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Abstract NVA1309 is a non-brain penetrant next-generation gabapentinoid shown to bind Cavα2δ at R243 within a triple Arginine motif forming the binding site for gabapentin and pregabalin. In this study we have compared the effects of NVA1309 with Mirogabalin, a gabapentinoid drug with higher affinity for the voltage-gated calcium channel subunit Cavα2δ-1 than pregabalin which is approved for post-herpetic neuralgia in Japan, Korea and Taiwan. Both NVA1309 and mirogabalin inhibit Cav2.2 currents in vitro and decrease Cav2.2 plasma membrane expression with higher efficacy than pregabalin. Mutagenesis of the classical binding residue arginine R243 and the newly identified binding residue lysine K615 reverse the effect of mirogabalin on Cav2.2 current, but not that of NVA1309.

Abstract Introduction Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. Methods The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). Results Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach’s alpha = 0.96) and test-retest reliability (Intraclass Correlation Coefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53–0.64) and significant differences between severity groups (p

Raw goat and ewe’s milk samples were used for the isolation of seven lactic acid bacteria new strains. After testing hemolytic activity and resistance to antibiotics, specific functional properties were evaluated; Lactococcus lactis subsp. lactis FBM_1321 and Lacticaseibacillus paracasei FBM_1327 strains resulted in the highest cholesterol assimilation percentages ranging from 28.78 to 30.56%. In addition, strong adhesion capacity to differentiated Caco-2 cells (1.77–21.04%) was mapped, and the lactobacilli strains exhibited strong antagonistic activity against foodborne pathogens compared to lactococci. The strains were able to grow at low pH and high NaCl concentrations, conditions that prevail in food systems (cell counts ranged from 1.77 to 8.48 log CFU/mL after exposure to pH 3 and from 5.66 to 9.52 log CFU/mL after exposure to NaCl concentrations up to 8%). As a next step, freeze-dried immobilized Lc. paracasei FBM_1327 cells on oat flakes were used for the preparation of functional yoghurt and ayran products. Cell loads of the functional strain remained high and stable in both products (7.69 log CFU/g in yoghurt and 8.56 log CFU/g in ayran after 30 days of storage at 4 °C) throughout their shelf life. No significant changes in the volatile profile were noticed, and the new products were accepted by the panel during the sensory evaluation.

In this study, we introduce a versatile and scalable optimization tool designed to address several critical project management needs. Our aim is to provide project managers with a robust decision support system that enhances and streamlines decision-making processes. Building upon our previously proposed global scheme—which optimizes project schedules by adjusting dates to match each task’s optimal period—we introduce a novel local scheme. This innovative addition leverages a Machine Learning pipeline, specifically utilizing the Silverkite algorithm, to facilitate long-horizon forecasting. By synergistically combining global and local optimization strategies, we elevate project management efficiency, maximizing potential benefits. This tool is equipped to handle a wide array of variables, offering real-time, consultative support throughout the project’s lifecycle. Through the demonstration of various scenarios, we showcase the effectiveness and adaptability of our optimization tool, underscoring its value in contemporary project management contexts.

An unsustainable rate of resource production and consumption is evident in urban environments. The absence of innovative approaches in conjunction with the exponential urbanization and expansion of the global population will inevitably result in substantial environmental consequences. There are two emerging alternatives: circular economy (CE) and urban metabolism (UM). The integration of these principles into novel methodology casts doubt on the linear model of contemporary economic and urban systems, which includes extraction, production, utilization, and disposal. In the development of a distinctive urban framework known as circular urban metabolism, the current study has illustrated the application of these principles. We design this study to motivate urban planners and decision-makers to investigate, develop, and supervise ecologically sustainable cities. Scholars from a variety of academic disciplines, intrigued by the intricacies of urban planning, design, and administration, can foster interdisciplinary collaboration in the circular urban metabolism (CUM) region. To address the research question, we implemented a bibliometric analysis, which involved the examination of 627 pertinent research papers, utilizing the R (R 3.6.0+) statistical programming language. The results emphasize the fundamental characteristics and significance of CUM in the management of refuse. In addition, the findings underscore the importance of creating a novel framework that incorporates the principles of urban political ecology, CUM, sustainability, and the novel dimension of waste metabolism. It is the goal of this framework to emphasize the significance of recycling in the informal sector as a waste management strategy in low- and medium-income countries (LMICs).

Abstract Introduction Lichen planus (LP) is an inflammatory skin disorder that can present in various forms across the body, including lesions on the skin (cutaneous LP [CLP]), scalp (lichen planopilaris [LPP]) and mucosal regions (mucosal LP [MLP]). Several existing patient-reported outcome measures (PROMs) were identified for potential use in LP clinical development programs. This study aimed to assess the content validity and psychometric measurement properties of the Dermatology Life Quality Index (DLQI), Epworth Sleepiness Scale (ESS), Scalpdex and Oral Lichen Planus Symptom Severity Measure (OLPSSM) in an LP population. Methods Patients completed the PROs at various time points as part of an international Phase 2 clinical study in adults with MLP (n = 37), LPP (n = 37) and CLP (n = 37). Test-retest reliability, construct validity and sensitivity to change were assessed. In addition, qualitative cognitive debriefing interviews were conducted with adults with MLP (n = 20), LPP (n = 19) and CLP (n = 19) in the USA and Germany to examine the PROM content validity. Results The DLQI demonstrated adequate reliability and validity, although its ability to detect change was modest and most items were considered not relevant in qualitative interviews. The ESS had good reliability but limited evidence of validity and ability to detect change. Conceptual relevance varied according to the qualitative interview data. The Scalpdex was miscellaneous across domains, but the ‘Symptoms’ domain performed well overall. Overall, Scalpdex concepts were reported as relevant by most LPP patients interviewed. The OLPSSM demonstrated good psychometric properties and strong evidence of content validity. Conclusions The psychometric and qualitative findings support the use of the OLPSSM and Scalpdex within specific LP subtypes but cautioned use of the DLQI. Administration of the ESS is not recommended in LP because of its poor psychometric performance. Given these limitations, further validation of non-specific disease measures is needed and/or the development of additional LP-specific PROMs. Trial Registration NCT04300296.

IntroductionCanine osteoarthritis (OA) causes pain and mobility impairment. This can reduce dog quality of life (QoL), owner QoL and owners’ satisfaction with, and adherence to, treatments. No existing canine OA-specific instrument assesses all three impacts. This study aimed to develop and psychometrically evaluate an owner-completed canine OA-specific measure of dog QoL, owner QoL and owner treatment satisfaction; the “Canine OA Quality of Life and Treatment Satisfaction Questionnaire” (CaOA-QoL-TS).MethodsThe CaOA-QoL-TS was developed using a conceptual model derived from a meta-synthesis of published literature followed by cognitive interviews with ten owners of dogs with OA, to evaluate content validity.ResultsBased on interview findings, ten items were reworded, four removed, and two added; resulting in 26 items that all owners understood and considered relevant. The recall period and response options were well understood and appropriate to almost all owners. To evaluate its psychometric properties, the CaOA-QoL-TS (draft 26-item version) was administered, across six timepoints in a phase 4 field study, to owners of OA treated dogs, recruited from veterinary practices (N = 93). Inter-item correlations suggested items clustered into three distinct domains: Dog QoL, Owner QoL and Treatment Satisfaction, as hypothesized. Confirmatory factor analysis supported deletion of two items and calculation of the three domain scores, with acceptable model fit. The resulting 24-item CaOA-QoL-TS instrument demonstrated strong internal consistency and good to excellent test–retest reliability. Convergent validity was supported by moderate to strong correlations with concurrent measures. Known groups validity was supported by statistically significant differences between groups categorized by owner global impression of QoL. Ability to detect change was demonstrated through statistically significant improvements over time in Owner and Dog QoL, with larger within-group effect sizes reported for the mean of ‘improved’ dogs compared to the mean of ‘stable’ dogs. Only a small sample of dogs worsened throughout the study. Anchor-based analyses supported-0.9 and-1.0-point within-group responder definitions for dog and owner QoL domains, respectively.DiscussionFindings support the content validity of the CaOA-QoL-TS in canine OA. The 24-item CaOA-QoL-TS is a reliable and valid instrument to measure owner and canine QoL and TS and is sensitive to improvements following OA treatment.

The AMP‐activated protein kinase (AMPK)‐related kinase NUAK1 (NUAK family SNF1‐like kinase 1) has emerged as a potential vulnerability in MYC‐dependent cancer but the biological roles of NUAK1 in different settings are poorly characterised, and the spectrum of cancer types that exhibit a requirement for NUAK1 is unknown. Unlike canonical oncogenes, NUAK1 is rarely mutated in cancer and appears to function as an obligate facilitator rather than a cancer driver per se. Although numerous groups have developed small‐molecule NUAK inhibitors, the circumstances that would trigger their use and the unwanted toxicities that may arise as a consequence of on‐target activity are thus undetermined. Reasoning that MYC is a key effector of RAS pathway signalling and the GTPase KRAS is almost uniformly mutated in pancreatic ductal adenocarcinoma (PDAC), we investigated whether this cancer type exhibits a functional requirement for NUAK1. Here, we show that high NUAK1 expression is associated with reduced overall survival in PDAC and that inhibition or depletion of NUAK1 suppresses growth of PDAC cells in culture. We identify a previously unknown role for NUAK1 in regulating accurate centrosome duplication and show that loss of NUAK1 triggers genomic instability. The latter activity is conserved in primary fibroblasts, raising the possibility of undesirable genotoxic effects of NUAK1 inhibition.

Family businesses have distinct characteristics that differentiate them from other firms. Researchers must meticulously analyze issues, with a specific focus on the interplay of family business dynamics, considering this factor. The main objective of this research was to provide insight into the adverse effects of family companies, particularly how the power dynamics inside these organizations might enable corruption or fraud and how corporate governance can help in mitigating these phenomena. Specifically, family businesses can be investigated by considering unique characteristics such as ownership and control, generational dynamics, and corporate governance. To address the study topic, a bibliometric analysis was conducted using the R statistical programming language and the bibliometric tools Biblioshiny and VOSviewer. Data were obtained from the Scopus database and examined in documents. The lack of unbiased external evaluation, the ineffectiveness of internal audits, disputes between different generations, the dominance of family members, and the narrow extent of governance all contribute to the exacerbation of tensions that promote corruption inside family firms. Moreover, the findings indicate that CEO duality correlates with the occurrence of corruption and fraudulent activities, such as manipulating profits. Furthermore, the findings suggest a correlation between the qualities of the board and instances of corruption and bribery inside family firms. These factors also increase the probability of financial statement fraud.

Background/Objectives: Failure to thrive (FTT) is mostly caused by insufficient consumption of nutrient-rich food, recurrent infections like diarrhea and intestinal worms, substandard caregiving practices, and limited availability of health and other vital services. Furthermore, there was a correlation between the educational level of mothers and the occurrence of FTT in children aged 6–12 months. Thus, the objective of the current research is twofold: (i) to investigate other factors related to FTT and (ii) to evaluate the impact of them on FTT in Sub-Saharan African countries and their urban areas. Methods: We used weight entropy and TOPSIS methods to approach the research question. In particular, the entropy-weight method is effective for precisely evaluating the relative significance of the selected criteria for TOPSIS computation. Thus, data were retrieved from the database of UNICEF for the year 2019 for nine Sub-Saharan countries, and based on the methods used, five criteria have been selected for consideration. Those of mothers in higher education were identified as having a higher weight, which means that this can affect positively the ability of mothers to mitigate the situation of FTT and protect their children. Results: The findings of the study highlight the factors of maternal education at a higher level and unhealthy habits as those with the greatest weight and impact on the FTT. Moreover, the results indicate that the association between maternal education, and especially higher education, and FTT is stronger in Ethiopia. Despite the limited amount of research on the specified relationship in Sub-Saharan countries, this study is among the initial ones to examine it. Conclusions: The current study can aid policymakers in devising appropriate policies and implementing effective measures to tackle FTT in Sub-Saharan Africa, like enhancing the number of mothers in these countries to be integrated into the educational system to help both themselves and their children mitigate or avoid the symptoms of FTT.

The emerging of green entrepreneurship and digital transformation improve businesses’ efficiency and meet consumers’ demand for environmentally sustainable products, reducing the environmental footprint and strengthening corporate responsibility to society. Moreover, the COVID-19 pandemic has become a key event changing our lives while businesses have to change their daily operations and working from home has become the norm. So, it is possible to say that business activities and business models have undergone some form of digital transformation due to the COVID-19 pandemic. In Greece, the Food Industry can be characterized as one of the most dynamic and competitive economic sectors which is distinguished for its growth prospects. The aim of this study is twofold: (i) to investigate the impact of green entrepreneurship and digital transformation into the performance of Greek SMEs in the food sector and (ii) to highlight the new trends integrated in new business models in the sector. To meet the research purpose, a bibliometric and co-citation analysis was used based on the R package and graphene as a subject of research for bibliometric analysis. The knowledge gained in this article shows how the digital transformation changed the functioning of the companies in the food industry. The conclusions of this article are mainly for the enterprises that are considering their own digitalization, which contributes to the long-term sustainability of them.

Osteoarthritis (OA) is a degenerative disease of the joints that affects greatly the elderly population and the health care systems and is on the increase due to aging and obesity. Interventions aim at palliative care and pharmaceutical therapies entail serious adverse events. Whereas polyphenols constitute a promising holistic approach in the arsenal of physicians, trials investigating biomarkers and questionnaires are scarce. As such, a randomized controlled trial (RCT) was conducted to evaluate the potency of a standardized polyphenolic supplement in the management of systemic inflammation, oxidative stress, pain and general quality of life (QoL) in patients with osteoarthritis. Sixty subjects were randomized to receive either a polyphenol supplement (curcuma phospholipid, rosemary extract, resveratrol, ascorbic acid), or an active comparator (ascorbic acid) twice, daily for 12 weeks. The group that received the polyphenols exhibited significantly lower symptoms of pain and improved physical function and QoL as it was depicted by validated questionnaires, compared to the control group. Furthermore, post intervention, inflammation was restrained in the polyphenol group. Since systemic inflammation promotes local inflammation, the decrease of pain herein might be attributed to the attenuation of systemic inflammation by the polyphenols.

Vitis vinifera, an economically significant grapevine species, is known for wine, juice, and table grape production. The berries of wine grapes host a diverse range of microorganisms influencing both grapevine health and the winemaking process. Indigenous to Greece, the emblematic variety Assyrtiko, renowned for high-quality white wines, originated from Santorini and spread to various Greek regions. Despite existing studies on the microbiota of several varieties, the carposphere microbiota of Assyrtiko grapes remains unexplored. Thus, we conducted a spatiotemporal metagenomic study to identify the epiphytic microbial community composition of Assyrtiko grapes. The study was conducted in two consecutive vintage years (2019 and 2020) across three different and distinct viticulture regions in Greece (Attica, Thessaloniki, Evros). We performed amplicon sequencing, targeting the 16S rRNA gene for bacteria and the ITS region for fungi, with subsequent comprehensive bioinformatic analysis. Our data indicate that the distribution and relative abundance of the epiphytic carposphere microbial communities of the Assyrtiko variety are shaped both by vintage and biogeography.

Sweet basil is a popular culinary herb used in many cuisines around the world and is widely grown commercially for retail as a live potted plant. However, basil is easily damaged by temperatures below 12 °C meaning plants must be transported from the grower to the retailer in a warm transport chain, adding considerable commercial cost in temperate countries. Improvement of chilling tolerance has been demonstrated in post-harvest crops such as tomato fruits and, indeed, fresh cut basil, by manipulation of the red:far red ratio of light provided to plants throughout the photoperiod and for a significant duration of the growing process in controlled environment chambers. We tested the effectiveness of periodic short-duration end-of-production supplementary far red light treatments designed for use with basil plants grown in a large scale commercial glasshouse for the live potted basil market. Four days of periodic, midday supplementary far red light given at end of production induced robust tolerance to 24 h of 4 °C cold treatment, resulting in greatly reduced visual damage, and reduced physiological markers of chilling injury including electrolyte leakage and reactive oxygen species accumulation. Antioxidant levels were also maintained at higher levels in live potted basil following this cold treatment. RNAseq-based analysis of gene expression changes associated with this response pointed to increased conversion of starch to soluble raffinose family oligosaccharide sugars; increased biosynthesis of anthocyanins and selected amino acids; inactivation of gibberellin signaling; and reduced expression of fatty acid desaturases, all previously associated with increased chilling tolerance in plants. Our findings offer an efficient, non-invasive approach to induce chilling tolerance in potted basil which is suitable for application in a large-scale commercial glasshouse.

In the last two decades, plant taxonomy has bloomed, following the development of a novel technique, namely, DNA barcoding. DNA barcodes are standardized sequences, ideally unique, coding or non-coding, either from the genome of the organism or from its organelles, that are used to identify/classify an organismal group; in short, the method includes amplification of the DNA barcode, sequencing and comparison with a reference database containing the relevant sequences from different species. In plants, the use a universal DNA barcode, such as COI, which is used in animals, has not been achieved so far. This review provides a comprehensive overview of the progress made in DNA barcoding within the field of plant taxonomy. It highlights the success of various barcode loci, the emergence of super barcodes from the chloroplast genome, and the overall impact of next-generation sequencing technologies on the field. The discussion of different approaches reflects the ongoing efforts to refine and optimize DNA barcoding techniques for plants, contributing to the advancement in our understanding of plant biodiversity.

As the food and pharmaceutical industry is continuously seeking new probiotic strains with unique health properties, the aim of the present study was to determine the impact of short-term dietary intervention with novel wild-type strains, isolated from various sources, on high-fat diet (HFD)-induced insulin resistance. Initially, the strains were evaluated in vitro for their ability to survive in simulated gastrointestinal (GI) conditions, for adhesion to Caco-2 cells, for bile salt hydrolase secretion, for cholesterol-lowering and cellular cholesterol-binding ability, and for growth inhibition of food-borne pathogens. In addition, safety criteria were assessed, including hemolytic activity and susceptibility to antibiotics. The in vivo test on insulin resistance showed that mice receiving the HFD supplemented with Pediococcus acidilactici SK (isolated from human feces) or P. acidilactici OLS3-1 strain (isolated from olive fruit) exhibited significantly improved insulin resistance compared to HFD-fed mice or to the normal diet (ND)-fed group.

Essential oils exhibit numerous medicinal properties, including antimicrobial, anti-inflammatory and antioxidant effects. Recent studies also indicate that certain essential oils demonstrate anti-amyloidogenic activity against β-amyloid, the protein implicated in Alzheimer’s disease. To investigate whether the anti-aggregating properties of essential oils extend to α-synuclein, the protein involved in Parkinson’s disease, we constructed and employed a whole-cell biosensor based on the split-luciferase complementation assay. We validated our biosensor by using baicalein, a known inhibitor of α-synuclein aggregation, and subsequently we tested eight essential oils commonly used in food and the hygienic industry. Two of them, citron and sage, along with their primary components, pure linalool (the main constituent in citron essential oil) and pure eucalyptol (1,8-cineole, the main constituent in sage essential oil), were able to reduce α-syn aggregation. These findings suggest that both essential oils and their main constituents could be regarded as potential components in functional foods or incorporated into complementary Parkinson’s disease therapies.

Abstract Background Socio-cultural perceptions surrounding death have profoundly changed since the 1950s with development of modern intensive care and progress in solid organ transplantation. Despite broad support for organ transplantation, many fundamental concepts and practices including brain death, organ donation after circulatory death, and some antemortem interventions to prepare for transplantation continue to be challenged. Attitudes toward the ethical issues surrounding death and organ donation may influence support for and participation in organ donation but differences between and among diverse populations have not been studied. Objectives In order to clarify attitudes toward brain death, organ donation after circulatory death and antemortem interventions in the context of organ donation, we conducted a scoping review of international English-language quantitative surveys in various populations. Study appraisal A search of literature up to October 2020 was performed, using multiple databases. After screening, 45 studies were found to meet pre-specified inclusion criteria. Results 32 studies examined attitudes to brain death, predominantly in healthcare professionals. In most, around 75% of respondents accepted brain death as equivalent to death of the person. Less common perspectives included equating death with irreversible coma and willingness to undertake organ donation even if it caused death. 14 studies examined attitudes to organ donation following circulatory death. Around half of respondents in most studies accepted that death could be confidently diagnosed after only 5 min of cardiorespiratory arrest. The predominant reason was lack of confidence in doctors or diagnostic procedures. Only 6 studies examined attitudes towards antemortem interventions in prospective organ donors. Most respondents supported minimally invasive procedures and only where specific consent was obtained. Conclusions Our review suggests a considerable proportion of people, including healthcare professionals, have doubts about the medical and ethical validity of modern determinations of death. The prognosis of brain injury was a more common concern in the context of organ donation decision-making than certainty of death.

A growing need for the development of novel hop (Humulus lupulus) varieties has emerged as a result of the increasing demand for beers with distinct organoleptic characteristics and the expected impact of climate change on hop cultivars. As the genetic variation in the existing hop cultivars is low, wild hop germplasm can be used as a source for the development of novel cultivars. In this work, we analyzed, for the first time, the genetic diversity of H. lupulus var. lupulus wild germplasm in Greece. A SNP-NGS genotyping approach using a set of nine specific genetic markers, was employed in order to determine individual genotypes and to perform population structure analyses of wild hops from a region with complex topography, namely the Region of Central Greece. Our results revealed low differentiation among populations, with the spatial genetic patterns observed relating mainly to topographical elements rather than geographic distance. Interestingly, within wild hop populations, high genetic diversity was observed, showing that in the region of Central Greece, wild H. lupulus germplasm has significant potential that can be exploited in breeding programs towards the development of local, well adapted and potentially superior hop varieties.

In the present work, a novel foam burner design is proposed and experimentally evaluated for operation with highly diluted syngas mixtures. The lab-scale burner consists of a purpose-built, square-shaped, high-temperature-grade stainless steel tubular reactor filled with square-sectioned siliconized silico carbide (SiSiC) foams. The assembly was installed in an electrical furnace. Spatially resolved temperature measurements were obtained along the reactor axis, while simultaneous measurements of CO, CO2, H2, O2, and N2 were taken at the burner exit and the water levels were recorded upstream and downstream of the reactor. The results clearly show that flames can be stabilized along the reactor for a range of foam characteristics and operating conditions. Hydrogen conversion efficiencies in excess of 98%, and overall thermal efficiencies close to 95% were achieved for the selected operating conditions. Overall, the denser 10 ppi foam demonstrated superior combustion characteristics in terms of stability, lower enthalpy rises, and a wider operating range at the expense of a very modest pressure drop penalty. Finally, scanning electron microscopy, coupled with energy dispersion spectroscopy (SEM/EDS) and Raman spectroscopy analyses, was used to determine the morphological and compositional characteristics of the pristine and aged foams. After more than 100 h of operation, no significant performance degradation was observed, even though the burner design was subjected to considerable thermal stress.

Background: Functional restoration of abdominal wall defects represents one of the fundamental challenges of reconstructive surgery. Synthetic grafts or crosslinked animal-derived biological grafts are characterized by significant adverse reactions, which are mostly observed after their implantation. The aim of this study was to evaluate the efficacy of the decellularization protocol to produce a completely acellular full-thickness abdominal wall scaffold. Methods: Full-thickness abdominal wall samples were harvested from Wistar rats and submitted to a three-cycle decellularization process. Histological, biochemical, and DNA quantification analyses were applied to evaluate the effect of the decellularization protocol. Mechanical testing and immunogenicity assessment were also performed. Results: Histological, biochemical, and DNA analysis results showed efficient decellularization of the abdominal wall samples after the third cycle. Decellularized abdominal wall scaffolds were characterized by good biochemical and mechanical properties. Conclusion: The data presented herein confirm the effective production of a rat-derived full-thickness abdominal wall scaffold. Expanding this approach will allow the exploitation of the capacity of the proposed decellularization protocol in producing acellular abdominal wall scaffolds from larger animal models or human cadaveric donors. In this way, the utility of biological scaffolds with preserved in vivo remodeling properties may be one step closer to its application in clinical studies.

Abracl (ABRA C-terminal-like protein) is a small, non-typical winged-helix protein that shares similarity with the C-terminal domain of the protein ABRA (Actin-Binding Rho-Activating protein). The role of Abracl in the cell remains elusive, although in cancer cells, it has been implicated in proliferation, migration and actin dynamics. Our previous study showed that Abracl mRNA was expressed in the dividing cells of the subpallial subventricular zone (SVZ), in the developing cortical plate (CP), and in the diencephalic SVZ; however, the molecular identities of the Abracl-expressing cell populations were not defined in that work. In this study, we use double immunofluorescence to characterize the expression of Abracl on sections of embryonic murine (E11.5-E18.5) and feline (E30/31-E33/34) telencephalon; to this end, we use a battery of well-known molecular markers of cycling (Ki67, Ascl1, Dlx2) or post-mitotic (Tubb3, Gad65/67, Lhx6 and Tbr1) cells. Our experiments show that Abracl protein has, compared to the mRNA, a broader expression domain, including, apart from proliferating cells of the subpallial and diencephalic SVZ, post-mitotic cells occupying the subpallial and pallial mantle (including the CP), as well as subpallial-derived migrating interneurons. Interestingly, in late embryonic developmental stages, Abracl was also transiently detected in major telencephalic fiber tracts.

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.

Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

The telencephalon develops from the alar plate of the secondary prosencephalon and is subdivided into two distinct divisions, the pallium, which derives solely from prosomere hp1, and the subpallium which derives from both hp1 and hp2 prosomeres. In this first systematic analysis of the feline telencephalon genoarchitecture, we apply the prosomeric model to compare the expression of a battery of genes, including Tbr1, Tbr2, Pax6, Mash1, Dlx2, Nkx2-1, Lhx6, Lhx7, Lhx2, and Emx1, the orthologs of which alone or in combination, demarcate molecularly distinct territories in other species. We characterize, within the pallium and the subpallium, domains and subdomains topologically equivalent to those previously described in other vertebrate species and we show that the overall genoarchitectural map of the E26/27 feline brain is highly similar to that of the E13.5/E14 mouse. In addition, using the same approach at the earlier (E22/23 and E24/25) or later (E28/29 and E34/35) stages we further analyze neurogenesis, define the timing and duration of several developmental events, and compare our data with those from similar mouse studies; our results point to a complex pattern of heterochronies and show that, compared with the mouse, developmental events in the feline telencephalon span over extended periods suggesting that cats may provide a useful animal model to study brain patterning in ontogenesis and evolution.

The effects of climate change, in combination with the recent energy crisis, have brought the energy efficiency issues of hospitals markedly to the fore. Hospitals are considered among the most energy-intensive buildings, which is why they have become a top priority for governments wishing to upgrade their energy efficiency. Given the critical nature of the work of hospitals and the model of healthcare provision (nursing cover 24 h per day, 7 days a week) it is very hard to achieve energy cuts. The international literature shows that the energy efficiency of hospitals is a complex process that requires further research. This need is covered by the present systematic literature review, which captures the existing knowledge on energy monitoring strategies, assessment, and upgrading through technology, resources-saving strategies, and the relationship between energy efficiency and the quality of the service provision, while also identifying future research considerations and the potential for supporting researchers’ work. Additionally, this study adds aggregated data to the literature, as far as the energy performance of buildings is concerned, and allows investors to have data exported from energy surveys at their disposal. At the same time, it suggests the further exploration of alternative energy technologies, based on all renewable energy sources rather than only solar power systems. This highlights the need for a comparative examination of hospitals with different climatic and socio-economic environments, to better determine what technologies effectively serve the energy needs of each region. Finally, this survey considers it necessary to connect the energy efficiency of hospital units with the awareness of the management and workforce in the saving of energy resources. Due to the fact that most studies are oriented toward the energy performance of very large-sized hospitals, it is suggested that in the future, the research lens should also be focused on the smaller private and public sectors’ health units.

Carbon capture on-board ships represents a powerful technological measure in order for the shipping industry to meet the very stringent GHG emission reduction requirements. Operation within the ship environment introduces a number of constraints associated mainly with space, energy supply, and safety which have to be addressed using compact yet efficient solutions. To this end, solvent-based membrane CO2 capture offers several advantages and has the necessary technological maturity for on-board installation. Solvent choice remains a critical issue both for reasons associated with process efficiency as well as on-board safety. In this paper, we present an up-to-date comprehensive review of the different solvents that can be used for post-combustion CO2 capture. Furthermore, we investigated the solvents’ performance as determined by their inherent characteristics, properties, and behavior for a range of operating conditions against the strict shipping requirements. A preliminary qualitative comparative assessment was carried out based on appropriately selected key performance indicators (KPIs) pertinent to the requirements of the shipping industry. The identified solvent classes were compared using the most critical KPIs for system integration with the ship. It was concluded that at present, no solvent category can efficiently address all the requirements of the ship. However, widely used solvents such as secondary amines showed relatively good compatibility with the majority of the introduced KPIs. On the other hand, more recently developed molecules, such as phase change solvents and ionic liquids, can easily prevail over the vast majority of the identified solvents as long as they are brought to the same level of technological maturity with benchmark solvents. Such a conclusion points toward the need for accelerating research on more tailor-made and performance-targeted solvents.

Background:. Live Surgery Meetings have been established as a vey effective means to demonstrate certain surgical techniques and intraoperative decision-making. However, many authors still question the ethics of this approach. We present our experience as organizers of the Live Makeover Aesthetic Surgery Symposium, an annual international live surgery meeting taking place in Athens, Greece. Methods:. Throughout the course of our meetings, 2 surveys were performed, 1 after Live Makeover Aesthetic Surgery Symposium 3, comparing the educational value between live surgery and pre-recorded videos, and the second after LMASS 6, re-evaluating the educational value of live surgery, as well as the ethics of this educational method and the patient safety. In addition, we studied the results of the patients operated on in all of our meetings, and their level of satisfaction. Results:. Based on the results of the first survey, the superior educational value of live surgery was obvious. The second survey confirmed those valuable educational benefits. In addition, the concerns on both surgical outcomes and patient safety were minimal. The patients showed a very high level of satisfaction through their answers. The complications encountered were only 2 of the 49 live surgical demonstrations and were not directly related to the live demonstration. Conclusions:. Based on our study, live surgery is an effective, safe educational tool. However, strict guidelines have to be followed to ensure high educational value and patient safety. Based on our 9-year experience with our live surgery meeting, we provide detailed guidelines for optimal outcomes.

Purpose: Behcet's disease is an immune-mediated condition which can commonly have ocular involvement. We present a case of Behcet's associated neuroretinitis, which is a rare ocular manifestation of Behcet's disease. Observations: The patient experienced significant improvement in her neuroretinitis without initiation of treatment. After 28 days of observation there was spontaneous resolution of exam findings and return of Snellen visual acuity to 20/20. Conclusionand Importance: There are only two other cases reported in the literature of Behcet's associated neuroretinitis. Both cases report bilateral involvement with concomitant frosted branch angiitis. This is also the only reported case with spontaneous resolution of abnormal exam findings with return to 20/20 visual acuity. This case highlights the complexity of ocular involvement in Behcet's disease.

Few studies have investigated transient global amnesia (TGA) in the context of a concussion and the concussion sequelae following TGA. Here we review the case of a 43-year-old male with onset of transient global anterograde and retrograde amnesia 22 days after a sustained concussion. The patient's head CT, MRI of brain, and EEG were reported normal, and the patient regained full cognitive function 8 h after the TGA episode, with no recollection of the conspiring events. Following the TGA episode, the patient experienced notable worsening of concussive symptoms, including headache, head pressure, anxiety, neck pain, feeling slowed down, fogginess, not feeling right, difficulty remembering, and fatigue. The patient remained symptomatic for 32 days after the TGA episode. We suggest that a lingering window of post-concussion cerebral vulnerability, which may extend beyond clinical recovery, could lead to increased susceptibility to acute cognitive deficits, such as TGA.

Phytoremediation is an emerging concept for contaminated soil restoration via the use of resilient plants that can absorb soil contaminants. The harvested contaminated biomass can be thermochemically converted to energy carriers/chemicals, linking soil decontamination with biomass-to-energy and aligning with circular economy principles. Two thermochemical conversion steps of contaminated biomass, both used for contaminated biomass treatment/exploitation, are considered: Supercritical Water Gasification and Fast Pyrolysis. For the former, the vast majority of contaminants are transferred into liquid and gaseous effluents, and thus the application of purification steps is necessary prior to further processing. In Fast Pyrolysis, contaminants are mainly retained in the solid phase, but a part appears in the liquid phase due to fine solids entrainment. Contaminants include heavy metals, particulate matter, and hydrogen sulfide. The purified streams allow the in-process re-use of water for the Super Critical Water Gasification, the sulfur-free catalytic conversion of the fuel-rich gaseous stream of the same process into liquid fuels and recovery of an exploitable bio-oil rich stream from the Fast Pyrolysis. Considering the fundamental importance of purification/decontamination to exploit the aforementioned streams in an integrated context, a review of available such technologies is conducted, and options are shortlisted. Technologies of choice include polymeric-based membrane gas absorption for desulfurization, electrooxidation/electrocoagulation for the liquid product of Supercritical Water Gasification and microfiltration via ceramic membranes for fine solids removal from the Fast Pyrolysis bio-oil. Challenges, risks, and suitable strategies to implement these options in the context of biomass-to-energy conversion are discussed and recommendations are made.

This work investigates the use of a commercial optical product monitor to achieve in-line real-time water content analysis. Test fluids were used and optical measurements of attenuation of light intensity at four colours were made. These measurements were used to identify any relationship between these and the water quality parameters of turbidity and colour. Variation in light attenuation for turbidities up to 1700 NTU was successfully resolved by the instrument, with optical data for turbidities ≥ 20 NTU fitting well the Beer-Lambert model. The sensor was also able to clearly identify the effect of filtering out suspended solids with unfiltered samples (apparent colour) exhibiting significantly higher attenuation coefficients than filtered samples (true colour). Further studies will concentrate on whether the instrument can analyse samples with turbidities higher than 1700 NTU, together with further investigating the variation in the attenuation coefficient seen with turbidity and colour of light. Keywords: Food manufacturing, Water consumption, Water content, Optical sensor, Turbidity, Colour

To trial the concept of in-plant real-time manufacturing water content characterisation, a commercial optical system for measuring light absorption and backscatter intensity was used with samples of food industry wastewater, and the results compared with conventional laboratory based water analysis. It is shown that the instrumentation is capable of coping with the range of turbidities presented by the wastewater and that there is some correlation between the absorption and backscatter measurements with the conventional parameters COD and TSS. It is suggested that combining backscatter and absorption data may provide an optical fingerprint of effluent that can be used as a management parameter, for example to identify unexpected contamination events. Potential uses of the instrumentation are discussed, including to provide rapid feedback on effects of system changes on effluent production, and in a feedback control loop to allow reuse of water without compromising product safety. Keywords: Industrial water sustainability, Food industry, Water quality, In-line instrumentation, Turbidity, Optical fingerprint

PAXX functions as part of the nonhomologous end-joining pathway to repair double-strand DNA breaks. Here the authors show PAXX and its paralogs interact with polymerase lambda to promote joining of incompatible ends.

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69–0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68–0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48–8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32–23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.

We design, develop, and experimentally validate a complete integrated software/hardware platform for airborne cognitive networking in both indoor and outdoor environments. We first present the concept of all-spectrum cognitive networking and describe a distributed algorithm for maximizing network spectral efficiency by jointly optimizing channel access code-waveforms and routes in a multi-hop network. We then discuss system design parameters and implementation details for setting up a software-defined radio (SDR) testbed that enables reconfigurability at the physical (PHY), medium-access control (MAC), and network (NET) layers of the network protocol stack, either by a user or by means of autonomous decisions. Our algorithmic developments toward spectrally-efficient cognitive networking are software optimized on heterogeneous multi-core general-purpose processor-based SDR architectures by leveraging the design of a novel software-radio framework that offers self-optimization and real-time adaptation capabilities at the PHY, MAC, and NET layers of the network protocol stack. We verify our system design approach in a large-scale testbed deployment of ten terrestrial and one airborne SDR platforms at the Stockbridge Controllable Contested Environment at the Air Force Research Laboratory, Rome, NY, USA. Proof-ofconcept experimental results from both indoor and outdoor testbed deployments show that the proposed system can be used to build all-spectrum cognitive networks that withstand intentional interference at PHY and NET layers and can cognitively coexist with non-cross-layer optimized networks.

There is an emerging need for high-rate underwater acoustic (UW-A) communication platforms to enable a new generation of underwater monitoring applications including video streaming. At the same time, modern UW-A communication architectures need to be flexible to adapt and optimize their communication parameters in real time based on the environmental conditions. Existing UW-A modems are limited in terms of achievable data rates and ability to adapt the protocol stack in real time. To overcome this limitation, we present the design, implementation, and experimental evaluation of a new high-rate software-defined acoustic modem (SDAM) with real-time adaptation capabilities for UW-A communications. We introduce new physical-layer adaptation mechanisms that enable either joint adaptation of communication parameters such as modulation constellation and channel coding rate or seamless switching between different communication technologies such as orthogonal-frequency-division-multiplexing and direct-sequence-spread-spectrum. The performance of the proposed SDAM has been evaluated in both indoor (water tank) and outdoor (lake) environments. We demonstrated that the SDAM achieves 104 kbit/s with bit-error-rate (BER) of 2 × 10-5, 208 kbit/s with BER of 10-3, and 260 kbit/s with BER of 10-2 in real time over a 200 m horizontal link at a very-shallow lake environment.

Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer, and the main cause of prematurely aged skin that is referred to as photoaging. Collagen type I (COL I) is expressed differently along with the dermis between healthy and pathological skin tissues. The aim of this study was to understand the impact of solar radiation in the dermis and assess the impact of solar radiation to COL I. The hematoxylin and eosin staining protocol was performed in tissue paraffin blocks and then they were stained immunohistochemically with the rabbit monoclonal anti-COL I antibody. A total of 270 slides were studied with an Olympus BX 41 microscope; we scored positively the expression of COL I in dermis and statistically analyzed with IBM SPSS Statistics. Based on our results, we observed that solar elastosis changes the structure of the skin’s collagen. In healthy tissues, COL I had a uniform expression along with the dermis. In tissues with aging, COL I expression was weaker and lost homogeneity. In pathological tissues (non-melanoma skin cancers, NMSCs), precancerous lesions, and benign skin lesions), the expression of COL I was observed to be almost weaker than tissues with aging in all body parts and much weaker below the lesions. The most severe solar elastosis was observed in the extremities. The degree of severity of the solar elastosis in relation to age did not appear to be completely affected. Solar radiation divides the collagen more rapidly than normal biological aging and solar elastosis was observed into the skin tissues with photoaging, which replaces the collagen fibers of the skin. These results confirm previous studies, which have shown that skin COL I decreases during aging, more in photoaging and even more in skin cancers. We conclude that skin COL I expression is reduced as a result of ultraviolet radiation and leading to negative impacts on the skin.

CO2 mineralization is an alternative to conventional geological storage and results in permanent carbon storage as a solid, with no need for long-term monitoring and no requirements for significant energy input. Novel technologies for carbon dioxide capture and mineralization involve the use of gas-liquid membrane contactors for post-combustion capture. The scope of the present study is to investigate the application of hollow fiber membrane contactor technology for combined CO2 capture from energy-intensive industry flue gases and CO2 mineralization, in a single-step multiphase process. The process is also a key enabler of the circular economy for the cement industry, a major contributor in global industrial CO2 emissions, as CaCO3 particles, obtained through the mineralization process, can be directed back into the cement production as fillers for partially substituting cement in high-performance concrete. High CO2 capture efficiency is achieved, as well as CaCO3 particles of controlled size and crystallinity are synthesized, in every set of operating parameters employed. The intensified gas-liquid membrane process is assessed by calculating an overall process mass transfer coefficient accounting for all relevant mass transfer resistances and the enhanced mass transfer due to reactive conditions on the shell side. The obtained nanocomposite particles have been extensively characterized by DLS, XRD, TGA, SEM, TEM, and FTIR studies, revealing structured aggregates (1–2 μm average aggregate size) consisting of cubic calcite when the contactor mode is employed.

Aerosol formation of novel carbons offers potential for scale and purity unmatched by condensed phase processes. A microwave driven plasma drives decarbonization of methane to form solid carbon as an aerosol. Dependent upon gas mixture, different forms of carbon are produced: 2D nanographene and a 3D graphitic carbon black analogue. TEM reveals the morphological differences and nanostructure. The ability to tune the dominant form is demonstrated by control of the CH4/Ar ratio. TGA plots reveal the change in products with feed gas composition and quality by oxidation temperature shift. Corresponding Raman analysis illustrates control of graphene content and lamellae quality by peak ratios. To test the origins of the graphitic particles and nanographene, a commercial carbon black was seeded into the microwave reactor, demonstrating a path for graphitic nanostructure evolution and confirming the molecular growth origins for the nanographene.

Summary: Although poly-ADP-ribosylation (PARylation) of DNA repair factors had been well documented, its role in the repair of DNA double-strand breaks (DSBs) is poorly understood. NR4A nuclear orphan receptors were previously linked to DSB repair; however, their function in the process remains elusive. Classically, NR4As function as transcription factors using a specialized tandem zinc-finger DNA-binding domain (DBD) for target gene induction. Here, we show that NR4A DBD is bi-functional and can bind poly-ADP-ribose (PAR) through a pocket localized in the second zinc finger. Separation-of-function mutants demonstrate that NR4A PAR binding, while dispensable for transcriptional activity, facilitates repair of radiation-induced DNA double-strand breaks in G1. Moreover, we define DNA-PKcs protein as a prominent target of ionizing radiation-induced PARylation. Mechanistically, NR4As function by directly targeting poly-ADP-ribosylated DNA-PKcs to facilitate its autophosphorylation-promoting DNA-PK kinase assembly at DNA lesions. Selective targeting of the PAR-binding pocket of NR4A presents an opportunity for cancer therapy. : DNA damage induces poly-ADP-ribosylation (PARylation) of repair factors recruited to DNA lesions. Munnur et al. identify a zinc-finger-type poly-ADP-ribose-binding domain in NR4A nuclear orphan receptors that targets PARylated DNA-PKcs repair kinase, facilitating its autophosphorylation and repair of double-strand DNA breaks. Keywords: DNA repair, double-strand breaks, DSB, NHEJ, NR4A, DNA-PK, poly-ADP-ribose, PARP, non-homologous end joining, transcription factors