Multi-niche human bone marrow on-a-chip for studying the interactions of adoptive CAR-T cell therapies with multiple myeloma.

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.

Autoantibodies immuno-mechanically modulate platelet contractile force and bleeding risk.

Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysiology and symptomology. Using a micropatterned hydrogel-laden coverslip compatible with standard fluorescence microscopy, we conduct a clinical mechanobiology study, specifically focusing on immune thrombocytopenia (ITP), an autoantibody-mediated platelet disorder that currently lacks a reliable biomarker for bleeding risk.

Recommendations for defining disturbed flow as laminar, transitional, or turbulent in assays of hemostasis and thrombosis: communication from the ISTH SSC Subcommittee on Biorheology.

Blood flow is vital to life, yet disturbed flow has been linked to atherosclerosis, thrombosis, and endothelial dysfunction. The commonly used hemodynamic descriptor "disturbed flow" found in disease and medical devices is not clearly defined in many studies. However, the specific flow regime-laminar, transitional, or turbulent-can have very different effects on hemostasis, thrombosis, and vascular health.

PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells.

Respiratory virus detection and sequencing from negative SARS-CoV-2 rapid antigen tests.

Genomic epidemiology offers important insight into the transmission and evolution of respiratory viruses. We used metagenomic sequencing from negative SARS-CoV-2 antigen tests to identify a wide range of respiratory viruses and generate full genome sequences, offering a streamlined mechanism for broad respiratory virus genomic surveillance.

Less-deformable erythrocyte subpopulations biomechanically induce endothelial inflammation in sickle cell disease.

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, during which endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis.

Total Synthesis of a PSGL-1 Glycopeptide Analogue for Targeted Inhibition of P-Selectin.

The high affinity interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin is mediated by a multimotif glycosulfopeptide (GSP) recognition domain consisting of clustered tyrosine sulfates and a Core 2 -glycan terminated with sialyl Lewis (C2--sLe). These distinct GSP motifs are much more common than previously appreciated within a wide variety of functionally important domains involved in protein-protein interactions. However, despite the potential of GSPs to serve as tools for fundamental studies and prospects for drug discovery, their utility has been limited by the absence of chemical schemes for synthesis on scale.

"An app is just available at all times"-the process and outcomes of converting the Georgia Tuberculosis Reference Guide into a mobile application.

Background: The physical, paper-based Georgia TB Reference Guide has served as the clinical reference handbook on tuberculosis (TB) diagnostic and treatment guidelines for the state of Georgia in the United States. Supported by the Georgia Department of Public Health, the production of the 112-page palm-sized booklet was previously led by a team of Georgia-based TB experts at Emory University and printed every three-five years with updates to clinical management guidelines and TB consult contact information. However, the costs associated with editorial printing combined with delays in updating a static printed booklet with revised guidance hampered the utility of the tool.

BiliQML: a supervised machine-learning model to quantify biliary forms from digitized whole slide liver histopathological images.

The progress of research focused on cholangiocytes and the biliary tree during development and following injury is hindered by limited available quantitative methodologies. Current techniques include two-dimensional standard histological cell-counting approaches, which are rapidly performed, error prone, and lack architectural context or three-dimensional analysis of the biliary tree in opacified livers, which introduce technical issues along with minimal quantitation. The present study aims to fill these quantitative gaps with a supervised machine-learning model (BiliQML) able to quantify biliary forms in the liver of anti-keratin 19 antibody-stained whole slide images.

Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma.

Unlabelled: Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.

Redefining hyperviscosity in acute leukemia: Potential implications for red cell transfusions in the microvasculature.

Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature.

Comparison of RT-PCR and antigen test sensitivity across nasopharyngeal, nares, and oropharyngeal swab, and saliva sample types during the SARS-CoV-2 omicron variant.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.

Next generation microfluidics: fulfilling the promise of lab-on-a-chip technologies.

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches have stymied microfluidics from fulfilling this promise.

What's in a Name? Experimental Evidence of Gender Bias in Recommendation Letters Generated by ChatGPT.

Background: Artificial intelligence chatbots such as ChatGPT (OpenAI) have garnered excitement about their potential for delegating writing tasks ordinarily performed by humans. Many of these tasks (eg, writing recommendation letters) have social and professional ramifications, making the potential social biases in ChatGPT's underlying language model a serious concern.

Objective: Three preregistered studies used the text analysis program Linguistic Inquiry and Word Count to investigate gender bias in recommendation letters written by ChatGPT in human-use sessions (N=1400 total letters).

Performance of the Xpert™ Mpox PCR assay with oropharyngeal, anorectal, and cutaneous lesion swab specimens.

Anorectal and oropharyngeal exposures are implicated in sexual transmission of mpox, but authorized assays in the United States are only validated with cutaneous lesion swabs. Diagnostic assays for anorectal and oropharyngeal swabs are needed to address potential future outbreaks. The Cepheid Xpert® Mpox is the first point-of-care assay to receive FDA emergency use authorization in the United States and would be a valuable tool for evaluating these sample types.

Engaging Cancer Care Physicians in Off-Label Drug Clinical Trials: Human-Centered Design Approach.

Background: Using a human-centered design (HCD) approach can provide clinical trial design teams with a better understanding of the needs, preferences, and attitudes of clinical trial stakeholders. It can also be used to understand the challenges and barriers physician stakeholders face in initiating and completing clinical trials, especially for using off-label drugs (OLDs) to treat unmet clinical needs in cancer treatment. However, the HCD approach is not commonly taught in the context of clinical trial design, and few step-by-step guides similar to this study are available to demonstrate its application.

Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders.

Red blood cell (RBC) disorders such as sickle cell disease affect billions worldwide. While much attention focuses on altered properties of aberrant RBCs and corresponding hemodynamic changes, RBC disorders are also associated with vascular dysfunction, whose origin remains unclear and which provoke severe consequences including stroke. Little research has explored whether biophysical alterations of RBCs affect vascular function.

Multisite Mpox Infection and Viral Dynamics Among Persons With HIV in Metro Atlanta.

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction.

Standardization and Comparison of Emergency Use Authorized COVID-19 Assays and Testing Laboratories.

Motivation: The motivation for this work was the need to establish a predefined cutoff based on genome copies per ml (GE/ml) rather than Ct, which can vary depending on the laboratory and assay used. A GE/ml-based threshold was necessary to define what constituted 'low positives" for samples that were included in data sets submitted to the FDA for emergency use approval for SARS-CoV-2 antigen tests.

Summary: SARS-CoV-2, the causal agent of the global COVID-19 pandemic, made its appearance at the end of 2019 and is still circulating in the population.

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, their suboptimal uptake combined with the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples.

Challenges and Opportunities for Commercializing Technologies in the Pulmonary Arena: An Official American Thoracic Society Report.

"Translational medicine" has been a buzzword for over two decades. The concept was intended to be lofty, to reflect a new "bench-to-bedside" approach to basic and clinical research that would bridge fields, close gaps, accelerate innovation, and shorten the time and effort it takes to bring novel technologies from basic discovery to clinical application. Has this approach been successful and lived up to its promise? Despite incredible scientific advances and innovations developed within academia, successful clinical translation into real-world solutions has been difficult.