The COVID-19 crisis has resulted in a shortage of personal protective equipment (PPE) [1]. COVID-19 is currently the leading cause of death in the United States[2]. Health care providers caring for COVID-19 patients or at high risk of being exposed to the SARS-CoV-2 virus benefit from a face shield to protect against aerosol droplets that could hit the face and minimize the chance of inadvertently touching the face with contaminated hands, and air filtration to filter out aerosolized SARS-CoV-2. Adapting commercially available full-faced snorkel masks has been proposed as an alternative to narrow the gap in PPE [3]. Here we explore a full-faced snorkel mask with commercially available particulate filters.

Both the sustainability discourse and the debate on citizen science are strongly focused on the natural and technical sciences. Yet, numerous participatory research activities can be identified in the social sciences and humanities that address sustainability issues of various kinds. These have hardly been studied so far, and their contribution to addressing sustainability challenges is poorly known. The study investigates which sustainability topics are taken up by citizen science in the humanities and social sciences, which factors influence the choice of topics, and its implications. For this purpose, the concept of Citizen Social Science (CSS) is taken up and sustainability is operationalized via the Sustainable Development Goals (SDG) and its specific Targets. Based on a collection of CSS activities in Germany, the addressed sustainability topics are identified accordingly. It is then analyzed how these patterns depend on the main characteristics of CSS projects. The findings indicate a focus on three SDGs related to education, sustainable cities and partnerships for the Goals, while at the same time the project consortia are very heterogeneous. CSS shows particular strengths here through its multi-stakeholder approach. Going forward, the linkage of Citizen Science to the SDGs needs to be further formalized so that its transformative effects can be incorporated into SDG monitoring and the scientific institutions need additional incentives to participate in CSS.

The exact dynamics of emergence remains one of the most prominent outstanding questions for the field of complexity science. I first discuss various perspectives on emergence in various contexts, then offer a different perspective on understanding emergence in a graph-theoretic representation. From the discussion, an observer’s choice in state space seems to have an effect for that observer to detect emergent behavior. To test these ideas, I analyze the dynamics of all possible spatial state spaces near the critical temperature in an Ising model. As a result, state space topologies that appear more deterministic flip more bits than topologies that appear more random, which is contrary to our intuitions about randomness. In addition, the size of different state spaces constrain a system’s ability to explore various states within the same time frame. These results are important to understanding emergent phenomena in biological systems, which are layered with various state spaces and observational perspectives.

Keywords: lactic acid; ceramide; folate; nicotinamide; Alzheimer’s disease

Canine Hemangiosarcoma (HSA) is a devastating cancer affecting blood vessels in numerous sites within the body that is primarily seen in middle to older aged dogs. It is marked by its rapid aggressive metastatic pathology that often results in a lack of apparent symptoms in early stages. In most cases, disease becomes apparent due to hemorrhagic events following the rupture of the malignant vascular cell structures that can capture and pool blood cells, resulting in necrosis of the affected tissues. The poor survival times in affected patients cause a hindrance to the ability to carry out large scale studies, leaving numerous knowledge gaps to be filled in future research. The pathologic similarities between this and human angiosarcoma (HA) provides the potential for translatable research to be carried out that would improve outcomes across species. Here, current knowledge is outlined in order to improve understanding HSA holistically and suggest future direction. Emphasis is placed on the potential to improve veterinary practices in ways that will improve the ability to quickly and accurately diagnose patients in order to establish better client communication and provide clarity in collaborating to create the best informed treatment plan possible.

Bioenergy produced from perennial feedstocks such as woody biomass could serve as an opportunity to strengthen local and regional economies and also jointly produce various environmental services. In order to assess the potential for biomass- based bioenergy, it’s essential to characterize the interest that potential biomass suppliers have in such an endeavor. In the U.S. Great Plains region, this largely means assessing relevant perceptions of farmers and ranchers. We conducted a series of farmer and rancher oriented focus groups in North Dakota, South Dakota, Nebraska and Kansas to qualitatively explore opinions about the role that trees can play in agriculture and interest in woody biomass systems within existing Northern Great Plains (NGP) farms and ranches. Our findings suggest that farmer and ranchers generally value the role that trees, or tree-based practices like windbreaks can play in agriculture particularly on marginal farmland in terms of conservation or crop protection. Yet relative to the potential of trees as a biomass crop there is a distinct lack of knowledge and skepticism. Farmers and ranchers also noted variable degrees of risk concern and uncertainty regarding investing in tree-based systems, as well as a number of perceived external market related constraints to integrating trees within their managed systems. Most of the participants recognized that if biomass production or an increase in tree planting and management in general were to expand in the NGP region, government programs would likely be required to provide much needed technical guidance and financial incentives. As the NGP regional bioeconomy continues to emerge and expand, private and public investment relative to niche bioenergy feedstocks such as woody biomass should address the type of information needs that farmers and ranchers have relative to integrating biomass production into existing farm and ranch systems.

This review article aims at improving understanding of the theoretical discussion on technonationalism. Reviewing conventional works of the literature proposes protectionist, innovationist, and strategic industrial approaches toward high-tech industries. The findings show that technonationalism is a concept linking technology and national security, seeking geoeconomic interests in the integrated global market to exert state power for economic statecraft. The nature of industry highly relies on the global value chain, and technological innovation in the high-tech sectors occurs mainly in the private sector; thus, this article points out the issue of embracing business interests into the state’s strategic addenda as a critical criterion of technonationalism. Also, technonationalism is a narrowly defined concept with state actors involved in national security affairs and high-tech business actors.

This research work was aimed at investigating and determining the depth resolution of a 500Mhz GPR Antenna. The survey was conducted in an open space at the Physics Department, College of science-KNUST. The MALA GPR equipment with 500MHz shielded Antenna in the common offset-mode was used to investigate the depth at which materials were buried. Concrete block, tree roots, plastic bottle with water, glass bottle and Electric wire were each buried in cavities with five different burial depths. The real depth of each material was measured both along and across the cavity and compared to their corresponding GPR measured depth. The comparison of the Real depth and the GPR depth showed almost identical depth measurements with a root mean square deviation of 0.028m. The implication of this is that the 500 Mhz GPR antenna can accurately locate and detect the position of buried materials in the subsurface at a depth within the range (0.20-0.66) m.

Mastitis is an inflammation of the mammary gland initiated by pathogenic bacteria. In fact, mastitis is the second most important reason for the culling of cows from dairy herds, after infertility. In this review we focus on various forms of mastitis, including subclinical and clinical mastitis. We also stress the importance of the dry-off period as an important time when pathogenic bacteria might start their insult to the mammary gland. An important part of the review is the negative effects of mastitis on milk production and composition, as well as economic consequences for dairy farms. The two most important groups of bacteria that are involved in infection of the udder, Gram-negative and Gram-positive bacteria, are also discussed. Although all cows have both innate and adaptive immunity against most pathogens, some are more susceptible to the disease than others. That’s why we summarize the most important components of innate and adaptive immunity so that the reader understands the specific immune responses of the udder to pathogenic bacteria. One of the most important sections of this review is interrelationship of mastitis with other diseases, especially retained placenta, metritis and endometritis, ketosis, and laminitis. Is mastitis the cause or the consequence of this disease? Finally, the review concludes with treatment and preventive approaches to mastitis.

In addition to the canonical loss-of-function mutations, mutations in proteins may additionally result in gain-of-function through the binary activation of cryptic ‘structural capacitance elements’. Our previous bioinformatic analysis allowed us to propose a new mechanism of protein evolution - structural capacitance – that arises via the generation of new elements of microstructure upon mutations that cause a disorder-to-order (DO) transition in previously disordered regions of proteins. Here we propose that the DO transition is a necessary follow-on from expected early codon-anticodon and tRNA acceptor stem-amino acid usage, via the accumulation of structural capacitance elements - reservoirs of disorder in proteins. We develop this argument further to posit that structural capacitance is an inherent consequence of the evolution of the genetic code.

As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for design of new therapeutics. In response, clinical therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in cytosolic environments. Where multi-specificity is challenging with an antibody format that is prone to mis-pairing of chains, FN3 domains in the fibronectin assembly already interact with a large number of molecules. As such, multiple monobodies engineered for interaction with therapeutic targets are being combined in a similar beads-on-a-string assembly which improves both efficacy and pharmacokinetics. Furthermore, full length fibronectin is able to fold into multiple conformations as part of its natural function and a greater understanding of how mechanical forces allow for the transition between states will lead to advanced applications that truly differentiate the FN3 domain as a therapeutic scaffold.

What drives an individual police officer to activate his body-worn camera (BWC)? Some evidence suggests officer attitudes and resistance to the technology contributes to the equivocal results in studies testing for BWCs effect on use-of-force, complaints, and other outcomes of interest. Leveraging a novel survey and administrative dataset, we investigate the predictors of BWC activation among 147 police officers in a single agency. With a test of three nested models, we find job function covariates offer robust predictive power of how often an officer activates her or his BWC. Neither demographic nor attitudinal measures significantly predict BWC activations, except for a negative relationship with how officers perceive BWC impacts on professional discretion. The study furnishes empirical support for understanding officers as Principled Agents: job function, guided by administrative policy is the most explanatory and parsimonious, while models of attitudes and demographics fail to improve upon the job function model.

Computational methods are essential to support and advance nuclear technologies due to the hazards of handling and analysing highly radioactive materials such as spent nuclear fuel (SNF). However, many such methods, including those thatcan predict SNF compositions and decay heat parameters, require expensive, proprietary software, alongside significant programming experience and computational power for utilisation, severely limiting availability of data and hampering research throughput. Although some datasets are available, many are incomplete or only cover certain fuel systems for older reactor types. Research investigating new methods for SNF recycling, for example, requires compositional and decay heat data for fuel systems not covered by extant data, though analogous source data may be available. With this in mind, we have developed a simple, accessible, and flexible method for extrapolation of isotopic, elemental, and decayheat compositions for SNF at discharge and following decay storage before recycling, based on an extant dataset. This semi-empirical method uses physical and mathematical first principles and can be performed using software accessible to all researchers. This provides outputs accurate to within 1% of reference values interpolated within the range of available data for isotopic compositions, with sensible extrapolations at higher burnups beyond those reported, withoverall elemental outputs accurate to within 0.1%of expected totals. In this publication, we present the developmental methodology, some sample data, the present limitations, and options for future development and expansion of functionality.

We seek to examine effective collaboration when engaging in value cocreation with the customer for mobile financial services in EMs. Our study is a motivation for multi-stakeholder engagement in value cocreation with financial inclusion of all consumers including marginalized populations. Furthermore, our work discovers that social sustainability is a product of social creativity and results in financial inclusion. We apply a qualitative descriptive methodology utilizing exemplars from extant research and phenomenology to analyze the data from the contexts of Ghana and Kenya. The results show that value is co-created for mobile financial services in networks in emerging markets when actors integrate resources for social and environmental sustainability as essential elements for mobile financial inclusion.

By framing the problem of determining the state of Schrodinger’s cat as a problem of searching for Hidden Markov Model (HMM), this work shows that Schrodinger’s cat is dead with stationary probabilities P(Cat = Dead) = 1 and P(Cat = Alive) = 0 consistently in various observation-based modelling of the HMM.

Plant-based diets are increasingly popular for health as well as financial, ethical, and religious reasons. The medical literature clearly demonstrates that plant-based diets can be both nutritionally sufficient and medically beneficial. However, any person on an intentionally restrictive but poorly-informed diet may predispose themselves to clinically-relevant nutritional deficiencies. For persons on a poorly-informed plant-based diet, deficiencies are possible in both macronutrients (protein, essential fatty acids) and micronutrients (vitamin B12, iron, calcium, zinc and vitamin D). Practitioner evaluation of symptomatic patients on a plant-based diet requires special consideration of 7 key nutrient concerns for plant-based diets. This article translates these concerns into 7 practical questions that all practitioners can introduce into their patient assessments and clinical reasoning. Ideally, persons on plant-based diets should be able to answer these 7 questions. Each serves as a heuristic prompt for both clinician and patient attentiveness to a complete diet. As such, these 7 questions support increased patient nutrition knowledge and practitioner capacity to counsel, refer, and appropriately focus clinical resources.

The rise in population density, vehicle ownership, and urban development has significantly influenced travel demand and altered travel patterns, leading to traffic congestion in rapidly growing urban centers like Accra, Ghana. The traditional approach of expanding roadways to accommodate rising traffic is no longer environmentally sustainable. Instead, emphasis has shifted towards travel demand management (TDM) strategies as a more sustainable solution. This study aimed to investigate a range of TDM strategies that can be adopted in Accra to improve traffic flow through the lenses of everyday road users. The study employed a questionnaire survey and a stratified sampling technique to gather data from 615 respondents for relative importance index (RII) ranking, and Chi-square statistical analysis. The findings reveal that the topmost preferred strategies were mass transit improvements, walking and cycling improvements, and alternative work schedules. Notably, mass transit improvements emerged as the most preferred strategy. The study also unveiled a statistically significant correlation between variables such as age, education level, marital status, income level, and mode of transportation with all selected TDM preferences. However, no significant relationship was found between gender and car ownership with all selected TDM preferences. The study provides valuable insights regarding road users’ preferences for TDM strategies that can aid in planning future urban mobility systems to proactively manage travel demand, alleviate congestion, and promote sustainable transportation options for the city’s residents.

Workplace exercise programs are imperative for improving employee health and wellbeing. Employee cognition and productivity can also benefit from such programs; however, the practical application of interventions to influence these outcomes is poorly understood. This research aimed to assess the suitability of a university Staff Fitness Program for improving employee productivity and cognition. Forty-seven participants were included in the study, comprising 27 Staff Fitness participants and 20 control group participants. A two (groups) x three (time-points) between-subjects/within-subjects design was employed over 14 weeks, comprising ten weeks of once-weekly exercise intervention for Staff Fitness participants. All participants completed the Victoria Stroop Colour and Word Test and the Health and Work Questionnaire at each time-point, to assess cognition and productivity, respectively. Participants also completed the International Physical Activity Questionnaire (short form) at time-point one, three and during training weeks (excluding week one) to measure physical activity. Appropriate T-tests and non-parametric equivalents were used to assess group differences in outcome measures and across time-points. There were no significant between group or longitudinal differences indicative of improved productivity or cognition. The Staff Fitness group demonstrated a non-significant improvement (Z = 73.00, p = .055) in physical activity from time-point one (M = 1540.93 MET-min-week, SD = 1083.74) to three (M = 2077.32 MET-min-week, SD = 1401.48) with a large effect size (d = 0.97), while control group physical activity significantly decreased (Z = 10.00, p = .013). The present Staff Fitness Program benefited employees by improving physical activity, despite no improvements in productivity or cognition. Future research should further explore the application of workplace exercise programs and the manipulation of exercise parameters to show improvements in employee productivity and cognition.

Toxocarosis remains an important neglected parasitic infection representing one of the most common zoonotic infections caused by the parasite Toxocara canis or less frequently by Toxocara cati. The epidemiology of the disease is complex due to its transmission route by accidental ingestion of embryonated Toxocara eggs or larvae from tissues from domestic or wild paratenic hosts. Even though Toxocara infects about 1,4 billion people worldwide, global epidemiological data regarding the relationship between seropositivity and toxocarosis is limited. Although the vast majority of the infected individuals remains asymptomatic or experiences a mild disease, the infection is associated with important health and socioeconomic consequences, particularly in underprivileged, tropical, and subtropical areas. Toxocarosis is a disease with multiple clinical presentations, which are classified into five distinct forms: the classical visceral larva migrans, ocular toxocarosis, common toxocarosis, covert toxocarosis, and cerebral toxocarosis or neurotoxocarosis. Anthelmintic agents as for example albendazole or mebendazole is the recommended treatment, whereas a combination with topical or systemic corticosteroids for specific forms is suggested. Prevention strategies include educational programs, behavioural and hygienic changes, enhancement of the role of veterinarians, and anthelmintic regimens to control active infections.

There is a disproportionate increase in the incidence of diet-related cardiometabolic disorders in racial and ethnic minority groups. This systematic review examines the extent to which diet-induced changes in health outcomes have been discussed by race or ethnicity in randomized controlled trials recruiting both minority and non-Hispanic White groups. Databases i.e. PubMed, Cochrane library and Web of Science were searched up to November 2019. Studies that discussed effects of defined dietary interventions on health outcomes by racial or ethnic minority group vs. non-Hispanic Whites (n=29) were included in the review. Most studies were conducted in Black vs. White people testing effects of energy restriction, macronutrient modification, sodium reduction, or variations of the Dietary Approaches to Stop Hypertension (DASH) diet on cardiometabolic outcomes. There was limited focus on other minority groups. Evidence suggests greater blood pressure reduction for Black people compared to Whites particularly on DASH (or similar) diets. Overall, there was limited consideration for group-specific eating patterns and diet acceptability in most studies. Adequately powered studies are needed for accurate interpretation of race by diet effects. With emerging precision nutrition initiatives, it is imperative to ensure adequate representation of racial and ethnic subgroups for addressing nutrition-related health disparities.

Climate change and development have increased urban flooding, requiring modernization of stormwater infrastructure. Retrofitting standard passive systems with controllable valves/pumps is promising, but requires real-time control (RTC). One method of automating RTC is reinforcement learning (RL), a general technique for sequential optimization and control in uncertain environments. The notion is that an RL algorithm can use inputs of real-time flood data and rainfall forecasts to learn a policy for controlling the stormwater infrastructure to minimize measures of flooding. In real-world conditions, rainfall forecasts and other state information, are subject to noise and uncertainty. To account for these characteristics of the problem data, we implemented Deep Deterministic Policy Gradient (DDPG), an RL algorithm that is distinguished by its capability to handle noise in the input data. DDPG implementations were trained and tested against a passive flood control policy. Three primary cases were studied: (i) perfect data, (ii) imperfect rainfall forecasts, and (iii) imperfect water level and forecast data. Rainfall episodes (100) that caused flooding in the passive system were selected from 10 years of observations in Norfolk, Virginia, USA; 85 randomly selected episodes were used for training and the remaining 15 unseen episodes served as test cases. Compared to the passive system, all RL implementations reduced flooding volume by 70.5% on average, and performed within a range of 5%. This suggests that DDPG is robust to noisy input data, which is essential knowledge to advance the real-world applicability of RL for stormwater RTC.

Intramammary infections (mastitis) of dairy cows, along with other periparturient diseases, have become problematic within the dairy industry as they lead to loss of milk production. The main objective of this study was to determine whether elevated somatic cell counts (SCC) in cows prior to drying off are related to the incidence of other periparturient diseases. Additionally, we de-termined whether milk composition and milk yield are affected by a high SCC prior to drying off. Somatic cell counts of milk samples were determined prior to dry off (n = 140) and were used to classify cows in the study as high (>200,000 cells/mL) or low (<200,000 cells/mL) SCC. The com-position of milk was analyzed before drying off and at 1 and 2 weeks after calving. The results showed that an elevated SCC before drying off was related to the incidence of ketosis. Cows with a high SCC at drying off also showed an increased likelihood of retained placenta, metritis, and lameness postpartum; however, it was not statistically significant. Milk lactose was lower in cows with high SCC, while protein content was lower after parturition. Milk production was lower for cows with pre-drying elevated SCC, particularly for cows with retained placenta, keto-sis, and mastitis. In conclusion, cows with pre-drying elevated SCC were more likely to develop disease after parturition and produce less milk and with lower lactose and protein content.

Children with hearing loss have been found to have significantly more behavioral and emotional challenges than their typically hearing peers, though these outcomes are variable at the individual level. Working memory deficits have been found to relate to executive functioning and overall emotion regulation, leading to behavior challenges. Language development is essential for development of social relationships and communicating one’s needs - this may lead to distress when children cannot communicate effectively. Based on prior findings in children with hearing loss and their typically hearing peers, working memory and language skills were hypothesized to be related to parent and teacher report of socioemotional functioning. Participants were 35 children with hearing loss (66% female, M = 5.17 years old, SD = ±1.97) whose language, working memory, and socioemotional functioning were evaluated during the course of treatment and educational planning. Bivariate analyses indicated that working memory was related to a number of socioemotional domains (e.g., functional communication, atypicality, withdrawal), as were language scores (e.g., social skills, inattention). The direction of these associations was such that stronger working memory and language skills were related to more regulated socioemotional functioning. A call to action of the current study includes more education with regard to profiles and presentations of children with hearing loss, and an early focus on socioemotional learning to foster the development of regulatory skills.

Presentation of case: A 20 year old men from Simanjiro district in northern Tanzania presented with a 3 year history of splenomegaly, fatigue, cachexia, skin maculae and recent onset of watery diarrhea at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. Due to laboratory findings of pancytopenia, diagnostic workup included bone marrow aspiration cytology and biopsy. Although the rapid test (IT LEISH, rK39 RDT) was negative, blood smear showed amastigote forms of Leishmaniasis in macrophages. Repeat bone marrow aspiration and PCR eventually confirmed VL. The patient denied travel to known endemic areas of visceral leishmaniasis (VL). Treatment was initiated with Amphotericin B, but the patient died on the fourth day of treatment from respiratory insufficiency. An autopsy revealed massive organ manifestations of VL. Case discussion: This is the first reported autochthonous case of VL in Tanzania. Clark et al. detected the vector Phlebotomous martini in Northern Tanzania in 2013, in a region boardering the district of our patient. The negative rapid test draws attention to the fact that sensitivity and specificity was found to be low in East African VL patients as displayed earlier by a Kenyan study. Therefore, tissue samples (spleen or bone marrow) remain necessary for diagnosis. The variety of symptoms in this presented case was remarkable, including the occurrence of Post Kala Azar Dermal Leishmaniasis (PKDL) and VL at the same time. This has been described in East African VL cases before as well as the occurrence of chronic diarrhea. An elongated undiagnosed period likely led to a mixed clinical picture that included: hepato-splenomegaly, PKDL, cachexia, and diarrhea.

Background and Aims Insulin resistance is pivotal in the pathogenesis of Metabolic Syndrome (MetS), which predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (Ty-G index), a validated measure of insulin resistance also predicts MetS, T2DM, severity of albuminuria and ASCVD. There is scantly data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Patients and Methods Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver operating Characteristic (ROC) curve analysis revealed that TyG index was an excellent predictor of MetS with an area under the curve of 0.87 and it correlated with both hepatic and adipose tissue insulin ressitance .Both serum FFA levels and non-HDL-cholesterol increased significantly over tertiles of TyG index. Based on TyG index tertiles and or correlations, C reactive protein, endotoxin, chemerin , interleukin-6 levels and monocyte toll-like receptor (TLR)- 4 and TLR-2 and their cellular signaling were significantly associated with TyG index . Conclusion: Increased non-HDL-C and most importantly a pro-inflammatory state evidenced by both circulating and cellular biomarkers could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD.

The study purpose was to train and validate a deep-learning approach to detect micro-scale streetscape features related to pedestrian physical activity. This work innovates by combining computer vision techniques with Google Street View (GSV) images to overcome impediments to conducting audits (e.g., time, safety, and expert labor cost). The EfficientNETB5 architecture was used to build deep-learning models for eight micro-scale features guided by the Microscale Audit of Pedestrian Streetscapes-Mini tool: sidewalks, sidewalk buffers, curb cuts, zebra and line crosswalks, walk signals, bike symbols, and streetlights. We used a train--correct loop, whereby images were trained on a training dataset, evaluated using a separate validation dataset, and trained further until acceptable performance metrics were achieved. Further, we used trained models to audit participant (N=512) neighborhoods in the WalkIT Arizona trial. Correlations were explored between micro-scale features and GIS-measured- and participant reported-macro-scale walkability. Classifier precision, recall, and overall accuracy were all >84%. Total micro-scale was associated with overall macro-scale walkability (r=0.300,p<.001). Positive associations were found between model-detected and self-reported sidewalks (r=0.41,p<.001) and sidewalk buffers (r=0.26,p<.001). Computer vision model results suggest an alternative to trained human raters, allowing for audits of hundreds or thousands of neighborhoods for population surveillance or hypothesis testing.

Corynebacterium glutamicum is prominent for the industrial production of secreted amino acids. Notably, it naturally accumulates the carotenoid pigment decaprenoxanthin in its membranes. Metabolic engineering enabled production of astaxanthin. Here, a bioprocess for astaxanthin production in lab-scale stirred bioreactors was established by a DoE-guided approach to optimize the basic process parameters pH, rDOS, aeration rate as well as inoculation cell density. The DoE-guided approach from 2 L scale cultivation revealed that the pH showed the strongest effect on the product formation. Subsequently, an optimum at pH 8, an aeration rate of 0.25 vvm, 30 % rDOS and an initial optical density of 1 was established that allowed production of 7.6±0.6mg L-1 astaxanthin in batch mode. These process conditions were successfully transferred to a fed-batch process resulting in a high cell density cultivation with up to 60 g CDW L-1 biomass and 64 mg L-1 astaxanthin and thus demonstrating an about 9-fold improvement compared to optimal batch conditions. Moreover, pH shifts experiments indicate that the cells can quickly adapt to a change from pH 6 to 8 and start producing astaxanthin showing the possibility of a biphasic bioprocesses for astaxanthin production.

Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD) there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an on-line survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood while surgery and the Atkin’s/Modified Atkin’s Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau-Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but none-the-less these data provide some insight into novel relationships that may assist in a better understanding of epilepsy in ASD and providing insight into personalizing epilepsy care in ASD.

Background: Exercise is increasingly understood as an important resource for people with harmful substance use, including those in prison. Little is known about how inmates adopt various health behaviors during incarceration, without interventions. Methods: This study analyzed self-reports from 1468 inmates in Norwegian prisons, compared them according to harmful substance use pre-incarceration, and explored changes in exercise and nicotine use during incarceration. Results were presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results: Inmates with harmful substance use reported higher rates of smoking, smokeless tobacco, and physical inactivity pre-incarceration than inmates without harmful use. However, inmates with harmful use also exhibited more behavioral changes: they adopted exercise, ceased smoking, and adopted smokeless tobacco at higher rates during incarceration than the non-harmful group. Conclusions: Exercise is being taken up by a significant proportion of inmates, and may in particular be a replacement behavior for substance use. However, unhealthy behaviors are also begun or maintained. If prisons were used as an arena to facilitate healthy behaviors, the public health benefits to a marginalized group such as substance-using inmates could be substantial.

There is a potential for synergy effects in utilizing CO2 for both enhanced gas recovery (EGR) and geothermal energy extraction (CO2-plume geothermal, CPG) from natural gas reservoirs. This “combined CO2-EGR–CPG system” has been introduced as a feasible approach that constitutes a CO2 Capture double-Utilization and Storage (CCUUS) system. In this study, we carry out reservoir simulations, using TOUGH2, to evaluate the sensitivity of the natural gas recovery, pressure buildup, and geothermal power generation performance of the combined system to various key reservoir and operational parameters. The reservoir parameters include horizontal permeability, permeability anisotropy, reservoir temperature, and pore-size-distribution index; while the operational parameters include wellbore diameter and ambient surface temperature. Using an example of a natural gas reservoir model, we also investigate the effects of different strategies of transitioning from the CO2-EGR stage to the CPG stage on the energy-recovery performance metrics and on the two-phase fluid-flow regime in the production well. The simulation results show that overlapping the CO2-EGR and CPG stages and having a relatively brief period of CO2 injection but no production (which we call the CO2-plume establishment stage) achieves the best overall energy (natural gas and geothermal) recovery performance. Permeability anisotropy and reservoir temperature are the parameters the natural gas recovery performance of the combined system is most sensitive to. The geothermal power generation performance is most sensitive to the reservoir temperature and the production wellbore diameter. The results of this study pave the way for future CPG-based geothermal power-generation optimization studies. For a CO2-EGR–CPG project, the results can be a guide regarding the required accuracy of the reservoir parameters during exploration and data acquisition.

In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and geochemical changes to soil ecosystems over several million years, while high elevation refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17kya) were characterized using 16S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 meter displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the last glacial maximum. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale.

The concentration of all-trans-retinoic acid, the bioactive derivative of vitamin A, is critically important for the optimal performance of numerous physiological processes. Either too little or too much of retinoic acid in developing or adult tissues is equally harmful. All-trans-retinoic acid is produced by the irreversible oxidation of all-trans-retinaldehyde. Thus, the concentration of retinaldehyde as the immediate precursor of retinoic acid has to be tightly controlled. However, the enzymes that produce all-trans-retinaldehyde for retinoic acid biosynthesis and the mechanisms responsible for the control of retinaldehyde levels have not yet been fully defined. The goal of this review is to summarize the current state of knowledge regarding the identities of physiologically relevant retinol dehydrogenases, their enzymatic properties and tissue distribution, and to discuss potential mechanisms for the regulation of the flux from retinol to retinaldehyde.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

To gain insight into the real-life care of patients in the healthcare system, data from hospital information systems and insurance systems are required. Consequently, linking clinical data with claims data is necessary. To ensure their syntactic and semantic interoperability, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen. However, there is no detailed guide that would allow researchers to follow a consistent process for data harmonization. Thus, the aim of this paper is to conceptualize a generic data harmonization process for OMOP CDM. For this purpose, we conducted a literature review focusing on publications that address the harmonization of clinical or claims data in OMOP CDM. Subsequently, the process steps used and their chronological order were extracted for each included publication. The results were then compared to derive a generic sequence of the process steps. From 23 publications included, a generic data harmonization process for OMOP CDM was conceptualized, consisting of nine process steps: dataset specification, data profiling, vocabulary identification, coverage analysis of vocabularies, semantic mapping, structural mapping, extract-transform-load-process, qualitative and quantitative data quality analysis. This process can be used as a step-by-step guide to assist other researchers in harmonizing source data in OMOP CDM.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, as well as present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have been successful mostly in detecting the presence of these animals in field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored this matter by sampling lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months, attempting to detect differences in eDNA accumulation using a qPCR assay. Only one sample of the highest density pond readily amplified eDNA. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present a “shedding hypothesis”–the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms–as a potential challenge for turtle eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva so infection events are likely to be common. Indeed it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection, and HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. The properties of the Leak Pathway, such as its molecular mechanism, its regulation, and whether or not it has a size limit, remain controversial. This review will trace the evolution of the Leak Pathway concept from its origins, will discuss the current information about the properties of the Leak Pathway, and will discuss recent research suggesting a possible molecular basis for the Leak Pathway. Based on these findings, we propose a model for the molecular mechanism underlying the Leak Pathway and its regulation.

This study focused on demonstrating the potential of classification algorithm in the chemical composition characterization of transiting exoplanets. The Python-based module PLATON 5.3 for forward modelling of transiting planet spectra was used to simulate a set of transmission spectra of an exoplanet with size R_p = 1.40*R_jupiter, and mass M_p = 0.73*M_jupiter orbiting around the host star of size M_s = 1.16*M_sun and surface temperature of 1200 Kelvin. The gas composition of the exoplanet atmosphere was varied at low and high levels of 3-gas mix of CO₂, O₂, N₂ and CH₄ resulting to eight classes of spectra. The transit spectra were then used as input data to a forward neural network classifier with the eight gas composition classes as target outputs. The trained classifier achieved at most 97.9% overall accuracy.

Prescribed burning and other active forest management treatments have been proven to be essential for maintaining suitable habitat conditions for many wildlife species, including the federally endangered red-cockaded woodpecker (RCW). This study examines the perception of forest management treatments of recreation users participating in various activities (hunting, hiking/backpacking, camping, off-highway vehicle riding, and canoeing/kayaking) in terms of scenic beauty and recreation satisfaction. We used photographic images to capture various forest management treatments of different intensity levels and times after treatments, and assessed users’ perception of scenic beauty and recreation satisfaction. Results indicated variation among users participating in different recreation activities, but that good quality RCW habitat offered both higher scenic beauty and higher recreation satisfaction than poor quality habitat for most user groups. Finally, recreation satisfaction was statistically equal to perceived scenic beauty from both good and poor-quality RCW habitats for most of the user groups, thus suggesting the importance of scenic beauty on forest sites in determining recreation users’ attainment of visit satisfaction. Findings conclude that forest sites developed as good quality RCW habitat in the present state also offer quality experience to recreation users, thus supporting multi-objective forestry practices in public forests.

Increased demand for wearing face masks, lack of surgical masks and N95 respirators during the coronavirus pandemic created alternative needs for cloth masks. Therefore, to determine filtration efficacy, reusability and duration of wearing new and hand washed cloth masks, the bacteria filtration efficacy was tested using Staphylococcus aureus and Escherichia coli. Cotton cloth masks; single layer without pleats and with pleats, double layer with canvas filter in the middle, double layer with stiff filter in the middle, double layer with pleats on both sides and locally made and imported surgical masks and N95 respirators were used. Bacterial suspension was sprayed over outer surface and swabbed from inner surface at 0hrs, 4thhr, 8thhr and 12thhr. Similar procedure was performed to hand washed and ironed cotton cloth masks. After 24 hours of incubation, single layer without pleats and with pleats had no filtration efficacy(0-100%). Double layer with stiff filter in the middle and double layer with pleats on both sides had higher filtration efficacy(99.96-100%), this filtration efficacy remained up to three occasions of hand washing with soap and water, conferring protection up to 12hours. Filtration efficacy of surgical masks made locally, imported and N95 respirators were 90-100%, 99.99-100%, and 99.99-100% respectively.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

Asphalt pavement temperature has several applications, including pavement structural design and evaluation, asphalt mixture design, asphalt binder grade determination and material aging characterization. However, available asphalt pavement temperature prediction models were mostly developed for temperate climatic conditions, outside of the tropics. Before such models are adopted for use in a tropical climate, their applicability must be evaluated. This study evaluated five empirical asphalt pavement temperature prediction models developed by Lukanen et al. [1], Park et al. [2], Diefenderfer et al. [3], Taamneh [4] all in the United States and Asefzadeh et al. [5] in Canada to ascertain their prediction accuracy in tropical climate, using Ghana as a case study. In-situ asphalt pavement temperature data were measured at two sites for eight months: Kumasi and Tamale in the Forest and Savannah climatic zones, respectively. The measured pavement temperature data were statistically compared with predicted temperatures, and it was found that the Park et al. [2] model provided a more accurate pavement temperature prediction in both climatic zones. The other models either over-predicted or under-predicted asphalt pavement temperature with significant error margins. However, there is a need to improve the prediction accuracy of the Park et al. [2] model or a local model developed.

In Ultra-wideband (UWB)-based wireless ranging or distance measurement, differentiation between line-of-sight~(LOS), non-line-of-sight~(NLOS), and multi-path (MP) conditions are important for precise indoor localization. This is because the accuracy of the reported measured distance in UWB ranging systems is directly affected by the measurement conditions (LOS, NLOS or MP). However, the major contributions in literature only address the binary classification between LOS and NLOS in UWB ranging systems. The MP condition is usually ignored. In fact, the MP condition also has a significant impact on the ranging errors of the UWB compared to the direct LOS measurement results. Though, the magnitudes of the error contained in MP conditions are generally lower than completely blocked NLOS scenarios. This paper addresses machine learning techniques for identification of the mentioned three classes (LOS, NLOS, and MP) in the UWB indoor localization system using an experimental data-set. The data-set was collected in different conditions at different scenarios in indoor environments. Using the collected real measurement data, we compare three machine learning (ML) classifiers, i.e., support vector machine (SVM), random forest (RF) based on an ensemble learning method, and multilayer perceptron (MLP) based on a deep artificial neural network, in terms of their performance. The results show that applying ML methods in UWB ranging systems are effective in identification of the above-mentioned three classes. In specific, the overall accuracy reaches up to 91.9% in the best-case scenario and 72.9% in the worst-case scenario. Regarding the F1-score, it is 0.92 in the best-case and 0.69 in the worst-case scenario. For reproducible results and further exploration, we (will) provide the publicly accessible experimental research data discussed in this paper at PUB - Publications at Bielefeld University. The evaluations of the three classifiers are conducted using the open-source python machine learning library scikit-learn.

Factors affecting the host-virus interaction must be understood for the effective application of bacteriophages to combat bacterial pathogens. Two novel E. coli phages, the T1-like siphophage LL5 and the rV5-like myophage LL12, were subjected to forward genetic screens against the Keio collection, a library of single non-essential gene deletions in E.coli str. BW25113. These genome-wide screens and subsequent experiments identified eight genes required for efficient propagation of phage LL5 and six genes required for propagation of LL12. The majority of the genes identified were involved in production of the phage receptors. E. coli mutants deficient in heptose II and the phosphoryl substituent of heptose I of the inner core lipopolysaccharide (LPS) were unable to propagate phage LL5, as were mutants deficient in the outer membrane protein TolC. Mutants lacking glucose I of the LPS outer core failed to propagate LL12. Two cytoplasmic chaperones, PpiB and SecB, were found to be required for efficient propagation of phage LL5 but not LL12. This approach may be useful for identifying phage receptors and required host factors in other phages, which would provide valuable information for their potential use as therapeutics and for phage engineering.

Targeted radioisotope-guided sentinel lymph node dissection (sLND) has shown high diagnostic accuracy in prostate cancer (PCa). To overcome the downsides of the radioactive tracers, magnetometer-guided sLND using superparamagnetic iron oxide nanoparticles (SPIONs) was successfully applied in PCa. This prospective study (SentiMag Pro II, DRKS00007671) determined the diagnostic accuracy of magnetometer-guided sLND in intermediate- and high-risk PCa. Fifty intermediate- or high-risk PCa patients (PSA≥10 ng/ml and/or Gleason score ≥7; median PSA 10.8 ng/ml, IQR 7.4–19.2 ng/ml) were enrolled. After intraprostatic SPIONs injection a day earlier, patients underwent magnetometer-guided sLND and eLND, followed by radical prostatectomy. SLNs were detected in vivo and in ex vivo samples. Diagnostic accuracy of sLND was assessed using eLND as the reference. SLNs were detected in all patients (detection rate 100%), with 447 SLNs (median 9, IQR 6–12) being identified and 966 LNs (median 18, IQR 15-23) being removed. Thirty-six percent (18/50) of patients had LN metastases (median 2, IQR 1–3). Magnetometer-guided sLND had 100% sensitivity, 97.0% specificity, 94.4% positive predictive value, 100% negative predictive value, 0.0% false negative rate, and 3.0% additional diagnostic value (LN metastases only in SLNs outside the eLND template). In vivo, one positive SLN/LN-positive patient was missed, resulting in a sensitivity of 94.4%. In conclusion, this new magnetic sentinel procedure has high accuracy for nodal staging in intermediate- and high-risk PCa. The reliability of intraoperative SLN detection using this magnetometer system requires verification in further multicentric studies.

Human milk (HM) feedings are associated with reduced risks of neurodevelopmental and neurocognitive delays and systemic inflammatory diseases in infants born prematurely and/or at a low birth weight. Utilizing a neonatal piglet model, HM feedings were compared to bovine milk-derived infant formula (IF)-feedings with the aim of understanding the underlying mechanisms involved in reducing these risks. Six male piglets at postnatal-day (PD)2 were randomized into two feeding groups: HM-fed (n = 3) or IF-fed (n = 3) for 28 days. At 3- and 4-weeks-old, piglet memory and learning performance were assessed using novel object recognition (NOR). At PD30 piglets were euthanized, and whole brains were excised, weighed, and preserved for further analyses, and brain microglial morphology, and systemic inflammatory cytokines were quantified. During NOR, HM-fed piglets had significantly more non-novel revisits at both 3- and 4-weeks-old compared to IF-fed piglets. Microglia of HM-fed piglets had longer processes, more branch points, more endpoints, and a larger territorial volume compared to IF-fed piglets at PD30. In a neonatal piglet model, HM-feedings may improve cognition and reduce brain inflammatory response compared to IF-feedings.

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

This study introduces a low-cost solution provided by a specialized source measure unit (SMU), offering an alternative to conventional source meter units. Through precise IV curve measurements for graphene-channel FETs, the SMU demonstrates its capability in accurately characterizing these devices with minimal noise and high accuracy. This cost-effective solution presents a promising avenue for researchers and developers seeking reliable tools for sensor development and characterization, providing valuable insights into the behavior of graphene-channel FETs and the effect of surface illumination without the need for expensive equipment. Additionally, the SMU was validated with known passive and active components, along with probe station integration for microscale connection, ensuring its effectiveness in capturing accurate measurements. The SMU’s focus on collecting IV curves, coupled with its ability to identify device defects, such as Schottky junctions, contributes to its utility in quality testing for semiconductor devices. Its low-cost nature makes it accessible for various research endeavors, enabling efficient data collection and analysis for graphene-based sensor applications.

Background – The profound impact of COVID-19 on the U.S. healthcare industry cannot be overstated. Telemedicine utilization exploded virtually overnight as healthcare systems, hospitals, and clinical practices rushed to implement this delivery model to ensure accessibility and continuity of patient care access across myriad service lines and dimensions. Objective – The purpose of this systematic literature review is to examine the measures that were implemented to accommodate community and individual patient needs not only to afford access to critical services, but to also maintain safety standards for affected parties. Methods – Boolean operators were crafted with the expressed intent of identifying articles within multiple database domains germane to our chosen topic. Results – 52,206 articles were captured from a general search query and subsequently distilled to 44 through group consensus based on pertinence to our basic research question. The four health service lines identified encountered similar, surmountable obstacles in their care delivery models, but adapted accordingly to the respective needs of their patient populations. Conclusion – This review showcased the healthcare industry’s ability to rapidly acclimate and change due to the pervasive spread of COVID-19 throughout the U.S. Although imperfect, unique responses were developed within telemedicine platforms to broadly and effectively mitigate disruptions in care and treatment modalities.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

This study assessed the acute effects of oral methylliberine (DynamineTM) supplementation on cognitive function and indices of well-being. This was a double-blind, randomized, within-subject crossover trial. 25 healthy men and women (33.5±10.7yr, 172.7±8.6cm, 73.3±11.0kg) underwent pretesting before ingesting methylliberine (100mg) or placebo (PLA) for 3 days. On the fourth day participants were tested before their 4th dose (baseline) and every hour post-ingestion for 3 hours. After a one-week washout period, participants repeated testing with the alternate investigational product. The testing battery consisted of vitals, Stroop test and Trail Making Test-B, and visual analog scales that assessed various indices of well-being. Mixed factorial ANOVA with repeated measures were used to assess all variables. There were significant (p≤0.050) interactions in concentration, motivation, and mood. Methylliberine improved concentration 1- and 3-hours, motivation 3 hours, and mood 1-, 2-, and 3 hours (p≤0.050). Methylliberine improved energy, sustained energy, and mood in all participants to a greater extent than PLA at 1-hour and 3-hours relative to baseline (p≤0.050). PLA improved motivation at 1- and 2-hours and mood at 2-hours (p≤0.050). Methylliberine improved concentration, well-being, and the ability to tolerate stress to a greater extent than PLA at 3-hours relative to baseline (p≤0.050). Women observed elevations in sustained energy 1- and 3-hours (p≤0.050) in methylliberine vs. PLA. Methylliberine had negligible influence on cognitive function, vitals (p>0.050), and no adverse events were reported. Methylliberine significantly improved subjective feelings of energy, concentration, motivation, and mood, but not cognitive function. PLA improved motivation and mood at hours 1 and 2, while methylliberine sustained benefits for longer. Methylliberine also improved concentration, well-being, and the ability to tolerate stress to a greater degree than PLA while having no detrimental effects on vital signs. Methylliberine also seems to have a positive impact on sustained energy in women.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

Inorganic nanoparticles are utilized for therapeutic, diagnostic, or in combination, theranostic purposes. The latter involves simultaneous sensing, imaging, or tracking of drug delivery. Furthermore, these nanoparticles can differ in their morphologies, which affect outcomes such as the effectiveness of hyperthermia, induction, drug loading, circulation time by escaping the body's immune system, imaging modality clarity, and biosensing. However, design of these theranostics is limited by the lack of a method to predict their therapeutic efficacy. Herein, we report a simple and novel computational approach via algebraic and geometric calculations of surface area (SA) to volume (V) ratios (SA:V) which can help predict the efficacy of the inorganic nanoparticles of the investigated morphologies. The approach comprises a coding platform for the program and uses Python 3 on a Windows 10 operating system. Analyses of 29 polyhedral morphologies that inorganic nanoparticles could assume ex silico showed that only particular concave and convex morphologies in this size regime are more productive over the standard sizes as well as a few noted in literature for baseline comparison. Our results provide a method that can aid in predicting the efficacy of inorganic nanoparticles with certain morphology giving rise to their fundamental basis and eventual implementation ex silico.

Free-living terrestrial mites (Acari) have persisted through numerous glacial cycles in Antarctica. Very little is known, however, of their genetic diversity and distribution, particularly within the Ross Sea region. To redress this gap, we sampled for mites throughout the Ross Sea region, East Antarctica, including Victoria Land and the Queen Maud Mountains (QMM), covering a latitudinal range of 72-85oS, as well as from Lauft Island near Mt Siple (73oS) in West Antarctica and Macquarie Island (54oS) in the sub-Antarctic. We assessed genetic diversity using mitochondrial cytochrome c oxidase subunit I gene sequences (COI-5P DNA barcode region), and also morphologically identified voucher specimens. We obtained 130 sequences representing four genera: Nanorchestes (n = 30 sequences), Stereotydeus (n = 46), Coccorhagidia (n = 18) and Eupodes (n = 36). Tree-based analyses (maximum likelihood) revealed 13 genetic clusters, representing as many as 23 putative species indicated by Barcode Index Numbers (BINs) from the Barcode of Life Datasystems (BOLD) database. We found evidence for geographically-isolated cryptic species, e.g. within Stereotydeus belli and S. punctatus, as well as unique genetic groups occurring in sympatry (e.g. Nanorchestes spp. in QMM). Collectively, these data confirm high genetic divergence as a consequence of geographic isolation over evolutionary timescales. From a conservation perspective, additional targeted sampling of understudied areas in the Ross Sea region should be prioritised, as further diversity is likely to be found for these short-range endemic mites.

Population genetic data underpin many studies of behavioral, ecological, and evolutionary processes in wild populations and contribute to effective conservation management. However, collecting genetic samples can be challenging when working with endangered, invasive, or cryptic species. Environmental DNA (eDNA) offers a way to sample genetic material non-invasively without requiring visual observation. While eDNA has been trialed extensively as a biodiversity and biosecurity monitoring tool with a strong taxonomic focus, it has yet to be fully explored as a means for obtaining population genetic information. Here, we review current research that employs eDNA approaches for the study of populations. We outline challenges facing eDNA-based population genetic methodologies, and suggest avenues of research for future developments. We advocate that with further optimizations, this emergent field holds great potential as part of the population genetics toolkit.

The use of small Unmanned Aircraft Systems (sUAS ) as platforms for data capture has rapidly increased in recent years. However, while there has been significant investment in improving the aircraft, sensors, operations, and legislation infrastructure for such, little attention has been paid to supporting the management of the complex data capture pipeline sUAS involve. This paper reports on the outcomes of a four-year-long community-engagement-based investigation into what tools, practices, and challenges currently exist for particularly researchers using sUAS as data capture platforms. The key results of this effort are: (1) sUAS captured data – as a set that is rapidly growing to include data in a wide range of Physical and Environmental Sciences, Engineering Disciplines, and many civil and commercial use cases – is characterised as both sharing many traits with traditional remote sensing data and also as exhibiting – as common across the spectrum of disciplines and use cases – novel characteristics that require novel data support infrastructure. And (2), given this characterization of sUAS data and its potential value in the identified wide variety of use case, we outline eight challenges that need to be addressed in order for the full value of sUAS captured data to be realized. We then conclude that there would be significant value gained and costs saved across both commercial and academic sectors if the global sUAS user and data management communities were to address these challenges in the immediate to near future, so as to extract the maximal value of sUAS captured data for the lowest long-term effort and monetary cost.

Hallux valgus deformity (HVD) involves subluxation of the first metatarsophalangeal joint. While HVD is primarily considered a forefoot condition, midfoot instability may play a significant role in its development and severity. Therefore, this review had a particular focus on understanding midfoot instability based upon weightbearing imaging assessments of the TMT joint. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched five databases for studies on midfoot instability in HVD patients. Severity of HVD was defined by hallux valgus angle (HVA) and distal metatarsal articular angle (DMAA). Data was extracted, and articles were graded using the Methodological Index for Non-Randomized Studies (MINORS). Of 547 initially retrieved articles, 23 met inclusion criteria. Patients with HVD showed higher HVA and DMAA on weight-bearing radiographs (WBRG) and weight-bearing computed tomography (WBCT) compared to healthy individuals. Midfoot instability was assessed through intermetatarsal angle (IMA) and tarsometatarsal angle (TMT angle). Patients with HVD exhibited greater IMA and TMT angles on both WBRG and WBCT. This review highlights the importance of weight-bearing imaging assessments for midfoot instability in HVD. IMA and TMT angles can differentiate between healthy individuals and HVD patients, emphasizing the significance of midfoot assessment in understanding HVD pathology.

Oncology clinical pharmacists are uniquely positioned to make interventions to increase patient activation and engagement. To accomplish this goal, pharmacists can target health system-related, provider-related, and patient-related factors to help enhance patient-centered care and drive behavioral health changes. Interventions that pharmacists must tackle include educating team members and patients on the medication acquisition process, communicating urgency of treatment, optimizing workflows, facilitating guideline recommendations, preventing, and managing treatment toxicities, and promoting patient self-advocacy through education and shared decision-making. As crucial members of the healthcare team, oncology clinical pharmacists can simplify highly complex treatment regimens to facilitate and optimize patients’ ownership of their care. This review will focus on the example of venetoclax treatment in acute myeloid leukemia to demonstrate the impact that pharmacists provide that leads to behavioral change of patients and clinicians.

This review focuses on developments that quantify grain quality with a range of spectral sensors in an on-farm setting. If the application of sensor technologies were expanded and adopted on-farm, growers could identify the impact and manage the harvesting operation to meet a range of quality targets and provide an economic advantage to the farming enterprise.

Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ERBB4 is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the JM-a and CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0±3.2 months) than was no p-ERBB4 (22.5±9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.

(S)-1-Methyl-2-oxoimidazolidine-4-carboxylic acid 1 is an analog of (S)-pyroglutamic acid, a key component of naturally occurring peptide hormones and synthetic pharmaceutical candidates. Reaction of (S)-2-amino-3-(methylamino)propionic acid with COCl2 and aqueous NaHCO3 followed by ion exchange afforded 1, which was recrystallized from acetonitrile and then characterized by IR, 1H NMR, 13C NMR, polarimetry, elemental microanalysis, high resolution mass spectrometry and single crystal X-ray diffraction. The acid 1 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.2275(4) Å, b = 8.3963(5) Å, c = 24.9490(14) Å. The X-ray crystal structure reveals that two distinct conformers of 1 occur at alternating positions within helices which are supported by hydrogen-bonding. Each molecule of 1 is linked to its two neighbors in the helix by a total of three hydrogen bonds and four molecules of 1 are contained within each turn of the helix. The pattern of hydrogen bonds illustrates a preference for the carboxylic acid group to act as a hydrogen bond donor and for the urea unit to be a hydrogen bond acceptor.

Background: Risk tratification based on pre-test probability may improve the diagnostic accuracy of temporal artery high-resolution compression sonography (hrTCS) in the diagnostic workup of cranial giant cell arteriitis (cGCA). Methods: A logistic regression model with candidate items was derived from a cohort of patients with suspected cGCA (n = 87). The diagnostic accuracy of the model was tested in the derivation cohort and in an independent validation cohort (n = 114) by receiver operator characteristics (ROC)-analysis. The clinical items were composed to a clinical prediction rule, integrated into a stepwise diagnostic algorithm together with CRP-values and hrTCS-values. Results: The model consisted of 4 clinical variables (age &gt; 70, headache, jaw claudication, anterior ischemic optic neuropathy). The diagnostic accuracy of the model for discrimination of patients with and without a final clinical diagnosis of cGCA was excellent in both cohorts (AUC 0.96 and AUC 0.92, respectively). The diagnostic algorithm improved the positive predictive value of hrCTS substantially. Within the algorithm, 32.8% of patients (derivation cohort) and 49.1% (validation cohort) would not have been tested by hrtCS. None of these patients had a final diagnosis of cGCA. Conclusion: A diagnostic algorithm based on a clinical prediction rule improves the diagnostic accuracy of hrTCS.

Mental health in Puerto Rico is a complex and multifaceted issue that has been shaped by the island’s unique history, culture, and political status. Recent challenges, including disasters, economic hardships, and political turmoil, have significantly affected the mental well-being of the population coupled with the limitations in the accessibility of mental health services. Puerto Rico has fewer mental health professionals per capita than any other state or territory in the United States. This comprehensive review examines the impact of disasters on mental health and mental health services in Puerto Rico. Given the exodus of Puerto Ricans from the island, the review also provides an overview of mental health resources available on the island as well as the continental United States. The review identifies efforts to address mental health issues, with the intent of gaining a proper understanding of the available mental health services, key trends, as well as observable challenges and achievements within the mental health landscape of the Puerto Rican population.

Immobility during hospitalization is widely recognized as a contributor to deconditioning, functional loss, and increased need for institutional post-acute care. Several studies have demonstrated that inpatient walking programs can mitigate some of these negative outcomes, yet hospital mobility programs are not widely available in U.S. hospitals. STRIDE is a supervised walking program for hospitalized older adults that fills this important gap in clinical care. Herein we describe how STRIDE works and how it is being disseminated to other hospitals using the Replicating Effective Programs (REP) framework. Guided by REP, we define core components of the program and areas where the program can be tailored to better fit the needs and local conditions of its new context (hospital). We describe key adaptations made by 4 hospitals who have implemented the STRIDE program and discuss lessons learned for successful implementation of hospital mobility programs.

Overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma . Predominately, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS) -induced apoptosis. Here, we showed a novel link between BRF2 and DNA damage response. Due to the lack of BRF2 specific inhibitors, through virtual and molecular dynamics screening, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested Bexarotene as a potential BRF2 inhibitor. We found that Bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress (Tert-butylhydroquinone (tBHQ))-induced levels of BRF2 and consequently, lead to a decrease in cellular proliferation of cancer cells which may in part be due to drug pretreatment induced reduction of ROS generated by the oxidizing agent. Our data thus, provide the first experimental evidence that BRF2 is a novel player in DNA damage response pathway and Bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.

Yeasts belonging to the Metschnikowia genus are particularly interesting for the unusual formation of only two needle-shaped ascospores during their mating cycle. Presently, the meiotic process that can lead to only two spores from a diploid zygote is poorly understood. The expression of fluorescent nuclear proteins should allow the meiotic process to be visualized in vivo; however, no large-spored species of Metschnikowia has ever been transformed. Accordingly, we aimed to develop a transformation method for Metschnikowia borealis, a particularly large-spored species of Metschnikowia, with the goal of enabling the genetic manipulations required to study biological processes in detail. Genetic analyses confirmed that M. borealis, and many other Metchnikowiacea, are CUG-Ser yeasts. Codon-optimized selectable markers lacking CUG codons were used to successfully transform M. borealis by electroporation and lithium acetate, and transformants appeared to be the result of random integration. Mating experiments confirmed that transformed-strains were capable of generating large asci and undergoing recombination. Finally, random integration was used to transform an additional 18 yeast strains, and all attempts successfully generated transformants. The results provide a simple method to transform many yeasts from an array of different clades and can be used to study or develop many species for various applications.

Wastewater (WW) analysis is a critical step in various operations such as control of a WW treatment facility, and speeding-up the analysis of WW quality can significantly improve such operations. This work demonstrates the capability of neural network (NN) regression models to estimate WW characteristic properties such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), ammonia (NH3-N), total dissolved substances (TDS), total alkalinity (TA), and total hardness (TH) by training on WW spectral reflectance in the visible to near-infrared spectrum (400nm-2000nm). The dataset contains samples of spectral reflectance intensity, which were the inputs, and the WW parameter levels (BOD, COD, NH3-N, TDS, TA, and TH), which were the outputs. Various NN model configurations were evaluated in terms of regression model fitness. The mean-absolute-error (MAE) was used as the metric for training and testing the NN models, and the coefficient of determination (R2) between the model predictions and true values was also computed to measure how well the NN models predict the true values. With online spectral measurements, the trained neural network model can provide non-contact and real-time estimation of WW quality at minimum estimation error.

Obesity has been identified as an emerging health concern for Chinese American children; however, very little is known about diets in Asian American children. The objective of our paper was to describe the dietary intakes of urban Chinese American schoolchildren using a state-of-the-art approach for dietary assessment. Data for this analysis come from the Food Journal Project 2017, a pilot and feasibility study conducted by a multi-sector collaboration. Children aged 8-12 (n=83) completed two dietary assessments using a food diary from January-June 2017. Children were then interviewed using the food diary as a guide and dietary data were entered into the online ASA24 system by study staff. Chinese American children were identified using surname, and were compared to non-Chinese peers with respect to nutrient intake and the Healthy Eating Index 2010 (HEI-2010). Chinese American children consumed more sodium dense diets, more protein, and less sugar compared to non-Chinese children. With regards to the HEI-2010, Chinese American children had less favorable whole grains and sodium scores; and more favorable seafood protein and empty calories scores compared to non-Chinese children. Sodium reduction and increasing whole grain intakes may be warranted in this group, but should be verified with additional studies.

Blast charge initiation procedures have a significant impact on both mining safety and production rates. In this study, the inventory benefit of an electric initiation system was investigated to assess its influence on both fragmentation and blast-induced damages. The Wipfrag software's was used to examine the size distribution and productivity of 12 small-scale blasts initiated by both non-electric and electric detonators. All blast rounds was initiated with plain type of electric and NONEL detonators. The average burden, spacing, stemming length, and charge weight were, respectively, 0.85 m, 1.10 m, 0.66m, and 1.1kg. The results showed that the mesh through which 80% of the blast fragments will pass for the electric blast is smaller than the mesh through which the material products from the NONEL blast will pass. The results also demonstrate that the generated blast-induced ground vibration (PPV) from all blast rounds for electric blast varies from 0.4–1.2 mm/s and 80–105dB, while that for non-electric blast ranges from 0.05–0.2mm/s and 72–95dB. As a result, the electric blast initiation technique was found to produce good fragmentation, with a higher percentage of optimum fragment sizes on spec than non-electrically initiated blasts.

This study evaluates the R3THA™ technology-supported assessment protocol for home-based rehabilitation in children with cerebral palsy (CP). It focuses on the reliability and validity of R3THA™ in assessing hand and arm function, comparing kinematic assessments with standard clinical assessments. Conducted during a 4-week summer camp, the study involved children with CP aged 3-18, assessing their functional and impairment levels. The findings suggest that R3THA™ is more reliable for children aged 8 and older, indicating that age significantly influences the protocol's effectiveness. Results also showed that R3THA-AP's kinematic measurements of hand and wrist movements were positively correlated with the Box and Blocks Test Index (BBTI), reflecting hand function and dexterity. Additionally, R3THA-AP's accuracy metrics for hand and wrist activities aligned with the Melbourne Assessment 2's Range of Motion (MA2-ROM) scores, suggesting a meaningful relationship between R3THA-AP data and clinical assessments of motor skills. However, no significant correlations were observed between R3THA-AP and MA2's accuracy and dexterity measures, indicating areas for further research. These findings validate R3THA-AP's utility in assessing motor abilities in CP, supporting its integration into clinical practice.

Using optical characterization, it is evident that the spin state of the spin crossover molecular complex [Fe{H2B(pz)2}2(bipy)] (pz = tris (pyrazol-1-1y)-borohydride, bipy = 2,2’-bipyridine) depends on the ferroelectric polarization of an adjacent thin film of the polymer ferroelectric polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP). The UV-Vis spectroscopy reveals that room temperature switching of [Fe{H2B(pz)2}2(bipy)] molecules in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] as a function of ferroelectric polar polarization. The electric polarity dependence of bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] shows a strong dependence on the thickness of the PVDF-HFP layer. The PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] interface may affect polarization retention in the PVDF-HFP thin film limit.

Indwelling urinary catheters are common in healthcare settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified Enterococcus faecalis and Proteus mirabilis as the most prevalent and persistent co-colonizers. Clinical isolates of both species successfully co-colonized in a murine model of CAUTI, and they were observed to co-localize on catheter biofilms during infection. We further demonstrate that P. mirabilis preferentially adheres to E. faecalis during biofilm formation, and that contact-dependent interactions between E. faecalis and P. mirabilis facilitate establishment of a robust biofilm architecture that enhances antimicrobial resistance for both species. E. faecalis may therefore act as a pioneer species on urinary catheters, establishing an ideal surface for persistent colonization by more traditional pathogens such as P. mirabilis.

Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. Intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. We aim to evaluate the efficacy and safety of SLN sampling in CAH managed by the da Vinci robotic platform. A total of 113 patients with a preoperative diagnosis of CAH were included in this retrospective cohort study. All underwent a robot assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy with 69 patients undergoing SLN sampling. Statistical analysis calculated the probability of cancer, SLN map rate, and surgical complications. Predictors of cancer were evaluated. Forty-seven percent of the entire cohort were diagnosed with endometrial cancer. Median age was 63 years in the SLN cohort (N = 69) and 61 in the No SLN cohort (N = 44) (p= 0.363).  Median BMI was 34 Kg/m2 in the SLN cohort and 40 in the No SLN cohort (p= 0.004). Bilateral SLN map was 92.8% and unilateral SLN map rate was 7.2%. There were no grade 3-4 complications in the SLN cohort, and 4 grade 3-4 complications in the No SLN group (p=0.021). A preoperative diagnosis of CAH bordering on or cannot rule out cancer was the only predictor of cancer.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Background: This year has seen the emergence of two major crises, a significant increase in frequency and severity of hurricanes and the COVID-19 pandemic. However, little is known as to how each of these two events have impacted the other. A rapid qualitative assessment was conducted to determine the impact of the pandemic on preparedness and response to natural disasters and the impact of past experiences with natural disasters in responding to the pandemic. Methods: Semi-structured interviews were conducted with 26 representatives of 24 different community-based programs in southern Louisiana. Data were analyzed using procedures embedded in the Rapid Assessment Procedure – Informed Community Ethnography methodology, using techniques of immersion and crystallization and focused thematic analysis. Results: The pandemic has impacted the form and function of disaster preparedness, making it harder to plan for evacuations in event of a hurricane. Specific concerns included being able to see people in-person, providing food and other resources to residents who shelter in place, finding volunteers to assist in food distribution and other forms of disaster response, competing for funds to support disaster-related activities, developing new support infrastructures, and focusing on equity in disaster preparedness. However, several strengths based on disaster preparedness experience and capabilities were identified, including providing a framework for how to respond and adapt to COVID and integration of COVID response with their normal disaster preparedness activities. Conclusions: Although prior experience has enabled community-based organizations to respond to the pandemic, the pandemic is also creating new challenges to preparing for and responding to natural disasters.

While genetic testing is becoming mainstream in the management of patients with potentially inherited cardiovascular disease, the prevalence of uncertain results severely limits its utility. One promising approach is to generate variant effect maps that report the function of all possible variants in a gene prospectively. The proactive clinical application of these maps is nascent, and it requires careful integration with current American College of Medical Genetics guidelines for variant interpretation. Here, we describe three pediatric cases of cardiac arrest or sudden cardiac death with variants of uncertain significance in calmodulin genes. We demonstrate the prospective clinical utility of a calmodulin variant effect map to inform variant interpretation, and therefore diagnosis and family care, in each case. This study was approved by the Stanford University and Vanderbilt University Medical Center IRBs. Consent was waived based on low risk of de-identified retrospective data collection per the IRB.

There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

Background: Nurses are essential members of the healthcare workforce and were among the first line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of contracting the disease, resulting in a significant number of reported deaths among them. Several preventive measures were adopted to contain the spread of this potentially lethal virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. Method: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) of Barbados from December 2020 to July 2021, was conducted. Participants completed a questionnaire capturing socio-demographic information and knowledge and practices related to hand hygiene, using face masks, and social distancing . Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). Results: Of 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). Findings revealed that 45.8% had poor knowledge of hand hygiene, and the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% CI 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask-wearing, 53.6% of nurses had average and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% CI 1.5, 7.4) of having good knowledge compared to nursing assistants. 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by WHO. Conclusion: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

Nanoparticle-mediated radiation therapy (NPRT) is an emerging modality for radiosensitization of highly resistant cancers such as brain cancers. This is due to the ability of specific nanoparticles (NPs) to increase physical dose deposition and subsequent direct damage to cells and DNA within their local vicinity, through enhanced generation of reactive oxygen species, ROS. Here, we report the successful use of PEGylated (biocompatible) core-shell quantum dots (QDs) and carbon quantum dots (CQDs) to simultaneously enhance and assess ROS generation while radiosensitizing highly radioresistant brain cancer cell lines: T98G and U87 Glioblastoma cells. Relative peak fluorescence intensity ratio calculations and average intensity comparisons show highly significant (***p&lt;0.001) enhancement of ROS generation, for 5 Gy and 20 Gy irradiation, applied using a Faxitron Cell Irradiator. By quantifying post-radiotherapy cell attachment, proliferation, migration, cell survival and cell death using electric cell-substrate impedance sensing and clonogenic assays, we demonstrate potentially improved in vitro radiotherapeutic outcomes for brain cancer cells radiosensitized using PEGylated CdSe/ZnS QDs and CQDs.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Earth’s extinction crisis is escalating, and threat classification schemes are increasingly important for assessing which human activities are the most prominent drivers of species declines. However, a quantitative understanding of the conservation responses needed to abate threatening processes, and avoid species extinctions, is often lacking. Here, we provide a threat abatement framework which groups threats based on the shared conservation goal of the actions needed to abate their impact. We apply this framework to Australia’s threatened species to quantify the relative importance of achieving different conservation response goals. Our analysis shows the most important conservation responses across Australia are habitat retention and restoration, due to the combined impact of threatening processes causing habitat destruction and degradation (e.g. logging, mining, urbanisation and agriculture), which affects the majority (86%) of Australia’s threatened species and the effective control of invasive species (82%). Most species also require conservation responses focussed on improved fire management (66%). We show that implementing responses in isolation will be inadequate for abating species extinctions as almost all species (89%) require multiple, integrated management responses to redress their threats. We also acknowledge that already small and potentially genetically compromised taxa may require more direct interventions (e.g. captive insurance populations or genetic rescue). Our analysis highlights the necessity of addressing multiple threats at appropriate geographic scales across Australia. Our threat abatement framework ensures that core conservation actions can be identified and aid recovery of threatened species, and can be applied to other geographic regions and conservation contexts.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.

The effects of hypothermia on neonatal encephalopathy may vary regionally, spatially, and cytopathologically in the gyrencephalic neocortex with manifestations potentially influenced by seizures that alter the severity and distribution of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia with continuous encephalographic (cEEG) monitoring for seizures to study injury in neocortex. Neonatal piglets were randomized to naïve, HI-normothermia (NT), overnight hypothermia (HT) initiated 2 hours after HI, sham-NT, or sham-HT treatments. Some piglets within sham and HI groups received cEEG monitoring during recovery. Survival was 2-7 days (piglets were unmedicated and those with poor recovery and unresolving seizures were euthanized early); there was no differences in survival among groups (p&gt;0.078). Neuropathology was assessed by hematoxylin and eosin staining and immunohistochemistry for RNA Binding FOX-1 Homolog 3 (Rbfox3/NeuN). Normal and ischemic-necrotic neurons were counted (layers II-VI collectively) in somatosensory, motor, and prefrontal cortices, identified by cytoarchitecture and connectomics, and in inferior parietal cortex by layer. Seizure burden was determined. HI-NT piglets had reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to naïve, sham-NT, and sham-HT piglets in anterior and posterior motor and somatosensory cortices. Frontal cortex was vulnerable in the prefrontal lateral bank after HI-NT with ischemic-necrosis. HI-HT piglets had higher normal/total neuron ratios and lower ischemic-necrotic/total neuron ratios than HI-NT piglets in anterior/posterior motor and somatosensory cortices. Total normal neuron density in layer III of inferior parietal cortex was reduced in HI-NT piglets compared to sham piglets and was protected by HT. Laminar analysis of Rbfox3 in somatosensory cortex revealed three types of neurons: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT. Cortical neuron Rbfox3-depletion was partly rescued by HT. Seizure burden was more severe in HI piglets compared to sham piglets, but HI-NT and HI-HT piglets were similar. We conclude that 1) the neonatal piglet neocortex has a suprasylvian spatial vulnerability to HI and seizures; 2) HT protects against neuropathology in functionally different regions of the neonatal gyrencephalic neocortex; 3) neurons in neonatal neocortex have a limited cytopathology repertoire seen by H&amp;E staining; 4) higher seizure burden correlates with more ischemic-necrotic neurons in somatosensory cortex; 5) seizure presence associates with damage spread to inferior parietal cortex; 6) seizure presence is insensitive to HT, and 7) Rbfox3 immunophenotyping identifies a novel neuronal RNA splicing protein nuclear-depletion pathology that appears reversible by HT. This work demonstrates that HT protection of neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores depleted neuronal RNA splicing factor.

There is rapidly emerging evidence from pre-clinical studies, patient samples and patient subpopulations that certain chemotherapeutics inadvertently produce prometastatic effects. Prior to this, we showed that doxorubicin and daunorubicin, stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. Here, we investigate which other anti-cancer drugs might have similar prometastatic effects by altering the biophysical properties of cells. We treat myelogenous (K562) leukemic cancer cells with the drugs nocodazole and hydroxyurea, and then measure their mechanical properties using the microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation and enables the measurement of cell mechanical properties via transit times through the device. We also quantify the morphological properties of cells to explore biophysical mechanisms underlying the MMM results. Results from MMM measurements show that nocodazole- and hydroxyurea-treated K562 cells exhibit significantly altered transit times. Nocodazole caused significant (p &lt; 0.01) increase in transit times, implying a stiffening of cells. This work shows the feasibility of using the MMM to explore possible biophysical mechanisms that might contribute to chemotherapy-induced metastasis. Our work also suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies in general.

Epigenetics, specifically DNA methylation, allows for estimation of animal age from blood or remotely sampled skin. This multi tissue epigenetic aging clock uses 110 longitudinal samples from 34 Navy bottlenose dolphins (Tursiops truncatus), identifying 195 cytosine-phosphate-guanine sites associated with chronological aging via leave-one-individual-out-cross-validation (R2=0.95). With a median absolute error of 2.5 years this clock improves age estimation capacity in wild dolphins, expanding conservation efforts, enabling better understanding of population demographics.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

The X-ray induced spin crossover transition of an Fe(II) molecular thin film in the presence and absence of a magnetic field has been investigated. The thermal activation energy barrier in the soft X-ray activation of the spin crossover transition for [Fe{H2B(pz)2}2(bipy)] molecular thin films is reduced in the presence of an applied magnetic field, as measured through X-ray absorption spectroscopy at various temperatures. The influence of a 1.8 T magnetic field is sufficient to cause deviations from the expected exponential spin state transition behavior that is measured in the field free case. We find that orbital moment diminishes with increasing temperature, relative to the spin moment in the vicinity of room temperature.

In this retrospective analysis, we examined the prognostic value of serum albumin at diagnosis prior to any therapy in a cohort of patients with acute myeloid leukemia (AML) irrespective of treatment modality. Data were collected retrospectively in a cohort of 257 AML patients who received treatment between 2002 to 2019. The cohort included patients who received conventional 7+3 induction, patients who were not candidates for induction receiving lower-intensity chemotherapy or targeted therapy, and patients who were placed on clinical trials. Patients were classified into two groups, by serum albumin level at presentation, normal albumin (≥3.5 g/dL) and hypoalbuminemia [HA](

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. Neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. This systematic review provides an overview on the value of NfL in early detection of neuropathy, central nervous system involvement, monitoring of neuropathy progression, and treatment effect in systemic amyloidosis. A literature search in PubMed, Embase and Web of Science was performed on 14-02-2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene variant (TTRv) carriers. Only studies containing original data were included. Included were twelve full-text articles and six abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has potential to be used for early detection of neuropathy, monitoring treatment effect, and monitoring disease progression in patients with systemic amyloidosis.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Currently available COVID-19 mRNA vaccines have demonstrated high efficacy in clinical trials.1-3 However, cancer patients, including those with hematological malignancies, were largely excluded from these trials. In this prospective, observational study we measured anti-S protein IgG titers as well as avidity in lymphoma patients (n=67) vaccinated with a COVID-19 mRNA vaccine. Serological response rates in lymphoma patients who were treatment naïve (100% in CLL, 88.9% in other, non-CLL non-Hodgkin lymphoma patients), or who were last treated more than 24 months prior to vaccination (100% in CLL, 90% in other-NHL), were similar to healthy controls (100%). Patients on active therapy, however, had a diminished response rate (40% in CLL, 21.0% in other-NHL). No patient who received anti-CD20 monoclonal antibodies (mAb) within six months of vaccination responded. Thus, the utility of testing anti-S titers should be explored in patients on active therapy or with recent anti-CD20 mAb exposure, to assess their response to vaccination. We also propose studying passive protection with S-protein mAbs as an alternative prophylactic strategy for patients who respond poorly to vaccination.

Adaptation to climate change is being addressed in many domains. This means that there are multiple perspectives on adaptation; often with differing visions resulting in disconnected responses and outcomes. Combining singular perspectives into coherent, combined perspectives that include multiple needs and visions can help to deepen the understanding of various aspects of adaptation and provide more effective responses. Such combinations of perspectives can help to increase the range and variety of adaptation measures available for implementation or avoid maladaptation compared with adaptations derived from a singular perspective. The objective of this paper is to present and demonstrate a framework for structuring the local adaptation responses using the inputs from multiple perspectives. The adaptation response framing has been done by: (i) contextualizing climate change adaptation needs; (ii) analyzing drivers of change; (iii) characterizing measures of adaptation; and (iv) establishing links between the measures with a particular emphasis on taking account of multiple perspectives. This framework was demonstrated with reference to the management of flood risks in a case study Can Tho, Vietnam. The results from the case study show that multiple perspective framing of adaptation responses enhance the understanding of various aspects of adaptation measures, thereby leading to flexible implementation practices.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.