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Envisioning trajectories towards sustainability encompasses enacting significant changes in multiple spheres (i.e., infrastructure, policy, practices, behaviors). These changes unfold within the intricate landscapes of wicked problems, where diverse perspectives and potential solutions intersect and often clash. Advancing more equitable and sustainable trajectories demands recognition of and collaboration with diverse voices to uncover meaningful synergies among groups striving to catalyze substantial change. Projects of this nature necessitate the exploration of varied tools and methodologies to elicit, convey, and integrate ideas effectively. Creating spaces for reflexivity is essential for catalyzing more meaningful impact as individuals engage in discussions aimed at sharing and questioning the coherence of their projects while forging synergies, identifying common objectives, and planning long-term outcomes. We present the initial phase of an endeavor in which we developed a software that elicits causal networks based on mapping relations between projects' actions and outcomes. To illustrate our approach, we describe the results of using this software within collaborative workshops with groups spearheading projects initiated by a government entity in Mexico City. By adapting elements of the Theory of Change model, this software transcends the dominant linear project logic by guiding participants in designing causation networks that unveil how different projects can articulate to identify potential common elements and find new possibilities for coordination among initiatives. We discuss the potential of such software application as a dynamic tool to guide and promote reflection and coherence when crafting projects that aim to more meaningfully address sustainability problems. [ABSTRACT FROM AUTHOR]

1. This study investigated the effects of incorporating yellow mealworm (Tenebrio molitor) larval meal as a partial and/or complete substitute for soybean meal on carcass and meat quality in slow-growing chickens.2. A total of 256 one-day-old male broilers were randomly allocated to 1 of 32 experimental units distributed among four treatments (n = 8): the control treatment (C), where soybean (SB) meal was the protein source, and three experimental treatments, in which SB meal was replaced by Tenebrio molitor (TM) larval meal at levels of 50% (T1), 75% (T2) and 100% (T3), respectively. Three different feed phases (1–29; 29–57 and 57–92 d of age) were used for each treatment. All chickens were slaughtered at 92 d of age, with eight animals per treatment randomly selected to assess carcass and meat quality. Near-infrared reflectance spectroscopy (NIR) was used to classify meat quality.3. Carcass traits were not significantly different between treatments, except for head and thigh weight, which were higher in the control group (p < 0.01). In terms of physicochemical characteristics, treatment T2 showed less yellowness (p < 0.05), while water and cooking losses were lower in treatments T1 and T2 (p < 0.01). Meat from both T1 and T2 groups had lower shear forces (p < 0.01), higher moisture content (p < 0.01) and less protein (p < 0.05) compared to treatments C andT3. Birds fed T3 had the highest meat ash content (p < 0.01). Chickens consuming TM had higher monounsaturated fatty acid (MUFA) levels and lower polyunsaturated fatty acid (PUFA) and n-6 acidsPUFA (p < 0.01).4. Substitution of SB with TM is a protein alternative for slow-growing chickens that supports carcass and meat quality comparable to those fed a conventional diet. [ABSTRACT FROM AUTHOR]

Background and Aims: There are few data favoring the need for septotomy at the time of peroral endoscopic myotomy (POEM) or if POEM alone is sufficient. Our aim was to compare POEM outcomes with and without septotomy (POEM+S or POEM-S) in patients with symptomatic epiphrenic diverticula (ED) and an underlying motility disorder., Methods: This was an international, multicenter retrospective study involving 21 centers between January 2014 and January 2023. Patients with ED and an underlying motility disorder who underwent POEM were included. The primary outcome was clinical success (Eckardt score [ES] ≤3 or a 1-point drop in ES for patients with baseline ES <3) without the need for repeat surgical/endoscopic interventions during follow-up., Results: A total of 85 patients (mean age, 64.29 ± 17.1 years; 32 [37.6%] female) with ED and underlying motility disorder underwent POEM+S (n = 47) or POEM-S (n = 38). Patients in the POEM+S group had a significantly higher mean pre-POEM ES (7.3 ± 2.1 vs 5.8 ± 2; P = .002). The most common indication for POEM was achalasia (51% in the POEM+S cohort and 51.8% in the POEM-S cohort; P = .7). A posterior approach was favored in the POEM+S group (76.6% vs 52.6%; P = .02). A similar rate of technical success was seen in both groups (97.9% vs 100%; P = .1). The rate of adverse events was similar between the 2 cohorts (4.2% vs 8.1%; P = .6). The median length of hospital stay after POEM-S was significantly longer compared with POEM+S (2 days [interquartile range (IQR), 1-4 days] vs 1 day [IQR, 1-2 days]; P = .005). Clinical success was equivalent between the 2 groups (83% vs 86.8%; P = .6) at a median follow-up duration of 8 months (IQR, 3-19 months)., Conclusions: In patients with ED and an underlying motility disorder, both POEM+S and POEM-S are equally safe and effective, with similar procedure duration and a low recurrence rate at short-term follow-up. Future comparative prospective studies with long-term follow-up are required to validate these findings., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Schlachterman: receives monetary support from Lumendi, ConMed, Olympus, and Fujifilm. V. Velanovich: Consultant for Enterra Medical, Inc. R. Pawa: Consultant for Boston Scientific and Cook Medical. S. Pawa: Consultant for Boston Scientific. R. Bechara: receives monetary support from Olympus (consultant), Pentax (consultant) and Medtronic (advisory committee or review panels). M. A. Al-Haddad: Consultant for Boston Scientific and Interpace Diagnostics; grant/research support from Amplified Sciences, Cook Endoscopy, and Creatics LLC. M. Ujiki: receives grant funding from Medtronic; board member for Boston Scientific; consultant for Olympus and Cook; and receives payment for lectures from Gore, Medtronic, and ERBE. M. Barret: consultant for Medtronic and Norgine. K. Chang: receives monetary support from Apollo, Aqua Medical, Boston Scientific, Cook Medical, Creo Medical, Endogastric Solutions, ERBE, Medtronic, Mauna Kea, Olympus, Ovesco, and Pentax. H. Inoue: advisor for Olympus and Top Corporation; and receives educational grants from Olympus and Takeda Pharmaceuticals. M. A. Khashab: consultant for Boston Scientific, Olympus, Medtronic, Laborie, Pentax, and Apollo Endosurgery; and receives research/grant support from Boston Scientific and royalties from UpToDate and Elsevier. All other authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Therapy resistance is a major clinical hurdle in bone cancer treatment and seems to be largely driven by poorly understood microenvironmental factors. Recent evidence suggests a critical role for a unique subpopulation of mesenchymal stem cells with inflammatory features (iMSC), though their origin and function remained unexplored. We demonstrate that cancer-secreted extracellular vesicles (EV) trigger the development of iMSCs, which hinder therapy response in vivo, and set out to identify strategies to counteract their function., Experimental Design: The role of iMSCs in therapy resistance was evaluated in an orthotopic xenograft mouse model of osteosarcoma. EV-induced alterations of the MSC transcriptome were analyzed and compared with single-cell RNA sequencing data of biopsies from patients with osteosarcoma and multiple myeloma. Functional assays identified EV components driving iMSC development. We assessed the efficacy of clinical drugs in blocking iMSC-induced resistance in vivo., Results: We found that iMSCs are induced by interaction with cancer EVs and completely abrogate the antimetastatic effect of TGFβ signaling inhibition. Importantly, EV-induced iMSCs faithfully recapitulate the inflammatory single-cell RNA signature of stromal cells enriched in biopsies from patients with multiple myeloma and osteosarcoma. Mechanistically, cancer EVs act through two distinct mechanisms. EV-associated TGFβ induces IL6 production, whereas the EV-RNA cargo enhances TLR3-mediated chemokine production. We reveal that simultaneous blockade of downstream EV-activated pathways with ladarixin and tocilizumab disrupts metastasis formation and overcomes iMSC-induced resistance., Conclusions: Our observations establish iMSCs as major contributors to drug resistance, reveal EVs as triggers of iMSC development, and highlight a promising combination strategy to improve therapy response in patients with bone cancer., (©2024 American Association for Cancer Research.)

A full-scale passive treatment plant using barium carbonate (BaCO 3 ), the mineral witherite, as a Dispersed Alkaline Substrate (DAS) for strongly contaminated acid mine drainage was implemented for the first time globally at Mina Concepción, located in the Iberian Pyrite Belt (SW Spain). The plant was monitored over a 105-day period, covering the wettest months of the hydrological year and with a mean flow around 4 L s -1 . The AMD treated in the plant exhibits a high strength, with an average sulfate concentration around 1500 mg L -1 and net acidity close to 1000 mg L -1 as CaCO₃ equivalent. According to the above, the loading rate for SO 4 and Fe was around 400 and 80 kg day -1 , respectively. The treatment process produced an alkaline effluent with low metal content. Nearly complete removal of most metal(loid)s was achieved, with significant sulfate decrease to below 500 mg L -1 in the alkaline outflow of the barium carbonate tank. Barium carbonate demonstrated superior performance compared to magnesia, particularly in enhancing alkalinity and lowering net acidity and concentrations of sulfate and manganese. The high efficiency attained by the plant after the barium carbonate treatment is evidenced by compliance with environmental water quality standards for most contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Macrophages are usually present in solid tumors where they participate in tumor progression, angiogenesis, immunosuppression and metastasis. The design of nanocarriers capable of delivering therapeutic agents to specific cell populations has received considerable attention in the last decades. However, the capacity of many of these nanosystems to deliver multiple therapeutic agents with very different chemical properties is more limited. Herein, a novel multitasking nanoplatform capable of delivering large macromolecules and cytotoxic drugs to macrophages is presented. This novel nanosystem has exhibited excellent skills in performing simultaneous tasks, macrophage depletion and glucose starvation, maintaining the oxygen levels in the tissue. This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. The external surface of the silica core was coated with a lipid bilayer to avoid the premature release of the housed drugs. Finally, polymeric nanocapsules loaded with catalase were covalently anchored on the outer lipid bilayer, and carboxy-mannose was attached to the exposed side of the nanocapsules to provide selectivity to the macrophages. These nanoassemblies were able to transport enzymes (Gox and CAT), maintaining their catalytic activity. Therefore, they could induce glucose starvation, keeping the oxygen levels in the tissue, owing to the tandem enzymatic reaction. The capacity of these nanoassemblies to deliver therapeutic agents to macrophages was evaluated both in static and under flow conditions, showing a rapid capture of the nanoparticles by the macrophages. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.

Background: Despite a shortage of potential donors for heart transplant in the United States, most potential donor hearts are discarded. We evaluated predictors of donor heart acceptance in the United States and applied machine learning methods to improve prediction., Methods: We included a nationwide (2005-2020) cohort of potential heart donors in the United States (n=73 948) from the Scientific Registry of Transplant Recipients and a more recent (2015-2020) rigorously phenotyped cohort of potential donors from DHS (Donor Heart Study; n=4130). We identified predictors of acceptance for heart transplant in both cohorts using multivariate logistic regression, incorporating time-interaction terms to characterize their varying effects over time. We fit models predicting acceptance for transplant in a 50% training subset of DHS using logistic regression, least absolute shrinkage and selection operator, and random forest algorithms and compared their performance in the remaining 50% (test) of the subset., Results: Predictors of donor heart acceptance were similar in the nationwide and DHS cohorts. Among these, older age ( P value for time interaction, 0.0001) has become increasingly predictive of discard over time while other factors, including those related to drug use, infection, and mild cardiac diagnostic abnormalities, have become less influential ( P value for time interaction, <0.05 for all). A random forest model (area under the curve, 0.908; accuracy, 0.831) outperformed other prediction algorithms in the test subset and was used as the basis of a novel web-based prediction tool., Conclusions: Predictors of donor heart acceptance for transplantation have changed significantly over the last 2 decades, likely reflecting evolving evidence regarding their impact on posttransplant outcomes. Real-time prediction of donor heart acceptance, using our web-based tool, may improve efficiency during donor management and heart allocation., Competing Interests: None.

A 38-year-old man presented with an erythematous papule over a longstanding back tattoo. Dermoscopic examination revealed a polymorphous vascular pattern with serpentine and dotted vessels, and shiny white-blueish lines indicating a fibrous stroma mixed with tattoo pigment. Histopathological analysis confirmed fibroepithelioma of Pinkus (FeP). FeP typically presents as an erythematous or hypopigmented tumor and may mimic benign and malignant lesions. This case highlights the unique presentation of FeP over a tattoo, underscoring the importance of dermoscopy in differential diagnosis. Surgical excision remains the treatment of choice. This is the first documented case of FeP arising over a tattoo., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Three experiments with rats examined the impact of a retrieval-extinction procedure on ABA and AAB renewal of instrumental learning. In all experiments, rats were trained to run down an alley for alcoholic beer in Context A. Then, the instrumental response underwent extinction, which was conducted in Context B for Experiments 1 and 2, and in Context A for Experiment 3. In each experiment, one group of animals received a brief exposure to the beer prior to each extinction session, whereas this beer exposure was omitted for a second group. Moreover, Experiment 2 comprised a third group that was exposed to non-alcoholic beer before each extinction session. Finally, all rats were tested in their extinction context and in a second context, which was Context A for Experiments 1 and 2, and Context B for Experiment 3. We found ABA (Experiments 1 and 2) and AAB (Experiment 3) renewal of beer seeking in those animals for which beer exposure prior to extinction was omitted. However, response recovery was not evident when animals received exposure to beer before extinction, regardless of whether alcoholic or non-alcoholic beer was used. Our results suggest that the renewal of alcohol seeking can be prevented by means of the retrieval-extinction paradigm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Gene Regulatory Network (GRN) inference is a fundamental task in biology and medicine, as it enables a deeper understanding of the intricate mechanisms of gene expression present in organisms. This bioinformatics problem has been addressed in the literature through multiple computational approaches. Techniques developed for inferring from expression data have employed Bayesian networks, ordinary differential equations (ODEs), machine learning, information theory measures and neural networks, among others. The diversity of implementations and their respective customization have led to the emergence of many tools and multiple specialized domains derived from them, understood as subsets of networks with specific characteristics that are challenging to detect a priori. This specialization has introduced significant uncertainty when choosing the most appropriate technique for a particular dataset. This proposal, named MO-GENECI, builds upon the basic idea of the previous proposal GENECI and optimizes consensus among different inference techniques, through a carefully refined multi-objective evolutionary algorithm guided by various objective functions, linked to the biological context at hand., Methods: MO-GENECI has been tested on an extensive and diverse academic benchmark of 106 gene regulatory networks from multiple sources and sizes. The evaluation of MO-GENECI compared its performance to individual techniques using key metrics (AUROC and AUPR) for gene regulatory network inference. Friedman's statistical ranking provided an ordered classification, followed by non-parametric Holm tests to determine statistical significance., Results: MO-GENECI's Pareto front approximation facilitates easy selection of an appropriate solution based on generic input data characteristics. The best solution consistently emerged as the winner in all statistical tests, and in many cases, the median precision solution showed no statistically significant difference compared to the winner., Conclusions: MO-GENECI has not only demonstrated achieving more accurate results than individual techniques, but has also overcome the uncertainty associated with the initial choice due to its flexibility and adaptability. It is shown intelligently to select the most suitable techniques for each case. The source code is hosted in a public repository at GitHub under MIT license: https://github.com/AdrianSeguraOrtiz/MO-GENECI. Moreover, to facilitate its installation and use, the software associated with this implementation has been encapsulated in a Python package available at PyPI: https://pypi.org/project/geneci/., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Victor M. Barberá reports financial support was provided by Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Spain. Camino de Juan Romero and Miguel Saceda reports financial support was provided by Carlos III Health Institute, Spain and the Consellería de Innovación, Universidades, Ciencia y Sociedad Digital (Generalitat Valenciana), Spain., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Background: Viral infections are known to impact the pancreato-biliary system; however, there are limited data showing that the same is true of COVID-19. Endoscopic retrograde cholangiopancreatography (ERCP) can safely be performed in patients with COVID-19 infection, but outcomes of patients with COVID-19 infections and concomitant pancreatic and biliary disease requiring endoscopic intervention are unknown., Aims: This study aims to evaluate the severity of pancreaticobiliary diseases and post-ERCP outcomes in COVID-19 patients., Methods: Patients with pancreato-biliary disease that required inpatient ERCP from five centers in the United States and South America between January 1, 2020, and October 31, 2020 were included. A representative cohort of patients from each month were randomly selected from each site. Disease severity and post-ERCP outcomes were compared between COVID-19 positive and COVID-19 negative patients., Results: A total of 175 patients were included: 95 COVID positive and 80 COVID negative. Mean CTSI score for the patients who had pancreatitis was higher in COVID-positive cohort by 3.2 points (p < .00001). The COVID-positive group had more cases with severe disease (n = 41) versus the COVID-negative group (n = 2) (p < .00001). Mortality was higher in the COVID-19 positive group (19%) compared to COVID-negative group (7.5%) even though the COVID-19-negative group had higher incidence of malignancy (n = 17, 21% vs n = 7, 7.3%) (p = 0.0455)., Conclusions: This study shows that patients with COVID infection have more severe pancreato-biliary disease and worse post-ERCP outcomes, including longer length of stay and higher mortality rate. These are important considerations when planning for endoscopic intervention., Clinicaltrials: gov: (NCT05051358)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry., Methods: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (Steris, Mentor, Ohio, USA) (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma. Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated., Results: Among 138 subjects with low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after 2 years and 67% and 92% after 3 years. In RFA-naïve patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 0.22-0.69) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n = 6) at a mean follow-up of 2.5 years after CEIM., Conclusion: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for the treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort, approximately 50% attained CEIM at 3 years., Competing Interests: Disclosure The following authors disclosed financial relationships: V. Kaul: Ad hoc consultant for Steris. B. Greenwald: consultant for Steris Endoscopy. N. J. Shaheen: grant support from Steris, Lucid, Pentax, Interpace, and CDx Medical. Consultant for Exact Sciences. All other authors disclosed no financial relationships. This study was supported by grants from CSA Medical, Steris, and National Institutes of Health award number K23DK121338 (to S. Eluri)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for patients with gastric outlet obstruction without the risks of surgical bypass and the limited long-term efficacy of enteral self-expanding metal stent placement. However, due to its novelty, there is a lack of significant data comparing long-term outcomes of patients with EUS-GE, based on the underlying disease. In this study, we compare outcomes of EUS-GE on benign versus malignant indications., Methods: Consecutive patients from 12 international, tertiary care centers who underwent EUS-GE over 3 years were extracted in a retrospective registry. Demographic characteristics, procedure-related information and follow-up data was collected. Primary outcome was the rate of adverse events associated with EUS-GE and the comparison of the rate of adverse events in benign versus malignant diseases. Secondary outcomes included technical and clinical success as well as hospitalization admission., Results: A total of 103 patients were included: 72 malignant and 31 benign. The characteristics of the patients undergoing EUS-GE is shown in Table 1. The mean age of the cohort was 68 years and 58 years for malignant and benign etiology. Gender distribution was 57% and 39% being females in malignant and benign etiology group, respectively. Clinical success, technical success, average procedure time, and hospital length of stay were similar in both groups. Patients with benign underlying etiology had significantly higher number of surgically altered midgut anatomy ( P =0.0379)., Conclusion: EUS-GE is equally efficient regardless of the underlying etiology (malignant vs. benign), and the adverse events both groups were comparable., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Trypanosoma cruzi , the causative agent of Chagas disease ( American trypanosomiasis ), is a highly complex zoonosis that is present throughout South America, Central America, and Mexico. The transmission of this disease is influenced by various factors, including human activities like deforestation and land use changes, which may have altered the natural transmission cycles and their connection to the environment. In this study conducted in the Argentine Chaco region, we examined the transmission dynamics of T. cruzi by collecting blood samples from wild and domestic animals, as well as triatomine bugs from human dwellings, across five sites of varying anthropic intervention. Samples were analyzed for T. cruzi infection via qPCR, and we additionally examined triatomines for bloodmeal analysis via NGS amplicon sequencing. Our analysis revealed a 15.3% infection rate among 20 wild species (n = 123) and no T. cruzi presence in 9 species of domestic animals (n = 1359) or collected triatomines via qPCR. Additionally, we found chicken (34.28%), human (21.59%), and goat (19.36%) as the predominant bloodmeal sources across all sites. These findings suggest that anthropic intervention and other variables analyzed may have directly impacted the spillover dynamics of T. cruzi 's sylvatic cycle and potentially reduced its prevalence in human habitats.

Background: Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb., Objectives: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin., Study Design: Randomised cross-over in vivo experiment., Methods: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay., Results: Measurable concentrations of morphine were apparent in the RCJ of all horses. Median C MAX of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median C MAX of synovial amikacin was 322.6 (157.5-1371.6 μg/mL)., Main Limitations: Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included., Conclusions: IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects., (© 2024 EVJ Ltd.)

Presently, there has been a noticeable rise in the consumption of poultry meat within the general population, particularly focusing on poultry sourced from alternative rearing systems as opposed to intensive ones. This study evaluated the impact of incorporating house cricket (Acheta domesticus,AD) larvae meal into the diet of 2 slow-growing chicken strains on their carcass traits and meat quality. A total of 256 one-day-old male chicks were utilized, with 128 belonging to the Red (R) strain and 128 to the Naked Neck (NN) strain. Chicks from each strain were randomly assigned to 16 replicates of 8 chicks each. Eight replicates were allocated to 2 distinct treatments (n=64 chicks/treatment) based on the diet employed: the control treatments for the Red (R-C) and Naked Neck (NN-C) strains were fed soybean meal, while the other 2 treatments were fed AD meal (R-AD and NN-AD). Three different rations were used throughout the growth cycle of the animals, tailored to meet the nutritional needs of the birds. All chickens were slaughtered at 95 d of age, and eight chickens per treatment were randomly chosen to assess carcass traits and meat quality. Near-infrared reflectance spectroscopy (NIRS) was employed to classify meat based on the feed and the chick strain, achieving a correct discrimination of 100% of the samples. The carcass traits exhibited significant alterations due to the inclusion of insect larval meal in the diet, resulting in reduced values across all parameters for chickens consuming AD meal, irrespective of genotype. The pH and cooking losses were generally higher for chicks fed cricket meal, as occurred with moisture. However, protein content was lower in the meat of chicks consuming cricket meal. Fat content showed lower values for NN chickens. There were minimal differences in the fatty acid profile, with lower C18:3n-3 values for chickens fed cricket meal. Therefore, including Acheta domesticus meal in the diets of slow-growing chick strains is a viable alternative to replace soybean meal. It provides meat quality characteristics comparable to those obtained in conventional systems., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate., Animals: 7 healthy horses., Methods: Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay., Results: The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004)., Clinical Relevance: Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses.

Background: Potential organ donors often exhibit abnormalities on electrocardiograms (ECGs) after brain death, but the physiological and prognostic significance of such abnormalities is unknown., Objectives: This study sought to characterize the prevalence of ECG abnormalities in a nationwide cohort of potential cardiac donors and their associations with cardiac dysfunction, use for heart transplantation (HT), and recipient outcomes., Methods: The Donor Heart Study enrolled 4,333 potential cardiac organ donors at 8 organ procurement organizations across the United States from 2015 to 2020. A blinded expert reviewer interpreted all ECGs, which were obtained once hemodynamic stability was achieved after brain death and were repeated 24 ± 6 hours later. ECG findings were summarized, and their associations with other cardiac diagnostic findings, use for HT, and graft survival were assessed using univariable and multivariable regression., Results: Initial ECGs were interpretable for 4,136 potential donors. Overall, 64% of ECGs were deemed clinically abnormal, most commonly as a result of a nonspecific St-T-wave abnormality (39%), T-wave inversion (19%), and/or QTc interval >500 ms (17%). Conduction abnormalities, ectopy, pathologic Q waves, and ST-segment elevations were less common (each present in ≤5% of donors) and resolved on repeat ECGs in most cases. Only pathological Q waves were significant predictors of donor heart nonuse (adjusted OR: 0.39; 95% CI: 0.29-0.53), and none were associated with graft survival at 1 year post-HT., Conclusions: ECG abnormalities are common in potential heart donors but often resolve on serial testing. Pathologic Q waves are associated with a lower likelihood of use for HT, but they do not portend worse graft survival., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP., Methods: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety., Results: A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%)., Conclusion: We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies., Clinicaltrials: gov, Number: NCT02693093., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Despite the wealth of publicly available single-cell datasets, our understanding of distinct resident immune cells and their unique features in diverse human organs remains limited. To address this, we compiled a meta-analysis dataset of 114,275 CD45+ immune cells sourced from 14 organs in healthy donors. While the transcriptome of immune cells remains relatively consistent across organs, our analysis has unveiled organ-specific gene expression differences (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are linked to different transcriptional factor activities and pathways including metabolism. TNF-α signaling through the NFkB pathway was found in several organs and immune compartments. The presence of distinct expression profiles for NFkB family genes and their target genes, including cytokines, underscores their pivotal role in cell positioning. Taken together, immune cells serve a dual role: safeguarding the organs and dynamically adjusting to the intricacies of the host organ environment, thereby actively contributing to its functionality and overall homeostasis., (© 2024. The Author(s).)

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study., Methods: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops., Results: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care., Conclusion: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention., Competing Interests: Competing interests: NS, JG-N, KAI and JH report no competing interests. LJB was funded by an ESRC Post-doctoral fellowship ES/X005259/1 and was supported by the NIHR Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. CMN reports funding from the Royal Brompton and Harefield Charity, National Institute for Health Research for Patient Benefit and Brunel University London BRIEF award. WD-CM reports grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Duodenoscope-related multidrug-resistant organism (MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography (ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy., Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score (1 to 10) on performance rating of the single-use duodenoscope, and adverse event (AE) rate., Results: A total of 66 patients (26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47 (71.2%) grade 3 and 19 (28.8%) grade 4. The technical success rate was 98.5% (65/66). Procedural duration was 64 (interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66 (1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients (6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis (PEP), 1 cholangitis and 1 bleeding., Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)