Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach in cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support a role of ERVs in tumor development and encourage further search for antiretroviral agents to treat malignancies in which endogenous retroviruses are active.

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

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.

Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early phase clinical trials in cancer patients. However, mutations that predict YAP/TAZ-TEAD activation are not commonly found in most cancer types, making it hard to determine which tumors are de-pendent upon YAP/TAZ-TEAD. Here, we used a combination of RNA-seq and bioinformatics analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be an effective tool to predict tumor cell sensitivity to YAP/TAZ-TEAD inhibition, and thus provide a means to identify patients likely to benefit from TEAD inhibitors.

In tropical Africa, forests and savannas are the two most widespread biomes and potentially represent alternative stable states with divergent species composition. A classic, but untested, hypothesis posited by White (1983) suggests that the transition zones between forests and savannas contain a floristically impoverished assemblage with few representatives from each biome. Further, the evolutionary dimension of diversity has received limited attention, despite its importance for understanding the biogeographic history of biomes. Here, we quantify species richness and several measures of evolutionary diversity in 1° grid cells, using c. 300K occurrence records of trees and shrubs combined with biome affiliation data for 3,125 species. We find that assemblages in transition zones hold fewer woody species than assemblages in forest and savanna zones, as posited by White. However, transition zones hold more phylogenetic diversity than expected given their species richness, whether one considers forest and savanna assemblages separately or together. We also show that the Congo basin forest has low levels of phylogenetic diversity given the number of species and highlight south-eastern African savannas as a centre of savanna woody species richness and phylogenetic diversity. Regions with high phylogenetic diversity given the number of both forest and savanna species were centred around the Dahomey Gap and Cameroon, mainly in transition zones. Overall, our study shows that even if floristically impoverished, transition zones lead to unexpectedly high evolutionary diversity, suggesting they are important centres of evolutionary innovation and diversification.

The article concerns a relatively small but important fragment of John Paul II's pastoral activity, namely his pilgrimages to Poland: the nature of these pilgrimages, their historical background and teaching - especially to the extent that went beyond the immediate and Polish context. The text is the result not only of reading papal statements, but also of personal observation of the political and social atmosphere. The first two parts contain a concise description of the Pope's eight pilgrimages to Poland (before and after the political transformation). The third highlights out the main universal themes raised by the Pope: the dignity of the person, truth and freedom. During consecutive pilgrimages to Poland, he deepened and expanded the themes of his teaching. This collection of his sermons and speeches to Poles constitutes a comprehensive (devoid of redundant repetitions and omissions) treatment of important social, philosophical and theological issues. John Paul II, when speaking to Poles and about Poles, did not lose his universal perspective; he appealed both to Christians and to all people of good will. Papal pilgrimages to Poland are a significant part of modern Polish history, and their message is a valuable intellectual and spiritual gift.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

It is generally accepted that the human abdominal wall is comprised of skin, subcutaneous tissues, muscles and their aponeuroses, and the parietal peritoneum. Understanding these layers and their mechanical properties provides valuable information to those designing procedural skills trainers, supporting surgical procedures (hernia repair), and engineering-based work (in silico simulation). However, there is little literature available on the mechanical properties of the abdominal wall in layers or as a composite. This work characterizes the tensile properties of the human abdominal wall by layer and as a partial composite. Tissues were collected from fresh-never-frozen and fresh-frozen cadavers and tested in uniaxial tension at a rate of 5 mm/min until failure. Stress-strain curves were created for each sample, and the values for elastic moduli, ultimate tensile strength, and strain at failure were obtained. The experimental outcomes from this study demonstrated variation of tensile properties within and between tissues. The data also suggest that the tensile properties of composite abdominal walls are not additive. Ultimately, this body of work contributes to a deeper comprehension of these mechanical properties and will serve to enhance patient care, refine surgical interventions, and assist with more sophisticated engineering solutions.

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and one of the leading causes of blindness globally. Due to the progressive nature of the disease, earlier detection and timely treatment can lead to substantial reductions in the incidence of irreversible vision-loss. Artificial intelligence (AI) screening systems have offered clinically acceptable and quicker results in detecting diabetic retinopathy from retinal fundus and optical coherence tomography (OCT) images. Thus, this systematic review and meta-analysis of relevant investigations was performed to document the performance of AI screening systems that were applied to fundus and OCT images of patients from diverse geographic locations including North America, Europe, Africa, Asia, and Australia. A systematic literature search on Medline, Global Health, and PubMed was performed and studies published between October 2015 and January 2020 were included. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and AI-based investigations were mandatory for studies inclusion. The abstracts, titles, and full-texts of potentially eligible studies were screened against inclusion and exclusion criteria. Twenty-one studies were included in this systematic review; 18 met inclusion criteria for the meta-analysis. The pooled sensitivity of the evaluated AI screening systems in detecting diabetic retinopathy was 0.93 (95% CI: 0.92-0.94) and the specificity was 0.88 (95% CI: 0.86-0.89). The included studies detailed training and external validation datasets, criteria for diabetic retinopathy case ascertainment, imaging modalities, DR-grading scales, and compared AI results to those of human graders (e.g., ophthalmologists, retinal specialists, trained nurses, and other healthcare providers) as a reference standard. The findings of this study showed that the majority AI screening systems demonstrated clinically acceptable levels of sensitivity and specificity for detecting referable diabetic retinopathy from retinal fundus and OCT photographs. Further improvement depends on the continual development of novel algorithms with large and gradable sets of images for training and validation. If cost-effectiveness ratios can be optimized, AI can become a financially sustainable and clinically effective intervention that can be incorporated into the healthcare systems of low-to-middle income countries (LMICs) and geographically remote locations. Combining screening technologies with treatment interventions such as anti-VEGF therapy, acellular capillary laser treatment, and vitreoretinal surgery can lead to substantial reductions in the incidence of irreversible vision-loss due to proliferative diabetic retinopathy.

Current epidemiological data reports that adults aged 65 years and older comprise the most vulnerable age group with the highest proportion of CAP-attributable hospitalizations. Pneumococcal vaccine efficacy (VE) has been shown to decrease over time, contributing to increasing incidence rates of CAP. A holistic evaluation of age, sex, seasonality, and VE are is conducted in this systematic review and meta-analysis of 12 prospective and retrospective cohort studies. The findings suggest that incidence and age are positively associated and that incidence in females is more often reported to be higher in females than in males. In studies that observed seasonality of CAP, high seasons and low seasons were reported to be in winter and summer months, respectively. Lastly, studies that reviewed the effect of vaccination on incidence consistently found decreased observance of CAP in elderly adults following reception of PCV13 or PPSV23. However, one study suggested that such vaccinations may have decreased effectiveness in elderly populations and that research examining potential explanations for this require further investigation. Furthermore, distinct diagnostic and case ascertainment standards, descriptive measures, and methods of prevention and treatment of CAP used across the US are outlined in this review. Public health guidance such as encouraging the reception of pneumococcal vaccinations and mask-wearing during high seasons of CAP, and communicating the risks of not adhering to the aforementioned preventative measures can facilitate an effort to reduce the incidence of CAP and its associated adverse outcomes in the US elderly population.

The rapid expansion of social media and instant messaging applications, such as WhatsApp, has transformed how individuals and organizations communicate and engage. This think piece explores the potential of integrating WhatsApp as a customer relationship management (w-CRM) tool within the education sector to foster and sustain long-term relationships among students, teaching staff, and non-teaching staff. By leveraging real-time features and the widespread use of WhatsApp, educational institutions can create a more interactive and dynamic learning environment, benefiting all stakeholders involved. The literature highlights the importance of establishing clear frameworks for mutual engagement and interaction and the potential of w-CRM to improve communication between students' families and educational institutions. There are potential risks associated with the pervasive use of WhatsApp, and call for future research to explore strategies for mitigating these risks while maximizing the benefits of w-CRM in the education sector. Longitudinal studies are recommended to evaluate the long-term impact of w-CRM on stakeholder relationships, student outcomes, and overall institutional performance.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based studies using these datasets require thoughtful modification to sample selection and analytic strategies, relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings. This paper offers some practical guidance to the full analytical process, demonstrates methods for estimating causal treatment effects on several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying repeated measures outcomes, and aims to increase transparency and reproducibility. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2 or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce an increase in a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines including interleukins IL-1, IL-6, CCL2 protein and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: Low-dose oral interferon-alpha, microdose DNA, low-dose thimerosal and phytocannabinoids.

Observing air quality from sensors onboard light rail cars in Salt Lake County, Utah began as a pilot study in 2014 and has now evolved into a five-year state-funded program. This metropolitan region suffers from both elevated ozone levels during summer and high PM2.5 events during winter. Pollution episodes result predominantly from local anthropogenic emissions but are also impacted by regional transport of dust, chemical precursors to ozone, and wildfire smoke as well as being exacerbated by the topographical features surrounding the city. Two electric light-rail train cars from the Utah Transit Authority light-rail Transit Express (“TRAX”) system were outfitted with PM2.5 and ozone sensors to measure air quality at high spatial and temporal resolution in this region. Pollutant concentration data underwent quality control procedures to determine whether the train motion affected the readings and how the sensors compared against regulatory sensors. Quality assurance results from data obtained over the past year show that TRAX Observation Project sensors are reliable, which corroborates earlier preliminary validation work. Two case studies from summer 2019 are presented to illustrate the strength of the finely-resolved air quality observations: 1) an elevated ozone event and 2) elevated particulate pollution resulting from 4th of July fireworks. The mobile observations were able to capture spatial gradients as well as pollutant hotspots during both of these episodes. Sensors have been recently added to a third light rail train car, which travels on a north-south oriented rail line along which we were unable to monitor air quality previously. The TRAX Observation Project is currently being used to provide reliable pollutant data for health studies and inform urban planning efforts. Links to real-time data displays and updated information on the quality-controlled data from this study are available at https://atmos.utah.edu/air_quality/trax/.

Zircon xenocrysts from alkali basalts in Ratanakiri Province, Cambodia, represent a unique low-Hf zircon, within a 12,000 km long Indo-Pacific megacryst zone. Colourless, yellow, brown and red crystals ({100}, {101}, subordinate {211}, {1103}), with hopper growth and corrosion features, range up to 20 cm in size. Zircon chemistry implicates juvenile, Zr-saturated, mantle-derived alkaline melt (Hf 0.6–0.7 wt%, Y <0.2 wt%, U+Th+REE <600 ppm, Zr/Hf 66–92, Eu/Eu*_N ~ 1, positive Ce/Ce*_N, HREE enrichment). Incompatible element depletion with increasing Yb/Sm_N from core to rim at ~ constant Hf suggests single stage growth. Ti-in-zircon temperatures (~570–740 °C) are lower than predicted by crystal morphology (800–900 °C) and decrease from core to rim (D_T = 10–50 °C). The d¹⁸O values (4.88 to 5.01‰ VSMOW) are relatively low for xenocrysts from the zircon Indo-Pacific zone (ZIP). The ¹⁷⁶Hf/¹⁷⁷Hf values (+ εHf 4.5–10.2) give T_{Depleted Mantle} model source ages of 260–462 Ma and T_Crustal ages of 391–754 Ma. The source magmas reflect variably depleted lithospheric mantle with little supracrustal input. Zircon U-Pb (0.88–1.56 Ma) and (U-Th)/He (0.86–1.02 Ma) ages are older than host basalt ages (~0.7 Ma), suggesting limited residence before transport. Zircon genesis suggests Zr-saturated, Al-undersaturated, carbonatitic-influenced, low-degree partial melting (<1%) of peridotitic mantle at ~60 km beneath the Indochina terrane.

South Africa is a water stressed country experiencing mass urbanisation especially towards coastal cities. The country is already enduring the impacts of global warming and climate change with risk of water scarcity in many areas. The risk was evident with Cape Town near encounter with ‘Day Zero’ i.e., the day when water supplies would have been switched off and residents required to queue for daily water rations. The drought exposed the inadequa-cies of the existing water supply system. Paradoxically, in the same drought period, vast amounts of unutilized stormwater that could have augmented water supply run unabated into the ocean through rivers around the city. The study determined that the problem was not necessarily water shortage but lack of adequate water storage. This study investigated the suitability of coastal reservoirs for stormwater harvesting on the over 3000 km South African coastline. The objective was to identify suitable locations for coastal reservoirs. The study un-dertook a systematic process of selecting several candidate locations and eliminating unsuita-ble sites based on international best practice i.e., coastal topography, climate, hydrology, fluvi-al environment, catchment size and river water quality. Nine candidate sites were identified and ranked based on suitability and associated benefits. The identified locations in order of ranking include Knysna River, Berg River, Buffalo River, Kowie River, Thukela River, Orange River, Port of Richards Bay, Port of Durban, and Lourens River. The Knysna site, with a mean annual precipitation of 600 - 800 mm/annum and mean annual runoff of 100 - 500 Mm3/annum, was determined to be the most optimal location.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

The aim of this systematic review and meta-analysis is to evaluate the prevalence of depression, anxiety, insomnia, stress, PTSD, and distress in Chinese healthcare workers (HCWs) and the changes in prevalence before and after the peak incidence of COVID-19 in China. 20 cross-sectional studies assessing the aforementioned psychological outcomes were included. Eligible studies were searched from the following databases: PubMed, Scopus, and Web of Science. Comparative analysis based on the time period of the included studies was conducted to assess changes in prevalence before and after peak incidence. Additionally, subgroup analyses based on study quality, province, survey tools, gender and healthcare profession, frontline or non-frontline working status, and severity of psychological outcomes were conducted to evaluate the prevalence of outcomes across various study methods, geographic regions, and professions. The findings of this study suggest that the overall prevalence of depression, anxiety, insomnia, stress, PTSD, and distress before peak incidence were 36.2%, 34.2%, 22.4%, 31.3%, 9.8%, and 56.7% as opposed to 31.8%, 24.1%, 34.4%, 59.0%, 20.9%, and 40.7% after the peak. The higher prevalence of depression, anxiety, and distress prior to the peak incidence of COVID-19 in China and of insomnia, stress, and PTSD thereafter serve as evidence that the mental health decline of HCWs is dynamic and should be addressed with adaptive approaches that provide tailored treatments.

The state of community lock-down due to COVID-19 pandemic caused restricted movements of people. There are existing evidence of the negative impact of quarantine and isolation to the mental health of a person in different contexts. A scoping review of literature using Google Scholar was conducted to discover records about the public mental health while in a community quarantine due to COVID-19 pandemic. A methodological approach suggested by Arksey and O’Malley was utilized. It comprised (a) identifying the research questions, (b) identifying relevant literatures, (c) selecting literature, (d) charting the extracted data, and (e) summarizing, analyzing, and reporting the results. As of April 17, 2020, there were only 4 original articles found that discuss psychosocial aspect of the COVID-19 crisis. After an online survey, they present evidence that (1) there is an outward change in the people’s behavior toward self-care during the pandemic and (2) trusting the community governing bodies can minimize the level of anxiety and stress. Other literatures found are original articles in preprint (n=8), letters, commentaries, editorial (n=6), review paper (n=4), and WHO guideline (n=1). It is evident that the psychosocial aspect of COVID-19 crisis needs more attention from the scholars and a large research gap can be lessened trough expansion of online platforms.

Soccer is the most played sport worldwide, with over 265 million participants. It is an incredibly demanding sport, with many different technical skills and physical loads placed on the body. This makes post-match recovery strategies amongst high level soccer players of great importance. The aim of this review is to summarize the existing literature on stretching for post-match recovery, examining its relation to injury prevention, Delayed Onset Muscle Soreness (DOMS), and performance. Scientific evidence of the highest quality and relevance was extracted and reviewed. Despite its common practice, evidence does not support static stretching as a modality to improve recovery post-match amongst soccer players. Larger trials with important outcome measures are needed to determine if a post-match stretching regimen to facilitate recovery exists.

In both managed and unmanaged forests, termites are functionally important members of the dead-wood-associated (saproxylic) insect community. However, little is known about regional-scale environmental drivers of geographic distributions of termite species, and how these environmental factors impact co-occurrence among congeneric species. Here we focus on the southern Appalachian Mountains—a well-known center of endemism for forest biota—and use Ecological Niche Modeling (ENM) to examine the distributions of three species of Reticulitermes termites (i.e., R. flavipes, R. virginicus, and R. malletei). To overcome deficiencies in public databases, ENMs were underpinned by field-collected high-resolution occurrence records coupled with molecular taxonomic species identification. Spatial overlap among areas of predicted occurrence of each species was mapped, and aspects of niche similarity were quantified. We also identified environmental factors that most strongly contribute to among-species differences in occupancy. Overall, we found that R. flavipes and R. virginicus showed significant niche divergence, which was primarily driven by dry-season precipitation. Also, all three species were most likely to co-occur in the mid-latitudes of the study area (i.e., northern Alabama and Georgia, eastern Tennessee and western North Carolina), which is an area of considerable topographic complexity. This work provides important baseline information for follow-up studies of local-scale drivers of these species’ distributions. It also identifies specific geographic areas where future assessments of the frequency of true syntopy vs. micro-allopatry, and associated interspecific competitive interactions, should be focused.

Molecular autism research is evolving towards a biopsychosocial framework that is more informed by autistic experiences. In this context, research aims are moving away from correcting external autistic behaviors and towards alleviating internal distress. Autism Spectrum Conditions (ASCs) are associated with high rates of depression, suicidality and other comorbid psychopathologies, but this relationship is poorly understood. Here, we integrate emerging characterizations of internal autistic experiences within a molecular framework to yield insight into the prevalence of psychopathology in ASC. We demonstrate that descriptions of social camouflaging and autistic burnout resonate closely with the accepted definitions for early life stress (ELS) and chronic adolescent stress (CAS). We propose that social camouflaging could be considered a distinct form of CAS that contributes to allostatic overload, culminating in a pathophysiological state that is experienced as autistic burnout. Autistic burnout is thought to contribute to psychopathology via psychological and physiological mechanisms, but these remain largely unexplored by molecular researchers. Building on converging fields in molecular neuroscience, we discuss the substantial evidence implicating mitochondrial dysfunction in ASC to propose a novel role for mitochondrial allostatic load in the relationship between autism and psychopathology. An interplay between mitochondrial, neuroimmune and neuroendocrine signaling is increasingly implicated in stress-related psychopathologies, and these molecular players are also associated with neurodevelopmental, neurophysiological and neurochemical aspects of ASC etiology. Together, this suggests an increased exposure and underlying molecular susceptibility to ELS that increases the risk of psychopathology in ASC. This article describes an integrative framework shaped by autistic experiences that highlights novel avenues for molecular research into mechanisms that directly affect the quality of life and well-being of autistic individuals. Moreover, this framework emphasizes the need for increased access to diagnoses, accommodations, and resources to improve mental health outcomes in autism.

Disruptive selection arises when extreme phenotypes have a fitness advantage compared to more intermediate phenotypes. Theory and evidence suggest that intraspecific resource competition is a key driver of disruptive selection. However, while competition can be indirect (exploitative) or direct (interference), the role of interference competition in disruptive selection has not been tested, and most models of disruptive selection assume exploitative competition. We experimentally investigated whether the type of competition affects the outcome of competitive interactions using a system where disruptive selection is common: Mexican spadefoot toads (Spea multiplicata). Spea tadpoles develop into alternative resource-use phenotypes: carnivores, which consume fairy shrimp and other tadpoles, and omnivores, which feed on algae and detritus. Tadpoles intermediate in phenotype have low fitness when competition is intense, as they are outcompeted by the specialized tadpoles. Our experiments revealed that the presence of carnivores significantly decreased foraging behavior in intermediate tadpoles, and that intermediate tadpoles had significantly lower growth rates in interference competition treatments with carnivores but not with omnivores. Interference competition may therefore be important in driving disruptive selection. As carnivore tadpoles are also cannibalistic, the ‘fear’ effect may have a greater impact on intermediate tadpoles than exploitative competition alone, similarly to non-consumptive effects in predator-prey or intraguild relationships.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

This review discusses a broad range of recent advances (2013-2017) of chemical imaging using electrochemical methods, with a particular focus on techniques that have been applied to study cellular processes, or techniques that show promise for use in this field in the future. Non-scanning techniques such as microelectrode arrays (MEAs) offer high time-resolution (< 10 ms) imaging, however at reduced spatial resolution. In contrast, scanning electrochemical probe microscopies (SEPMs) offer higher spatial resolution (as low as a few nm per pixel) imaging, with images collected typically over many minutes. Recent significant research efforts to improve the spatial resolution of SEPMs using nanoscale probes, and to improve the temporal resolution using fast scanning have resulted in movie (multiple frame) imaging with frame rates as low as a few seconds per image. Many SEPM techniques lack chemical specificity or have poor selectivity (defined by the choice of applied potential for redox-active species). This can be improved using multifunctional probes, ion-selective electrodes and tip-integrated biosensors, although additional effort may be required to preserve sensor performance after miniaturization of these probes. We discuss advances to the field of electrochemical imaging, and technological developments which are anticipated to extend the range of processes that can be studied. This includes imaging cellular processes with increased sensor selectivity and at much improved spatiotemporal resolution than has been previously customary.

Background: Pleurotus ostreutus is one of the world’s most commonly consumed mushrooms. Cultivation of mushrooms using wood resources usually results in environmental issues of deforestation. Juncao grass Pennisetum sp, Arundo Donax, and Methodology: Miscanthus are the culture mediums used in this research which offered a composting system most particularly for a simple formulation, cheap and feasible for small farms in cultivating oyster mushrooms. Results: The present study assessed the different junco grass as a substrate for growing Pleurotus ostreatus given the enzyme activities, growth, and yields. In addition, on the other hand, Lignin peroxidase (LiP) was the most active enzyme in each culture material among the other enzyme activities expressed differently between substrate and growing stages. Fruiting bodies harvested on giant grass,Arundo donax,and miscanthus,substrate weighed 159.2g/bag,132g/bag, and 65.1g/bag on average respectively. The biological efficiency of pleurotus cultivated in three different substrates was 75.2%, 63.4%, and 28.7%, respectively. Lignin peroxidase (LiP) was the most active enzyme followed by Laccase in each substrate. At the same time, other enzyme activities were differently expressed between substrate and different developmental stages. Nutrient analysis revealed significant variations, with differences in polysaccharides, proteins, and amino acids among substrates as well as the presence of heavy metals as arsenic, lead, mercury, and cadmium content in all samples was within safe limits. Conclusion: Findings from this study will serve as a solid foundation for future studies aimed at characterizing different substrate responses on enzyme activity. This research provides a sustainable footprint for subsequent research promoting eco-friendly mushroom production. The obtained results indicate that Arundo donax should be a good substrate in place of giant grass, using miscanthus is not productive based on the results obtained in this research the juncao grasses offer a sustainable approach that reduces reliance on wood-based substrates and enhances environmental sustainability.

Kluyveromyces marxianus (K. marxianus) is a newly emerging industrially relevant yeast. It is known to possess a highly efficient Non-Homologous End Joining (NHEJ) pathway that promotes random integration of non-homologous DNA fragments into its genome. The nature of the integration events was traditionally analyzed by Southern blot hybridization. However, the precise DNA sequence at the insertion sites were not fully explored. We transformed a PCR product of the Saccharomyces cerevisiae URA3 gene (ScURA3) into an uracil auxotroph K. marxianus wildtype strain and picked 24 stable Ura+ transformants for sequencing analysis. We took advantage of rapid advances in DNA sequencing technologies and developed a method using a combination of Illumina MiSeq and Oxford Nanopore sequencing. This approach enables us to uncover the Gross Chromosomal Rearrangements (GCRs) that are associated with the ScURA3 random integration. Moreover, it will shine a light on understanding DNA repair mechanisms in Eukaryotes, which could potentially provide insights for cancer research.

This study presents a comprehensive comparative analysis of retrofitting techniques aimed at enhancing the seismic resilience of seismically vulnerable historical buildings. Recognizing the dual objectives of structural safety and architectural preservation, this research evaluates and compares several advanced retrofitting methods, including base isolation, strengthening of masonry, steel bracing systems, Fiber-Reinforced Polymer (FRP) wrapping, and damping devices. Each technique is critically assessed based on its effectiveness in mitigating seismic risks, its compatibility with historical architectural features, and its applicability to various building types. Base isolation is highlighted for its ability to decouple buildings from ground motion, thereby significantly reducing seismic forces and protecting architectural integrity. Strengthening of masonry through the use of fiber-reinforced polymers and steel elements enhances the ductility and strength of masonry walls, making them more resilient to seismic forces. Steel bracing systems are shown to provide essential lateral support, particularly in timber-framed structures, improving overall stability and reducing deformation during earthquakes. FRP wrapping is identified as a versatile technique that strengthens structural elements without compromising aesthetic value, making it suitable for reinforcing concrete and masonry components. Damping devices, including viscous dampers and tuned mass dampers, are discussed for their ability to dissipate seismic energy and control structural vibrations, offering a minimally invasive solution that preserves historical aesthetics. The study also addresses several challenges and research gaps associated with these retrofitting techniques, such as ensuring architectural compatibility, assessing long-term material performance, optimizing cost-effectiveness, and navigating complex regulatory frameworks. By advancing knowledge in these areas, the research aims to foster interdisciplinary collaboration and innovation in the development of retrofitting solutions. Ultimately, this study contributes to the ongoing efforts to safeguard historical buildings against seismic hazards. By leveraging cutting-edge technologies and best practices in structural engineering and architectural conservation, stakeholders can develop sustainable, cost-effective, and culturally sensitive retrofitting strategies that protect valuable cultural heritage for future generations.

Background: In recent years, computational aesthetics and neuroaesthetics have provided novel insights into understanding beauty. Building upon the findings of traditional aesthetics, this study aims to combine these two research methods to explore an interdisciplinary approach to studying aesthetics; Method: Abstract artworks were used as experimental materials. Based on traditional aesthetics and in combination, features of composition, tone, and texture were selected. Computational aesthetic methods were then employed to correspond these features to physical quantities: blank space, gray histogram, GLCM, LBP, and Gabor filters. An EEG experiment was carried out, in which participants conducted aesthetic evaluations of the experimental materials in different contexts (genuine, fake), and their EEG data was recorded to analyze the impact of various feature classes in the aesthetic evaluation process. Finally, a SVM was utilized to model the feature data, EEG data, context data, and subjective aesthetic evaluation data; Result: Behavioral data revealed that higher aesthetic ratings in the genuine context. EEG data indicated that genuine contexts elicited more negative deflections in the prefrontal lobes between 200-1000ms. Class II compositions demonstrated more positive deflections in the parietal lobes at 50-120ms, while Class I tones evoked more positive amplitudes in the occipital lobes at 200-300ms. Gabor features showed significant variations in the parieto-occipital area at an early stage. Class II LBP elicited a prefrontal negative wave with a larger amplitude. The results of the SVM models indicated that the model incorporating aesthetic subject and context data (ACC=0.76866) outperforms the model using only parameters of the aesthetic object (ACC=0.68657); Conclusion: A positive context tends to provide participants with a more positive aesthetic experience, but abstract artworks may not respond to this positivity. During aesthetic evaluation, the ERP data activated by different features show a trend from global to local. The SVM model based on multimodal data fusion effectively predicts aesthetics, further demonstrating the feasibility of the combined research approach of computational aesthetics and neuroaesthetics.

Background: Symmetry is a special kind of balance. This study aims to systematically explore and apply the role of balanced composition in aesthetic judgments by focusing on balanced composition features and employing research methods from computational aesthetics and Neuroaesthetics. Methods: First, experimental materials were classified by quantifying balanced composition using several indices, including symmetry, center of gravity, and negative space. An EEG experiment was conducted with 18 participants, who were asked to respond dichotomously to the same stimuli under different judgment tasks (balance and aesthetics), with both behavioral and EEG data being recorded and analyzed. Subsequently, participants' data were combined with balanced composition indices to construct and analyze various SVM classification models. Results: Participants largely used balanced composition as a criterion for aesthetic evaluation. ERP data indicated that from 300-500ms post-stimulus, brain activation was more significant in the aesthetic task, with unbeautiful and imbalanced stimuli eliciting larger frontal negative waves and occipital positive waves. From 600-1000ms, beautiful stimuli caused smaller negative waves in the PZ channel. The results of the SVM models indicated that the model incorporating aesthetic subject data (ACC=0.9989) outperforms the model using only balanced composition parameters of the aesthetic object (ACC=0.7074). Conclusions: Balanced composition is a crucial indicator in aesthetics, with similar early processing stages in both balance and aesthetic judgments. Multimodal data models validated the advantage of including human factors in aesthetic evaluation systems. This interdisciplinary approach not only enhances our understanding of the cognitive and emotional processes involved in aesthetic judgments but also enables the construction of more reasonable machine learning models to simulate and predict human aesthetic preferences.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

The steady state tube furnace (SSTF) (ISO/TS 19700) was used to assess the effects altering the reaction zone of a flame had on smoke toxicity measurements. The gas inlet of the apparatus was modified to allow for a mixture of nitrogen and air to be introduced into the system. The volume of air used in each test remained at 2 L min-1 , and additional volumes of nitrogen were varied between tests altering the total volume of gas used in the primary gas inlet. The chosen conditions were representative of under-ventilated flaming by using a restricted oxygen environment. The research shows that the increase in volume flow of gas over a sample increased the smoke toxicity of the materials tested (CO and HCN). When increasing the volume of the primary air-flow through the tube furnace, the flow causes thinning of the flame zone in the apparatus and results in gaseous species spending less time in the reaction zone, resulting in less time available for chemical reactions to occur. This resulted in less complete combustion occurring, and hence an increased yield of measured products of incomplete combustion (CO and HCN), and a decreased yield of products of complete combustion (CO2).

This article describes the transition of an undirected active network, used for numerical and logical analysis, and made up of communicating operators and nodes, and being self-extensible, into a network of semantic structures, and the extensions necessary to handle language. The network, called Active Structure, was infused with knowledge in the form of tens of thousands of definitions taken from a human-readable dictionary. Where the dictionary fell short, from circularity, lack of a hierarchical form for its senses and sub senses, or inadequate detail around verbs, the entries were extensively curated. The result is a machine which has access to every meaning of every word in its vocabulary, and needs to manage the right meaning for every use of a word, a task that our unconscious minds now handle. To demonstrate that such a network can aspire to human-level tasks, we have begun loading an Anti-Money Laundering Act so that the machine can devise and test strategies against money launderers. There is a higher goal being aimed at, the breaking of the Four Pieces Limit. That is, the network is not intended to save money on human cognitive labor, but to raise an absurdly low limit on it.

The eastern subterranean termite, Reticulitermes flavipes, currently inhabits previously glaciated regions of the northeastern U.S., as well as the unglaciated southern Appalachian Mountains and surrounding areas. We hypothesized that Pleistocene climatic fluctuations have influenced the distribution of R. flavipes, and thus the evolutionary history of the species. We estimated contemporary and historical geographic distributions of R. flavipes by constructing Species Distribution Models (SDM). We also inferred the evolutionary and demographic history of the species using mitochondrial (cytochrome oxidase I and II) and nuclear (endo-beta-1,4-glucanase) DNA sequence data. To do this, genetic populations were delineated using Bayesian spatial genetic clustering, competing hypotheses about population divergence were assessed using approximate Bayesian computation (ABC), and changes in population size were estimated using Bayesian skyline plots. SDMs identified areas in the north with suitable habitat during the transition from the Last Interglacial to the Last Glacial Maximum, as well as an expanding distribution from the mid-Holocene to the present. Genetic analyses identified three geographically cohesive populations, corresponding with northern, central, and southern portions of the study region. Based on ABC analyses, divergence between the Northern and Southern populations was the oldest, estimated to have occurred 64.80 thousand years ago (kya), which corresponds with the timing of available habitat in the north. The Central and Northern populations diverged in the mid-Holocene, 8.63 kya, after which the Central population continued to expand. Accordingly, phylogeographic patterns of R. flavipes in the southern Appalachians appear to have been strongly influenced by glacial-interglacial climate change.

Bioprospecting native Australian plants offers potential discovery of latent and novel bioactive compounds. Promising cytotoxic and antibacterial activity of methanolic extracts of Pittosporum angustifolium and Terminalia ferdinandiana led to further fractionation and isolation using our laboratory’s bioassay guided fractionation protocol. Hence, the aim of this study was to further evaluate the bioactivity of the fractions and subfractions and characterize bioactive compounds using liquid chromatography mass spectroscopy (LC-MS/MS) and gas chromatography MS (GC-MS). Compounds tentatively identified in P. angustifolium Fraction 1 using LC-ESI-QTOF-MS/MS were chlorogenic acid and/or neochlorogenic acid, bergapten, berberine, 8’-epitanegool and rosmarinic acid. GC-MS analysis data showed the presence of around 100 compounds, mainly comprising of carboxylic acids, sugars, sugar alcohols, amino acids, and monoalkylglycerols. Furthermore, the fractions obtained from T. ferdinandiana flesh extracts showed no cytotoxicity, except against HT29 cell lines, and only Fraction 2 exhibited some antibacterial activity. The reduced bioactivity observed in the T. ferdinandiana fractions could be attributed to the potential loss of synergy as compounds become separated within the fractions. As a result, further fractionation, and separation of compounds in these samples were not pursued. However, additional dose-dependent studies are warranted to validate the bioactivity of T. ferdinandiana flesh fractions, particularly since this is an understudied species. Moreover, LC-MS/GC-MS studies confirm the presence of bioactive compounds in P. angustifolium Fraction 1/subfractions which helps to explain the significant acute anti-cancer activity of this plant. The screening process designed in this study has the potential to pave the way for developing scientifically validated phytochemical/bioactivity information on ethnomedicinal plants, thereby facilitating further bioprospecting efforts, and supporting the discovery of novel drugs in modern medicine.

ICEpMERPH, the first integrative conjugative element [ICE] of the SXT/R391 family isolated in the United Kingdom and Europe was analyzed to determine the nature of its adaptive functions, its genetic structure and homology to related elements normally found in pathogenic Vibrio or Proteus species. Whole Genome Sequencing of Escherichia coli isolate KH802 [which contains the ICE pMERPH] was carried out using Illumina sequencing technology. ICEpMERPH has a size of 110 Kb and has 112 putative open reading frames [ORFs], the “Hotspot regions” of the element were found to contain putative restriction digestion systems, insertion sequences and heavy metal resistance genes that encode resistance to mercury, as previously reported but also surprisingly to arsenate. A novel arsenate resistance system was identified in Hotspot 4 of the element, and unrelated to other SXT/R391 elements. This arsenate resistance system is potentially linked to two genes, orf 69, encoding an organoarsenical efflux MFS transporter-like protein related to ArsJ and orf70, encoding an NAD-dependent glyceraldehyde-3-phosphate dehydrogenase. Phenotypic analysis using isogenic strains of AB1157 with and without the ICE revealed resistance to low levels of arsenate in the range 15-25 mM. This novel, low level resistance may have an important adaptive function in polluted environments, which often contain low levels of arsenate contamination. Bioinformatic analysis on the novel determinant and the phylogeny of ICEpMERPH is presented.

Expansion tube is ideal energy absorber which dissipates kinetic energy through plastic deformation and friction. There is an urgent need to understand the influence of key parameter, e.g. semi angle, tube material, and friction coefficient, on the mechanical response and energy absorption characteristics of expansion tube. In the present work, the material properties of the tubes were tested under quasi-static loading condition, and the numerical simulations were carried out by using commercial software ABAQUS. Based on the validated finite element simulation, all the semi angle, tube material, and friction have significant effects on the energy absorption capacity of expansion tube. The expansion tube with high tensile stress of parent material have high energy absorption capacity, while the specific energy absorption is linear with the tensile stress/density of tube material. This work would give a guidance to the structural design and parent materials selection for expansion tubes.

Large blocks and boulders of banded iron formation and massive hematite up to 40 x 27 x 6 m and in excess of 10,000 metric tonnes were detached from outcrop of the Wilgie Mia Formation during the ca 2.20 Ga marine transgression at the base of the Paleoproterozoic Windplain Group, and deposited in a broad band on the wave-cut surface 900 to 1200 m to the east. At the same time sand and shingle was scoured from the sea floor, leaving remnants only on the western side of the Wilgie Mia Formation and on the eastern sides of the boulders. Evidence suggesting that the blocks were detached and transported and the sea floor scoured by a tsunami bore with a height of at least 40 m is provided by (1) the deposition of the blocks indicates transportation by a unidirectional sub-horizontal force, whereas the smaller boulders are randomly oriented (2) 900 -1200m separating the BIF outcrop and the blocks (3) the absence of the basal conglomerate between the blocks (4) the blocks and boulders rest directly on the wave-cut surface of deeply weathered amphibolites (5) the blocks and boulders are surrounded and overlain by fine-grained sandstone of the Windplain Group.

Consumption of refined foods and beverages high in sugar make the teeth susceptible to the formation of biofilm, and lead to dental caries and diseases of the oral cavity such as periodontitis and periodontal disease. The aim of the present study was to determine the ability of selected probiotics to inhibit growth and biofilm formation by the cariogenic bacterium Streptococcus mutans in vitro. We screened strains of latic acid bacteria (LAB) (n=120) from the Bioresources Collection and Research Center (BCRC), saliva of healthy adults and infant stool. The antimicrobial activity of LAB in vitro was evaluated by agar spot culture and co-culture of the S. mutans strains. We determined the effect of heating and dilution factors (2- and 4-fold) on the antagonistic activity of LAB. Antagonistic substances in the spent culture suspensions (SCS) of LAB were precipitated by extraction with ammonium sulphate and chloroform to characterise the protein and lipophilic fractions. Results of co-culturing show that the SCS of the three LAB strains (Lactobacillus pentosus 13-1, 13-4 and Lactobacillus crispatus BCRC 14618) subjected to heat treatment showed significantly high antimicrobial activity. We found that substances produced by L. pentosus 13-4 which have the potential to exhibit antimicrobial properties might be lipophilic proteins. Additionally, we infer that the mechanism of reducing biofilm formation by Lactobacillus strains is associated with sucrose-dependent cell–cell adhesion and the gtfC level of glucosyltransferases (Gtfs) in the biofilm. Native LAB strains screened in our study may be used in chewing gums and other processed foods for preventing tooth decay.

A Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using Caenorhabditis elegans as a model system to study presenilin function, we found that loss of C. elegans presenilin orthologue, SEL-12, results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in sel-12 mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in sel-12 mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.

Agricultural activities are the second largest source of greenhouse gas emissions, and carbon emissions from agricultural land use (CEALU) have become a hot issue across the world. However, few scholars explored the impact of agricultural land policies on carbon emissions, such as the High-standard farmland construction(HSFC) in China.Thus，by relying on provincial panel data for China for the period 2005-2017, the effect of the high-standard basic farmland construction policy on carbon emissions from agricultural land use per unit area and its regional differences were quantitatively analyzed using the difference-in-difference (DID) model. The results showed that: 1) China's CEALU per unit area presented a fluctuating upward trend during the period 2005-2017, from 392.58 kg/ha to 457.72 kg/ha, with an average annual growth rate of 1.31%. 2) The high-standard farmland construction(HSFC) policy produced a significant carbon emission reduction effect in agricultural land use, and reduced the CEALU per unit area by 10.80% on average. With the promotion of this policy, its carbon emission reduction effect in agricultural land use presented an overall increasing trend. 3) The carbon emission reduction effect of the high-standard farmland construction policy in agricultural land use was significant in central China, but non-significant in eastern China and western China.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined as exocrine gland hypofunction resulting in dry eyes and dry mouth. Recent interest in biological therapies for pSS has been garnered, however achieving FDA-approval has been challenging due to the numerous complications in the trials. Current literature lacks insight and a molecular target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren's syndrome”. Articles published between 2000 and 2021 in English language were included. Our findings revealed the potential targets for pSS treatment in clinical trials and the most recent advances in understand-ing of molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is overlooking the treatment of extraglandular symptoms such as fatigue, depression and anxiety which pervade most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways and immune reaction have been studied and proved the efficacy and safety. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grad-ing systems adding extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene therapy, stem cell and tissue engineering ther-apy.

Lightning is responsible for most annually burned area by wildfires in the extratropical region of the Northern Hemisphere. Hence, predicting the occurrence of wildfires requires reliable forecasting of the chance of cloud-to-ground lightning strikes during storms. Here, we describe the development and verification of a probabilistic lightning-strike algorithm designed to run on a uniform 20-km grid over the Continental USA and Alaska. The algorithm consists of a large set of logistic equations parameterized via logistic regression using long-term data records of observed lightning strikes and meteorological reanalysis fields from NOAA. Principal Component Analysis was employed to extract 13 Principal Components (strong predictors) from a list of 611 potential predictors. Our statistical analysis revealed that the occurrence of cloud-to-ground lightning strikes primarily depends on three factors: horizontal temperature distribution by pressure levels, amount of low-level atmospheric moisture, and wind vectors. These physical variables impact the vertical separation of electric charges in the lower troposphere during storms causing the voltage potential between ground and the cloud deck to increase to a level that triggers electrical discharges. Results from a forecast verification using independent data showed excellent model skill, thus making this algorithm suitable for inclusion into software systems forecasting the chance of wildfire ignitions.

One of the tools for optimal crop production is regular monitoring and assessment of crops. During the growing season of fruit trees, the bloom period has increased photosynthetic rates that correlate with the fruiting process. This paper presents the development of an image processing algorithm to detect peach blossoms on trees. Images of an experimental peach orchard were acquired from the Parma Research and Extension Center of the University of Idaho using an off-the-shelf unmanned aerial system (UAS), equipped with a multispectral camera (Near-infrared, Green, Blue). The orchard has different stone fruit varieties and different plant training system. Individual tree images (high-resolution) and arrays of trees images (low-resolution) were acquired to evaluate the detection capability. The image processing algorithm was based on different vegetation indices. Initial results showed that the image processing algorithm could detect peach blossoms and demonstrate good potential as a monitoring tool for orchard management.

Precision agriculture is a farm management technology that involves sensing and then responding to the observed variability in the field. Remote sensing is one of the tools of precision agriculture. The emergence of small unmanned aerial vehicles (sUAV) have paved the way to accessible remote sensing tools for farmers. This paper describes the comparison of two popular off-the-shelf sUAVs: 3DR Iris and DJI Phantom 2. Both units are equipped with a camera gimbal attached with a GoPro camera. The comparison of the two sUAV involves a hovering test and a rectilinear motion test. In the hovering test, the sUAV was allowed to hover over a known object and images were taken every second for two minutes. The position of the object in the images was measured and this was used to assess the stability of the sUAV while hovering. In the rectilinear test, the sUAV was allowed to follow a straight path and images of a lined track were acquired. The lines on the images were then measured on how accurate the sUAV followed the path. Results showed that both sUAV performed well in both the hovering test and the rectilinear motion test. This demonstrates that both sUAVs can be used for agricultural monitoring.

Technological advancements in the Internet of Things (IoT), unmanned aerial vehicles (UAVs), and novel technological tools have transformed disaster management practices from localized approaches to a global framework. These innovations necessitate a unified understanding and application of diverse methodologies at an international level, ensuring they are accessible and operational across different sectors. This integration is crucial not only for technical personnel but also for medical teams, who play a pivotal role in disaster response and management. By fostering a comprehensive grasp of these methods, we can enhance coordination, efficiency, and effectiveness in addressing disasters on a global scale. The authors aimed to provide a comprehensive overview of emerging techniques that are driving shifts in strategic approaches and treatment technologies. Recognized as a domain of continuous research and development, this overview, by necessity, remains an incomplete snapshot of an evolving field. It highlights the dynamic nature of technological and strategic advancements, underscoring the importance of ongoing investigation and innovation to stay abreast of current trends and future directions. The article also highlights the importance of international collaboration beyond societal and national boundaries A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Silicon carbide single crystal (SiC) has been widely used in the field of power devices, while it is difficult to fabricate ultra-flat surface by traditional manufacturing technologies due to its difficult-to-machine property. This paper investigates the interaction process during femtosecond laser ablation of crystalline silicon carbide based on the two-temperature model simulation and experimental study. The findings reveal that parameters such as laser pulse energy, scanning interval, and defocus amount exert significant influence on ablation depth, roughness, and surface morphology. The femtosecond laser proves effective in removing surface defects from cut SiC substrates, albeit resulting in increased surface roughness. However, subsequent polishing treatment of the laser-ablated silicon carbide surface can mitigate this roughness, underscoring the feasibility of laser surface ablation for silicon carbide single crystals.

With increasing research focus on industrial anomaly detection, numerous methods have emerged in this domain. Notably, memory bank-based approaches, coupled with kNN distance metrics, have demonstrated remarkable performance in anomaly detection (AD) and anomaly segmentation (AS). However, upon examination of the Back to the Feature (BTF) method applied to the Mvtec-3D AD dataset, it was observed that while it exhibited exceptional segmentation performance, its detection performance was lacking. To address this discrepancy, this study base improves the implementation of BTF, especially the improvement of the anomaly score metric. It posits that different "clusters" necessitate distinct k values in kNN distance metrics. For simplify, this assumption is distilled into the proposition that AD and AS tasks impose differing requirements on the k value in kNN distance metrics. Consequently, the paper introduces the BTM method, which utilizes distinct distance metrics for AD and AS tasks. This innovative approach yields superior AD and AS performance (I-AUROC 93.0%, AURPO 96.9%, P-AUROC 99.5%), representing a substantial enhancement over the BTF method (I-AUROC 5.7% ↑, AURPO 0.5% ↑, P-AUROC 0.2% ↑).

People have always hoped to be able to fill an entire plane with ``single unit cells'' without periodicity. This wish was realized after the mathematician discovered a 13-sided ``single unit cell'' named `einstein'. These non-periodic tessellations generally exhibit anisotropic properties, making them superior in terms of mechanical performance compared to periodic structures. From the perspective of information entropy, the reason behind the improved mechanical properties of these structures is the higher entropy associated with non-periodic configurations. To quantify the disorder of non-periodic structures, we propose an entropy expression for the `einstein' metamaterial. To demonstrate the mechanical properties of these high-entropy structures, we fabricate specimens using 3D printing and conducte mechanical experiments. For comparative analysis, we also use ABAQUS to perform finite element analysis of the problem. The research results reveal that the mechanical properties of high-entropy structures created by the non-periodic stacking of cells are significantly improved compared to those of low-entropy structures created by periodic stacking. The conclusions drawn from the study of individual issues are generalizable and may be of assistance in future material and structural design.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Mild traumatic brain injury (mTBI) is the most common brain injury, seen in sports, falls, vehicle, or workplace injuries. Concussion is the most common type of mTBI. Assessment of impairments from concussion are evolving, with oculomotor testing suggested as a key component in a multi-modality diagnostic protocol. The aim of this study was to evaluate the reliability of one eye-tracking system, the EyeGuide Focus. Seventy-five healthy adolescent and adult participants (adolescents: n=28; female=11, male=17, mean age 16.5 ± 1.4 years; adults n=47; female=22; male=25, mean age 26.7 ± 7.0 years) completed three repetitions of the EyeGuide Focus within the one session. Intraclass correlation coefficient (ICC) analysis showed the EyeGuide Focus had overall good reliability (ICC 0.79, 95%CI: 0.70, 0.86). However, a familiarization effect showing improvements in subsequent trials was noticeable in both cohorts (p<0.001) with adolescent participants showing greater familiarisation effects than adults. No differences were observed between sexes (p=0.69). Overall, the EyeGuide Focus was found to be reliable, but the observation of familiarization effects suggests that a standardized protocol of a minimum of three trials be employed, similar to other eye-movement testing applications.

Transportation contributes significantly to greenhouse gas emissions, with electrification offering a promising solution. This study evaluates the degradation of State of Health (SOH) over 2.5 years for electrified buses under different charging protocols: DC Fast charging and Flash charging. The vehicles’ models, charging protocols, and financial implications are discussed. High-level simulations reveal that after 2.5 years, the Flash charging vehicle’s SOH reaches 88.93%, while the DC fast charging vehicle reaches 89.46%, showing a 0.47% difference. This slight variance is attributed to Flash charging vehicles avoiding full charge/discharge cycles, reducing battery aging impact. Considering this minimal SOH degradation difference, the choice between DC Fast charging and Flash charging primarily hinges on capital expenditure disparities. Flash charging, with its lower initial battery capacity and reduced capital costs, presents a compelling alternative for city busoperators seeking to electrify their fleets.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

This paper proposes an approach for image data extraction and driving behavior analysis using geographic information and driving data. Information derived from geographic and global positioning systems was used for image data extraction. In addition, we used an onboard diagnostic II and a controller area network bus logger to record driving data for driving behavior analysis. Driving behavior was analyzed using sparse automatic encoders and data exploration to detect abnormal and aggressive behavior. A regression analysis was used to derive the relationship between aggressive driving behavior and road facilities. Several traffic improvements were proposed for specific intersections and roads. The results indicate that lane ratios without lane markings and with straight lane markings are important features that affect aggressive driving behaviors.

1) Background: A population-based cross-sectional study was conducted to understand how green cover and accessibility of common public open spaces in compact urban areas affect physical activeness of resident. 2) Methods: A total of 554 residents completed a structured questionnaire on quality-of-life, physical activity level, and healthy eating practice. 3) Results: The sampled population lived with green cover averaged 10.11 ± 7.95% (ranged 1.56–9.88), whereas majority (90%) of the residents performed physical activities at medium and high levels. Metabolic Equivalent of Task (MET)-minutes/week was associated with the green cover percentage (Pearson r = 0.092; p < 0.05). Irrespective of age and physical activity level, active residents commonly used public open spaces within district for performing exercise, especially parks and promenade were mostly used by older residents while sports facilities by the younger groups. 4) Conclusions: Current findings suggested promotion of exercise could be achieved by the design or redesign of built environment to include more parks accessible to the residents with the increase of vegetation.

Direct measurement of strain within muscle is important for understanding muscle function in health and disease. Current technology (kinematics, dynamometry, electromyography) provides limited ability to measure strain within muscle. Regional fiber orientation and length are related with active/passive strain within muscle. Currently, ultrasound imaging provides the only non-invasive means of observing regional fiber orientation within muscle during dynamic tasks. Previous attempts to automatically estimate fiber orientation from ultrasound are not adequate, often requiring manual region selection, feature engineering, providing low-resolution estimations (one angle per muscle), and deep muscles are often not attempted. Here, we propose deconvolutional neural networks (DCNN) for estimating fiber orientation at the pixel-level. Dynamic ultrasound images sequences of the calf muscles were acquired (25 Hz) from 8 healthy volunteers (4 male, ages: 25–36, median 30). A combination of expert annotation and interpolation/extrapolation provided labels of regional fiber orientation for each image. We then trained DCNNs both with and without dropout using leave one out cross-validation. Our results demonstrated robust estimation of regional fiber orientation with approximately 3° error, which was an improvement on previous methods. The methods presented here provide new potential to study muscle in disease and health.

Purpose: This study aims to provide a foundational understanding of patient-centric perceptions of telemedicine implementation in rural Minnesota. Methods: This retrospective cohort study utilized a mail questionnaire to assess patient attitudes and behaviors regarding telemedicine during the emergency response to COVID-19. The target population was patients of a Primary Care clinic in eastern Minnesota. Descriptive statistics were used to assess respondents’ level of agreement with survey items scored on a 0-10 scale. Results: A majority of the respondents indicated that they were satisfied with using telemedicine (73.96%); that they gained an additional sense of control over their health condition due to the availability of telemedicine (52.08%); that they would support the use of telemedicine in the future (61.05%); that telemedicine increased access to care (65.63%); telemedicine was preferred over the clinic (61.46%), and that they would purchase new equipment to increase the utility of telemedicine services (54.17%). 51.04% of the respondents indicated a 10/10 level of satisfaction with telemedicine services. 48.96% indicated the strongest level of disagreement related to difficulty using telemedicine or a preference for in-person clinical appointments. Conclusions: Patients were found to have favorable perceptions of telemedicine overall. Though providers continue to recognize the benefit of face-to-face visits, their patients show an increased predilection for virtual care and telemedicine will likely remain an essential tool for providers to reach patients who would otherwise choose not to seek care.

Physical-law based models are widely utilized in the aerospace industry. One such use is to provide flight dynamics models for use in flight simulators. For human-in-the-loop use, such simulators must run in real-time. Due to the complex physics of rotorcraft flight, to meet this real-time requirement, simplifications to the underlying physics sometimes have to be applied to the model, leading to model response errors in the predictions compared to the real vehicle. This study investigated whether a machine-learning technique could be employed to provide rotorcraft dynamic response predictions, with the ultimate aim of this model taking over when the physics-based model's accuracy degrades. In the current work, a machine-learning technique was employed to train a model to predict the dynamic response of a rotorcraft. Machine learning was facilitated using a Gaussian Process (GP) non-linear autoregressive model, which predicted the on-axis pitch rate, roll rate, yaw rate and heave responses of a Bo105 rotorcraft. A variational sparse GP model was then developed to reduce the computational cost of implementing the approach on large data sets. It was found that both of the GP models were able to provide accurate on-axis response predictions, particularly when the input contained all four control inceptors and one lagged on-axis response term. The predictions made showed improvement compared to a corresponding physics-based model. The reduction of training data to one-third (rotational axes) or one-half (heave axis) resulted in only minor degradation of the GP model predictions.

Eye movements support memory encoding by binding distinct elements of the visual world into coherent representations. However, the role of eye movements in memory retrieval is less clear. We propose that eye movements play a functional role in retrieval by reinstating the encoding context. By overtly shifting attention in a manner that broadly recapitulates the spatial locations and temporal order of encoded content, eye movements facilitate access to, and reactivation of, associated details. Such mnemonic gaze reinstatement may be obligatorily recruited when task demands exceed cognitive resources, as is often observed in older adults. We review research linking gaze reinstatement to retrieval, describe the neural integration between the oculomotor and memory systems, and discuss implications for models of oculomotor control, memory, and aging.

Vibrational overtones in deeply bound molecules are sensitive probes for variation of the proton-to-electron mass ratio μ. In nonpolar molecules, these overtones may be driven as two-photon transitions. Here, we present procedures for experiments with O₂⁺, including state-preparation through photoionization, a two-photon probe, and detection. We calculate transition dipole moments between all X²П_g vibrational levels and those of the A²П_u excited electronic state. Using these dipole moments, we calculate two-photon transition rates and AC-Stark-shift systematics for the overtones. We estimate other systematic effects and statistical precision. Two-photon vibrational transitions in O₂⁺ provide multiple routes to improved searches for μ variation.

Identifying punch types as part of punch kinematic analysis is a key component for both coaches and players, providing critical insights into the variety and effectiveness of punches, which are essential for refining overall performance. Existing research indicates that punch type classification typically relies on data from either wearables or video data. Both approaches have their merits and demerits but require a significant amount of labeled data for modeling the classification algorithm. In this work, we propose a novel approach that significantly reduces the labeling effort by one-sixth by leveraging video data to enhance the training information of sensor data. This enriched training phase enables more accurate punch classification with reduced labeled data. Subsequently, the real-time punch identification and classification use only the wearable data. On a real dataset, with 15% of the labeling efforts, our approach achieved an accuracy rate of 91.41% for rear hand punch recognition and 91.91% for lead hand punch recognition, along with 92.33% and 94.56% for punch classification, respectively. Through the development of our Smart Boxer system, we aim to revolutionize punch analytics in boxing, providing comprehensive insights while enhancing the overall training and competitive experience for athletes and enriching fan engagement with the sport.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in animals and a suspected cause of Crohn’s disease (CD) in humans. Crohn’s Disease is a progressive, detrimental granulomatous enteritis of which common therapies are targeted to suppressing certain components of the immune system. The efficacy of these treatments can be variable and temporary with no clear process of selection for the individual patient. However, diagnosis of MAP has been elusive in patients with Crohn’s Disease. In animals it can be detected by several different techniques, including bacterial cell culture, polymerase chain reaction (PCR), and immunological targets. To move to an understanding of the possible pathogenicity of MAP and the sup-posed cause of CD in humans, it is necessary to demonstrate the presence of cell wall deficient mycobacterial (CWDM) forms of MAP in blood and tissue cultures from patients with CD. From this, more tailored and accurate therapies can be implemented and be developed to eradicate this infectious organism from humans. Current anti-mycobacterial antibiotics have limited efficacy as MAP is subtly different from tuberculosis. Newer methods, such as vaccination and gut microbiome remediation will be essential as part of combination therapies.

Rose (Rosa spp.), especially R. hybrida, is one of the most popular ornamental plants in the world and the third largest cut flower crop in Taiwan. Rose mosaic disease (RMD), showing mosaic, line patterns and ringspots on leaves, is a common rose disease caused by complex infection of various viruses. Due to pests and diseases, the rose planting area in Taiwan has been decreasing since 2008; however, no rose virus disease has been reported in the past five decades. In the spring of 2020, rose samples showing RMD-like symptoms were observed at an organic farm in Chiayi, central Taiwan. The virome in the farm was analyzed by RNA-seq. Rose genomic sequences were filtered from the obtained reads. The remaining reads were de novo assembled to generate 294 contigs, 50 of which were annotated as viral sequences corresponding to 10 viruses. Through reverse transcription-polymerase chain reaction validation, a total of seven viruses were detected, including six known rose viruses, namely apple mosaic virus, prunus necrotic ringspot virus, rose partitivirus, apple stem grooving virus, rose spring dwarf-associated virus and rose cryptic virus 1, and a novel ilarvirus. After completing the whole genome sequencing and sequence analysis, the unknown ilarvirus was demonstrated as a new species, tentatively named rose ilarvirus 2. This is the first report of the rose viruses in Taiwan.

Repurposing previously approved drugs may fast track the route to clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We carried out a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary screening for senescence-associated beta galactosidase (SAB) activity, based on effect size, direction and/or molecule identity. Selected molecules then underwent a more detailed assessment of senescence phenotypes including proliferation, apoptosis, DNA damage, senescence-associated secretory phenotype (SASP) expression and regulators of alternative splicing. A selection of the molecules demonstrating effects on senescence were then used in a new bioinformatic structure-function screen to identify common structural motifs. 90 molecules displayed altered CDKN2A expression at one or other dose, of which 15 also displayed effects on SAB positivity in primary human dermal fibroblasts. Of these, three were associated with increased SAB activity, and 11 with reduced activity. The female synthetic sex hormones; diethylstilboestrol, ethynyl estradiol and levonorgestrel; were all associated with a reduction in aspects of the senescence phenotype in male cells, with no effects visible in female cells. Finally, we identified that the 30 compounds that decreased CDKN2A activity the most had a common substructure linked to this function. Our results suggest that several drugs licenced for other indications may warrant exploration as future senotherapies, but that different donors and potentially different sexes may respond differently to senotherapeutic compounds. This underlines the importance of consideration of donor-related characteristics when designing drug screening platforms.

1). BACKGROUND: Cell wall deficient mycobacteria (CWDM) have seldom been isolated in bacterial culture from human subjects. particularly in clinical disease, such as Crohn’s disease. Techniques have focused on the use of polymerase chain reaction (PCR) for the detection of CWDM in association with inflammatory bowel disease. (IBD). This paper is a report of the development of methods to demonstrate the presence of CWDM using the Ziehl-Neelsen (ZN) stain. This is in addition to the detection of the growth of CWDM in fluid media. 2). METHODS: The use of the ZN stain is suitable for the demonstration of CWDM in clinical samples and cultures, when the staining methods that were common prior to the 1970’s, are adopted. Specific culture media are developed and tested in parallel. Alterations in the concentration of basic fuchsin, and changes in the decolourising solutions are necessary. Decolourising solutions such as 20% concentrated sulphuric acid in water are preferable for detection of CWDM in cultures. 3). RESULTS: CWDM can be readily demonstrated using the simple methods outlined in this report. The ability to visualise the presence of CWDM opens the door to the development of specific fluid media for the isolation of CWDM in culture. 4). CONCLUSION: The ZN stain methods optimised for the demonstration of Mycobacterium tuberculosis complex (MTBC) are not suitable for research into infectious causes of inflammatory bowel disease (IBD), as well as for the detection of CWDM in latent tuberculosis. Revisiting the techniques for the detection of CWDM may also refocus attention on inflammatory diseases considered to be idiopathic, but having hallmarks of an infectious process.

In this paper, a class of semi-linear elliptic equations involving Hardy-Sobolev critical exponents has been investigated. This problem comes from the consideration of standing waves in the anisotropic Schr\"{o}dinger equation, also it is very important in the field of hydrodynamics, glaciology, quantum field theory and statistical mechanics. By a detailed estimation for the extremum function and using Mountain Pass Lemma with $\left( PS\right) _{c}$ conditions, the existence of positive solutions has been obtained. On the other hand, by establishing Pohozaev-type identity and using the properties of Bessel function, the nonexistence of positive solution also has been obtained. These results are extensions of E. Jannelli's research (\cite[Theorem 1.A-1.C]{EJ}).

Purpose: To report a novel application of excimer ablation for normalization of central corneal refractive irregularity, combined with higher fluence CXL in the effective management and visual rehabilitation of progressive keratoconus. Methods: 17 cases with progressive keratoconus were treated with a corneal surface excimer laser ablation normalization using the topographyguided (Contura) myopic ablation for customized corneal re-shaping using a 6mm optical zone. The epithelial removal was accounted for by adding a -2.75 diopters correction in the topographyguided normalizing surface ablation followed by, a second, wavefront-optimized hyperopic excimer treatment of + 2.75 diopters at 6mm optical zone. The 2 sequential excimer ablations were followed by the corneal crosslinking (CXL). Visual acuity, refraction, and keratoconus documentation via keratometry, topography, and pachymetry, as well as endothelial cell density were evaluated over 36 months. Results: Keratoconus stabilized in all cases. The severity of keratoconus stage by Amsler-Krumeich criteria improved for the OD from an average 2.2 to 1. Mean UDVA showed marked improvement at one-year follow-up all values in decimal: from 0.21±0.18 pre-operative to 0.51±0.25 at 12 months, with small additional improvement through the 3 years to 0.51±0.16. CDVA respectively increased from 0.55±0.11 to 0.77±0.14 at 1 year, and to 0.79±0.16 at 3 years. Mean minimal corneal thickness decreased significantly from 466.74±34.25 µm to 396.17±45.17 µm (P<.01) as recorded the first year postoperatively and then slightly increased to 405.17±32.21 µm at the 3-year follow-up. Conclusions: We introduce herein initial clinical data with the use of novel, off-label therapeutic excimer laser surface ablation application: Designed to perform both epithelial removal and anterior corneal stroma reshaping, to be combined with CXL, in order to apply the Athens Protocol CXL with US excimer laser approved specifications.

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

In this article, we present the use of the coupled land surface model and groundwater flow model SWAT-MODFLOW with the decision support tool WEAP (Water Evaluation and Planning software) to predict future surface water abstraction scenarios in a complex river basin, under conditions of climate change. The modeling framework is applied to the Dee River catchment in Wales, United Kingdom. Regarding hydrology, the coupled model improves overall water balance and low streamflow conditions, compared to a stand-alone SWAT model. The calibrated SWAT-MODFLOW is employed with high resolution climate model data from the UKCP18 project with future scenario of RCP85 from 2020 to 2040. Then, water supply results from SWAT-MODFLOW are fed into WEAP as input for the river reach in the downstream region of the river basin. This system is utilized to create various future scenarios of surface water abstraction of public water supply in the downstream region: maximum licensed withdraw, 50 % authorized abstractions, monthly time series with 1% increase of water use, and maximum water withdraw year based on historical records repeated every year with 1% increase of water use, to estimate the unmet demands and streamflow requirement. This modeling approach can be used in other river basins to manage scenarios of supply and demand.

Wearable sensors have the potential to enable comprehensive patient characterization and optimized clinical intervention. Critical to realizing this vision is accurate estimation of biomechanical time-series in daily-life, including joint, segment, and muscle kinetics and kinematics, from wearable sensor data. The use of physical models for estimation of these quantities often requires many wearable devices making practical implementation more difficult. However, regression techniques may provide a viable alternative by allowing the use of a reduced number of sensors for estimating biomechanical time-series. Herein, we review 46 articles that used regression algorithms to estimate joint, segment, and muscle kinematics and kinetics. We present a high-level comparison of the many different techniques identified and discuss the implications of our findings concerning practical implementation and further improving estimation accuracy. In particular, we found that several studies report the incorporation of domain knowledge often yielded superior performance. Further, most models were trained on small datasets in which case nonparametric regression often performed best. No models were open-sourced, and most were subject-specific and not validated on impaired populations. Future research should focus on developing open-source algorithms using complementary physics-based and machine learning techniques that are validated in clinically impaired populations. This approach may further improve estimation performance and reduce barriers to clinical adoption.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

This study presents a methodology to reveal traces of viral particles, as aerosol with known chemical and molecular structure, in a sample by means of photon and electron interactions. The method is based on Monte Carlo simulations and on the analysis of photon-electron fluxes-spectra through energy channels counts as a function of different aerosol viral concentrations in the air sample and looking at the peculiar photon/electron interactions with the potential abnormal atomic hydrogen (H), oxygen (O), carbon (C), and phosphorus (P) compositions present in the air sample as a function of living and nonliving matter with PO4 group RNA/DNA strands in a cluster configuration.

In thermodynamic theory, free energy (i.e., available energy) is the concept facilitating the combined applications of the theory’s two fundamental laws, the first and the second laws of thermodynamics. The critical step was taken by Kelvin, then by Helmholtz and Gibbs— that in natural processes, free energy dissipates spontaneously. With the formulation of the second law of entropy growth, this may be referred to as the dissymmetry proposition manifested in the spontaneous increase of system/environment-entropy towards equilibrium. Because of Kelvin’s pre-entropy-law formulation of free energy, our concept of free energy is still defined, energy-centrally, as body’s internal energy or enthalpy, subtracted by energy that is not available within a framework on the premise of primacy of energy, in which free energy dissipates spontaneously and universally. This primacy of energy is called into question because the driving force to cause a system’s change is the purview of the second law. This paper makes a case for an engineering thermodynamics framework, instead, to be based on the premise of the primacy of dissymmetry over free energy. With Gibbsian thermodynamics undergirded with dissymmetry proposition and engineering thermodynamics with the dissymmetry premise, the two branches of thermodynamics are unified to become classical thermodynamics.

The purpose of this work is to study the mechanism of running-in during the friction and to determine the informative parameters characterizing the degree of its completion. During the friction, contact interaction of rough surfaces causes various wave phenomena covering a wide range of frequencies, the subsequent frequency analysis can provide information about the sizes of wave sources and thereby clarify the mechanism of interaction between surface roughness. The using of the wavelet transform for processing of the signals of audible acoustic emission made it possible to determine the beginning and the end of the change in the frequency ranges of the interaction of roughness. The code developed by the authors was used to analyze the acoustic emission signals by using wavelet energy and entropy criteria. The mother wavelet was chosen by carefully evaluating the effectiveness of 54 preliminary candidates for the mother wavelet from 7 wavelet families, ac-cording to three criteria: 1) maximum wavelet energy; 2) Shannon entropy minimum; 3) maximum energy-to-Shannon entropy ratio.

When limited area models of the hydrodynamics of the atmosphere and of the ocean are 1 run over an extended time, variability unrelated to external "drivers" emerge - this variability is 2 colloquially named "hydrodynamical noise" or just "noise". This article summarises what we have 3 learned in the past few years about the properties of such noise, and the implications for numerical 4 experimentation and analysis. The presence of this noise can be identified easily in ensembles of 5 numerical simulations, and it turns out that the intensity of the noise is closely linked to the scale- 6 dependent "memory". At the system level, this "memory" term as given by Hasselmann’s Stochastic 7 Climate model plays a key role. In the case of marginal seas, the process of baroclinic instability 8 modulated by tides and the formation of seasonal thermoclines are significant aspects. Some more 9 general aspects are discussed, such as the applicability of the Stochastic Climate model to systems 10 outside of atmospheric and oceanic dynamics, the irreversibility of tipping points and the challenges 11 of detecting changes beyond a noise level and of the attribution of causes of change.

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

Milk is a complex liquid, and the concentrations of many of its components are under genetic control. Many genes and pathways are known to regulate milk compositon, and the purpose of this review is to highlight how the discoveries of quantitative trait loci (QTL) for milk phenotypes can elucidate these pathways. The main body of this review focusses primarily on QTL discovered in cattle (Bos taurus) as a model species for lactation biology, with occasional references to other ruminant species, and some comparisons with human milk composition are also presented. The following section describes a range of techniques that can be used to help identify the causative genes underlying QTL when the underlying mechanism involves the regulation of gene expression. As genotype and phenotype data bases continue to grow and diversify, new QTL will continue to be discovered, and, although proving the causality of underlying genes and variants remains difficult, these new data sets will further enhance our understanding of lactation biology.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

We review and assess the classic SIR and SEIR epidemiological models regarding possible applications to the COVID-19 pandemic. In spite of numerous more complicated models, we show how the qualitative features of the solution to the SIR and SEIR models continue to provide valuable public health insights in some scenarios. Using estimated COVID-19 data as of this date, the SEIR model shows that if it were possible to reduce R₀ from 2.5 to 1.25 through social distancing and other measures, the maximum fraction of the population that would become infected at any particular time would drop from 17% to 4%, provided that all of the model assumptions are satisfied. Finally, we compare the classic SIR model with a recent stochastic model with favorable results. Since this comparison underscores the importance of underlying connectivity assumptions, we conclude with Monte-Carlo simulations with specific connectivity that reproduce the classical SIR model with standard incidence.

This study examined the relationship between financial sector liberalization and agricultural sector output in Nigeria using annual data spanning the period 1986-2020. Specifically, the objectives of the study are to examine the relationship between lending rate, exchange rate, commercial bank credit to agriculture, inflation rate and agricultural sector output in Nigeria. Ex-post facto research design was employed and the annual time series data were collated from Central Bank of Nigeria (CBN) Statistical Bulletin. The econometrics methods of unit root, co-integration and error correction mechanism were used for the analyses. The outcome of the ADF unit root test show that the variables were stationary. Also the co-integration result showed that there exist co-integration amongst the variables in the model. The results from Error Correction Model indicates that lending rate and inflation rate have a negative relationship on agricultural sector output while exchange rate and commercial bank credit to agriculture have positive relationship on agricultural sector output. Based on these results, this study recommends that government and policy makers in Nigerian should initial policies that will boost investments in the agricultural sector through direct provision of credits to agriculturist and banks should also lend at a very low and subsidized interest rate to enable farmers’ access agricultural loans that will boost agricultural productivity in the economy.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Trees provide key ecosystem services, but the health and sustainability of these plants is under increasing biotic and abiotic threat, including from the growing incidences of non-native invasive plant pests (including pathogens). The island of Ireland (Ireland and Northern Ireland) is generally accepted to have a high plant health status, in part due to its island status and because of the national and international regulations aimed at protecting plant health. To establish a baseline of the current pest threats to tree health for the island of Ireland, the literature and unpublished sources were reviewed to produce a dataset of pests of trees on the island of Ireland. The dataset contains 396 records of pests of trees on the island of Ireland, the majority of pests being arthropods and fungi, and indicating potentially more than 44 non-native pest introductions. The reliability of many (378) of the records was judged to be high, therefore the dataset provides a robust assessment of the state of pests of trees recorded on the island of Ireland. We analyse this dataset and review the history of plant pest invasions, including (i) discussion on notable native and non-native pests of trees, (ii) pest interceptions at borders and (iii) pests and climate change. The dataset establishes an important baseline for the knowledge of plant pests on the island of Ireland, and will be a valuable resource for future plant health research and policy making.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

A strong correlation between karyotype diversity and species richness in mammals was first reported over forty years ago: in mammalian phylogenetic clades, standard deviation of karyotype diversity (KD) closely corresponds to the standard deviation of species richness (SR). These initial studies, however, did not control for phylogenetic signal, raising the possibility that the correlation was due to phylogenetic relatedness among species in a clade. Accordingly, karyotype diversity trivially reflects species diversity simply as a passive consequence of adaptive radiations. A more recent study in mammals has controlled for phylogenetic signal and established the correlation as phylogenetically independent, suggesting that species diversity cannot, in itself, explain the observed corresponding karyotype diversity. The correlation is therefore remarkable because the mechanisms contributing to karyotype diversity are evolutionarily independent of the mechanisms contributing to species diversity. Recently, it was shown in salamanders that the two processes generating genetic diversity and species diversity are indeed independent and operate in parallel, suggesting a potential non-adaptive and non-causal relationship between the two fundamental variables involved in adaptive radiations. The following will examine the relationship between KD and SR in the context of Motoo Kimura’s theory of non-adaptive radiation.

During the last twenty years around the world there has been a rapid increase in the number of people visiting long established religious shrines as well as the creation of new sites by those operating outside the boundaries of institutional religion. This increase is intimately associated with the revival of traditional routes, the creation of new ones and the invention of new rituals (religious, spiritual and secular). To examine this process I will focus on the European region and two contrasting destinations in particular – the Catholic shrine of Lourdes, France, and the pre-Christian shrine of Avebury, England – drawing on my personal involvement in travelling to both destinations and being involved in ritual activities along the route and at the two destinations. In the discussion section of the paper I will explore the relevance of these two case studies to the analysis of power, agency and performance and the ways in which they expose (a) the role of institutions and entrepreneurs in creating rituals and sacred places and (b) the relationship between people and the domesticated landscape.

Dispersion tests based on the second order component of smooth test statistics are related to Fisher’s Index of Dispersion test, used for testing for the Poisson distribution when there are no covariates present. Such tests have been recommended in [1] to test for the Poisson distribution when covariates are present. The modified Borel-Tanner (MBT) distribution seems suited to data with extra zeroes, a monotonic decline in counts and longer tails. Here we recommend a dispersion test for the MBT distribution for both when covariates are absent and when they are present.

We explored the trends and the diversity of the mortality and risk factors of age-standardized cardiovascular diseases (CVD) and cerebrovascular disease (CBD) from 2000 to 2020 in five advanced Asian countries, including China, Japan, Singapore, South Korea, and Taiwan. Data were obtained from the Global Burden of Disease (GBD) report. Overall, the CVD mortality rates decreased gradually in all five Asian countries. Singapore had the highest rates before 2011, but Taiwan replaced Singapore as the nation of the highest mortality rates after 2012. Additionally, South Korea had the highest CBD mortality rates before 2016, while Taiwan experienced a peak in 2011 and remained high thereafter. The absolute difference (AD) and relative difference (RD) for CVD mortality rates showed clear declining trends in all five countries, with South Korea and China displaying the highest reductions, respectively. It is noteworthy that overweight and obesity exhibited an increasing trend in all these five Asian countries, with China demonstrating the highest AD and RD. Except for Taiwan, where a negative association of r=-0.732 was observed, CVD mortality was positively associated with CBD, hypertension, and DM mortality in all other four countries, therefore, further investigation into these relationships are needed.

Climate change, biodiversity loss, and other social and environmental problems pose grave risks. Progress so far has been incremental and insufficient, and as a result scientists, global policy experts, and the general public increasingly conclude that bold change is required across all sectors of society. At least two kinds of bold change are conceivable: reform of existing societal systems (e.g., financial, economic, legal, and governance systems), including their institutions, policies, rules, and priorities; and transformation, understood as the de novo development of and migration to new, improved systems. This paper is the second in a series of three that together propose a novel science-driven research and development program aimed at societal transformation. Moreover, the series advances a conceptual framework and formal mechanics by which societal transformation might be approached. Two of the underlying hypotheses are that new societal systems can be developed in a science-driven process to be fit for purpose, and system fitness can be compared across designs. Societies are viewed as superorganisms, and systems are viewed as a societal cognitive architecture. The first paper in the series provides definitions, aims, hypotheses, and a worldview. This paper discusses motivations, the role of science in societal transformation, a theory of change, and fitness metrics. The proposed R&amp;D program and theory of change are sound, viable, and affordable. The local-global-viral strategy invites the global science community to play a unique co-leadership role with local communities in the development, testing, and monitoring of new societal systems. Systems are implemented via a novel civic club model, where participation is voluntary. Clubs grow and replicate based on merit and aided by club networks, whose systems are also viewed as societal cognitive architectures. Benefits of the program and strategy are discussed.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

A half-harmonic oscillator, which gets its name because the coordinate is strictly positive, has been quantized and determined that it was a physically correct quantization. This positive result was found using affine quantization (AQ). The main purpose of this paper is to compare results of this new quantization procedure with those of canonical quantization (CQ). Using Ashtekar-like classical variables and CQ, we quantize the same toy model. While these two quantizations lead to different results, they both would reduce to the same classical Hamiltonian if $\hbar\rightarrow0$. Since these two quantizations have differing results, only one of the quantizations can be physically correct. Two brief sections illustrate how AQ can correctly help quantum gravity and the quantization of most field theory problems.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

The rapid growth of the sharing economy has propelled shared mobility to the forefront of attention. The continuous advancement of autonomous driving technology also brings new opportunities and challenges to the shared mobility market. This study comprehensively analyzes the market potential concerning autonomous vehicles (AVs) to provide shared mobility services, utilizing SWOT analysis, PESTLE analysis, and Porter’s Five Forces. The findings reveal that AVs can provide improved shared mobility services by increasing transportation safety, reducing emissions, reducing costs, enhancing traffic efficiency, and increasing customer satisfaction and the profitability of shared mobility services. However, challenges such as technological and policy uncertainties, safety concerns, high initial costs, inadequate public communication infrastructure, and the absence of standardized regulations can hinder the widespread adoption of AVs. The benefits are also restricted with a low market penetration rate of AVs. To promote AVs in the shared mobility market, this study also provides implications for AV stakeholders tailored to the evolving shared mobility market dynamics.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

Accurate and timely testing has become an essential measure in combatting the COVID-19 global pandemic. Currently, polymerase chain reaction (PCR) based assays are the most relied on methods for SARS-CoV-2 detection. This traditional workflow involves a viral RNA extraction from the viral transport media storing nasopharyngeal swabs collected from patients, followed by PCR based detection. While accurate, this methodology is time consuming and resource heavy, causing for delays in receiving results or limited access to testing. Herein, we demonstrate a validated method for SARS-CoV-2 detection from viral transport media using a two-step, direct-to-PCR workflow revolving around shaker-mill homogenization. This method completely bypasses the extraction steps of the traditional workflow, replacing it with 30 seconds of mechanical disruption sufficient to allow for COVID-19 detection with a 96.43% sensitivity and 100% specificity when compared to traditional extraction to PCR based methods.

There is a long trail of research studies testing the in vitro and in vivo efficacy of chloroquine and its derivatives in treating and preventing infection by various coronavirus species. More recent findings have highlighted the possibility of treating patients infected with the 2019 novel coronavirus, SARS-CoV-2. This review describes the mechanism of coronavirus infection, the mechanism of action of chloroquine, and summarizes the available literature highlighting the efficacy of chloroquine as an anti-coronavirus agent. These findings should encourage the wider scientific community to conduct thorough research on the possible efficacy of chloroquine and its derivatives in treating and preventing SARS-CoV-2 infection.

Introduction People are presenting with chronic musculoskeletal pain at a younger age, and many fulfil criteria for fibromyalgia. We have recently shown a strong association between fibromyalgia symptoms and autistic traits in a self-selected community population, with the relationship mediated in part by the presence of hypermobility. Many respondents also described food sensitivities and intolerances. This study explores relationships between food issues and fibromyalgia symptoms in this population Methods The study used a nonexperimental, correlational design with data collected from a volunteer sample of 442 adults (aged 18-60) who completed online self-report questionnaires assessing each of fibromyalgia symptoms (ACR criteria), autistic traits (RAADS score) and hypermobility (Beighton’s test). Subjects were also asked to record any food sensitivities, allergies, or intolerances, along with their consequences. Correlation analyses and linear regressions were used to test the relationships between these features and each of fibromyalgia, autistic traits and hypermobility. Data was analysed using parametric and non-parametric techniques to assess the strength and significance of relationships, causes of variance and the potential mediating effect of food-related symptoms in the correlation between fibromyalgia features and autistic traits Results Our self-selected community population had a mean age of 24 years and was 77% female. The prevalence of fibromyalgia, autistic traits and hypermobility was 40%, 65% and 44% respectively. Half of all subjects reported food sensitivity and 31% reported food intolerance. The incidence of food-related symptoms was higher among subjects who met criteria for fibromyalgia than those who reported autistic traits or hypermobility. Food sensitivity and food intolerance were both more significantly associated with fibromyalgia (r=0.24, p>0.001 and r=0.38, p>0.001) than with autistic traits (r=0.15, p>0.01 and r=0.17, p>0.01). Discussion This is the first community study to provide evidence for a direct association between features of fibromyalgia and reported food intolerance and sensitivity. Although self-selected, the findings in our predominantly young population suggest that gluten and lactose consumption may be associated with higher levels of musculoskeletal pain. Avoidance of these foodstuffs was commonly reported to reduce symptoms. Dietary adjustment may merit further investigation as a therapeutic modality for some patients with fibromyalgia.