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Abstract BackgroundThe 2022 mpox outbreak in the United States disproportionately affected gay, bisexual, and other men who have sex with men (GBMSM). Uptake of mpox testing may be related to symptomology, sociodemographic characteristics, and behavioral characteristics. ObjectiveThis study aimed to describe suspected mpox symptoms and testing uptake among a sample of GBMSM recruited via the internet in the United States in August 2022. MethodsWe conducted a rapid internet-based mpox survey from August 5 to 15, 2022, among cisgender men 15 years and older who had previously participated in the 2021 American Men’s Internet Survey. We estimated the prevalence of suspected mpox symptoms (fever or rash or sores with unknown cause in the last 3 mo) and uptake of mpox testing. We calculated adjusted prevalence ratios (aPRs) and 95% CIs for associations between participant characteristics and suspected mpox symptoms and summarized characteristics of GBMSM reporting mpox testing. Among symptomatic GBMSM who did not receive mpox testing, we described testing self-efficacy, barriers, and facilitators. ResultsOf 824 GBMSM, 126 (15.3%) reported at least 1 mpox symptom in the last 3 months; 58/126 (46%) with rash or sores, 57 (45.2%) with fever, and 11 (8.7%) with both. Increased prevalence of suspected mpox symptoms was associated with condomless anal sex (CAS; aPR 1.53, 95% CI 1.06‐2.20). Mpox testing was reported by 9/824 GBMSM (1%), including 5 with symptoms. Most GBMSM reporting mpox testing were non-Hispanic White men (7/9 vs 1 Black and 1 Hispanic or Latino man), and all 9 lived in urban areas. Most reported having an sexually transmitted infections test (8/9), 2 or more partners (8/9), CAS (7/9), and group sex (6/9) in the last 3 months. Of those tested, 3 reported living with HIV and all were on treatment, whereas the remaining 6 men without HIV reported current pre-exposure prophylaxis (PrEP) use. Of symptomatic GBMSM who did not report mpox testing, 47/105 (44.8%) had low mpox testing self-efficacy. Among those with low self-efficacy, the most common barriers to testing were not knowing where to get tested (40/47, 85.1%) and difficulty getting appointments (23/47, 48.9%). Among those with high testing self-efficacy (58/105, 55.2%), the most common facilitators to testing were knowing where to test (52/58, 89.7%), convenient site hours (40/58, 69%), and low-cost testing (38/58, 65.5%). ConclusionsWhile all GBMSM who reported testing for mpox were linked to HIV treatment or PrEP, those with symptoms but no mpox testing reported fewer such links. This suggests targeted outreach is needed to reduce structural barriers to mpox services among GBMSM in rural areas, Black and GBMSM, and GBMSM living with HIV. Sustaining and scaling community-tailored messaging to promote testing and vaccination represent critical interventions for mpox control among GBMSM in the United States.

Introduction: This research aims to characterize disparities in mpox- and vaccine-related knowledge in gay, bisexual, and other men who have sex with men in the U.S. Methods: The authors conducted a study using the American Men's Internet Survey, which includes 823 cisgender (defined as their gender identity matching their sex assigned at birth) males aged ≥15 years from August 5 to 15, 2022. The authors evaluated sociodemographic and behavioral factors associated with mpox knowledge, including race/ethnicity, region, age group, and HIV pre-exposure prophylaxis use using chi-square tests. Results: The authors identified knowledge gaps, with many participants unsure about whether individuals need 2 doses of the vaccine (34.4%) and whether the vaccine confers immediate protection (27.2%). The authors observed racial and regional disparities (p

Severe COVID-19 and MIS-C are rare but serious outcomes associated with SARS-CoV-2 infection. The onset of MIS-C often involves the gastrointestinal system, suggesting a potential connection with gut microbiota. This study aims to compare the gut microbiota of children with severe COVID-19 and those with MIS-C using various biomolecular approaches. Gut microbiota composition and specific microbial modulations were analyzed using fecal samples collected at hospital admission. The study included hospitalized patients (mean age 6 ± 5 years) diagnosed with severe COVID-19 (37 patients) or MIS-C (37 patients). Microbial differences were assessed using both NGS and qRT-PCR methodologies. In 75% of cases, pharmacological treatments included antibiotics and corticosteroids, which influenced the microbiota composition. Early age was found to have the most significant impact on microbiota diversity. Significant differences in alpha and beta diversity were observed between COVID-19 and MIS-C patients, particularly concerning low-abundance species. Levels of Bacteroides spp., Bifidobacterium spp., and Akkermansia muciniphila were comparable between groups, while an increased activity of Bifidobacterium spp. was noted in children with positive fecal samples (p = 0.019). An in-depth evaluation of lesser-known gut species may be key to reducing the risk of severe outcomes and developing microbiota-based biomarkers for the early diagnosis of MIS-C.

Background & Aims: Patients with intrahepatic cholangiocarcinoma can now be managed with targeted therapies directed against specific molecular alterations. Consequently, tissue samples submitted to the pathology department must produce molecular information in addition to a diagnosis or, for resection specimens, staging information. The pathologist’s role when evaluating these specimens has therefore changed to accommodate such personalised approaches. Methods: We developed recommendations and guidance for pathologists by conducting a systematic review of existing guidance to generate candidate statements followed by an international Delphi process. Fifty-nine pathologists from 28 countries in six continents rated statements mapped to all elements of the specimen pathway from receipt in the pathology department to authorisation of the final written report. A separate survey of ‘end-users’ of the report including surgeons, oncologists, and gastroenterologists was undertaken to evaluate what information should be included in the written report to enable appropriate patient management. Results: Forty-eight statements reached consensus for inclusion in the guidance including 10 statements about the content of the written report that also reached consensus by end-user participants. A reporting proforma to allow easy inclusion of the recommended data points was developed. Conclusions: These guiding principles and recommendations provide a framework to allow pathologists reporting on patients with intrahepatic cholangiocarcinoma to maximise the informational yield of specimens required for personalised patient management. Impact and Implications: Biopsy or resection lesional tissue from intrahepatic cholangiocarcinoma must yield information about the molecular abnormalities within the tumour that define suitability for personalised therapies in addition to a diagnosis and staging information. Here, we have developed international consensus guidance for pathologists that report such cases using a Delphi process that sought the views of both pathologists and ‘end-users of pathology reports. The guide highlights the need to report cases in a way that preserves tissue for molecular testing and emphasises that reporting requires interpretation of histological characteristics within the broader clinical and radiological context. The guide will allow pathologists to report cases of intrahepatic cholangiocarcinoma in a uniform manner that maximises the value of the tissue received to facilitate optimal multidisciplinary patient management.

Food authentication significantly impacts consumer health and the credibility of Food Business Operators (FBOs). As European regulations mandate the verification of food authenticity and supply chain integrity, competent authorities require access to innovative analytical methods to identify and prevent food fraud. This study utilizes the DNA metabarcoding approach on meat preparations, sampled during an official control activity. It assesses animal and plant composition by amplifying DNA fragments of the 12S rRNA and trnL (UAA) genes, respectively. The results not only confirmed the declared species but also revealed undeclared and unexpected taxa in products labelled as containing a single animal species and various unspecified plant species. Notable findings such as the presence of Murinae, Sus scrofa, Ovis aries, and Pisum sativum could raise public health concerns, compromise consumer choices made for ethical or religious reasons, and reflect the hygienic conditions of the processing plant. This study demonstrates that the DNA metabarcoding approach looks to be a promising support tool for official control authorities to ensure food authenticity and safety, and to develop risk profiles along the supply chain.

IntroductionMalgré l’association connue entre consommation de cannabis et prévalence accrue d’idées suicidaires et de tentatives de suicide, on n’a pas encore mesuré l’effet de la légalisation et de la réglementation du cannabis au Canada sur les lésions auto-infligées. MéthodologieNous avons utilisé des séries chronologiques interrompues des taux de consultation aux urgences et d’hospitalisation pour lésions auto-infligées pour 100 000 habitants en Ontario et en Alberta entre janvier ou avril 2010 et février 2020. Les effectifs mensuels globaux de consultations aux urgences et d’hospitalisations pour lésions auto-infligées (codes X60-X84 et R45.8 selon la CIM-10) ont été obtenus grâce respectivement au Système national d’information sur les soins ambulatoires et à la Base de données sur les congés des patients. RésultatsLa légalisation et la réglementation du cannabis au Canada n’ont pas été associées de manière statistiquement significative à une modification des taux de consultation aux urgences pour lésions auto-infligées en Ontario (niveau = 0,58 avec IC à 95 % : −1,14 à 2,31; tendance = −0,17 avec IC à 95 % : −0,35 à 0,01) ou en Alberta (niveau = −0,06 avec IC à 95 % : −2,25 à 2,12; tendance = −0,07 avec IC à 95 % : −0,27 à 0,13). Les hospitalisations pour lésions auto-infligées sont également demeurées inchangées en Ontario (niveau = −0,14 avec IC à 95 % : −0,48 à 0,20; tendance = 0,01 avec IC à 95 % : −0,03 à 0,04) et en Alberta (niveau = −0,41 avec IC à 95 % : −1,03 à 0,21; tendance = −0,03 avec IC à 95 % : −0,08 à 0,03). ConclusionLa légalisation et la réglementation du cannabis au Canada n’ont pas entraîné d’augmentation des taux de consultation aux urgences ou d’hospitalisation pour lésions auto-infligées en Ontario ou en Alberta. Des analyses à l’échelle individuelle tenant compte des caractéristiques individuelles et incluant d’autres provinces et territoires sont nécessaires.

IntroductionDespite the association between cannabis use and higher prevalence of suicidal ideation and attempt, the effect of cannabis legalization and regulation in Canada on intentional self-harm has not been determined. MethodsWe used an interrupted time series of population-based rates of emergency department (ED) visits and hospitalizations for intentional self-harm per 100 000 in Ontario and Alberta from January/April 2010 to February 2020. Aggregate monthly counts of ED visits and hospitalizations for intentional self-harm (ICD-10 codes X60–X84, R45.8) were obtained from the National Ambulatory Care Reporting System and Discharge Abstract Database, respectively. ResultsThe legalization and regulation of cannabis in Canada was not significantly associated with a change in rates of ED visits for intentional self-harm in Ontario (level = 0.58, 95% CI: −1.14 to 2.31; trend = −0.17, 95% CI: −0.35 to 0.01) or Alberta (level = −0.06, 95% CI: −2.25 to 2.12; trend = −0.07, 95% CI: −0.27 to 0.13). Hospitalizations for intentional self-harm also remained unchanged in Ontario (level = −0.14, 95% CI: −0.48 to 0.20; trend = 0.01, 95% CI: −0.03 to 0.04) and Alberta (level = −0.41, 95% CI: −1.03 to 0.21; trend = −0.03, 95% CI: −0.08 to 0.03). ConclusionLegalization and regulation of cannabis in Canada has not increased rates of ED visits or hospitalizations for intentional self-harm in Ontario and Alberta. Individual-level analyses that account for demographic characteristics and include other provinces and territories are needed.

Abstract A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner’s Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner’s Glands and in PDGs nearest the duodenum, and in humans are in Brunner’s Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors’ responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as “not at all” (87%), “somewhat” (11%), “moderately” (1%) and “very much so” (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96–100%. The five lowest rated items (range 78–85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.

Extra virgin olive oil (EVOO) is a precious and healthy ingredient of Mediterranean cuisine. Due to its high nutritional value, the interest of consumers in the composition of EVOO is constantly increasing, making it a product particularly exposed to fraud. Therefore, there is a need to properly valorize high-quality EVOO and protect it from fraudulent manipulations to safeguard consumer choices. In our study, we used a straightforward and easy method to assess the molecular traceability of 28 commercial EVOO samples based on the use of SSR molecular markers. A lack of correspondence between the declared origin of the samples and the actual origin of the detected varieties was observed, suggesting possible adulteration. This result was supported by the identification of private alleles based on a large collection of national and international olive varieties and the search for them in the molecular profile of the analyzed samples. We demonstrated that the proposed method is a rapid and straightforward approach for identifying the composition of an oil sample and verifying the correspondence between the origin of olives declared on the label and that of the actual detected varieties, allowing the detection of possible adulterations.

The global construction industry significantly contributes to energy consumption and greenhouse gas emissions, necessitating immediate action for sustainable development. Recognizing the impact of buildings on emissions, the United Nations has set ambitious energy-related goals for 2030. Retrofitting buildings emerges as a strategic method for reducing energy consumption, offering lower environmental impact and life cycle costs. However, retrofitting is a complex process influenced by diverse factors such as policies, available resources, techniques, building-specific data, and uncertainties. Thus, this paper reviews the existing literature on retrofitting strategies for tropical and humid climates to identify effective approaches for enhancing energy efficiency, thermal comfort, and overall building performance in these regions. Through comprehensive analyses, including bibliometric analysis using VOSviewer version 1.6.18 and systematic assessments, this study investigates various retrofitting strategies. This study categorizes tropical climates into Af (Tropical Rainforest Climate) and Aw (Tropical Savanna Climate) based on the Köppen climate classification. It reveals distinct emphases, with Af climates concentrating on office buildings and Aw climates prioritizing residential structures. Passive strategies were predominantly favored in office buildings, with glazing being the most commonly implemented approach. Residential structures, on the other hand, adopted a combination of passive strategies such as phase change materials along with active methods like appliance replacement. Educational buildings tended to rely on passive strategies, including roof covers, shading, and glazing. The absence of specific cost values underscores the importance of establishing baseline metrics, revealing significant challenges in retrofit techniques. This study further highlights an opportunity to explore passive methods in educational buildings, stressing the need for comprehensive guidelines, especially in institutional settings. Moreover, it emphasizes the urgency for ambitious regulations to address carbon emissions and optimize energy efficiency in tropical climates.

Background & Aims: Primary sclerosing cholangitis (PSC) leads to ductular reaction and fibrosis and is complicated by vascular dysfunction. Cholangiocyte and endothelial cell crosstalk modulates their proliferation in cholestatic models. Endothelin (ET)-1 and ET-2 bind to their receptor, ET-A, and cholangiocytes are a key source of ET-1 after bile duct ligation. We aimed to evaluate the therapeutic potential of ET-A inhibition in PSC and biliary-endothelial crosstalk mediated by this pathway. Methods: Wild-type and multidrug resistance 2 knockout (Mdr2-/-) mice at 12 weeks of age were treated with vehicle or Ambrisentan (ET-A antagonist) for 1 week by daily intraperitoneal injections. Human control and PSC samples were used. Results: Mdr2-/- mice at 4, 8, and 12 weeks displayed angiogenesis that peaked at 12 weeks. Mdr2-/- mice at 12 weeks had enhanced biliary ET-1/ET-2/ET-A expression and secretion, whereas human PSC had enhanced ET-1/ET-A expression and secretion. Ambrisentan reduced biliary damage, immune cell infiltration, and fibrosis in Mdr2-/- mice. Mdr2-/- mice had squamous cholangiocytes with blunted microvilli and dilated arterioles lacking cilia; however, Ambrisentan reversed these alterations. Ambrisentan decreased cholangiocyte expression of pro-angiogenic factors, specifically midkine, through the regulation of cFOS. In vitro, ET-1/ET-A caused cholangiocyte senescence, endothelial cell angiogenesis, and macrophage inflammation. In vitro, human PSC cholangiocyte supernatants increased endothelial cell migration, which was blocked with Ambrisentan treatment. Conclusions: ET-A inhibition reduced biliary and liver damage in Mdr2-/- mice. ET-A promotes biliary angiocrine signaling that may, in turn, enhance angiogenesis. Targeting ET-A may prove therapeutic for PSC, specifically patients displaying vascular dysfunction.

The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial–mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFβ receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFβ signaling in regulating this process.

To achieve sustainable cities and communities, it is necessary to decarbonize existing buildings. Actions need to be taken to reduce the buildings’ energy demand and ensure that the low remaining demand is met by energy produced from renewable sources. This leads to Net Zero Energy Buildings (NZEBs), whose impact on energy consumption is zero or positive, meaning that they are able to produce more energy than they require. The “zero” objective may be difficult to reach in hot and humid climates, where the cooling demand is prevalent. In this case, a combination of active and passive measures, together with appropriate interaction with users, is a viable way to obtain NZEBs. The present study aims to explore technological solutions for renovating existing buildings to NZEBs in a tropical climate. The analysis is developed through a parametric analysis, a sensitivity analysis, and an optimization directed at minimizing the site’s net energy and hours of discomfort. Evaluations are conducted for a case study consisting of a single-family house located in Panama City. The results showed that photovoltaic size, cooling operation schedule, and cooling set-point temperature are the most influential variables for the attainment of NZEBs in a hot climate. Regarding the building envelope, the outcomes suggest the low insulation of dispersing structures and local solar shading of windows as recommended measures.

Abstract Bile ducts are heterogenous in structure and function, and primary sclerosing cholangitis (PSC) damages specific bile ducts leading to ductular reaction (DR), mast cell (MC) infiltration, increased histamine release, inflammation, and fibrosis. Bile duct ligation (BDL) induces large duct damage via cyclic adenosine monophosphate (cAMP)/extracellular signal‐related protein kinase (ERK) signaling, and large cholangiocytes express H2 histamine receptor (H2HR). We evaluated how MCs interact with large cholangiocytes during cholestasis. Male wild‐type (WT) and MC‐deficient (KitW‐sh) mice 10–12 weeks of age were subjected to BDL for 7 days. Select KitW‐sh mice were injected with MCs pretreated with control or H2HR antagonist (ranitidine, 25 μm, 48 h) via tail vein injection. In vitro, MC migration toward small mouse cholangiocytes (SMCCs) and large mouse cholangiocytes (LMCCs) treated with lipopolysaccharide or histamine (±ranitidine) was measured. LMCCs were stimulated with MC supernatants pretreated with control, α‐methyl‐dl‐histidine (to block histamine release), or ranitidine. Liver damage, large duct DR/senescence, inflammation, fibrosis, and cAMP/ERK immunoreactivity increased in BDL WT and KitW‐sh+MC mice but decreased in BDL KitW‐sh and KitW‐sh+MC‐H2HR mice. In vitro, MCs migrate toward damaged LMCCs (but not SMCCs) blocked by inhibition of H2HR. Loss of MC histamine or MC‐H2HR decreases LMCC proliferation, senescence, H2HR, and cAMP/ERK levels. Human PSC livers have increased MC number found near DR, senescent ducts, and H2HR‐positive ducts. Conclusion: Infiltrating MCs preferentially interact with large ducts via H2HR signaling promoting biliary and liver damage. Mediation of MCs may be a therapeutic strategy for PSC.

Fibroblast growth factor 1 (FGF1) belongs to a family of growth factors involved in cellular growth and division. MicroRNA 16 (miR‐16) is a regulator of gene expression, which is dysregulated during liver injury and insult. However, the role of FGF1 in the progression of biliary proliferation, senescence, fibrosis, inflammation, angiogenesis, and its potential interaction with miR‐16, are unknown. In vivo studies were performed in male bile duct–ligated (BDL, 12‐week‐old) mice, multidrug resistance 2 knockout (Mdr2−/−) mice (10‐week‐old), and their corresponding controls, treated with recombinant human FGF1 (rhFGF1), fibroblast growth factor receptor (FGFR) antagonist (AZD4547), or anti‐FGF1 monoclonal antibody (mAb). In vitro, the human cholangiocyte cell line (H69) and human hepatic stellate cells (HSCs) were used to determine the expression of proliferation, fibrosis, angiogenesis, and inflammatory genes following rhFGF1 treatment. PSC patient and control livers were used to evaluate FGF1 and miR‐16 expression. Intrahepatic bile duct mass (IBDM), along with hepatic fibrosis and inflammation, increased in BDL mice treated with rhFGF1, with a corresponding decrease in miR‐16, while treatment with AZD4547 or anti‐FGF1 mAb decreased hepatic fibrosis, IBDM, and inflammation in BDL and Mdr2−/− mice. In vitro, H69 and HSCs treated with rhFGF1 had increased expression of proliferation, fibrosis, and inflammatory markers. PSC samples also showed increased FGF1 and FGFRs with corresponding decreases in miR‐16 compared with healthy controls. Conclusion: Our study demonstrates that suppression of FGF1 and miR‐16 signaling decreases the presence of hepatic fibrosis, biliary proliferation, inflammation, senescence, and angiogenesis. Targeting the FGF1 and miR‐16 axis may provide therapeutic options in treating cholangiopathies such as PSC.