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Background. The large number of lesions detected via high-definition (HD) imaging during colonoscopy calls for the reliable real-time histological characterization of polyps, especially diminutive and small ones, to permit tailored management based on the neoplastic risk, such as a “resect-and-discard” or a “diagnose-and-leave” strategy for low-risk adenomas and hyperplastic polyps (HPs). The Kudo classification of glandular pit pattern is currently used for predicting polyp histology. Aim. The aim in this study was to assess whether Kudo’s glandular pit pattern, assessed via HD digital chromoendoscopy (i-Scan) without magnification and optical enhancement, reliably predicts polyp histology and differentiates neoplastic lesions (NLs) from non-neoplastic lesions (non-NLs) during routine colonoscopy. Methods. Consecutive colorectal lesions recorded in a database over 12 months, with Kudo’s glandular pit pattern classification, were retrospectively compared with histology. The diagnostic accuracy and negative predictive value (NPV) for adenomatous histology of Kudo’s pit patterns were assessed separately for diminutive (≤5 mm) and small (6–9 mm) polyps, accordingly to the American Society for Gastrointestinal Endoscopy (ASGE) Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI), and in large (≥10 mm) lesions. Results. A total of 2230 lesions were recorded: 898 diminutive, 704 small, and 628 large. Kudo’s type II pit pattern was prevalent in diminutive polyps and recognized mostly in HPs (83.27%); it was also found in 38.8% of adenomas. In the right colon, Kudo’s type II pit pattern was prevalent in adenomas (70.04% vs. 20.74% in HPs); among the serrated lesions, it was evenly distributed between HPs and adenomas. Kudo’s type IIIL/IIIs/IV pit pattern was prevalent in NLs (61% vs. 8.37% of non-NLs) in diminutive polyps, evenly distributed between non-NLs and NLs in small polyps, and found only in NLs in large polyps. Kudo’s type Vi/Vn pit pattern correctly identified all but one adenocarcinoma. The NPV for adenomatous histology did not reach the recommended 90% PIVI threshold for differentiation between NLs and non-NLs in diminutive polyps showing Kudo’s type II pit pattern and in small polyps showing type IIIL/IIIs/IV pit pattern. Conclusions. Kudo’s pit pattern classification carried out with digital chromoendoscopy (i-Scan) during routine colonoscopy does not allow the reliable differentiation between non-NLs and NLs in diminutive and small polyps, so a “diagnose-and-leave” strategy for diminutive polyps may leave undetected adenomas, while a “resect-and-discard” strategy could miss lesions requiring closer follow-up.

O presente trabalho tem como objetivo mapear a presença da Geografia no currículo do Novo Ensino Médio (NEM) da Rede Estadual de Santa Catarina. Discutiu-se a característica simplista de resolução dos problemas que o NEM traz, assim como a importância da Geografia para a formação dos estudantes e as implicações que o novo modelo tem para os professores. Foram feitas análises documentais dos cadernos do Currículo Base do Território Catarinense e do Plano de Implementação do NEM. Percebeu-se uma diminuição da carga horária da disciplina, mesmo que o número de objetos do conhecimento e habilidades relacionadas a ela seja elevado. Destacou-se as trilhas de aprofundamento e os Componentes Curriculares Eletivos que compreendem a Geografia, verificando que muitas temáticas são deixadas de fora. Conclui-se que o NEM em Santa Catarina leva os professores a uma maior desprofissionalização, precarização e à uma diminuição dos conteúdos capazes de tensionar uma transformação na sociedade.

Chronic hepatitis B is the leading cause of hepatocellular carcinoma and a significant global health issue, affecting over 296 million people worldwide, with 15 million people coinfected with hepatitis delta virus (HDV) suffering accelerated disease progression. Recent advances in single-cell sequencing and spatial transcriptomics offer promising insights to improve the understanding of the liver’s immune responses and hepatitis B virus (HBV)-infected cell distribution, with the final goal being the achievement of an HBV ‘functional cure’. In this issue of eGastroenterology, Cross et al used the GeoMx nanostring digital spatial profiling (DSP) technology to study gene expression in the liver tissues of three patients (one HBV-monoinfected, one HBV/HDV coinfected and one HBV/human immunodeficiency virus (HIV) coinfected). Unlike other spatial transcriptomics techniques, GeoMx DSP allows targeted selection of specific tissue regions (regions of interest) for analysis, enabling precise gene expression mapping. The study revealed spatially distinct transcriptomic signatures related to immune features and viral burden, identifying a component of underinvestigated immune cells. Despite the small sample size, this proof-of-concept study demonstrates the feasibility of spatial transcriptomics in analysing HBV infections. Future advances, such as integrating viral proteins and nucleic acids, will enhance the understanding of spatial viral replication. Challenges in tissue processing, data analysis and costs remain before spatial transcriptomics can be applied as a diagnostic tool, but ongoing multiomics approaches offer promise for improved diagnosis and therapy.

Background & Aims: Circulating HBV RNAs have been proposed as a biomarker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA) and may help to evaluate HBV treatment activity. Different research assays have been proposed and, although two PCR-based research use only investigational assays have been developed, the lack of standardized protocols represents an important limitation. Here we have designed and generated a stable clonal cell line producing an RNA-based standard for the calibration of PCR-based circulating HBV RNA assays. Methods: HBV RNA-producing Huh7-derived stable cell lines were generated by transfecting pTriEX plasmids containing 1.1 unit length HBV DNA genomes carrying mutations in the catalytic site (YMAA mutation) and the TP domain (Y63F) of the polymerase, and the ε-loop of the pregenomic (pg)RNA (mutation A1G). Results: The clonal cell line (Huh7-3D29), carrying a double YMAA and Y63F mutation, displayed, and maintained over several passages in culture, a high RNA secretion phenotype with negligible residual secreted HBV DNA. Density gradient centrifugation showed that most of the secreted HBV RNA from Huh7-3D29 cells was detected in naked capsid and virion-like particles and only a minority in small extracellular vescicles. Nanopore sequencing of 5’RACE products shows that the majority of the Huh7-3D29-secreted HBV RNAs start at the 5' end of pgRNA and pgRNA-derived spliced RNAs. Finally, Huh7-3D29 cells showed a high and up-scalable secreted RNA yield allowing 1,300 standard curves in 9 days from one flask. Conclusion: We generated a clonal cell line that produces high quantities of HBV RNAs with very low quantities of contaminating HBV DNAs, representing a stable source of RNA standard for HBV RNA assay calibration. Impact and implications:: Several investigational assays and two research use only assays have been developed to detect and quantify circulating HBV RNAs, an emerging biomarker of covalently closed circular DNA transcriptional activity and target engagement by new HBV treatments. The lack of a unique molecular standard for circulating HBV RNA quantification represents an important limitation. Here we describe the generation of a stable clonal cell line producing and secreting an RNA-based standard containing all the HBV RNA species found in HBV patients’ sera (e.g. pgRNA, HBx transcripts). This new RNA standard can be used to calibrate all PCR-based assays for circulating HBV RNA quantification to evaluate, in a non-invasive manner, the size of the transcriptionally active cccDNA pool and the activity of novel strategies aimed at curing HBV infection.

Plataformas digitais de ensino têm ganhado popularidade em sua utilização nos últimos anos, e na mesma velocidade, as lacunas acerca dessa área de pesquisa. O escopo deste artigo é analisar os conhecimentos docentes acerca dessas plataformas, num curso de formação continuada de plataforma digitais, tendo como referencial de análise o TPACK (Technological Pedagogical Content Knowledge) com foco no Ensino de Ciências, buscando construtos teóricos na área de Formação de Professores, Plataformas Digitais de Ensino, Tecnologias Digitais de Informação e Comunicação (TDICs). A pesquisa foi delineada a partir de um curso sobre plataformas digitais de ensino de Ciências para professores unidocentes que lecionam nos anos iniciais. Para esse artigo utilizou-se os questionários de concepções prévias acerca de plataformas digitais, bem como o plano de aula elaborado durante o curso e entrevista após o curso. Como resultados foram encontradas evoluções nos conhecimentos sobre plataformas digitais de ensino de Ciências da professora unidocente, bem como foi possível identificar possíveis lacunas nas formações dessa professora para trabalhar com as Tecnologias Digitais, indicando a sua potencialidade no processo de Ensino. Percebe-se ainda que o local de trabalho da professora influenciou nas suas escolhas pedagógicas e estratégias para a utilização dessas tecnologias.

Summary: The liver microenvironment contains a wide variety of monocyte and macrophage populations. Here, we present a protocol for the specific isolation of liver-resident macrophages, known as Kupffer cells (KCs), from human liver resections. We describe steps for dissociating human liver tissues, separating non-parenchymal cells into fractions by a 2-phase iodixanol gradient, and positive selection of KCs based on the expression of CD163. We then provide instructions for validating the procedure by immunofluorescence to detect CD163.For complete details on the use and execution of this protocol, please refer to Roca Suarez, Plissonnier, et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

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.

Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintaining viral persistence. Recent advances in CRISPR/Cas technology offer innovative strategies to inhibit HBV by directly targeting both cccDNA and integrated HBV DNA or indirectly by degrading HBV RNAs or targeting host proteins. This review provides a comprehensive overview of the latest advancements in using CRISPR/Cas to inhibit HBV, with a special highlight on newer non-double-strand (non-DSB) break approaches. Beyond the canonical use of CRISPR/Cas for target inhibition, we discuss additional applications, including HBV diagnosis and developing models to understand cccDNA biology, highlighting the diverse use of this technology in the HBV field.

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.

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

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).

Chronic hepatitis B virus (HBV) infection remains a global health problem due to the lack of treatments that prevent viral rebound from HBV covalently closed circular (ccc)DNA. In addition, HBV DNA integrates in the human genome, serving as a source of hepatitis B surface antigen (HBsAg) expression, which impairs anti-HBV immune responses. Cytosine base editors (CBEs) enable precise conversion of a cytosine into a thymine within DNA. In this study, CBEs were used to introduce stop codons in HBV genes, HBs and Precore. Transfection with mRNA encoding a CBE and a combination of two guide RNAs led to robust cccDNA editing and sustained reduction of the viral markers in HBV-infected HepG2-NTCP cells and primary human hepatocytes. Furthermore, base editing efficiently reduced HBsAg expression from HBV sequences integrated within the genome of the PLC/PRF/5 and HepG2.2.15 cell lines. Finally, in the HBV minicircle mouse model, using lipid nanoparticulate delivery, we demonstrated antiviral efficacy of the base editing approach with a >3log10 reduction in serum HBV DNA and >2log10 reduction in HBsAg, and 4/5 mice showing HBsAg loss. Combined, these data indicate that base editing can introduce mutations in both cccDNA and integrated HBV DNA, abrogating HBV replication and silencing viral protein expression.

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.

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).

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.

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.