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Background: The LGBTQI + community encounters distinct healthcare challenges due to discrimination and inadequate understanding of their needs. Dermatologists play a crucial role in addressing this by fostering inclusiveness, recognizing individual concerns, and adopting tailored approaches, thereby promoting a more equitable healthcare system., Objective: To address the need for an inclusive healthcare space, the authors established the first dermatological practice exclusively for transgender and non-binary patients. This article presents a comprehensive two-year experience in a public hospital., Methods: The authors conducted a retrospective and descriptive study, analyzing the medical records of 114 patients evaluated at a specialized dermatological practice between June 2021 and May 2023. Key variables assessed included self-identified gender, age, residence, access to private healthcare, human immunodeficiency virus status, hormonal treatment, surgical interventions, consultation motives, employment stability, and family support during gender expression transition., Results: The present study included 114 patients, 49.1% trans men, 39.5% trans women, and 8.8% non-binary individuals. Trans men, on average younger than trans women (p < 0.001), predominantly sought care for body modification-related concerns, particularly acne and androgenetic alopecia. In contrast, trans women exhibited a more diverse range of consultation motives typically unrelated to hormonal or surgical procedures., Study Limitations: This study is retrospective and limited in geographic scope. Additionally, the patient population lacked diversity in terms of Black ethnicity., Conclusions: The pioneering dermatological practice for transgender and non-binary patients exemplifies healthcare equity and cultural competence. Effective LGBTQI + healthcare requires addressing unique dermatological concerns while fostering inclusiveness and continuous learning within the medical community., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery., Methods: A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., 68  Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [ 68 Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue., Results: The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation., Conclusion: This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals., (© 2024. The Author(s).)

Allodynia is a neuropathic pain triggered by a normally painless stimulus: for example, a slight touch on the skin or slight sensation of hot or cold is extremely painful. Rehabilitation is long and uncertain. Protecting the painful area from stimuli is a priority of care. This type of care is complex and challenging for the care team: the pain caused in manufacturing a classic molded orthosis is unbearable for the patient, and the orthosis has a limited lifetime, and experience shows that it is not possible to produce two identical splints. The present study consisted in creating protective splints by 3D printing, designed from data collected with the 3D surface scanner used in our forensic imaging and anthropology unit. The pros and cons of the 3D orthosis versus standard molded orthoses from the point of view of the patient and the practitioner are discussed, with evaluation of related indications of this technology., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Virtual Anthropology (VA) transposes the traditional methods of physical anthropology to virtual environments using imaging techniques and exploits imaging technologies to devise new methodological protocols. In this research, we investigate whether the measurements used in the Diagnose Sexuelle Probabiliste (DSP) and Ischio-Pubic Index (IPI) differ significantly when 3D models of a bone are generated using 3D surface scans (3DSS) and Multidetector Computed Tomography (MDCT) scans. Thirty pelvises were selected from the SIMON identified skeletal collection. An equal ratio of females to males was sought, as well as a good preservation of the bones. The pelvises were scanned using an MDCT scanner and a 3D surface scanner. The measurements of the DSP and IPI methods on the dry bones (referred to as macroscopic measurements here), and then to the 3D models. The intra- and interobserver, using the Technical Error of Measurement (TEM) and relative Technical Error of Measurement (rTEM) error was assessed, and we aimed to observe if the measurements made on the MDCT and 3DSS generated models were significantly different from those taken on the dry bones. Additionally, the normality of the data was tested (Shapiro-Wilk test) and the differences in measurements was evaluated using parametric (Student t-tests) and non-parametric (Wilcoxon) tests. The TEM and rTEM calculations show high intra and interobserver consistency in general. However, some measurements present insufficient inter- and intraobserver agreement. Student t and Wilcoxon tests indicate potentially significant differences of some measurements between the different environments. The results show that especially in the virtual environment, it is not easy to find the right angle for some of the DSP measurements, However, when comparing the measurement differences between dry and virtual bones, the results show that most of the differences are less than or equal to 2.5 mm. Considering the IPI, the landmarks are already difficult to determine on the dry bone, but they are even more difficult to locate in the virtual environment. Nevertheless, this study shows that quantitative methods may be better suited for application in the virtual environment, but further research using different methods is needed., 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 © 2023. Published by Elsevier B.V.)

Objective: To evaluate the self-perception of cardiology residents in Argentina regarding their abilities to help their patients stop smoking, as well as their opinions about their knowledge and skills in this area., Materials and Methods: A cross-sectional study was carried out using secondary data from a study carried out in five Latin American countries and Spain, focusing on the information provided by cardiology residents in Argentina. Discrete variables were expressed as median and interquartile range, and categorical variables were expressed as percentages, and were analyzed using the chi-square test or Fisher's exact test, depending on the relative frequency of the expected values., Results: 447 residents participated; 87.5% routinely provided brief advice to quit smoking, and 11.6% used validated questionnaires to assess the degree of addiction. Furthermore, 32.1% stated that they prescribed pharmacological treatment, but 53.1% were only familiar with a single drug. When asked about their self-perception of getting their patients to stop smoking, the median response was 5 (scale from 1 to 10); only 13.7% responded with a score of 8 or more., Conclusions: The present study suggests that cardiology residents in Argentina recognize the importance of carrying out smoking cessation interventions, but a high proportion of them do not feel qualified to do so., Competing Interests: Conflictos de interés: Los autores declaran no tener ningún conflicto de interés. Si bien el Dr. Andrés Rosende es consultor de la Organización Panamericana de la Salud, el contenido de la presente publicación no necesariamente representa la visión o política de la organización

One of today's main challenges in molecular radiation therapy is to assess an individual dosimetry that allows treatment to be tailored to the specific patient, in accordance with the current paradigm of 'personalized medicine'. The evaluation of the absorbed doses for tumor and organs at risk in molecular radiotherapy is typically based on MIRD schema acquiring few experimental points for the assessement of biokinetic parameters. WIDMApp, the wearable individual dose monitoring apparatus, is an innovative approach for internal dosimetry based on a wearable radiation detecting system for individual biokinetics sampling, a Monte Carlo simulation for particle interaction, and an unfolding algorithm for data analysis and integrated activity determination at organ level. A prototype of a WIDMApp detector element was used to record the photon emissions in a body phantom containing 3 spheres with liquid sources ( 18 F, 64 Cu and 99 m Tc) to simulate organs having different washout. Modelling the phantom geometry on the basis of a CT scan imaging, the Monte Carlo simulation computed the contribution of each emitting sphere to the signal detected in 3 positions on the phantoms surface. Combining the simulated results with the data acquired for 120 h, the unfolding algorithm deconvolved the detected signal and assessed the decay half-life ( T 1/2 ) and initial activity values ( A (0)) that best reproduces the observed exponential decays. A 3%-18% level of agreement is found between the actual A (0) and T 1/2 values and those obtained by means of the minimization procedure based on the Monte Carlo simulation. That resulted in an estimation of the cumulated activity <15%. Moreover, WIDMApp data redundancy has been used to mitigate some experimental occurrences that happened during data taking. A first experimental test of the WIDMApp approach to internal radiation dosimetry is presented. Studies with patients are foreseen to validate the technique in a real environment., (Creative Commons Attribution license.)

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)-dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21 KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.

Glans penis morphology has been used as a powerful tool in mammal taxonomy to differentiate cryptic species. Neotropical rodent species Akodoncursor and A.montensis are cryptic, and interspecific hybrids are like their parental species. We investigated non-metric and metric phallic characters aiming to differentiate A.cursor from A.montensis . We also evaluated the parental species' influence of the phallic characters on hybrids. We analysed 96 male adults-56 A.cursor , 27 A.montensis , and 13 hybrids, subgrouping species by locality and hybrids by parental species (paternal vs maternal). We verified that A.cursor and A.montensis are distinguishable by penile-shape morphology: A.cursor has an elongated penile form with a flare in the distal portion and A.montensis has a barrel-shaped form. Also, dark spots in ventral view, if present in A.montensis , distinguish A.montensis from A.cursor . Although the non-metric characters differentiate the species, they do not distinguish the subgroups of A.cursor , A.montensis , and hybrids. The metric phallic characters indicated a significant difference between species and hybrids. These characters also differentiate the population groups of A.cursor . However, A.montensis subgroups and hybrids subgroups did not present a significant difference. This study shows the importance of penis morphology in the taxonomy of the cryptic rodent species A.cursor and A.montensis , representing a powerful tool to discriminate male specimens in mammal collections without karyotyping or sequencing, even though the specimens occurred in sympatric areas. Since most taxidermy protocols do not preserve the penis in mammal preparations, liquid preservation of some specimens or the removal of the penis before taxidermy for liquid preservation could be beneficial. We also recommend the organisation in museum collections of a penis bank for the A.cursor species group (or even all rodent species) to avoid losing this important information for species identification., (Leonardo Campana, Letícia Rosário Cruz, Roberta Paresque, Valéria Fagundes.)

Carbapenemase-producing Enterobacterales (CPE) are considered a major public health issue. In the frame of the EU Harmonized AMR Monitoring program conducted in Italy in 2021, 21 epidemiological units of fattening pigs (6.98%; 95% CI 4.37-10.47%; 21/301) and four epidemiological units of bovines <12 months (1.29%; 95% CI 0.35-3.27%, 4/310) resulted positive to OXA-48-like-producing E. coli ( n  = 24 OXA-181, n  = 1 OXA-48). Whole Genome Sequencing (WGS) for in-depth characterization, genomics and cluster analysis of OXA-181-(and one OXA-48) producing E. coli isolated, was performed. Tracing-back activities at: (a) the fattening holding of origin of one positive slaughter batch, (b) the breeding holding, and (c) one epidemiologically related dairy cattle holding, allowed detection of OXA-48-like-producing E. coli in different units and comparison of further human isolates from fecal samples of farm workers. The OXA-181-producing isolates were multidrug resistant (MDR), belonged to different Sequence Types (STs), harbored the IncX and IncF plasmid replicons and multiple virulence genes. Bioinformatics analysis of combined Oxford Nanopore Technologies (ONT) long reads and Illumina short reads identified bla OXA-181 as part of a transposon in IncX1, IncX3, and IncFII fully resolved plasmids from 16 selected E. coli, mostly belonging to ST5229, isolated during the survey at slaughter and tracing-back activities. Although human source could be the most likely cause for the introduction of the bla OXA-181 -carrying IncX1 plasmid in the breeding holding, concerns arise from carbapenemase OXA-48-like-producing E. coli spreading in 2021 in Italian fattening pigs and, to a lesser extent, in veal calf holdings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carfora, Diaconu, Ianzano, Di Matteo, Amoruso, Dell'Aira, Sorbara, Bottoni, Guarneri, Campana, Franco, Alba and Battisti.)

Human subcutaneous dirofilariasis caused by Dirofilaria repens is a vectorborne zoonotic disease mostly transmitted from dogs to humans through a mosquito's blood meal. Heartworms replication is amplified by the climate change, the increase of the range of suitable vectors, the facilitation of pet travel and the high rate of undiagnosed dirofilariasis in dogs. We describe a case of a young Romanian woman, resident in Rome for 18 years, that came to our attention for the appearance for five months of a subcutaneous nodule in the left arm. The patient reported that she first felt an insect bite, after which she noticed the onset of an erythematous and itchy wheal in the same skin area, turned into a subcutaneous nodule within a few weeks. The ultrasound examination showed a hypoechoic subcutaneous formation of 1,2 cm in diameter, containing a ribbon-like structure made up of hyperechoic parallel double lines, reminiscent of a warm. Based on this suspicion, we opted for the surgical radicalization of the lesion. The histological examination confirmed the radiological hypothesis of a warm-like foreign body morphologically compatible with Dirofilaria repens . Our experience shows how a clinical nonspecific skin nodular lesion may conceal an unexpected and unsettling diagnosis of subcutaneous Dirofilaria repens., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Background: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma., Objectives: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome., Methods: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m 2 ; 1000 IU mL/cm 3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis., Results: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001)., Conclusions: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond., (This article is protected by copyright. All rights reserved.)

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS., (© 2022. The Author(s).)

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease., Competing Interests: Declaration of interests S.J.F. and J.D.M.C. are founders and scientific advisors of Resolution Therapeutics Ltd (not related to this study). D.C.H. is a founder, director, and shareholder at Stemnovate Limited and Stimuliver ApS (not related to this study)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

During a Disaster Victims Identification (DVI) mission, international protocols rely on interdisciplinary work, especially between specialists from forensic imaging and anthropology. In case of air crashes or explosions, DVI units may face thousands of fragmented human remains (FHRs). The physical re-association of FHRs and the identification process is very complex and challenging, and relies upon expensive and destructive DNA analysis. A virtual re-association (VRA) of these fragments, using Multidetector Computed Tomography (MDCT), could be a helpful tool in forensic anthropology analysis, as it could assist in reducing the number of DNA samples. However, there is no standardized protocol for including such an approach into a DVI procedure. The aim of this study was to summarize and analyze existing techniques through a systematic review and to develop a protocol for virtual re-association of FHRs, adapted to the DVI context. A keyword-based literature search was conducted, focusing on the VRA methods using MDCT imaging and 3D surface scan methodology. Reviews and primary articles, published between 2005 and 2020 in the fields of forensic anthropology, paleoanthropology, archeology, and fracture reduction surgery were sorted out. A total of 45 publications were selected and analyzed based on their content and relevance. The results show that research on the re-association of FHRs increased significantly during the last five years. Seven steps regarding the MDCT-based method for the virtual re-association of FHRs could be identified: acquisition of 3D-images, segmentation of the MDCT-data, post-processing and surface generation, identification of intact and fracture surfaces, identification and registration of matching fragments, and validation of the re-association. The literature is surprisingly sparse regarding the FHRs re-association as a forensic tool, and mainly consists in case reports, whereas validated methods were presented in archeology and surgery publications. However, we were able to adapt the MDCT-based approach for the virtual re-association of the FHRs and propose an innovative protocol for DVI missions. This protocol includes the needed details, from the acquisition of MDCT imaging to the virtual re-association of 3D models and its validation. Each step has to be fully tested, adapted and validated in future studies., (Copyright © 2021. Published by Elsevier B.V.)

Background: Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents' attitudes and perspectives about antibiotic use., Methods: Prospective observational study was conducted in all Italian Regions between February 1 and April 30, 2020, using a standardized questionnaire., Results: Six thousand six hundred twenty-five parents from all Italian regions completed the survey. Seventy-six percent of parents were aware that only bacteria are the target of antibiotics, but 92.9% knew that the antibiotic has no direct effect on fever. Antibiotic self-prescription (10.4%) or by remote consultation by phone call (19.9%) or message (9.6%) were relatively common. Ninety-three percent of parents were aware that excessive use of antibiotics could select resistant bacteria and 84.7% of them knew that they could actively fight antibiotic resistance. About two thirds of participants (66.1%) received information on antibiotic resistance from their family pediatrician. Parents born of Italy or those with lower income had a higher probability of having less information from pediatricians or knowledge of proper antibiotic use., Discussion: Our study suggests that parents' knowledge and attitudes toward antibiotic use and prescription are improving compared with previous studies, while there is still a gap regarding antibiotic resistance, particularly on practices that can reduce its burden. Our study's negative finding is that families from low-income settings or those born abroad have significantly more misconceptions about important antibiotic practices., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Liver regeneration is a complex process involving the crosstalk of multiple cell types, including hepatocytes, hepatic stellate cells, endothelial cells and inflammatory cells. The healthy liver is mitotically quiescent, but following toxic damage or resection the cells can rapidly enter the cell cycle to restore liver mass and function. During this process of regeneration, epithelial and non-parenchymal cells respond in a tightly coordinated fashion. Recent studies have described the interaction between inflammatory cells and a number of other cell types in the liver. In particular, macrophages can support biliary regeneration, contribute to fibrosis remodelling by repressing hepatic stellate cell activation and improve liver regeneration by scavenging dead or dying cells in situ. In this Review, we describe the mechanisms of tissue repair following damage, highlighting the close relationship between inflammation and liver regeneration, and discuss how recent findings can help design novel therapeutic approaches., (© 2021. Springer Nature Limited.)

Background & Aims: Cholangiocarcinoma (CCA) is a cancer of the hepatic bile ducts that is rarely resectable and is associated with poor prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is known to signal via its receptor fibroblast growth factor-inducible 14 (Fn14) and induce cholangiocyte and myofibroblast proliferation in liver injury. We aimed to characterise its role in CCA., Methods: The expression of the TWEAK ligand and Fn14 receptor was assessed immunohistochemically and by bulk RNA and single cell transcriptomics of human liver tissue. Spatiotemporal dynamics of pathway regulation were comprehensively analysed in rat and mouse models of thioacetamide (TAA)-mediated CCA. Flow cytometry, qPCR and proteomic analyses of CCA cell lines and conditioned medium experiments with primary macrophages were performed to evaluate the downstream functions of TWEAK/Fn14. In vivo pathway manipulation was assessed via TWEAK overexpression in NICD/AKT-induced CCA or genetic Fn14 knockout during TAA-mediated carcinogenesis., Results: Our data reveal TWEAK and Fn14 overexpression in multiple human CCA cohorts, and Fn14 upregulation in early TAA-induced carcinogenesis. TWEAK regulated the secretion of factors from CC-SW-1 and SNU-1079 CCA cells, inducing polarisation of proinflammatory CD206 + macrophages. Pharmacological blocking of the TWEAK downstream target chemokine monocyte chemoattractant protein 1 (MCP-1 or CCL2) significantly reduced CCA xenograft growth, while TWEAK overexpression drove cancer-associated fibroblast proliferation and collagen deposition in the tumour niche. Genetic Fn14 ablation significantly reduced inflammatory, fibrogenic and ductular responses during carcinogenic TAA-mediated injury., Conclusion: These novel data provide evidence for the action of TWEAK/Fn14 on macrophage recruitment and phenotype, and cancer-associated fibroblast proliferation in CCA. Targeting TWEAK/Fn14 and its downstream signals may provide a means to inhibit CCA niche development and tumour growth., Lay Summary: Cholangiocarcinoma is an aggressive, chemotherapy-resistant liver cancer. Interactions between tumour cells and cells that form a supportive environment for the tumour to grow are a source of this aggressiveness and resistance to chemotherapy. Herein, we describe interactions between tumour cells and their supportive environment via a chemical messenger, TWEAK and its receptor Fn14. TWEAK/Fn14 alters the recruitment and type of immune cells in tumours, increases the growth of cancer-associated fibroblasts in the tumour environment, and is a potential target to reduce tumour formation., Competing Interests: Conflict of interest S.J.F. is supported by funds from Wellcome Trust UK, Medical Research Council, UKRMP and Syncona Ltd. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Virtual anthropology (VA) is based on applying anthropological methods currently used to analyse bones to 3D models of human remains. While great advances have been made in this endeavour in the past decade, several interrogations concerning how reliable these models are and what their proper use should be remain unanswered. In this research, a fundamental assumption of VA has been investigated: if the way we perceive and apply an anthropological method is truly similar when looking at bones macroscopically and through various 3D media. In order to answer, 10 skulls of known age and sex were scanned using a computed tomography (CT) scanner and a 3D surface scanner. Two observers separately applied a defined staging method to eight suture sites on these skulls, first looking at the bone macroscopically, then at the 3D surface scan, and finally on the CT scan. Two rounds of observation were carried out by each observer. Intra- and inter-observer error were evaluated, and two sample t -tests used to evaluate if the different types of medium used yielded significantly different observations. The results show a high degree of inter-observer error, and that data obtained from 3D surface scans differ from macroscopic observation (confidence level 95%, P  ≤ 0.05). CT scans, in these settings, yielded results comparable to those obtained through macroscopic observations. These results offer many possibilities for future research, including indications on the kind of anthropological methods and anatomical landmarks that might be reliably transferable to the virtual environment. All current methods used in traditional anthropology should be tested, and if they prove unreliable, new techniques to analyse bones from virtual models should be developed.Key pointsLarge discrepancies between observation on dry bones and computer-generated 3D models (surface scans or CT scans) could lead to the re-evaluation of the suitability of traditional anthropological methods for application on 3D models.This preliminary study evaluates whether macroscopic, 3D surface scans, and CT scans viewings generate different observations.The results indicate that the data are not always coherent across all three media of observation.Explanations include the aspect given to the bone by the 3D software, differences between handling bones in real life versus on a computer, and level of expertise of the observers., Competing Interests: The authors declare that they have no conflict of interest and that this work has not received any funding., (© 2020 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science.)

Background: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters., Methods: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field., Results: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration., Conclusions: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices., Competing Interests: Conflict of interest statement The following authors have conflict of interest: A.J.P.C. reports receiving travel fees for a meeting related to manuscript preparation by IGEA. F.d.T. is an employee of IGEA. J.O. reports receiving travel fees and accommodation fees from IGEA. L.G.C. reports receiving travel support for the International Network for Sharing Practice in Electrochemotherapy (InspECT) meeting from IGEA. D.M. reports receiving travel fees and accommodation fees for InspECT meeting from IGEA. A.D.M.R. reports receiving flight and accommodation fees for electrochemotherapy meeting and has aso received an honorarium. J.G. reports receiving travel fees and accommodation for a meeting related to manuscript preparation from IGEA. The other authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background & Aim: Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate immunological function and paracrine activity. Syngeneic primary bone marrow-derived macrophages (BMDMs) were tested as a cell-based therapy in a mouse model of APAP-induced ALI (APAP-ALI)., Methods: Several phenotypically distinct BMDM populations were delivered intravenously to APAP-ALI mice when hepatic necrosis was established, and then evaluated based on their effects on injury, inflammation, immunity, and regeneration. In vivo phagocytosis assays were used to interrogate the phenotype and function of alternatively activated BMDMs (AAMs) post-injection. Finally, primary human AAMs sourced from healthy volunteers were evaluated in immunocompetent APAP-ALI mice., Results: BMDMs rapidly localised to the liver and spleen within 4 h of administration. Injection of AAMs specifically reduced hepatocellular necrosis, HMGB1 translocation, and infiltrating neutrophils following APAP-ALI. AAM delivery also stimulated proliferation in hepatocytes and endothelium, and reduced levels of several circulating proinflammatory cytokines within 24 h. AAMs displayed a high phagocytic activity both in vitro and in injured liver tissue post-injection. Crosstalk with the host innate immune system was demonstrated by reduced infiltrating host Ly6C hi macrophages in AAM-treated mice. Importantly, therapeutic efficacy was partially recapitulated using clinical-grade primary human AAMs in immunocompetent APAP-ALI mice, underscoring the translational potential of these findings., Conclusion: We identify that AAMs have value as a cell-based therapy in an experimental model of APAP-ALI. Human AAMs warrant further evaluation as a potential cell-based therapy for APAP overdose patients with established liver injury., Lay Summary: After an overdose of acetaminophen (paracetamol), some patients present to hospital too late for the current antidote (N-acetylcysteine) to be effective. We tested whether macrophages, an injury-responsive leukocyte that can scavenge dead/dying cells, could serve as a cell-based therapy in an experimental model of acetaminophen overdose. Injection of alternatively activated macrophages rapidly reduced liver injury and reduced several mediators of inflammation. Macrophages show promise to serve as a potential cell-based therapy for acute liver injury., Competing Interests: Conflict of interest P.S.L., L.F., and S.J.F. have patents pending, entitled ‘Macrophage-based therapy’ in national territories of USA, Europe, Japan, China and Australia. These patents have been derived from PCT/GB2017/052769 filed 18/09/2017 and claim priority from UK application 1615923.8 filed 19/09/2016. Both of the original patents have now been abandoned because the original UK patent and PCT patent are no longer live and have now been replaced by the national patents. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Manual ventilations during cardiac arrest are frequently performed outside of recommended guidelines. Real-time feedback has been shown to improve chest compression quality, but the use of feedback to guide ventilation volume and rate has not been studied. The purpose of this study was to determine whether the use of a real-time visual feedback system for ventilation volume and rate improves manual ventilation quality during simulated cardiac arrest., Methods: Teams of 2 emergency medical technicians (EMTs) performed two 8-min rounds of cardiopulmonary resuscitation (CPR) on a manikin during a simulated cardiac arrest scenario with one EMT performing ventilations while the other performed compressions. The EMTs switched roles every 2 min. During the first round of CPR, ventilation and chest compression feedback was disabled on a monitor/defibrillator. Following a 20-min rest period and a brief session to familiarize the EMTs with the feedback technology, the trial was repeated with feedback enabled. The primary outcome variables for the study were ventilations and chest compressions within target. Ventilation rate (target, 8-10 breaths/minute) and tidal volume (target, 425-575 ml) were measured using a novel differential pressure-based flow sensor. Data were analyzed using paired t tests., Results: Ten teams of 2 EMTs completed the study. Mean percentages of ventilations performed in target for rate (41% vs. 71%, p < 0.01), for volume (31% vs. 79%, p < 0.01), and for rate and volume together (10% vs. 63%, p < 0.01) were significantly greater with feedback., Conclusion: The use of a novel visual feedback system for ventilation quality increased the percentage of ventilations in target for rate and volume during simulated CPR. Real-time feedback to perform ventilations within recommended guidelines during cardiac arrest should be further investigated in human resuscitation.