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The cell envelope is a multilayered structure that insulates the interior of bacterial cells from an often chaotic outside world. Common features define the envelope across the bacterial kingdom, but the molecular mechanisms by which cells build and regulate this critical barrier are diverse and reflect the evolutionary histories of bacterial lineages. Intracellular pathogens of the genus Brucella exhibit marked differences in cell envelope structure, regulation, and biogenesis when compared to more commonly studied gram-negative bacteria and therefore provide an excellent comparative model for study of the gram-negative envelope. We review distinct features of the Brucella envelope, highlighting a conserved regulatory system that links cell cycle progression to envelope biogenesis and cell division. We further discuss recently discovered structural features of the Brucella envelope that ensure envelope integrity and that facilitate cell survival in the face of host immune stressors. [ABSTRACT FROM AUTHOR]

The Algerian coastal territories have very distinctive morphological characteristics, this has helped to develop several activities we find the tourism sector at the forefront. In this context, the study addresses the introduction of Pescatourism as a new ecosystem in Algeria and how can it contribute to increasing coastal territories capacity and competitiveness. The results showed that this activity has significant potential opportunities for the tourism sector, as well as for the fishing sector in Algeria's coastal regions, by increasing competitiveness and economic, social and material absorptive capacity on the one hand, In addition to maintaining artisanal fishing activity as a socio-cultural heritage, on the other hand. [ABSTRACT FROM AUTHOR]

The use of vinegar as a culinary seasoning in various global cuisines to enhance the taste characteristics and profiles of foods has been extensively documented in the culinary literature. Particularly notable is traditional Taiwanese-style thick soup, where the incorporation of vinegar plays a fundamental role in imparting distinct flavors. In the context of this experimental investigation, the foundational base of Taiwanese-style thick soup serves as the platform for a meticulously planned sensory and dietary behavior evaluation. Our research methodology combines the use of survey questionnaires and experimental techniques, employing purposive sampling and snowball sampling methods to recruit participants. The central focus of this study is to understand consumers' culinary preferences when presented with a choice between two contrasting types of vinegar—specifically, black vinegar and balsamic vinegar—as alternative gastronomic enhancements. This precise orchestration of data collection and systematic evaluation provides a perceptive window into participants' culinary inclinations and food choices, resulting in a detailed and profound understanding of their taste preferences. The empirical findings stemming from this experimentation reveal notably significant differences in the sensory assessments among participants engaging in diverse culinary experiences. Notably, distinct variations are observed in terms of visual perceptions, olfactory distinctions, and overall sensory satisfaction. This study occupies a crucial position within existing research paradigms by strategically expanding the scope of sensory investigations within the realm of Taiwanese-style thick soup. This introduces an innovative aspect represented by the introduction of balsamic vinegar as a compelling alternative to the customary black vinegar. As a result, the emerging findings not only offer compelling insights into the nuanced food choice and taste preferences of consumers, but also open up new and innovative directions within the complex tapestry of Chinese gastronomy. [ABSTRACT FROM AUTHOR]

Facing climate change and rapid urbanization, urban flooding has exposed human and properties to increasing disaster risks. The attention from researchers and decision‐makers to understand the key role of flood regulation service (FRS) in flood management has arisen. However, the mechanism of FRS supply–demand is little known from landscape scale. The FRS assessment methodology considering interacts between source, sink, and flow landscape was proposed in this study. The spatial distributions of surface runoff generation, runoff reduction capacity, and flood inundation were mapped using one‐dimensional rainfall–runoff method SCS‐CN and two‐dimensional flood propagation model CADDIES. Four 3‐hour designed rainfall scenarios ranging from nuisance to extreme events (3a, 11a, 56a, and 100a) were simulated. The Liuyang River Watershed in Changsha Municipality, China was selected for case study. The results showed that, the differences of runoff reduction coefficient and runoff generation volume between vegetation and built‐up landscape have shortened. The peak flood depth, extent of flood inundation, and peak flood velocity have increased continuously with the growing rainfall intensity. The number of source–sink mismatch catchment was the highest under 56 and 100a, and the most of source‐sink match catchments were observed under 3a. Under four rainfall scenarios, the changes of source–sink relationships were witnessed and the potentials of flow zone in source–sink mismatch catchments have increased. The FRS management framework concerning supply–demand connections has been proposed based on source–sink–flow analysis. These findings could provide a scientific basis for sustainable urban flood management and disaster risk mitigation. [ABSTRACT FROM AUTHOR]

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Treatment of visceral artery pseudoaneurysms (VAPs) is always indicated regardless of their diameters, as their risk of rupture is significantly higher than that of visceral artery aneurysms. The invasiveness of surgery and its associated complications have led to a shift in favor of radiological interventions as the initial treatment of choice. However, there are still some unanswered questions on endovascular treatment of VAPs regarding the optimal endovascular technique and the efficacy and safety outcomes. The purpose of this multicenter study was to retrospectively evaluate the effectiveness and safety of endovascular treatment of visceral pseudoaneurysms using Ethylene-Vinyl Alcohol (EVOH) Copolymer-Based Non-Adhesive Liquid Embolic Agents (NALEAs). Materials and Methods: Consecutive patients who underwent endovascular embolization with EVOH-based NALEAs for visceral artery pseudoaneurysms between January 2018 and June 2023 were retrospectively evaluated. Results: 38 embolizations were performed. Technical success was achieved in all patients. The clinical success rate was high (92.1% overall), with no significant differences between ruptured and unruptured VAPs (p = 0.679). Seven patients (18.4%) experienced procedure-related complications, related to one case of non-target embolization, four splenic abscesses due to end-organ infarction, and two femoral pseudoaneurysms. The rates of procedure-related complications, end-organ infarction, and vascular access-site complications did not significantly differ between ruptured and unruptured VAPs (p > 0.05). Conclusions: Both ruptured and unruptured visceral pseudoaneurysms can be effectively and safely treated with NALEA-based endovascular embolization. We suggest considering the use of NALEAs, particularly in specific clinical cases that highlight their advantages, including patients with coagulopathy, fragile vessels, and embolization targets that are located at a considerable distance from the microcatheter tip and are otherwise difficult to reach. [ABSTRACT FROM AUTHOR]

Background: Tick-borne diseases, caused by bacterial pathogens, pose a growing threat to public health in Europe. This paper provides an overview of the historical context of the discovery of the most impactful pathogens transmitted by ticks, including Borrelia burgdorferi sensu lato, Rickettsia spp., Anaplasma spp., Francisella spp., Ehrlichia spp., and Neoehrlichia mikurensis. Understanding the historical context of their discovery provides insight into the evolution of our understanding of these pathogens., Methods and Results: Systematic investigation of the prevalence and transmission dynamics of these bacterial pathogens is provided, highlighting the intricate relationships among ticks, host organisms, and the environment. Epidemiology is explored, providing an in-depth analysis of clinical features associated with infections. Diagnostic methodologies undergo critical examination, with a spotlight on technological advancements that enhance detection capabilities. Additionally, the paper discusses available treatment options, addressing existing therapeutic strategies and considering future aspects., Conclusions: By integrating various pieces of information on these bacterial species, the paper aims to provide a comprehensive resource for researchers and healthcare professionals addressing the impact of bacterial tick-borne diseases in Europe. This review underscores the importance of understanding the complex details influencing bacterial prevalence and transmission dynamics to better combat these emerging public health threats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alzheimer's disease (AD) affects 50 million people worldwide, an increase of 35 million since 2015, and it is known for memory loss and cognitive decline. Considering the morbidity associated with AD, it is important to explore lifestyle elements influencing the chances of developing AD, with special emphasis on nutritional aspects. This review will first discuss how dietary factors have an impact in AD development and the possible role of Artificial Intelligence (AI) and Machine Learning (ML) in preventative care of AD patients through nutrition. The Mediterranean-DASH diets provide individuals with many nutrient benefits which assists the prevention of neurodegeneration by having neuroprotective roles. Lack of micronutrients, protein-energy, and polyunsaturated fatty acids increase the chance of cognitive decline, loss of memory, and synaptic dysfunction among others. ML software has the ability to design models of algorithms from data introduced to present practical solutions that are accessible and easy to use. It can give predictions for a precise medicine approach to evaluate individuals as a whole. There is no doubt the future of nutritional science lies on customizing diets for individuals to reduce dementia risk factors, maintain overall health and brain function., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status., Materials and Methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications)., Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy., Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers., Clinical Relevance Statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status., Trial Registration: ClinicalTrials.gov NCT02400229., Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Interferon regulatory factor 2 (IRF2) participates in the differentiation of immune T cells. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes can secret mRNA, miRNAs, and proteins to regulate tumor microenvironment. The present study focused on the miRNA/IRF2 axis in regulating Th1/Th2 ratio and cell apoptosis in acute myeloid leukemia (AML). The flow cytometry analysis was performed to examine the Th1/Th2 ratio and AML apoptosis in vivo and in vitro. The contents of Interferon γ (IFN-γ) and Interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assay. StarBase was used to predict the potential binding site between miR-222-3p and the 3 ′ untranslated region of IRF2. Luciferase reporter assay was applied for validating the combination of miR-222-3p and IRF2. BM-MSC exosomes were successfully isolated. BM-MSC exosomes increased Th1/Th2 ratio and promoted apoptosis of AML cells. Further analysis showed that IRF2 was targeted by miR-222-3p. Overexpression of miR-222-3p promoted Th1/Th2 ratio and AML cell apoptosis. IRF2 partially reversed the effect that is exerted by miR-222-3p on Th1/Th2 ratio and AML cell apoptosis. Overexpression of miR-222-3p promoted Th1/Th2 ratio and caspase 3 expression in vivo. To sum up, miR-222-3p promotes Th1/Th2 ratio and AML cell apoptosis by regulating IRF2 expression, which provided crucial targets for the treatment of AML. [ABSTRACT FROM AUTHOR]

Increasing frequency of extreme rainfall induced catastrophic urban flood events in recent decades demands proactive efforts to assess flood risk and vulnerability. Here, we develop an integrative framework for fine spatiotemporal scale assessment of urban flood response to historical and future projected changes in extreme precipitation. The framework includes three main components—nonstationary modeling of historical extreme precipitation, modeling of future precipitation, and urban flood simulations. It also provides robust estimates of uncertainty in design precipitation from statistical modeling, multiple climate models and stochastic uncertainty, estimated using machine learning techniques. We demonstrate the proposed framework for White Oak Bayou watershed in Houston, Texas, US. Two‐dimensional hydrologic‐hydraulic Interconnected Channel and Pond Routing model is used to simulate flood response from design precipitation for historical (1986–2020) and two future (2021–2050 and 2071–2100) periods in three (SSP1‐2.5, SSP2‐4.5, and SSP5‐8.5) future climate scenarios. Results show that nonstationary design estimates for historical precipitation are 14%–25% higher than the stationary estimates for 100‐year event of 1‐ to 24‐hr duration. Contrary to general global trends, we found a significant reduction in future design precipitation in all three emission scenarios. Additionally, stochastic uncertainty in future design precipitations is found to be larger than the modeling uncertainty in historical estimates and climate model uncertainty in future estimates. Flood response in terms of peak flood and total flood volume suggests that the difference in stationary versus nonstationary historical and future design precipitation are substantial to cause considerable change in simulated flood. Plain Language Summary: Global warming induced increase in extreme precipitation events has been the primary cause of frequent catastrophic floods in the recent decades—majorly impacting the urban agglomerations. Informed flood mitigation planning requires adequate consideration of these changes in extreme precipitation. So far, researchers have developed methodologies to model flood response to either the historical observed or future projected change in precipitation, but not for simultaneous consideration of both. Regional‐scale evidence shows that the changes in historical observations can be inconsistent or sometimes contrasting to the changes in future projections from global climate models. Therefore, a collective assessment that includes the information of both historical and future changes in extreme precipitation is crucial. Here, we develop a comprehensive framework that incorporates both historical as well as future projected changes in extreme precipitation for fine spatiotemporal scale assessment of urban flood response. The framework also provides robust estimates of uncertainty from multiple components involved in the methodology which allows a reliable communication of attained information to stake holders and water resources planners for efficient decision making. The framework is independent of any regional assumption, thus can be used with confidence for other major cities of the world. Key Points: A framework is proposed for fine‐scale assessment of urban floods that incorporates historical as well as future changes in precipitationIt also provides estimates of uncertainty from statistical modeling of extremes, multiple climate models, and stochastic uncertaintyThe framework is demonstrated for an urbanized watershed in Houston, Texas, United States to answer two important research questions [ABSTRACT FROM AUTHOR]

The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 μg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose–response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease. [ABSTRACT FROM AUTHOR]

Social impact investing and social entrepreneurship have great potential for solving global problems. However, practitioners and researchers know little about the entrepreneurial process and the investors' criteria. Therefore, we identify the determinants of access to external finance for social enterprises in an emerging economy using a quantitative approach in a large sample (N = 601). We found that impact sector, business model, entrepreneurial support, development stage, and the adoption of technologies impact access to finance by social enterprises. We also show that green technologies have greater funding access than other enterprises and that social impact investors are more aware of environmental issues and less concerned with financial returns. To raise more funding, we suggest that social entrepreneurs include environmental issues in their business, quickly validate their idea, add an intermediary company between the enterprise and the consumer, seek the support of incubators or accelerators, and adopt emerging technologies in the product or service offered. [ABSTRACT FROM AUTHOR]

Objectives : The aim of this study was to evaluate the clinical outcomes of diode laser as an adjunct to nonsurgical periodontal therapy (NSPT) for residual periodontal pockets in mandibular second molars. Materials and methods : Sixty-seven mandibular second molars (154 residual periodontal pockets) were recruited into the study and randomly assigned to the Laser + NSPT group and the NSPT group. The Laser + NSPT group underwent NSPT adjunct with diode laser radiation (wavelength: 810 nm, power: 1.5 W, 40 s maximum), while the NSPT group underwent nonsurgical periodontal therapy alone. Clinical parameters were measured at baseline (T0) and 4(T1), 12(T2), and 24(T3), weeks after treatment. Results: Periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP) in both groups showed significant improvements at the end of study compared to baseline. The reductions of PPD, CAL, and BOP in the Laser + NSPT group were significantly greater than NSPT group. At T3, the Laser + NSPT group had a mean PPD of 3.06 ± 0.86 mm, CAL of 2.58 ± 0.94 mm and BOP of 15.49%, while the NSPT group had a mean PPD of 4.46 ± 1.57 mm, CAL of 3.03 ± 1.25 mm and BOP of 64.29%. Conclusions: The diode laser as an adjunct to nonsurgical periodontal therapy may contribute to clinical outcomes for residual periodontal pockets. However, the approach may cause reduction of keratinized tissue width. Trial registration number: This study was registered in the Chinese Clinical Trial Registry ChiCTR2200061194. Clinical relevance: Diode laser as an adjunct to nonsurgical periodontal therapy may contribute to the clinical outcomes for residual periodontal pockets in mandibular second molars. [ABSTRACT FROM AUTHOR]

This paper studies the preferences of consumers for olive oil in Spain, which is the largest producer and consumer of olive oil worldwide. Olive oil is a prominent, sustainable, healthy, and distinctive product associated with the Mediterranean diet. Based on a survey conducted among a sample of 402 consumers, we apply the Best Worst Scaling method to measure the importance of some attributes that influence consumer preferences for olive oil. Our results show that consumers rate price, geographical origin, protected designation of origin label, and olive variety, as important product attributes. Conversely, attributes such as organic label certification, size, and packaging material are considered less important. As the perceived importance of olive oil attributes differs across individuals, we further estimate a five-class solution and describe each class in terms of knowledge and consumption of Extra Virgin Olive Oil (EVOO) and the socio-demographic characteristics of the respondents. Finally, we discuss the implications of studying consumer preferences for olive oil and provide managerial insights. [ABSTRACT FROM AUTHOR]

Dirofilariasis is a zoonotic disease of domestic and wild carnivores and humans. Subcutaneous migration of the parasite Dirofilaria repens Railliet & Henry, 1911 may cause local swelling with variable localisation. In humans, this parasite can cause damage to the lungs, male genitalia and eyes. The range of D. repens is constantly expanding into new areas and, considering the zoonotic potential of this parasite, it is important to extend the existing data on the morphology of D. repens. The present study provides a morphometric description of D. repens nematodes obtained from subcutaneous tissues of dogs in Ukraine. The aim of this study was to highlight the key features for the identification of parasites of this species. For males, 27 morphometric characteristics were identified, characterising the overall size of the body and the oesophagus, the thickness of the cuticle in the region of the mouth opening, the localisation of the nerve ring and the cloaca, the morphological structure and metric parameters of the spicules, and the length of the tail. For females, 18 morphometric traits were identified that, in addition to common parameters, characterize cuticle thickness in the region of the vulva, localisation of the vulva and anus, body width in the regions of the anus and vulva, and tail length. This report adds to the existing data on the morphological and metric characteristics of D. repens nematodes. [ABSTRACT FROM AUTHOR]

The clinical aspects of SARS-CoV-2 infection, as well as the COVID-19 vaccines' safety, efficacy and effectiveness in pediatric patients with asthma, are crucial to adapting clinical management in this fragile population and for prevention strategies. The aim of this narrative review was to evaluate the impact of SARS-CoV-2 infection in children with asthma and the impact of COVID-19 vaccination. Systematic research using the principal medical databases was conducted using specific search query strings from the early spreading of COVID-19 globally until March 2023; further relevant data were drawn from the main national and supranational institutions. No significant differences in SARS-CoV-2 incidence and morbidity were found in asthmatic pediatric patients compared to non-asthmatic ones; however, subjects with uncontrolled asthma were found to be at increased risk of developing a serious disease during SARS-CoV-2 infection. Regarding COVID-19 vaccines, accumulating data support their safety, efficacy and effectiveness on asthmatic children regardless of asthma severity. Further cohort-based studies are needed as the evidence of new epidemic waves caused by new viral variants makes the current knowledge outdated. [ABSTRACT FROM AUTHOR]

The potential of the joined/box-wing aircraft as an environmentally friendly airliner that is capable of meeting current and future emission thresholds led to the investigation of this concept. This study reviews the evolution and current trends in the aerodynamic design of the box-wing aircraft with specific emphasis on box-wing theory, airfoil characteristics, and aerodynamic issues of the box-wing aircraft. The study was undertaken to highlight the distinct features of the box-wing configuration which make it very attractive for future airliners. The study reveals that the box-wing aircraft possesses a significant aerodynamic advantage over conventional aircraft. The boxwing aircraft configuration is also a less radical departure from the conventional concept. It thus could be developed with existing triedand- tested aircraft design technologies, methodologies, and processes. Hence this article is a commentary that highlights the enormous potential of the box-wing aircraft and the need for further studies in this research domain. [ABSTRACT FROM AUTHOR]

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Background/Aim: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. Patients and Methods: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. Results: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. Conclusion: Platinumbased chemotherapy had a similar effect on patients with mUTUC and mUBC. [ABSTRACT FROM AUTHOR]

Africa has a rich diversity of indigenous crops whose commercial and economic value have been underutilized. Eragrostis tef is a crop with great potential for production and commercialization in Ethiopia. The nutritional and curative values of tef are recognized not only in Ethiopia but also in the global market. Economically, tef and its value chain are a source of livelihood for more than six million small-scale Ethiopian farmers. Its large-scale commercialization has the potential to transform the livelihoods of many impoverished people. However, little research has been conducted to assess Ethiopian consumers' attitudes toward tef products. The objective of this study is to understand product attributes that would affect consumer purchasing decisions. The study is based on pasta and baby food, the two most important products that could be made out of tef. The attributes analyzed are the inclusion of tef in the products, price, organic certification, and brand origin. The study relies on survey data that were randomly collected from 318 respondents and secondary data from the central statistical agency. The attributes were subjected to conjoint analysis, a method that is commonly used in consumer market research with hypothetical products consisting of multiple attributes to understand customers' preference for different components of the product. The results of the analysis show that the inclusion of tef flour in the products is the most important factor consumers would consider when buying pasta or baby food. Further, consumers are interested in brand origin as they have a strong inclination to buy domestic brands and prefer products with organic certification. In the case of baby food, Ethiopians are likely to buy products containing more tef flour, packaged in sealed can rather than a paper bag, and concentrated in iron or protein. However, they are less willing to pay a premium even for products they perceive to be of greater utility. The preference for domestic brands and processed food with tef implies that there is opportunity for local brands to grow if they can understand and satisfy consumer expectations. It also means that consumers are interested in business practices that promote sustainable livelihoods. Overall, these findings suggest the potential for commercialization of tef products in Ethiopia and that the development of its value chain could combat nutritional deficiencies in the country. [ABSTRACT FROM AUTHOR]

Background and Objectives: Transcatheter arterial embolization (TAE) is the mainstay of treatment for acute major hemorrhage, even in patients with coagulopathy and spontaneous bleeding. Coagulopathy is associated with worsening bleeding severity and higher mortality and clinical failure rates. Furthermore, some unanswered questions remain, such as the definition of coagulopathy, the indication for TAE or conservative treatment, and the choice of embolic agent. This study aims to assess the efficacy and safety of TAE for spontaneous non-neurovascular acute bleeding in patients with coagulopathy. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients with coagulopathy who had undergone, from January 2018 to May 2023, transcatheter arterial embolization for the management of spontaneous hemorrhages. Results: During the study interval (January 2018–May 2023), 120 patients with coagulopathy underwent TAE for spontaneous non-neurovascular acute bleeding. The abdominal wall was the most common bleeding site (72.5%). The most commonly used embolic agent was polyvinyl alcohol (PVA) particles or microspheres (25.0%), whereas coils and gelatin sponge together accounted for 32.5% of the embolic agents used. Technical success was achieved in all cases, with a 92.5% clinical success rate related to 9 cases of rebleeding. Complications were recorded in 12 (10%) patients. Clinical success was significantly better in the group of patients who underwent correction of the coagulopathy within 24 h of TAE. Conclusions: Transcatheter arterial embolization (TAE) is effective and safe for the management of acute non-neurovascular bleeding in patients with coagulopathy. Correction of coagulopathy should not delay TAE and vice versa, as better clinical outcomes were noted in the subgroup of patients undergoing correction of coagulopathy within 24 h of TAE. [ABSTRACT FROM AUTHOR]

Background and Objectives: Roughly 10% of cancer patients experience an episode of bleeding. The bleeding severity can range from occasional trivial bleeds to major bleeding. The treatment for the bleeding may vary, depending on the clinical condition and anatomical site, and may include various strategies, among which TAE is a cornerstone of major bleeding management. However, the existing literature on tumor hemorrhages is inconsistent. The objective of this multicenter retrospective cohort study was to evaluate the effectiveness and safety of arterial embolization in the treatment of tumor hemorrhages in patients with solid cancers. Materials and Methods: The data for patients with solid cancers undergoing TAE for the management of tumor hemorrhages from January 2020 to May 2023 were gathered. Results: A total of 92 patients with cancer-related bleeding were treated between January 2020 and May 2023. No bleeding was detected by X-ray angiography (XA) in 12 (13%) cases; therefore, a blind embolization was performed. The most common bleeding site was the liver (21.7%). A total of 66 tumor hemorrhages were spontaneous. The most commonly used embolic agent was polyvinyl alcohol (PVA) particles (30.4%). Technical success was achieved in 82 (89.1%) cases, with an 84.8% clinical success rate related to 14 cases of rebleeding. Proximal embolization was performed for 19 (20.7%) patients. Complications were recorded for 10 (10.9%) patients. The 30-day bleeding-related mortality was 15.2%. The technical success, clinical success, proximal embolization rate, and 30-day rebleeding were worse in the subset of patients undergoing TAE with coils. Conclusions: Transcatheter arterial embolization (TAE) represents a viable and potentially life-saving therapeutic approach in the management of tumor hemorrhages, demonstrating a notable effectiveness and safety. The TAE of bleeding tumors using coils resulted in a higher rate of non-superselective proximal embolization, with a trend toward lower clinical success rates and higher rebleeding episodes. [ABSTRACT FROM AUTHOR]

The current food environment exposes individuals to continuous unhealthy signals. The present study investigates the effectiveness of a default option nudge - framed as a Dish of the Day - in guiding healthier food choices of Millennials (aged between 19 and 30 years old), a demographic particularly vulnerable to unhealthy eating. A between-subjects field experiment with two opposite treatments (i.e.: healthy and unhealthy default option) and a control group (no default) was performed on a random, convenience sample (N=341). Results show a limited impact of the healthy default option (3.9%) and suggest that this nudging intervention has a stronger influence on individuals who already prioritize health in their everyday lifestyle. Similarly, the default option is more effective on subjects who do not believe that health and taste are conflicting. [ABSTRACT FROM AUTHOR]

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities. [ABSTRACT FROM AUTHOR]

The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6, respectively, are the most abundantly expressed connexins in the inner ear. Connexin 43, which is encoded by GJA1, appears to be widely expressed in various organs, including the heart, skin, the brain, and the inner ear. The mutations that arise in GJB2, GJB6, and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns. As it is predicted that connexins include at least 20 isoforms in humans, the biosynthesis, structural composition, and degradation of connexins must be precisely regulated so that the gap junctions can properly operate. Certain mutations result in connexins possessing a faulty subcellular localization, failing to transport to the cell membrane and preventing gap junction formation, ultimately leading to connexin dysfunction and hearing loss. In this review, we provide a discussion of the transport models for connexin 43, connexins 30 and 26, mutations affecting trafficking pathways of these connexins, the existing controversies in the trafficking pathways of connexins, and the molecules involved in connexin trafficking and their functions. This review can contribute to a new way of understanding the etiological principles of connexin mutations and finding therapeutic strategies for hereditary deafness. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is common worldwide, and has aggressive features and high rates of relapse despite treatments. Approximately 30% of patients present with muscle invasive disease, and therefore, high risk of metastasis. This review provides an overview of the state of the art for the 'Vesical Imaging Reporting and Data System' (VI-RADS). This scoring system presents a tool for the local staging of BC and has been validated across several institutions. We discuss the current application and the potential future clinical implications of VI-RADS in BC diagnosis, management and follow-up. [ABSTRACT FROM AUTHOR]

The healthy conscious brain is thought to operate near a critical state, reflecting optimal information processing and high susceptibility to external stimuli. Conversely, deviations from the critical state are hypothesized to give rise to altered states of consciousness (ASC). Measures of criticality could therefore be an effective way of establishing the conscious state of an individual. Furthermore, characterizing the direction of a deviation from criticality may enable the development of treatment strategies for pathological ASC. The aim of this scoping review is to assess the current evidence supporting the criticality hypothesis, and the use of criticality as a conceptual framework for ASC. Using the PRISMA guidelines, Web of Science and PubMed were searched from inception to February 7th 2022 to find articles relating to measures of criticality across ASC. N = 427 independent papers were initially found on the subject. N = 378 were excluded because they were either: not related to criticality; not related to consciousness; not presenting results from a primary study; presenting model data. N = 49 independent papers were included in the present research, separated in 7 sub-categories of ASC: disorders of consciousness (DOC) (n = 5); sleep (n = 13); anesthesia (n = 18); epilepsy (n = 12); psychedelics and shamanic state of consciousness (n = 4); delirium (n = 1); meditative state (n = 2). Each category included articles suggesting a deviation of the critical state. While most studies were only able to identify a deviation from criticality without being certain of its direction, the preliminary consensus arising from the literature is that non-rapid eye movement (NREM) sleep reflects a subcritical state, epileptic seizures reflect a supercritical state, and psychedelics are closer to the critical state than normal consciousness. This scoping review suggests that, though the literature is limited and methodologically inhomogeneous, ASC are characterized by a deviation from criticality, though its direction is not clearly reported in a majority of studies. Criticality could become, with more extensive research, an effective and objective way to characterize ASC, and help identify therapeutic avenues to improve criticality in pathological brain states. Furthermore, we suggest how anesthesia and psychedelics could potentially be used as neuromodulation techniques to restore criticality in DOC. [ABSTRACT FROM AUTHOR]

Background: Q fever is a zoonotic infectious disease characterized by fever, malaise, chills, significant weakness, and muscle pain. In some cases, the disease can become chronic and affect the inner membranes of the heart, such as the valves, leading to endocarditis and a high risk of death. Coxiella burnetii (C. burnetii) is the primary causative agent of Q fever in humans. This study aims to monitor the presence of C. burnetii in ticks collected from small mammals and cattle in the Republic of Guinea (RG). Methods: Rodents were trapped in the Kindia region of RG during 2019–2020, and ticks were collected from cattle in six regions of RG. Total DNA was extracted using a commercial kit (RIBO-prep, InterLabService, Russia) following the manufacturer's instructions. Real-time PCR amplification was conducted using the kit (AmpliSens Coxiella burnetii-FL, InterLabService, Russia) to detect C. burnetii DNA. Results and Conclusions: Bacterial DNA was detected in 11 out of 750 (1.4%) small mammals and 695 out of 9620 (7.2%) tick samples. The high number of infected ticks (7.2%) suggests that they are the main transmitters of C. burnetii in RG. The DNA was detected in the liver and spleen of a Guinea multimammate mouse, Mastomys erythroleucus. These findings demonstrate that C. burnetii is zoonotic in RG, and measures should be taken to monitor the bacteria's dynamics and tick prevalence in the rodent population. [ABSTRACT FROM AUTHOR]

Peritoneal carcinosis is a condition characterized by the spread of cancer cells to the peritoneum, which is the thin membrane that lines the abdominal cavity. It is a serious condition that can result from many different types of cancer, including ovarian, colon, stomach, pancreatic, and appendix cancer. The diagnosis and quantification of lesions in peritoneal carcinosis are critical in the management of patients with the condition, and imaging plays a central role in this process. Radiologists play a vital role in the multidisciplinary management of patients with peritoneal carcinosis. They need to have a thorough understanding of the pathophysiology of the condition, the underlying neoplasms, and the typical imaging findings. In addition, they need to be aware of the differential diagnoses and the advantages and disadvantages of the various imaging methods available. Imaging plays a central role in the diagnosis and quantification of lesions, and radiologists play a critical role in this process. Ultrasound, computed tomography, magnetic resonance, and PET/CT scans are used to diagnose peritoneal carcinosis. Each imaging procedure has advantages and disadvantages, and particular imaging techniques are recommended based on patient conditions. Our aim is to provide knowledge to radiologists regarding appropriate techniques, imaging findings, differential diagnoses, and treatment options. With the advent of AI in oncology, the future of precision medicine appears promising, and the interconnection between structured reporting and AI is likely to improve diagnostic accuracy and treatment outcomes for patients with peritoneal carcinosis. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to extend the current knowledge about how food neophobia and food technology neophobia can influence whether consumers choose fish farmed with insect-based flours (FFIF). Design/methodology/approach: The authors used an online survey questionnaire and a sample of 567 young Italian adults. The answers were analysed using fuzzy-set qualitative comparative analysis and structural equation modelling. Findings: Both methodologies highlighted the relevance of food technology neophobia in influencing consumers' attitudes and intentions, even when foodstuffs were not produced through technology-intensive processes. Research limitations/implications: Despite being focussed on a sample containing people of similar ages and food cultures, this study offers evidence that it is not necessarily the technological level of a food production process that sparks feelings of technology-related neophobia. Thus, this study highlights the importance of consumers' perceptions of foodstuff choices. Practical implications: The findings provide valuable insights into how informative campaigns should address the problem of increasing the acceptance of novel foods, such as FFIF. Originality/value: The present study provides empirical evidence that food technology neophobia can influence whether consumers choose FFIF. Furthermore, using a mixed-method approach is novel in the field of new foods. [ABSTRACT FROM AUTHOR]

In this study, an exact solution using the Generalized Integral Transform Technique (GITT), for the laminar forced convection problem of non-Newtonian fluid flow in elliptical duct by considering the viscous dissipation effects is provided. The proposed solution has been validated by comparison with the numerical solution based on the Dynamic Alternating Direction Implicit (DADI) method developed in this study and with the results available in literature. Results of the analysis showed that the temperature distribution is highly influenced by the Brinkman number as well as the aspect ratio. The use of elliptical duct enhances the viscous heating and the heat transfer coefficient compared to the circular duct. The analytical solution was used to investigate the polyalkylene–glycol–TiO2 non-Newtonian nanofluids flow in microchannels. The results showed that the addition of nanoparticles reduces viscous dissipation effect due to the shear-thinning behavior and the increase in thermal conductivity. In addition, the elliptical microchannel showed a significant enhancement in the heat transfer rate and reduction by half of the thermal length compared to the circular microchannel. These two advantages are with high importance in development of micro-electro-mechanical system (MEMS). [ABSTRACT FROM AUTHOR]

Background and Objectives: Increasing attention is being paid to the coagulation disorders associated with SARS-CoV-2 infection. Bleeding accounts for 3–6% of COVID-19 patient deaths, and is often a forgotten part of the disease. The bleeding risk is enhanced by several factors, including spontaneous heparin-induced thrombocytopenia, thrombocytopenia, the hyperfibrinolytic state, the consumption of coagulation factors, and thromboprophylaxis with anticoagulants. This study aims to assess the efficacy and safety of TAE in the management of bleeding in COVID-19 patients. Materials and Methods: This multicenter retrospective study analyzes data from COVID-19 patients subjected to transcatheter arterial embolization for the management of bleeding from February 2020 to January 2023. Results: Transcatheter arterial embolization was performed in 73 COVID-19 patients for acute non-neurovascular bleeding during the study interval (February 2020–January 2023). Coagulopathy was observed in forty-four (60.3%) patients. The primary cause of bleeding was spontaneous soft tissue hematoma (63%). A 100% technical success rate was recorded; six cases of rebleeding resulted in a 91.8% clinical success rate. No cases of non-target embolization were observed. Complications were recorded in 13 (17.8%) patients. The efficacy and safety endpoints did not differ significantly between the coagulopathy and non-coagulopathy groups. Conclusions: Transcatheter Arterial Embolization (TAE) is an effective, safe and potentially life-saving option for the management of acute non-neurovascular bleeding in COVID-19 patients. This approach is effective and safe even in the subgroup of COVID-19 patients with coagulopathy. [ABSTRACT FROM AUTHOR]

Due to an ever‐increasing demographic pressure, coastal areas are hotspots of anthropogenic impact on marine ecosystems. Understanding the extent and nature of these impacts is critical for developing effective conservation and management strategies to protect and restore coastal marine ecosystems and the services they provide. The Gulf of Naples is a coastal embayment in the Tyrrhenian Sea, Western Mediterranean Sea, which is severely impacted by human activities. Here, we discuss the intertwining of anthropogenic pressures and climate variations in regulating phytoplankton biomass dynamics in the Gulf and the presence of possible long‐term changes. We analysed three decades of T‐S, nutrient, and chlorophyll a data collected at a fixed station, the LTER‐MC site. Despite some spikes in nutrient concentrations (up to 9.92 mmol m−3 for NO3−, 13.12 mmol m−3 for NH4+, 0.75 mmol m−3 for PO43−, and 13.59 mmol m−3 for Si(OH)4), median surface and depth‐integrated concentrations are relatively low (0.73 mmol m−3 and 0.45 mmol m−3 for NO3−, 0.73 mmol m−3 and 0.47 mmol m−3 for NH4+, 0.07 mmol m−3 and 0.04 mmol m−3 for PO43−, 1.61 mmol m−3 and 1.44 mmol m−3 for Si(OH)4, respectively). Chlorophyll a concentrations, here taken as a proxy of phytoplankton biomass, occasionally display high values (up to 17.33 mg m−3) and fluctuating highs and lows lasting several months, with an overall median value of 1.37 mg m−3 at the surface, and 0.55 mg m−3 as integrated mean. These values are nine and three times higher than the offshore concentrations. The plankton food web at the site is mostly driven by terrestrial inputs. The effect of large‐scale–long‐term trends in nutrient inputs (e.g., phosphate load reduction) is comparable to that of local drivers, also because of the relatively shallow depth (75 m) of the station and its vicinity to the coastline. Importantly, the physical dynamics, despite the more closed morphology of the Gulf with respect to other bays in the Tyrrhenian Sea, efficiently removes excess nutrients and biomass, preventing dystrophic phenomena. [ABSTRACT FROM AUTHOR]

A dual-target strategy was designed for the application of lignin nanoparticles in the lipase mediated biosynthesis of novel 3-O-ethyl-L-ascorbyl-6-ferulate and 3-O-ethyl-L-ascorbyl-6-palmitate and in their successive solvent-shift encapsulation in order to improve stability and antioxidant activity against temperature and pH-dependent degradation. The loaded lignin nanoparticles were fully characterized in terms of kinetic release, radical scavenging activity and stability under pH 3 and thermal stress (60 °C), showing improved antioxidant activity and high efficacy in the protection of ascorbic acid esters from degradation. [ABSTRACT FROM AUTHOR]

Olive oil is one of the basic products in the Mediterranean diet, and, due to its nutritional value, it is becoming more and more widespread in the world. Even though it has traditionally been a rainfed crop, farmers are currently transforming their plantations into super-high-density orchards to increase production. However, the increasingly acute drought in Mediterranean countries forces the establishment of water control mechanisms that allow restriction the contribution of water without undermining the properties of the products obtained. Under this concept, hydroSOS crops and products arose. This study aims to analyze the influence of the application of deficit irrigation on the olive oil obtained from the Arbequina and Arbosana varieties. The sensory parameters descriptive profile and consumers satisfaction degree were measured using trained and consumers' panels, and the chemical parameters peroxide index, fatty acids, and volatile profile were analyzed using the methods from the International Olive Oil Council and gas chromatography. The experimental results showed that applying this type of irrigation leads to an oil that is more valued by consumers, with a higher concentration of aromatic compounds related with a greener aroma (hexanol, trans-2-hexen-1-ol, hexanal), a higher content of polyunsaturated fatty acids, and greater antioxidant capacity. Deficit irrigation strategies led to environmentally friendly olive oil with high acceptance by Spanish consumers. [ABSTRACT FROM AUTHOR]

Clear epigenetic signatures were found in hypertensive and pre-hypertensive patients using DNA methylation data and neural networks in a classification algorithm. It is shown how by selecting an appropriate subset of CpGs it is possible to achieve a mean accuracy classification of 86% for distinguishing control and hypertensive (and pre-hypertensive) patients using only 2239 CpGs. Furthermore, it is also possible to obtain a statistically comparable model achieving an 83% mean accuracy using only 22 CpGs. Both of these approaches represent a substantial improvement over using the entire amount of available CpGs, which resulted in the neural network not generating accurate classifications. An optimization approach is followed to select the CpGs to be used as the base for a model distinguishing between hypertensive and pre-hypertensive individuals. It is shown that it is possible to find methylation signatures using machine learning techniques, which can be applied to distinguish between control (healthy) individuals, pre-hypertensive individuals and hypertensive individuals, illustrating an associated epigenetic impact. Identifying epigenetic signatures might lead to more targeted treatments for patients in the future. [ABSTRACT FROM AUTHOR]

The self has been proposed to be grounded in interoceptive processing, with heartbeat-evoked cortical activity as a neurophysiological marker of this processing. However, inconsistent findings have been reported on the relationship between heartbeat-evoked cortical responses and self-processing (including exteroceptive- and mental-self-processing). In this review, we examine previous research on the association between self-processing and heartbeat-evoked cortical responses and highlight the divergent temporal-spatial characteristics and brain regions involved. We propose that the brain state relays the interaction between self-processing and heartbeat-evoked cortical responses and thus accounts for the inconsistency. The brain state, spontaneous brain activity which highly and continuously changes in a nonrandom way, serves as the foundation upon which the brain functions and was proposed as a point in an extremely high-dimensional space. To elucidate our assumption, we provide reviews on the interactions between dimensions of brain state with both self-processing and heartbeat-evoked cortical responses. These interactions suggest the relay of self-processing and heartbeat-evoked cortical responses by brain state. Finally, we discuss possible approaches to investigate whether and how the brain state impacts the self-heart interaction. [ABSTRACT FROM AUTHOR]

(1) Background: Children and young adults with cancer are poorly represented in COVID-19 vaccination studies, and long-term protection conferred by vaccination is not known. (2) Objectives: 1. To determine the adverse effects associated with BNT162B2 vaccination in children and young adults with cancer. 2. To assess its efficacy in stimulating immunological response and in preventing severe COVID-19 disease. (3) Methods: Retrospective single-center study evaluating patients aged 8 to 22 years, with cancer, who underwent vaccination from January 2021 to June 2022. ELISA serologies and serum neutralization were collected monthly from the first injection. Serologies below 26 were considered negative, while those above 264 BAU/mL were considered positive and indicative of protection. Antibodies titers were considered positive above 20. Data on adverse events and infections were collected. (4) Results: 38 patients were included (M/F = 1.7, median age 16 years), of whom 63% had a localized tumor and 76% were undergoing treatment at the time of the first vaccination. Two or three vaccine injections were administered in 90% of patients. Adverse events were mainly systemic and not severe, except for seven grade 3 toxicities. Four cancer-related deaths were reported. Median serology was negative the month following the first vaccination and became protective during the third month. At 3 and 12 months, median serology was 1778 and 6437 BAU/mL, respectively. Serum neutralization was positive in 97% of the patients. COVID-19 infection occurred despite vaccination in 18%; all were mild forms. (5) Conclusions: In children and young adults with cancer, vaccination was well tolerated and conferred effective serum neutralization. COVID-19 infections were mild, and vaccine seroconversion persisted after 12 months in most patients. The value of additional vaccination should be further established. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate AI biases and errors in estimating bone age (BA) by comparing AI and radiologists' clinical determinations of BA. Methods: We established three deep learning models from a Chinese private dataset (CHNm), an American public dataset (USAm), and a joint dataset combining the above two datasets (JOIm). The test data CHNt (n = 1246) were labeled by ten senior pediatric radiologists. The effects of data site differences, interpretation bias, and interobserver variability on BA assessment were evaluated. The differences between the AI models' and radiologists' clinical determinations of BA (normal, advanced, and delayed BA groups by using the Brush data) were evaluated by the chi-square test and Kappa values. The heatmaps of CHNm-CHNt were generated by using Grad-CAM. Results: We obtained an MAD value of 0.42 years on CHNm-CHNt; this result indicated an appropriate accuracy for the whole group but did not indicate an accurate estimation of individual BA because with a kappa value of 0.714, the agreement between AI and human clinical determinations of BA was significantly different. The features of the heatmaps were not fully consistent with the human vision on the X-ray films. Variable performance in BA estimation by different AI models and the disagreement between AI and radiologists' clinical determinations of BA may be caused by data biases, including patients' sex and age, institutions, and radiologists. Conclusions: The deep learning models outperform external validation in predicting BA on both internal and joint datasets. However, the biases and errors in the models' clinical determinations of child development should be carefully considered. Key Points: • With a kappa value of 0.714, clinical determinations of bone age by using AI did not accord well with clinical determinations by radiologists. • Several biases, including patients' sex and age, institutions, and radiologists, may cause variable performance by AI bone age models and disagreement between AI and radiologists' clinical determinations of bone age. • AI heatmaps of bone age were not fully consistent with human vision on X-ray films. [ABSTRACT FROM AUTHOR]

Monitoring of tickborne diseases is critical for prevention and management. We analyzed 418 ticks removed from 359 patients during 2014-2021 in Marseille, France, for identification and bacteria detection. Using morphology, molecular methods, or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we identified 197 (47%) Ixodes, 136 (33%) Dermacentor, 67 (16%) Rhipicephalus, 8 (2%) Hyalomma, 6 (1%) Amblyomma, 2 (0.5%) Argas, and 2 (0.5%) Haemaphysalis tick species. We also detected bacterial DNA in 241 (58%) ticks. The most frequent bacterial pathogens were Rickettsia raoultii (17%) and R. slovaca (13%) in Dermacentor ticks, Borrelia spp. (9%) in Ixodes ticks, and R. massiliae (16%) in Rhipicephalus ticks. Among patients who were bitten, 107 had symptoms, and tickborne diseases were diagnosed in 26, including scalp eschar and neck lymphadenopathy after tick bite and Lyme borrelioses. Rapid tick and bacteria identification using a combination of methods can substantially contribute to clinical diagnosis, treatment, and surveillance of tickborne diseases. [ABSTRACT FROM AUTHOR]

Children with elevated liver enzymes are occasionally discovered through laboratory work-up from different clinical scenarios. Although the majority will have transient and/or benign conditions, a subgroup will have underlying liver disorders. The differential diagnosis is broad and therefore, a systematic approach is of utmost importance. In this article, we reviewed the most recent and relevant literature to provide a comprehensive overview of the main disease processes that cause hypertransaminasemia in children. Ultimately, we propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes in asymptomatic children. The first step is to obtain a complete history along with a thorough physical examination to exclude red flags, which should dictate urgent consultation with a paediatric gastroenterologist or hepatologist. Conclusion: Hypertransaminasemia is a challenging scenario in the primary care setting. The aetiology can be broad, ranging from hepatic and extrahepatic to transient versus chronic liver disease. Timely referral to a specialised centre is of paramount importance for conducting targeted research and to not miss the chance of identifying a progressive, but still asymptomatic, treatable liver disease. What is Known: • Elevated liver enzyme is a challenging scenario in the primary care setting. • There are few studies guiding the evaluation of asymptomatic hypertransaminasemia in the paediatric population and a standardised approach is lacking. What is New: • We propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes. [ABSTRACT FROM AUTHOR]

This study evaluated multiple aspects of flood risks and effects on the Cinan Feizuo flood protection area in the Huaihe River basin. Flooding remains a leading problem for infrastructure, especially in urban, residential areas of the region. Effective flood modeling for urbanized floodplains is challenging, but MIKE (ID-2D) is paramount for analyzing and quantifying the risk in the vulnerable region. The Saint-Venant equation and a one-dimensional (1D) MIKE 11 model were used to understand the flood dynamics in the Huaihe River, and a two-dimensional (2D) MIKE 21 model was applied to assess the risk in the Cinan Feizuo flood protection area. The finite volume method (FVM) was used for discrete grid problems, and the models were coupled through the weir equation to find the flow volume from the 1D domain to the 2D domain to investigate water level changes. Flood inundation maps were generated for the flood protection area. The maximum discharge, velocity, and submerged depth for 50- and 100-year flood events were assessed with flood risk. Chenbei indicated a high flood risk level in 50 to 100 years in which the water level exceeds a high level and inundates the maximum area with minimum time. Conversely, the 100-year flood inundation in the flood protection area was comparatively higher than the 50-year flood, with a lower time step. The risk analysis identified significant damage caused by the flood over the target regions. The findings of this study provide technical support for flood risk analysis and loss assessment within the flood protection area and have important reference values for regional flood control, disaster reduction decision making, and constructive planning. [ABSTRACT FROM AUTHOR]

The function of most lipases is controlled by the lid, which undergoes conformational changes at a water–lipid interface to expose the active site, thus activating catalysis. Understanding how lid mutations affect lipases' function is important for designing improved variants. Lipases' function has been found to correlate with their diffusion on the substrate surface. Here, we used single-particle tracking (SPT), a powerful tool for deciphering enzymes' diffusional behavior, to study Thermomyces lanuginosus lipase (TLL) variants with different lid structures in a laundry-like application condition. Thousands of parallelized recorded trajectories and hidden Markov modeling (HMM) analysis allowed us to extract three interconverting diffusional states and quantify their abundance, microscopic transition rates, and the energy barriers for sampling them. Combining those findings with ensemble measurements, we determined that the overall activity variation in the application condition is dependent on surface binding and lipase mobility when bound. Specifically, the L4 variant with a TLL-like lid and wild-type (WT) TLL displayed similar ensemble activity, but WT bound stronger to the surface than L4, while L4 had a higher diffusion coefficient and thus activity when bound to the surface. These mechanistic elements can only be de-convoluted by our combined assays. Our findings offer fresh perspectives on the development of the next iteration of enzyme-based detergent. [ABSTRACT FROM AUTHOR]

In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure. This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.p210401/full [ABSTRACT FROM AUTHOR]