Effect of Phase Encoding Direction on Image Quality in Single-Shot EPI Diffusion-Weighted Imaging of the Breast.

Background: In breast diffusion-weighted imaging (DWI), distortion and physiologic artifacts affect clinical interpretation. Image quality can be optimized by addressing the effect of phase encoding (PE) direction on these artifacts.

Purpose: To compare distortion artifacts in breast DWI acquired with different PE directions and polarities, and to discuss their clinical implications.

Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation?

Sarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types.

MicroRNAs in the Pathogenesis, Prognostication and Prediction of Treatment Resistance in Soft Tissue Sarcomas.

Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment are invariably poor. MicroRNAs (miRNAs), which are short non-coding RNA molecules, target and modulate multiple dysregulated target genes and/or signalling pathways within cancer cells.

Mature B cells and mesenchymal stem cells control emergency myelopoiesis.

Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here, we show that lymphotoxin-β receptor (LTβR) signaling in combination with TNF and IL-1 receptor signaling in bone marrow mesenchymal stem cells (MSCs) down-regulates expression to shut down lymphopoiesis during systemic inflammation.

Keeping pace with innovations in data visualizations: A commentary for mathematics education in times of crisis.

The mathematical medium of data visualization and other data representations (DV) has served as a primary means of communicating about the COVID-19 crisis. DVs about the pandemic are highly visible across news journalism and include an increasingly innovative and diverse set of representational forms. These representational forms employ multimodal, interactive, and narrative elements, among others, that create new possibilities for data storytelling.

Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome.

Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LTβR) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs.

A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma.

Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration.

Hematopoietic Stem Cell Niches and Signals Controlling Immune Cell Development and Maintenance of Immunological Memory.

Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals provided by bone marrow niches comprising of mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Because of their critical roles in HSC maintenance the niches formed by MSPCs and ECs are commonly referred to as HSC niches. For the most part, the signals required for HSC maintenance act in a short-range manner, which imposes the necessity for directional and positional cues in order for HSCs to localize and be retained properly in stem cell niches.

Improved Cancer Detection Using Artificial Intelligence: a Retrospective Evaluation of Missed Cancers on Mammography.

To determine whether cmAssist™, an artificial intelligence-based computer-aided detection (AI-CAD) algorithm, can be used to improve radiologists' sensitivity in breast cancer screening and detection. A blinded retrospective study was performed with a panel of seven radiologists using a cancer-enriched data set from 122 patients that included 90 false-negative mammograms obtained up to 5.8 years prior to diagnosis and 32 BIRADS 1 and 2 patients with a 2-year follow-up of negative diagnosis.

A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem Cells to Mature B Lymphocytes.

B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs) and sinusoidal endothelial cells. These niches are defined by function and location: MSPCs are mostly perisinusoidal cells that together with a small subset of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7), IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are morphologically heterogeneous, highly reticular, and form a vast cellular network in the bone marrow parenchyma capable of interacting with large numbers of hematopoietic cells.

Comparison of efficacy and tolerability of pharmacological treatment for the overactive bladder in women: A network meta-analysis.

Background: Overactive bladder syndrome (OAB) is a common medical condition that causes significant distress and impact on the quality of life in women. Muscarinic receptor antagonists remain the mainstay of therapy, but they are limited by their efficacy and adverse effects. The objective of the article was to compare the clinical efficacy and tolerability of medications used to treat OAB in women through network meta-analysis.

Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation.

Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis.

Prevalence of Mental Illness among Homeless People in Hong Kong.

Metholodogy: This study examined the prevalence and correlates of mental illness in homeless people in Hong Kong and explored the barriers preventing their access to health care. Ninety-seven Cantonese-speaking Chinese who were homeless during the study period were selected at random from the records of the three organisations serving the homeless population. The response rate was 69%.

Dupuytren's contracture: an analysis of outcomes of percutaneous needle fasciotomy versus open fasciectomy.

Background: Percutaneous needle fasciotomy (PNF) is a minimally invasive technique used to manage Dupuytren's contracture. We compared outcomes of PNF versus open fasciectomy (OF) to examine the suitability of PNF in Australia.

Method: A retrospective cohort study using two questionnaires regarding Dupuytren's treatment was used to assess patients with uncomplicated primary disease.

Extracellular matrix-mediated differentiation of human embryonic stem cells: differentiation to insulin-secreting beta cells.

Stem cells have tremendous potential for treating various human diseases. Protocols have been established to differentiate stem cells into specific lineages through the provision of signals in the form of growth factors, cytokines, or small molecules. Herein we investigate an alternative strategy for directed differentiation of human embryonic stem cells (hESCs)--extracellular-matrix (ECM) mediated differentiation.

Exploring the mode of action of bioactive compounds by microfluidic transcriptional profiling in mycobacteria.

Most candidate anti-bacterials are identified on the basis of their whole cell anti-bacterial activity. A critical bottleneck in the early discovery of novel anti-bacterials is tracking the structure activity relationship (SAR) of the novel compounds synthesized during the hit to lead and lead optimization stage. It is often very difficult for medicinal chemists to visualize if the novel compounds synthesized for understanding SAR of a particular scaffold have similar molecular mechanism of action (MoA) as that of the initial hit.

para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis.

para-Aminosalicylic acid (PAS) is one of the antimycobacterial drugs currently used for multidrug-resistant tuberculosis. Although it has been in clinical use for over 60 years, its mechanism(s) of action remains elusive. Here we report that PAS is a prodrug targeting dihydrofolate reductase (DHFR) through an unusual and novel mechanism of action.

A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis.

Growing evidence suggests that the presence of a subpopulation of hypoxic non-replicating, phenotypically drug-tolerant mycobacteria is responsible for the prolonged duration of tuberculosis treatment. The discovery of new antitubercular agents active against this subpopulation may help in developing new strategies to shorten the time of tuberculosis therapy. Recently, the maintenance of a low level of bacterial respiration was shown to be a point of metabolic vulnerability in Mycobacterium tuberculosis.