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The invasive hornet Vespa velutina affects apiculture, biodiversity, and human health. The use of baited traps with the aim of reducing the population and mitigating its impacts is a common practice. However, the lack of impact on the number of colonies and the high capture rate of non-target insects make it controversial. Our objective was to compare the effectiveness and selectiveness of four trap models. We measured effectiveness as the capture rate of V. velutina per day per trap, and selectiveness as the capture rate of V. velutina/capture rate of non-target species. The E trap had better performance with a higher selectiveness and effectiveness. Traps V and X had a higher effectiveness but the lowest selectiveness, with high capture rates of native insects, including threatened species. The R trap had the lowest effectiveness and selectiveness. Results show that small changes in the design can contribute to achieving more sustainable tools. Otherwise, with the current tools, bait trapping continues to be non-sustainable from an environmental perspective due to the impacts on native biodiversity.

Stainless-steel tanks and wooden barrels are the most common wine ageing and storage vessels. Wooden barrels are often toasted to improve their chemical composition and influence on wine. The aim of this study was to investigate the changes in Merlot red wine aroma from the 2020 and 2021 vintages during 12-month storage (with sampling every 3 months) in a stainless-steel tank (SST), Excellence oak barrels with medium (EMT), medium plus (EMT+) and medium long (EMLT) toasting and a Premium oak barrel with medium toasting (PMT). The results showed that even slight differences in the time and temperature of medium toasting influenced the extraction of aroma compounds from wood to wine. The changes in individual aroma compounds depended on the vessel type, toasting level, initial wine composition and storage time. An increase in the total concentration of compounds with smoky, spicy and woody notes occurred in both wine vintages stored in wooden barrels, especially during longer storage. In samples from SST, floral, fruity and herbal aromas were more pronounced, according to the gas chromatography and sensory evaluators. Sensory evaluators rated the samples according to the 100-point test, and after 12 months of storage, 2020 and 2021 vintage Merlot stored in PMT obtained the highest points.

Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Methods: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. Results: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. Conclusions: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.

In this study, numerical and experimental research of residual stresses was carried out on an I-profile structure model and welded by using the Metal-cored Arc Welding (MCAW) technique. The numerical research was carried out by sequential simulation, using the birth and death element in the thermal analysis, while the same was omitted in the mechanical analysis in order to speed up the calculation process. The measurement of residual stresses was conducted on the outer surfaces of the model at a depth of 0.015 mm below the surface. It was determined that the longitudinal stresses in the weld and its immediate surroundings are tensile, while towards the ends of the model, they change to compressive. Transversal residual stresses exist mainly around the weld itself, and the immediate surroundings and decrease towards the ends of the model. A high agreement between the numerical and experimental results was found.

Methionine adenosyltransferases (MATs) are essential enzymes for life as they produce S-adenosylmethionine (SAMe), the biological methyl donor required for a plethora of reactions within the cell. Mammalian systems express two genes, MAT1A and MAT2A, which encode for MATα1 and MATα2, the catalytic subunits of the MAT isoenzymes, respectively. A third gene MAT2B, encodes a regulatory subunit known as MATβ which controls the activity of MATα2. MAT1A, which is mainly expressed in hepatocytes, maintains the differentiated state of these cells, whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver (e.g., hepatic stellate and Kupffer cells). The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1. A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation, but this change in the expression pattern of MATs results in reduced hepatic SAMe level. Decades of study have utilized the Mat1a-knockout (KO) mouse that spontaneously develops non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis. An increasing volume of work indicates that MATs have SAMe-independent functions, distinct interactomes and multiple subcellular localizations. Here we aim to provide an overview of MAT biology including genes, isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation. We will highlight recent breakthroughs in the field and underscore the importance of MAT's in liver tumorigenesis as well as their potential as targets for cancer therapy.

BackgroundData regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.MethodsIn a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.ResultsA total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P

PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. NAFLD covers a spectrum that ranges from simple steatosis, nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, to cirrhosis, which is a major risk factor for hepatocellular carcinoma. Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity, type 2 diabetes mellitus and dyslipidemia, with a global prevalence of 25%. NAFLD arises when the uptake of fatty acids (FA) and triglycerides (TG) from circulation and de novo lipogenesis saturate the rate of FA β-oxidation and very-low density lipoprotein (VLDL)-TG export. Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH, and therefore, alterations in liver and serum lipidomic signatures are good indicators of the disease's development and progression. This review focuses on the importance of the classification of NAFLD patients into different subtypes, corresponding to the main alteration(s) in the major pathways that regulate FA homeostasis leading, in each case, to the initiation and progression of NASH. This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments.

Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.

Prohibitin 1 (PHB1) is a mitochondrial chaperone whose expression is dysregulated in cancer. In liver cancer, PHB1 acts as a tumor suppressor, but the mechanisms of tumor suppression are incompletely understood. Here we aimed to determine PHB1 target genes to better understand how PHB1 influences liver tumorigenesis. Using RNA-Seq analysis, we found interleukin-8 (IL-8) to be one of the most highly up-regulated genes following PHB1 silencing in HepG2 cells. Induction of IL-8 expression also occurred in multiple liver and nonliver cancer cell lines. We examined samples from 178 patients with hepatocellular carcinoma (HCC) and found that IL-8 mRNA levels were increased, whereas PHB1 mRNA levels were decreased, in the tumors compared with adjacent nontumorous tissues. Notably, HCC patients with high IL-8 expression have significantly reduced survival. An inverse correlation between PHB1 and IL-8 mRNA levels is found in HCCs with reduced PHB1 expression. To understand the molecular basis for these observations, we altered PHB1 levels in liver cancer cells. Overexpression of PHB1 resulted in lowered IL-8 expression and secretion. Silencing PHB1 increased c-Jun N-terminal kinase (JNK) and NF-κB activity, induced nuclear accumulation of c-JUN and p65, and enhanced their binding to the IL-8 promoter containing AP-1 and NF-κB elements. Conditioned medium from PHB1-silenced HepG2 cells increased migration and invasion of parental HepG2 and SK-hep-1 cells, and this was blocked by co-treatment with neutralizing IL-8 antibody. In summary, our findings show that reduced PHB1 expression induces IL-8 transcription by activating NF-κB and AP-1, resulting in enhanced IL-8 expression and release to promote tumorigenesis.

Abstract Background Very few data are available on predictors of minimal disease activity (MDA) in patients with recent-onset psoriatic arthritis (PsA). Such data are crucial, since the therapeutic measures used to change the adverse course of PsA are more likely to succeed if we intervene early. In the present study, we used predictive models based on machine learning to detect variables associated with achieving MDA in patients with recent-onset PsA. Methods We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset contained data for the independent variables from the baseline visit and from follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a random forest–type machine learning algorithm to analyze the association between the outcome measure and the variables selected in the bivariate analysis. In order to understand how the model uses the variables to make its predictions, we applied the SHAP technique. We used a confusion matrix to visualize the performance of the model. Results The sample comprised 158 patients. 55.5% and 58.3% of the patients had MDA at the first and second follow-up visit, respectively. In our model, the variables with the greatest predictive ability were global pain, impact of the disease (PsAID), patient global assessment of disease, and physical function (HAQ-Disability Index). The percentage of hits in the confusion matrix was 85.94%. Conclusions A key objective in the management of PsA should be control of pain, which is not always associated with inflammatory burden, and the establishment of measures to better control the various domains of PsA.

Abstract Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p

Abstract Background Long distance heavy goods vehicle (HGV) drivers exhibit higher than nationally representative rates of obesity, and obesity-related co-morbidities, and are underserved in terms of health promotion initiatives. The purpose of this study was to evaluate the effectiveness of the multicomponent ‘Structured Health Intervention For Truckers’ (SHIFT), compared to usual care, at 6- and 16–18-month follow-up. Methods We conducted a two-arm cluster RCT in transport sites throughout the Midlands, UK. Outcome measures were assessed at baseline, at 6- and 16–18-month follow-up. Clusters were randomised (1:1) following baseline measurements to either the SHIFT arm or usual practice control arm. The 6-month SHIFT programme included a group-based interactive 6-h education and behaviour change session, health coach support and equipment provision (Fitbit® and resistance bands/balls to facilitate a ‘cab workout’). The primary outcome was device-assessed physical activity (mean steps/day) at 6 months. Secondary outcomes included the following: device-assessed sitting, physical activity intensity and sleep; cardiometabolic health, diet, mental wellbeing and work-related psychosocial variables. Data were analysed using mixed-effect linear regression models using a complete-case population. Results Three hundred eighty-two HGV drivers (mean ± SD age: 48.4 ± 9.4 years, BMI: 30.4 ± 5.1 kg/m2, 99% male) were recruited across 25 clusters (sites) and randomised into either the SHIFT (12 clusters, n = 183) or control (13 clusters, n = 199) arms. At 6 months, 209 (55%) participants provided primary outcome data. Significant differences in mean daily steps were found between groups, in favour of the SHIFT arm (adjusted mean difference: 1008 steps/day, 95% CI: 145–1871, p = 0.022). Favourable differences were also seen in the SHIFT group, relative to the control group, in time spent sitting (− 24 mins/day, 95% CI: − 43 to − 6), and moderate-to-vigorous physical activity (6 mins/day, 95% CI: 0.3–11). Differences were not maintained at 16–18 months. No differences were observed between groups in the other secondary outcomes at either follow-up. Conclusions The SHIFT programme led to a potentially clinically meaningful difference in daily steps, between trial arms, at 6 months. Whilst the longer-term impact is unclear, the programme offers potential to be incorporated into driver training courses to promote activity in this at-risk, underserved and hard-to-reach essential occupational group. Trial registration ISRCTN10483894 (date registered: 01/03/2017)

Wild animals´ illegal or prohibited trade is a global problem and constitutes a serious risk to threatened and endangered species. The research was carried out in Niceto Pérez municipality, Río Frío locality in Guantánamo province. The objective was to determine the species of wild birds that are illegally traded and their abundance in the municipality. A total of 95 surveys were applied to people involved in poaching for various purposes. A total of 16 most traded species in the municipality were identified during the period from November 2018 to May 2019. 15 census routes of four m wide by 1 000 m long for a total of 6 ha were surveyed, within which ten counting points were established in each one, with a distance from each other of 100 m. All birds seen or heard during ten minutes were inventoried. As a result of the inventory, 20 bird species were counted, grouped into six orders, 15 families and 21 genera. The order Passeriformes was the most representative, 62 % were permanent residents; of these, only six species coincided with those reported in the surveys as illegally hunted. It was found that, there are significant differences in the areas studied between the months monitored, especially in those that coincide with the reproductive period of the species.

Abstract The contribution of domestic cattle in human societies is enormous, making cattle, along with other essential benefits, the economically most important domestic animal in the world today. To expand existing knowledge on cattle domestication and mitogenome diversity, we performed a comprehensive complete mitogenome analysis of the species (802 sequences, 114 breeds). A large sample was collected in South‐east Europe, an important agricultural gateway to Europe during Neolithization and a region rich in cattle biodiversity. We found 1725 polymorphic sites (810 singletons, 853 parsimony‐informative sites and 57 indels), 701 unique haplotypes, a haplotype diversity of 0.9995 and a nucleotide diversity of 0.0015. In addition to the dominant T3 and several rare haplogroups (Q, T5, T4, T2 and T1), we have identified maternal line in Austrian Murbodner cattle that possess surviving aurochs’ mitochondria haplotype P1 that diverged prior to the Neolithization process. This is convincing evidence for rare female‐mediated adaptive introgression of wild aurochs into domesticated cattle in Europe. We revalidated the existing haplogroup classification and provided Bayesian phylogenetic inference with a more precise estimated divergence time than previously available. Occasionally, classification based on partial mitogenomes was not reliable; for example, some individuals with haplogroups P and T5 were not recognized based on D‐loop information. Bayesian skyline plot estimates (median) show that the earliest population growth began before domestication in cattle with haplogroup T2, followed by Q (~10.0–9.5 kyBP), whereas cattle with T3 (~7.5 kyBP) and T1 (~3.0–2.5 kyBP) expanded later. Overall, our results support the existence of interactions between aurochs and cattle during domestication and dispersal of cattle in the past, contribute to the conservation of maternal cattle diversity and enable functional analyses of the surviving aurochs P1 mitogenome.

Prohibitin1 (PHB1) is a mitochondrial chaperone with diverse functions that include cell proliferation, apoptosis, and mitochondrial homoeostasis. Liver-specific Phb1 knockout (KO) mice develop spontaneous injury and hepatocellular carcinoma (HCC). Our previous work demonstrated that PHB1 negatively regulates the H19-insulin-like growth factor 2 (IGF2)-H19-IGF2 axis signaling pathway and E-box activity in hepatocytes and HCC cells. Phb1 KO livers exhibited increased expression of multiple wingless/integrated (WNT) target genes compared to control littermates. Therefore, we hypothesized that PHB1 is a negative regulator of WNT-beta-catenin signaling in the liver. Analysis of livers from Phb1 KO mice demonstrated an activation of the WNT-beta-catenin pathway as determined by phosphorylation of glycogen synthase kinase 3 (GSK3)betaserine [Ser]9 and protein kinase B (AKT)Ser473. Phb1 KO livers showed increased messenger RNA (mRNA) levels of multiple WNT ligands, with Wnt7a (79-fold), Wnt10a (12-fold), and Wnt16 (48-fold) being most highly overexpressed compared to control littermates. Subcellular fractionation of liver cells from Phb1 KO mice indicated that hepatocytes are the main source of WNT ligands. Immunostaining and cellular colocalization analysis of Phb1 KO livers demonstrated expression of WNT7a, WNT10a, and WNT16 in hepatocytes. Chromatin immunoprecipitation revealed increased binding of transcription factor E2F1 (E2F1) to the Wnt10a promoter in Phb1 KO livers and WNT9A in HepG2 cells. PHB1 silencing in HepG2 cells activated WNT signaling, whereas its overexpression caused inactivation of this pathway. PHB1 silencing in HepG2 cells induced the expression of multiple WNT ligands of which WNT9A induction was partly regulated through E2F1. Conclusion: PHB1 acts as a negative regulator of WNT signaling, and its down-regulation causes the induction of multiple WNT ligands and downstream activation of canonical WNT-beta-catenin signaling in murine liver and human HCC cells, in part through E2F1.

Machine learning is an important applied research area in particle physics, beginning with applications to high-level physics analysis in the 1990s and 2000s, followed by an explosion of applications in particle and event identification and reconstruction in the 2010s. In this document we discuss promising future research and development areas in machine learning in particle physics with a roadmap for their implementation, software and hardware resource requirements, collaborative initiatives with the data science community, academia and industry, and training the particle physics community in data science. The main objective of the document is to connect and motivate these areas of research and development with the physics drivers of the High-Luminosity Large Hadron Collider and future neutrino experiments and identify the resource needs for their implementation. Additionally we identify areas where collaboration with external communities will be of great benefit.

An 89-year-old man was hospitalized with severe pneumonia. Chest computed tomography showed a foreign body in the left main bronchus. We moulded a three-dimensional (3D) model of the foreign body with a low-cost 3D printer and found it had the shape of a tooth. We simulated grasping the model with several forceps and succeeded in grasping it with a retrieval net and shark-tooth forceps. Bronchoscopy was performed after his respiratory condition improved. We found a dental foreign body that had accidentally moved and become stuck in the right upper bronchus. We scraped it out with a retrieval net and grasped the recess site of the foreign body with a shark-tooth forceps as performed in the simulation. Removal was successful, and the total bronchoscopy time was 9 min. The bronchial foreign body was safely grasped and removed in a short time after simulation with several forceps using a low-cost 3D printer.

IntroductionTransforming consumption and lifestyles toward sustainability cannot be achieved by individual behavior change alone but requires changes in the structures in which this behavior is embedded. However, “structure” is a blurry concept and scholars use it in a multitude of ways. What often remains implicit in studies on structural phenomena are different types of structures, how they may or may not restrict the agency of individuals in particular ways, and how these restrictions support sustainable consumption patterns at the societal level. To move beyond the current state of research, this article systematizes political, economic, technological, and societal structural factors the literature identifies as impactful regarding the sustainability of consumption and lifestyles compatible with the targets of the Paris Agreement.MethodsWe draw on a systematic review of existing research and use empirical observations to develop conceptual terms that revisit the structure-agency dilemma and offer ways going forward about (un)sustainable consumption.ResultsWe do so based on the material or ideational, as well as shallow or deep nature of these factors. Thereby, the article throws light on the deep and opaque material and ideational structural factors lying underneath and shaping the sustainability impact of the more visible, shallow structural factors typically considered in public debates about sustainability governance.DiscussionThe article, thus, highlights the need to consider and address these deep structural factors for any effective pursuit of transformation.

Cancer cells harbor many genetic mutations and gene expression profiles different from normal cells. Patient-derived cancer cells (PDCC) are preferred materials in cancer study. We established patient-derived spheroids (PDSs) and patient-derived organoids (PDOs) from PDCCs isolated from the malignant pleural effusion in 8 patients. The morphologies suggested that PDSs may be a model of local cancer extensions, while PDOs may be a model of distant cancer metastases. The gene expression profiles differed between PDSs and PDOs: Gene sets related to inflammatory responses and EMT were antithetically regulated in PDSs or in PDOs. PDSs demonstrated an attenuation of the pathways that contribute to the enhancement of transforming growth factor beta (TGF-β) induced epithelial mesenchymal transition (EMT), while PDOs demonstrated an attenuation of it. Taken together, PDSs and PDOs have differences in both the interaction to the immune systems and to the stroma. PDSs and PDOs will provide a model system that enable intimate investigation of the behavior of cancer cells in the body.

Introducción: Se estima que 8% de la población experimenta dificultad para consumir alimentos sólidos y líquidos. Los pacientes con dieta de textura modificada suelen tener ingesta alimentaria variable. Objetivos: Medir el grado de adecuación a los requerimientos calóricos y proteicos en pacientes hospitalizados con dietas de textura modificada IDDSI niveles 4, 5 y 6. Determinar si existe asociación entre el porcentaje de adecuación y los niveles de textura. Materiales y métodos: Se evaluó la ingesta mediante un método de desperdicio de plato de 3 días. Los valores calóricos y proteicos fueron comparados con las IDR según estado nutricional. Se calculó el porcentaje de adecuación calórico y proteico. El análisis estadístico se realizó utilizando el Test de Kruskal Wallis para la comparación de medias según nivel IDDSI. Resultados: La muestra quedó conformada por 52 pacientes hospitalizados mayores de 18 años con indicación de dieta de textura modificada. La media del porcentaje de adecuación calórica fue 72,31%, 79,35%, 83,9 % para IDDSI 4, 5 y 6 respectivamente. La adecuación proteica fue del 71,89%, 77,25% y 80,75% para IDDSI 4, 5 y 6 respectivamente. Conclusiones: No existen diferencias estadísticamente significativas en el grado de adecuación calórica y proteica en cada uno de los grupos según los niveles de IDDSI. Se observa una tendencia a presentar un mayor porcentaje en la adecuación a los requerimientos tanto calóricos como proteicos a medida qué se incrementan los niveles de IDDSI. Palabras clave: IDDSI, adecuación a requerimientos calórico-proteicos, dieta de textura modificada.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a CAG repeat expansion in the ATXN3 gene. Though the ATXN3 protein is expressed ubiquitously throughout the CNS, regional pathology in SCA3 patients is observed within select neuronal populations and more recently within oligodendrocyte-rich white matter tracts. We have previously recapitulated these white matter abnormalities in an overexpression mouse model of SCA3 and demonstrated that oligodendrocyte maturation impairments are one of the earliest and most progressive changes in SCA3 pathogenesis. Disease-associated oligodendrocyte signatures have recently emerged as significant contributors to several other neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, but their role in regional vulnerability and disease progression remains unexplored. Here, we are the first to comparatively assess myelination in human tissue in a region-dependent manner. Translating these findings to SCA3 mouse models of disease, we confirmed endogenous expression of mutant Atxn3 leads to regional transcriptional dysregulation of oligodendrocyte maturation markers in Knock-In models of SCA3. We then investigated the spatiotemporal progression of mature oligodendrocyte transcriptional dysregulation in an overexpression SCA3 mouse model and how it relates to the onset of motor impairment. We further determined that regional reduction in mature oligodendrocyte cell counts in SCA3 mice over time parallels the onset and progression of brain atrophy in SCA3 patients. This work emphasizes the prospective contributions of disease-associated oligodendrocyte signatures to regional vulnerability and could inform timepoints and target regions imperative for biomarker assessment and therapeutic intervention in several neurodegenerative diseases.

COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.

Summary: Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a−/− mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a−/− mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a−/− mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins. A common mechanism found in both pre-disease and NASH livers was a hyperphosphorylation signature consistent with casein kinase 2α (CK2α) and AKT1 activation, which was normalized by SAMe administration. This was mimicked in human NAFLD with a metabolomic signature (M-subtype) resembling Mat1a−/− mice. In conclusion, we have identified a common proteome/phosphoproteome signature between Mat1a−/− mice and human NAFLD M-subtype that may have pathophysiological and therapeutic implications.

Abstract Background In recent years, various home‐use health devices have gained popularity. The abdominal roller is one of these. Spinal cord injury without radiological abnormality is known to occur even with relatively minor injuries, but there are few reports of such injuries caused by a roller. Case Presentation Two cases of spinal cord injuries caused by a roller are reported. In both cases, injuries occurred during the standing rollout by a patient in an inebriated state, and the patients were rushed to an emergency department. Conclusion Because the use of abdominal rollers may result in extremely serious disabilities, it is necessary to emphasize the appropriate use of such equipment.

Introduction: Extracellular vesicles (EVs) participate in cell-to-cell paracrine signaling and can be biomarkers of the pathophysiological processes underlying disease. In intracerebral hemorrhage, the study of the number and molecular content of circulating EVs may help elucidate the biological mechanisms involved in damage and repair, contributing valuable information to the identification of new therapeutic targets.Methods: The objective of this study was to describe the number and protein content of blood-derived EVs following an intracerebral hemorrhage (ICH). For this purpose, an experimental ICH was induced in the striatum of Sprague-Dawley rats and EVs were isolated and characterized from blood at baseline, 24 h and 28 days. The protein content in the EVs was analyzed by mass spectrometric data-dependent acquisition; protein quantification was obtained by sequential window acquisition of all theoretical mass spectra data and compared at pre-defined time points.Results: Although no differences were found in the number of EVs, the proteomic study revealed that proteins related to the response to cellular damage such as deubiquitination, regulation of MAP kinase activity (UCHL1) and signal transduction (NDGR3), were up-expressed at 24 h compared to baseline; and that at 28 days, the protein expression profile was characterized by a higher content of the proteins involved in healing and repair processes such as cytoskeleton organization and response to growth factors (COR1B) and the regulation of autophagy (PI42B).Discussion: The protein content of circulating EVs at different time points following an ICH may reflect evolutionary changes in the pathophysiology of the disease.

Patients with chronic lymphocyticleukemia (CLL) typically have innate/adaptive immune system dysregulation, thus the protective effect of coronavirus disease 2019 (COVID-19) vaccination remains uncertain. This prospective review evaluates vaccination response in these patients, including seropositivity rates by CLL treatment status, type of treatment received, and timing of vaccination. Antibody persistence, predictors of poor vaccine response, and severity of COVID-19 infection in vaccinated patients were also analyzed. Practical advice on the clinical management of patients with CLL is provided. Articles reporting COVID-19 vaccination in patients with CLL, published January 1, 2021–May 1, 2022, were included. Patients with CLL displayed the lowest vaccination responses among hematologic malignancies; however, seropositivity increased with each vaccination. One of the most commonly reported independent risk factors for poor vaccine response was active CLL treatment; others included hypogammaglobulinemia and age >65–70 years. Patients who were treatment-naive, off therapy, in remission, or who had a prior COVID-19 infection displayed the greatest responses. Further data are needed on breakthrough infection rates and a heterologous booster approach in patients with hematologic malignancies. Although vaccine response was poor for patients on active therapy regardless of treatment type, CLL management in the context of COVID-19 should aim to avoid delays in antileukemic treatment, especially with the advent of numerous strategies to mitigate risk of severe COVID-19 such as pre-exposure prophylaxis, and highly effective antivirals and monoclonal antibody therapy upon confirmed infection. Patients with CLL should remain vigilant in retaining standard prevention measures such as masks, social distancing, and hand hygiene.

Abstract Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.

Considering the challenging market conditions for dairy farms, calf gender management should be one of the tools used to increase profitability. The objective of this paper was to examine the effect of calf gender on lactation milk traits in Holstein and Simmental cows. Holstein cows that calved a female calf had a higher milk yield (p

Lower activity of MATα1, which catalyzes the synthesis of the methyl donor S-adenosylmethionine, and mitochondrial dysfunction occur in alcohol-associated liver disease (ALD). Here the authors report that the peptidyl-prolyl cis/trans isomerase PIN1 mediates a selective depletion of MATα1 in the mitochondria, which contributes to mitochondrial dysfunction and fat accumulation, in mouse models of ALD.