Cholangioblastic Cholangiocarcinoma (NIPBL::NACC1 cholangiocarcinoma): Expanded Morphologic Spectrum and Further Genetic Characterization.

The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Police officer occupational health: a model of organizational constraints, trauma exposure, perceived resources, and agency.

Background: Police officers constitute a work force at high risk due to their highly demanding work conditions. In a realistic paradigm, these conditions, and other determinants of their psychological health, can be linked to a multitude of variables that interplay altogether. However, current literature that simultaneously models-quantitatively from observed data-such a multitude of variables is sparse.

The development and validation of the beliefs about Baby Crying at Night (BBCN) scale.

Objective: What are young children trying to express when they cry at night? According to Sadeh, parental beliefs about why their child is crying may play a role in the development and persistence of their child's insomnia. The aim of this study was to create a scale that specifically assesses these parental interpretations in different dimensions.

Methods: Children aged between 6 months and 3 years with either good sleep habits or behavioural insomnia were recruited.

Highly Multiplexed Immunofluorescence PhenoCycler Panel for Murine Formalin-Fixed Paraffin-Embedded Tissues Yields Insight Into Tumor Microenvironment Immunoengineering.

Spatial proteomics profiling is an emerging set of technologies that has the potential to elucidate the cell types, interactions, and molecular signatures that make up complex tissue microenvironments, with applications in the study of cancer, immunity, and much more. An emerging technique in the field is CoDetection by indEXing, recently renamed as the PhenoCycler system. This is a highly multiplexed immunofluorescence imaging technology that relies on oligonucleotide-barcoded antibodies and cyclic immunofluorescence to visualize many antibody markers in a single specimen while preserving tissue architecture.

Concordance of Whole-Slide Imaging and Conventional Light Microscopy for Assessment of Pathologic Response Following Neoadjuvant Therapy for Lung Cancer.

Pathologic response is an endpoint in many ongoing clinical trials for neoadjuvant regimens, including immune checkpoint blockade and chemotherapy. Whole-slide scanning of glass slides generates high-resolution digital images and allows for remote review and potential measurement with image analysis tools, but concordance of pathologic response assessment on digital scans compared with that on glass slides has yet to be evaluated. Such a validation goes beyond previous concordance studies, which focused on establishing surgical pathology diagnoses, as it requires quantitative assessment of tumor, necrosis, and regression.

Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.

SREBP-Dependent Regulation of Lipid Homeostasis Is Required for Progression and Growth of Pancreatic Ductal Adenocarcinoma.

Unlabelled: Solid tumors undergo metabolic reprogramming when growth outstrips local nutrient supply. Lipids such as cholesterol and fatty acids are required for continued tumor cell proliferation, and oncogenic mutations stimulate de novo lipogenesis to support tumor growth. Sterol regulatory element-binding protein (SREBP) transcription factors control lipid homeostasis by activating genes required for lipid synthesis and uptake.

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1.

Development of a peptide-generated antibody to rabbit hemorrhagic disease virus 2 VP60 and its immunohistochemical application in natural cases.

Rabbit hemorrhagic disease virus 2 (RHDV2) has spread across the United States infecting and causing death in domestic and wild rabbits. Immunohistochemistry (IHC) would be a useful tool for the detection of RHDV2 antigen in tissues as it is inexpensive and readily achievable in most diagnostic laboratories. However, there is no readily available antibody for this purpose.

Integration of Clinical Trial Spatial Multiomics Analysis and Virtual Clinical Trials Enables Immunotherapy Response Prediction and Biomarker Discovery.

Due to the lack of treatment options, there remains a need to advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models to human trials to advance novel systemic therapies that improve treatment outcomes for patients with cancer. Computational methods that simulate tumors mathematically to describe cellular and molecular interactions are emerging as promising tools to simulate the impact of therapy entirely in silico, potentially greatly accelerating delivery of new therapeutics to patients.

Declining Antibody Affinity Over Time After Human Vaccination With a Plasmodium falciparum Merozoite Vaccine Candidate.

Unlabelled: Maintaining high-affinity antibodies after vaccination may be important for long-lasting immunity to malaria, but data on induction and kinetics of affinity is lacking. In a phase 1 malaria vaccine trial, antibody affinity increased following a second vaccination but declined substantially over 12 months, suggesting poor maintenance of high-affinity antibodies.

Clinical Trials Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000552482.

As fast as an X-ray: real-time magnetic resonance imaging for diagnosis of idiopathic scoliosis in children and adolescents.

Background: Idiopathic scoliosis is common in adolescence. Due to the rapid growth of the spine, it must be monitored closely with radiographs to ensure timely intervention when therapy is needed. As these radiographs continue into young adulthood, patients are repeatedly exposed to ionizing radiation.

Evidence for a competitive relationship between executive functions and statistical learning.

The ability of the brain to extract patterns from the environment and predict future events, known as statistical learning, has been proposed to interact in a competitive manner with prefrontal lobe-related networks and their characteristic cognitive or executive functions. However, it remains unclear whether these cognitive functions also possess a competitive relationship with implicit statistical learning across individuals and at the level of latent executive function components. In order to address this currently unknown aspect, we investigated, in two independent experiments (N = 186, N = 157), the relationship between implicit statistical learning, measured by the Alternating Serial Reaction Time task, and executive functions, measured by multiple neuropsychological tests.

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments.

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated.

Impact of confrontation to patient suffering and death on wellbeing and burnout in professionals: a cross-sectional study.

Background: Palliative care and oncology generate a risk of burnout and psychological distress in professionals. The purpose of this study is to identify both psychopathological and positive factors related to mental health at work. It aims (i) to explore the extent to which these professionals are confronted with suffering, illness, and death; and to explore the prevalence of psychological distress and/or burnout, (ii) to identify potential determinants of burnout and psychological wellbeing at work, (iii) to develop an integrative model of mental health; and to identify frequency and impact of confrontations with death, and (iv) to identify profiles of professionals are at risk of developing a mental health disorder or, conversely, characterized by wellbeing.

Comparing anti-tumor and anti-self immunity in a patient with melanoma receiving immune checkpoint blockade.

Background: Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity.

Methods: Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy.

Are thoughts and behaviours of individuals with schizophrenia more susceptible to being influenced during pandemic situations? A glimpse provided by the COVID-19 pandemic.

Individuals with psychotic disorders such as schizophrenia may be more vulnerable during pandemics, but research on this topic is limited. This study examined COVID-19 impact on a population affected by schizophrenia during the COVID-19 pandemic. Levels of psychological distress and COVID-19-related behaviours, from the COVID-related Thoughts and Behavioral Symptoms (Cov-Tabs) Scale, were compared between 107 patients with schizophrenia and 70 control participants.