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Abstract The complexity of Multiple Myeloma (MM) is driven by several genomic aberrations, interacting with disease-related and/or -unrelated factors and conditioning patients’ clinical outcome. Patient’s prognosis is hardly predictable, as commonly employed MM risk models do not precisely partition high- from low-risk patients, preventing the reliable recognition of early relapsing/refractory patients. By a dimensionality reduction approach, here we dissect the genomic landscape of a large cohort of newly diagnosed MM patients, modelling all the possible interactions between any MM chromosomal alterations. We highlight the presence of a distinguished cluster of patients in the low-dimensionality space, with unfavorable clinical behavior, whose biology was driven by the co-occurrence of chromosomes 1q CN gain and 13 CN loss. Presence or absence of these alterations define MM patients overexpressing either CCND2 or CCND1, fostering the implementation of biology-based patients’ classification models to describe the different MM clinical behaviors.

Abstract Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Summary: Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40–1.73, p

In recent years, a multitude of datasets of human-human conversations has been released for the main purpose of training conversational agents based on data-hungry artificial neural networks. In this paper, we argue that datasets of this sort represent a useful and underexplored source to validate, complement, and enhance cognitive studies on human behavior and language use. We present a method that leverages the recent development of powerful computational models to obtain the fine-grained annotation required to apply metrics and techniques from Cognitive Science to large datasets. Previous work in Cognitive Science has investigated the question-asking strategies of human participants by employing different variants of the so-called 20-question-game setting and proposing several evaluation methods. In our work, we focus on GuessWhat, a task proposed within the Computer Vision and Natural Language Processing communities that is similar in structure to the 20-question-game setting. Crucially, the GuessWhat dataset contains tens of thousands of dialogues based on real-world images, making it a suitable setting to investigate the question-asking strategies of human players on a large scale and in a natural setting. Our results demonstrate the effectiveness of computational tools to automatically code how the hypothesis space changes throughout the dialogue in complex visual scenes. On the one hand, we confirm findings from previous work on smaller and more controlled settings. On the other hand, our analyses allow us to highlight the presence of "uninformative" questions (in terms of Expected Information Gain) at specific rounds of the dialogue. We hypothesize that these questions fulfill pragmatic constraints that are exploited by human players to solve visual tasks in complex scenes successfully. Our work illustrates a method that brings together efforts and findings from different disciplines to gain a better understanding of human question-asking strategies on large-scale datasets, while at the same time posing new questions about the development of conversational systems.

Key Clinical Message A 46‐year‐old woman with congenitally corrected transposition of the great arteries (ccTGA) associated with dextrocardia, situs viscerus inversus, and left superior vena cava persistence presented with an incessant supraventricular tachycardia. Electrophysiological study was not conclusive in differential diagnosis of atrial tachycardia versus atypical atrioventricular (AV) nodal reentrant tachycardia, also due to the unconventional anatomy of the coronary sinus. By a comprehensive mapping of cardiac chambers, a double side slow‐pathway was localized in both atrial chambers and subsequently ablated by radiofrequency delivery without tachycardia changes. Aortic root and cusps were devoid of electrical activity. The muscular part of the sub‐pulmonary ventricle at the level of interatrial septum showed an earliest activation signal of −90 ms and ablation of this site was effective in abolish the tachycardia. This is the first case to report technical concerns of septal atrial tachycardia ablation in ccTGA associated with multiple anatomical malformations. Moreover, some peculiarities have been reported for the first time including the presence of double‐side AV nodal slow‐pathway and atypical localization of the tachycardia origin into the muscular part of the sub‐pulmonary ventricle instead of posterior pulmonary cusp.

ABSTRACT Kaolinite is the main clay mineral in most soils around the world and has been widely used for industrial purposes. This research aimed to study chemical, morphological and crystallographic characteristics of kaolinite, and establish the origin of kaolinitic samples on Serra do Mar and kaolinitic layers on peatlands, located at Southern Brazil. Samples were collected on different geomorphological positions: two samples at Serra do Mar (kaolinitic saprolite – SAP, and kaolinitic layers - KL); and two cores at the peatland with Sapric Histosols from Quaternary sedimentary basin. Granulometry and total organic carbon (TOC) were determined in soil samples. Kaolinite in silt and clay fractions was studied by chemical extractions, X-ray diffraction (XRD), thermal analysis (DTA/TG), and scanning electron microscopy with energy dispersive spectroscopy – SEM/EDS. Chemical and mineralogical characteristics of kaolinite were divided into two groups, according to the particle size and the location of the deposit in the relief. Silt fraction: i) SAP – genesis mainly derived from mica weathering; ii) peatland, containing pseudomorph crystals smaller than those found in Serra do Mar; Clay fraction: i) Serra do Mar – there was a larger contribution of K-feldspar weathering in the genesis of kaolinite from KL in relation to SAP; ii) peatland – the stronger weathering and the hydromorphic conditions resulted in less neoformed crystalline kaolinites. For both environments, the substitution of Al3+ by Fe3+ into the octahedral sheet led to a reduction in the mineral thickness and also increased the occurrence of structural deformations in clay kaolinite. Kaolinite in peatland is a combination of the following genesis processes: transportation from Serra do Mar (mainly in the silt fraction) and; formation in situ through neogenesis process (dominant in the clay fraction).

Abstract A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.

Background: The COVID-19 pandemic has impacted the lives of individuals, families, and children worldwide. In Italy, the implementation of measures such as lockdowns and distance learning in schools affected the mental health of children and families. Methods: This article employs a qualitative method to explore the efficacy of a death education project that aimed to help primary school children process the emotions and losses that they experienced during the COVID-19 pandemic. The study encompassed both the children who took part in the death education project and their teachers and parents to investigate their perspectives on the emotions of the minors and the effectiveness of the project. Results: Distance learning posed challenges for the learning process and exacerbated social inequalities. The children suffered from limited social contact with their friends and experienced negative emotions, including anger, fear, and concern for the health of their loved ones. The death education project provided a safe space for children’s emotional expression and facilitated their acquisition of coping strategies. Open communication between adults and children about illness and death proved effective in mitigating the psychological impacts of loss and preventing traumatic bereavement. Conclusion: The findings highlight the utility of death education in enhancing children’s ability to express their emotions and approach the topic of death more frankly.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

BackgroundThis systematic review examined the existing literature to determine the evidence supporting the efficacy of online group treatments for anxiety-, obsessive-compulsive- and trauma-related disorders (AOTDs).MethodsA systematic review using the PUBMED, PsycInfo, Web of Science, and ClinicalTrials databases with no language, date, or study design filters was performed. The inclusion criteria comprised studies that examined individuals who had received a formal diagnosis of AOTDs, were aged 18 years or older, and had baseline and endpoint assessments of symptom severity using formal tools.ResultsFive studies on social anxiety disorder (SAD), four on post-traumatic stress disorder (PTSD) and one on tic disorders (TDs) were found. The studies were open-label (n = 2) and randomized controlled trials (RCTs) (n = 8), with five of the RCTs being non-inferiority trials. Most studies were conducted in the US and investigated psychological CBT based interventions via internet-based therapies (IBT: n = 4), video teleconferencing (VTC: n = 5) or a combination of both (n = 1). In SAD, IBT studies associated with a clinician assisted web-based forum (here termed “forum-enhanced” studies) were superior to waiting lists and not inferior to similar versions that were also “forum enhanced” but self-guided, “telephone enhanced” by a contact with a non-specialist, and “email enhanced” by a contact with a clinician individually. Studies involving VTC have shown comparable effectiveness to in-person interventions across some online group CBT based treatments for PTSD. Two open trials also demonstrated symptoms reductions of social anxiety and tics through VTC.ConclusionThere is evidence supporting the effectiveness of online group treatments for SAD and PTSD. Further studies from different research groups may be needed to replicate the use of these and other forms of online treatments in individuals with SAD, PTSD, and other clinical populations, such as OCD, panic disorder, agoraphobia and specific phobias.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023408491.

Purpose Regulatory authorities including the Food and Drug Administration and the European Medicines Agency are encouraging to conduct clinical trials using routinely collected data. The aim of the TransFAIR experimental comparison was to evaluate, within real-life conditions, the ability of the Electronic Health Records to Electronic Data Capture (EHR2EDC) module to accurately transfer from EHRs to EDC systems patients’ data of clinical studies in various therapeutic areas.Methods A prospective study including six clinical trials from three different sponsors running in three hospitals across Europe has been conducted. The same data from the six studies were collected using both traditional manual data entry and the EHR2EDC module. The outcome variable was the percentage of data accurately transferred using the EHR2EDC technology. This percentage was calculated considering all collected data and the data in four domains: demographics (DM), vital signs (VS), laboratories (LB) and concomitant medications (CM).Results Overall, 6143 data points (39.6% of the data in the scope of the TransFAIR study and 16.9% when considering all data) were accurately transferred using the platform. LB data represented 65.4% of the data transferred; VS data, 30.8%; DM data, 0.7% and CM data, 3.1%.Conclusions The objective of accurately transferring at least 15% of the manually entered trial datapoints using the EHR2EDC module was achieved. Collaboration and codesign by hospitals, industry, technology company, supported by the Institute of Innovation through Health Data was a success factor in accomplishing these results. Further work should focus on the harmonisation of data standards and improved interoperability to extend the scope of transferable EHR data.

O contexto da educação básica brasileira caracteriza-se, de modo geral, na atuação de docentes com descompassos formativos, que ministram aulas de diversas disciplinas, no caso dos anos iniciais do ensino fundamental, ou que lecionam disciplinas diversas de sua área de formação, no caso das séries finais e ensino médio. Nessa linha, diversos estudos apontam para a evidência de lacunas e imprecisões conceituais no planejamento de intervenções didáticas, devido ao precário desenvolvimento profissional. Desse modo, o presente artigo traz uma revisão teórica sistemática sobre o tema relacionado aos conhecimentos profissionais do magistério e busca contribuir com tal debate, trazendo como resultado a proposta de uma visão do processo de construção de saberes docentes com base em modelos do conhecimento pedagógico de conteúdo articulados com os processos de criação vigotskianos. Tal proposta possibilitou possíveis implicações das articulações apresentadas em associação com as pesquisas relacionadas à formação docente, bem como com propostas formativas, que levem em consideração o contexto cultural do professor, especificamente seus esquemas repertoriais, aqui representados pelo espectro criativo. Desse modo, pretende-se que os contextos formativos utilizem e incrementem o repertório professoral, repertório este fundamental para o desenvolvimento de novos Conhecimentos Pedagógicos de Conteúdo em um caráter transformativo, possibilitando práticas que permitam o desenvolvimento profissional docente.

Abstract Background In older patients with acute myeloid leukemia (AML), the definition of fitness, prognosis, and risk of death represents an open question. Methods In the present study, we tested the impact on survival of disease‐ and patient‐related parameters in a large cohort of elderly AML patients homogeneously assigned to treatment with hypomethylating agents (HMAs). Results In 131 patients with a median age of 76 years, we confirmed that early response (

Abstract This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4. Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel‐group phase II–III study investigated this issue. The phase II dose‐finding part of the study evaluated H2, CH4, and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split‐dose 2 L polyethylene glycol (PEG)‐Asc preparation (2 L PEG‐Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG‐Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019‐002856‐18).

Chronic hepatitis B (CHB) virus infection is a major public health burden and the leading cause of hepatocellular carcinoma. Despite the efficacy of current treatments, hepatitis B virus (HBV) cannot be fully eradicated due to the persistence of its minichromosome, or covalently closed circular DNA (cccDNA). The HBV community is investing large human and financial resources to develop new therapeutic strategies that either silence or ideally degrade cccDNA, to cure HBV completely or functionally. cccDNA transcription is considered to be the key step for HBV replication. Transcription not only influences the levels of viral RNA produced, but also directly impacts their quality, generating multiple variants. Growing evidence advocates for the role of the co-transcriptional regulation of HBV RNAs during CHB and viral replication, paving the way for the development of novel therapies targeting these processes. This review focuses on the mechanisms controlling the different co-transcriptional processes that HBV RNAs undergo, and their contribution to both viral replication and HBV-induced liver pathogenesis.

Losing a child is a traumatic event, disrupting life’s natural cycle, profoundly affecting the family system, and causing enduring grief. Perinatal death, including ectopic pregnancies, miscarriages, stillbirths, and neonatal deaths, exacerbates this distress. Additionally, the COVID-19 pandemic has challenged healthcare systems and supporting services available to individuals in need. Thus, this research explores experiences of parents facing perinatal loss in 2020–2021, further focusing on the pandemic’s impact. Using a mixed-methods design with self-reports and qualitative interviews, this paper presents results from the quantitative protocol, involving an update and follow-up of a previous study. It compares measurements across scales: COVID-19: The Impact of Event Scale-Revised; The Prolonged Grief-13; The Parental Assessment of Paternal/Maternal Affectivity; The Dyadic Adjustment Scale (short version); The Daily Spiritual Experiences Scale; and The Inventory of Complicated Spiritual Grief. In the baseline measurement, 45 parents participated (37 mothers and 8 fathers), with 20 (13 mothers and 7 fathers) contributing to the follow-up and 9 engaging in interviews. Baseline results showed higher scores for mothers compared to fathers, with effect sizes ranging from small to medium (ranging from −0.02 to 0.29), though statistical significance was limited due to the small sample size. Multiple regression analysis for distress measures at baseline identified two significant predictors: maternal/paternal affectivity and gestational week. Additionally, positive support from healthcare professionals emerged as a mitigating factor, particularly in relation to Avoidance. A significant reduction in stress measures and parental affectivity was observed at the 6-month follow-up. Qualitative analysis revealed three themes: Shifts in Self-Perception and Post-Loss Growth; Conflicted Relationship with One’s Body; and Negative Impact of COVID-19 vs. Unexpectedly Positive Aspects. In conclusion, the findings emphasize the significance of psychological and psychosocial interventions based on meaning-making processes, along with the importance of spiritual care and empowerment for those navigating perinatal loss.

Abstract Background The need to spread the culture of palliative care and to train health care professionals from undergraduate courses is recognised internationally. The article presents the outcomes of a project devoted to palliative care training in university courses in four countries. Aims This article considered the outcomes of a course designed for university students who had the potential to work in a palliative care team. The main aim was to check the efficacy of the course and the motivation to work in palliative care settings, considering the impact of fear and representations of death. Methods The project presented the essential contents related to palliative care, using psychodramatic and photo-voice techniques. Longitudinal measurements were taken using a quantitative method design to detect changes among the students involved. The project involved 341 students at the first administration of the survey consisted of a protocol composed of standardized questionnaires in five countries (Austria, Israel, Italy, Poland and Romania), of whom 276 completed the pre- and post-surveys—165 of them in the experimental group and 111, in the control group. Results The experience showed that it is possible to address death-related issues seriously and competently without necessarily causing discomfort and despondency in students. The results of the changes over time in the experimental and control groups highlight how the view of death as annihilation is correlated with the fear of death and the need for avoidance of thoughts concerning dying. The main result is that competence in palliative care facilitates familiarisation with issues of death and dying, as well as the ability to work in this area, thereby enhancing interpersonal skills. Conclusion The project showed that it is possible to implement death education on palliative care topics in undergraduate courses to increase motivation to work in this field.

Background & Aims: Finite duration of treatment associated with HBsAg loss is the current goal for improved therapeutic approaches against chronic HBV infection, as it indicates elimination or durable inactivation of intrahepatic covalently closed circular DNA (cccDNA). To assist drug development, the definition of early predictive markers of HBsAg loss by assessing their value in reflecting intrahepatic cccDNA levels and transcriptional activity is essential. Fine needle aspirates (FNAs) have recently emerged as a less invasive alternative to core liver biopsy (CLB) and showed to be useful for investigating intrahepatic immune responses. The aim of this study was to optimise and validate the use of FNA vs. CLB to evaluate the intrahepatic viral reservoir. Methods: Paired FNA/CLB samples were obtained from patients with HBeAg+ chronic hepatitis (n = 4), HBeAg− chronic hepatitis (n = 4), and HBeAg− chronic infection (n = 1). One HBeAg+ patient was undergoing tenofovir treatment. HBV 3.5-kb RNA and cccDNA were quantified by droplet digital PCR. Results: cccDNA was quantifiable in all but one FNA/CLB pair, showing the highest levels in untreated HBeAg+ patients, except for the tenofovir-treated patient. Similarly, 3.5-kb RNA was detectable in all but one FNA sample and showed higher levels in HBeAg+ patients. When comparing cccDNA and 3.5-kb RNA quantification in FNA vs. CLB samples, no statistically significant differences were identified. Conclusions: These results demonstrate the possibility to quantify cccDNA and assess its transcriptional activity in patients with chronic hepatitis B by combining FNA and droplet digital PCR. This supports the use of FNA in clinical trials to evaluate the intrahepatic viral reservoir during the development of new antivirals and immunomodulatory agents. Impact and implications: Chronic hepatitis B infection is characterised by a complex interplay between immune responses and viral replication in the liver, which determines the long-term outcome of the disease. In this study, we show that fine needle aspiration of the liver, a less-invasive alternative to core biopsies, allows the assessment of the hepatic viral reservoir.

Background and aimsHepatitis B virus (HBV) infection affects 300 million individuals worldwide, representing a major factor for the development of hepatic complications. Although existing antivirals are effective in suppressing replication, eradication of HBV is not achieved. Therefore, a multi-faceted approach involving antivirals and immunomodulatory agents is required. Non-human primates are widely used in pre-clinical studies due to their close evolutionary relationship to humans. Nonetheless, it is fundamental to identify the differences in immune response between humans and these models. Thus, we performed a transcriptomic characterization and interspecies comparison of the early immune responses to HBV in human and cynomolgus macaques.MethodsWe characterized early transcriptomic changes in human and cynomolgus B cells, T cells, myeloid and plasmacytoid dendritic cells (pDC) exposed to HBV ex vivo for 2 hours. Differentially-expressed genes were further compared to the profiles of HBV-infected patients using publicly-available single-cell data.ResultsHBV induced a wide variety of transcriptional changes in all cell types, with common genes between species representing only a small proportion. In particular, interferon gamma signaling was repressed in human pDCs. At the gene level, interferon gamma inducible protein 16 (IFI16) was upregulated in macaque pDCs, while downregulated in humans. Moreover, IFI16 expression in pDCs from chronic HBV-infected patients anti-paralleled serum HBsAg levels.ConclusionOur characterization of early transcriptomic changes induced by HBV in humans and cynomolgus macaques represents a useful resource for the identification of shared and divergent host responses, as well as potential immune targets against HBV.

Summary: Background: Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer. Methods: We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201. Findings: We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2–96.5), specificity 41.7% (95% CI 33.9–44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%–80.9%), specificity 61.9% (95% CI 56.6–66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3–83.8), followed by p16 test, 64.1% (95% CI 51.0–75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4–70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9–84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity. Interpretation: Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance. Funding: There was no funding source for this study.

Background & Aims: A single hepatitis B virus (HBV) particle is sufficient to establish chronic infection of the liver after intravenous injection, suggesting that the virus targets hepatocytes via a highly efficient transport pathway. We therefore investigated whether HBV uses a physiological liver-directed pathway that supports specific host-cell targeting in vivo. Methods: We established the ex vivo perfusion of intact human liver tissue that recapitulates the liver physiology to investigate HBV liver targeting. This model allowed us to investigate virus-host cell interactions in a cellular microenvironment mimicking the in vivo situation. Results: HBV was rapidly sequestered by liver macrophages within 1 hour after a virus pulse perfusion but was detected in hepatocytes only after 16 hours. We found that HBV associates with lipoproteins in serum and within machrophages. Electron and immunofluorescence microscopy corroborated a co-localization in recycling endosomes within peripheral and liver macrophages. Recycling endosomes accumulated HBV and cholesterol, followed by transport of HBV back to the cell surface along the cholesterol efflux pathway. To reach hepatocytes as final target cells, HBV was able to utilize the hepatocyte-directed cholesterol transport machinery of macrophages. Conclusions: Our results propose that by binding to liver targeted lipoproteins and using the reverse cholesterol transport pathway of macrophages, HBV hijacks the physiological lipid transport pathways to the liver to most efficiently reach its target organ. This may involve transinfection of liver macrophages and result in deposition of HBV in the perisinusoidal space from where HBV can bind its receptor on hepatocytes.

Introduction. Elective abortion has always been considered taboo. The event can sometimes be experienced as traumatic, as the woman finds herself struggling against a range of emotions: fear, shame, ambivalence, and a sense of guilt. Multidisciplinary support is therefore fundamental to guide women during this complex phase, and social workers usually play a key role in the process. The present study aimed therefore to explore the experiences and perspectives of social workers who worked with women who decided to have abortions, focusing on the strongest and weakest aspects of their support process. Methodology. The study involved 10 social workers working in family counselling services in Italy. All of them were female, with a mean age of 47 years, and a mean of 16.7 years of experience in the field. The study followed a qualitative approach, based on semi-structured interviews that were studied following the principles of thematic analysis. Results. Three fundamental themes emerged from the data analysis: “Limits of the family counselling procedures and organization”; “The emotional dimension of elective abortion”; and “The issue of conscientious objectors”. Discussion. The study highlighted how family counselling services are facing a crisis due to the lack of resources, personnel, and projects allowing for women’s proper sexual education and support. It also showed how the social worker’s role, which is fundamental, has instead been reduced, especially regarding elective abortions. Moreover, there was a lack of social and sanitary contexts integration and professional training that would provide the operators with specific skills and make them feel prepared to address such delicate situations. Conclusions. The need has emerged for a new, multidisciplinary perspective on the issue of voluntary interruption of pregnancy and social workers play a major role. However, the support system still presents many shortcomings for the women in need of assistance. The present study offers innovative and practical suggestions to properly fill these gaps.