Under one-health perspective and the worldwide antimicrobial resistance concern, we investigate extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. Ninety-one (46.2%) isolates were classified as ExPEC and/or UPEC including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST64815) and (ii) 15 had been shown to be displayed by previously published isolates causing extraintestinal infections in humans. Twenty-eight (14.2%) isolates were classified as MDR, associated with B1, D and E phylogroups and included 24 clones, of which eight had also been identified among human isolates causing infections. We selected 23 ST372 strains, 21 healthy dogs faecal isolates and two human clinical isolates for whole genome sequencing and built a SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. The analysis of these 197 genomes allowed to identify six clusters. Cluster 1 comprised 74.6% of the strain genomes that were mostly composed of canine strain genomes (P < 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3 and 5 were significantly associated with human strain genomes. All these findings suggest that dogs are reservoirs of ExPEC, UPEC and MDR E. coli isolates with zoonotic potential.

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

Gelatinization of starch content in pet foods can be impacted by several factors including moisture, retention time, and ingredients used. Starch gelatinization has been associated with digestibility but isn’t well studied using ingredients common in non-traditional canine diets. The objective of this research was to examine the impacts of dietary ingredient profile (traditional vs non-traditional) and assess impacts to total starch content and starch gelatinization. Traditional diets (n = 10) utilizing meat-based ingredients including chicken, chicken by-product meal, meat and bone meal and plant-based ingredients including rice, barley, oats, and corn were examined in comparison with non-traditional diets (n = 10) utilizing meat-based ingredients including alligator, buffalo, venison, kangaroo, squid, quail, rabbit, rabbit and salmon along with plant-based ingredients including tapioca, peas, chickpeas, lentils, potato, and pumpkin. Representative samples were collected via grab sample technique (5 samples/diet) and were assessed for total starch content as well as percent starch gelatinization. Difference between ingredient type was assessed using a Students t-test in SAS 9.4. Significance was set at P < 0.05. Distribution of total starch content based on ingredient type (traditional vs non-traditional) revealed that mean total starch content was higher in traditional diets as compared to non-traditional diets (P <0.0001). Conversely, starch gelatinization was found to be higher in non-traditional diets (P < 0.0001). Total starch content and total gelatinized starch had a strong negative correlation (P < 0.01) in traditional diets, though no correlation was observed in non-traditional diets. This negative correlation indicates a decrease in total gelatinized starch associated with increased total starch content. These novel data reveal important differences between starch content and gelatinization and could impact manufacturing processes for ingredient types as well as feeding recommendations. Unpredicted variation between ingredient formulations could potentially lead to decreased digestibility and absorption and may result in nutrient deficiencies.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

Purpose: The purpose of this study is to further explore how e-loyalty and E-marketing influences E-trust and satisfy the demand by offering fresh perspectives based on research as well as emphasis on the factors influencing the E-trust such as culture as a mediator. This study not only contributed theoretically but also presented practical implementations. Design/methodology/approach: Online survey was used to obtain data by focusing the Hospitality sector (Hotel Industry) and verifying the conceptual framework. Data was collected in multiple time lags. Findings: Findings showed that the E-trust influenced by E-loyalty and E-Marketing. E-trust comes from the previous experiences, e-loyalty and e-marketing. Further, some trends such as culture influenced the e-trust. Research limitation/implications: The present study is quite suitable for those Researchers interested in learning more about the effects of E-loyalty and E-marketing on user E-trust and how to mitigate cultural influences can benefit from the current study. This research also has implications for those who wish to improve market allure and survival in digital world. This study focused on the hospitality sector (Hotel Industry) in China; however, the sector and geography could be altered to suit the needs of the study's participants. Practical implications: The present study delivers the practical guidelines which are quiet suitable for understanding the formation of E-loyalty, E-marketing, and E-trust through which specific E-marketing strategy can be designed to deal with the consumer’s E-loyalty and their expectations as per their Cultural perspective. At some particular regions/countries, cultural trends are more important than practical market. This research study practically showed that how culture changed the consumer set of mind. Originality/value: The relationship between E-loyalty, E-marketing, E-trust, specifically with the cultural influence in digital market has been the subject of few research.

Households and businesses are generating unprecedented levels of electrical and electronic wastes (e-waste), fueled by modernisation and rapid obsolescence. While the challenges imposed by e-waste are similar everywhere in the world, disparities in progress to deal with it exists; with developing nations such as South Africa lagging. The increase in e-waste generation increases the need to formulate strategies to manage it. This paper presents an overview of e-waste management on a global and South African scenarios with a specific case for Cathode Ray Tube (CRT) waste management practices in South Africa. CRTs present the biggest problem for recyclers and policy makers because they contain hazardous elements such as lead and antimony. Common disposal practices have been either landfilling or incineration. The research into the South African practices with regards to CRT waste management showed that there is still more to be done to effectively manage this waste stream. This is despite clear waste regulatory frameworks in the country. However, recent developments have placed e-waste as a priority waste stream, which should lead to intensified efforts in dealing with it. Overall, these efforts should aim to maximise diversion from landfilling and to create value-addition opportunities, leading to social and environmental benefits.

In West Africa, research on the hepatitis E virus (HEV) is barely covered despite the recorded outbreaks. The still low level of access to safe water and adequate sanitation is one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Here, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A total of 1,227 consenting participants attending antenatal clinics responded to our questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. HEV global seroprevalence was 7.9% with 0.5% and 7.4% for HEV IgM and HEV IgG, respectively. One participant's sample was IgM/IgG positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p&lt;0.0001), by the regularity of income (p=0.0043) and by access to sanitation services (p=0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental and behavioral aspects for a better management of HEV infection in Senegal.

The development of biofuels and biodiesel industry specifically, has resulted in the generation of large amounts of glycerol as a surplus. The conversion of glycerol, into chemicals with indus-trial interest, through anaerobic fermentation using E. coli as a biocatalyst is an attractive alter-native to improve economic performance in the biodiesel industry, for example through the bi-otransformation of residual glycerol into ethanol. For 2019, the size of the global ethanol market was valued at $ 89.1 billion US dollar. Biodiesel can be produced from several materials like rapeseed, palm, soya, corn, palm kernel, frying oil or olive-pomace oil (OPO). The last, can be extracted from alperujo, byproduct of olive oil process. However, olive-pomace oil converting into biodiesel is not enough established to achieve a global olive-oil/biodiesel derived process with minimized waste generation. Traditionally biodiesel production process produces an equivalent of 10% by mass of glycerol as a waste or by-product. This work explores the conver-sion of residual glycerol into chemicals like ethanol and hydrogen with a focus on projecting raw material potential availability from OPO, contributing to the promotion of the use of biofu-els and biodegradable compounds.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the non-structural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and in particular the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. By contrast, MetPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent as MetPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.

In recent years, it has become common for individuals to juggle employment and unpaid care work. This is just as true for the England-based academic workforce, our focus in this article. We discuss how, in the context of English HE, support for carers is enacted and negotiated through policies and practices of care. Our focus on academics with a diverse range of caring responsibilities is unusual insofar as the literature on care in academia is overwhelmingly concerned with parents, usually mothers. The article is informed primarily by critical and post-structuralist feminist perspectives. We draw on a corpus of 47 interviews conducted with academics representing a broad range of caring responsibilities, subjects, and positions. A thematic analysis reveals how carers’ relationship with the provision and policies of care support at institutional level is characterised by ambiguity. On the one hand, participants approve of societal and institutional policy support for carers. On the other hand, they are often reluctant to position themselves as the beneficiary of such policies, expressing instead a general preference for support from outside the workplace or for workplace-based inter-individual and informal care arrangements. This resistance is particularly noticeable in the case of participants with caring responsibilities other than the parenting of healthy, able-bodied children and of those whose gender, class, racial, or sexual identity do not conform with the figure of the ‘ideal academic’, contributing to their othering in the academic realm. These findings have significant implications for policies supporting carers, pointing to the need for greater visibility and recognition of caring responsibilities in academia, especially in terms of their diverse identities.

The expression "Follow the water" is used in order to recognize inside the universe, life as it exists on Earth. It is shown here that the expression "Follow the water in its high-subcritical state" can be used in order to recognize the components of life which form prior to the emergence of life. This specific state of water leaves signatures inside the minerals which are produced during high-subcritical water/rock interaction.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Anthropomorphism is a natural tendency in humans, but it is also influenced by many characteristics of the observer (the human) and the observed entity (here, the animal species). This study asked participants to complete an online questionnaire about three videos showing epimeletic behaviours in three animal species. In the videos, an individual (a sparrow, an elephant and a macaque, respectively) displayed behaviours towards an inanimate conspecific that suddenly regained consciousness at the end of the footage. A fourth video showed a robot dog being kicked by an engineer to demonstrate its stability. Each video was followed by a series of questions designed to evaluate the degree of anthropomorphism of participants, from mentaphobia (no attribution of intentions and beliefs, whatever the animal species) to full anthropomorphism (full attribution of intentions and beliefs by animals, to the same extent as in humans) and to measure how far the participants had correctly assessed each situation in terms of biological reality (current scientific knowledge of each species). There is a negative correlation (about 61%) between the mental states attributed to animals by humans to animals and the real capability of animals. The heterogeneity of responses proved that humans display different forms of anthropomorphism, from rejecting all emotional or intentional states in animals to considering animals to show the same intentions as humans. However, the scores participants attributed to animals differed according to the species shown in the video and to human sociodemographic characteristics. Understanding the potential usefulness of these factors can lead to better relationships with animals and encourage a positive view of human-robot interactions. Indeed, reflective or critical anthropomorphism can increase our humanity.

In this study, we asked participants to answer an online questionnaire about videos showing animal epimeletic behaviours: an individual (a sparrow, an elephant and a macaque) displayed behaviours towards an inanimate conspecific who suddenly got back to conscious at the end of the footage. A fourth video showed a dog-robot kicked by an engineer to demonstrate its stability. After each video, questions were asked to score the degree of anthropomorphism of participants, from mentophobia (no attribution whatever the species) to full anthropomorphism and to measure how close participants are to biological reality (actual scientific knowledge). A first important result is that there is a negative correlation (about 61%) between the anthropomorphism score (AS) and the biological reality one (BRS) showing a wrong statement. The heterogeneity of responses proved that all levels of anthropomorphism are covered from mentaphobia to full anthropomorphism. However, the scores participants attributed to animals differ according to the species shown in the video and to human characteristics. Understanding how one can play with these factors can conduct to better relationships with animals as encourage human-robot interactions. Finally, such reflective anthropomorphism can lead to an increase of human empathy and sociality, finally increasing our humanity.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Wearable antennas are increasingly vital in modern healthcare, facilitating continuous monitoring and communication for medical purposes. These antennas are integrated into wearable devices, allowing for the transmission and reception of vital health data, such as heart rate, body temperature, and blood pressure, to medical professionals or monitoring systems in real time. This instantaneous data transmission enables timely interventions, thus improving the quality of healthcare services. This review aims to comprehensively synthesize recent research from reputable databases, focusing on the functionality and effectiveness of wearable antennas in medical applications. The primary objectives of each study were categorized, including antenna design and integration, the performance of medical wearable antenna technology, safety considerations in wearable antenna biomedicine, and the use of antennas in clinical applications and their impact. This synthesis provides valuable insights for researchers and practitioners aiming to develop and deploy wearable antennas in medical settings, ultimately enhancing healthcare delivery and patient outcomes.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Pituitary adenomas are benign brain tumors that pose a heavy burden on patients worldwide. However, the local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity. As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was done in four patients, and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

In 2020, students of Pakistan had to adapt to the online environment for the very first time. This study aims to analyze the perceptions of medical, dental, and allied health students about online education in Pakistan. A descriptive, cross-sectional study was done to assess the level of acceptance of undergraduate students. A pre-validated questionnaire regarding demographics, past-experience of e-learning, advantages disadvantages of e-learning, and general perception of students towards e-learning was distributed. Descriptive statistics were computed for demographics, Mann-Witney-U test was used to compare the differences of perceptions between pre-clinical year and clinical years students. Kruskal-Wallis test was applied to compare the results of three specialties of students. Chi-square was used to compare overall category-wise positive and negative responses of students. 1200 students participated in the study. The major advantage identified by all students was the ‘comfortable environment’ in which they studied online. The major disadvantage selected by preclinical year students was ‘anxiety due to social isolation’ and that chosen by clinical year students was ‘lack of patient interaction’. Overall, 72% of students had a negative perception of e-learning. Student-teacher training, student counselling sessions, and innovative techniques need to be introduced to enhance student engagement and reduce pandemic stress.

Abstract: This comprehensive review seeks to deepen our comprehension of the African plant Momordica balsamina L. by elucidating its therapeutically important molecules and micronutrient composition. Commonly referred to as the balsam apple, this plant species is extensively harnessed for its diverse therapeutic potentials across its various organs including leaves, fruits, roots, and stems. Numerous bioactive molecules have been isolated or identified within this plant, notably encompassing polyphenols, flavonoids, terpenes, and carotenoids. These compounds exhibit a wide array of biological activities, ranging from antioxidative, anti-inflammatory, anti-diabetic, anti-carcinogenic, to anti-malarial properties, among others. Furthermore, the leaves of Momordica balsamina L. stand out for their abundant micronutrients, proteins, and amino acids. This investigation aims to shed light not only on the botanical characteristics of the Momordica balsamina plant and its potential applications in traditional medicine, but also on its chemical composition, biological functionalities, and physicochemical attributes, thus accentuating its nutritional advantages. Nonetheless, an intriguing avenue presents itself for the exploration of strategies to conserve this species, delve deeper into its potential within the cosmetics industry, and innovate methodologies for the synthesis or biosynthesis of these bioactive molecules.

The rapid growth of the global wearable technologies market is projected to reach $61.30 billion by 2030 which reflects a shift towards personalised health monitoring embedded in everyday activities. This paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. Experimental results demonstrate the sensor’s capability to detect water droplets and glucose concentrations, showcasing promising applications for health monitoring. The embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

The German Constitutional Court’s climate verdict provides a re-interpretation of liberal- democratic core concepts and is highly relevant for liberal constitutional law in general – including EU and international law. The verdict accepts human rights as intertemporal and globally applicable; it applies the precautionary principle to these rights and frees them from the misleading causality debate. However, the court fails to address the most important violations of human rights, and it categorised climate policy as a greater threat to freedom than climate change. And the court does not make it clear that the Paris 1.5-degree limit implies a radically smaller carbon budget. Furthermore, little attention has so far been paid to the fact that the ruling implies an obligation for more EU climate protection, especially since most emissions are regulated supranationally. To be effective, the EU emissions trading system demands a reform, which should go well beyond the existing EU proposals to enable societal transformation to sustainability.

The morphology and maturation process of gonads of 70 Burmeister´s porpoises, with body lengths ranging 135–183 cm (n= 34 females) and 64.5-182 cm (n= 36 males) were described. Samples were collected in six ports of central and northern Peru in 1987-1999. In the field, females were classified as immature, mature (resting, lactating, pregnant) and males as immature, pubescent and mature based on, respectively, the presence of ovarian corpora and the relative quantity of semen in cut epididymides. The ovaries of P. spinipinnis are ovoid or bean-shaped and flattened, with corpora modifying surface appearance. In the laboratory, ovaries were examined macro- and microscopically, measured, weighed and sliced in 1-3 mm sections. The number of corpora ovarica (lutea, albicantia, atretica) found in each ovary as well as their macroscopic and microscopic characteristics were documented in some detail. The follicles, their oocytes and nucleus were measured. Follicular development in P. spinipinnis is predominantly left-sided, but occurs in both ovaries in 16.3% of females, mainly in those with numerous corpora. Macroscopically, several corpora atretica with luteinization had characteristics similar to those of corpora albicantia, making microscopic determination essential. Inconclusive evidence of recent ovulation was found in January. Two of three immature females showed good follicular development in March and April. The body length at 50% sexual maturity in females was estimated at 152.7 cm. There was no evidence of reproductive senescence. The testes of P. spinipinnis are elongated and cylindrical. Of the 36 males examined macroscopically, 7 were immature, 5 pubescent and 24 mature. The histological analysis determining the presence and abundance of Sertoli cells, spermatogonia, spermatocytes, spermatids and spermatozoa, the relative amount of interstitial tissue, the elongation and mean diameter of the seminiferous tubules and the relative size of the lumen allowed to confidently determine sexual maturity status. The field evaluation of maturity based on the presence of sperm in the epididymides is a useful but, in 8.3% of cases, not exact method. For males the body length at 50% sexual maturity was estimated at 157 cm. No histological evidence of male reproductive seasonality was found. Spermatogenesis was perceptible year-round and tubule diameters had non-specific variations for each month.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Objective: In this pilot study, we described the gross motor development of infants aged 4 to 24 months with congenital heart disease (CHD) and assessed through a systematic develop­mental screening programme, with individualised motor interventions. Methods: Thirty infants who had cardiac repair underwent gross motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 80% of 4-month-old infants had a delay in gross motor development and required physical therapy. Gross motor abilities significantly improved by 24 months. Infants who benefited from regular physiotherapy tended to show better improvement in motor scores. Conclusion: Our study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in those at-risk. Further research is needed to assess the effectiveness of systematic developmental screening and individualized inter­vention programmes at identifying at risk patients, and their impact on developmental outcomes.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

As customer demand for green products increases in the digital economic era, this study analyses the green innovation of the e-tailer and supplier in drop shipping models. Moreover, drop shipping e-tailers and suppliers with a drop shipping option need to make choices regarding whether to provide green or normal products to the market. When a supplier with a drop shipping option produces green products, more fees may be invested on the production of green products than on normal products. The drop shipping e-tailers and suppliers with a drop shipping option can also choose to sell normal products at a low cost, as before. This study designs four models of drop shipping e-teilers and suppliers with a drop shipping option under different choices, analyzes their operational process in drop shipping models, and investigates five theorems. The optimal pricings decisions and green degree of drop shipping e-tailers and suppliers with a drop shipping option were evaluated in this study. The impacts of the green innovation factor, green elasticity coefficient, manufacturing and distribution costs on the drop shipping e-tailers and suppliers with a drop shipping option, and the effect of other environmental parameters on the green degree of green products are also analyzed through computer simulation. The findings of the simulation analysis provide valuable guidance for e-tailers and suppliers with green innovation in drop shipping models and offer important academic and practical implications for e-commerce and the digital economy.

Whistler mode waves play a major role in regulating the lifetime of trapped electrons in the Earth's radiation belts. Specifically, whistler mode hiss waves are one of the mechanisms that maintains the slot region between the inner and outer radiation belts. The generation mechanism of hiss is a topic still under debate with at least three prominent theories present in the literature. Lightning generated whistlers in their ducted or non-ducted modes, are considered to be one of the possible sources of hiss. We present a study of new observations from the Radio Receiver Instrument (RRI) on the Enhanced Polar Outflow Probe (ePOP: currently known as SWARM-E). RRI consists of two orthogonal dipole antennas, which enables polarization measurements, when the satellite boresight is parallel to the geomagnetic field. Here we present 75 passes of ePOP - RRI from 2014 - 2018, in which lightning whistlers and hiss waves were observed. In more than 50% of those passes hiss is found to co-exist with the lightning whistlers. Moreover, the whistler observations are correlated with observations of wave power at the lower-hybrid resonance. The observations and a whistler mode ray-tracing study suggest that multiple-hop lightning induced whistlers can be a source of hiss and plasma instabilities in the magnetosphere.

Irregular female migration to Europe is a growing phenomenon, as more and more women are fleeing their countries of origin due to gender inequality and violence. During the migration process, women experience physical, psychological and social problems that affect their sex lives. The aim of our study is to describe and understand how irregular migrant wom-en living in humanitarian reception centers experience their sexuality at different stages of the migration process. This qualitative phenomenological study collected data through a sixteen in-depth interviews with irregular migrant women between January and February 2023. Data anal-ysis was carried out using ATLAS-ti 23.0 software, from which three themes were extracted: 1) The sexual reality of sub-Saharan women, 2) In search of a better life: take the risk or surrender, and 3) The migrant sexual revolution. The sexual reality of sub-Saharan women is subject to a complex normative order. The migratory process has severe consequences on migrant women's sex life. The sexual needs of irregular migrant women admitted to humanitarian reception cen-ters undergo a process of change that must be understood by healthcare providers in order to make improvements to care provision.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

Data on helminth parasites and epizoites is presented for the long-beaked and short-beaked common dolphins from the Southeast Pacific. Sampling in 1985-2000 was conducted mainly at six fishing ports in Peru and Ecuador where cetaceans were landed. From a total of 473 common dolphins sampled, we identified helminths including three species of Trematoda: Nasitrema globicephalae, Pholeter gastrophilus and Braunina cordiformis; three species of Nematoda, which includes Anisakis spp., Crassicauda sp. and Halocercus sp.; and two cestodes Tetrabothrius forsteri and Clistobothrium delphini (formerly Phyllobothrium delphini). No acanthocephalans were observed. No statistically significant sexual and ontogenetic variation in helminth prevalence was detected after which samples were pooled. The highest prevalence in the long-beaked common dolphin (n=440) was observed for N. globicephalae (96.3%) in cranial sinuses, Crassicauda sp. (83.3%) in mammary glands, Crassicauda sp. (78.8%) infesting the cranial sinuses, followed by Cl. delphini (28.6%) in the blubber and P. gastrophilus and B. cordiformis (20.4%) in the digestive tract. Although comparative testing was unfeasible due to minimal samples of short-beaked common dolphin (n=33), several of the same helminth species were found, but not N. globicephalae nor B. cordiformis. No cyamids were encountered while pseudo-stalked barnacles Xenobalanus globicipitis were common. No new (global) helminth host records are revealed for common dolphins, but this study presents a first checklist of parasites separately for the Southeast Pacific long-beaked and short-beaked common dolphins. Future work should include exhaustive laboratory-based necropsies, enhanced sampling of the short-beaked form, focus on intermediate hosts and parasitic pathology, including potential human health impact from consumption of small cetaceans.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family - E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be dif-ferent. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that E. radiata EAq was effective against all three strains, while E. cinerea EAq was only effective against E. coli. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a pro-tein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 75% at a concentration of 250 g/ml, significantly higher than the placebo. Ellagic acid, a pri-mary phytochemical found in the extracts, demonstrated noteworthy toxic and pharmacokinetic characteristics and a maximum binding energy of -7.53 kcal/mol for its anti-TyrRS activity in sili-co. The study suggests that the extracts and their primary phytochemicals could enhance the effi-cacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As phar-maceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

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.

Because of the need to replace the current clinical artemisinins in artemisinin combination therapies, we are evaluating fitness of amino-artemisinins for this purpose. These include the thiomorpholine derivative artemiside obtained in one scalable synthetic step from dihydroartemisinin (DHA) and the derived sulfone artemisone. We have recently shown that artemiside undergoes facile metabolism via the sulfoxide artemisox into artemisone and thence into the unsaturated metabolite M1; DHA is not a metabolite. Artemisox and M1 are now found to be approximately equipotent with artemiside and artemisone in vitro against asexual P. falciparum (Pf) blood stage parasites (IC50 1.5 – 2.6 nM). Against Pf NF54 blood stage gametocytes, artemisox is potently active (IC50 18.9 nM early-stage, 2.7 nM late-stage). Comparative drug metabolism and pharmacokinetic (DMPK) properties were assessed via po and iv administration of artemiside, artemisox and artemisone in a murine model. Following oral administration, the composite Cmax value of artemiside plus its metabolites artemisox and artemisone formed in vivo is some 2.6-fold higher than that attained following administration of artemisone alone. Given that efficacy of short half-life rapidly-acting antimalarial drugs such as the artemisinins is associated with Cmax, it is apparent that artemiside will be more active than artemisone in vivo, due to additive effects of the metabolites. As is evident from earlier data, artemiside indeed possesses appreciably greater efficacy in vivo against murine malaria. Overall, the higher exposure levels of active drug following administration of artemiside coupled with its synthetic accessibility indicate it is much the preferred drug for incorporation into rational new artemisinin combination therapies.

Bangladesh's railway system mostly uses typical manual railway crossing technique or boom gates through its 2,955.53 km rail route all over the country. The accidents are frequently happening in the railway crossings due to not having obstacle detectable and quickly operating gate systems, and also for fewer safety measures in the railway crossing. Currently, there are very few automatic railway crossing systems (without obstacle detectors) available, however, all of them are dependent on the national power grid without a backup plan for any emergency cases. Bangladesh is still running a bit behind in the power generation of its consumption, hence it is not possible to have a continuous power supply at all times all over the countryside. We aim to design and develop a smart railway crossing system with an obstacle detector to prevent common types of accidents in the railway crossing points. We design to use two infrared (IR) sensors to operate the railway crossing systems which will be controlled by the Arduino Uno. This newly designed level crossing system will be run with the help of sustainable renewable energy which is cost-effective, eco-friendly, and apply under the national green energy policy towards achieving sustainable development in Bangladesh as a part of the global sustainable goal to face climate change challenges. We have summarized the simulated results of several renewable energy sources including a hybrid system and optimized the Levelized Cost of Energy (LCOE), and the payback periods.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Background Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on people and society. The study's goal is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, lipid profiles, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects, divided into control D1: Diabetics without cardiovascular issues. D2: Diabetics with heart disease. D3: Diabetics with stroke. D4: Diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia, defined as elevated levels of total cholesterol, triglycerides, LDL, HDL, and VLDL, as well as uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM, were linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 75.4% of the population, with greater rates among the elderly. Stage 2 hypertension was more prevalent in all age groups. Apolipoprotein E gene polymorphism was discovered, with genotypes 3/3, 4/4, 2/3, and 3/4 being the most prevalent. Genotype 3/4 was more common in diabetics who had IHD/stroke or both problems, whereas genotype 2/3 was linked to DM and stroke. Conclusion: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in diabetic patients by affecting the lipid profile.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

In a context of increasingly necessary energy transition, precise modelling of profiles for low-voltage (LV) network consumers is crucial to enhance hosting capacity. Typically, load curves for these consumers are estimated through measurement campaigns conducted by Distribution System Operators (DSO) for a representative subset of customers or through the aggregation of load curves from household appliances within a residence. With the instrumentation of smart meters becoming more common, a new approach to modelling profiles for residential customers is proposed to make the most of the measurements from these meters. The disaggregation model estimates the load profile of customers on a low-voltage network by disaggregating the load curve measured at the secondary substation level. By utilizing only the maximum power measured by Linky smart meters, along with the load curve of the secondary substation, this model can estimate the daily profile of customers. For 48 secondary substations in our dataset, the model obtained an average symmetric mean average percentage error (SMAPE) error of 4.91% in reconstructing the load curve of the secondary substation from the curves disaggregated by the model. This methodology can allow the estimation of the daily consumption behaviors of the low-voltage customers. In this way, we can safely envision solutions that enhance the grid hosting capacity.

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. To solve this difficulty, we analyzed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from non-host environments. MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. Results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species to the exception of P. polonicum. Yet, 6 strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, the P. versatile species, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. Analysis of P. versatile strains revealed that this species is endemic all over the world on various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from fresh water environment. Our work also revealed new host plants for several Pectobacterium spp.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

The Leguminosae (legume family) is divided into three sub-families, the Caesalpiniodeae, Mimosoideae and Papilionoideae. Here, the literature on legume-rhizobia symbioses was reviewed, and genotypically characterised rhizobia related to the taxonomy of the legumes they were isolated from. Only data from field soils were considered. The objective of the work was to assess to what extent legume specificity for rhizobial symbiont is related to legume taxonomy. Bradyrhizobium spp. were the exclusive rhizobial symbionts of species in the Caesalpinioideae but data are limited. Where tested, species within the two Mimosoideae tribes, Ingeae and Mimoseae were nodulated by different rhizobial genera. Generally, Papilionoideae species with indeterminate nodules were promiscuous in relation to rhizobial symbionts but high specificity for rhizobial partners appears to hold at tribe level for the Fabeae (Rhizobium spp.), genus level for Medicago (Ensifer spp.), Cytisus (Bradyrhizobium spp.) and Lupinus (Bradyrhizobium spp.), and species level for Galega spp. (Neorhizobium galegeae), Hedysarum coronarium (Rhizobium sullae), Cicer arietinum (Mesorhizobium spp.) and New Zealand native Sophora spp. (Mesorhizobium spp.). High legume specificity for rhizobial symbionts was linked to specific rhizobial symbiosis genes. For Papilionoideae species with determinate nodules, the Dalbergieae were primarily nodulated by Bradyrhizobium but were promiscuous with respect to Bradyrhizobium spp. while those in the Desmodieae, Phaseoleae, Psoraleae and Loteae were promiscuous across different rhizobial genera. Possible advantages and disadvantages of high specificity or promiscuity are discussed.

There have been beaching events of the marine alga pelagic sargassum in coastal regions of the Caribbean Sea, West African countries, and the north-northeast region of Brazil since 2011. Its presence has caused environmental and socioeconomic impacts while several studies were conducted in order to understand the causes of this phenomenon, as well as alternatives to mitigate its impacts. The objective of this research was to evaluate pelagic sargassum biomass as a raw material for the manufacture of medium-density multilayer particleboards. These are composed of 30% sargassum particles in their inner layer and 70% sugarcane bagasse particles on their outer layers which are bonded with castor oil-based polyurethane resin. A physical and chemical characterization was carried out in order to evaluate sargassum particles while physical and mechanical tests were carried out in order to evaluate the panels. Results were subsequently compared with indications from NBR 14810-2:2018 and ISO 16893:2016 standards. A life cycle assessment based on ISO 14040:2006 and 14044:2006 was carried out as to complement the feasibility study of these panels and to compare their different manufacturing processes. The multilayer panels met the minimum requirements for physical and mechanical properties established by regulations, indicating that the Sargassum spp. biomass can be used as filling. The life cycle assessment study indicates that sargassum panels produced in the Belém-PA-Brazil region present lower environmental impacts in four of seven evaluated categories when compared to conventional panels. As such, they constitute an alternative way to mitigate environmental impacts generated by beaching events.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

The Eurasian grapevine (Vitis vinifera L.) is the most widely grown horticultural crop in the world and is important for the economy of many countries. In the wine production chain, grape varieties play an important role as they directly influence the authenticity and classification of the product. Identifying the different grape varieties is therefore fundamental for quality control and inspection activities, as well as for regulating production. Currently, ampelography and molecular analysis are the main approaches to identifying grape varieties. However, both methods have limitations. Ampelography is subjective and prone to errors and is experiencing enormous difficulties as ampelographers are increasingly scarce. On the other hand, molecular analyses are very demanding in terms of cost and time. In this scenario, Deep Learning (DL) and Machine Learning (ML) methods have emerged as a classification alternative to deal with the scarcity of ampelographs and avoid molecular analyses. In this study, the most recent and current methods for identifying grapevine varieties using DL classification-based approaches are presented through a systematic literature review. The classification pipeline of the 31 studies found in the literature was described, highlighting its pros and cons. Most of the studies used DL-based models trained with leaf images acquired in a controlled environment at a maximum distance of 1.2 metres to classify grape varieties. In addition, there is a large gap between practical applications and the datasets used: a great lack of varieties, limited data acquired in the field and a lack of tests on plants under adverse conditions. Potential directions for improving this area of research were also presented.

Woodland strawberry (Fragaria vesca L.) is an underutilized plant species, appreciated by consumers for its qualitative features. Utilizing technical means of production, such as plant biostimulants, that can increase crop productivity and quality could be highly important in woodland strawberry cultivation. The scope of the present study was to appraise the influence of two biostimulants (Trichoderma atroviride and plant protein hydrolysate) - used either alone or combined - on plant performance and economic profitability of two woodland strawberry genotypes (‘Alpine’ and ‘Regina delle Valli’). Overall, data showed that ‘Alpine’ had the highest productive performances, whereas ‘Regina delle Valli’ revealed the highest fruit qualitative traits. T. atroviride inoculation and V-PH application significantly boosted plant marketable yield (+20.5% for T. atroviride and +12.9% for V-PH), total sugars (+1.9% for Trichoderma and +1.4% for V-PH) and anthocyanins (+14.1% for T. atroviride and +9.8% for V-PH) compared to non-treated plants. Plants supplied with both biostimulants had higher marketable yield (+34.8%), mean fruit weight (+6.0%), fruit dry matter (+13.8%), total sugars (+3.5%), ascorbic acid (+12.7%), flavonoid (+26.3%) and anthocyanins (+29.9%) compared to non-treated plants. Furthermore, our study revealed that the highest fruit polyphenols concentration was recorded in both genotypes treated with the combination of biostimulants and in ‘Regina delle Valli’ sprayed with V-PH, whereas the highest antioxidant activity was found in ‘Regina delle Valli’ fruit when plants were supplied with both biostimulants. Our study pointed out that the application of microbial and non-microbial biostimulants, especially in combination, might be an useful strategy for improving performances of underutilized species and, therefore, encourage its cultivation, valorisation and economic profitability (+10195.3 €/ha when plants were exposed to both biostimulants).

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful in discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NET), calprotectin, DNase plasma levels by ELISA, and a panel of pro-inflammatory cytokines by ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and more in hospitalized than non-hospitalized ones. C5a and sC5b-9, and other acute phase proteins correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NET, and neopterin are important proinflammatory parameters potentially useful in discriminating between COVID-19 patients at risk for hospitalization.

Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori. H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and miti-gating the burden of this life-threatening disease. This review aims to provide an overview of our current under-standing of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

This study assesses attitudes of young adults' (18-30 years old) consumption on local and traditional products in7 European countries. A clustered sample (n=836) from natives of Greece, Bulgaria, Romania, Slovenia, Croatia, Denmark and France was collected, by distributing questionnaires through social media and university mail services. Sample was examined by implementing Principal Component Analysis (PCA) in three different samples; overall and two subgroups, Eastern and Western European countries. Six major factors revealed: consumer behavior, health issues, cost, influence from media and close environment and availability on store. As a result, young adults have a positive attitude to local and traditional food products but they express insecurity for health issues. Cost factor influences less people from Eastern European countries than those from the overall sample (3rd and 5th factor accordingly). Influence of close environment is a different factor in Eastern countries comparing to Western ones that it common with influence from media. Females and older people (25-30 years old) doubt less about TFPs, while media have high influence on consumers’ decisions. Aim of this survey is to create consumer profiles of young adults and create different promotion strategies of local and traditional products among the two groups of countries.

Conservation of wildlife depends on precise and unbiased knowledge on the abundance and distribution of species. It is challenging to choose appropriate methods to obtain a sufficiently high detectability and spatial coverage matching the species characteristics and spatiotemporal use of the landscape. In remote regions, such as in the Arctic, monitoring efforts are often resource-intensive and there is a need for cheap and precise alternative methods. Here, we compare an uncrewed aerial vehicle (UAV; quadcopter) pilot-survey of the non-gregarious Svalbard reindeer to traditional population abundance surveys from ground and helicopter to investigate whether UAVs can be an efficient alternative technology. We found that the UAV survey underestimated reindeer abundance compared to the traditional abundance surveys when used at management relevant spatial scales. Observer variation in reindeer detection on UAV imagery was influenced by the RGB greenness index and mean blue channel. In future studies, we suggest to test long-range fixed-wing UAVs to increase the sample size of reindeer and area coverage and incorporate detection probability in animal density models from UAV imagery. In addition, we encourage focus on more efficient post-processing techniques, including automatic animal object identification with machine learning and analytical methods that account for uncertainties.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

The growing attention for plug-in electric vehicles, and the associated high-performance demands, have initiated a development trend towards highly efficient and compact on-board battery chargers. These isolated ac-dc converters are most commonly realized using two conversion stages, combining a non-isolated power factor correction (PFC) rectifier with an isolated dc-dc converter. This, however, involves two loss stages and a relatively high component count, limiting the achievable efficiency and power density and resulting in high costs. In this paper a single-stage converter approach is analyzed to realize a single-phase ac-dc converter, combining all functionalities into one conversion stage and thus enabling a cost-effective efficiency and power density increase. The converter topology consists of a quasi-lossless synchronous rectifier followed by an isolated dual active bridge (DAB) dc-dc converter, putting a small filter capacitor in between. To show the performance potential of this bidirectional, isolated ac-dc converter, a comprehensive design procedure and multi-objective optimization with respect to efficiency and power density is presented, using detailed loss and volume models. The models and procedures are verified by a 3.7 kW hardware demonstrator, interfacing a 400 V dc-bus with the single-phase 230 V, 50 Hz utility grid. Measurement results indicate a state-of-the-art efficiency of 96.1% and power density of 2.2 kW/dm³, confirming the competitiveness of the investigated single-stage DAB ac-dc converter.

Regeneration is crucial for forest continuity in natural and managed stands. Analyzing intra-annual dynamics improves the understanding between growth and climate, identifying survival thresholds. The objective was to determine microclimate constraints (rainfall, air and soil temperatures) over Nothofagus antarctica regeneration growing at closed, open, and edge forests in Patagonia. We measured stand characteristics (forest structure, understory, soil properties, animal use), microclimate, and daily growth of regeneration using dendrometers (n = 6) during two growing seasons. We found significant differences in the studied variables (e.g. overstory, light, soil, understory, animal use). These changes defined microclimate across overstory gradient (e.g. soil moisture), influencing the daily growth across seasons (lag, exponential, stationary). Rainfall influenced more than temperature. Daily growth in closed forests indicating shrinkage (-0.0082 mm day-1 without rain, and -0.0008 mm day-1 with 0.0-0.2 mm day-1 rainfall), while above 0.2 mm day-1 rainfall, growth always increased. Open forests presented shrinkage during days without rain (-0.0051 mm day-1), showing positive growths according rainfall. Edge forests always presented positive daily growths. The resilience of regeneration under these changed conditions was related with overstory. Main outputs indicated that regeneration was vulnerable during non-rainy days, suggesting the needs of long-term monitoring to develop better silvicultural proposals.

Isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was obtained 95% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction at room temperature for 190 minutes in dichloromethane. The structure of isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was established by NMR, FTIR, and the high resolution of mass spectroscopies. In vitro sun protection factor evaluation exhibited value of 37.10 ± 0.03 which indicates that isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) as a sunscreen agent with high protection.

The Universe has a gravitational horizon with a radius R_h = c/H coincident with that of the Hubble sphere. This surface separates null geodesics approaching us from those receding, and as free-falling observers within the Friedmann-Lemaitre-Robertson-Walker spacetime, we see it retreating at proper speed c, giving rise to the eponymously named cosmological model R_h = ct. As of today, this cosmology has passed over 20 observational tests, often better than LCDM. The gravitational radius R_h therefore appears to be highly relevant to cosmological theory, and in this paper we begin to explore its impact on fundamental physics. We calculate the binding energy of a mass m within the horizon and demonstrate that it is equal to mc². This energy is stored when the particle is at rest near the observer, transitioning to a purely kinetic form equal to the particle's escape energy when it approaches R_h. In other words, a particle's gravitational coupling to that portion of the Universe with which it is causally connected appears to be the origin of rest-mass energy.

The purpose of this study is to find out the e-reputation management of the hotel industry, as well as the social media channels used as the tools of hotel e-reputation building. This study used a qualitative approach by analyzing the in-depth interviews with hotel marketing communication practitioners of 15 hotel companies in Bandung City. The findings identified that e-reputation is considered a crucial factor in determining hotel performance due to the change of customers’ behaviors today and identified also three types of e-reputation management activities implemented by hotel companies, such as online activities, offline activities, and online/offline activities. The results of this study have implications for the hospitality industry, as a reference for formulating their marketing strategies.

Nanotechnology has become a popular topic in agricultural and animal research, generating sig-nificant global interest. Nanoparticles (NPs)-enabled agriculture and animal husbandry (AHs) products have three main principles: crop production, protection, and nutrient enrichment. Re-search on this topic has grown exponentially in recent years, with an increasing number of peer-reviewed literature and patents on NPs-enabled agriculture and AH products. This study examines and collects data on the various applications of NPs-enabled agricultural products for crop production, protection, and livestock improvement from the core nanotechnological database. The search returned several types of NPs and products used in agriculture and AH, countries that utilize these products at a commercial level, and analysis of these data by phyton, R-statistical software. Our findings show remarkable growth of nanotechnology in agriculture, AH, and re-search fields for future sustainability goals in the era of climate change

The criteria of “Distinctness, Uniformity and Stability” as well as a high "overall quality index” are used to register the Italian modern varieties to the national register. Differently, local conservation varieties can be certified under different EU Directives having, as overall objective, the preservation of biodiversity and the containment of genetic erosion. In recent years, products derived from an-cient grains are perceived to be healthier and more sustainable by consumer, especially in Italy, with consequent higher market prices. Ancient tetraploid wheat varieties registered in the national reg-ister of conservation varieties are 28, 24 of which are Sicilian. They are supposed to have a wide genetic variability compared to modern ones, making them vulnerable of fraud because they are difficult to trace. It is therefore important to have tools able to discriminate the autochthonous Si-cilian varieties. This can be done by gluten proteins composition, which also gives information on the technological properties of derived products. Fifty-one accessions belonging to 22 ancient va-rieties of Sicilian tetraploid (mostly durum) wheat were analyzed. Although a wide intra-accession and intra-varietal variability was assessed, the gliadin pattern of bulks of seeds belonging to each variety was discriminatory. Moreover, differences in technological attitudes were found between landraces. This paves the way to use gluten protein patterns for traceability allowing local farmers and producers to valorize their products and assure consumers about the transparency of the entire supply chain.

As AI models become more and more common in business and even in our daily lives, it is important to understand what the carbon impact of these models is. Recent papers have shown that this impact can be quite great, i.e., the training of a single high-end model can result in emissions of more than 500t of CO2eq. In this paper we discuss the factors that influence the carbon footprint of AI models, explore what impact different decisions have, and show how the footprint can be reduced. We also examine the footprint of different models to give a guideline on how urgent action is for different organizations.

Social and spatial characteristics of a population often interact to influence health outcomes, suggesting a need to jointly analyze both to offer useful insights in community health. However, researchers have used either social or spatial analyses to examine community-based health issues and inform intervention programs. We propose a combined socio-spatial analytic approach to develop a social network with spatial weights and a spatial statistic with social weights, and apply them to an ongoing study of mental and physical well-being of rural Latino immigrants in North Florida, USA. We demonstrate how this approach can be used to calculate measures, such as social network centrality, support contact dyads, and spatial kernel density based on a health survey data. Findings reveal that the integrated approach accurately reflected interactions between social and spatial elements, and identified community members (who) and locations (where) that should be prioritized for community-based health interventions.

Maternal obesity is increasingly prevalent and is associated with elevated morbidity and mortality rates in both mothers and children. As the interface between the mother and fetus, the placenta has mediates the impact of the maternal environment on fetal development. Most of the literature data on the effects of maternal obesity on placental functions do not exclude potential confounding factors like metabolic diseases (e.g. gestational diabetes). Moreover, it is now clear that the placental response to maternal environment depends on the fetal sex. In this context, we reviewed how maternal obesity (in the absence of gestational diabetes) affects the human placenta in terms of (i) endocrine function, (ii) morphological characteristics, (iii) nutrient exchanges and metabolism, (iv) inflammatory/immune status, (v) oxidative stress, and (vi) transcriptome, with a focus on fetal sex specificities. A better understanding of sex-specific placental responses to maternal obesity is crucial for improving pregnancy outcomes and the health of mothers and children.

Volatile organic compounds (VOCs) released from plants have been correlated with disease-status. Analysis of VOCs using GC-MS is time-consuming, laboratory-based, and requires specialist training. Electronic nose devices (E-nose) provide a portable alternative. Three different E-nose devices were compared to assess how accurately they could detect Mango Twig Tip Dieback and Panama disease in banana. The devices were initially trained on known volatiles, then pure cultures of Pantoea sp., Staphylococcus sp., and Fusarium odoratissimum, and finally, on infected and healthy mango leaves and field-collected, infected banana pseudo-stems. The experiments were repeated three times with six replicates for each host-pathogen pair. The variation between healthy and infected host materials was evaluated by principal component and linear discriminant analysis, cross-validation and chemometric data analysis. GC-MS analysis was conducted contemporaneously and identified an 80% similarity between healthy and infected plant material. The portable C 320 was 100% successful in discriminating known volatiles but had a low capability in differentiating healthy and infected plant substrates. The advanced devices (PEN 3 / MSEM 160) successfully detected healthy and diseased samples with a high variance. The results suggest that E-nose devices are more sensitive and accurate in detecting changes of VOCs between healthy and infected plants compared to headspace GC-MS.

This paper addresses the conceptual exploration of various issues that form an integral part of the ethical dimensions surrounding the use of artificial intelligence (AI) in the field of marketing. We critically review some of the main ethical challenges AI poses to humanity: privacy, data security, bias, transparency, and accountability. Therefore, we will discuss the delicate balance between exploiting the transformation potential of AI for personally designed marketing strategies and ethical imperatives to safeguard the rights of consumers to retain trust. Then, the present regulatory landscape responding to these ethical challenges will be assessed by building on effective regulation, like the GDPR, existing proposed legislative frameworks, and industry guidelines. To underscore the role of an ongoing dialogue between marketers, technologists, ethicists, and regulators for developing a responsible AI ecosystem in marketing. Further, strategic recommendations for implementing company-based ethical AI marketing practices. The further strong guidelines provide enhancement transparency to consumers and investment in research to remove biases from algorithms. It also underscores principal scopes of further research and development, focusing on the need for new-age solutions to guide the ethical quagmires that AI-led marketing throws up. We suggest that integration should be done proactively and collaboratively. Thus, if attention is paid more to ethics and multidisciplinary dialogue, only such hyperbolic promises can be realized by AI-driven marketing. There are such promises through which AI-driven marketing will meet business goals and be huge at societies' values.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a treatment for Friedreich Ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted this pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Thirty-five patients were stratified into 3 severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T-4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T+4). Etravirine was well tolerated. Etravirine completely stopped the progression of the SARA score during the 4-months treatment period, compared to the 4 months pre and post treatment. It increased peak workload, while the improvement of peak oxygen uptake was not statistically significant. No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. In this open trial etravirine significantly improved neurological function and was generally safe and reasonably tolerated. This suggests that etravirine represents a potential therapeutic agent in FRDA deserving testing in a randomized placebo controlled clinical trial.

Gut microbiota affects progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg Lpps /L, but not 0.25 and 1mg Lpps/L significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. Arthritis index (AI) was also reduced in CAIA mice. In CIA protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher caecal and colon E. coli and lower caecal L.murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA protected mice triggered by LPS secreted higher Il-10 than control ones. However, higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs recruitment. Labeled bacteria with Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16h post-gavage but not in Peyer’s patches and spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24h. FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.

Combined awareness about the power and limitations of bioinformatics and molecular biology enables advanced research based on high-throughput data. Despite an increasing demand for scientists with a combined background in both fields, the education in dry lab and wet lab is often separated. This work describes an example of integrated education with focus on genomics and transcriptomics. Participants learn computational and molecular biology methods in the same practical course. Peer-review is applied as a teaching method to foster cooperative learning of students with heterogeneous backgrounds. Evaluation results indicate acceptance and appreciation of this approach.