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Ocular Surface Squamous Neoplasia In Situ Secondary to Bruton Tyrosine Kinase Inhibitor Therapy.

Eye Contact Lens

November 2024

School of Medicine (R.F.B.), University of South Carolina, Columbia, SC; Department of Ophthalmology (M.V.S., D.T.B.), Charlie Norwood Veterans Affairs Medical Center, Augusta, GA; and Department of Ophthalmology (T.E.F.), Medical College of Georgia, Augusta, GA.

Bruton tyrosine kinase (BTK) inhibitors have become an important therapeutic option in treating B-cell malignancies including non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, a noted morbidity associated with their use is the potential for the development of second primary malignancy related to immunomodulation. In this case, we report a second primary malignancy of ocular surface squamous neoplasia (OSSN) owing to BTK therapy.

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This systematic review with meta-analysis compared the diagnostic accuracy of neuromuscular ultrasound (NMUS) and electrodiagnostic studies (EDX) as confirmatory tests for carpal tunnel syndrome (CTS) diagnosis. We used bivariate random-effects models to estimate pooled sensitivity and specificity and generate hierarchical summary receiver-operating characteristic curves to assess diagnostic test accuracy. Nine paired accuracy studies were included, representing 1751 hands (743 clinically diagnosed CTS; 1008 without CTS) that underwent NMUS and EDX.

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Gastric and esophageal cancers, the predominant forms of upper gastrointestinal malignancies, contribute significantly to global cancer mortality. Routine detection methods, including medical imaging, endoscopic examination, and pathological biopsy, often suffer from drawbacks such as low sensitivity and laborious and complex procedures. Raman spectroscopy is a non-invasive and label-free optical technique that provides highly sensitive biomolecular information to facilitate effective tumor identification.

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Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon. A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer. Here we show that an interleukin-4 fusion protein (Fc-IL-4), a typical type 2 cytokine, directly acts on CD8 T cells and enriches functional terminally exhausted CD8 T (CD8 T) cells in the tumour.

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Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL), approximately 50% of patients relapse within the first year, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.

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Unveiling the Therapeutic Potential of Paclitaxel Combinations Against Breast Carcinoma and Identification of In Vivo Biomarkers.

Chem Biol Drug Des

September 2024

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China.

Breast cancer (BC) is one of the leading causes of high mortality rates in women worldwide. Although advancements have been made in the design of therapeutic strategies and drug discovery, drug resistance remains one of the key challenges. One of the ways to overcome drug resistance is finding potential drug combinations since the efficacy of combined drugs is higher than their individual efficacies if the combination is a synergistic pair.

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Article Synopsis
  • Gaultheria trichophylla Royle, traditionally used for treating arthritis, was assessed for its anti-arthritic effects through various scientific analyses, including animal studies and molecular docking.
  • The extract and salicylate-rich fractions (SRF) demonstrated dose-dependent effectiveness, evidenced by reduced joint swelling, increased pain tolerance, and improved blood parameters compared to a control group.
  • Key active compounds like methyl salicylate were identified, and the overall findings suggest that G. trichophylla could be a promising option for reducing joint inflammation in rheumatoid arthritis.
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A "watch and wait" strategy, delaying treatment until active disease manifests, is adopted for most CLL cases; however, prognostic models incorporating biomarkers have shown to be useful to predict treatment requirement. In our prospective O-CLL1 study including 224 patients, we investigated the predictive role of 513 microRNAs (miRNAs) on time to first treatment (TTFT). In the context of this study, six well-established variables (i.

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Background: An atrioventricular node (AVN) ablation and permanent pacing have been previously reported as effective treatments for patients with atrial tachyarrhythmias. However single-ventricle patients requiring chronic ventricular pacing are at a higher risk of developing ventricular dysfunction and atrioventricular valve regurgitation. We report a case of successful AVN ablation in a 3-month-old infant with hypoplastic left heart syndrome and ectopic atrial tachycardia (EAT).

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Chronic tympanic membrane (TM) perforation is a tubotympanic disease caused by either traumatic injury or inflammation. A recent study demonstrated significant progress in promoting the regeneration of chronic TM perforations through the application of nanofibers with radially aligned nanostructures and controlled release of growth factors. However, radially aligned nanostructures with stem cell-stimulating factors have never been used.

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Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic.

Cell

September 2024

Institut d'Écologie et des Sciences de l'Environnement (IEES-Paris, UMR 7618), CNRS, Sorbonne Université, UPEC, IRD, INRAE, Paris, France. Electronic address:

Article Synopsis
  • Zoonotic viruses, like SARS-CoV-2, can spill over from animals to humans, often linked to animal trade, with COVID-19 traced back to the Huanan Seafood Wholesale Market.
  • Analysis of environmental samples from the market in early 2020 shows high genetic diversity of SARS-CoV-2, especially near a wildlife stall that had a variety of wildlife DNA, including potential intermediate hosts.
  • The research combines genomic techniques to identify specific animal species and suggest which ones should be prioritized for further research on their role in transmitting the virus.
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  • Osimertinib is more effective than first-generation EGFR-TKIs for treating EGFR-mutated non-small cell lung cancer, but its overall survival benefits for Japanese patients needed further investigation.
  • A study was conducted using real-world data from 46 hospitals in Japan to compare the overall survival of patients receiving osimertinib versus other EGFR-TKIs; the study included 1,062 patients and lasted from April 2010 to April 2023.
  • Results showed no significant difference in overall survival between patients receiving first-line osimertinib and those on other first-line treatments, while those receiving osimertinib as a later-line treatment had notably longer survival times.*
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WONOEP appraisal: Genetic insights into early onset epilepsies.

Epilepsia

November 2024

Saul R. Korey Department of Neurology, Isabelle Rapin Division of Child Neurology, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.

Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants.

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Article Synopsis
  • Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a poor prognosis, leading researchers to explore the repurposing of existing drugs like valproic acid (VPA) and statins for potentially more effective treatments alongside standard chemotherapy.* -
  • The VESPA clinical trial is designed to investigate the combination of VPA and simvastatin (SIM) with gemcitabine/nab-paclitaxel in mPDAC patients, aiming to enhance treatment efficacy compared to chemotherapy alone.* -
  • The trial will enroll 240 patients across multiple centers, assessing outcomes like progression-free survival and overall survival, with a hypothesis that the combination therapy could extend progression-free survival from 6 to
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Article Synopsis
  • - Asciminib is a targeted treatment for BCR::ABL1 that minimizes side effects from disrupting other kinases, with a study of 49 patients showing it is generally well tolerated over a median follow-up of 14 months.
  • - Most patients (59%) continued treatment, with only 12% stopping due to intolerance; however, treatment cessation was primarily due to intolerance rather than drug resistance (65% vs. 35%).
  • - Out of 44 patients evaluated, 66% achieved a complete cytogenetic response, with lower success rates seen in patients with specific genetic variants; further analysis indicated that the drug can influence the growth of certain resistant cancer cell populations.
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The Revised upper limb module (RULM) has been increasingly used in clinical trials and in clinical settings. The aim of this study was to use the 'shift analysis' to assess the patterns of lost or gained abilities for each item on the RULM in an untreated cohort, stratified by SMA type, age, SMN2 copy number, and motor functional status. The analysis was performed on 222 12-month paired assessments from 129 individuals (115 assessment from type II and 107 from type III) who had at least two assessments at yearly intervals.

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Lung cancer is the most common causes of death among all cancer-related diseases. A lung scan examination of the patient is the primary diagnostic technique. This scan analysis pertains to an MRI, CT, or X-ray.

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Background:  Imaging and Clinical Informatics are domains of biomedical informatics. Imaging Informatics topics are often not covered in depth in most Clinical Informatics fellowships. While dedicated Imaging Informatics fellowships exist, they may not have the same rigor as ACGME (Accreditation Council for Graduate Medical Education) accredited Clinical Informatics fellowships and they do not provide a direct path toward subspecialty board certification.

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Background: Idiopathic pulmonary fibrosis (IPF) is a severe lung condition, and finding better ways to diagnose and treat the disease is crucial for improving patient outcomes. Our study sought to develop an artificial neural network (ANN) model for IPF and determine the immune cell types that differed between the IPF and control groups.

Methods: From the Gene Expression Omnibus (GEO) database, we first obtained IPF microarray datasets.

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Development and validation of a prognostic nomogram in patients aged ≥65 years with stage I-II non-small cell lung cancer treated with stereotactic body radiotherapy.

J Geriatr Oncol

November 2024

Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address:

Article Synopsis
  • This study evaluates the effectiveness and safety of stereotactic body radiotherapy (SBRT) for older adults (age 65+) with early-stage non-small cell lung cancer (NSCLC) and creates a predictive tool for patient outcomes.
  • The research involved 142 patients and analyzed survival rates, failure incidences, and treatment side effects, revealing promising 1-, 3-, and 5-year progression-free and overall survival rates.
  • Results indicate that SBRT is a viable treatment for older patients with early-stage NSCLC, showing favorable survival rates with manageable side effects, alongside a useful nomogram for predicting individual patient outcomes.
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Article Synopsis
  • ALS is a neurodegenerative disorder that affects both motor neurons and skeletal muscle, with muscle metabolic disruptions appearing before the onset of classic symptoms.
  • Research found that ALS muscle cells show impaired myogenesis and glucose oxidation, linked to the FOXO1 transcription factor, suggesting this factor plays a critical role in the disease's muscle-related issues.
  • Targeting FOXO1 may offer a new therapeutic strategy for ALS by improving muscle function and potentially alleviating some symptoms associated with the disorder.
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Ponsegromab for the Treatment of Cancer Cachexia.

N Engl J Med

December 2024

From the Internal Medicine Research Unit (J.D.G., I.K., M.A.H., A.R.S.) and Clinical Pharmacology (R.Q.), Pfizer, Cambridge, MA; Duke Cancer Institute, Duke University Medical Center, Durham, NC (J.C.); Global Biometrics and Data Management, Pfizer R&D UK, Sandwich (S.M.C.), and Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh (M.F.) - both in the United Kingdom; Translational Clinical Sciences, Pfizer, Collegeville, PA (S.L.); Knight Cancer Institute, Oregon Health and Science University, Portland (E.J.R.); the Cancer Supportive Care Center, Shizuoka Cancer Center, Shizuoka (T.N.), and the Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto (K.T.) - both in Japan; Cedars-Sinai Medical Center, Los Angeles (A.E.H.); the Ottawa Hospital Cancer Centre, Ottawa (T.A.); Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY (R.F.D.); Translational Clinical Sciences, Pfizer, Groton, CT (C.A.N.); and the Internal Medicine Research Unit, Pfizer, Tampa, FL (M.R.).

Background: Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels.

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Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

N Engl J Med

January 2025

From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) - all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana-Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) - both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) - both in New York; the University of Chicago Comprehensive Cancer Center, Chicago (R.F.S., C.W., Y.W., O.H.), and Loyola University Medical Center, Maywood (M.W.) - both in Illinois; the Alliance Protocol Operations Office, University of Chicago, Chicago (C.W., Y.W., O.H.); Fox Chase Cancer Center, Philadelphia (D.M.G.); Fred Hutchinson Cancer Center and the University of Washington, Seattle (P.G.); Rogel Cancer Center, University of Michigan, Ann Arbor (Z.R.R.); Yale Cancer Center, Yale School of Medicine, New Haven, CT (J.W.K., D.P.); Winship Cancer Institute, Emory University, Atlanta (M.A.B.); Mayo Clinic Comprehensive Cancer Center, Phoenix, AZ (P.S.); Oklahoma University Health Stephenson Cancer Center, Oklahoma City (A. Tripathi); University of Texas Southwestern Medical Center, Dallas (S.C.); Stanford University, Stanford (S.S.), and Kaiser Permanente Riverside Medical Center, Riverside (H.M.) - both in California; and Vanderbilt-Ingram Cancer Center, Nashville (A. Tan).

Background: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.

Methods: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation.

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Development and Evaluation of [Ga]Ga-Labeled Riboflavin Derivative for RFVT3-Targeted PET Imaging of Melanoma in Mice.

Mol Pharm

October 2024

Theranostics and Translational Research Center, Institute of Clinical Medicine & Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.

The limited progress in treatment options and the alarming survival rates in advanced melanoma emphasize the significant research importance of early melanoma diagnosis. RFVT3, a crucial protein at the core of energy metabolism reprogramming in melanoma, might play a pivotal role in early detection. In this study, [Ga]Ga-NOTA-RF, based on riboflavin (RF), was rationally developed and validated, serving as an innovative tool for positron emission tomography (PET) imaging of RFVT3 expression in melanoma.

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