Radiation for Multiple Myeloma in the Era of Novel Agents: Indications, Safety, and Dose Selection.

Survival outcomes for multiple myeloma (MM) have drastically improved over the past two decades with the advent of highly effective biologic agents and integration of autologous stem cell transplant (ASCT) for select patients. Despite these advances, MM remains an incurable disease and duration of remission decreases with each relapse. Palliative radiotherapy (RT) for MM, including treatment of pain, relief of compression, and prevention of fracture, is highly effective and generally well tolerated.

Irradiated Bone Marrow Volume is Associated With Hematologic Toxicity in Patients With Multiple Myeloma.

Purpose: Palliative radiation therapy (RT) is effective for multiple myeloma (MM) but may cause cytopenia. Bone marrow volume receiving 10 Gy (BMV10Gy) has been associated with hematologic toxicity (HT) in cervical cancer, but no studies have investigated this in MM. We hypothesized that absolute BMV10Gy is associated with acute HT in MM patients receiving palliative RT.

A roadmap for modelling radiation-induced cardiac disease.

Cardiac risk mitigation is a major priority in improving outcomes for cancer survivors as advances in cancer screening and treatments continue to decrease cancer mortality. More than half of adult cancer patients will be treated with radiotherapy (RT); therefore it is crucial to develop a framework for how to assess and predict radiation-induced cardiac disease (RICD). Historically, RICD was modelled solely using whole heart metrics such as mean heart dose.

Feasibility of Left Anterior Descending Coronary Artery Sparing Radiation Therapy for Locally Advanced Lung Cancer.

Efforts to mitigate radiation therapy (RT)-associated cardiotoxicity have focused on constraining mean heart dose. However, recent studies have shown greater predictive power with cardiac substructure dose metrics, such as the left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) ≥10%. Herein, we investigated the feasibility of LAD radiation sparing in contemporary intensity modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) lung cancer plans.

AAV6 mediated Gsx1 expression in neural stem progenitor cells promotes neurogenesis and restores locomotor function after contusion spinal cord injury.

Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA.

Rapid Genome Sequencing Shows Diagnostic Utility In Infants With Congenital Heart Defects.

Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant mortality. CHD often has a genetic etiology and recent studies demonstrate utility in genetic testing. In clinical practice, decisions around genetic testing choices continue to evolve, and the incorporation of rapid genome sequencing (rGS) in CHD has not been well studied.

Feasibility and acceptability of ChatGPT generated radiology report summaries for cancer patients.

Objective: Patients now have direct access to their radiology reports, which can include complex terminology and be difficult to understand. We assessed ChatGPT's ability to generate summarized MRI reports for patients with prostate cancer and evaluated physician satisfaction with the artificial intelligence (AI)-summarized report.

Methods: We used ChatGPT to summarize five full MRI reports for patients with prostate cancer performed at a single institution from 2021 to 2022.

Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians.

Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.

Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians.

Enhancement of Radiation Therapy through Blockade of the Immune Checkpoint, V-domain Ig Suppressor of T Cell Activation (VISTA), in Melanoma and Adenocarcinoma Murine Models.

Radiation therapy (RT) has recently demonstrated promise at stimulating an enhanced immune response. The recent success of immunotherapies, such as checkpoint inhibitors, CART cells, and other immune modulators, affords new opportunities for combination with radiation. The aim of this study is to evaluate whether and to what extent blockade of VISTA, an immune checkpoint, can potentiate the tumor control ability of radiation therapy.

Simulating Subject-Specific Aortic Hemodynamic Effects of Valvular Lesions in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is a neglected tropical disease despite the substantial global health burden. In this study, we aimed to develop a lower cost method of modeling aortic blood flow using subject-specific velocity profiles, aiding our understanding of RHD's consequences on the structure and function of the ascending aorta. Echocardiography and cardiovascular magnetic resonance (CMR) are often used for diagnosis, including valve dysfunction assessments.

Experimental ectoparasite removal has a sex-specific effect on nestling telomere length.

Parasites are a strong selective force that can influence fitness-related traits. The length of chromosome-capping telomeres can be used to assess the long-term costs of parasitism, as telomere loss accelerates in response to environmental stressors and often precedes poorer survival prospects. Here, we explored the sex-specific effects of ectoparasite removal on morphology and telomere length in nestling tree swallows ().

Left Anterior Descending Coronary Artery Radiation Dose Association With All-Cause Mortality in NRG Oncology Trial RTOG 0617.

Purpose: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) ≥10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets.

Methods And Materials: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used.

Inhibition of Epigenetic Modifiers LSD1 and HDAC1 Blocks Rod Photoreceptor Death in Mouse Models of Retinitis Pigmentosa.

Epigenetic modifiers are increasingly being investigated as potential therapeutics to modify and overcome disease phenotypes. Diseases of the nervous system present a particular problem as neurons are postmitotic and demonstrate relatively stable gene expression patterns and chromatin organization. We have explored the ability of epigenetic modifiers to prevent degeneration of rod photoreceptors in a mouse model of retinitis pigmentosa (RP), using rd10 mice of both sexes.

Kindergarteners' symbolic number abilities predict nonsymbolic number abilities and math achievement in grade 1.

Research has shown that two different, though related, ways of representing magnitude play foundational roles in the development of numerical and mathematical skills: a nonverbal approximate number system and an exact symbolic number system. While there have been numerous studies suggesting that the two systems are important predictors of math achievement, there has been substantial debate regarding whether and how these basic numerical competencies may be developmentally interrelated. Specifically, the causal direction of their relation has been the subject of debate: whether children's approximate number abilities predict later symbolic number abilities (the mapping account) or the other way around (the refinement account).

Toxicity Induced by a Bispecific T Cell-Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice.

Bispecific T cell engagers have demonstrated clinical efficacy; however, their use can be accompanied by severe toxicity. Mechanistic understanding of these toxicities is limited by a lack of suitable immunocompetent preclinical models. In this study, we describe an immunocompetent mouse tumor model that exhibits bispecific T cell engager-induced toxicity and recapitulates key features similar to those in human cytokine release syndrome.

The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development.

The transition of rod precursor cells to post-mitotic rod photoreceptors can be promoted by extrinsic factors such as insulin-like growth factor 1 (IGF-1), which regulates phosphatidylinositide concentration, and consequently the 3-phosphoinositide-dependent protein kinase-1 (PDPK-1). PDPK-1 is a 63 kDa cytoplasmic kinase that controls cell proliferation and differentiation. In the mouse retina, PDPK-1 and its phosphorylated derivative p-PDPK-1 (Ser241), showed peak expression during the first postnatal (PN) day with a substantial decline by PN7 and in the adult retina.

Prosocial apathy for helping others when effort is required.

Prosocial acts - those that are costly to ourselves but benefit others - are a central component of human co-existence1-3. While the financial and moral costs of prosocial behaviours are well understood4-6, everyday prosocial acts do not typically come at such costs. Instead, they require effort.

Identification and prediction of alternative transcription start sites that generate rod photoreceptor-specific transcripts from ubiquitously expressed genes.

Transcriptome complexity is substantially increased by the use of multiple transcription start sites for a given gene. By utilizing a rod photoreceptor-specific chromatin signature, and the RefSeq database of established transcription start sites, we have identified essentially all known rod photoreceptor genes as well as a group of novel genes that have a high probability of being expressed in rod photoreceptors. Approximately half of these novel rod genes are transcribed into multiple mRNA and/or protein isoforms through alternative transcriptional start sites (ATSS), only one of which has a rod-specific epigenetic signature and gives rise to a rod transcript.

Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina.

Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas, we used a pharmacological approach that showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12) but not lysine 27 of histone 3 (H3K27) and led to maintained expression of progenitor-specific genes such as and with concomitant block of expression of rod-specific genes.

hnRNPs and ELAVL1 cooperate with uORFs to inhibit protein translation.

Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG.

Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina.

Purpose: To characterize the mouse retina lacking fatty acid binding protein (FABP7-/-).

Methods: Immunohistochemistry (IHC) was performed in 8-week-old mice to localize FABP7 in the retina. Retinal thickness was measured using image-guided spectral-domain optical coherence topography images.

LSD1-Mediated Demethylation of H3K4me2 Is Required for the Transition from Late Progenitor to Differentiated Mouse Rod Photoreceptor.

Epigenetic modifiers can work in concert with transcription factors to control the transition of cells from proliferating progenitors into quiescent terminally differentiated cells. This transition involves changes in histone methylation and one of the key regulators of this is the H3K4me2/1 histone demethylase LSD1. Here, we show that the highest expression of LSD1 occurs in postmitotic retinal cells during the peak period of rod photoreceptor differentiation.

T-helper1/T-helper2 cytokine imbalance in the iris of patients with glaucoma.

The mechanistic study of glaucoma pathogenesis has shifted to seeking to understand the effects of immune responses on retinal ganglion cell damage and protection. Cytokines mediate the biological effects of the immune system, and our previous study revealed an imbalance of T-helper (Th) 1-derived and Th2-derived cytokines in the serum of patients with glaucoma. In this study, we collected irises from normal individuals and patients with primary open-angle closure (POAG) or chronic angle-closure glaucoma (CACG).