Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models.

KRAS is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with G12C mutation and advanced our understanding of its function. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors.

Outcomes of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants an Independent Prognostic Designation.

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN.

Common pitfalls and diagnostic challenges in the application of LI-RADS CT/MRI algorithms: a comprehensive review.

The Liver Imaging Reporting and Data System (LI-RADS) was developed to standardize the interpretation and reporting of liver observations in at-risk populations, aiding in the diagnosis of hepatocellular carcinoma (HCC). Despite its advantages, the application of LI-RADS can be challenging due to the complexity of liver pathology and imaging interpretation. This comprehensive review highlights common pitfalls encountered in LI-RADS application and offers practical strategies to enhance diagnostic accuracy and consistency among radiologists.

Neoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI.

Background An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy.

Characterization of LiF TLD-100 in carbon ion beams for remote audits.

Background: A passive dosimeter framework for the measurement of dose in carbon ion beams has yet to be characterized or implemented for regular use.

Purpose: This work determined the dose calculation correction factors for absorbed dose in thermoluminescent dosimeters (TLDs) in a therapeutic carbon ion beam. TLD could be a useful tool for remote audits, particularly in the context of clinical trials as new protocols are developed for carbon ion radiotherapy.

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using or strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive.

Performance Comparison of 10 State-of-the-Art Machine Learning Algorithms for Outcome Prediction Modeling of Radiation-Induced Toxicity.

Purpose: To evaluate the efficacy of prominent machine learning algorithms in predicting normal tissue complication probability using clinical data obtained from 2 distinct disease sites and to create a software tool that facilitates the automatic determination of the optimal algorithm to model any given labeled data set.

Methods And Materials: We obtained 3 sets of radiation toxicity data (478 patients) from our clinic: gastrointestinal toxicity, radiation pneumonitis, and radiation esophagitis. These data comprised clinicopathological and dosimetric information for patients diagnosed with non-small cell lung cancer and anal squamous cell carcinoma.

Feasibility of quantitative relaxometry for prostate target localization and response assessment in magnetic resonance-guided online adaptive stereotactic body radiotherapy.

Purpose: Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL).

Machine Learning to Predict the Individual Risk of Treatment-Relevant Toxicity for Patients With Breast Cancer Undergoing Neoadjuvant Systemic Treatment.

Purpose: Toxicity to systemic cancer treatment represents a major anxiety for patients and a challenge to treatment plans. We aimed to develop machine learning algorithms for the upfront prediction of an individual's risk of experiencing treatment-relevant toxicity during the course of treatment.

Methods: Clinical records were retrieved from a single-center, consecutive cohort of patients who underwent neoadjuvant treatment for early breast cancer.

Outcomes of CD19 CAR T in Transformed Indolent Lymphoma Compared to De Novo Aggressive Large B-Cell Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of aggressive large B-cell lymphoma (aLBCL). Patients with transformed indolent non-Hodgkin lymphoma (tiNHL) were included in key CAR trials, but outcomes of CAR for this distinct, historically high-risk group are poorly understood. We conducted a multicenter retrospective study of 1182 patients with aLBCL receiving standard-of-care CAR T between 2017 and 2022, including 338 (29%) with tiNHL.

Immune checkpoint inhibitors-associated vasculitis: a heterogeneous condition with possible severe disease course.

Objective: To describe presentation, treatment and outcome of immune checkpoint inhibitor (ICI) associated-vasculitis in cancer patients in a multicentre study.

Methods: Thanks to the ImmunoCancer International Registry (ICIR), a multidisciplinary network focused on the research of the immune related adverse events related to cancer immunotherapies, patients presenting with a clinical and/or radiological suspicion of vasculitis, and histological evidence of vasculitis after being exposed to ICIs were retrospectively identified.

Results: Twenty eight cases were identified in the ICIR registry.

SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to individual agents cannot be easily delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Herpes zoster ophthalmicus temporally after COVID-19 vaccination: a systematic review of uncontrolled case reports and case series.

Purpose: Herpes zoster ophthalmicus (HZO) following COVID-19 vaccination has been reported previously but the clinical characteristics, onset, treatment, and outcomes of these cases have not been previously systematically reviewed.

Methods: A systematic review, guided by PRISMA guidelines, surveyed PubMed and Embase databases from April 2021 to June 2023 for case reports and series detailing HZO following COVID-19 vaccination. Studies excluded were abstracts, reviews, and clinical trials.

The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel.

Maintaining a balance of inorganic phosphate (Pi) is vital for cellular functionality due to Pi's essential role in numerous biological processes. Proper phosphate levels are managed through Pi import and export, facilitated by specific Pi transport proteins. Although the mechanisms of Pi import have been extensively studied, the processes governing Pi export remain less understood.

BH3 Mimetics Augment Cytotoxic T Cell Killing of Acute Myeloid Leukemia via Mitochondrial Apoptotic Mechanism.

Adoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins.

The Significance of Detecting an Unusual Myeloblast Immunophenotype in a Presumptive Clinical Diagnosis of Myelodysplastic Syndromes.

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Artificial Intelligence Assessment of Chest Radiographs for COVID-19.

Background: The sensitivity of reverse-transcription polymerase chain reaction (RT-PCR) is limited for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest computed tomography (CT) is reported to have high sensitivity; however, given the limited availability of chest CT during a pandemic, the assessment of more readily available imaging, such as chest radiographs, augmented by artificial intelligence may substitute for the detection of the features of coronavirus disease 2019 (COVID-19) pneumonia.

Methods: We trained a deep convolutional neural network to detect SARS-CoV-2 pneumonia using publicly available chest radiography imaging data including 8,851 normal, 6,045 pneumonia, and 200 COVID-19 pneumonia radiographs.

Optimization of a digital health intervention to enhance well-being among adolescent and young adult cancer survivors: Design and methods of the EMPOWER full factorial trial.

Adolescent and young adult cancer survivors (AYAs) experience clinically significant distress and have limited access to supportive care services. Interventions to enhance psychological well-being have improved positive affect and reduced depression in clinical and healthy populations and have not been routinely tested in AYA survivors. We are optimizing a web-based positive skills intervention for AYA cancer survivors called Enhancing Management of Psychological Outcomes With Emotion Regulation (EMPOWER) by: (1) determining which intervention components have the strongest effects on well-being and (2) identifying demographic and individual difference variables that mediate and moderate EMPOWER's efficacy.

Examining provider perspectives surrounding cultural competencies: An integrative review.

Aim: This review explores the provider perspectives regarding cultural competency to pinpoint common themes that emerge from the existing literature.

Background: Cultural competency is vital in healthcare and remains a burgeoning area of interest in the healthcare landscape. Nevertheless, achieving mastery of these competencies remains challenging as health inequities persist that affect the care received by minority populations.

Disseminated protothecosis caused by Prototheca bovis in two dogs.

Protothecosis is an infectious disease caused by unicellular algae of the genus Prototheca, which are mainly known for causing mastitis in farm animals. However, there are reports of protothecosis in humans and other animals, such as dogs and cats, which develop cutaneous lesions or systemic lesions. Dogs with the systemic form generally develop bloody diarrhoea and blindness and neurological signs may also occur.