Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections

Facial expressions play a key role in interpersonal communication when it comes to negotiating our emotions and intentions, as well as interpreting those of others. Research has shown that we can connect to other people better when we exhibit signs of empathy and facial mimicry. However, the relationship between empathy and facial mimicry is still debated. Among the factors contributing to the difference in results across existing studies is the use of different instruments for measuring both empathy and facial mimicry, as well as often ignoring the differences across various demographic groups. This study first looks at the differences in empathetic abilities of people across different demographic groups based on gender, ethnicity and age. The empathetic ability is measured based on the Empathy Quotient capturing a balanced representation of both emotional and cognitive empathy. Using statistical and machine learning methods, the study then investigates the correlation between the empathetic ability and facial mimicry of subjects in response to images portraying different emotions displayed on a computer screen. Unlike the existing studies measuring facial mimicry using electromyography, this study employs a technology detecting facial expressions based on video capture and deep learning. This choice was made in the context of increased online communication during and post the COVID-19 pandemic. The results of this study confirm the previously reported difference in the empathetic ability between females and males. However, no significant difference in the empathetic ability was found across different age and ethnic groups. Furthermore, no strong correlation was found between empathy and facial reactions to faces portraying different emotions shown on a computer screen. Overall, the results of this study can be used to inform the design of online communication technologies and tools for training empathy team leaders, educators, social, and health care providers.

The oviparous blow fly Calliphora vicina has shown potential as a managed pollination species to support honeybee (Apis mellifera) usage in Australian horticulture. This blow fly species lays eggs onto carrion soon after death and the resultant larvae that hatch are necrophagous and feed on the decomposing tissues of the dead animal. Newly hatched larvae of this fly were provided with plant-based meals (soya bean and canola) and compared with animal-derived meatmeal to determine if plant-based meal could be used to mass rear this blow fly species. Both soyabean and canola meal media did not support the survival of any larvae through to adult eclosion. The addition of only 10% whole egg powder to the plant-based meals enabled survival to eclosion of 39% and 13% on soyabean and canola based medias respectively compared with 76% on animal-based meatmeal with 10% whole egg powder. Larvae fed livestock meatmeal with 10% whole dried egg powder had the fastest development to the pupal stage, the highest pupation rate, the heaviest pupae and the highest subsequent adult eclosion. This study concluded that the use of plant-based meals in the mass rearing of the blow fly C. vicina was neither viable, nor economically viable.

We conducted a study to determine if antenatally collected maternal urine cotinine (a me- 13 tabolite of nicotine) measurements can be used to assess the neonatal impact of nicotine exposure 14 during pregnancy. This was a prospective longitudinal cohort of mother-infant dyads. Only term 15 singleton pregnancies were included. The primary outcome measure was the correlation between 16 maternal urine cotinine and infant birth weight. We analysed data from 238 mother-neonates' dy- 17 ads. Urine cotinine was detected in 50.4 % (120/238) women from the whole cohort, but only 16% 18 (38/238) self-reported as smokers (chi-square 39.7, p<0.0001), and these women had significantly 19 smaller babies (p=0.010). There was a significant negative correlation between maternal urine co- 20 tinine and birth weight (Spearman's coefficient = -0.0226, p=0.013). Female babies born to women 21 with nicotine in the urine were significantly smaller (p= 0.001). The number of women exposed to 22 nicotine during late pregnancy (measured in urine) was markedly higher than self-reported and 23 National smoking percentages, suggesting an urgent need for improvement of medical record re- 24 porting on smoking habits to better assess neonatal outcomes.

The Australian tropical montane cloud forest (TMCF) is home to approximately 18 percent of the nation’s total vascular plant species. Over the past century, human activity and industrial development have caused global climate changes, posing a severe and irreversible danger to the entire land-based ecosystem, and WTWHA is no exception. The current average annual temperature of WTWHA in FNQ is 24 °C. However, in the coming years (by 2030), the average annual temperature increase is estimated to be between 0.5 and 1.4 °C compared to the climate observed between 1986 and 2005. Looking further ahead to 2070, the anticipated temperature rise is projected to be between 1.0 and 3.2 °C, with the exact range depending on future emissions. We identified 84 plant species endemic to the WTWHA in FNQ, which are already experiencing climate change threats. Few of these plants are used in herbal medicines. This study comprehensively reviewed metabolomics studies conducted on these 84 plant species until now toward understanding their physiological and metabolomics responses to global climate change. This review also discusses: i) recent developments in plant metabolomics studies that can be applied to study and understand the interactions of wet tropical plants with climatic stress, ii) medicinal plants and isolated phytochemicals with structural diversity, and iii) reported biological activities of crude extracts and isolated compounds.

This research paper aims to evaluate and model the performance of rice husk gasifier cook stoves for household energy use, a byproduct of rice milling. The study aims to address environmental issues and promote the use of rice husk as a renewable energy source and pest repellent in stoves. The study compared insulated and non-insulated gasifier stoves using rice husk gasification. The study compared the start-up time of insulated and non-insulated gasifier stoves, where the insulated stove showed a lower start-up time, but there was no significant difference at a 5% probability level. The temperature change also was not significant, as heat transfer and temperature change started when the husk was ignited. The burner stoves had different size and volume. The maximum operated or flame temperature was 1,190.30oC at room or minimum temperature of 27.33 oC, whereas the average temperature was 758.916oC for the non-insulated type of gasifier stove. The insulated gasifier stove also observed maximum and average temperatures of 518.30 oC and 289.014oC respectively at the same room temperature. The operating time of stoves directly influences the fuel consumption rate, specific gasification rate, and combustion zone rate of stoves. The fuel consumption rate has a significant effect on the type of gasifier stove, with the maximum rates being 3.820 and 2.099 kg/hr. The time to consume rice husks to gasify them depends on the density of the rice husk, reactor volume, and fuel consumption rate. The average specific gasification rate for insulated and non-insulated stoves is 106.45 and 120.63 kg/m2h, respectively. The fuel or rice husk holding capacity of each type of stove is significant at a 5% level, with the amount of rice husk and biochar produced being 1.18kg and 0.27kg for insulated stoves, and 2.511kg and 0.688kg for non-insulated stoves, respectively. The performance of gasifier stoves varies based on the bio char conversion rate, with non-insulated stoves producing a higher bio char mass per rice husk. Multiple regression analysis was used to model the relationship between time elapse with temperature and heat energy. The Squirrel-2020 data logger was used to measure the temperature produced by burning rice husks in the reactor of the stove as well as related generated and losses of heat. A relationship between the heat energy produced and the operating time of gasifier stoves was conducted to estimate the model. The cubic polynomial model was found to be the best predictive model fit for all variables of this study.

Gastrointestinal parasites (GIP) are diverse parasitic organisms known to have coevolved with bacterial populations inside the gut of mammalian hosts. These helminths produce small molecules, peptides and proteins to evade or fight their hosts' immune systems. Small molecules include polar compounds, amino acids, lipids and carbohydrates. Metabolomics is an emerging field of research recently applied to study helminth infections and host-parasite interactions. This review comprehensively discusses metabolomics studies of small molecules of GIP in animals, providing insights into the available tools and techniques, databases, and analytical software. Most metabolomics investigations employed LC-MS, MS or MS/MS, NMR, or a combination thereof. Recent advancements in metabolomics platforms, including artificial intelligence (AI)-assisted software tools and databases, have propelled helminth metabolomics forward, offering new avenues to explore host-parasite interactions, immunomodulation, and the intricacies of parasitism. As our understanding of helminth metabolomics continues to expand, it promises to unveil novel perspectives and enrich the knowledge of these complex host-parasite relationships.

Fluxgate magnetometers require calibration methods appropriate to their application levels and particularities; however the development of fully controlled calibration procedures presents a particular challenge regarding the inevitable influence of the local geomagnetic field and other external interferences when a laboratory with magnetically shielded walls is not available. In that context, we discussed the development of an automated calibration method for fluxgate magnetometers, considering those limitations in time and space, and avoiding some of the problems commonly found in other proposed solutions for the same challenge. For this task, we designed and built a new set of high level procedures, electronic systems and software, which perform active testing and automated calibration of fluxgate magnetometers, considering some resource constraints and employing instruments commonly found in electronic calibration laboratories.

Contact tracing is one of the oldest social network health interventions used to reduce the diffusion of various infectious diseases. However, some infectious diseases like COVID-19 amass at such a great scope that traditional methods of conducting contact tracing (e.g., face-to-face interviews) remain difficult to implement, pointing the need to develop reliable and valid survey approaches. The purpose of this research is to test the effectiveness of three different egocentric survey methods for extracting contact tracing data: (1) a baseline approach, (2) a retrieval cue approach, and (3) a context-based approach. A sample of 397 college students were randomized into one of each condition and were prompted to anonymously provide contacts and populated places visited from the past four days. After controlling for various demographic, social identity, psychological, and physiological variables, participants in the context-based condition were significantly more likely recall more contacts (medium effect size) and places (large effect size) than the other two conditions. Theoretically, the research supports suggestions by field theory that assume network recall can be significantly improved by activating relevant activity foci. Practically, the research contributes to developing innovative social network data collection methods for contract tracing survey instruments.

Botulinum neurotoxin (BoNT) intoxication can lead to the disease botulism, characterized by flaccid muscle paralysis that can cause respiratory failure and death. Due to the significant morbidity and mortality costs associated with BoNTs high toxicity, developing highly sensitive, rapid, and field-deployable assays are critically important to protect the nation’s food supply against either accidental or intentional contamination. We report here that the B-cell based biosensor assay (CANARY^® Zephyr) detects BoNT/A in buffer and various food matrices rapidly in ≤ 40 min, in small volumes ≈ 50 μL, with minimal processing of samples, and is extremely portable (suitcase-sized equipment). BoNT/A was detected at limits of detection (LOD) < 0.075 ng ± 0.02 in assay buffer while milk matrices (non-fat, 2 %, whole milk) increased the LOD to < 0.175 – 0.314 ng. Limits of detection for the assay in complex foods were < 1 ng ± 0.0 (neutralized acidic juices-carrot, orange and apple); < 16.7 ng ± 7.7 (liquid egg); and varied from < 0. 39 – 3.125 ng for solid complex foods (ground beef, green bean baby puree, smoked salmon). These results show that the CANARY^® Zephyr assay can be a highly useful tool in clinical, environmental, and food safety surveillance programs.

The aim of the present study was to provide initial validity evidence of a Greek translation of the 24-item Brunel Mood Scale, referred to as the BRUMS-Greek, a measure of anger, confusion, depression, fatigue, tension, and vigour. Data were collected from 1,417 Greek adult exercise participants and 369 physically inactive adults, totaling 1,786 adults (male = 578, female = 1,208) aged 18–64 years (M = 34.73 ± 11.81 years). Given the large univariate and multivariate non-normality, confirmatory factor analyses treating responses as ordered categorical variables was conducted, which supported the hypothesised six correlated-factor measurement model. Internal consistency reliability of BRUMS-Greek subscales was supported via Cronbach alpha coefficients. Construct validity of scales was supported (a) via correlations in the hypothesised direction with trait positive and negative affect, (b) with more positive and less negative moods reported immediately after participation in a single exercise class compared to pre-exercise mood, and (c) with exercise participants reporting more positive and less negative mood states compared to physically inactive adults. Women reported higher tension and lower vigour scores than men. Tension scores were higher and confusion scores lower among younger participants (≤ 35 years) than older participants (≥ 36 years). Participants with obesity reported higher negative mood scores than those who were underweight or normal weight. In sum, the BRUMS-Greek demonstrated acceptable psychometric characteristics, and is proposed to be a suitable measure for use with exercise participants, physically inactive adults, and other Greek populations to explore research questions related to mood.

The Arctic is a remote region that has become increasingly globalised yet remains extremely vulnerable to many risks. The COVID-19 pandemic presented new challenges to the region. Using the Search, Appraisal, Synthesis and Analysis (SALSA) approach to conduct a meta-synthesis of the academic and grey literature on the impacts of the pandemic, an assessment is conducted of the types of risks that have been presented by the COVID-19 pandemic, the scales, and the national response strategies for mitigating the risks. Two case studies are explored, Iceland and Greenland, island nations that exemplify the extremes of the Arctic and reliance on tourism, a sector that was nearly entirely suspended by the pandemic. An evaluative matrix is employed which combines five different scales of risk – nano, micro, meso, macro and cosmic – with a sustainability categorisation of impacts. The risks of the pandemic cut across the respective scale and categories, with the potential for macro-scale events (systemic risk) to unfold linked to economic spillover effects driven by the curtailment of tourism and various supply chain delays. Both Iceland and Greenland have exemplified risk mitigation strategies which prioritise health over wealth, very strictly in the case of the latter. Strict border controls and domestic restrictions have enabled Iceland and Greenland to have much lower case and death numbers than most nations. In addition, Iceland has led the way, globally, in terms of testing and accumulating scientific knowledge concerning the genetic sequencing of the virus. The academic contribution of the paper concerns its broadening of understanding concerning systemic risk, which extends beyond financial implications to includes sustainability dimensions. For policymakers and practitioners, the paper highlights successful risk mitigation and science-based measures that will be useful for any nation tackling a future pandemic, regardless of whether they are island states, Arctic nations or another country.

The topic of technology development and its disruptive effects has been the subject of much debate over the last 20 years with numerous theories at both macro and micro scale offering potential models of technology progression and disruption. This paper focuses on how the potential theories of technology progression can be integrated and considers whether suitable indicators of this progression and any subsequent disruptive effects (particularly considering these geographically) might be derived, based on the use of big data analytic techniques. Given the magnitude of the economic, social and political implications of many disruptive technologies, the ability to quantify disruptive change at the earliest possible stage could deliver major returns by reducing uncertainty, assisting public policy intervention and managing the technology transition through disruption into deployment. However, determining when this stage has been reached is problematic because small random effects in the timing, direction of development, the availability of essential supportive technologies or “platform” technologies, market response or government policy can all result in failure of a technology, its form of adoption or optimality of implementation. This paper reviews some of the key models of technology evolution and their disruptive effect including, in particular, the geographical spread of disruption. It suggests a methodology for utilising the recent explosion of open and web-discoverable data to determine a methodology to achieve this earlier determination and considers the potential exploitation of big data modelling and predictive analytical techniques to achieve this goal.

INTRODUCTION There have been several advances in the treatment of hepatitis C virus (HCV) infection which have resulted in major reductions in the morbidity and mortality from liver-associated disease. These are not widely available in the Caribbean, due in part, to lack of knowledge of the epidemiology of infections with HCV. As efforts are made to eliminate HCV from the region, these and other existing barriers such as lack of an established database on HCV must be addressed. This review seeks to identify gaps in the knowledge of HCV in the Caribbean with respect to seroprevalence, genotype distribution and general epidemiologic characteristics. MATERIALS AND METHODS The literature for the period January 1, 2005, to October 2022, was reviewed to gather country specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases. The usage pattern of HCV drugs was determined from data obtained from Pharmacists and Infectious Diseases Specialists across the region. RESULTS The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate prevalence. Notably, data from specific countries were limited. The prevalence of HCV among intravenous drug users (21.9-58.8%); persons living with HIV/AIDS (0.8 to 58.5%); prisoners (32.8-64%) and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83% was most prevalent followed by genotypes 2 (7.2%) and 3(2.1%), respectively. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (Sofosbuvir/velpatasvir), and Harvoni (Ledipasvir/sofosbuvir). Some of these drugs, are only available in the private sector and are sourced externally whenever needed. CONCLUSION There is a paucity of current data on the seroprevalence of HCV in the Caribbean and well-designed prospective studies are indicated to drive the implementation of treatment and control programs for HCV in the region. Barriers which need to be first overcome include unavailability and high cost of drugs used to treat HCV infections, injecting drug use and limited access to medical care and laboratory testing.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

Objective: In low- and middle-income countries (LMICs), household survey data are a main source of information for planning, evaluation, and decision-making. Standard surveys are based on censuses, however, for many LMICs it has been more than ten years since their last census and they face high urban growth rates. Over the last decade, survey designers have begun to use modelled gridded population estimates as sample frames. We summarize the state of the emerging field of gridded population survey sampling, focussing on LMICs. Methods: We performed a systematic review and identified 43 national and sub-national gridded population-based household surveys implemented across 29 LMICs. Findings: Gridded population surveys used automated and manual approaches to derive clusters from WorldPop and LandScan gridded population estimates. After sampling, many surveys interviewed all households in each cluster or segment, though some sampled households from larger clusters. Tools to select gridded population survey clusters include the GridSample R package, Geo-sampling tool, and GridSample.org. In the field, gridded population surveys generally relied on geographically accurate maps based on satellite imagery or OpenStreetMap, and a tablet or GPS technology for navigation. Conclusions: For gridded population survey sampling to be adopted more widely, several strategic questions need answering regarding cell-level accuracy and uncertainty of gridded population estimates, the methods used to group/split cells into sample frame units, design effects of new sample designs, and feasibility of tools and methods to implement surveys across diverse settings.

Despite knowledge concerning stakeholders and the economic advantages of consultation, collaboration and innovation, analysis of the sustainability implications of the geothermal industry has tended to take a high-level or systemic overview of national performance. This study seeks to begin to fill this gap in the academic and grey literature, investigating the following research question: how do projects in the Icelandic geothermal energy sector create co-benefits with stakeholders and reflect the integration of sustainable energy development (SED)? The focus of its analysis is on identifying who are the stakeholders, what are the sustainability benefits co-created with stakeholders, and when in the project lifecycle do these occur. Based on eleven semi-structured interviews with project managers in Iceland’s geothermal industry, the study identifies a broad array of stakeholders in the sector, including national and municipal governments and public sector institutions, businesses, the public, employees and landowners. The sustainability co-benefits of Iceland’s geothermal power projects are broad and cut cross all six themes of SED and multiple phases of the project lifecycle. Although the sustainability benefits are very apparent, trade-offs are reported between the pursuit of an economically efficient energy system and nature conservation. This relates to unsustainable utilization of the resources and the environmental externalities of power production and consumption. Efforts to mitigate these effects are ongoing and the further pursuit of SED is likely in Iceland given its recognition within the nation’s new energy policy and to meet ambitious greenhouse gas emissions reduction targets in the government’s climate action plan. These are issues that are prominent in other nations seeking to decarbonize energy systems through increased utilization of geothermal resources.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Acute pancreatitis (AP) is a leading gastrointestinal disease that cause hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer’s solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. Routine use of prophylactic antibiotics is generally limited, and the procalcitonin based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and prevent recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP.

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

Apple (Malus x domestica) fruit size is dependent on cell division and cell expansion, processes which are subsequently regulated by plant hormones such as auxins, gibberellins, and cytokinins. In this study, we investigated the role of cell division and cell expansion in apple growth and identified which of the two was more deterministic to final fruit size. Three cultivars of different sizes were selected, namely, ‘Twenty Ounce’ (large-sized), ‘Royal Gala’ (medium-sized), and ‘Crabapple’ (small-sized). Gene expression and cell size analyses were conducted over the course of two consecutive seasons. The expression patterns of three classes of genes were markedly similar across all cultivars. Two cell division markers, namely, MdCDKB2;2 and MdANT2, were discovered to be correlatively expressed as both displayed initially high expression levels, which gradually declined from the early to late stages of growth time course. For cell expansion markers, MdEXP3 was upregulated as the cells expanded, while MdARF106 was expressed in both the cell division and expansion stages. Meanwhile, the ripening related gene MdACO1 was expectedly expressed only during the ending stages associated with ripening. Interestingly, the cell measurements taken regularly from each cultivar throughout the same eperimental timespan showed that cell sizes were unaltered and remained constant from initial pollination at the zeroth Days After Pollination (DAP), to ripening at 120 Days After Full Bloom (DAFB).

The material undergoes high temperature and high strain rate deformation process during cutting process, may induce the dynamic recrystallization behavior and result the evolution of dynamic mechanical properties of the material to be machined. In this paper, the modified Johnson-Cook(J-C) model for Nickel based powder metallurgy superalloy considering dynamic recrystallization behavior in high strain rate and temperature is proposed. The dynamic mechanical properties of the material under different strain rates and temperature conditions are obtained by quasi-static compression test and split Hopkinson pressure bar (SHPB) test. The coefficients of the modified J-C model are obtained by linear regression method. The modified model is verified by comparison with experimental and model prediction results. The results show that the modified J-C model proposed in this paper can accurately describe the mechanical properties of nickel-based powder metallurgy superalloys at high temperature and high strain rate. Which provides help for studying the cutting mechanism and finite element simulation of nickel-based powder metallurgy superalloy.

Empirical models help us understand the process of plant residue decomposition and nutrient release into the soil. The objective of this study was to determine an appropriate model to describe the decomposition of hairy vetch (Vicia villosa Roth) and cereal rye (Secale cereale L.) cover crop (CC) residue and nitrogen (N) release. Data pertaining to above and belowground CC residue mass loss and N release for up to 2633 cumulative decomposition degree days (112 d) after litterbag installation were obtained from two cropping system experiments, one conducted in 2015 and the other in 2017 and 2018 at the humid subtropical environment of southern IL, USA. Six exponential and two hyperbolic models were fit to percent mass and N remaining data to find the one with minimum Akaike Information Criterion (AIC) and residual sum of squares. Modified three-parameter single exponential and two- or three-parameter hyperbolic models best met the assumed criteria of selection for above and belowground CC residue, respectively. Fitting a double exponential model to a combined data for percent mass and N remaining, which identified two mass and N pools, a fast and a slow pool with different rate constants. A five-parameter double exponential with an asymptote met the preset criteria and passed all tests for normally distributed population, constant variance, and independence of residuals at α = 0.05 when fit to combined data of hairy vetch shoot mass and N remaining. However, a two-parameter hyperbolic and three-parameter asymptotic hyperbolic model provided the best fit to a combined data of cereal rye shoot mass and N remaining, respectively. Both hyperbolic decay models showed a good fit for belowground mass decomposition and N release for both CCs. Cereal rye had poorer fit than hairy vetch for mass and N remaining of both above and belowground mass. The best-selected decay models can be used to estimate the decomposition and N release rates of hairy vetch and cereal rye above and belowground residue in a similar environment.

This study investigates the transformative impact of ChatGPT, a cutting-edge AI language model developed by OpenAI, on the financial sector. We explore ChatGPT's applications in financial analysis, focusing on its ability to perform tasks traditionally handled by human analysts. By creating a set of multi-step and advanced reasoning financial tasks, and establishing several task-specific evaluation metrics, our experimental results demonstrate that ChatGPT-4o can effectively perform both basic and some complex financial analysis tasks comparable to those executed by humans. However, our empirical evaluation reveals limitations in its performance on complex tasks that require comprehensive understanding and critical thinking. The study highlights the necessity for meticulous task formulation and robust evaluation to achieve consistent functionality. While ChatGPT enhances efficiency in financial analysis, its integration with human expertise remains crucial for effective decision-making. This study contributes to the understanding of AI's role in finance and provides insights into its potential and constraints, guiding future integration of AI technologies in financial practices.

This study evaluated the impact of rough, smooth, and very smooth Titanium (Ti) and zirconia (Zr) surfaces on the neutrophil expression of elastase (NE), matrix metalloproteinase (MMP)-8, MMP-9 and extracellular traps (NETs). Ti and Zr disks with a diameter of 10mm and a thickness of 1.5mm were processed using diamond-impregnated polishing burs and paste to generate rough (R; Ra= > 3µm), smooth (S; Ra= ≥1 to 1.5µm) and very smooth (VS; Ra= <0.1µm) surfaces. Peripheral neutrophils from Wistar rats were cultured on these surfaces and the culture supernatants subsequently analyzed for the presence of NE, MMP-8, and MMP-9 by ELISA, while NETs formation was demonstrated immunohistochemically by staining neutrophils with CD16b and DNA with DAPI. Overall, the expression of NE and MMP-8 were significantly higher from neutrophils cultured on both on Ti and Zr rough surfaces compared to the very smooth surface (R>S>VS) after 2h and 4h of culture. The expression of MMP-9 also increased with culture time however no significant surface effects on expression were observed. Similarly, rough Ti and Zr surfaces (R & S) also showed significantly larger NETs formation compared to the very smooth surface (VS) after 4h and 8h culture. Our findings suggest that increasing surface roughness on Ti and Zr triggers higher secretion of NE, MMP-8 and NETs formation.

The dispersal potential of crown-of-thorns starfish (CoTS) larvae is important in understanding both the initiation and spread of population outbreaks, and is fundamentally dependent upon how long larvae can persist while still retaining the capacity to settle. This study quantified variation in larval survivorship and settlement rates for CoTS maintained at three different chlorophyll concentrations (0.1, 1.0 or 10.0 µg.L^-1), achieved by varying densities of single-celled flagellate phytoplankton, Proteomonas sulcata. Based on the larval starvation hypothesis we expected that low to moderate algal concentrations would significantly constrain both survival and settlement. CoTS larvae were successfully maintained for up to 50 days post-fertilization, but larval survival differed significantly between treatments. Survival was greatest at intermediate (1.0 µg.L^-1) chlorophyll concentrations, and lowest at highest (10.0 µg.L^-1) chlorophyll concentrations. Rates of settlement were also highest at intermediate (1.0 µg.L^-1) chlorophyll concentrations and peaked at 22 days post-fertilization. Peak settlement was delayed at low chlorophyll concentrations, probably reflective of delayed development, but there was no evidence of accelerated development at high chlorophyll concentrations. CoTS larvae were capable of settling 17-43 days post-fertilization, but under optimum conditions with intermediate chlorophyll concentrations, peak settlement occurred at 22 days post-fertilization. Moderate increases in nutrient concentrations and algal densities may increase the number of CoTS that effectively settle, but are unlikely to influence dispersal dynamics.

3D printing facilitates the straightforward construction of microchannels with complex three-dimensional architectures. Here, we demonstrate 3D-printed modular mixing components that operate on the basis of splitting and recombining fluid streams to decrease interstream diffusion length. These are compared to helical mixers that operate on the principle of chaotic advection.

This case report elucidates the clinical trajectory of a 60-year-old male with a history of mild cytopenias, subsequently diagnosed with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) characterized by a complex karyotype and a TP53 mutation. The initial diagnostic evaluation included a bone marrow biopsy revealing 34% myeloid blasts with aberrant immunophenotyping and complex cytogenetic abnormalities, including losses and gains of chromosomal regions. Genetic analysis confirmed a high Variant Allele Frequency of 80% for the TP53 mutation. The patient’s management strategy commenced with a combination of Inqovi (decitabine and cedazuridine) and Venetoclax, supported by prophylactic measures to mitigate tumor lysis syndrome and vigilant infection control. While offering a glimmer of hope for improving outcomes in this high-risk cohort, this treatment approach underscores the inherent challenges posed by the aggressive nature of the disease and the TP53 mutation’s contribution to therapeutic resistance. The case highlights the critical need for personalized treatment regimens and rigorous follow-up to optimize patient care and advance our understanding of this complex malignancy.

Small boat fishers are often the lifeblood of remote coastal communities in Iceland, contributing to employment, jobs and economic prosperity. This study conducts exploratory but highly practical research into the efficiency of onboard catch handling practices by Icelandic small boat fishers using fish handling tools called automatic jigging machines. Using applied research methods, this study researches whether standardisation of operations could be applied to make catch handling practices on small boats more time and resource efficient, leading to reduced waste, a consistently higher quality product, and potential increases in economic efficiency and sustainability. Thematic analysis, value stream mapping, flow analysis and Kaizen ideology were adopted to identify gaps and continuous improvement opportunities to standardise processes, leading to exemplary performance. Eight core recommendations are identified, seven of which are classed as straight-forward, ‘do now’ measures according to a Kaizen Priority Matrix. These include human and technological interventions in the areas of safety, organisational arrangements, hygiene, fish handling and bleeding, and cooling. Questionnaire responses reveal four main themes of importance to the sub-sector: changes in recent decades; the importance of small boat fishers; education and improvement; and the particularities of the sub-industry. The latter include the perception of a ‘race against time’ to land the catch, an issue that sometimes contributes to sub-optimal catch handling practices. Although this study has decidedly practical connotations for small boat fishers, its outcomes are also likely to be of interest to academics, particularly those focused on the organisational management of natural resources and general applications of the project management methodology and applied research methods as a means of solving practical problems in everyday life.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

The usage of Quantum Similarity through the equation Z = {∀θ ∈ Z → ∃s ∈ S ∧ ∃t ∈ T : θ = (s, t)}, represents a way to analyze the way communication works in our DNA. Being able to create the object set reference for z being (s, t) in our DNA strands, we are able to set logical tags and representations of our DNA in a completely computational form. This will allow us to have a better understanding of the sequences that happen in our DNA. With this approach, we can also utilize mathematical formulas such as the Euler–Mascheroni constant, regression analysis, and computational proofs to answer important questions on Quantum biology, Quantum similarity, and Theoretical Physics.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Conventional data visualization software have greatly improved the efficiency of the mining and visualization of biomedical data. However, when one applies a grid computing approach the efficiency and complexity of such visualization allows for a hypothetical increase in research opportunities. This paper will present data visualization examples presented in conventional networks, then go into higher details about more complex techniques related to leveraging parallel processing architecture. Part of these complex techniques include the attempt to build a basic general adversarial network (GAN) in order to increase the statistical pool of biomedical data for analysis as well as an introduction to the project utilizing the decentralized-internet SDK. This paper is meant to show you said conventional examples then go into details about the deeper experimentation and self contained results.

Osteoarthritis (OA) is a debilitating degenerative joint disease that results in chronic pain and inflammation due to progressive mechanical and proteolytic cartilage degradation. Articular chondrocytes, the main cell type present in cartilage, are responsible for the deposition and maintenance of the cartilage extracellular matrix (ECM). However, following damage and inflammation, chondrocytes undergo hypertrophy, apoptosis, and contribute to inflammation and ECM degradation. NF-κB signaling is known to be dysregulated in OA. TRAPPC9, a vesicle trafficking protein, is known to directly activate NF-κB signaling in neuronal and bone cells, however, the biological significance of this protein in chondrocytes has yet to be elucidated. Here, we demonstrate that TRAPPC9 enhances pro-inflammatory gene and protein expression in murine primary articular chondrocytes. Furthermore, we show that TRAPPC9 elicits these responses via phosphorylation of P-100 that activates non-canonical NF-κB signaling. Taken together, these findings suggest TRAPPC9 may be a potential therapeutic target to decrease inflammation and matrix degradation during OA pathology.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

A well-prepared public health workforce is essential for reducing disease burdens and improving population health, requiring an education that addresses global and complex challenges. This paper examines the integration of the relational employability framework in public health education to cultivate critical global citizenship among students and graduates. Our research, conducted at Edith Cowan University in Perth, Western Australia, involved two case studies using qualitative interviews. Case Study 1, drawn from Cook’s doctoral research, explored student experiences with the relational employability framework within an undergraduate capstone unit. Case Study 2, a school-funded project, gathered graduate perspectives to inform ongoing curriculum development. The findings indicate that the relational employability framework enhances global competencies among students and graduates, through research skills development and critical reflective practice. Students reported improved awareness of their learning needs, self-confidence, and an increased ability to engage with diverse perspectives and societal challenges. Graduates highlighted the framework’s role in understanding ethical standards, conducting rigorous research and applying evidence-based practices in professional settings. Additionally, the framework supported the development of a reflective mindset, enabling graduates to make informed, value-based career decisions and advance their professional growth. The study suggests that adopting a relational employability approach can effectively prepare globally competent and reflective public health professionals. We advocate for the broader implementation of this framework in health education and higher education, offering practical recommendations for curriculum transformation. Such an approach will equip future professionals to contribute meaningfully to public health debates and embody the principles of global citizenship in their practice.

Resistance training increases myofiber hypertrophy, but the morphological adaptations that occur within myofibers remain largely unresolved. Fifteen males with minimal training experience (24±4 years, 17.9±1.4 kg/m2 lean body mass index) performed 10 weeks of conventional, full-body resistance training (2x weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained one week prior to and 72 hours following the last training bout. Fiber typing and the quantification of myofibril and mitochondrial areas per fiber were performed using histology/immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, various strength metrics, and mean and type II fiber cross sectional areas (fCSA) (p<0.05). Myofibril areas in type I or II fibers were not altered with training, suggesting a proportional expansion with fCSA increases. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018). However, CS activity levels remained unaltered with training. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in type I+II myofibril areas (r=0.600, p=0.018). Shorter-term resistance training seemingly involves a proportional expansion of myofibrils and an accelerated expansion of mitochondria in type I and II fibers. Additionally, histological and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes in muscle tissue.

Background: As long-lived organisms, urban trees often encounter development and redevelopment activities in close proximity during their lifespans. These activities can damage tree roots, often through methods like root severing during trenching or excavation. Methods: In 2017, we simulated trenching damage on mature Quercus virginiana Mill. trees at three different distances from the base (3x, 6x, and 12x the stem diameter). After five years, we revisited these trees to assess root regrowth based on the cut root's cross-sectional area (CSA) and distance from the base. Results: We observed regrowth in all but 38 (6.7%) of the 557 cut roots revisited. The lack of regrowth in some roots was not associated with our original treatments, the CSA of the roots at the time of trenching, or distance between the cut root end and the trunk (minimum P-value = 0.841). On average, the observed CSA of the regrowth was 22.2% of the original root's CSA. Only our original trenching treatments significantly predicted the level of regrowth observed five years after pruning (P-value = 0.024). Discoloration due to root pruning was minimal. Conclusion: In summary, our findings indicate that root systems require many years to recover from trenching damage. Increasing the distance between trenching activities and trees may have a minor effect on root regrowth but primarily helps reduce initial stress on the tree.

More than 90% of patients affected by mastocytosis are characterized by a somatic point mutation of c-KIT, which induces ligand-independent activation of the receptor and downstream signal triggering, ultimately leading to mast cell proliferation and survival. The most frequent mutation is c-KIT p.D816V, but other rarer mutations can also be found. These mutations often have a very low variant allele frequency (VAF), well below the sensitivity of common next-generation sequencing (NGS) methods used in routine diagnostic panels. Highly sensitive methods are developing for detecting mutations. This review summarizes the current indications on the recommended methods and on how to manage and interpret molecular data for the diagnosis and follow-up of patients with mastocytosis.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

The development of major economic sectors can provide the bedrock on which long-lasting national economic prosperity is formed. Iceland’s tourism sector is an example of a rapidly expanded industry in recent years, to the extent that it has become the largest sectoral contributor to the nation’s economy. The growth of the sector has led to a number of sustainability impacts, thus presenting opportunities and challenges in terms of meeting the seventeen Sustainable Development Goals (SDGs) of the United Nations. Using the case study of Iceland, this paper aims to advance conceptual understanding of the synergies and trade-offs between a nation’s tourism sector and performance across the 169 targets of the SDGs. Empirical results were derived from four theme-based focus groups, comprised of expert participants, who were tasked with completing scoresheets concerning their perception of the extent of synergies and trade-offs for each target. The majority (126 in number) of the mean scoresheet outcomes for the SDG targets revealed neither synergies nor trade-offs. However, 32 synergies and 11 trade-offs were identified. Many of the target synergies related to new economic opportunities, such as jobs, employment and training for young people. Target trade-offs tended to be environmental and social. In particular, concern was voiced about the greenhouse gas emissions of the Icelandic tourism sector, which derives from international aviation, cruise ships and rental car usage. The outcomes of this study are of particular relevance to tourism companies, policy-makers and governance institutes, all of whom are increasingly endeavouring to link their activities with the fulfilment of the SDGs, maximising synergies, mitigating the extent of any potential trade-offs, and potentially transforming trade-offs into synergies. Furthermore, the results are likely of interest to academics focused on researching the broad sustainability impacts of economic sectors and their contribution to meeting the visionary goals of the SDGs.

The impact of riparian wetlands on the cycling, retention and export of nutrients from land to water varies according to local environmental conditions and is poorly resolved in catchment management approaches. To determine the role a specific wetland might play in a catchment mitigation strategy, an alternative approach is needed to the high frequency and spatially detailed monitoring programme that would otherwise be needed. Here, we present a new approach using a combination of novel and well-established geochemical, geophysical and isotope ratio approaches. This was developed and tested against a 2-year high-resolution sampling programme in a lowland permeable wetland in the Lambourn catchment, UK. The monitoring programme identified multiple pathways and water sources feeding into the wetland, generating large spatial and temporal variations in nutrient cycling, retention and export behaviours within the wetland. This complexity of contributing source areas and biogeochemical functions within the wetland were effectively identified using the new toolkit approach. We propose that this technique could be used to determine the likely net source/sink function of riparian wetlands prior to their incorporation into any catchment management plan, with relatively low resource implications when compared to a full high frequency nutrient speciation and isotope geochemistry-based monitoring approach.

Dual generalized commutative quaternions have broad application prospects in many fields. Additionally, the matrix equation AXB = C has important applications in mathematics and engineering, especially in control systems, economics, computer science, and other disciplines. However, research on the matrix equation AXB = C over the dual generalized commutative quaternions remains relatively insufficient. In this paper, we derive the necessary and sufficient conditions for the solvability of the dual generalized commutative quaternion matrix equation AXB = C. Furthermore, we provide the general solution expression for this matrix equation, when it is solvable. Finally, a numerical algorithm and an example are provided to confirm the reliability of the main conclusions.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on 1) the therapeutic potential of exosomes in stroke treatment, 2) the optimization process of upstream and downstream production, and 3) preclinical application in stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognised disease limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence also that statins may also influence osseointegration, enhancing bone growth at the bone-implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users vs never users, and a time dependent effect of statin administration on reduction in risk of revision. In this article we review the clinical and scientific evidence linking statins and risk of revision arthroplasty.

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

This study aims to evaluate the effectiveness of inactivating Salmonella enteritidis in fresh chicken breast by irradiation using a combination of short-wave UV (0, 3, 6, 9, 12 and 15 J / cm2) and a natural antimicrobial such as caffeine (0, 5, 10, 15 and 20 nM/g) as alternative proposals to conventional techniques to reduce pathogens in food. The temperatures used were from 2 to 22°C. The most suitable models were double Weibull in 60% of cases with an adjustment of R2 0.9903-0.9553 and Weibull + cola, in 46.67%, with an adjustment of R2 of 0.9998-0.9981. Noting that the most effective combination in the reduction of Salmonella was 12 J/cm2 of UV light and 15 nM/g of caffeine, with a reduction of 6 CFU/g and an inactivation rate of 0.72. The synergistic effect was observed by increasing caffeine and UV light. Furthermore, the physic-chemical characteristics of the food matrix were not affected by the combination of both technologies. Therefore, these results suggest that this combination can be used in the food industry to effectively inactivate Salmonella enteritidis, without deteriorating product quality.

A hand-held laser-induced breakdown spectroscopy device was used to acquire spectral emission data from laser-induced plasmas created on the surface of cerium-gallium alloy samples with Ga concentrations ranging from 0 to 3 weight percent. Ionic and neutral emission lines of the two constituent elements were then extracted and used to generate calibration curves relating the emission line intensity ratios to the gallium concentration of the alloy. The Ga I 287.4 nm emission line was determined to be superior for the purposes of Ga detection and concentration determination.A limit of detection below 0.25% was achieved using a multivariate regression model of the Ga I287.4 nm line ratio versus two separate Ce II emission lines. This LOD is considered a conservative estimation of technique’s capability given the type of the calibration samples available and low power( 5 mJ per 1 ns pulse) and resolving power (λ/∆λ= 4000) of this handheld device. Nonetheless, the utility of the technique is demonstrated via a detailed mapping analysis of the surface Ga distribution of a Ce-Ga sample which reveals significant heterogeneity resulting from the sample production process.

For broadcast spawning invertebrates such as the crown-of-thorns starfish, early life history stages (from spawning to settlement) may be exposed to a wide range of environmental conditions, and could have a major bearing on reproductive success and population replenishment. Arrested development in response to multiple environmental stressors at the earliest stages can be used to define lower and upper limits for normal development. Here, we compared sperm swimming speeds and proportion of motile sperm and rates of fertilization and early development under a range of environmental variables (temperature: 20-36°C, salinity: 20-34 psu, and pH: 7.6-8.2) to identify environmental tipping points and thresholds for reproductive success. We also tested the effects of water-soluble compounds derived from eggs on sperm activity. Our results demonstrate that gametes, fertilization, and early development are robust to a wide range of temperature, salinity, and pH levels that are outside the range found at the geographical limits of adult distribution and can tolerate environmental conditions that exceed expected anomalies as a result of climate change. Water-soluble compounds associated with eggs also enhance sperm activity, particularly in environmental conditions where sperm motility is initially limited. These findings suggest that fertilization and embryonic development of crown-of-thorns starfish are tolerant to a wide range of environmental conditions, though environmental constraints on recruitment success may occur at later ontogenic stages.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently emerged as global infections with consequential disability adjusted life years (DALYs) and economic burden. This study aimed to explore the spatiotemporal heterogeneity in the occurrence of CHIKV and ZIKV outbreaks throughout Barranquilla, Colombia during 2014 and 2016 and explored the potential for clustering. Incidence data were fitted using multiple Bayesian Poisson models based on a suite of explanatory variables as potential risk factors and multiple options for random effects. A best fit model was used to analyse the case incidence risk for both epidemics to identify any risk factors during their epidemics. Neighbourhoods in the northern region of Barranquilla were hotspots for the outbreaks of both CHIKV and ZIKV. Additional hotspots occurred in the south-western and central regions of the CHIKV and ZIKV outbreaks, respectively. Multivariate conditional autoregressive models strongly identified higher socioeconomic strata (SES) and residing in detached houses as risk factors for ZIKV case incidences. These novel findings challenge the belief that these infections are driven by social vulnerability and merits further study both in Barranquilla and throughout the tropical and subtropical regions of the world.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently emerged as global infections with consequential disability adjusted life years (DALYs) and economic burden. This study aimed to explore the spatiotemporal heterogeneity in the occurrence of CHIKV and ZIKV outbreaks throughout Barranquilla, Colombia during 2014 and 2016 and explored the potential for clustering. Incidence data were fitted using multiple Bayesian Poisson models based on a suite of explanatory variables as potential risk factors and multiple options for random effects. A best fit model was used to analyse the case incidence risk for both epidemics to identify any risk factors during their epidemics. Neighbourhoods in the northern region of Barranquilla were hotspots for the outbreaks of both CHIKV and ZIKV. Additional hotspots occurred in the south-western and central regions of the CHIKV and ZIKV outbreaks, respectively. Multivariate conditional autoregressive models strongly identified higher socioeconomic strata (SES) and residing in detached houses as risk factors for ZIKV case incidences. These novel findings challenge the belief that these infections are driven by social vulnerability and merits further study both in Barranquilla and throughout the tropical and subtropical regions of the world.

This article explores the Role and Contributions of Small and Medium Enterprises (SMEs) in a globalized and innovative economy, looking specifically at the challenges and opportunities. The establishment and expansion of new firms provides a sizable amount of net new jobs. While high-expectation entrepreneurial enterprises and gazelles are usually found among innovative and technology-based new organizations, it is also essential that there be a sizable supply for them to play a significant part in economic growth. In other words, encouraging all forms of en-trepreneurship is likely to increase the number of innovative, fast-growing enterprises as well as entrepreneurship. In many European countries, entrepreneurship needs to be encouraged. Findings show the crucial role the SME sector plays in the South African economy in tackling sustainable development. About 90% of all official firms in South Africa are thought to be small, medium, or micro-enterprises. The study concluded that one of the major contributions to the South African economy is the SME sector. The SME is not just viewed as a source of new jobs, but also as a sector that absorbs laid-off workers from both the private and public sectors.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Background: Since the onset of widespread COVID-19 vaccination campaigns, there have been concerns about serious cardiovascular adverse events, including myocarditis, myocardial infarction, and venous thromboembolisms, all of which can lead to cardiopulmonary arrest. This study aimed to estimate excess cardiopulmonary arrest mortality in King County, WA, and investigate any association with COVID-19 vaccination rates. Methods: Data was obtained from the annual King County, WA, EMS reports, the U.S. Census Bureau, and The Tennessean COVID-19 Vaccine Tracker. An exploratory data analysis was performed. Excess deaths were calculated using the 2015-2020 cardiopulmonary arrest mortality trend line. The relationship between excess cardiopulmonary arrest mortality and vaccination rates was analyzed using polynomial regression analysis. A quadratic regression model was used to generate expected population growth trends. The excess mortality model for King County was used to calculate yearly estimates for excess cardiopulmonary arrest fatalities in the USA. Results: Approximately 98% of the King County population received at least one dose of a COVID-19 vaccine by 2023. Our analysis revealed a 25.7% increase in total cardiopulmonary arrests and a 25.4% increase in cardiopulmonary arrest mortality from 2020 to 2023 in King County, WA. Excess cardiopulmonary arrest deaths were estimated to have increased by 1,236% from 2020 to 2023, rising from 11 excess deaths (95% CI: -12, 34) in 2020 to 147 excess deaths (95% CI: 123, 170) in 2023. A quadratic increase in excess cardiopulmonary arrest mortality was observed with higher COVID-19 vaccination rates. The general population of King County sharply declined by 0.94% (21,300) in 2021, deviating from the expected population size. Applying our model from these data to the entire United States yielded 49,240 excess fatal cardiopulmonary arrests from 2021-2023. Conclusions: We identified a very strong ecological and temporal association between excess cardiopulmonary arrest mortality and the COVID-19 vaccination campaign, which resulted in high vaccination rates. The biological plausibility of death from acute cardiac and pulmonary causes after COVID-19 vaccination has been previously demonstrated and is concerning given these real-world observations. Urgent further research is needed to determine if similar trends are observed in other regions with attention to risk mitigation for incident events and improved survival with resuscitation.

This paper considers the solution of the equations for ruin probabilities in infinite continuous time. Using the Fourier Transform and certain results from the theory of complex functions, these solutions are obtained as com- plex integrals in a form which may be evaluated numerically by means of the inverse Fourier Transform. In addition the relationship between the re- sults obtained for the continuous time cases, and those in the literature, are compared. Closed form ruin probabilities for the heavy tailed distributions: mixed exponential; Gamma (including Erlang); Lognormal; Weillbull; and Pareto, are derived as a result (or computed to any degree of accuracy, and without the use of simulations).

Ultraviolet imaging has been applied in volcanology over the last ten years or so. This provides considerably higher temporal and spatial resolution volcanic gas emission rate data than available previously, enabling the volcanology community to investigate a range of far faster plume degassing processes, than achievable hitherto. To date this has covered rapid oscillations in passive degassing through conduits and lava lakes, as well as puffing and explosions, facilitating exciting connections to be made for the first time between previously rather separate sub disciplines of volcanology. Firstly, there has been corroboration between geophysical and degassing datasets at ≈ 1 Hz expediting more holistic investigations of volcanic source-process behaviour. Secondly, there has been the combination of surface observations of gas release, with fluid dynamic models (numerical, mathematical and laboratory) for gas flow in conduits, in attempts to link subterranean driving flow processes to surface activity types. There has also been considerable research and development concerning the technique itself, covering error analysis and most recently adaptation of smartphone sensors for this application, to deliver gas fluxes at a significantly lower instrumental price point than possible previously. At this decadal juncture in the application of UV imaging in volcanology, this article provides an overview of what has been achieved to date as well as a forward look to potential future research directions, in particular covering the first use of UV cameras to generate volcanic gas composition ratio imagery.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

The Kanchenjunga Conservation Area (KCA) is a high mountain protected area in eastern Nepal undergoing socio-economic and environmental changes that are unprecedented in the region’s history. In the following paper, we discuss recent changes involving new road construction, climate change, adventure tourism, and the wildlife/forest cover/medicinal plant sectors. Our assessments are based on the collective results of past and recent field research, remote sensing analysis, oral histories, and literature reviews. While similar changes are occurring in mountain protected areas (MPA) throughout Nepal, it is suggested that the KCA differs from other regions in that it still retains the option of conducting detailed feasibility, environmental, and impact assessments prior to the implementation of major change-associated projects, particularly the construction of roads. In turn, the KCA might avoid many of the environmental, social, and economic problems experienced elsewhere in Nepal, while enhancing its status, income-generating capacities, and sustainability as a global destination for adventure, nature, and cultural tourism.

Introduction Despite efforts to use scaffolds to treat meniscus tears, minimal progress has been made in facilitating meniscus regeneration and return of function. Our research objective was to develop a meniscus repair and regeneration implant by applying a resorbable scaffold in combination with cells and growth factors. We report here the results of using platelet-rich plasma (PRP) as a source of growth factors to induce fibrochondrogenic differentiation of human adipose-derived mesenchymal stem cells (hADSC) in a three-dimensional (3D) Type I collagen-based scaffold in vitro. Methods Scaffold Preparation. Type I collagen scaffolds were prepared following a protocol previously published. Two different densities of scaffolds, high density (HD) and low density (LD), were produced for in vitro study. hADSC and PRP Preparation. hADSCs were cultured to the fifth passage to reach the desired number for experimentation. PRP was collected from human blood and activated. Cell Culture Procedure. Effects of PRP on hADSC proliferation and differentiation into fibrochondrogenic cells were examined in four scaffold groups: LD, HD, LD+PRP and HD+PRP. hADSCs were seeded onto scaffolds (n=5) at a concentration of 2 × 106 cells/scaffold. 1% of PRP was added to the experimental media. Cellular proliferation was assessed at 1, 7, 14, and 21 days. Differentiation was measured using qRT-PCR on Days 14 and 21. qRT-PCR analysis of gene expression was completed with primers for COLLAGEN 1 and AGGRECAN. Data Analysis. ANOVAs were conducted (two-tailed tests) at the .05 significance level. Results Cellular proliferation of hADSCs seeded on each scaffold increased over time. Similar trend was observed for cells seeded on HD scaffolds with and without PRP. hADSC showed significant increase in cellular proliferation on the LD scaffolds at Days 1 and 7. At Day 21, PRP treatment and LD scaffold had a synergistic positive effect on Type I collagen gene expression. PRP did not elevate type I collagen gene in the HD group, the HD scaffold alone had the same level of type I collagen gene expression as LD+PRP. Aggrecan expression was elevated in the presence of PRP in both the HD and LD scaffold groups, indicating enhanced fibrochondrogenic differentiation of hADSCs. Effective cell infiltration was observed across both HD and LD scaffolds with and without PRP treatment. HD scaffolds displayed larger cell clusters and more extensive cell migration over time compared to LD scaffolds. However, LD scaffolds resulted a more uniform cellular distribution than HD scaffolds. Conclusion Our study demonstrates that PRP can play an important role in directing hADSCs towards fibrochondrogenic differentiation in Type I collagen-based scaffolds in vitro. Additionally, our study shows that collagen scaffold density can influence the spatial distribution and cellular behavior of infiltrated cells.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C&gt;T, not yet reported, and c.838C&gt;T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Human and animal waste, including waste products originating from human or animal digestive systems such as urine, feces, and animal manure, have constituted a nuisance to the environment. Inappropriate disposal and poor sanitation of human and animal waste often cause negative impacts on human health through contamination of the terrestrial environment, soil, and water bodies. Therefore, it is necessary to convert these wastes into useful resources to mitigate their adverse environmental effect. The present study provides an overview and research progress of different thermochemical and biological conversion pathways for the transformation of human- and animal-derived waste into valuable resources. The physicochemical properties of human and animal waste are meticulously discussed as well as nutrient recovery strategies. In addition, a bibliometric analysis is provided to identify the trends in research and knowledge gaps. The results reveal that the U.S.A, China and England are the dominant countries in the research areas related to resource recovery from human or animal waste. In addition, researchers from the University of Illinois, the University of California Davis, the Chinese Academy of Science and Zhejiang University are front runners in research related to these areas. Future research should be centred on developing technologies for the on-site recovery of resources, exploring integrated resource recovery pathways, and exploring different safe waste processing methods.

Anion exchange of the halides, Br and I, is demonstrated through the direct mixing of two pure perovskite quantum dot solutions, CsPbBr3 and CsPbI3, and is shown to be both facile and result in a completely alloyed single phase mixed halide perovskite. Anion exchange is also observed in an interlayer printing method utilizing the pure, unalloyed perovskite solutions and a commercial inkjet printer. The halide exchange was confirmed by optical absorption spectroscopy, photoluminescent spectroscopy, X-ray diffraction, and X-ray photoemission spectroscopy characterization, and indicates that alloying is thermodynamically favorable, while the formation of a clustered alloy is not favored. Additionally, a surface-to-bulk photoemission core level transition is observed for the Cs 4d photoemission feature which indicates the electronic structure of the surface is different from the bulk. Time resolved photoluminescence spectroscopy indicates the presence of multiple excitonic decay features which is argued to originate from states residing at surface and bulk environments.

There are few longitudinal studies on the association between dietary vitamin C and sleep disorders. The aim of this study was to investigate the association between dietary vitamin C intake and various types of sleep disorders, including sleep apnea and insomnia, as well as recommended dietary intakes. A total of 68,221 participants from the UK Biobank were enrolled in the study. Dietary vitamin C intake was calculated by a 24-hour dietary recall questionnaire. We used Cox regression model to assess the association between dietary vitamin C and sleep disorders and restricted cubic spline models to explore potential nonlinear relationships. Stratified analyses and sensitivity analyses were also performed to further test the results. The results showed that vitamin C intake at the Q4 level (132.88-191.51 mg/d) was significantly protective against sleep disorders with an HR (95% CI) of 0.78 (0.65-0.94), and against sleep apnea with an HR (95% CI) of 0.75 (0.62-0.92). The protective effect remained significant in stratified analyses of men and age ≤60 years, and the results were robust in sensitivity analyses. Adequate dietary vitamin C intake may have a protective effect in preventing sleep disorders.

Many metrics exist for the evaluation of binary classifiers, all with their particular advantages and shortcomings. Recently an “Efficiency Index” for the evaluation of classifiers has been proposed, based on the consistency, or matching, and contradiction, or mismatching, of outcomes. This metric and its confidence intervals are easy to calculate from base data in a 2x2 contingency table, and values can be qualitatively and semi-quantitatively categorised. For medical tests, in which context the Efficiency Index was originally proposed, it facilitates communication of risk (of correct diagnosis versus misdiagnosis) to both clinicians and patients. Variants of the efficiency index (balanced, unbiased) which take into account disease prevalence and test cut-offs have also been described. The objectives of the current paper were firstly to extend the EI construct to other formulations (balanced level, quality) and secondly to explore the utility of EI and all four of its variants when applied to the dataset of a large prospective test accuracy study of a cognitive screening instrument. This showed that the balanced level, quality, and unbiased formulations of EI are more stringent measures.

Offsite construction is increasingly being presented as a way to increase housing delivery and reduce the housing crisis. Housing Associations play a pivotal role in the delivery of affordable homes and therefore offsite construction could be beneficial in alleviating the crisis. For offsite construction uptake to increase, the conceptual and pragmatic advantages and challenges surrounding offsite housing in relation to evolving social domestic needs to be explored and understood. The purpose of this paper is to discuss the viability of offsite construction as not only a full-service solution to social housing provision, but an integral strategic partner for meeting the range of specialised fabrication needs for these new properties. A literature review is carried out to explore the conceptual and pragmatic advantages and challenges encountered by HAs adopting offsite construction methods. The paper also investigates which the housing tenures are most suited to offsite construction technology. The paper highlighted that whilst individual case studies and example homes offer one mode of justification for Housing Associations to move forward, it is the cumulative effect of cost savings, sustainability, specialised skill sets, labour reduction, structural innovation, and rate of construction that should be weighed and incorporated into this consideration-making process.

Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, which contributes significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wavefunction just prior to the entrance of ‘gravitons’ to a small region of space-time prior to a nonsingular start to the universe. We compare this to a solution worked out using Klauder Enhanced quantization, for the same given problem. The solution of the first Cosmological Constant problem relies upon the geometry of the multiverse generalization of CCC cosmology which is explained in this paper. The second solution, used involves Klauder enhanced quantization. We look at energy given by our methods and compare and contrast it with the negative energy of the Rosen model for a mini sub universe and estimate GW frequencies

Conclusions: The quantitative method provides a large-scale overview of the biometry measurements of an entire practice. Image audits can then be focused on sonographers whose measurements are outliers, avoiding the time, complexity, and expense of auditing those whose measurements fall within the expected range. We encourage commercial software developers to include tools in their ultrasound reporting software to facilitate such quantitative review.

The existences of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both of the total interaction energies of S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in the complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

As urban development increases in density, the space to grow urban trees becomes more constrained. In heavily developed areas, small stature trees can be planted to reduce both above- and below-ground conflicts with infrastructure elements. However, even these species have their limits when placed in extremely confining conditions. In this study, we build on past work to determine the minimum planting widths of small stature urban trees. We found that species, stem diameter, and the height at which stem diameter measurements occurred were all strong predictors of trunk flare diameter (adjusted R² of 0.843). Additionally, we modelled the relationship between planting space and the presence or absence of hardscape conflicts – using the predictions derived from this effort to project the potential cost savings in two United States cities. Study results provide a guideline to create sufficient space for urban trees and minimize infrastructure damage and associated cost savings.

There is a need for developmental screening that is easily administered in resource-poor settings. 1) We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. 2) The sample included 100 healthy Ugandan children aged 6-59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child’s developmental age group, and absence of home electricity. 3) In the sample, 14% (n=14) of children failed one or more milestones on the screener. Lead levels or stunting did not predict failing the screener after controlling for covariates. 4) Though this tool was feasibly administered, it did not demonstrate preliminary construct validity and is not yet recommended for screening in high-risk populations. Future research should include a larger sample size and cognitive interviews to ensure it is contextually relevant.

Urban Tree Canopy (UTC) greatly enhances the livability of cities by reducing urban heat buildup, mitigating stormwater runoff, and filtering airborne particulates, among other ecological services. These benefits, combined with the relative ease of measuring tree cover from aerial imagery, have led many cities to adopt management strategies based on UTC goals. In this study, we conducted canopy analyses for the 300 largest cities in Florida to assess the impacts of development practices, urban forest ordinances, and hurricanes on tree cover. Within the cities sampled, UTC canopy ranged from 5.9% to 68.7% with a median canopy coverage of 32.3% Our results indicate that the peak gust speeds recorded during past hurricanes events were a significant predictor of canopy coverage (P-value = <0.001) across the sampled cities. As peak gust speeds increased from 152 km/h (i.e., a lower-intensity Category 1 storm) to 225 km/h (lower-intensity Category 4 and the maximum gusts captured in our data), predicted canopy in developed urban areas decreased by 7.7%. Beyond the impacts of hurricanes and tropical storms, we found that historic landcover and two out of eight urban forest ordinances were significant predictors of existing canopy coverage (P-landcover <0.001; P-tree preservation ordinance = 0.02, P-heritage tree ordinance = 0.03). Results indicate that local policies and tree protections can protect or enhance urban tree canopy, even in the face of rapid development and periodic natural disturbances.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, using the Rosen and Israelit model of a nonsingular universe. In doing so we are in addition to obtaining a wavelength 10^30 times greater than Planck’s length so we can calculate DE, may be able to with the help of the Rosen and Israelit model have a first approximation as to the arrow of time, and a universe with massive gravity. We have left the particulars of the nonsingular starting point undefined but state that the Rosen and Israelit model postulates initial temperatures of 10^-180 Kelvin and also a value of about Planck temperature, at 10^-3 centimeters radii value which may satisfy initial conditions asked by t’Hooft for describing an arrow of time. A key assumption is that the DE is formed at 10^-3 cm, after an expansion of 10^30 times in radii, from the Planck length radius nonsingular starting point. The given starting point for DE in this set of assumptions is where there is a change in the cosmic acceleration, to a zero value, according to Rosen and Israel, with time t = 1.31 times 10^-42 seconds. Which may be where we may specify a potential magnitude, V, which has ties into inflaton physics. The particulars of the model from Rosen and Israelit allow a solution to be found, without discussion of where that nonsingular starting point came from, a point the author found in need of drastic remedies and fixes.

In 2021, the American Association of Colleges of Nursing (AACN) added “the impact of climate change on environmental and population health” into The Essentials: Core Competencies for Professional Nursing Education. Presently, little guidance exists for nursing faculty new to climate education. The year prior, the Nurses Climate Challenge (NCC) - a campaign to educate 50,000 health professionals about health impacts of climate change - launched the School of Nursing Commitment through a series of focus groups and collaborative content development. With an aim of increasing access to knowledge and tools to support education about the health impacts of climate change, the NCC Commitment partners with nursing schools and provides a community of practice. Partner schools use NCC resources in courses and report the number of students educated. Within three years, 61 nursing schools in 30 states joined the Commitment. Participants included academic health centers, research institutions, multi-state schools, and small private colleges, and programs ranged from AD to PhD. Faculty 1) integrated resources into didactic and clinical settings such as population or organ-system content, leadership, and policy and 2) used resources to support assignments. In four years, faculty reported educating over 37,700 students using NCC resources in 439 educational sessions. The Commitment may be valuable for faculty fulfilling AACN Essentials by bringing climate change to the classroom, community, and bedside. Furthermore, the Commitment may be a replicable model for health professional education and inspiring action on climate change.

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and the safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked both by cytotoxicity assays and flow cytometry.

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

Ageing is the strongest known risk factor for many of the neurodegenerative diseases causing cognitive decline and dementia. Identification of cognitive impairment may be a prelude to appropriate treatment, hopefully disease-modifying. Use of cognitive screening instruments may be an equitable way to identify cognitive impairment. This study examined the use of two such instruments, Free-Cog and Mini-Addenbrooke’s Cognitive Examination (MACE), in patient cohorts referred to a dedicated cognitive disorders clinic based at a tertiary neurosciences centre. Results showed that: (1) specificity and positive predictive value increased with patient age for both tests with some loss of sensitivity and negative predictive value. (2) In the oldest age groups (≥75 and ≥70 years respectively) where specificity was at maximum, a positive test result (i.e. below the specified test cut-off) rules in the diagnosis of cognitive impairment. (3) Values of an “Efficiency Index” for each test indicated qualitatively a moderate change in the probability of correct diagnosis and quantitatively an approximately 15-25% increase in the probability of correct diagnosis. These findings show that both Free-Cog and MACE may be used with confidence for the identification of cognitive impairment and dementia in older patient cohorts. These findings may have implications for public health policies directed to case-finding in clinical practice as opposed to population-based screening.

The endocannabinoid system (ECS) is a complex neuromodulatory network in the human body that have enormous impact in developing the central nervous system, as well as modulates various physiological processes. The ECS is made up of anandamide, 2-arachidonoylglycerol (2-AG), which are responsible for the synthesis and degradation of endocannabinoids, and enzymes such as FAAH and MAGL ensures the precise control over endocannabinoid levels. The ECS relies on CB1 receptors found in the central nervous system (CNS), and CB2 receptors found in the peripheral nervous system and immune cells. Dysregulation of the ECS has been associated with several health conditions, prompting investigations into its association with phytocannabinoids to harness their therapeutic potential. The ECS is intricately linked with the nervous system, and it is known to modulate neuronal activities in the CNS, influencing pain and mood modulation. The ECS is also associated with neuropathies-peripheral nerve damage leading to symptoms such as weakness, numbness and pain as evidenced in diabetic neuropathy, Guillain-Barré Syndrome, carpal tunnel syndrome, peripheral neuropathy, and postherpetic neuralgia. The focus of this review is on the interplay between 2-arachidonoylglycerol and anandamide amidohydrolase in neuropathy, elucidating their roles in pain regulation, inflammation, and specific neuropathies. The knowledge generated is expected to have broad implications, providing comprehensive insights into neuropathic conditions and how to improve on them. Ultimately, this understanding may lead to more effective treatments and improved quality of life for individuals affected by these conditions.

Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, leaving a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequent frequent variants and associated mechanisms. Variants of unknown significance (VUS) in these genes are discovered at a rate that outpaces current ability to classify them using databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns, and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

The Great Reset has been presented by the World Economic Forum (WEF) in response to the COVID-19 pandemic in 2022 as a model through which a “stakeholder economy” would achieve “resilient, equitable and sustainable” economic, social and environmental goals. A more equitable distribution of resources, better working conditions, and ecological transitions are included in a social, economic and environmental reform agenda. This article raises the question of whether the Great Reset project should be interpreted as a “realistic utopia” and what is its reform potential. In an attempt to answer the question of whether the Great Reset as a realist utopia is consistent with the current state of science and philosophy, the article re-examines the idea of utopia in the light of recent philosophical and scientific approaches, such as critical realism in philosophy, so-cial systems theory in sociology and complexity theory in science. A comparative conceptual analysis is carried out and discussed introducing the idea of a realist utopia in Rawls' theory of justice as fairness. In the final discussion, some doubts are raised about the logical coherence, rigor of scientific theorizing, policy prescriptions, and predictive potential of the Great Reset emerging paradigm. It is concluded that utopian projects of radical reform can become realistic when they offer explanations of the deep structural changes that underlie social and economic evolution, drawing from these explanations the policy implications and prescription that can support struc-tural changes, rather than from assumed long-term effects of exogenous shocks or “black swan” events such as the COVID-19 pandemic.

There are a large number of wildlife and insect species that are in trouble on this planet, and most believe that monarch butterflies in eastern North America are too, because of the well-publicized declines of their winter colonies in central Mexico in the last 25 years. A small number of studies over the last decade have cast doubt on this claim by showing declines are not evident at other stages of the annual cycle. To determine how extensive this pattern is, I conducted an exhaustive review of peer-reviewed and grey literature on (eastern) monarch population censuses and studies, conducted across all seasons, and extracted data from these sources to evaluate how monarch abundance has or has not changed over time. I identified 20 collections of data that included butterfly club reports, compilations of citizen-science observations, migration roost censuses, long-term studies of isotopic signatures, and even museum records. These datasets range in duration from 15 years to over 100 years, and I endeavored to also update each with information from the most current years. I also re-examined the winter colony data after incorporating historical records of colony measurements dating back to 1976. This represents the most complete and up-to-date synthesis of information regarding this population. When I examined the long-term trajectory within each dataset a distinct pattern emerged. Modest declines are evident within the winter colonies (over the full 45 year dataset), and, within three censuses conducted during the spring recolonization. Meanwhile, 16 completely separate monitoring studies conducted during the summer and fall (and from varying locations) revealed either no trend at all or in fact an increase in abundance. While each of these long-term studies has inherent limitations, the fact that all 16 sources of data show the same pattern is undeniable. Moreover, this evidence is consistent with recently-conducted genetic work that shows a lack of decline. Collectively, these results indicate that despite diminishing winter colonies and spring migrations, monarchs in eastern North America are capable of rebounding fully each year, implying that milkweed is not limiting within their collective range. Moreover, there is no indication from these data that the summer population was ever truly diminished by changing agricultural practices in the Midwest that reduced milkweed in crop fields within that region. It is possible that the larger population is not as dependent on Midwestern agricultural milkweed as once thought, and/or that monarchs are adapting to increasingly human-altered landscapes. These results are timely and should bear on the upcoming USFWS decision on whether the monarch requires federal protection in the United States. Importantly, they argue that despite losses of many insects globally, the eastern North American monarch population is not in the same situation.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, while using Karen Freeze’s criteria as to the breakup of primordial black holes to give radiation era contributions to GW generation. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes of the order of Planck mass (10^15 grams) which isabout when the mass of relic black holes is created, 10^-27 or so seconds after expansion starts. Need to state a key result will be in the initial potential V calculated, in terms of other input variables

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.