New treatments for adult T-cell leukemia/lymphoma.

Adult T cell leukemia lymphoma (ATL) is a mature T cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). ATL is endemic in specific geographic regions of the world closely related to areas with high prevalence of HLTV-1 infection, including Southwestern Japan, the Caribbean Basin, Central Africa, South America, Northern and Central Australia. HLTV-1 is primarily transmitted through breastmilk in asymptomatic carriers with a long latency period before transformation into ATL in 3 - 5 % of carriers after acquisition of multiple leukemogenic mutations.

2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

PARADIGM-PV: a randomized, multicenter phase 4 study to assess the efficacy and safety of ropeginterferon alfa-2b in patients with low- or high-risk polycythemia vera.

Polycythemia vera (PV) is characterized by clonal hematopoietic stem or progenitor cells with constitutively active somatic mutation(s) in the Janus kinase 2 gene. Phlebotomy (Phl) and aspirin are often used alone for low-risk PV patients. However, data from the Low-PV study demonstrated that Phl and aspirin may not be adequate for patients.

A Complete Assembly and Annotation of the American Shad Genome Yields Insights into the Origins of Diadromy.

Transitions across ecological boundaries, such as those separating freshwater from the sea, are major drivers of phenotypic innovation and biodiversity. Despite their importance to evolutionary history, we know little about the mechanisms by which such transitions are accomplished. To help shed light on these mechanisms, we generated the first high-quality, near-complete assembly and annotation of the genome of the American shad (Alosa sapidissima), an ancestrally diadromous (migratory between salinities) fish in the order Clupeiformes of major cultural and historical significance.

A super-resolution algorithm to fuse orthogonal CT volumes using OrthoFusion.

OrthoFusion, an intuitive super-resolution algorithm, is presented in this study to enhance the spatial resolution of clinical CT volumes. The efficacy of OrthoFusion is evaluated, relative to high-resolution CT volumes (ground truth), by assessing image volume and derived bone morphological similarity, as well as its performance in specific applications in 2D-3D registration tasks. Results demonstrate that OrthoFusion significantly reduced segmentation time, while improving structural similarity of bone images and relative accuracy of derived bone model geometries.

Role of MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Fertility-sparing treatment (FST) has become a key aspect of managing gynecologic cancers in reproductive-age patients who wish to preserve fertility. Several leading clinical societies, including the European Society of Gynecological Oncology, the European Society for Radiotherapy and Oncology, the European Society of Pathology, and the European Society of Human Reproduction and Embryology, have recently published evidence-based guidelines on fertility-sparing strategies and posttreatment surveillance of patients with early-stage gynecologic cancers, in particular endometrial and cervical cancers. These guidelines highlight MRI as essential to initial patient selection and follow-up.

Fine-Tuned Expression of Evolutionarily Conserved Signaling Molecules in the Notochord.

The notochord is an axial structure required for the development of all chordate embryos, from sea squirts to humans. Over the course of more than half a billion years of chordate evolution, in addition to its structural function, the notochord has acquired increasingly relevant patterning roles for its surrounding tissues. This process has involved the co-option of signaling pathways and the acquisition of novel molecular mechanisms responsible for the precise timing and modalities of their deployment.

Role of Antiplatelets and Anticoagulation Therapies in Pregnancy.

Thrombosis is an important cause of morbidity and mortality worldwide. Pregnancy is a hypercoagulable state, and thrombotic complications in pregnancy are a major cause of maternal and fetal morbidity and mortality. Current guidelines support the selective use of aspirin, heparin, and warfarin in pregnant women.

Comparative Analysis of Outcomes in Adult Spinal Deformity Patients with Proximal Junctional Kyphosis or Failure Initially Fused to Upper Versus Lower Thoracic Spine.

Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included.

Artificial Intelligence in the Non-Invasive Detection of Melanoma.

Skin cancer is one of the most prevalent cancers worldwide, with increasing incidence. Skin cancer is typically classified as melanoma or non-melanoma skin cancer. Although melanoma is less common than basal or squamous cell carcinomas, it is the deadliest form of cancer, with nearly 8300 Americans expected to die from it each year.

Chemokine CXCL12 Activates CXC Receptor 4 Metastasis Signaling Through the Upregulation of a CXCL12/CXCR4/MDMX (MDM4) Axis.

Background: The metastasis-promoting G-protein-coupled receptor CXC Receptor 4 (CXCR4) is activated by the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1). The CXCL12/CXCR4 pathway in cancer promotes metastasis but the molecular details of how this pathway cross-talks with oncogenes are understudied. An oncogene pathway known to promote breast cancer metastasis in MDA-MB-231 xenografts is that of Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX).

Frailty in older adults with systemic lupus erythematosus and emergency department utilization: an administrative claims data analysis of Medicare beneficiaries.

Introduction / Objectives: While presence of concomitant SLE and frailty has been associated with greater emergency department (ED) use than SLE alone in young/mid-aged adults, whether frailty increases ED use in older adults with SLE remains unknown. In a nationally representative United States administrative claims dataset, we investigated the association of frailty duration with use of ED services in the SLE population compared with individuals without systemic rheumatic disease (SRD).

Method: We identified Medicare beneficiaries ≥ 65 years with SLE and matched them (1:4) by age and gender with non-SRD comparators with osteoarthritis.

Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice.

Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions.

Changes in Medication Complexity and Post-Hospitalization Outcomes in Older Adults Hospitalized for Heart Failure.

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes.

A Comprehensive Metabolomic and Microbial Analysis Following Dietary Amino Acid Reduction in Mice.

Nutritional metabolomics provides a comprehensive overview of the biochemical processes that are induced by dietary intake through the measurement of metabolite profiles in biological samples. However, there is a lack of deep phenotypic analysis that shows how dietary interventions influence the metabolic state across multiple physiologic sites. Dietary amino acids have emerged as important nutrients for physiology and pathophysiology given their ability to impact cell metabolism.

Impact of hospital lead extraction volume on management of cardiac implantable electronic device-associated infective endocarditis.

Aims: Utilization of transvenous lead extraction/removal (TLE) for the management of cardiac implantable electronic device (CIED)-associated infective endocarditis (IE) remains low. The aim of this study was to examine the impact of hospital TLE procedural volume on TLE utilization and outcomes for patients with CIED-associated IE.

Methods And Results: Using the Nationwide Readmissions Database, we evaluated 21 545 admissions for patients (mean age 70 years, 39% female) with CIEDs hospitalized with IE at TLE centres.

Temporal Changes in PROMs Improvement and Recovery Kinetics Following Transforaminal Endoscopic Lumbar Discectomy.

Study Design: Retrospective cohort study.

Objective: to analyze trends in PROMs improvement and recovery kinetics following transforaminal endoscopic lumbar discectomy and foraminotomy (TELD).

Summary Of Background Data: As TELDs become an increasingly common alternative to fusions for lateral disc herniations, it is important to understand patients' postoperative recovery timelines to manage patient expectations.

Arterial conduits for coronary bypass grafting: the set-point concept.

Endothelial cells control the vascular tone of arterial grafts used for coronary artery bypass surgery and react to changes in local shear stress. The vascular adaptations induced by endothelial cell activation affect the outcome of surgical grafts and can be predicted based on the set-point theory. In this Hypothesis piece, it is proposed that the set-point concept should inform surgical decision making for coronary artery bypass surgery.

Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.

Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields.

Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs.

Patterns of reconstruction following margin-controlled surgery for melanoma of the lentigo maligna type of the head and neck.

Melanoma of the lentigo maligna (LM) type is most commonly located on the head and neck region. This subtype of melanoma poses surgical challenges due to its location on anatomically sensitive areas and frequent presence of subclinical extension. To analyze the reconstruction patterns of LM patients undergoing margin-controlled surgery.