Breast Cancer Specificities of Patients With Anti-Ri Paraneoplastic Neurologic Syndromes.

Background And Objectives: Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).

Implementation outcomes of 1-3-7 focus investigation for malaria in a low transmission setting in Southern Province, Zambia: A mixed methods study.

Eleven countries have been certified as malaria free since 2016, but none of these are in subSaharan Africa where elimination challenges are unique. The 1-3-7 focus investigation approach is an implementation strategy that requires case reporting, case investigation/classification, and focal classification/response to be completed one, three, and seven days, respectively, after index case diagnosis. Real-time short-messaging-service reports are sent at each step to add accountability and data transparency.

Tail Anchored protein insertion mediated by CAML and TRC40 links to neuromuscular function in mice.

Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.

Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis.

Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.

Mucin Colocalizes with Influenza Virus and Preserves Infectivity in Deposited Model Respiratory Droplets.

The stability of influenza virus in respiratory particles varies with relative humidity (RH) and protein content. This study investigated the decay, or loss of infectivity, of influenza A virus (IAV) in 1-μL respiratory droplets deposited on a surface with varying concentrations of mucin, one of the most abundant proteins in respiratory mucus, and examined the localization of virions within droplets. IAV remained stable at 0.

Extracellular vesicles: from intracellular trafficking molecules to fully fortified delivery vehicles for cancer therapeutics.

Extracellular vesicles (EVs) are emerging as viable tools in cancer treatment due to their ability to carry a wide range of theranostic activities. This review summarizes different forms of EVs such as exosomes, microvesicles, apoptotic bodies, and oncosomes. It also sheds the light onto isolation methodologies, characterization techniques and therapeutic applications of all discussed EVs.

Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning.

Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Super-Resolution Goes Viral: T4 Virus Particles as Versatile 3D-Bio-NanoRulers.

In the burgeoning field of super-resolution fluorescence microscopy, significant efforts are being dedicated to expanding its applications into the 3D domain. Various methodologies have been developed that enable isotropic resolution at the nanometer scale, facilitating the visualization of 3D subcellular structures with unprecedented clarity. Central to this progress is the need for reliable 3D structures that are biologically compatible for validating resolution capabilities.

MicroRNA in neuroexosome as a potential biomarker for HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorder (HAND) is a complication of chronic inflammation caused by HIV infection that impairs cognitive and motor functions. HAND can occur at any age, regardless of the duration of infection, even in people living with HIV (PLWH) whose blood viral load is controlled by antiretroviral therapy. The diagnosis of HAND requires a battery of neuropsychological tests, which is time-consuming and burdensome, limiting its effectiveness for screening PLWH.

Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis.

Adipogenesis is the healthy expansion of white adipose tissue (WAT), serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the body. Therefore, the identification of novel regulatory molecules in adipogenesis, specifically membrane receptors such as G protein-coupled receptors (GPCRs), holds significant clinical promise. These receptors can serve as viable targets for pharmaceuticals, offering potential for restoring metabolic homeostasis in individuals with obesity.

Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.

The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.

Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma.

Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.

Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.

Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival.

Mortality after cancer diagnosis among children with congenital heart disease in Denmark and Sweden.

Background: Recent decades have witnessed tangible improvements in childhood cancer survival. However, the prognosis for children with congenital heart disease (CHD), the most prevalent birth defect, remains unclear. Due to improved survival of CHD and childhood cancer, evaluating outcomes within this intersection is important for clinical practice.

Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle.

TPX2 is an elongated molecule containing multiple α-helical repeats. It stabilizes microtubules (MTs), promotes MT nucleation, and is essential for spindle assembly. However, the molecular basis of how TPX2 performs these functions remains elusive.

Immune Microenvironment in Breast Cancer Metastasis.

Metastatic disease is the final stage of breast cancer that accounts for vast majority of patient death. Mounting data over recent years strongly support the critical roles of the immune microenvironment in determining breast cancer metastasis. The latest single-cell studies provide further molecular evidence illustrating the heterogeneity of this immune microenvironment.

The Roles of Myeloid Cells in Breast Cancer Progression.

This chapter reviews tumor-associated myeloid cells, including macrophages, neutrophils, and other innate immune cells, and their multifaceted roles in supporting breast cancer progression and metastasis. In primary tumors, myeloid cells play key roles in promoting tumor epithelial-mesenchymal transition (EMT) and invasion. They can facilitate intravasation (entry into the bloodstream) and colonization, disrupting the endothelial cell layer and reshaping the extracellular matrix.

RANK/RANKL Signaling Pathway in Breast Development and Cancer.

RANK pathway has attracted increasing interest as a promising target in breast cancer, given the availability of denosumab, an anti-RANKL drug. RANK signaling mediates progesterone-driven regulation of mammary gland development and favors breast cancer initiation by controlling mammary cell proliferation and stem cell fate. RANK activation promotes luminal mammary epithelial cell senescence, acting as an initial barrier to tumorigenesis but ultimately facilitating tumor progression and metastasis.

The Microenvironment in DCIS and Its Role in Disease Progression.

Ductal carcinoma in situ (DCIS) accounts for ~20% of all breast cancer diagnoses but whilst known to be a precursor of invasive breast cancer (IBC), evidence suggests only one in six patients will ever progress. A key challenge is to distinguish between those lesions that will progress and those that will remain indolent. Molecular analyses of neoplastic epithelial cells have not identified consistent differences between lesions that progressed and those that did not, and this has focused attention on the tumour microenvironment (ME).

A Guide to Breast Cancer Research: An Introduction.

"A Guide to Breast Cancer Research: From Cells and Molecular Mechanisms to Therapy" is designed as a comprehensive reference for early career investigators and postgraduate students. This book aims to provide a broad overview of contemporary breast cancer research. It covers key areas including development and cancer, metastasis and immunology, subtypes, signalling, therapy, and resistance.

Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2.

A human oral commensal-mediated protection against Sjögren's syndrome with maintenance of T cell immune homeostasis and improved oral microbiota.

Sjögren's syndrome (SS) is a prevalent systemic autoimmune disease with substantial impacts on women's health worldwide. Although oral Haemophilus parainfluenzae is reduced in SS, its significance remains unclear. This study aimed to elucidate the pathophysiological role of H.

Exosomes in Autoimmune Diseases: A Review of Mechanisms and Diagnostic Applications.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation.

Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.

Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.

Maternal microchimeric cell trafficking and its biological consequences depend on the onset of inflammation at the feto-maternal interface.

Microchimerism is defined as the presence of a small population of genetically distinct cells within a host that is derived from another individual. Throughout pregnancy, maternal and fetal cells are known to traffic across the feto-maternal interface and result in maternal and fetal microchimerism, respectively. However, the routes of cell transfer, the molecular signaling as well as the timing in which trafficking takes place are still not completely understood.