Translational Outcomes Project in Neurotrauma (TOP-NT) Pre-Clinical Consortium Study: A Synopsis.

Traumatic brain injury (TBI) has long been a leading cause of death and disability, yet research has failed to successfully translate findings from the pre-clinical, animal setting into the clinic. One factor that contributes significantly to this struggle is the heterogeneity observed in the clinical setting where patients present with injuries of varying types, severities, and comorbidities. Modeling this highly varied population in the laboratory remains challenging.

Prospective Harmonization, Common Data Elements, and Sharing Strategies for Multicenter Pre-Clinical Traumatic Brain Injury Research in the Translational Outcomes Project in Neurotrauma Consortium.

Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing and validating noninvasive TBI assessment tools through team science.

Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

A Novel Grammar-Based Approach for Patients' Symptom and Disease Diagnosis Information Dissemination to Maintain Confidentiality and Information Integrity.

Disease prediction using computer-based methods is now an established area of research. The importance of technological intervention is necessary for the better management of disease, as well as to optimize use of limited resources. Various AI-based methods for disease prediction have been documented in the literature.

Real-world Clinical Outcomes and Prognostic Factors in Neuroendocrine Prostate Cancer.

Background: Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians.

Methods: This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases.

A review of antimicrobial usage practice in livestock and poultry production and its consequences on human and animal health.

Antimicrobials are employed in the control of contagious illnesses in humans and animals and are also utilized as growth enhancers in livestock and poultry. Improper application of antibiotics results in the development of multi-drug-resistant (MDR) bacteria, such as methicillin-resistant (MRSA), vancomycin-resistant (VRSA), colistin-resistant, extended-spectrum beta-lactamase (ESBL)-producing and fluoroquinolone-resistant . Transmission of MDR bacteria happens among animals, from human to animal, and vice versa, resulting in treatment failure, increased treatment cost, and high morality.

Investigational drugs in early phase trials for myelofibrosis.

Introduction: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation.

Tuned Manganese-Impregnated Mesoporous Silica Nanoparticles as a pH-Responsive Dual Imaging Probe.

The limitations of individual imaging modalities have led to significant interest in hybrid imaging methods that combine the advantages of multiple techniques. The development of diverse dual imaging agents, which offer the exceptional sensitivity of single-photon emission computed tomography (SPECT) and the high spatial resolution of magnetic resonance imaging (MRI), has been addressing the demand for more advanced diagnostic pharmaceuticals. In this study, Tc-labeled manganese oxide-loaded mesoporous silica nanoparticles (MSNs), conjugated with folic acid as the targeting moiety and the chelating agent Hpentapa-en-NH (Tc-MnO-MSN-FA-pa), were developed for targeted SPECT-MRI dual imaging.

Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia.

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.

Methods: This was a phase 2 trial of patients with newly diagnosed APL.

Preclinical efficacy of CDK7 inhibitor-based combinations against myeloproliferative neoplasms transformed to AML.

Rising blast-percentage or secondary (s) AML transformation (sAML) in MPNs leads to JAK inhibitor (JAKi) therapy-resistance and poor survival. Here, we demonstrate that the CDK7 inhibitor (CDK7i) SY-5609 treatment depletes phenotypically-characterized post-MPN-sAML stem/progenitor cells. In the cultured post-MPN sAML SET2 and HEL as well as patient-derived (PD) post-MPN-sAML cells, SY-5609 treatment inhibited growth and induced lethality, while sparing normal cells.

Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis.

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML.

VSV drives CD8 T cell-mediated tumour regression through infection of both cancer and non-cancer cells.

Oncolytic viruses (OV) are designed to selectively infect and kill cancer cells, while simultaneously eliciting antitumour immunity. The mechanism is expected to originate from infected cancer cells. However, recent reports of tumour regression unaccompanied by cancer cell infection suggest a more complex mechanism of action.

Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics.

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear.

Prognostic Significance of Regulatory T-Cells and PD-1 + CD8 T-Cells in Chronic Myeloid Leukemia Patients Treated with Generic Imatinib.

The impact of T-regulatory cells (Tregs), PD-1 + CD8 T-cells, and their dynamics during treatment with imatinib mesylate remains poorly understood in patients with chronic myeloid leukemia (CML). We conducted a prospective study on newly diagnosed, treatment-naïve adult (> 18 years old) patients with CML in the chronic phase (CP) and age- and sex-matched controls. Peripheral blood samples were collected at diagnosis and after three months of imatinib therapy to assess Tregs and PD-1 + CD8 T-cell levels using flow cytometry.

Expert Panel Consensus Recommendations for Allergic Rhinitis in Patients with Asthma in India.

Allergic rhinitis and asthma are commonly coexisting conditions, significantly impacting patient health and quality of life. Despite their interrelation, diagnosing allergic rhinitis in patients with asthma remains challenging, leading to underdiagnosis and suboptimal management. The expert consensus engaged a modified Delphi method involving 29 experts including pulmonologists, ear, nose, and throat surgeons, and allergologists.

Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.

Response to BH3 mimetics in multiple myeloma (MM) correlates with CCND1-rearrangement or expression of anti-apoptotic molecules, particularly Bcl-2 and Mcl-1. Our study investigates the relationship between cytogenetic abnormalities (CGAs) and intracellular Bcl-2 and Mcl-1 expression in myeloma plasma cells (MPCs) using flow cytometry (FCM). We measured median fluorescence intensity (MFI) of Bcl-2 and Mcl-1 in 163 bone marrow samples (143 MM, 20 controls) across various cell types.

Increased expression of proton pump and allergic inflammation genes predicts PPI failure in pediatric eosinophilic esophagitis.

Proton pump inhibitors (PPIs) are one of the standards of care of eosinophilic esophagitis (EoE) treatment, though PPI response rates are variable ranging from 23 to 63% in pediatric studies. We sought to determine if expression of select genes in esophageal mucosa can predict PPI responsiveness in EoE. Children with a new diagnosis of EoE (15 or more eosinophils/hpf on esophageal biopsy) were prospectively treated with 8 weeks of PPI therapy before follow-up esophagogastroduodenoscopy (EGD).

ISCCM Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis.

Unlabelled: Tuberculosis (TB) is an important cause of morbidity and mortality globally. About 3-4% of hospitalized TB patients require admission to the intensive care unit (ICU); the mortality in these patients is around 50-60%. There is limited literature on the evaluation and management of patients with TB who required ICU admission.

Genomic landscape of early-stage prostate adenocarcinoma in Mexican patients: an exploratory study.

Background: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients.