundant domains on our planet. Up to now, very limited studies have been conducted due to Ln3+ precipitation with some anions commonly present in the culture media. Therefore, the development of a minimal medium is essential to allow the study of Ln3+-microbial interactions, limiting considerably the precipitation as insoluble salts. In this regard, a new minimal culture medium capable of solubilizing large amounts of Ln3+, and allowing the growth of different microbial taxa, was successfully developed. Assays have shown that the medium is capable of solubilizing Ln3+ up to 100 times more than other common culture media and allowed the growth of 63 bacteria and 5 fungi. The kinetic growth of one yeast and one gram-positive bacterium has been defined, proving to support superior growth and biomass compared to other commonly used minimal media. Moreover, the sensitivity and uptake/absorption of a Bacillus stratosphericus strain was tested, highlighting its capability to tolerate concentrations up to 10 mM of either Cerium, Gadolinium or Lanthanum and accumulate different quantities of the three.

Rising antimicrobial resistance (AMR) in Salmonella serotypes host-adapted to cattle is of increasing concern to the beef and dairy industry. The bulk of the existing literature focuses on AMR post-slaughter. In comparison, the understanding of AMR in Salmonella among pre-harvest cattle is still limited, particularly in Texas, which ranks top five in beef and dairy exports in the United States; inherently, the health of Texas cattle has nationwide implications for the health of the United States beef and dairy industry. In this study, long-read whole genome sequencing and bioinformatic methods were utilized to analyze antimicrobial resistance genes (ARGs) in 98 isolates from beef and dairy cattle in the Texas Panhandle. Fisher exact tests and elastic net models accounting for population structure were used to infer associations between ARGs and antimicrobial phenotypic profiles and metadata. Gene mapping was also performed to assess the role of mobile genetic elements in harboring ARGs. ARG were found to be statistically different between the type of cattle operation and Salmonella serotypes. Beef operations were statistically significantly associated with more resistance genes compared to dairy operations. Salmonella Heidelberg, followed by Salmonella Dublin isolates, were associated with the most ARGs. Additionally, specific classes of ARGs were only present within mobile genetic elements.

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, Escherichia coli strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as dose increased. The shrinkage level correlated with the DNA fragmentation degree. Ciprofloxacin-resistant bacilli showed no change. Additionally, E. coli strains were incubated with ampicillin for 45 min and processed similarly. The ampicillin-susceptible strain revealed intercellular DNA fragments that increased with dose, unlike the resistant strain. Co-incubation with both antibiotics revealed that ampicillin did not modify the nucleoid condensation effect of ciprofloxacin, whereas the quinolone partially decreased the background of DNA fragments induced by ampicillin. Sixty clinical isolates, with different combinations of susceptibility-resistance to each antibiotic, were co-incubated with the EUCAST breakpoints of susceptibility of ciprofloxacin and ampicillin. The morphological assay correctly categorized all the strains for each antibiotic in 60 min, demonstrating the feasible independent evaluation of a mixture of quinolone and beta-lactam. The rapid phenotypic assay may shorten the incubation times and necessary microbial mass currently required for evaluation.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Background In this study we investigated in detail the role of cannabidiol (CBD), Beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods Briefly, Streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague Dawley rats and performed procedures including Randall Sellito Calipers, Von Frey Aesthesiometer, hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed by using the Laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, JC1 & Mitosox staining were done to determine mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides in-vitro. The rats were administered i.p with BC (30mg/kg), CBD (15mg/kg), or combination while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part, through reducing mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides. Further, BC and CBD combination treatment in-vivo could prevent the deterioration of mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, SIRT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1 and TFAM functions while downregulation of NLRP3 inflammasome, NFκB, COX2 and p62 activity was noted as determined by western blotting. Conclusion the present studies demonstrated that STZ & HG induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that CBD and BC combination ameliorate DN via modulating the mitochondrial quality control system.

Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often results in a loss of many productive years. SAH has a high mortality rate, and sur-vivors often suffer from early and secondary brain injuries. Understanding the pathophysiology of the SAH is crucial to identifying potential therapeutic agents. One promising target for diagno-sis and prognosis of SAH is circulating microRNAs, which regulate gene expression and are in-volved in various physiological and pathological processes. In this review, we discuss the poten-tial of microRNAs as a target for diagnosis, treatment, and prognosis in SAH.

A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

Personality changes have been reported to occur following organ transplantation, and most commonly among heart transplant recipients. We set out to examine whether personality changes do occur following transplantation, and specifically, what types of changes occur among heart transplant recipients compared to other organ recipients. A cross-sectional study was conducted in 2022, in which 47 participants (23 heart recipients and 24 other organ recipients) completed an online survey. In this study, 89% of all transplant recipients reported experiencing personality changes after receiving their organ transplant, which was similar for heart and other organ recipients. With the exception of physical attributes, the types of personality changes reported were similar between the two groups. These finding indicate that heart transplant recipients are not unique in their reported experience of personality changes following organ transplantation. Further studies are needed to deepen our understanding of what causes these personality changes following organ transplantation.

The Indian meal moth, Plodia interpunctella, poses a significant threat to global agricultural products. Although pheromone-based technologies show promise for P. interpunctella management, limitations like single-sex targeting necessitate exploring complementary strategies. Vegetable-based oils represent a potential alternative, but their efficacy, sex-specificity, and interaction with sex pheromones remain unclear. To answer these questions, we first examined attraction of P. interpunctella female and male adults to ten different vegetable oils, i.e., camellia, corn, olive, peanut, rapeseed, sesame, soybean, sunflower, walnut, and a blended oil (mixture of sunflower seed, rapeseed, soybean, peanut, and sesame oils), in the semi-field conditions. Sesame, olive, and blended oils demonstrated most attractive, capturing significantly more adults compared to other oils. We then evaluated effectiveness of these three attractive oils and their combinations with P. interpunctella sex pheromone in a grain warehouse. Traps baited with these oils captured significantly more females and males compared to control traps without attractants. However, sex pheromone addition did not improve male capture and significantly reduced female capture, suggesting an inhibitory effect. Our findings highlight the potential of blended, olive, or sesame oil trap alone as alternative monitoring and trapping tools for P. interpunctella, delivering novel insights into the development of efficient integrated pest management strategies for stored products.

Neurotrauma continues to contribute to significant mortality and disability. The need for better protective equipment is apparent. This review focuses on improved helmet design and the necessi-ty for continued research. We start by highlighting current innovations in helmet design for sport and subsequent utilization in the lay community for construction. The current standards by sport and organization are summarized. We then address current standards within the military envi-ronment. The pathophysiology is discussed with emphasis on how helmets provide protection. As innovative designs emerge, protection against secondary injury becomes apparent. Much research is needed, but this focused paper is intended to serve as a catalyst for improvement in helmet de-sign and implementation to provide more efficient and reliable neuroprotection across broad arenas.

We present a very computationally light and fast approximation algorithm and then verify it with genetic algorithm and simulated annealing. We show that our algorithm is on par with GA and SA in terms of output produced while having a tightly bounded time complexity. Our algorithm works best when there is a strong positive correlation between the reliability of a component and its cost. We present two algorithms with the same essence. One of them is system cost bounded and the other is target reliability bounded. Our proposed algorithm works on a subsystem level redundancy instead of component level redundancy.

Intertidal seagrass plays a vital role in estimating the overall health and dynamics of coastal environments due to its interaction with tidal changes. However, most seagrass habitats around the globe have been in steady decline due to human impacts, disturbing the already delicate balance in environmental conditions that sustain seagrass. Miniaturization of multi-spectral sensors has facilitated very high resolution mapping of seagrass meadows, which significantly improve the potential for ecologists to monitor changes. In this study, two analytical approaches used for classifying intertidal seagrass habitats are compared: Object-based Image Analysis (OBIA) and Fully Convolutional Neural Networks (FCNNs). Both methods produce pixel-wise classifications in order to create segmented maps, however FCNNs are an emerging set of algorithms within Deep Learning with sparse application towards seagrass mapping. Conversely, OBIA has been a prominent solution within this field, with many studies leveraging in-situ data and multiscale segmentation to create habitat maps. This work demonstrates the utility of FCNNs in a semi-supervised setting to map seagrass and other coastal features from an optical drone survey conducted at Budle Bay, Northumberland, England. Semi-supervision is also an emerging field within Deep Learning that has practical benefits of achieving state of the art results using only subsets of labelled data. This is especially beneficial for remote sensing applications where in-situ data is an expensive commodity. For our results, we show that FCNNs have comparable performance with standard OBIA method used by ecologists, while also noting an increase in performance for mapping ecological features that are sparsely labelled across the study site.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

This paper designed a new type of generator, transgenerator, that integrates the wind turbine and flywheel into one system, aiming to make the flywheel distributed energy storage (FDES) more modular and scalable than the conventional FDES. The transgenerator is a three-member dual-mechanical-port (DMP) machine with two rotating members (inner and outer rotors) and one stationary member (stator). The transgenerator-flywheel system is introduced with the system configuration, transgenerator overview, flywheel operation principle and power management strategies, and control system. Simulations are performed in MATLAB/ Simulink to verify the system viability, including control system verification and the flywheel storage performance evaluation. Results show that the inner and outer rotors can be controlled independently with accurate and fast control response, and the grid-side control works properly. The flywheel performs well with considerable charging power and storage capacity.

Reducing CO2 emissions is urgently needed to slow down the impacts of climate change. CO2 capture using an amine solution has been developed and implemented on pilot and commercial scales. However, amine scrubbing, in particular, produces a lot of degraded solvent as waste and is energy intensive. Solid sorbents have been called to overcome those drawbacks. In this work, waste biomass-derived carbon materials were developed and tested for CO2 capture and conversion. Advanced thermal chemical processes i.e. hydrothermal and pyrolysis were applied to produce materials from agri-food waste such as soybean and okara. It was found that the number of functional groups (-C=O and -OH) in activated carbon appears in the synthesized materials, implying the generation of surface oxygenated groups. Preliminary results showed that the synthesized activated carbons are obtained with good yields, and a relatively high surface area, which may be applied as CO2 adsorption materials to solve the CO2 emission problems.

Single-cell RNA sequencing data facilitates investigation of cell heterogeneity and subpopulations as well as differentially abundant states however modern single-cell RNA sequencing datasets are growing in size and complexity requiring advances in the bioinformatic methods that analyze them. Many methods exist for each step of analysis including read alignment, normalization, quality control, batch effect correction, imputation and dimensionality reduction. With so many options to choose from at each step of the analysis, benchmarking and a synthesis of the literature on the methods available is necessary to inform biological researchers on the most optimal workflow for their data. Here, recent key methods of analysis are highlighted with a focus on methods that facilitate identification of cell subpopulations and differentially abundant cell states. With a constantly expanding toolset for each step in single-cell RNA sequencing dataset analysis, biological researchers should stay informed to utilize the most applicable methods for their own analyses.

Traumatic brain injury (TBI) is a devastating event with severe long-term complications. TBI and its sequelae are one of the leading causes of death and disability in those under 50 years old. The full extent of secondary brain injury is still being intensely investigated; however, it is now clear that neurotrauma can incite chronic neurodegenerative processes. Chronic traumatic encephalopathy, Parkinson’s disease, and many other neurodegenerative syndromes have all been associated with a history of traumatic brain injury. The complex nature of these pathologies can make clinical assessment, diagnosis, and treatment challenging. The goal of this review is to provide a concise appraisal of the literature with focus on emerging strategies to improve clinical outcomes. First, we review the pathways involved in the pathogenesis of neurotrauma-related neurodegeneration and discuss the clinical implications of this rapidly evolving field. Next, because clinical evaluation and neuroimaging are essential to the diagnosis and management of neurodegenerative diseases, we analyze the clinical investigations that are transforming these areas of research. Finally, we briefly review some of the preclinical therapies that have shown the most promise in improving outcomes after neurotrauma.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015 TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of the production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015, TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The present study aims to measure the technical efficiency and establish core factors effecting rice production in Cambodia. Four-years dataset generated from the central government document “Profile on Economics and Social” of entire 25 provinces between 2012-2015 and the stochastic production frontier model (SFA) was applied. The results indicated that the level of output (quantity) of Cambodian rice production varied according to the different level of capital investment in agricultural machineries, total rice actual harvested area, and technically fertilizers application within provinces. Furthermore, evidence revealed the overall mean efficiency of rice production is 78.4% implies that there is still room to further improve technical efficiency by given the same level of inputs and technology. More importantly, the findings revealed that irrigation, production technique and amount of agricultural supporting staffs are being as the most important influencing factors of rice production’s technical efficiency in Cambodia. In conclusion, present study strongly recommends the development of irrigation systems and good water management practices to be considered and bring into more effective actions by the central government as well as related agencies for improving rice production in Cambodia in addition to capital investment and improving technical skills of supporting staffs and rural farmers.

Electrospun ultrathin fibers based on binary compositions of polylactide (PLA) and poly(ε-caprolactone) (PCL) with different ratios of polymer components from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the effect of biopolymers content on the characteristics of the crystal structure of PLA and PCL and the diffusive rotational mobility of the stable TEMPO radical in the amorphous regions of PLA/PCL compositions was shown. It was revealed that after PLA and PCL blending, significant changes in the degree of crystallinity of PLA, PCL segmental mobility, sorption capacity of the radical as well as activation energy of rotational diffusion in the amorphous regions of PLA/PCL composition are observed. The characteristic region of biopolymers’ composition from 50/50 to 30/70 % PLA/PCL blends ratio was found, where the inversion transition of PLA from dispersive medium to dispersive phase where an inversion transition is assumed when the continuous medium of the PLA transforms into a discrete phase. The performed studies made it possible for the first time to carry out a comprehensive analysis of the effect of the system component ratio on the structural and dynamic characteristics of the PLA/PCL film material at the molecular level.

Gliomas are central nervous system (CNS) derived tumors that originate from glial cells and affect six per 100,000 people in the United States. They are the most common form of CNS neoplasm and are highly diffusely infiltrative to surrounding brain tissue. Gliomas of diffusive nature are classified into different subcategories: astrocytomas, oligodendrogliomas, and ependymomas. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are used to determine tumor category and spread which may dictate treatment options. This paper focuses on emerging treatments of chemotherapy management with temozolomide and Avastin as well as emerging immune modulation treatment with vaccinations, manipulation of cellular checkpoints CTLA-4 and PD-1, co-receptor modulation of neuropilin-1, CAR-T cell therapy, and CRISPR-Cas9 gene editing. The employment of TMZ and BEV has been supported in the literature, however, more research is necessitated to fully optimize regimens and to avoid immune- and toxicity-related effects of these drugs. Moreover, an even closer consideration is warranted for current immunotherapies as they are in their infancy compared to TMZ and BEV. Thus, although promising emerging treatment options, therapies involving cancer vaccines, ICIs, immune modulation of neuropilin-1, CAR-T, and CRISPR-Cas9 technology require further investigation into their long-term efficacy and utility in treating gliomas.

Cotton is the most ubiquitous and profitable fiber with diverse industrial and domestic applications. Grown in over 100 countries, it has a global market value of about $40 billion and employs over 350 million people from fields to textile mills, contributing about 7% of total labor-force recruitment in developing economies. Cotton has an indeterminate growth habit and an extensive tap root system affected by soil physicochemical and environmental conditions. There is a consensus among experts that conventional cotton cultivation still has a long way to attain sustainability, which is essential if cotton will maintain its competitive edge over other natural and synthetic fibers like hemp, polyesters, and rayon. Despite several efforts already committed to growing cotton sustainably, sustainability has eluded cotton cultivation globally because of the intense farm inputs (freshwater, pesticides, and heavy-duty equipment) needs, especially in developing economies. Some of the technological advancements towards achieving the goal of sustainable cotton cultivation include the development of new varieties, improved irrigation and mulching and precision agriculture techniques, application of remote sensing and Unmanned Aerial Systems (UAS) combined with image processing, and the introduction of autonomous and multi-purpose robotic platforms for growing and harvesting cotton. This review attempts to evaluate the successes already achieved by stakeholders in moving cotton towards sustainable production and identify areas where efforts are still needed to reach sustainable production and improved profitability goals for cotton with projections for future research directions.

In this study, AlSi12 alloy was fabricated using the selective laser melting (SLM) technique to produce high density components with complex and customized parts for railway applications. Nonetheless, the production of dense samples necessitates the optimization of production process parameters. As a statistical design of experimental technique, the response surface methodology was used to optimise different combination of SLM parameters. The results were analysed using analyse of variance (ANOVA) and the signal-to-noise(S/N) ratios. The relationship between the hardness response to the process parameters (scanning speed and lase power) for determining the optimal processing conditions were examined. A hardness value of 133 HV was obtained. The process parameters were successfully optimized and the relationship between the parameters and the structures of the fabricated samples were reported.

Growth monitoring of crops is a crucial aspect of precision agriculture, essential for optimal yield prediction and resource allocation. Traditional crop growth monitoring methods are labor-intensive and prone to errors. This study introduces an automated segmentation pipeline utilizing multi-date aerial images and orthomosaics to monitor the growth of cauliflower crops (Brassica Oleracea var. Botrytis). The methodology employs YOLOv8, Grounding DINO, and the Segment Anything Model (SAM) for automatic annotation and segmentation. The YOLOv8 model was trained using initial datasets, which then facilitated the training of the Grounded SAM framework. This approach generated automatic annotations and segmentation masks, classifying crop rows for temporal monitoring and growth estimation. The study's findings highlight the efficiency of this automated system in providing accurate crop growth analysis, promoting informed decision-making in crop management and sustainable agricultural practices. Results indicate consistent and comparable growth patterns between aerial images and orthomosaics, with significant periods of rapid expansion and minor fluctuations over time. The integration of these advanced techniques demonstrates the potential for enhancing precision agriculture through reduced labor and increased accuracy in crop growth monitoring.

Modification of electrode surface with a selective layer gives the possibility to detect target ana-lytes of forensic interest. 3-(4-trifluoromethyl)-phenyl)-thiophene (ThPhCF3) was deposited on a graphite (G) electrode by electrochemical oxidation and characterized as a receptor for the recognition of synthetic stimulants (2-aminoindane, buphedrone, naphyrone). First, the structural characterization of the polymeric layer were obtained from Raman spectroscopy. Second, the electrochemical profiles of selected synthetic stimulants and their affinity to ThPhCF3/G-modified electrodes were studied using square wave voltammetry and electrochemical impedance spec-troscopy. The values of the adsorption constant show the importance of – PhCF3 groups in the interaction with synthetic stimulants, namely recognition by the formation of hydrogen bonds (Kads (buphedrone) < Kads (2-AI)) and interaction with aromatic H atoms (Kads (buphedrone) < Kads (naphyrone)). It was demonstrated that the polymeric layer derived from thiophene with – PhCF3 group is capable to increase the intensity of the electrochemical signal.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Indoor environmental comfort is fundamental to human health as people spend 90% of their time indoors. This aspect is even more crucial in hospitals, where the concept of health is closely linked to well-being, ethics, and environmental aspects. Emerging methodologies and technologies such as Digital Twin, Building Information Modeling, the Internet of Things, sensing technologies, and data analytics offer new opportunities to ensure healthier environments and more efficient building management. This paper provides an assessment of how digitalization can support decision-making processes related to maintaining high levels of indoor environmental comfort in hospital settings, particularly by analyzing how real-time data processing and the application of machine learning can promote proactive interventions in these facilities. The methodological approach was based on four phases: defining the objectives of the digital twin, identifying the input data to build and feed the digital model, defining the KPIs to evaluate the system's correct functioning, and identifying the enabling technologies to be integrated into the system to achieve the set goal. The result is a digital twin for managing the operating room and its related services, with the aim of guiding decisions based on accurate data and improving operational efficiency, levels of environmental comfort, and safety regarding the diffusion of medical gases.

A comprehensive modeling framework for the thermoforming of polymer matrix woven laminate composite was developed. Two numerical indicators, the slip path length and traction magnitude, have been identified to be positively correlated to matrix smearing and wrinkling defects. The material model has been calibrated with picture-frame experimental results, and the prediction accuracy for intra-ply shear and thickness distribution were examined with measurements on the physically formed parts. Finally, a parametric study was conducted to determine the relationship between various process parameters and the quality of the formed part. For the trapezoidal part, orienting the laminate at 45-degrees to the mold axis reduces the likelihood of matrix smear and wrinkling defects. Although this laminate orientation yielded a greater spatial variation of part thickness, the thickness deviation is lower than that for the 0-degree orientation case. Higher forming rates were found to result in more defects due to increased slip path lengths and traction magnitudes. Optimal forming speeds should balance rapid shaping within the operating temperature window while avoiding tear. It was discovered that shallower molds benefit from faster ramp rates, while deeper molds require slower rates to manage extensive shearing, stretching, and bending. Faster forming rates lead to smaller thickness increases at high intra-ply shear regions, indicating a shift from intra-ply shear to out-of-plane bending due to the visco-plastic effect of the molten laminate, and can negatively impact part quality. Lastly, it was shown that a well-conceived strategy using darts could improve the part quality by reducing the magnitude of the defect indicators.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

The ability of thermoresponsive polymers to respond to temperature with a reversible conformational change makes them promising ‘smart’ materials for solutions in medical and biotechnological applications. In this work, two such polymers and structural isomers were studied: poly(N-isopropyl acrylamide) (PNiPAm) and poly(2-isopropyl-2-oxazoline) (PiPOx). We compare the critical solution temperatures (CST) of these polymers in D2O and H2O in the presence of Hofmeister series salts, as results obtained under these different solvent conditions are often compared. D2O has a higher dipole moment and electronegativity than H2O, which could significantly alter the CST transition. We used two complementary methods to measure the CST, dynamic light scattering (DLS) and differential scanning calorimetry (DSC), and found that the CST decreased significantly in D2O compared to H2O. In the presence of highly concentrated kosmotropes, the CST of both polymers decreased in both solvents. The influence of the kosmotropic anions was smaller than the water isotope effect at low ionic strengths but considerably higher at physiological ionic strengths. However, the Hofmeister anion effect was quantitatively different in H2O than in D2O, with the largest relative differences observed for Cl-, where the CSTs in D2O decreased more than in H2O measured by DLS but less by DSC. PiPOx was more sensitive than PNiPAm to the presence of chaotropes. It exhibited much higher transition enthalpies and multistep transitions, especially in aqueous solutions. Our results highlight that measurements of thermoresponsive polymer properties in D2O cannot be compared directly or quantitatively to application conditions or even measurements performed in H2O.

Wildfires have continued to increase in frequency and severity in Southern California due in part to climate change. To gain a further understanding of microbial soil communities’ response to fire and functions that may enhance post-wildfire resilience, soil fungal and bacterial microbiomes were studied from different wildfire areas in the Gold Creek Preserve within the Angeles National Forest using 16S, FITS, 18S, 12S, PITS, and CO1 amplicon sequencing. Sequencing datasets from December 2020 and June 2021 samplings were analyzed using DNA Subway, ranacapa, stats, vcd, EZBioCloud, and mixomics. Significant differences were found among bacterial and fungal taxa associated with different fire areas in the Gold Creek Preserve. There was evidence of seasonal shifts in the alpha diversity of the bacterial communities. In the sparse partial least squares analysis, there were strong associations (r>0.8) between longitude, elevation, and a defined cluster of Amplicon Sequence Variants (ASVs). The Chi-square test revealed differences in fungi:bacteria (F:B) proportions between different trails (p=2*10^-16). sPLS results focused on a cluster of Green Trail samples with high elevation and longitude. Analysis revealed the cluster included the post-fire pioneer fungi Pyronema, and Tremella. Chlorellales algae, and pathogenic Fusarium sequences were elevated. Bacterivorous Corallococcus, which secretes antimicrobials, and bacterivorous flagellate Spumella, were associated with the cluster. There was functional redundancy in clusters that were differently composed, but shared similar ecological functions. These results implied a set of traits for post fire resiliency. These included photo-autotrophy, mineralization of pyrolyzed organic matter and aromatic/oily compounds, pathogenicity and parasitism, antimicrobials, and N-metabolism.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

Revealing the spatial distribution mechanism of the coupling effect between soil water and salt is essential for managing saline-alkali farmland. This study utilized the multifractal method to analyze soil water and salt under varying water content levels in arid saline-alkali farmland. Soil samples were collected on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after a rainfall event. The findings showed that a significant decrease in soil water content, contrasting with an increase in soil salt content throughout the soil layers post-rainfall. As water content decreased, the spatial variability of soil water initially increased from S1-3 and then decreased, while the spatial variability of soil salt decreased. The spatial distribution between soil water and salt exhibited a high correlation at S3-4 (with relative water content of soil ranging from 0.52 to 0.75) due to their coupling effect. However, soil salt was unevenly leached by rainfall at high water content levels (S1-2) and precipitated at low water content levels (S5), resulting in low spatial variability correlations between soil water and salt. This study elucidated the coupling process of soil water and salt, identifying their spatiotemporal distribution mechanism in dryland agricultural areas.

Purpose: The aim of this article is to analyze the incidence of undiagnosed obstructive sleep apnea OSA in patients affected by dento-skeletal malformation. We also evaluated the patterns most affected by the condition and calculated the post surgical changes. Methods: We conducted a retrospective cohort study on 71 patients including 35 men and 36 women. Patients were evaluated with Polysomnography before surgery and at least 6 months after surgery to assess any improvement or worsening of the apnea hypopnea index AHI index. Regarding AHI evaluation criteria an AHI > 5 was considered indicative of OSA, 4 5, com-pared to 20.5% described in the Italian population. Conclusion: In patients who receive orthognathic surgery the presence of Obstructive Sleep Apnea is significantly higher than in the general population. When planning the surgical correction of a dentoskeletal malformation, the surgeon must aim not only to the aesthetics results, but also to a proper stomatognathic and respiratory function, this cannot be done without taking poly-somnography information into account.

Brushless Synchronous Machines (BSM) are replacing conventional synchronous machines with static excitation in generation facilities due to the absence of sparking and lower maintenance. However, this excitation system makes challenging measuring electric parameters in the rotor. This fact highly difficult the detection of ground faults, which are the most common type of electrical fault in electric machines. In this paper, a ground fault detection method for BSM is proposed. It is based on an inductive AC/DC rotating current sensor installed in the shaft. In case of a ground fault in the rotating parts of the BSM, a fault current will flow through the rotor’s sensor, inducing voltage in its stator. Analyzing the frequency components of the induced voltage the detection of a ground fault in the rotating elements is possible. The ground faults detection method proposed covers the whole rotor and discern between DC and AC sides. To corroborate the detection method, experimental tests have been performed using a prototype of this sensor connected to laboratory synchronous machines achieving satisfactory results.

This paper analyses the application of deep learning techniques for predicting wave overtopping events in port environments using sea state and weather forecasts as inputs. The study was conducted in the outer port of Punta Langosteira, A Coruña, Spain. A video recording infrastructure was installed to monitor overtopping events from 2015 to 2022, identifying 3709 overtopping events. The data collected was merged with actual and predicted data for the sea state and weather conditions during the overtopping events, creating three datasets. We used these datasets to create several machine learning models to predict whether an overtopping event would occur based on sea state and weather conditions. The final models achieved a high accuracy level during the training and testing stages: 0.81, 0.73, and 0.84 average accuracy during training and 0.67, 0.48, and 0.86 average accuracy during testing, respectively. The results of this study have significant implications for port safety and efficiency, as wave overtopping events can cause disruptions and potential damage. Using deep learning techniques for overtopping prediction can help port managers take preventative measures and optimize operations, ultimately improving safety and helping to minimize the economic impact that overtopping events have on the port's activities.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Photovoltaic (PV) systems, which are renewable energy sources, are increasingly being utilized in distributed generation. To maintain a stable energy balance, energy storage systems such as batteries (BAT) play a vital role. Electric vehicles (EVs) offer a promising solution with rechargeable battery systems for operation. The BATs must maintain their state of charge within design boundaries, despite intermittent PV and load power fluctuations, and advanced power control and management techniques are essential for their effective operation. The article evaluates an intelligent controller that uses a Sliding Mode Control adaptive deep learning algorithm Convolutional Neural Networks (SMC-CNN) and a unique Strategy for managing supervisory power. (SPMS) for photovoltaic systems with battery energy storage for better regulation of DC bus voltage. SMC-CNN offers exceptional resilience and seamless functionality, minimizing fluctuations in DC bus voltage in the control strategy design requirements. The primary goals are maintaining a consistent power supply and ensuring continuous service by preventing system components from exceeding capacity. This study aims to enhance the control of DC bus voltage in the PV and battery system, with the primary significance focusing on the following aspects. The advanced SPMS has been created, incorporating control system constraints to enhance SOC balancing speed and reduce fluctuations in DC bus voltage. Power flow management involves optimizing energy flow between the PV system, battery system, and load while minimizing battery capacity requirements. The proposed SMC-CNN and SPMS are demonstrated through real-time simulation using Matlab/Simulink, as demonstrated in comprehensive case studies.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

This investigation explores the potential of enhancing aqueous zinc-ion batteries (AZIBs) through the introduction of a novel cathode material, NH4V4O10 (NVO), combined with reduced graphene oxide (rGO). Utilizing Density Functional Theory (DFT), it was hypothesized that the incorpora-tion of rGO would increase the interlayer spacing of NVO and diminish the charge transfer in-teractions, thus promoting enhanced diffusion of Zn2+ ions. These theoretical predictions were substantiated by experimental data acquired from hydrothermal synthesis, which indicated a marked increase in interlayer spacing. Significantly, the NVO-rGO composite exhibits remarkable cyclic durability, maintaining 95% of its initial specific capacity of 507 mAh g−1 after 600 cycles at a current density of 5 A g−1. The electrochemical performance of NVO-rGO not only surpasses that of pristine NVO but also outperforms the majority of existing vanadium oxide cathode materials reported in the literature. This study underscores the effective integration of theoretical insights and experimental validation, contributing to the advancement of high-performance energy storage technologies.

This study explores the enhancement of aqueous zinc-ion batteries (AZIBs) using ammonium-enhanced vanadium oxide cathodes. Density Functional Theory (DFT) calculations reveal that NH₄⁺ incorporation into V₆O₁₆ lattices significantly facilitates Zn²⁺ ion diffusion by reducing electrostatic interactions, acting as a structural lubricant. Subsequent experimental validation using (NH₄)₂V₆O₁₆ cathodes synthesized via a hydrothermal method corroborates the DFT findings, demonstrating remarkable electrochemical stability with a capacity retention of 90% after 2000 cycles at 5 A g⁻¹. These results underscore the potential of NH₄⁺ in improving the performance and longevity of AZIBs, providing a pathway for sustainable energy storage solutions.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

The effects of the ferrocenyl moiety to enhance the nucleophilicity of the carbonyl group, situated at its adjacent position, have been explored in a series of α-ferrocenyl ketocarboxylic acids. In the presence of trifluoroacetic anhydride, 3-ferrocenoylpropionic acid and 4-ferrocenoylbutyric acid gave 5-ferrocenyl-4-trifluoroacetyl-2(3H)-furanone and 6-ferrocenyl-5-trifluoroacetyl-3,4-dihydropyran-2-one, respectively. Under similar reaction conditions, 2-ferrocenylcarbonylbenzoic acid, a keto carboxylic acid without a β-hydrogen, gave a dimerized lactone, 3,3’-diferrocenyl-3,3’-diphthalide possibly due to radical coupling. The nucleophilic attack of carbonyl oxygen, activated by the ferrocenyl moiety, to the carboxylic carbon, is assumed to be the crucial mechanistic step in forming these lactones. When the carbonyl group was reduced to an alcohol to break its conjugation with the ferrocenyl moiety, saturated lactones were isolated after the acidic workup. These results indicate that the α-ferrocenyl carbinols readily undergo solvolysis under acidic conditions, giving ferrocenylcarbenium ions, which are attacked by the carboxy oxygen to give lactones.

The polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3’ kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV, but not by adenovirus, an unrelated small, non-enveloped DNA tumor virus. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3Kγ gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.

Background/Objectives Bowel endometriosis (BE) is defined as the presence of endometrial-like tissue in the muscular layer of the bowel wall. When BE does not cause severe obstruction to fecal transit, not leading to (sub)occlusive symptoms, the decision to operate becomes challenging as intestinal surgery is associated with higher complication rates and long-term bowel dysfunction. The aim of this cross-sectional study is to evaluate the quality of life (QoL) in patients with BE undergoing medical therapy or expectant management, investigating the impact of characteristics of BE nodules on QoL and intestinal function. Methods A retrospective cross-sectional analysis was conducted on 580 patients with BE who did not undergo surgery but were treated conservatively by medical therapy or expectant management between January 2017 and August 2022. The diagnosis of BE was done by transvaginal ultrasound and confirmed at double contrast barium enema. After at least one year of follow-up, QoL and intestinal function of patients were evaluated by the Endometriosis Health Profile-5 (EHP-5) questionnaire and Bowel Endometriosis Symptom score (BENS), whereas pain symptoms were assessed by the Visual Analogic Scale (VAS 0-10). Statistical analysis was performed to investigate possible associations between QoL and characteristics of bowel nodules (dimension, location, and evidence of stenosis) as well as type and length of eventual medical therapy. Results Patients with BE had a satisfying overall QoL with a mean EHP-5 score of 105.42 ± 99.98 points and VAS lower than 3 for all pain domains; additionally, they did not show a significant impartment of bowel function with mean BENS score of 4.89 ± 5.28 points. Notably, patients under medical therapy had a better QoL than patients without therapy (p

This study addresses the formidable challenge of solving large-scale Max-Cut problems (MCP). We introduce a rapid computational procedure utilizing a hybrid 1-flip/r-flip local search heuristic. This innovative strategy significantly reduces the computational time required for MCP problems while consistently generating solutions of exceptional quality. The paper presents substantial computational insights, showcasing the effectiveness of our approach on large-scale Max-Cut instances with varying densities. Our proposed heuristic is rigorously evaluated by comparing its performance against a quantum annealing solver, leveraging a multi-start Tabu Search framework. The results underscore the potency of this unique combination as an efficient and effective solution for large-scale QUBO problems. Notably, our hybrid heuristic consistently delivers high-quality solutions within the stringent CPU time limits of 600 seconds, demonstrating its efficacy across Max-Cut instances ranging from 10,000 to 40,000 variables. This research contributes to advancing the state-of-the-art in large-scale QUBO problem-solving, offering a powerful and time-efficient approach with broad applicability.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

This article presents an innovative approach to the design of a safe adaptive backstepping control system. Tailored specifically for underactuated marine robots, the system utilizes simple sensors for enhanced practicality and efficiency. Given their operation in diverse oceanic environments fraught with various sources of uncertainties, ensuring the system's safe and robust behavior holds paramount importance in the control literature. To address this concern, this paper introduces a control strategy designed to ensure robustness at both the kinematic and dynamic levels. By emphasizing the compensation for the system uncertainties, the design integrates a straightforward fuzzy system structure. To further ensure the system's safety, a funnel surface is defined, followed by the design of a suitable nonlinear sliding surface as a function of the funnel and tracking error. Specifically leveraging the Lyapunov function, the study formally establishes the Semi-globally Practically Finite-time Stability of the closed-loop system, validated through simulations conducted on underactuated marine robots.

The focus of this work lies in the construction of monitoring system designed in the form of a patch using a long-lasting potentiometric electrolyte concentration sensor from metal electrodes, in a galvanic cell configuration Mg(s)|NaCl(aq)|Cu(s). Initially, a mathematical analysis was conducted on the expected sensor output through the Nernst equation. The experimental phase involved conducting controlled tests in the laboratory using various molar concentrations of sodium chloride (NaCl) in aqueous solution. Results showed that the electrolyte sensor allows for monitoring electrolyte levels in NaCl in the range of 0.02 to 1 M/L, with electrode lifespan exceeding 10 days. On the other hand, when patch is using human sweat during controlled exercise routines, it showed the sensor's capability for monitoring changes in the subjects' hydration levels in real time. The sensor output potential is greater than 1.7 volts when the sensor electrodes are in contact with human sweat, which is equivalent to measuring molar concentrations at normal hydration and moderately high hydration levels. Sensor results indicate that the system can function in a self-powered manner without external batteries. Additionally, the extended lifespan of its electrodes allows for continuous monitoring of imbalances in the human body, showcasing the system capability for long-term health assessment.

The paper presents a method to assess the effect of electrolyte additives on the energy capacity of Pb-acid batteries. The method applies to any chemically unreactive additive, including suspensions and gels. The approach is thermodynamically based and it leads to the definition of a region of admissible concentrations –the battery’s admissible range– where the battery can undergo an indefinite number of charge/discharge cycles without suffering permanent damage. An experimental procedure to determine this range is presented. The obtained results provide a way to assess the potential of electrolyte additives to improve the energy capacity of Pb-acid batteries. The same results also provide a means to determine the additive concentration that produces the maximum energy capacity increase of the battery. The paper closes with an example of application of the proposed approach to a practical case.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

Using density functional theory (DFT), the density of states of NH4V3O8 (NVO) was analyzed pre and post-oxygen defects (Od) formation. The findings revealed a reduced bandgap in NVO after Od introduction, emphasizing the role of Od in enhancing conductivity of the material, thus improving its electrochemical attributes. Through the water bath method, both NVO and its oxygen-deficient counterpart, (NH4)2V10O25⸱8H2O (NVOd), were synthesized as potential cathode materials for aqueous zinc-ion batteries (AZIBs). Experimental outcomes resonated with DFT predictions, highlighting the beneficial role of oxygen defects in boosting electrical conductivity. Notably, the refined material displayed a remarkable capacity of 479.3 mAh g-1 at 0.1 A g-1, underscoring its promise for advanced energy storage solutions.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

This paper proposes two max-pooling engines, named the RTB-MAXP engine and the CMB-MAXP engine, with a scalable window size parameter for FPGA-based convolutional neural network (CNN) implementation. The max-pooling operation for the CNN can be decomposed into two stages, i.e., a horizontal axis max-pooling operation and a vertical axis max-pooling operation. These two one-dimensional max-pooling operations are performed by tracking the rank of the values within the window in the RTB-MAXP engine and cascading the maximum operations of the values in CMB-MAXP engine. Both the RBM-MAXP engine and the CMB-MAXP engine were implemented using VHSIC Hardware Description Language (VHDL) and verified by simulations. They have been employed for and tested in our CNN accelerator targeting at the CNN model YOLOv4-CSP-S-Leaky for object detection.

Despite their relatively low incidence globally, CNS tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes..

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Biodiversity has become an issue of global anxiety over the past decades due to its rapid decline worldwide. Bangladesh as one of the most densely populated countries in the world is no more exception. The country, although, was once very rich in biodiversity, during the last few decades as a consequence of the rapid reduction in forest area, urbanisation, habitat modification, unsustainable natural resources use and collection and overall climate change it has decreased alarmingly. Of late, the government, as a signatory of various regional and international conservation treaties, has taken various initiatives to improve country’s dwindling biodiversity. This paper reviews the present situation of biodiversity in Bangladesh, management trends and major causes of biodiversity loss. A separate statutory body is fundamental to ensure conservation, sustainable use and equitable sharing of benefits arisen from biodiversity in the country.

Fatal motorcycle accidents on- and off-road continue to be overlooked in the literature. Research is scant on morbidity and mortality due to neck injury, which leaves patients and their families debilitated chronically. Great Lakes EMS Inc. conducted a 10-year retrospective case study, which highlighted that motocross riders who do not wear a neck brace are at an 89% higher risk of a critical cervical spine injury; highly unstable cervical spinal fractures have a sustainably higher risk of morbidity and mortality. Proposed mechanisms of motocross neck braces displace the forces on the neck onto the helmet of the rider to provide a smooth distribution of forces, whereas lack of neck brace use places riders at risk for upper cervical spine fractures such as Jefferson fractures, Hangman's fractures, and Odontoid fractures. Further, evidence suggests the use of back protectors may increase the risk of thoracic and upper spine injuries during a motorcycle crash. The limited data on this topic continues to be a challenge, as there is a lack of understanding of the nature of these injuries, which are likely preventable with proper neck protection.

Background: The practice of self-medication is common worldwide and is an important component of medical self-care. However, the practice can be dangerous and is linked to various risks for the patients and the entire community. This study aimed to estimate the prevalence and factors associated with self-medication among Bangladeshi adults. Methods: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged &gt;19 years) using convenient sampling. A total of 1320 data were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with self-medication practice (SMP). Results: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SMP were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SMP were to get better services (30.59%), perceive SMP without side effects (23.28%), and save time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04 - 3.50) and &gt;12 years of schooling (AOR = 5.03; 95% CI: 2.27 - 11.15), being a businessman (AOR = 4.64; 95% CI: 1.74 - 12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40 - 3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10 - 2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08 - 2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06 - 1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17 - 0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22- 0.69) and herbal (AOR = 0.45; 95% CI: 0.21- 0.97) healing types. Conclusion: More than one-third of the study participants reported practicing self-medication. Increasing the community’s awareness of the extreme consequences of SMP and not just the average experience might sway individuals away from SMP, and implementing strict jurisdiction could be a way to minimize the SMP.

A total of 473 metabolites were identified from 4 sour cherry genotypes using UPLC-TOF-MS. Untargeted metabolomics revealed the dominant chemical groups present in sour cherries. PCA showed that the diversity in sour-cherry metabolites was due to the genotype differences indicating iditol, malic acid, chlorobenzene, 2-mercaptobenzothiazole, and pyroglutamic acid as the predominant contributors. The variable importance in the projection (VIP &gt; 1.0) in partial least-squares–discriminant analysis described 20 biomarker metabolites, representing the cherry metabolome profiles. A heatmap of Pearson’s correlation analysis between the 20 biomarker metabolites and antioxidant activities identified seven antioxidant determinants that displayed the highest correlations with different types of antioxidant activities. This study of correlating metabolomics and antioxidant activities elucidated that the higher nutritional value and biological functions of select sour cherry genotypes can be useful for the development of nutraceutical and functional foods.