CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.

Cross-talk between hematopoietic stem and progenitor cells (HSPCs) and bone marrow (BM) cells is critical for homing and sustained engraftment after transplantation. In particular, molecular and physical adaptation of sinusoidal endothelial cells (ECs) promote HSPC BM occupancy; however, signals that govern these events are not well understood. Extracellular vesicles (EVs) are mediators of cell-cell communication crucial in shaping tissue microenvironments.

Diagnostic accuracy of an exhaled breath test for TB in hospitalized patients with cough or risk.

Closing the TB diagnostic gap is an urgent priority, for which non-sputum-based tests are needed. We evaluated the diagnostic accuracy of Aeonose, an exhaled breath test (EBT), as a TB triage test.Patients with cough or TB risk factors admitted to a tertiary hospital in Lima, Peru, were prospectively enrolled and underwent EBT.

Diagnosis and Management of Periprosthetic Joint Infections After Total Ankle Arthroplasty.

Periprosthetic joint infection (PJI) after total ankle arthroplasty (TAA) is a dreaded complication that may lead to catastrophic outcomes. Risk factors include a history of surgery on the operated ankle, low preoperative function scores, diabetes, extended surgical time, and postoperative wound-healing problems. Clinical presentation varies and may include increasing ankle pain and swelling, high temperature, local erythema, wound drainage, and dehiscence.

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC, CC) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (C)/EC, were used to predict the potential in vivo efficacy.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.

Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche.

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche.

Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response.

Hematopoietic stem and progenitor cell (HSPC) transplantation serves as a curative therapy for many benign and malignant hematopoietic disorders and as a platform for gene therapy. However, growing needs for ex vivo manipulation of HSPC-graft products are limited by barriers in maintaining critical self-renewal and quiescence properties. The role of sphingolipid metabolism in safeguarding these essential cellular properties has been recently recognized, but not yet widely explored.

A Deeply Quiescent Subset of CML LSC depend on FAO yet Avoid Deleterious ROS by Suppressing Mitochondrial Complex I.

Background And Objective: Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are therapy resistant and the cause of relapse. A state of deep quiescence appears to enable cancer stem cells (CSC) to acquire new somatic mutations essential for disease progression and therapy resistance.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Introduction: Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.

Targeting integrins in drug-resistant acute myeloid leukaemia.

Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that interact with not only normal haematopoietic stem cells (HSC) but also leukaemia cells like AML. There are many adhesion molecules in the BM microenvironment; therein, integrins have been of central interest.

Altered physical phenotypes of leukemia cells that survive chemotherapy treatment.

The recurrence of cancer following chemotherapy treatment is a major cause of death across solid and hematologic cancers. In B-cell acute lymphoblastic leukemia (B-ALL), relapse after initial chemotherapy treatment leads to poor patient outcomes. Here we test the hypothesis that chemotherapy-treated versus control B-ALL cells can be characterized based on cellular physical phenotypes.

Electronic alerts for ambulatory patients with atrial fibrillation not prescribed anticoagulation: A randomized, controlled trial (AF-ALERT2).

Background: Despite widely available risk stratification tools, safe and effective anticoagulants, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is under-prescribed in ambulatory patients. To assess the impact of alert-based computerized decision support (CDS) on anticoagulation prescription in ambulatory patients with AF and high-risk for stroke, we conducted this randomized controlled trial.

Methods: Patients with AF and CHADSVASc score ≥ 2 who were not prescribed anticoagulation and had a clinic visit at Brigham and Women's Hospital were enrolled.

Proteogenomic Profiling of High-Grade B-Cell Lymphoma With 11q Aberrations and Burkitt Lymphoma Reveals Lymphoid Enhancer Binding Factor 1 as a Novel Biomarker.

High-grade B-cell lymphomas with 11q aberrations (HGBL-11q) represent a World Health Organization-defined group of lymphomas that harbor recurrent chromosome 11q aberrations involving proximal gains and telomeric losses. Although a limited number of HGBL-11q cases evaluated thus far appear to show a similar course and prognosis as Burkitt lymphoma (BL), many molecular differences have been appreciated, most notably the absence of MYC rearrangement. Despite biological differences between BL and HGBL-11q, histomorphologic and immunophenotypic distinction remains challenging.

Myeloid sarcoma with mutation may be clinically and genetically distinct from AML with mutation: a study from the Bone Marrow Pathology Group.

Myeloid sarcoma (MS) is currently considered equivalent to de novo acute myeloid leukemia (AML); however, the relationship between these entities is poorly understood. This retrospective multi-institutional cohort study compared 43 MS with mutation to 106 AML with mutation. Compared to AML, MS had more frequent cytogenetic abnormalities including complex karyotype ( = .

Ceramide-dependent trafficking of Epstein-Barr virus LMP1 to small extracellular vesicles.

Epstein-Barr virus (EBV) is a human herpesvirus that is associated with a multitude of cancers. The primary EBV oncogene latent membrane protein 1 (LMP1) is secreted from infected cancer cells in small extracellular vesicles (EVs). Additionally, the tetraspanin protein CD63 forms a complex with LMP1 and CD63 can be trafficked to EVs through a ceramide-dependent manner.

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis.

Background And Purpose: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear.

Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study.

Background: Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

Methods: TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada).

Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers.

Background: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs).

Methods: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa.