A time integration scheme based on semi-Lagrangian advection and Laplace transform adjustment has been implemented in a baroclinic primitive equation model. The semi-Lagrangian scheme makes it possible to use large time steps. However, errors arising from the semi-implicit scheme increase with the time step size. In contrast, the errors using the Laplace transform adjustment remain relatively small for typical time steps used with semi-Lagrangian advection. Numerical experiments confirm the superior performance of the Laplace transform scheme relative to the semi-implicit reference model. The algorithmic complexity of the scheme is comparable to the reference model, making it computationally competitive, and indicating its potential for integrating weather and climate prediction models.

Mangroves offer vital ecological advantages including air and water filtration, coastal and estuarine habitat provision, sediment stabilization, and wave energy absorption. Their intricate root systems play a key role in safeguarding shorelines from tsunamis and erosive storms by dissipating wave energy. Moreover, mangroves shield against boat wakes and wind-waves, bolstering shoreline defense. Wave dissipation is a function of forest width, tree diameter, and forest density. Restoration efforts of juvenile mangroves in Florida’s Indian River Lagoon (IRL) aim to reduce wave energy in areas vulnerable to erosion. Physical model testing of wave dissipation through mangroves is limited due to the complexity in representing the mangrove structure, where prop roots are non-uniform in both diameter and location. Previous studies have quantified wave dissipating effects through use of scaled and parameterized mangrove structures. This study measures the dissipation effects of live mangroves in a wave flume, forced by conditions representative of the IRL. These measurements are used to validate a parameterized dowel model. Error between wave attenuation factors for the live mangrove and dowel system was on average 2.5%. Validation of the modularized dowel system allowed for further parameterized testing to understand forest structure effects, such as sediment stabilization and wave attenuation.

Overweight and Obesity (Ow/Ob) is a risk factor for developing cardiometabolic disease, and metabolic dysfunction. Dietary interventions, such as caloric restriction (CR), have been explored but little is known about the acute effects of CR and often such diets are not standardized. PURPOSE: To assess the impact of a standardized 3-day CR diet (~590kcal/d) on cardiometabolic health and fat metabolism in Ow/Ob individuals. METHODS: Fifteen Ow/Ob men and women were assessed pre-post 3-day CR using standardized diet; specifically, body weight/composition (% body fat, visceral fat score (Vfs), waist-hip circumferences, blood pressure and vascular stiffness, resting energy expenditure (REE), substrate utilization (respiratory quotient, RQ), and blood glucose/lipid profile. RESULTS: CR induced changes in body weight (93.1±15.2 to 90.67±14.4 kg, p<0.001, d=1.9), body mass index (32.9±4.0 to 32.0±3.7 kg/m2, p<0.001, d=1.4), body fat (37.2±7.5 to 35.8±7.5%, p=0.002, d=1.1) and Vfs (13.1±4.5 to 12.2±3.9 a.u., p=0.002, d=1.1), but not body water (46.3±3.6 to 46.0±3.6%, p=0.29, d=0.3). CR had no effect on peripheral (86±5 to 89±5 mmHg, p=0.23, d=0.3) or central mean arterial pressure (86±5 to 87±6 mmHg, p=0.44, d=0.2), but lowered augmentation index (29.8±17.5 to 21.5±14.5%, p=0.05, d=0.6). Blood glucose (86±7 to 84±11 mg/dl, p=0.33, d=0.3) and blood lipids (total cholesterol (196±49 to 203±54 mg/dl, p=0.16, d=0.4) and TC/HDL (4.9±2.4 to 6.1±4.7, p=0.13, d=0.4)) were unchanged. RQ decreased with CR (0.84±0.01 to 0.76±0.00, p<0.001, d=1.9), though REE was unchanged (1718±274 to 1722±317 kcal/d, p=0.83, d=0.1). CONCLUSION: The 3-day CR significantly improved body weight and composition and fat metabolism, with minimal cardiovascular effects.

Keywords: pluripotency; naïve; stem; imprinting; primordial germ cells; trophoblast; CDK8; Mediator; enhancers.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

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

Large language models (LLMs) excel in providing natural language responses that sound authoritative, reflect knowledge of the context area, and can present from a range of varied perspectives. Agent Based Models and Simulation consist of simulated agents that interact within a simulated environment to explore societal, social, and ethical, among other, problems. Agents generate large volumes of data over time and discerning useful and relevant content is an onerous task. LLMs can help in communicating agents’ perspectives on key events by providing natural language narratives. However, these narratives need to be factual, transparent, and reproducible. To this end, we present a structured narrative prompt for sending queries to LLMs. Chi-square tests and Fisher’s Exact tests are applied to assess statistically significant difference in sentiment scores of the narrative messages between simulation generated narratives, ChatGPT-generated narratives, and real tweets. The narrative prompt structure effectively yields narratives with the desired components from ChatGPT. This structure is expected to be extensible across LLMs. In 14 out of 44 categories, ChatGPT generated narratives which has sentiment scores that were not discernibly different, in terms of statistical significance (alpha level of 0.05), from the sentiment expressed in real tweets. Three outcomes are provided: (1) a list of benefits and challenges for LLMs in narrative generation; (2) a structured prompt for requesting narratives of a LLM based on simulated agents’ information; and (3) an assessment of statistical significance in the sentiment prevalence of the generated narratives compared to real tweets. This indicates significant promise in the utilization of LLMs for helping to connect simulated agent’s experiences with real people.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS > 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (< 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS > 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

We firstly discuss classical stability for a dynamical system of two ions levitated in a 3D Radio-Frequency (RF) trap, assimilated with two coupled oscillators. We obtain the solutions of the coupled system of equations that characterizes the associated dynamics. In addition, we supply the modes of oscillation and demonstrate the weak coupling condition is inappropriate in practice, while for collective modes of motion (and strong coupling) only a peak of the mass can be detected. Phase portraits and power spectra are employed to illustrate how the trajectory executes quasiperiodic motion on the surface of torus, namely a Kolmogorov-Arnold-Moser (KAM) torus. In an attempt to better describe dynamical stability of the system, we introduce a model that characterizes dynamical stability and the critical points based on the Hessian matrix approach. The model is then applied to investigate quantum dynamics for many-body systems consisting of identical ions, levitated in 2D and 3D ion traps. Finally, the same model is applied to the case of a combined 3D Quadrupole Ion Trap (QIT) with axial symmetry, for which we obtain the associated Hamilton function. The ion distribution can be described by means of numerical modeling, based on the Hamilton function we assign to the system. The approach we introduce is effective to infer the parameters of distinct types of traps by applying a unitary and coherent method, and especially for identifying equilibrium configurations, of large interest for ion crystals or quantum logic.

Malaria is a disease spread by female mosquitos of the Anopheles genus. It is acutely prevalent in Sub-Saharan Africa, where 90% of malaria deaths occur annually. One Sub-Saharan African country historically impacted by malaria is Ethiopia. In the past twenty years, malaria prevalence has decreased throughout Sub-Saharan Africa; yet, anthropogenic environmental changes are changing the landscape of malaria. Scholarly literature has cited a positive relationship between hydroelectric dams and malaria in Sub-Saharan Africa. Ethiopia is currently expanding their hydroelectric infrastructure. The Gilgel Gibe III Dam is located on the Omo River in Southwestern Ethiopia. It began generating electricity in 2015 and its reservoir has a capacity of 14,700 million m3 of water. This research utilized Geographic Information Systems and Remote Sensing to identify populations at an increased risk of malaria due to Gilgel Gibe III Dam. Two different techniques were employed: the proximity approach and the remote sensing approach. The proximity approach was based on distance from the reservoir. It identified all populations living within three kilometers of the reservoir as being at an increased risk. The remote sensing approach evaluated the slope, elevation, water content, and land surface temperature of the study area to create a mosquito breeding habitat risk map. Then, populations living within three kilometers of the two main High-Risk areas were identified. This study suggests that mosquito breeding habitat risk is not equally distributed throughout the Gilgel Gibe III Reservoir. This causes certain populations to be at a heightened risk of malaria.

Lynch syndrome (LS) is an autosomal dominant genetic condition caused by mutations in the DNA mismatch repair (MMR) genes in the germline. Colorectal cancer and/or LS-associated cancer are more likely in people who carry pathogenic mutations in these genes. Cancers of the endometrium, small intestine, stomach, pancreas, and biliary tract, ovarian, brain, upper urinary tract, and skin are among the cancer types linked to LS. The criteria for a clinical diagnosis of LS, as well as the processes for genetic testing to identify carriers of pathogenetic mutations in MMR genes, have been known for a long time. The precise description of the pathogenicity associated with MMR genetic variants is critical in the mutation detection analysis, especially in order to enroll mutation carriers in endoscopic surveillance programs that are more suited to them. As a result, this may aid in the improvement of LS-related cancer prevention efforts. In this review, we discuss recent advances in the molecular genetics of LS.

Atmospheric correction is the processes of converting radiance measured at a spectral 1 sensor to the reflectance of the materials in a multispectral or hyperspectral image. This is an 2 important step for detecting or identifying the materials present in the pixel spectra. We present 3 two machine learning models for atmospheric correction trained and tested on 100,000 batches of 40 4 reflectance spectra converted to radiance using MODTRAN, so the machine learning model learns 5 the radiative transfer physics from MODTRAN. We created a theoretically interpretable Bayesian 6 Gaussian process model and a deep learning autoencoder treating the atmosphere as noise. We 7 compare both methods for estimating gain in the correction model to the well-know QUAC method 8 of assuming a constant mean endmember reflectance. Prediction of reflectance using the Gaussian 9 process model outperforms the other methods in terms of both accuracy and reliability.

Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (including colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesize that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss feasibility and propose the potential to: (a) identify personalised novel immunogenomic biomarkers, (b) reduce invasive cancer screening tests and thus increase non-invasive cancer surveillance, (c) improve compliance and adherence to recommended cancer screening guidelines in LSVH.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

Lifelong learning has been integral to advancement of the nutrition and dietetics profession and its practitioners. Both the Commission on Dietetic Registration (CDR) and the Academy of Nutrition and Dietetics (Academy) advocate for continuous skill development and professional growth. Responding to evolving environmental trends and diverse practice perspectives, CDR joined the Joint Accreditation for Interprofessional Continuing Education organization in 2020 and CDR is transforming its own continuing professional education (CPE) requirements and prior approval program. This paper, a historical perspective and current state review, chronicles past and recent developments in nutrition and dietetics CPE, including opportunities for reflective learning and interprofessional continuing education (IPCE). Also explored are the establishment and expansion of the Joint Accreditation organization and its standards, as well as applicable case examples. Additionally, the paper outlines CDR’s and the Academy's strategies to advance inclusion, diversity, equity, and access (IDEA) within the profession and identifies how CPE advancements may facilitate accessible and equitable CPE for an increasingly diverse membership of practitioners. Nutrition and dietetics professionals stand to benefit from a more comprehensive understanding of CPE changes and the opportunities they may bring to the future of the profession.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

Since its advent in the mid-twentieth century, the field of artificial intelligence (AI) has been heavily influenced by biology. From the structure of the brain to evolution by natural selection, core biological concepts underpin many of the fundamental breakthroughs in modern AI. Here, focusing specifically on artificial neural networks (ANNs) that have become commonplace in machine learning, we show the numerous connections between theories based on coevolution, multi-level selection, modularity and competition and related developments in ANNs. Our aim is to illuminate the valuable but often overlooked inspiration biologists have provided AI research and to spark future contributions at this intersection of biology and computer science. Although recent advances in AI have been swift, many significant challenges remain requiring innovative solutions. Thankfully, biology in all its forms still has a lot to teach us, especially when trying to create truly intelligent machines.

Camelina (Camelina sativa L.) is an oilseed with potential for use as a raw material in second-generation biofuels. Camelina has a seed yield of up to 2380 kg ha^-1 and contains around 45% fatty acids. Selection of a suitable site is critical for production optimization. The objective of this study was to determine Chilean agro-climatic suitability for establishing camelina as a productive alternative. Climate and soil requirements and geographical restraints were evaluated for the species, considering the climatological characteristics of its regions of origin, as well as regions where camelina is successfully grown in the rest of the world. The variables considered include factors (maximum temperatures of the warmest month, water deficits, and degree days) and limitations (altitude, geomorphology, and current land use), which permitted the evaluation of the national territory for a certain level of suitability. It was determined that 1.3% of the national territory (960,664 ha) has some degree of suitability for camelina adoption. Between the Biobío and Los Lagos regions, 49.0% of land (471,203 ha) is in the category of without thermic restrictions, with mild water restrictions, and mild soil restrictions or without information, which can be used for camelina production. The Los Ríos region had 21.4% surface area (321,176 ha) with some level of suitability for camelina, the most suitable region to establish this crop in Chile.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

Given the persistence of microplastics in the environment and their potential toxicity to ecosystems, understanding of likely microplastic accumulation ‘hotspots’ in rivers is urgently needed. To contribute to this challenge, this paper reports results of a microplastic survey from a heavily urbanised catchment, the River Tame, which flows through the city of Birmingham, UK. All sediment sampled was found to contain microplastics with an average abundance of 165 particles kg-1. While urban areas generally have a greater abundance of microplastics as compared with rural, there is no simple relationship between microplastic numbers and population density or proximity to wastewater treatment sites. The greatest change in microplastic abundance was due to the presence of a lake along the course of the River Tame i.e. on entering the lake flow velocities are reduced which promotes the deposition of fine sediment and potentially microplastics. This suggests that the greatest concentrations of microplastics will not be found in-channel but rather on the floodplain and other low velocity environments such as meander cutoffs. We also identified a new mechanism of microplastic fixation in freshwater environments through ecological engineers, specifically caddisfly that incorporated microplastics into their casing. These results highlight the need to explore further hydrodynamic and ecological impacts on microplastics fate and transport in rivers.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

Despite their limited spatial extent, freshwater ecosystems host remarkable biodiversity, including one third of all vertebrate species. This biodiversity is declining dramatically: globally, wetlands are vanishing three times faster than forests and freshwater vertebrate populations have fallen more than twice as steeply as terrestrial or marine populations. Threats to freshwater biodiversity are well- documented but co-ordinated action to reverse this decline is lacking. We present an Emergency Recovery Plan to “bend the curve” of freshwater biodiversity loss. Priorities for action include: 1) accelerating implementation of environmental flows, 2) improving water quality, 3) protecting and restoring critical habitats, 4) managing exploitation of freshwater species and riverine aggregates, 5) preventing and controlling non-native species invasions, and 6) safeguarding and restoring river connectivity. We recommend revised targets and indicators for the Convention on Biological Diversity and the Sustainable Development Goals, and investment in enabling conditions at national, river basin and local scales.

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Genetic variations at the Apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) loci have been implicated in multiple neurogenerative diseases, but their exact molecular mechanisms are unclear. In this study we performed transcript level linear modelling using the blood whole transcriptome data and genotypes of the 570 subjects in the Parkinson’s progression markers initiative (PPMI) cohort. ApoE, MAPT haplotypes and two SNPs at the SNCA locus (rs356181, rs3910105) were used to detect expression quantitative trait loci eQTLs associated with the transcriptome and differential usage of transcript isoforms. As a result, we identified 151 genes associated with the genotypic variations, 29 cis and 122 trans eQTL positions. Profound effect with genome-wide significance of ApoE e4 haplotype on the expression of TOMM40 transcripts was identified. This finding potentially explain in part the frequently established genetic association with the APOE e4 haplotypes in neurodegenerative diseases. Moreover, MAPT haplotypes had significant differential impact on 23 transcripts from the 17q21.31 and 17q24.1 loci. MAPT haplotypes had also the largest (256) and smallest (-178) effect sizes measured as beta values on two different transcripts from the same gene (LRRC37A2). Intronic SNP in the SNCA gene, rs3910105, differentially induces expression of three SNCA isoforms. In conclusion, this study established clear association between well-known haplotypic variance and transcript specific regulation in the blood. APOE e4 and MAPT H1/H2 haplotypic variants are associated with the expression of several genes related to the neurodegeneration.

Canada has committed to reducing greenhouse gas (GHG) emissions by increasing the non-emitting share of electricity generation to 90% by 2030. As solar energy costs have plummeted, agrivoltaics (co-development of solar photovoltaic (PV) systems and agriculture) provide an economic path to these goals. This study quantifies agrivoltaic potential in Canada by province using geographical information system analysis of agricultural areas and numerical simulations. Systems modeled would enable conventional farming of field crops to continue (and potentially increase yield) by using bifacial PV for single-axis tracking and vertical system configurations. Between a quarter (vertical) to more than one third (single axis tracking) of Canada’s electrical energy needs can be provided solely by agrivoltaics using only 1% of current agricultural lands. These results show that agrivoltaics could be a major contributor to sustainable electricity generation and provide the ability for Canada to render the power generation sector net zero/GHG emission free. It is clear that the potential of agrivoltaic-based solar energy production in Canada far outstrips current electric demand and can thus be used to electrify and decarbonize transportation, heating, expand economic opportunities by powering the burgeoning computing sector, and export green electricity to the U.S. to help eliminate their dependence on fossil fuels.

This brief report investigates the potential correlation between manual labor and opioid addiction, focusing on contributing factors such as chronic pain, regular exercise, healthcare access, and housing stability. Although manual labor is associated with higher rates of work-related injuries and chronic pain, the review finds no strong, direct correlation between manual labor and increased opioid addiction rates. The relationship is complex and influenced by a range of socio-economic factors. The findings highlight the need for further research, particularly longitudinal studies, to explore these dynamics in depth and develop targeted interventions for at-risk populations.

Probiotics in cosmetics is a new and burgeoning area of research attracting attention from cosmetic manufacturers and customers looking for natural or additional alternatives in their skincare regimens. Probiotics not only promote beneficial microbiomes to improve skin health but can also modulate the visual, topographical, and mechanical attributes to improve skin quality. This study was conducted in healthy adults to determine the effect of a topical serum formulation containing the live probiotic Micrococcus luteus Q24 on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin microbiome. Quantitative changes in various skin parameters were measured using a skin analyzer device and skin swabs were analysed using whole genome sequencing to monitor microbial diversity and levels of probiotic colonisation. Compared to the baseline, a significant reduction in the pore, spots, wrinkles, and impurities scores; and an increase of 101% in the hydration scores were observed. Additionally, 45-80% of participants showed a decrease in pores, spots, wrinkles, and impurities and 90% of participants showed an increase in hydration after 25 days of probiotic serum application. The WGS analysis of the skin swab samples showed a significant increase in the relative abundance of M. luteus Q24. The results from this study indicated that topical application of serum-containing probiotic M. luteus Q24 offers the benefit of improving skin health quality.

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries [1]. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease [1], all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under transcriptional regulation of both the nuclear and the mitochondrial genome, to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, to dynamics which regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function to cause disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs including the ovary (oocyte and granulosa cell), uterus, placenta, and circulation to cause reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in transgenerational transmission of PCOS and metabolic disorders.

Texas ranks first in number of natural hazard fatalities in the United States (U.S.). Based on data culled from the National Climatic Data Center databases from 1959 to 2016, the number of hydrometeorological fatalities in Texas have increased over the 58-year study period, but the per capita fatalities have significantly decreased. Spatial review found that flooding is the predominant hydrometeorological disaster in a majority of the Texas counties located in “Flash Flood Alley” and accounts for 43% of all hydrometeorological fatalities in the state. Flooding fatalities are highest on “Transportation Routes” followed by heat fatalities in “Permanent Residences”. Seasonal and monthly stratification identifies Spring and Summer as the deadliest seasons, with the month of May registering the highest number of total fatalities dominated by flooding and tornado fatalities. Demographic trends of hydrometeorological disaster fatalities indicated that approximately twice as many male fatalities occurred during the study period than female fatalities, but with decreasing gender disparity over time. Adults are the highest fatality risk group overall, children most at risk to die in flooding, and the elderly at greatest risk of heat-related death.

With rising rates of human obesity, the study aimed to determine the relationship between maternal diet-induced obesity and offspring morphometrics and behaviour in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of HFHS offspring was reduced for the first postnatal week but not thereafter with HFHS female offspring having higher body weights by weaning, due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. Maternal diet did not affect offspring locomotor activity or social behaviour in either sex. Both male and female HFHS offspring displayed reduced anxiety-related behaviours with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behaviour of male and female offspring, with sex-specific differences.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

Abstract: Mass spectrometry research laboratories reported multiple probes for ambient ionization in the last years. Combining them with a mechanical moving stage enables automated sampling and imaging applications. We developed a robotic platform, which is based on RepRap 3D-printer components, and therefore easy to reproduce and to adopt for custom prototypes. The minimal step width of the Open LabBot is 12.5 μm, and the sampling dimensions (x, y, z) are 18 × 15 × 20 cm. Adjustable rails in an aluminium frame construction facilitate the mounting of additional parts such as sensors, probes, or optical components. The Open LabBot uses industry-standard G-code for its control. The simple syntax facilitates the programming of the movement. We developed two programs: 1) LABI-Imaging, for direct control via a USB connection and the synchronization with MS data acquisition. 2) RmsiGUI, which integrates all steps of mass spectrometry imaging: The creation of G-code for robot control, the assembly of imzML files from raw data and the analysis of imzML files. We proved the functionality of the system by the automated sampling and classification of essential oils with a PlasmaChip probe. Further, we performed an ambient ionization mass spectrometry imaging (AIMSI) experiment of a lime slice with laser desorption low-temperature plasma (LD-LTP) ionization, demonstrating the integration of the complete workflow in RmsiGUI. The design of the Open LabBot and the software are released under open licenses to promote their use and adoption in the instrument developers’ community.

Temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals (CWCs). The present study employed a combination of histology and polymerase chain reaction diagnostic techniques to investigate potential pathogens present in the CWCs Lophelia pertusa and Madrepora oculata in the Porcupine Bank Canyon (PBC), NE Atlantic. No pathogen was observed in the Madrepora samples. Neither histology nor standard PCR detected Vibrio spp. in the corals, although using Illumina technology, V. shilonii was observed in some L. pertusa samples in low abundances (0.22%). A Rickettsiales-like organisms (RLOs) occurred at a prevalence of 8.0% and at a low infection intensity of 1 - 4. Lophelia showed a few RLOs infection from the PBC canyon head (2.7%) and high infections in the south branch (5.3%). Similarly, unidentified cells observed in L. pertusa from the south branch (4.0%) were more common than those found in the canyon head (1.3%) with a prevalence of 5.3%. Although the route of pathogen infection is unclear, a likely mode of entry could be associated with particulate availability and the feeding strategies of the scleractinian corals. This suggest that L. pertusa invests energy into an enhanced immune function and reduced susceptibility to global pathogens despite a changing ocean environment.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

This paper aims to research whether there is link between FDI inflows and Economic growth in the Republic of Seychelles Island. The ordinary least square results obtained shows that in the impact of FDI inflows on economic growth is low. Small Island Developing States attracts less FDI inflow because they are limited to few resources that attracts overseas firms which results in retarded development. The research lighted that impact of foreign direct investment on host countries does not only depend on the quality and quantity of the FDI inflows but some other variables such as the internal policies and the management skills, market structures, economic trends among others.

The United States is facing an alarming surge in cyberattacks, with data breaches rising by 72% since 2021, presenting grave national security risks. Notable incidents, including Chinese hackers attempting to access high-level government information and Iranian-linked cyber groups targeting U.S. water systems, highlight the fragility of critical infrastructure. These attacks pose dangers not only to national security but also to economic stability and public health, amplified by the rapid growth of interconnected technologies and global digitalization. In response to these escalating threats, the U.S. must take a multifaceted approach. Key strategies include strengthening cybersecurity education and workforce development, enforcing more rigorous regulatory frameworks, and enhancing preparedness through incident response and recovery planning. Additionally, increased international cooperation is essential to address state-sponsored cyber threats and foster a global framework for cybersecurity defense. As cyber threats continue to evolve, future efforts will rely on technological advancements such as artificial intelligence (AI) for real-time threat detection, the adoption of zero-trust security models, and the development of adaptive, resilient cybersecurity infrastructures. Collaboration between the public and private sectors, coupled with ongoing innovation and education, will be critical to maintaining national security and promoting economic growth in an increasingly interconnected digital landscape.

Assessment of meadow restoration benefits from understanding the connection between geomorphology, hydrology and vegetation, and multispectral imagery captured from unpiloted aerial vehicles (UAV) may provide the method most suitable in terms of cost, spatial resolution, support for vegetation indices, and frequency of acquisition. Our field studies of northern Sierra Nevada montane meadows (with <40 km2 watersheds) in various stages of restoration includes GPS + laser-leveling channel survey, laser-leveled cross section, aerial LiDAR, vegetation sampling, soil measurements, and UAV imaging using a sensor capturing calibrated blue (465-485 nm), green (550-570 nm), red (663-673 nm), near infrared (820-860 nm), and red edge (712-722 nm) bands at 5.5 cm resolution, providing multispectral false-color images and vegetation indices such as normalized difference vegetation index (NDVI) and red-edge Chlorophyll index (Clre). This fine-scale imagery extends our morphometric assessment of post-restoration channel scouring exhibiting bedform patterns and sinuosity related to Carex-influenced soil properties and Salix copses, but also provided a view of groundwater-related drainage effects including sinuous Carex-vegetated zones evident from spring snowmelt images as well as NDVI and Clre in growing to senescent phenological stages. Carex in particular was significantly associated with low bulk density and high soil moisture, NDVI, and Clre at lower elevations.

This study compares the physico-chemical characteristics of three different types of biochar produced from biomass residues in Vietnam as a basis for optimising their application in water purification and soil fertilisation. Wood biochar (WBC), rice husk biochar (RBC), and bamboo biochar (BBC) were produced under limited oxygen conditions using equipment available locally in Vietnam, known as a Top-Lid Updraft Drum (TLUD). The resulting biochars were characterised using a suite of state-of-the-art methods to understand their morphology, surface chemistry and cation exchange capacity. Surface areas (measured by BET) for WBC and BBC were 479.34 m²/g and 434.53 m²/g, respectively, significantly higher than that of RBC which was only 3.29 m²/g. The morphology as shown in SEM images corresponds with the BET surface area, showing a smooth surface for RBC, a hollow surface for BBC, and a rough surface for WBC. All three biochars produced alkaline, with pH values around 10, and all have high carbon contents (47.95 - 82.1 %). Cation exchange capacity (CEC) was significantly different (p<0.05) among the biochars, being 26.70 cmol/kg for RBC, 20.7 cmol/kg for BBC, and 13.53 cmol/kg for WBC, which relates to the cations (Ca, Mg, K) and functional groups with negative charge (carboxyl, hydroxyl) present on the biochar surfaces. The highest contents of Ca, Mg and K in rice husk BC may explain its highest CEC values. Thus, although the biochars were produced by the same method, the various feedstocks lead to quite different physico-chemical properties. Ongoing work is linking these physico-chemical properties to the biochar efficiencies in terms of nitrate and ammonia capture capacities for use as fertilisers, and for adsorption of heavy metals (Zn, Cu) or water filtration, in order to design optimal biochar properties for specific applications.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

Background Several quantitative studies have found a decline in physical activity in response to COVID-19 pandemic restrictions. The aim of the present study was to use large-scale free text survey data to qualitatively gain a more in-depth understanding of the impact of the COVID-19 pandemic on physical activity, then map barriers and facilitators to the Capability, Opportunity, Motivation, and Behaviour (COM-B) Model of Behaviour to aid future intervention development. Methods 17,082 participants provided a response to the free text module, and data from those who mentioned physical activity in any context were included. Data were analysed using thematic analysis and key themes identified. Results 5396 participants provided 7490 quotes related to physical activity. The sample were predominately female (84%), white (97%) and aged <60 years (57%). Seven key themes were identified: the importance of outdoor space, changes in daily routine, impact of COVID-19 restrictions, perceived risks or threats to participation, the importance of physical health, the importance of physical activity for mental health and the use of technology. Conclusion Future physical activity interventions could encourage people to walk outdoors, which is low cost, flexible, and accessible to many. Developing online resources to promote and support physical activity provides a flexible way to deliver quality content to a large audience.

The identification of floral visitation by pollinators provides an opportunity to improve our understanding of the fine-scale ecological interactions between plants and pollinators, contributing to biodiversity conservation and promoting ecosystem health. In this review we outline the various methods which can be used to identify floral visitation, providing a comparison between molecular and non-molecular methods. We review the literature covering the ways in which DNA metabarcoding has been used to answer ecological questions relating to plant use by pollinators and discuss the findings of this research. We present detailed methodological considerations for each step of the metabarcoding workflow, from sampling through to amplification and finally bioinformatic analysis. Detailed guidance is provided to researchers for utilization of these techniques, emphasizing the importance of standardization of methods and improving the reliability of results. Future opportunities and directions of using molecular methods to analyze plant-pollinator interactions are then discussed.

The river Teign in Devon has come under scrutiny for failing to meet Environmental Quality Standards for ecotoxic metals due to past mining operations. A disused mine known as Bridford Barytes mine, has been found to contribute a significant source of Zn, Cd and Pb to the river. Recently, studies have been focused on the remediation of such mine sites using low-cost treatment methods to help reduce metal loads to the river downstream. Red mud is a waste product from the aluminium industry, the utilization of this resource has proven an attractive low-cost treatment method for adsorbing toxic metals. Adsorption kinetics and capacity experiments reveal metal removal efficiencies of up to 70% within the first 2 hours when red mud is applied in pelletized form. Biochar is another effective adsorbent with the potential to remove >90% Zn using agricultural feedstock. Compliance of the Teign has been investigated by analysing dissolved metal concentrations and bioavailable fractions of Zn to assess if levels are of environmental concern. By applying a Real-World Application Model, this study reveals that compressed pellets and agricultural biochar offer an effective, low-cost option to reducing metal concentrations and thus improving the quality of the river Teign.

Despite the rising interest in smart city initiatives worldwide, governmental theories along with the managerial perspectives of city planning are a great lack in the literature. It is definitely understandable that the adoption of configurational pathways towards the ‘smart’ ‘governance’ models is required as key factor and smartness’ facilitator in modern cities. In this manuscript, we display an exhaustive analysis on the importance of the n-Helix models along with a benchmarking critical approach through selected European case-studies. The study, through the literature review, revealed the lack of exhaustive analyses for the methodological investigation, identification and adoption of the most appropriate governance model and collaborative approaches per project and collaborative approaches and create modular frameworks to address efficiently the continuous urban challenges, such as the rapid urbanization or the climate change.

Despite the increasing interest in ‘smart city’ initiatives worldwide, current literature still lacks the approaches and models that address challenges in organization and collaboration, which boost sustainability and ‘smartness’ in modern cities. This paper provides an overview of ‘smart city’ ecosystems as a mechanism to promote the expected outcomes of their sustainable development, and highlights the importance of conceptualizing cities from organizational and managerial perspectives. Representative exploratory models of ‘city organization’, which emphasize on the role of ‘governance’ and synergies, are presented to ‘decode’ complex city mechanisms and to determine key components that lead to ‘smart’ initiatives. Interesting case studies and applications are then analysed to examine the practical dimension of these approaches. As a review paper, this article lays out a general framework on the importance of ‘collaboration’, ‘governance’, ‘management’, and ‘ecosystem’. However, 'planning smartly’ and achieving ‘sustainability’ at the level of city ‘organization’ remain as challenges in this pioneering study of smart cities.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis; synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life-cycle of the ornate spiny lobster, Panulirus ornatus, relies on moulting in order to grow and develop. Many of these diverse life stages have been analysed to establish a comprehensive transcriptomic database for this species. The transcripts putatively encoding for CYP450s were mapped using transcriptomic analysis and identified across growth and development stages. With the aid phylogeny, 28 transcripts of 42 putative P. ornatus CYP450s were annotated, including the well conserved Halloween genes, which are involved in ecdysteroidogenesis. Expression patterns across the life-stages determined that only a subset of the CYP450s can be detected in each life-stage or tissue. Four Shed transcripts show overlapping expression between metamorphosis and adult tissues, suggesting pleotropic functions of the multiple Shed orthologs within P. ornatus.

One of the main drivers behind the urbanization process is attributed to economic fundamentals of urban growth, which boost migration from rural to urban context. This migration can be studied geographically, with increasing rates of population as the main component in developing countries, over Asia and Africa, specifically. Research has been focusing in creating models and adaptative schemes to manage and plan cities to promote sustainable development for housing large quantities of population and preserve a long-term living environment. The approach from a smart city perspective, adjusted to the rapid urbanization condition can be helpful to deal urban issues by convergence and interaction between urban agents and information technology. At academia, few works have addressed the role of Smart Cities to face the challenge of rapid urbanization. The aim of this study is to research and analyze if strategies with smart city vision can lessen environmental impacts at cases with rapid urbanization, and how can we leverage technology to promote environmental sustainability at rapid urbanization phenomena occurring at developing countries using RIAM environmental assessment method in the case of Beijing, China'.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

Significant problems have arisen in the last years, such as climate change, global warming, and hunger. These complications are correlated with the depletion and exploitation of natural resources and environmental contamination. Due to overcrowding, the list of challenges for the next few years is growing. A comprehensive approach was made to the agro-industrial production of Avocado (Persea americana) and the management of all its biomass waste. So, bioprocesses and biorefinery can be used to produce high added-value products. A large number of residues are composed of lignin and cellulose. They have many potentials to be exploited sustainably for chemical and biological conversion; physical, chemical, and natural treatments improve the following operations. There are some applications to many fields such as pharmaceutical, medical, material engineering, and environmental remediation. Possible pathways are mentioned to take advantage of Avocado as biofuels, drugs, bioplastics, and even in the environmental part and emerging technologies such as nanotechnology using bioprocesses and biotech. In conclusion, Avocado and its waste could be transformed into high value-added products in industries above to mitigate global warming and save non-renewable energy.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Cariogenic oral biofilms cause a considerable amount of recurrent dental caries around composite restorations every year, resulting in unprosperous oral health status and expensive restorative treatment for many patients. Quaternary ammonium monomers that can be copolymerized with the current dental resin systems have been increasingly explored for modulation of dental plaque biofilm growth over dental composite surfaces. Here, we investigated the effect of bis(2-methacryloyloxyethyl) dimethylammonium bromide (QADM), against human overlying mature oral biofilms grown intra-orally in human participants for 7 and 14 days, for the first time. Seventeen volunteers wore palatal devices containing composite specimens containing 10% by mass of QADM or a control composite without QADM. After 7 and 14 days, the adherent biofilms were collected for determination of bacterial counts via colony-forming unit (CFU) counts. The biofilm viability, chronological changes, and percentage coverage were also determined by live/dead staining. QADM composites caused a significant inhibition of S. mutans biofilm formation for up to seven days. No difference in the CFU values were found for the 14-day period. Our findings suggest that (1) QADM composite was successful in inhibiting 1-3 day biofilms in the oral environment in vivo; (2) QADM significantly reduced the portion of S.mutans group in a time course where patients at high risk of caries would develop initial enamel carious lesions; and (3) stronger antibiofilm activity is required for the control of mature long-term cariogenic biofilms. These results provide a perspective on the value of integrating bioactive restorative materials with traditional caries management approaches into clinical practice. Contact-killing strategies via dental materials aiming to prevent or at least reduce high numbers of cariogenic bacteria seem to be a promising approach in patients at high risk of recurrence of dental caries around composites.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Hydroponic farming systems play an increasingly important role in the sustainable production of nutrient-rich foods. The contamination of surfaces in hydroponic fresh produce production poses risks to the food safety of crops, potentially endangering public health and causing economic losses in the industry. While sanitizers are widely used in commercial hydroponic farms, their effectiveness against human pathogens on surfaces, and their impact on plant health and quality are not known. In this study, we evaluated the efficacy of chemical sanitizers in eliminating Salmonella Typhimurium from inanimate surfaces in commercial hydroponic Nutrient Film Technique (NFT) systems. Further, we assessed the impact of sanitizers on the yield, quality, and nutritional value of lettuce and basil. Sanitizers (Virkon, LanXess; Sanitate 12.0, Bi-oSafe Systems; Kleen Grow, Pace Chemical Ltd.; Green Shield, United Labs Inc.; Zerotol, BioSafe Systems; Bleach, Pure Bright), were tested against Salmonella Typhimurium inoculated on NFT surfaces (nutrient reservoirs, growing channels, top covers, drain lines). The effective treatments were then tested for their impact on lettuce and basil in a split-plot experiment conducted in commercial NFT units. Crop yield, color, and nutrient content were measured throughout the crop life cycle. While all quaternary ammonium compounds (QAC), SaniDate 12.0 (200ppm), Zorotol (5%), and Virkon (1%) eliminated Salmonella Typhimurium from commercial NFT surfaces, chlorine-based sanitizer treatments were statistically similar to water treatments on most surfaces. All chemical sanitizers impacted the yield, color, and nutritional value of lettuce and basil. SaniDate 12.0 (200ppm) was the least detrimental to crops and was identified as a potential candidate for further validation in commercial hydroponic settings. The findings of this study will be translated into recommendations for the industry and will contribute to the development of future food safety guidelines and policies.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Many young people are reluctant to seek support for mental health concerns and a preference for self-reliance has been identified as a key barrier. Yet, the conceptualisation and measurement of self-reliance is not well understood. This study examines the meaning of self-reliance as it affects young people’s help-seeking, with an emphasis on the role of trust (both in self and in others). 30 Australian young people aged 18-25 years were interviewed. Reflexive thematic analysis, using both inductive and deductive approaches, was used to construct themes about the relationships between trust, self-reliance, and help-seeking for young people. Participants identified that both self-reliance and help-seeking exist on a continuum from insufficient self-reliance to extreme self-reliance and excessive help-seeking to unwillingness to seek help. Trust was a key component of self-reliance, and a balance between trust in self and trust in others is necessary for self-reliance to be adaptive and appropriate help-seeking to occur. To maintain this balance, young people felt that a level of self-awareness was necessary. A high level of trust in self is considered to increase self-reliance, whereas a high level of trust in others increases help-seeking behaviours. Understanding the role of trust in self-reliance informs developmentally appropriate ways to address self-reliance as a barrier to mental health help-seeking for young people.

Driven by the growing interest of the scientific community and the proliferation of research in this field, cranial implants have seen significant advancements in recent years regarding design techniques, structural optimisation, appropriate material selection and fixation system method. Custom implants not only enhance aesthetics and functionality but are also crucial for achieving proper biological integration and optimal blood irrigation, critical aspects in bone regeneration and tissue health. This research aims to optimize the properties of implants designed from triply periodic minimal surface structures. The gyroid architecture is employed for its balance between mechanical and biological properties. Experimental samples were designed varying three parameters of the surface model: cell size, isovalue and shape factor. Computational simulation tools were used for determining the relationship between those parameters and the response variables: the surface area, permeability, porosity and Young modulus. These tools include computer aided design, finite element method and computational fluid dynamics. With the simulated values, the corresponding regression models were fitted. Using the NSGA-II, a multi-objective optimisation was carried out, finding the Pareto set which includes surface area and permeability as targets, and fulfil the constraints related with the porosity and Young modulus. From these non-dominated solutions, the most convenient for a given application was chosen, and an optimal implant was designed, from a patient computed tomography scan. An implant prototype was additively manufactured for validating the proposed approach.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Jamaica has one of the highest teenage pregnancy rate and therefore identifying the context of adolescent sexual and reproductive health is important, especially since there is paucity of research on preadolescents in the Jamaican context. The study was a nationally representative cross-sectional, interviewer administered, school-based survey of 10 -15 year olds. Summary statistics of the demographics and bivariate analyses were performed to assess the association of sexual initiation and given risk and resiliency factors. 1,422(47.4%) males, 1,581 (52.6%) females, mean age (SD) 12.5 (1.6) years were surveyed. Mean age of first sex was 11.0 (±2.5) years. Factors significantly with sexual initiation were, female sex (OR 0.17; 95% CI 0.12-0.23), caring relationships inside the home (OR 0.85; 95%CI 0.83-0.97) rare church attendance (OR1.36; 95%CI1.0-1.8), age (OR 1.75; 95%CI1.6-1.9) and community disorganization (OR 1.02 95% CI 1.01-1.07). Sexual initiation of early adolescents is positively influenced by environmental factors such as family connectedness and religious involvement. The negative correlates are societal risk factors such as community disorganization. Empowerment through learned sexual negotiation skills, should be incorporated into the education programme of pre-adolescents to facilitate adolescents embracing their intrinsic power to delay sexual debut and if sexually active to insist on condom use.

The presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

We describe a forecast system based on the Weather Research and Forecasting (WRF) model for the prediction of high-impact weather events affecting power utilities, particularly conditions conducive to wildfires. The system was developed for Pacific Gas and Electric Corporation (PG&E) to operationally forecast conditions in Northern and Central California. It was established in 2014 and has been periodically improved. In the current configuration, WRF forecasts are routinely performed multiple times each day on a 2-km grid, and the results are used as input to wildfire fuel moisture, fire probability, and wildfire spread models. Components of the system include a stochastically perturbed ensemble; an annually updated reanalysis covering more than 30 years; and validation against PG&E’s extensive mesonet and other observing networks. We describe the development and validation of the next operational edition. Configurations tested include irrigation triggered by crop growing season and an ensemble-based approach with intelligently sub-selected Global Ensemble Forecast System (GEFS) members. The latter approach allows for enhanced uncertainty sampling in WRF forecasts and can greatly improve WRF forecasts when calibrated by observations.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23-72 participated in one of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Background: Micrococcus luteus is a commensal bacterial member on the human skin and is essential in keeping the balance among the various microbial flora of the skin. M. luteus strain Q24 or BLIS Q24^TM was isolated from the skin of a healthy human adult and has been identified to produce a unique antimicrobial spectrum that is inhibitory towards pathogenic bacteria associated with many skin diseases such as acne. It has been developed as a probiotic with potential applications in improving overall skin health.Aim: This study aimed to evaluate the perceived changes in skin quality following topical application of a formulation containing skin commensal probiotic BLIS Q24^TM. Materials and methods: A 28-day study involving 100 adult participants with self-reported normal skin with occasional blemishes or breakouts, topically applied a serum formulation containing BLIS Q24^TM to the face. Participants quantitatively evaluated the probiotic serum effect on their skin at baseline Day 0 and then again on Day 10, 20 and 28 of the application. In addition, participants maintained a photo diary to record the perceived changes to their skin.Results: A total of 96 participants completed this research. In comparison to the baseline (Day 0), within 10 days, a significant reduction in blackheads (48%), oiliness (48%), blemishes (57%), dry areas (23%), redness/rosacea (45%) and flaky and rough skin (38%) were reported. The probiotic serum was also effective in a significant reduction in fine lines and wrinkles (38%), whiteheads (41%), pimples (55%), age spots (29%), and acne (21%) by the end of 28 days of probiotic application. Overall, there’s agreement that probiotic serum delivers or exceeds consumer expectations from the concept and performs just as well, or better, than their regular moisturiser.Conclusions: An approach of delivering a live probiotic packaged in an innovative formula to improve several skin conditions in otherwise healthy individuals was found to be successful. This study highlights that a serum formulation containing BLIS Q24^TM has a positive impact on skin health with it being effective topically in reducing the appearance of skin blemishes, oiliness, wrinkles, redness, and dryness. BLIS Q24^TM offers the potential for the prevention of skin health-related issues and routine maintenance of skin microbiome for healthy skin.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

In the past ten years, the generative artificial intelligence trend has evolved from simply enhancing the creation of audiovisuals using generative adversarial networks to becoming an entirely disruptive force, transforming operations in various industries and markets, including education and business. The introduction and subsequent widespread popularity of Open AI’s ChatGPT in 2022 raised concerns about the use of Generative AI in professional spaces and its impact on authenticity, innovation, data privacy, and integrity. This study seeks to assess the current applications of this disruptive technology in corporate America and build on that knowledge to provide insight into the current innovative practices and the factors driving its use. The research will further outline some risks associated with generative AI technology in business functions and industries and how this technology is being misused in industries worldwide. Following these revelations, recommendations will be made on the need for regulations surrounding the use of generative AI and the future of this technology for researchers and corporations alike. This study aims to equip corporate strategists and leaders with the knowledge needed to embrace AI, be aware of its possible challenges, and find the best ways to use Generative AI to gain competitive advantage. In addition, it seeks to further equip technology experts and professionals with key information about Generative AI to help them make informed choices when working. The study also aims at research management experts and personnel as it contains vital information that will set the foundation for future research.

This study explores the implementation of the ANSI/373: Sustainable Production of Natural Dimension Stone standard within the North American dimension stone industry to identify driving forces behind the initiative and consider potential outcomes as it advances. The method involves a thorough review of ANSI/373, comparing it with voluntary sustainability initiatives (VSIs) in the forest industry to assess its effectiveness and challenges, and semi-structured interviews with contacts in the dimension stone field. Key drivers such as corporate social responsibility and market pressures influence the adoption of sustainability standards. The results highlight the embedded environmental considerations within the emerging dimension stone standards and their implications for sustainable practices in the industry. While the ANSI/373 standard promotes sustainable awareness and practices, it faces challenges in certification credibility and industry acceptance, particularly due to inconsistency among firms in their response, rigorous certification demands, and skepticism about certification credibility. The research advocates for enhanced collaborative frameworks to increase the standard’s adoption and impact, suggesting that industry stakeholders prioritize showcasing dimension stone as a practical, environmentally considerate material.

Global climate change, particularly rising sea surface temperatures, profoundly impacts coral ecosystems, disrupting reproduction synchrony, symbiotic relationships with algae from the Symbiodiniceae family, and causing widespread bleaching and mortality among coral populations.  Oculina patagonica, a temperate scleractinian coral dominant in Mediterranean coastal waters, tolerates an annual temperature range of 10- 31°C. Moreover, in the past three decades, sea surface temperatures have rapidly risen in the Eastern Mediterranean Sea. O. patagonica offers insight into evolutionary adaptation to rapid environmental changes. This study investigated the effects of temperature changes on O. patagonica reproductive development, synchrony, and thermal sensitivity. Monthly monitoring of O. patagonica colonies for a year reveals no disruption in gonad development compared to previous studies, suggesting an unaffected sexual reproduction capacity. Thermal performance

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

Over the last several decades there has been an arms race to acquire credentials as higher education has shifted from an elitist system to mass education. From an individual perspective, given the higher education system and labor market conditions, it is rational to pursue advanced qualifications. However, whether the education system delivers improvements in human capital or is principally a signaling mechanism is questionable. Estimates of the proportion of labor market rewards due to signaling range as high as 80%, suggesting that education is not only expensive but inefficient. In an increasingly transactional environment in which education providers are highly motivated by financial considerations, this situation is only likely to be exacerbated by the rapid developments in AI. The use of AI has the potential to make learning more effective but, given that many students see credential acquisition as transactional, it may reduce both human capital and the value of the signaling effect. If the credibility of the credentials offered is further damaged, the sustainability of the higher education sector in its present form and scale may well be unsustainable. We examine the evidence on credential inflation, returns to education and mismatch of graduates to jobs before analyzing how AI is likely to affect these trends. We then suggest possible responses of prospective students, education providers and employers to the growing adoption of AI in both education and the workplace. We conclude that the current offerings of generalist degrees, as opposed to vocational qualifications, are not sustainable and that to survive, even in a downsized form, the sector must respond to this disruptive technology by changing both the nature of its offerings and its methods of ensuring that the credentials they offer reflect genuine student learning.

Integrated landscape approaches (ILA) aim to reconcile multiple, often competing, interests across agriculture, nature conservation, and other land uses. Recognized ILA design principles provide guidance for their implementation, yet application remains challenging, and a strong performance evidence-base is yet to be formed. A comprehensive literature review and focus group discussions with practitioners identified considerable diversity of ILA in actors, temporal, and spatial scales, inter alia. This diversity hampers learning from and steering these integrated planning approaches because of its intractable nature. Therefore, we developed a tool—an ‘ILA mixing board’—to structure the complexity of ILA into selectable and scalable attributes in a replicable way to allow planning, diagnostics, and comparative assessment of ILA. The ILA mixing board tool presents seven qualifiers, each representing a key attribute of ILA design and performance such as project flexibility, inclusiveness of the dialogue, and the centrality of the power distribution. Each qualifier has five (non-normative) outcome indicators that can be registered as present or absent. This process in turn guides planners, evaluators and other participating stakeholders involved in landscape management to diagnose the ILA type, and or its performance. We apply the ILA mixing board as a diagnostic tool to three ILA cases in Nicaragua, Madagascar, and the Congo Basin to show some of the many possible configurations of qualifiers on the mixing board. Overall, the tool allows comparative analyses of the complexity of ILA in a structured and manageable way.

This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.

Contaminants of Emerging Concern (CECs), a new category of contaminants in limelight, is a major issue of global concern. The pervasive nature of CECs and its harmful effects, such as cancer, reproductive disorders, neurotoxicity etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentration of CECs can cause great impacts on living beings. It also has a nature of bioaccumulation. Thus, it is the ultimate need to have efficient sensors for detection of CECs to ensure safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in literatures under each category for the detection of major CECs.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.

Macrophages are well known for the involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses; particularly for those of human cells. Isolation of tissue resident macrophages, from humans, is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes, and differentiation to monocyte-derived macrophages, may provide a useful tool with which to study, further, these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the REFINE project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination which may confound, potential, observations. The SOP was deployed in two partner institutions with, broadly, similar results. The work presented here shows the utility of this assay but, highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some, logistical, challenges to application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous, non-human, cell lines.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

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

High-throughput screening technologies continues to produce large amounts of multiomics data from different populations and cell types for various diseases, such as cancer. However, analysis of such data encounters difficulties due to cancer heterogeneity, further exacerbated by human biological complexity and genomic variability. There is a need to redefine the drug discovery development pipeline, bringing an Artificial Intelligence (AI)-powered informational view that integrates relevant biological information and explores new ways to develop effective anticancer approaches. Here, we show SynPred, an interdisciplinary approach that leverages specifically designed ensembles of AI-algorithms, links omics and biophysical traits to predict synergistic anticancer drug synergy. SynPred exhibits state-of-the-art performance metrics: accuracy – 0.85, precision – 0.77, recall – 0.75, AUROC – 0.82, and F1-score - 0.76 in an independent test set. Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application available online at http://www.moreiralab.com/resources/synpred/ was constructed to predict synergistic anticancer drug combinations requiring only the upload of the two drug SMILES to be tested, allowing easy access by non-expert researchers.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

The use of naturally available materials not conforming to traditional specifications or standards, in the base and sub-base layers of road pavement structures, stabilised with New-age (Nano) Modified Emulsions (NME), have been tested, implemented and successfully verified through Accelerated Pavement Testing (APT) in South Africa. This was made possible through the development and use of a design procedure addressing fundamental principles and based on scientific concepts, which are universally applicable. The understanding of and incorporation of the chemical interaction between the mineralogy of the materials and a NME stabilising agent (compatibility between the chemistry of the reactive agents and material mineralogy) into the design approach is key to achieving the required engineering properties. Stabilised materials evaluation is done using tests indicative of the basic engineering properties (physics) of compressive strengths, tensile strengths and durability. This article describes the basic materials design approach developed to ensure that organofunctional nano-silane modified emulsions can successfully be used for pavement layer construction utilising naturally available materials, at a low risk. The enablement of the use of naturally available materials in all pavement layers can have a considerable impact on the unit cost and life-cycle costs of road transportation infrastructure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

The extended cleavage specificities of two hematopoietic serine proteases originating from the ray-finned fish spotted gar (Lepisosteus oculatus) have been characterized using substrate phage display. The preference for particular amino acids at, and surrounding the cleavage site was further validated using a panel of recombinant substrates. For one of the enzymes, the gar granzyme G, a strict preference for the aromatic amino acid Tyr was observed at the cleavable P1 position. Using a set of recombinant substrates showed that the gar granzyme G had a high selectivity for Tyr, but also with lower activity cleaving after Phe but not after Trp. The second enzyme, gar DDN1, instead showed a high preference for Leu in the P1 position of substrates. This latter enzyme also showed high preference for Pro in the P2 position and Arg in both P4 and P5 positions. The selectivity for the two Arg residues in positions P4 and P5, suggest a highly specific substrate selectivity of this enzyme. Screening of the gar proteome with the consensus sequences obtained by substrate phage display for these two proteases resulted in a very diverse set of potential targets. Due to this diversity, a clear candidate for a specific immune function of these two enzymes cannot yet be identified. Antisera developed against the recombinant gar enzymes were used to study their tissue distribution. Tissue sections from juvenile fish showed expression of both proteases in cells in Peyer´s patch-like structures in the intestinal region, indicating they may be expressed in T or NK cells. However, due to the lack of antibodies to specific surface markers in the gar, it has not been possible to specify the exact cellular origin. A marked difference in abundance was observed for the two proteases where gar DDN1 was expressed at higher levels than gar granzyme G. However, both appear to be expressed in the same or similar cells, having a lymphocyte-like appearance.

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. FT specimens from 288 patients who underwent spinal cord detethering from 2013-2021 were analyzed. Histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. Patient details were extracted from electronic medical records. The study found that 97.6% of FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.

Objective: This analysis investigates patient experiences regarding pain management during gynecological procedures through a comprehensive survey, aiming to address the lack of clear guidelines in the clinical landscape and emphasize the importance of effective pain management strategies in enhancing patient care and satisfaction. Design: A cross-sectional survey with 258 respondents assessed pain management experiences during gynecological procedures. The survey was distributed via Qualtrics, and 258 responses were obtained. Participants/Materials, Setting, Methods: Participants provided demographic information and responded to questions regarding contraceptive methods, procedures undergone, pain management discussions, anxiety levels, and willingness to accept pain management interventions. Confidentiality and informed consent protocols were strictly observed throughout the study. Results: Most female respondents reported diverse contraceptive methods and procedures. Pain management discussions and provisions varied, with a significant portion reporting never being offered pain management. Many experienced anxiety and pain during procedures, with varying intensities, that were not addressed or discussed by their treating provider. Most expressed willingness to accept pain management interventions. Limitations: This study relies on self-reported data, potentially introducing recall bias, and has limited generalizability due to its cross-sectional design. Conclusions: Findings reveal a significant gap in pain management provision and discussion during gynecological procedures. Improved guidelines and practices are necessary to address patient discomfort effectively. Standardized pain management protocols are crucial to enhance patient experiences and outcomes, with further research needed to tailor strategies to individual patient needs.

While traditionally people relinquish their pets to an animal shelter or pound, the internet provides a newer method to re-home. We analysed advertisements (ads) on the largest website in Australia for trading dogs and cats, gumtree.com.au. Data was collected in 2016. Dogs were sampled on February 7, 16 and 24, 2016 and cats on February 9, 19 and 26, 2016 with 2640 ads for relinquished dogs, and 2093 ads for relinquished cats. It was estimated >31,000 puppies/dogs and >24,000 kittens/cats are relinquished on gumtree.com.au per year. The median age of dogs was 1.42 and cats 0.9 years of age. There were 23% of dog ads and 62% of cat ads for free animals. Compared to the human population there were proportionately more ads in Queensland and fewer ads in Victoria. A total of 15 people were surveyed who had relinquished a dog or cat using gumtree.com.au. The dog owners used gumtree.com.au because they believed the shelters were full (n = 4), and; they wanted to see/interview the new owner (n = 2). For cat owners it was because they had originally got the cat on gumtree.com.au (n = 2); they use gumtree.com.au for other things, and it works (n = 2), and; they wanted to see/interview the new owner (n = 2). The data collected will be valuable for implementation of policy and interventions to protect the welfare of un-wanted dogs and cats.

Outliers can influence regression model parameters and change the direction of the estimated effect, over-estimating or under-estimating the strength of the association between a response variable and an exposure of interest. Identifying visit-level outliers from longitudinal data with continuous time-dependent covariates is important especially when the distribution of such variable is highly skewed at follow-up visits. The primary objective was to identify potential outliers at follow-up visits using interquartile range (IQR) statistic, motivated by a large TEDDY dietary longitudinal and time-to-event data with a continuous time varying vitamin B12 intake as the exposure of interest and time to developing Islet Autoimmunity (IA) as the response variable. The IQR method was also applied to simulated data. To assess the impact of IQR-method detected outliers, data was analyzed using Cox-proportional hazard model with robust sandwich estimator. Partial residual diagnostic plots were used to detect highly influential outliers. Results showed how some of the detected outliers had large influence on the Cox regression model and changed both the direction of hazard ratios and the strength of association with the risk of developing IA. In conclusion, the IQR method is useful in identifying potential outliers at visit-level which can be further investigated.