Tissue programmed death ligand-1 (PD-L1) protein is the recognized predictive immune biomarker of immune checkpoint inhibitor (ICI) treatment benefit in metastatic non-small cell lung cancer (NSCLC). However, tissue PD-L1 protein testing can be limited by tumor heterogeneity and fraught with tissue acquisition difficulties. A plasma PD-L1 assay potentially overcomes these tissue limitations. Patients with metastatic NSCLC treated with first-line ICI-based treatment and available results of plasma cfRNA PD-L1 by real-time polymerase chain reaction (RT-PCR) and tissue PD-L1 protein PD-L1 with the Dako 22C3 monoclonal antibody were retrospectively assessed for median and landmark 3-year overall survival (OS). OS was identical whether positive plasma cfRNA PD-L1 expression or positive tissue PD-L1 protein expression (median OS 15 months; 3-year landmark OS 30%; hazard ratio (HR) 0.97; 95% CI, 0.44-2.10). Positive plasma cfRNA PD-L1 patients also demonstrated a numerically longer median and higher 3-year OS compared to patients lacking PD-L1 expression (median 15 months versus 8 months; 3-year landmark OS 30% versus 15%; HR 0.56; 95% CI, 0.27-1.17). Plasma cfRNA PD-L1 expression by RT-PCR was similarly predictive of ICI-based treatment benefit as tissue PD-L1 protein expression.

ARBTools is a Python library containing a Lekien-Marsden type tricubic spline method for interpolating three-dimensional scalar or vector fields presented as a set of discrete data points on a regular cuboid grid. ARBTools was developed for simulations of magnetic molecular traps, in which the magnitude, gradient and vector components of a magnetic field are required. Numerical integrators for solving particle trajectories are included, but the core interpolator can be used for any scalar or vector field. The only additional system requirements are NumPy.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

Scutellaria multicaulis, a member of the Lamiaceae, is a medicinal plant indigenous to Iran, Afghanistan, and Pakistan. It has been widely used as a prominent herb in traditional medicine for thousands of years. This plant is reported with baicalein, wogonin, and chrysin flavonoids as a significant group of chemical ingredients, which can cure different diseases such as breast cancer. S. multicaulis leave extract was used for the bioreduction of silver nanoparticles (SmL-Ag-NPs), and their phytochemical contents and antioxidant, antibacterial, anti-proliferative, and apoptotic activity were evaluated. Optimal physicochemical properties of SmL-Ag-NPs were obtained by mixing 5% of leave extract and 2 mM of aqueous AgNO3 solution and confirmed by characterization studies including UV–visible spectrophotometry, FE-SEM, EDX, DLS, zeta potential, TGA, SERS, XRD and FTIR Spectroscopy. SmL-Ag-NPs exhibited higher content of TPC (Total Phenolic Content) and TFC (Total Flavonoid Content) and potential antioxidant activity. SmL-Ag-NPs also demonstrated dose-dependent cytotoxicity against MDA-MB231 cells multiplication with an IC50 value of 37.62 μg/mL at 48h through inducing cell apoptosis. This is the first report on the biosynthesis of silver nanoparticles using S. multicaulis leave extract, which can provide treatment for cancer diseases and reduce some negative effects of chemotherapy.

Breast cancer is a global health concern, necessitating continuous advancements in diagnostic medical imaging technologies for early detection and improvement of treatment. This paper presents an overview of the past, present and future of breast cancer imaging using light and some results from the current studies. The paper specifically presents the role of Diffuse Optical Tomography (DOT) in breast cancer imaging. Conventional methods, such as X-ray mammography, face limitations. Diffuse Optical Tomography, a non-invasive light-based imaging modality can provide quantitative descriptive and architectural information about breast tissue. The paper discusses the key challenges and recent developments in breast cancer imaging using DOT to overcome some key challenges. This paper aims to contribute to the understanding of the evolving technological landscape in breast cancer imaging using light for improving early detection and patient outcomes.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

In contrast to lytic phages, filamentous phages are assembled in the inner membrane and secreted across the bacterial envelope without killing the host. For assembly and extrusion of the phage across the host cell wall, filamentous phages code for membrane-embedded morphogenesis proteins. In the outer membrane of E. coli, the protein gp4 forms a pore-like complex, while gp1 and gp11 form a complex in the inner membrane of the host. By comparing sequences with other filamentous phages, we identified putative Walker A and B motifs in gp1 with a conserved lysine in the Walker A motif (K14), and a glutamic and aspartic acid in the Walker B motif (D88, E89). In this work we demonstrate that both, Walker A and Walker B, are essential for phage production. The crucial role of these key residues suggest that gp1 is likely to be a molecular motor driving phage assembly. We further identified essential residues for the function of the assembly complex. Mutations in three out of six cysteine residues abolish phage production. Similarly, two out of six conserved glycine residues are crucial for gp1 function. We hypothesise that the residues represent molecular hinges allowing domain movement for nucleotide binding and phage assembly.

Early diagnosis of paroxysmal atrial fibrillation (PAF) could suggest patients to receive timely interventions in clinical practice. Various PAF onset prediction algorithms might benefit from accurate heart rate variability (HRV) analysis and machine learning classification but to be challenged in real-time monitoring scenarios. The aim of this study is to present an end-to-end deep learning based PAFNet model that integrates a sliding window technique on raw R-R interval of electrocardiogram (ECG) segments to achieve a real-time prediction of PAF onsets. This integration enable the deep convolutional neural network (CNN) to be customized as a light-weight architecture that accommodates the size of sliding windows simply by altering the input layer, specifically its effectiveness in making a new prediction with each new heartbeat. Catering to potential influence of input sizes, three CNN models were trained using 50, 100, and 200 R-R intervals, respectively. For each model, the performance of automated algorithms was evaluated for PAF prediction using a ten-fold cross-validation. As a results, a total of 56,381 PAFN-type and 56,900 N-type R-R interval segments was collected from publicly accessible ECG databases, and a promising prediction performance of the automated algorithm with a 100 R-R intervals was achieved in terms of the sensitivity of 97.12%, the specificity of 97.77%, and the accuracy of 97.45%, respectively. Importantly, the automated algorithm with a sliding windows step of 1 could process one sample in only 23.1 milliseconds and identify the onset of PAF at least 45 minutes in advance. The present results suggest that the sliding window technique on raw R-R interval sequences along by deep learning based algorithms may offers the possibility of providing an accurate, real-time, and end-to-end clinical tool for mass monitoring of PAF.

Threats emerging from microplastics pollution in the marine environment have received much global attention. This review assessed sources, fate, and impacts of microplastics in marine ecosystems and identified gaps. Most studies document ubiquity of microplastics and associated environmental effects. Effects include impacts to marine ecosystems, risks to biodiversity, and threats to human health. Microplastic leakage into marine ecosystems arises from plastic waste mismanagement and a lack of effective mitigative strategies. This review identified a scarcity of microplastics mitigation strategies across different stakeholders. Lack of community involvement in microplastic monitoring or ecosystem conservation exists due to limited existence of stakeholder co-management initiatives. Although some management strategies exist for controlling the effects of microplastics (often implemented by local and global environmental groups); a standardized management strategy to mitigate microplastics in coastal areas is urgently required. There is a need to identify focal causes of microplastic pollution in the marine environment through further environmental research. This would extend to creating more effective policies as well as harmonized and extended efforts of educational campaigns and incentives for counteraction and plastic waste reduction, while mandating stringent penalties for polluting the marine environment. This will help reduce microplastic leakage into the environment.

Yerba maté, an herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole body metabolism, were explored in healthy adult mice. Yerba maté treatment increased mitochondrial oxygen consumption in adipose, but not in other tissues examined. Yerba maté increased ATP concentration in skeletal muscle and decreased ATP concentration in adipose. Combined with observed changes in oxygen consumption, these data yielded a significantly higher ATP:O2, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O2 in adipose, which were consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting potential protective effects against oxidative stress and preservation of cellular function. Together, these data indicate beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity.

Conditional heteroskedastic financial time series are commonly modelled by (G)ARCH processes. ARCH(1) and GARCH were recently established in C[0,1] and L^2[0,1]. This article provides sufficient conditions for the existence of strictly stationary solutions, weak dependence and finite moments of (G)ARCH processes for any order in C[0,1] and L^p[0,1]. It deduces explicit asymptotic upper bounds of estimation errors for the shift term, the complete (G)ARCH operators and the projections of ARCH operators on finite-dimensional subspaces. The operator estimaton is based on Yule-Walker equations, and estimating the GARCH operators also involves a result estimating operators in invertible linear processes being valid beyond the scope of (G)ARCH. Moreover, our results regarding (G)ARCH can be transferred to functional AR(MA).

The Rose grain aphid, a notable agricultural pest, releases saliva while feeding. Yet, there is a need for a comprehensive understanding of the specific identity and role of secretory proteins released during probing and feeding. Therefore, a combined transcriptomic and proteomic approach was employed to identify putative secretory proteins. The transcriptomic sequencing result led to the assembly of 18030 unigenes out of 31344 transcripts. Among these, 705 potential secretory proteins were predicted and functionally annotated against publicly accessible protein databases. Notably, a substantial proportion of secretory genes (71.5%, 69.08%, and 60.85%) were predicted to encode known proteins in Nr, Pfam, and Swiss-Prot databases, respectively. Conversely, 27.37% and 0.99% of gene transcripts were predicted to encode known proteins with unspecified functions in the Nr and Swiss-Prot databases, respectively. Meanwhile, the proteomic analysis result discovered, 30 salivary proteins. Interestingly, most salivary proteins (53.3% proteins) showed close similarity to A. craccivora, while 36.67% to A. pisum and A. glycines. However, to verify the expression of these secretory genes and characterize the biological function of salivary proteins further intervention should be geared towards gene expression and functional analysis.

Formulating a novel concept about the origin of human aging has been constrained by the dominance of a “classic theory” that was proposed nearly 70 years ago. Despite concern over the validity of some of its assumptions, the theory remained basic to our understanding of aging’s relationship with natural selection (NS). However, the logic upon which it rests was tested and subsequently challenged. The present theory describes the single cause of human aging consistent with Darwin’s evolutionary requirement for selection of adaptive traits. It describes an emergent property of the developmental program (DP), that is expressed upon completion of ontogenesis. It involves redundant expression of regulatory processes from the last stage of the DP. That mechanism subsequently preserves a non-aging, stable interval of unchanging NS during which reproductive fitness is achieved. Thereafter, loss of DP regulatory redundancy due to reliability limits, stochastic mutation accumulation, reproductive and a specific type of DNA damage, initiates aging which causes an inexorable decline in strength of NS to begin. It starts approximately a decade later than proposed in the classic theory. Since reproduction and aging are inextricably linked by the same emergent property, selection of that regulatory mechanism makes both traits products of NS.

Two pilot scale desalination system employing carbon modified nano-sized, zero valent metals (n-ZVM) were maufactured and tested to determine (1) the degree to which high salt water (20 to 130 mS) could be desalinated and (2) if this degree of desalination could be maintained throughout an extended treatment period. Two pilot systems were tested (referred to as Generation 1 and Generation 2) consisting of parallel lines of 4 individual reactors in series, a settling tank and an activated carbon cell at the end of each reactor line. The system capacity was 300 gal in Generation 1 and 600 gal in Generation 2 total with a total hydraulic residence time of 6 hours per reactor line (one hour per cell/tank). A slurry of n-ZVM was introduced in the first reactor on each line to yield approximately 5 to 45 grams of nano-metal per 100 L of influent salt water. The n-ZVM slurry was made from mixing tea extract with metal salts (eg ferrous sulfate, ferric chloride) to produce the carbon modified metal slurry. Initial runs focused on dosing required to achieve maximum salt removal at each of three influent salt contents, 28 mS, 44 mS and 123 mS. Once dosing was set, continuous runs (14 days, 23 days and 9 days) were carried out to (1) examine the ability of the pilot to maintain the removal efficiency over an extended period, (2) to determine the weaknesses inherent in the pilot systems, and (3) to begin to develop CAPEX and OPEX estimates for the pilot and pre-design full scale mobile desalination unit (MDU) system. Results demonstrated that maximum removal occurred with 10 g/100L of salt for the 30 mS salt solution,16 g/100 L of salt for the 40 mS influent water and 40 g/100 L for the 130 mS influent. Salt removal (expressed as Na and Cl removed) approached 78% for the 30 mS influent and 41 mS influent respectively while removal for the highest salt influent (130 mS) approached 81 %. Addition of greater amounts of carbon modified slurry than those described resulted in a pH less than 6 which inhibits continued salt removal and would require addition of calcium or magnesium oxides/hydroxides or bicarbonate solutions at the influent side to achieve greater salt removal and of course greater cost per gallon. Continuous operation over the extended time-period showed no significant decrease in salt removal with typical day to day variation of no more than 10% suggesting that this approach to desalination could rapidly provide usable water from saline aquifers, seawater or even produced water. Treatment of saline waters at 30 mS or less yields effluent water in the range necessary for irrigation use of many crops while treatment of seawater or produced water levels of salt (40 mS or higher) yields effluent in the range of 8 to 10 mS a range ideal for RO influent that would prevent the production of large volumes of brine. Pilot testing continues with seawater extracted from Puget Sound, Seattle WA and higher levels of salt to better represent produced water.

We describe results from a Monte-Carlo simulation of Bell-CHSH type correlations in hydrodynamic walkers. We study feasibility of a real life walker test with relevant hydrodynamic parametric ranges. We observe the generic formation of pairs of walkers strongly anti-correlated both in position and momentum. With this source of entangled walkers, we model the insertion of 2 pins in the bath as a notion of measure, akin to the polarizers of photonic Bell tests. This insertion of pins, either static or dynamic, introduces 2 weak field signals. Each field has the physical form of a standing wave Bessel hat, representing the non-local (field mediated) influences of the measure on the walkers. With this representation of the measure, we develop protocol for a Bell game with actual hydrodynamic walkers. We model both static and dynamic insertion of pins in the walker bath. Static pins give us numerical S > 2, as a permissible Bell violation for a non-local (field based) effect. Dynamic insertion of the pins, however, leads to causal space separation of the two arms. We observe the again expected S ≤ 2. We argue for the hydrodynamic implementation and observation of these effects as a walker visualization of Bell inequalities.

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

Zoonoses are diseases transmitted from (vertebrate) animals to humans. Control and prevention of these diseases require an appropriate way to measure health for prudent and well-balanced decisions in public health. We propose a framework that aims to explore, understand and open up a conversation about the non-monetary value of animals through environmental and normative ethics. As an example of its application, participants can choose what they are willing to give in exchange for curing an animal in hypothetical scenarios selecting a human health condition to suffer, the amount of money, and lifetime as a tradeoff. We believe that considering animals beyond their monetary value in public health decisions will contribute to a more rigorous assessment of the burden of zoonotic diseases, among other health decisions. This method might help us complement the existing metrics in health, adding more comprehensive values for animal and human health for the “One Health” approach.

This data descriptor summarizes the process applied and data gathered from 50 publications/papers reporting on the use of photography generated by tourists, tour operators and members of the public, with a particular focus on the crowdsourcing of photographs through online platforms and social networking sites (SNSs) as a method of research for wildlife conservation and ecotourism. The papers were collected in a systematic literature review to inform a pilot study of the feasibility of using SNSs to crowdsource georeferenced photographs of endangered Bornean Pygmy Elephants (Elephas maximus borneensis) taken by ecotourists along the Lower Kinabatangan River region of Sabah, Malaysia. Papers were sourced using the Murdoch University Findit online-search tool to search over 100 databases, including Proquest, Scopus and Web of Science. The criteria for a paper to be included in the review (and shared via the dataset attached to this this data descriptor) were that it was peer-reviewed, published in English, between 1997 and the 31 December 2017, had the full text accessible online and reported on a study or studies that utilized photographs that tourists, tour operators and/or members of the public generated and shared via SNSs or online platforms.

Asaia bacteria commonly comprise part of the microbiome of many mosquito species in the genera Anopheles and Aedes, including important vectors of infectious agents. Their close association with multiple organs and tissues of their mosquito hosts enhances the potential for paratransgenesis for delivery of anti-malaria or anti-virus effectors. The molecular mechanisms involved in the interactions between Asaia and mosquito hosts, as well as Asaia and other bacterial members of the mosquito microbiome, remained unexplored. Here, we determined the genome sequence of the strain W12 isolated from Anopheles stephensi mosquitoes, compared them to other Asaia species associated with plants or insects, and investigated some properties of the bacteria relevant to their symbiosis with host mosquitoes. The assembled genome of strain W12 has a size of 3.94 MB, which is the largest among Asaia spp studied so far. At least 3,585 coding sequences were predicted. The insect-associated Asaia including strain W12 carried more glycoside hydrolase (GH) encoding genes (31 per genome) than those isolated from plants (22 per genome). W12 had the most predicted regulatory protein components (213) among the selected Asaia (ranging from 131 to 211), indicating its great capability to adapt to frequent environmental changes in the mosquito gut. Two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases (cyoABCD-1 and cyoABCD-2) were found in most of Asaia genomes, which possibly offer alternative terminal oxidases and allow the flexible transition of respiratory pathways. Genes involved in the production of acetoin and 2,3-butandiol have been identified in Asaia sp. W12.

A simple protocol for preparation of O-acylated enol form - (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by 1H-, 13C-and DEPT135 NMR spectra, including {1H,1H} COSY, {1H,13C} HSQC, {1H,13C} HMBC and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in 4-th position in the chroman ring and accounting the steric hindrance of the ester group in 3-th place was confirmed.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

Abstract: In order to accelerate deployment of distributed recycling by providing low-cost feed stocks of granulated post-consumer waste plastic, this study analyzes an open source waste plastic granulator system. It is designed, built and tested for its ability to convert post-consumer waste, 3-D printed products and waste into polymer feedstock for recyclebots of fused particle/granule printers. The technical specifications of the device are quantified in terms of power consumption (380 to 404W for PET and PLA, respectively) and particle size distribution. The open source device can be fabricated for less than USD$2000 in materials. The experimentally-measured power use is only a minor contribution to the overall embodied energy of distributed recycling of waste plastic. The resultant plastic particle size distributions were found to be appropriate for use in both recyclebots and direct material extrusion 3-D printers. Simple retrofits are shown to reduce sound levels during operation by 4dB-5dB for the vacuum. These results indicate that the open source waste plastic granulator is an appropriate technology for community, library, makespace, fab lab or small business-based distributed recycling.

Purpose: Social responsibility has been accepted as a core value of nursing profession, particularly in the area of health disparity, but it seems to be difficult to understand for what is meant by social responsibility. The purpose of this study was to explore ways to define the concept of social responsibility of nursing in order to understand the meaning of social responsibility in the field of nursing profession. Methods: The concept analysis process by Walker and Avant was used to clarify the meaning of social responsibility of nursing. Results: Defining attributes of social responsibility of nursing included praxis, as approach to strategizing for social and structural change of inequity, care for an oppressed group which is under social suffering caused by the privilege and power, and action for health policy change in social and political unequal contexts. The antecedents of social responsibility of nursing included reflectivities in identifying personal characteristics, taking seriously the perspective of other vulnerable population, recognizing social environmental status quo (‘fair or unfair’), developing competences in ethical and moral reasoning with social issues. Consequences of social responsibility of nursing were achieving social justice, as equal access to basic human health need in societal level, equal access to effective nursing practice delivery system and development of health promotion policy for world health administrative practices (“health for all”) in nursing. Conclusion: This study provides a guidance to direct future studies through the procedure of identifying conceptual attributes in the context of social responsibility of nursing. Future studies are suggested to develop instruments for social responsibility as well as development of educational programs to promote social responsibility competences in nursing students and nurses.

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

This paper discusses the tectonics of the St. Peter and St. Paul Archipelago (SPSPA) in the Equato-rial Atlantic Ocean, based on the joint-system geometry which show a North-South shorten-ing/transpressional uplift tectonism, is active leading to exhumation of the sub-oceanic mantle. These islets are the summits of a sigmoidal submarine ridge formed by mantle ultramafic rocks. The ridge is crossed by the principal transform deformation zone of the northern transform fault of the St. Paul Multifault System. The South flank ridge exposes serpentinized mantle perido-tites, while the North flank exposes strongly deformed/fractured ultramylonites, recording duc-tile and brittle deformation at lithospheric conditions. The SPSPA show multiple joint systems cutting mylonitic foliation of the exposed rocks, forming three main families: high-angle paral-lel joints of tectonic origin, serpentinization-related joints with random direction and load-release low-angle parallel joints. The tectonic joints show an average direction of N31°E and N28°W, forming a conjugate system with a N1ºW compression axes, coherent with a trans-pressive stress field. Accordingly, the earthquakes focal mechanism close to the islets also shows N-S compression. The previously reported active uplift with an average rate of 1.5 mm/year and the directions of the joint system here reported agreeing with a present-day active N-S compres-sive field at a high angle with the direction of the transform fault.

To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in the phosphate and composition of the renal filtrate, and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully this will raise questions and stimulate new ideas for further research.

Cryptosporidiosis is a common illness in young cattle that causes high morbidity and some mortality. A common prophylactic treatment are halofuginone products but it seems likely disease could be reduced by other other pharmacological products or some management strategies. We undertook a systematic review and meta-analyses on key outcomes for treatment of calves before and after 5 days of age with any management strategy, any nutritional strategy or any non-halofuginone product. A systematic literature search was undertaken with data extracted for outcomes = oocyst shedding, diarrhea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Control animals had to be observed concurrently in planned experiments (pre-post and case-control studies were not eligible). Both randomized and other clinically controlled trials were eligible. Results were subgrouped by study design and outcomes were described in detail where at least two articles described the same treatment strategy. 55 articles were found. Significantly lower incidence of oocyst shedding, diarrhea burden and mortality was reported in many experimental arms, especially when animals started treatment before 5 days old. Weight gain was not mostly affected by treatment, however, by three weeks of age. The evidence base is at least encouraging but insufficient about paromomycin, bumped kinase inhibitors and azithromycin treatment, especially for diarrhea and oocyst shedding, given late or early. Azithromycin is the most promising of these.

The primary goal of this research is to examine the α-amylase inhibitory effect of phytoconstituents found in the roots of the Cyclea peltata plant. The extract will also be used to investigate the effect of root extract on α-amylase inhibition assay. The roots were gathered, processed, and extracted in petroleum ether before being kept at 4ºC. The extract was exposed to a preliminary phytochemical examination. The extract was employed in the α-amylase inhibition experiment at concentrations of 50, 100, 200, 400, 600, 800, and 1000 µg/ml with acarbose as a control. Molecular docking analysis was performed on the phytoconstituents cycleapeltine, cycleadrine, cycleacurine, cycleanorine, cycleahomine chloride, and acarbose on human pancreatic alpha-amylase 1B2Y. A preliminary phytochemical study revealed the presence of alkaloids, saponins, and terpenoids. The tests came back negative for flavonoids, steroids, and tannin. The root extract inhibited α-amylase at 69.42 ± 0.74 % at 1000 µg/ml and acarbose at 94.63 ± 0.57 %. The IC50 value was calculated and found to be 484.08 µg/ml for the extract and 42.47 µg/ml. The docking studies, revealed that cycleacurine (-4.751 Kcal/mol) has a comparable anti-diabetic effect to Acarbose (-6.713 Kcal/mol). Furthermore, the function groups –OH and –NH found in phytoconstituents interacted with the active site of 1B2Y similarly to acarbose. This provides evidence that the function groups –OH and –NH present in the phytoconstituents might inhibit alpha amylase.

Dietary restrictions or reductions such as fasting for weight loss, are often difficult to adhere to in the long term due to increased appetite and food cravings. Recently, gastrointestinal delivery of bitter hops extract has been shown to be effective at reducing appetite in men. Our aim was to determine the effect of bitter hops on appetite and cravings in women, using a day-long, water-only fast. Thirty adult women were recruited and required to fast for 24 h from 1800 h to 1800 h on three occasions and given an ad libitum meal to break each fast. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 125 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. Treatment with both the HD and LD treatment groups exhibited a significant (p < 0.05) reduction in appetite and cravings for food. Two participants reported loose stools and one reported heart-burn while on the HD treatment, and one participant reported loose stools while on the LD treatment. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and shows that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

Alzheimer’s disease (AD) is the leading cause of dementia, characterised by beta-amyloid plaques, neurofibrillary tangles, and oxidative stress. Iron is suspected to enhance disease progression, and chelation may be a potential treatment. We propose that Aloysia citrodora Paláu (AC), a plant in the Verbenaceae family, can act as a moderate chelator of iron. It may reduce the effect of iron on beta-amyloid 1-42 (Aβ1-42) aggregation. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to demonstrate that AC can interact with iron (II) and iron (III), the two most abundant forms of iron within the body. DPV was also used to characterise Aβ1-42 aggregation, and two main features were obtained. The first is the tyrosine peak (~0.6 V) decreased in magnitude over time, which is a sign of aggregation and folding. The other is a conglomerate of peaks at ~0 V, whose identity is unknown. Furthermore, iron (II) increased the rate of tyrosine peak depreciation, and the addition of AC negated this induced effect. This implied that iron (II) increases Aβ1-42 aggregation into higher order, and AC may be an effective countermeasure.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

In modern data analysis, working with diverse dataset formats is essential for ensuring compatibility across different software tools and platforms. However, manual conversion between formats can be time-consuming and error-prone. To address this challenge, we developed an interactive Shiny application that facilitates the seamless conversion of datasets between popular software formats such as CSV, Excel, SAS, SPSS, Stata, and RData. This user-friendly app enables users to upload datasets, select an output format, and download the converted file with a single click. The application also incorporates a real-time progress indicator, enhancing the user experience by showing conversion progress. Built with simplicity and efficiency in mind, the app is designed for researchers, data analysts, and practitioners who regularly handle multiple file formats in their workflows. Additionally, the app features a clean, intuitive interface with clear guidance, making it accessible even to users with minimal technical background. The development process, key features, and potential applications of this tool are discussed in this article.

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Novel therapies for treatment of familial dilated cardiomyopathy (DCM) are lacking. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment which over time result in structural and functional maladaptations leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly in relation to mutant proteins and their impact on sarcomere molecular signaling, are currently the subject of controversy. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon Ca-activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale x-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering control of tension. We discuss these mechanisms that lead to different ideas related to how tension is controlled and disturbed by mutant sarcomere proteins linked to DCM including cardiac myosin, myosin-binding protein C, titin filaments, and thin filaments. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.

Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence

Lineage plasticity, the switching of cells from one lineage to another has been recognized to be a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of Epithelial-Mesenchymal Transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer.

This study proposes a machine-learning-based framework for detecting mechanical damage in pipelines, utilizing physics-informed datasets collected from simulations for mechanical damage. The framework provides an effective workflow from dataset generation to damage detection and identification for three types of pipeline events: welds, clamps, and corrosion defects. While the study initially focused on optimizing the CNN structure using various advanced optimizers, it also investigated the impact of sensing systems on data classification and the effect of noise on classification performance. The study's analysis highlights the importance of selecting the appropriate sensing system for the specific application. The authors also found that the proposed framework is robust to experimentally relevant levels of noise, suggesting its applicability in real-world scenarios where noise is present. Overall, this study contributes to the development of a more reliable and effective method for detecting mechanical damage in pipelines. The proposed framework provides an effective workflow for damage detection and identification, and the findings on the impact of sensing systems and noise on classification performance add to its robustness and reliability.

Electronic structure calculations have been carried out to examine the effect of protonation and water molecules on the heme group of peroxidases in different redox (ferric, ferrous, compounds I and II) and spin states. Shared geometries, spectroscopic properties at Soret region, and thermodynamics of peroxidases are discussed. B3LYP and M06-2X density functionals with different basis sets were employed on a common molecular model of the active site (Fe-centred porphine and proximal imidazole). Computed Gibbs free energies indicate that the corresponding aquo complexes are not thermodynamically stable, supporting the five-coordinate Fe(III) centre in native ferric peroxidases, with a water molecule located at a non-bonding distance. Protonation of the ferryl oxygen of compound II is discussed in terms of thermodynamics, Fe–O bond distances, and redox properties. It is demonstrated that this protonation is necessary to account for the experimental data and computed Gibbs free energies that reveal pKa values of compound II about 8.5 – 9.0. Computation suggests that the origin of the general oxidative properties of peroxidase species, as well as their reactivity towards water and protons and Soret spectral properties, mostly resides on the iron porphyrin and its proximal ligand histidine.

Significant Wave Height(SWH) is a crucial parameter in oceanographic research, essential for understanding various marine and atmospheric processes. Traditional methods for obtaining SWH, such as ship-based and buoy measurements, face limitations like limited spatial coverage and high operational costs. With the advancement of Global Navigation Satellite Systems reflectometry(GNSS-R) technology, a new method for retrieving SWH has emerged, demonstrating promising results. This study utilizes Radio occultation sounder(GNOS) data from the FY-3E satellite and incorporates the latest Vision Transformer(ViT) technology to investigate GNSS-R-based SWH retrieval. We designed and evaluated various deep learning models, including ANN-Wave, CNN-Wave, Hybrid-Wave, Trans-Wave, and ViT-Wave. Through comparative training using ERA5 data, the ViT-Wave model was identified as the optimal retrieval model. The ViT-Wave model achieved an Root Mean Square Error(RMSE) accuracy of 0.4052 meters and Mean Absolute Error(MAE) accuracy of 0.2700 meters, significantly outperforming both traditional methods and newer deep learning approaches utilizing Cyclone Global Navigation Satellite Systems(CYGNSS) data. These results underscore the potential of integrating GNSS-R technology with advanced deep learning models to enhance SWH retrieval accuracy and reliability in oceanographic research.

Background: As a result of the pandemic, families and children have faced physical, emotional, and mental challenges. However, there has been little attention given to the relationship between the COVID-19 pandemic and child development. This systematic review aims to identify the impact of the pandemic on child development, globally. Methods: This study follows the PRISMA guidelines for the systematic review of 16 quantitative and qualitative studies conducted between 2020-2023. Results: This systematic review suggest that the COVID-19 pandemic played a crucial role in hindering child development in early childhood. Conclusion: Therefore, it is important to promote and implement the use of policies and strategies to overcome these obstacles.

Primates are traditionally considered to have a poor sense of smell. However, olfaction is important for non-human primates as demonstrated by conspicuous scent-marking behaviours in lemurs. We studied two family groups (N=4) of crowned lemurs (Eulemur coronatus) housed at Colchester and Twycross zoos (UK) by combining behavioural observations and chemical analyses of scent-marks. We recorded observations of olfactory behaviours for 201 h using instantaneous scan sampling. We investigated the volatile compounds of ano-genital odour secretions using solid-phase microextraction and gas chromatography-mass spectrometry. Males scent-marked most frequently, displaying ano-genital marking for allomarking, head marking for countermarking and wrist marking in specific areas of the enclosure. Females displayed ano-genital marking predominantly on feeding devices. We detected a total of 38 volatile components in all male ano-genital scent-marks and 26 in all female samples of ano-genital odour secretions, including a series of esters, aldehydes, ketones, alcohols, terpenes, volatile fatty acids and hydrocarbons that have been identified in odour profiles of other primates. In conclusion, we found sexual dimorphism in crowned lemurs. Male head and wrist marking behaviours might play defensive territorial functions, while ano-genital marking would be related to socio-sexual communication as chemical mate-guarding. Female ano-genital marking might be involved in resource defense.

An accurate, economical, and reliable device for detecting falls in persons ambulating with the assistance of an orthopedic walker is crucially important for the elderly and patients with limited mobility. Existing wearable devices such as wristbands are not designed for walker users, and patients may not wear them at all times. This research proposes a novel idea of attaching an internet-of-things (IoT) device with an inertial measurement unit (IMU) sensor directly to an orthopedic walker to perform real-time fall detection as well as activity logging. A dataset is collected and labeled for walker users in four activities, including idle, motion, step, and fall. Classic machine learning algorithms are evaluated using the dataset by comparing their classification performance. Deep learning with convolutional neural network (CNN) is also explored. Furthermore, the hardware prototype is designed by integrating a low-power microcontroller for onboard machine learning, an IMU sensor, a rechargeable battery, and Bluetooth wireless connectivity. The research results show the promise of improved safety and well-being of walker users.

Wild germplasm can be classified as the raw material essential for crop improvement. Introgression of wild germplasm is normally used in breeding to increase crop quality or resilience to evolving biotic and abiotic threats. Here, we explore the potential of introgressing Vaccinium elliottii into commercial blueberry germplasm. Vaccinium elliottii is a wild diploid blueberry species endemic to the southeastern United States that possesses highly desirable and economically important traits for blueberry breeding such as: short bloom to ripe period, adaptation to upland sandy soils, disease resistance, firmness, and pleasant flavor. To examine the potential of hybridization, we evaluated populations of interspecific hybrids across multiples stages of breeding (i.e., F1, F2, and backcrosses) in two crop seasons. We used our extensive pedigree data to generate breeding values for pre-breeding blueberry hybrid populations. Hybrid performance was evaluated considering fitness (i.e., plant vigor and plant height) in addition to evaluating six fruit-quality and marketable-related traits (i.e., size, firmness, acidity, soluble solids, weight, and yield). Overall, F2 and backcrosses rapidly achieved market thresholds, presenting values not significantly different from commercial blueberry germplasm. Our results confirmed the potential of exploiting the high genetic variability contained in V. elliotii for interspecific hybridization. Additionally, we developed germplasm resources that can be further evaluated and utilized in the breeding process, advancing selections for fruit quality and environmental adaptation.

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.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

CC16 plays many protective roles within the lung; however, the complete biological functions, es-pecially regarding the pulmonary epithelium during infection, remain undefined. We have previ-ously shown that CC16 deficient (CC16-/-) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden, compared to CC16 sufficient (WT) MTECs; therefore, in this study, we wanted to fur-ther define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air-liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When chal-lenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16-/- MTECs have increased apical protein secretion compared to their unchallenged controls. Fol-lowing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16-/- MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings sug-gest that CC16 is instrumental in providing protection within the pulmonary epithelium during respiratory infection with Mp, the major causative agent of community-acquired pneumoniae.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

The first two decades of the 21st-century have seen the emergence of the modern citizen science movement, increased demand for niche eco and wildlife tourism experiences, and the willingness of people to voluntarily share information and photographs online. To varying extents, the rapid growth of these three phenomena has been driven by the availability of portable smart devices, access to the Web 2.0 internet from almost anywhere on the planet, and the development of applications and services, including social media/networking sites (SNSs). In addition, the number of peer-reviewed publications that explore how text and images shared on SNSs can be data-mined for academic research has surged in recent years. This systematic quantitative review has two goals. The first goal is to provide an oversight of how the photographs that ecotourists share online are contributing to wildlife tourism research. The second goal is to promote the emerging photovoice technique as a theoretical context for social research based on the photographs and comments that ecotourists share on SNSs. From the perspectives of community benefits, conservation behaviours, and environmental education, there are many similarities between authentic ecotourism experiences and quality ecological citizen science programs. Much of the literature regarding the theory and practice of citizen science reports on the difficulties of attracting, training, motivating and retaining community members. The synthesis of this review is that crowdsourcing wildlife and tourism data from comments and photographs that ecotourists share on SNSs is a credible method of research that provides a self-replenishing pool of citizen scientists.

Abstract Introduction: Although ankle fractures and Achilles tendon injuries are among the most common traumatic presentations when they occur individually, concomitant Achilles tendon rupture and ipsilateral ankle fractures are quite unusual. To our knowledge this is the first report of acute Achilles tendon rupture associated with missed ipsilateral closed bimalleolar ankle fracture. Case Presentation: A 34 years old male patient presented with a traumatic right Achilles tendon rupture after sustaining road traffic accident one day prior. There was an open wound over the tendon substance with absent active plantaflexion of the involved leg. After confirming complete Achilles tendon rupture with positive Thompson test, the patient was prepared for emergency debridement and possible tendon repair differing imaging studies, which missed ipsilateral closed bimalleolar ankle fracture. Conclusion: Routine anteroposterior and lateral X-rays should be used in conjunction with a complete history and physical examination to detect any concomitant fracture with open Achilles tendon rupture.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

Patients often need the use of their arms to assist with functional activities, but after bone disruption, pushing is frequently limited to less than 4.5 kg. No method exists to measure arm weight bearing objectively in clinical settings. This project aimed to design, construct, and test a walker for patients who need to limit arm force to prevent excessive bone stress during post-fracture (iatrogenic or traumatic) ossification. First, a qualitative study was conducted to obtain critiques of a Clinical Force Measuring (CFM) walker prototype from rehabilitation professionals. Key statements and phrases were coded that allowed “themes” to emerge from transcribed interviews, which guided device revisions. Next, a second CFM Walker prototype was designed based on the qualitative data and device criteria/constraints and finally tested. The result was fabrication of a new lightweight, streamlined, and cost-effective prototype walker with a simple visual display and auditory cue with upper limit alarms. Key features included attachments for medical equipment and thin film force-sensing resistors integrated into the walker handles that progressively activated 3 LEDs and a buzzer when arm force exceeded programmed thresholds. The innovative CFM Walker will help patients with restricted arm weight bearing, especially elderly adults, recover safer and faster in the future.

Most quantum gravity theories endow space-time with a discreet nature by space quantization on the order of Planck length (lp ). This discreetness could be demonstrated by confirmation of Lorentz invariance violations (LIV) manifested at length scales proportional to lp. In this paper, space-time line elements compatible with the uncertainty principle are calculated for a homogeneous, isotropic expanding Universe represented by the Friedmann-Lemaitre-Robertson-Walker solution to General Relativity (FLRW or FRW metric). To achieve this, the covariant geometric uncertainty principle (GeUP) is applied as a constraint over geodesics in FRW geometries. A generic expression for the quadratic proper space-time line element is derived, proportional to Planck length-squared and dependent on two contributions. The first is associated to the energy-time uncertainty, and the second depends on the Hubble function. The results are in agreement with space-time quantization on the expected length orders, according to quantum gravity theories and experimental constraints on LIV.

The classification of goods involved in international trade in Brazil is based on the Mercosur Common Nomenclature (NCM). The classification of these goods represents a real challenge due to the complexity involved in assigning the correct category codes especially considering the legal and fiscal implications of misclassification. This work focuses on the training of a classifier based on Bidirectional En-coder Representations from Transformers (BERT) for the tax classification of goods with NCM codes. In particular, this article presents results from using a specific Portuguese Language tuned BERT model as well results from using a Multilingual BERT. Experimental results justify the use of these models in the classification process and also that the language specific model has a slightly better performance.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field.

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to their numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy of using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5'-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5 bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

Gait abnormalities are one of the distinguishing symptoms of patients with Parkinson's disease (PD) that contribute to fall risk. Our study compares the gait parameters of people with PD when they walk through a predefined course without assistance, with a conventional walker, and with a motorized walker under different speed cues. Six PD subjects were recruited at the New York Institute of Technology College of Osteopathic Medicine to participate in this study. Spatial posture and gait data of the test subjects were collected via a VICON motion capture system. We developed a framework to process and extract gait features and applied statistical analysis on these features to examine the significance of the findings. The results showed that motorized walkers with haptic cues significantly improved gait symmetry of PD subjects. Specifically, the asymmetry index of the gait cycle time was reduced from 6.7% when walking without assistance to 0.56% and below when using a walker. Furthermore, the double support time of a gait cycle was reduced by 4.88% compared to walking without assistance.

This article discusses a focused study on visualizing the flow patterns in a two-phase pulsating heat pipe (PHP) using Fe₃O₄/water as the working fluid at 3 V/V% concentration. The research also aims to meticulously examine phase change phenomena in the heating section, particularly focusing on bubble formation and expansion processes. A high-speed video camera was utilized to capture dynamic insights into the behavior of the Fe₃O₄/water mixture. Based on the findings, a straightforward model was developed to explain bubble generation and growth in the mixture, serving as a useful reference for future PHP designs and optimizations. Visual observations also noted the stable nature of the Fe₃O₄/water nanofluid over a four-day period, confirming its consistency throughout the experiments. Moreover, the impact of heat load variation on the evaporator section was assessed using controlled heat inputs ranging from 10 to 80 Watts. Observations on the arrangement of slugs and plugs at a 50% filling ratio revealed interesting self-adjusting flow patterns in response to increasing heat inputs, providing valuable insights into PHP operational dynamics. Notably, the oscillatory flow behavior of Fe₃O₄/water, the chosen working fluid, exhibited greater activity in comparison to water. This distinctive flow behavior contributed to achieving heightened thermal performance efficiency for the Fe₃O₄/water system, attributed to its faster attainment of the annular flow condition.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

Government-led legislation is a key strategy to reduce plastic pollution; however, societal perception can heavily influence government intervention for environmental issues. To understand the public acceptability of government action to reduce plastic pollution, we examine the perception of existing and upcoming legislative action on single-use plastics by means of a structured survey with additional semi-structured interviews. Our focus is on the four Atlantic provinces of Canada, which was the first region in Canada to implement provincial-wide legislation for plastic reduction at the consumer level in 2019. Results show strong public support (77 %, n = 838) for bans on single-use plastic bags at the consumer level, and for further plastic pollution reduction legislation. However, the level of support differed between regions and by demographics. Semi-structured interviews show that decision-makers should increase efforts in raising consumer awareness and standardizing regulations across jurisdictions for smoother transitions prior to legislative action.

Pelagic stingray (Pteroplatytrygon violacea) is the only species of stingray (Dasyatidae) that utilizes both pelagic and demersal habitats. It is the main bycatch species in pelagic longline fisheries targeting bluefin tuna in the Gulf of Lions. In the Mediterranean Sea, their stock structure, behavioural ecology and movements are unknown. For the first time in the Mediterranean, 17 individuals (39 to 60 cm disc width) were tagged with pop-up satellite archival transmitting tags using a novel method of tag attachment, to investigate horizontal and vertical movements. The tags were attached for between two and 60 days. Between the months of July and October, pelagic stingray occupied a temperature range of 12.5 to 26.6°C, and a depth range extending from the surface to 480 m. Monthly trends in catch-per-unit-effort (CPUE) of pelagic stingray peaked in August and decreased by late autumn. Pelagic stingray may aggregate on the continental shelf during summer, and move southwards in early autumn, and this movement pattern is considered in relation to the reproductive cycle and overwintering. Future work and options for bycatch mitigation are discussed.

Dielectric elastomers, such as thermoplastic polyurethanes (TPU), are widely used as dielectric layer, emulation layer and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become an urgent need to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This article reports a device for in-situ measuring the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.47 to 2.94. In addition, combined Fourier-transform infrared spectroscopy, X-ray scattering technique, and atomic force microscopy have been utilized to characterize the evolution of microstructure under strain. The investigation under tensile strain reveals that a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction of the dielectric constant parallel to the electric field in TPU. Our work provides valuable experimental reference for improving the stability of flexible sensors and actuators based on dielectric elastomers.

Adiponectin (APN) has been thoroughly investigated for its role in various human disorders. It is fascinating to note that this peptide plays an essential role as a therapeutic agent to cure a plethora of disorders. Our aim is to elucidate the applications and therapeutic potential of this peptide, demonstrating its involvement in age-related macular degeneration (AMD) and other metabolic disorders. APN has been correlated with many ocular disorders and metabolic disorders. The localization and expression of APN in various tissues were the first markers of its local actions. Screening this peptide on a wider platform helps to confirm its application as a novel peptide in various diseases. Altered levels of APN have been well elucidated in the progression of metabolic disorders, and its targeted administration has resulted in combating dysregulation of biochemical and molecular pathways involved in disease pathology. A close association of oxidative stress is also known to contribute to the onset of retinal disorders. Among so many APN has been shown to have a promising response in the context of wet AMD, but further studies are needed to elucidate its full potential in humans.

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

(R)-2-Amino-1-hydroxyethylphosphonic acid 2 was prepared by hydrolytic kinetic resolution of rac-diethyl oxiran-2-ylphosphonate followed by reaction with benzylamine, acid hydrolysis, catalytic hydrogenolysis and anion exchange chromatography. Recrystallization from water-ethanol gave 2, which was characterized by IR, 1H NMR, 13C NMR, 31P NMR, polarimetry, elemental microanalysis, high-resolution mass spectrometry and single-crystal X-ray diffraction. The acid 2 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.303(2) Å, b = 7.104(2) Å, c = 11.627(3) Å. The X-ray crystal structure confirmed the (R)-configuration of 2 and revealed that 2 is zwitterionic in the solid state, with extensive intermolecular hydrogen bonding between the hydroxyl, ammonium cation and phosphonate anion groups.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

The combination of e-commerce and the green economy allows enterprises to distribute their green products directly to consumers through Internet channels. This paper investigates the impact of service spillovers on emission reduction and channel decisions in a two-echelon supply chain,in which the supplier is a Stackelberg leader and the retailer is a follower.By comparing the equilibrium outcomes of the single-channel and dual-channel supply chain in a setting with and without retail services, we observe that the supplier prefers to encroach on the market when services that retail locations provide largely spillover to and benefit the direct sales channel. Contrary to popular belief, a higher degree of service spillovers is beneficial for the retailer to get more returns under the dual-channel structure, whereas supplier encroachment will lead to a decline in the service level if the spillover degree is relatively low. In addition, the emission reduction level of products under supplier encroachment is always higher than that employed in the single-channel structure if consumers have both low-carbon preference and high degree of service sensitivity. Furthermore, we extend the equilibrium decisions under a carbon cap-and-trade (CCT) mechanism; the results fully verify the above conclusions. Interestingly, the implementation of a carbon price not only motivates carbon emission abatement and supplier encroachment, but also helps achieve a win-win outcome for supply chain members when service spillovers happen.

Information on the nutritive value and in vitro fermentation characteristics of native shrubs in New Zealand is scant. This is despite their potential as alternatives to exotic trees and shrubs for sup-plementary fodder, and mitigation of greenhouse gas and soil erosion on hill country sheep and beef farms. The objectives of this study were to measure the in vitro fermentation gas production, predict parameters of in vitro fermentation kinetics and to estimate in vitro fermentation of volatile fatty acids (VFA), microbial biomass (MBM) and greenhouse gases of four native shrubs (Coprosma robusta, Griselinia littoralis, Hoheria populnea and Pittosporum crassifolium) and an exotic fodder tree species, Salix schwerinii. Total in vitro gas production was higher (p<0.05) for natives than S. schwerinii. Prediction using the single pool model resulted in biologically incorrect negative in vitro total gas production from the immediately soluble fraction of the native shrubs. However, the dual pool model better predicted in vitro total gas production and was in alignment with measured in vitro fermentation end products. In vitro VFA and greenhouse gas production from fermentation of leaf and stem material were higher (p<0.05), and MBM lower (p<0.05), for native shrubs com-pared to S. schwerinii. The lower in vitro total gas production, VFA and greenhouse gases produc-tion, and higher MBM of S. schwerinii may be explained by the presence of condensed tannins (CT), although this was not measured and requires further study. In conclusion, results from this study suggests that when consumed by ruminant livestock, the browsable native shrubs can provide adequate energy and microbial protein, and that greenhouse gas production from these species is within ranges reported for typical New Zealand pastures.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

Tidal stream energy is a low carbon energy source. Tidal stream turbines operate in a turbulent environment, and the effect of the structure between the turbine and seabed on this environment is not fully understood. An experimental study using 1:72 scale models based on a commercial turbine design was carried out to study the support structure influence on turbulence intensity around turbine blades. The study was conducted using the wave-current tank at LABIMA, University of Florence. A realistic flow environment (ambient turbulent intensity = 11%) was established. Turbulence intensity was measured upstream and downstream of a turbine mounted on two different support structures (one resembling a commercial design, the other the same with an additional vertical element), in order to quantify any variation in turbulence and performance between the support structures. Turbine drive power was used to calculate power generation. Acoustic Doppler Velocimetry was used to record and calculate upstream and downstream turbulence intensity. In otherwise identical conditions, performance variation of only 4% was observed between two support structures. Turbulent intensity at 1, 3 and 5 blade diameters, both upstream and downstream, showed variation up to 21% between the two cases. The additional turbulent structures generated by the additional element of the second support structure appears to cause this effect, and the upstream propagation of turbulent intensity is believed to be permitted by surface waves. This result is significant for the prediction of turbine array performance.

Laser-induced periodic surface structures (LIPSS) have gained significant attention due to their ability to modify the surface morphology of materials at the micro-nanoscale and show great promise for surface functionalization application. In this study, we specifically investigate the formation of LIPSS in silicon substrates and explore their impact on Surface-Enhanced Raman Spectroscopy (SERS) applications. This study reveals a stepwise progression of LIPSS formation in silicon, involving three distinct stages of LIPSS: 1) integrated Low-Spatial-Frequency LIPSS (LSFL) and High-Spatial-Frequency LIPSS (HSFL), 2) principally LSFL and 3) LSFL at the edge of the irradiated spot, elucidating the complex interplay between laser fluence, pulse number, and resulting surface morphology. Furthermore, from an application standpoint, these high-quality multi-scale periodic patterns lead to the next step of texturing the entire silicon surface with homogeneous LIPSS for SERS application. The potential of LIPSS-fabricated silicon substrates for enhancing SERS performance is investigated using thiophenol as a test molecule. The results indicate that the Au-coated combination of LSFL and HSFL substrate showcased the highest enhancement factor (EF) of 1.38 × 10^6. This pronounced enhancement is attributed to the synergistic effects of Localized Surface Plasmon Resonance (LSPR) and Surface Plasmon Polaritons (SPPs), intricately linked to HSFL and LSFL characteristics. These findings contribute to understanding LIPSS formation in silicon and their applications in surface functionalization and SERS, paving the way for sensing platforms.

In the field of quality analysis of food and flavoring products, gas chromatography – quadrupole mass spectrometry – ion mobility spectrometry (GC-QMS-IMS) is a powerful technique for the simultaneous detection of volatile organic compounds (VOC) by both QMS and IMS. GC is an established technique for the separation of complex VOC-rich foods such as beverages, dairy and fruit products as well as flavorings in general. While the subsequent detection by IMS features soft ionization of fragile compounds (e.g., terpenes) with characteristic drift times, MS provides the analytes’ m/z-values for database substance identification. A limitation of the prominently used static headspace-based GC-QMS-IMS systems is the substantially higher sensitivity of IMS in comparison to full scan QMS, which results in the detection of relevant VOC only in IMS, but not in the QMS analyzer. The present study describes a new prototypic trapped-headspace (THS)-GC-QMS-IMS setup, with optimized active flow regulation, able to gain valuable data of both detectors. This ultimately allows the combination of a soft ionization with m/z values obtained from database-searchable electron ionization (EI) spectra and as such, offers a substantial advantage in fields of quality control. The new setup features aligned retention times for IMS and MS and sufficient signal intensities for QMS and IMS. The analytical setup was evaluated with a set of mango puree samples from various provenances and the data was evaluated by suitable machine learning approaches. The results demonstrate that THS-GC-QMS-IMS allows for the classification of mango purees from different cultivars and can be a promising alternative method for authenticity control of food, flavors, and beverages.

Faraday's Law of induction is often stated as "a change in magnetic flux causes an EMF"; or, more cautiously, "a change in magnetic flux is associated with an EMF"; It is as well that the more cautious form exists, because the first "causes" form can be shown to be incompatible with the usual expression for EMF. This is not, however, to deny the causality as reasonably inferred from experimental observation ­ it is the equation for Faraday's Law of induction which does not represent the claimed cause-and-effect relationship. Here we investigate a selection of different approaches, trying to see how an explicitly causal mathematical equation, which attempts to encapsulate the "a change in magnetic flux causes ..." idea, might arise.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.

Particles and photons appear to be total opposites; the former has rest mass which requires space to exist; the latter has kinetic energy which requires time to occur (oscillate). But they do share certain properties (e.g., quantization) that remain invariant when one is transformed (swapped) for the other. This gauge invariance is developed in some detail.The symmetry between particle and photon turns out to be one of inversion. It is the equalities of special relativity that support this inversion and the accompanying invariances: mass transformed to energy; space transformed to time. The great advantage of these symmetries (inversions) is that they provide guidance for an object little understood (the photon) based upon an object well understood (the particle). On this basis, progress can be made in the understanding of some long-standing issues: wave-particle duality, time’s arrow, the constant speed of light and nonlocality.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Identification and segmentation of rock particles is very important in geology, mining, engineering construction, and environmental monitoring. Traditional methods for recognizing the rock particle characteristics are time-consuming, labor-intensive, and limited by the geographical scope of the sampling sites, which makes it more difficult to represent the spatial distribution of the rock particles accurately. Recent advancements in deep learning techniques offer promising solutions to automate this process. This study aims at utilizing state-of-the-art (SOTA) Mask R-CNN deep learning algorithm from the Detectron2 framework, to capture global features of rocks that will enable the recognition of rock particles more efficiently, just from having the rock images. These images are subject to image processing techniques such as a Gaussian filter, to denoise and smoothen the image, and an Illumination Adaptive Transformer (IAT) framework, to adjust the lighting exposure; all of which add to improve the quality of the image dataset. Afterward, the Mask R-CNN and Detectron2 models are utilized in training the images using transfer learning. Experimental results from evaluating the performance of the proposed algorithms showcase the effectiveness of the approach, thereby highlighting its potential to revolutionize rock particle segmentation across various domains.

(R)-(+)-3,5-Dinitro-N-(1-phenylethyl)benzothioamide 1 is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers by 1H NMR spectroscopy. The single enantiomer of 1 was synthesized from commercially (R)-(+)-a-methylbenzylamine 2 in two-steps with 85% yield.

We study certain function algebras and their operator algebra completions on r-discrete abelian groupoids, the corresponding conditional expectations, maximal abelian subalgebras (masa) and eigen-functionals.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Spatial Data Infrastructures (SDI) support the harvesting, curating, storage, and sharing of data along with providing access to development, analytic, and visualization tools that enable the building of innovative applications to address broad or specific challenges. SDIs can be especially powerful in bringing together data and tools supporting a particular theme – and this paper discusses and demonstrates the value of an SDI focused on Health. Many potential benefits of a Health SDI are proposed, and the case of supporting emergency response efforts is developed in detail. Leveraging a Health SDI, a Health Risk Index was created that provides emergency response personnel (both Emergency Operations Managers and Emergency Medical Responders) key insights into the unique health risks the impacted population faces due to the disaster. In order to establish the Health Risk Index, datasets from multiple national and global sources representing health data and social data that influences health outcomes – typically called social determinants of health – are harvested, merged, and republished to support further efforts at advancing the Health Risk Index. Visualizations of the Health Risk Index at the global, national, and sub-national levels down to the address level are presented along with demonstrations of its use.

Phosphorus is required by laying hens for a variety of biological functions. It is usually provided in excess, in a readily digestible inorganic form in diet formulations. However, this does not represent an efficient use of a finite resource and can result in water pollution. Plant bound phosphorus in phytate, is common in commercial poultry diets, and represents an alternate source of phosphorus, however poultry lacks the enzyme to digest it. By adding enzymes to their diets, the availability of this phytate-bound phosphorus can be increased allowing for the reduced inclusion of inorganic P in the diet formulation. Therefore, this study was conducted to examine the effect of a natural enzyme complex that contains phytase and xylanase in layer diets. Novogen Brown Classic layers (n=314) were fed one of two diets: (T1) control diet or (T2) control diet plus a natural mixed-enzyme product with both, phytase and xylanase. Experimental diets were provided for 12 days after which the excreta from each pen were collected for an additional three days to determine total retention and ileal digestibility of phosphorus and gross energy. At the end of the trial the birds were euthanized, and their ileal contents were collected. Productivity parameters were also recorded over the course of the study. The amount of phosphorus detected in the excreta of the control group was significantly higher than the amount detected in the enzyme-supplemented group (P<0.05). Both phosphorus retention and phosphorus ileal digestibility were significantly higher in the enzyme-supplemented birds (P<0.001). Gross energy digestibility was significantly higher in the enzyme-supplemented birds for both the total tract and ileal samples (P<0.001). There were only numerical improvements, not significant, in the layer productivity parameters. This study showed that the enzyme supplement can improve total retention and ileal digestibility of phosphorus and gross energy in older layers.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

Rationale: Examining trends in patient characteristics, processes of care and outcomes, across an epidemic, provides important opportunities for learning. Objectives: To report and explore changes in admission rates, patient characteristics, processes of care and outcomes for all patients with COVID-19 admitted to intensive care units (ICUs) in England, Wales and Northern Ireland. Methods: Population cohort of 10,287 patients with COVID-19 in the Case Mix Programme national clinical audit from 1 February to 2 July, 2020. Analyses were stratified by time period (pre-peak, peak, post-peak) and geographical region. Multivariable logistic regression was used to estimate differences in 28-day mortality, adjusting for patient characteristics over time. Main results: Admissions to ICU peaked simultaneously across regions on 1 April, with ongoing admissions peaking ten days later. Compared with pre- and post-peak periods, patients admitted during the peak were slightly younger but had greater respiratory and renal dysfunction. Use of invasive ventilation and renal replacement reduced over time. Twenty-eight-day mortality reduced from 43.5% (95% CI 41.6% to 45.5%) pre-peak to 34.3% (95% CI 32.3% to 36.2%) post-peak; a difference of −8.8% (95% CI: −5.2%, −12.3%) after adjusting for patient characteristics. London experienced the highest admission rate and had higher mortality during the peak period but a greater reduction in post-peak mortality. Conclusion: This study highlights changes in patient characteristics, processes of care and outcomes, during the UK COVID-19 epidemic. After adjusting for the changes in patient characteristics and first 24-hour physiology, there was substantial improvement in 28-day mortality over the course of the epidemic.

We prove that the probability of “A OR B”, where A and B are events or hypotheses that are recursively dependent (OR is the logico-probabilistic operator) is given by a "Hyperbolic Sum Rule” (HSR) relation isomorphic to the hyperbolic-tangent double-angle formula, and that this HSR is Maximum Entropy (MaxEnt). The possibility of recursive probabilities is excluded by the “Conventional Sum Rule” (CSR) which we also prove MaxEnt (within its narrower domain of applicability). The concatenation property of the HSR is exploited to enable analytical, consistent and scalable calculations for multiple recursive hypotheses: such calculations are not conveniently available for the CSR, and are also intrinsic to current artificial intelligence and machine learning architectures presently considered intractable to analytical study and methodological validation. We also show that it is as reasonable to state that “probability is physical” (it is not merely a mathematical construct) as it is to state that “information is physical” (now recognised as a truism of communications network engineering). We relate this treatment to the physics of Quantitative Geometrical Thermodynamics which is defined in complex hyperbolic (Minkowski) spacetime, and show how the HSR is isomorphic to other physical quantities including certain components important for digital signal processing.

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease, and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2,035 single nucleotide polymorphisms [SNPs], 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus.