Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma.

Purpose: In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.

Methods: ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL.

Negative Effect of the Calendering Process on the Interphase Formation and Electrochemical Behavior of Reduced Graphene Oxide Electrodes.

Many studies on electrode material development for rechargeable batteries have focused on improving the intrinsic physicochemical and electrochemical properties of active materials, but the electrochemical performances of batteries are exhibited by the overall electrode unit consisting of active materials, conductive additives, and a binder. Additionally, the electrodes have undergone an essential calendering process to enhance the physical contact between those components. Therefore, the electrochemical behavior and performance of a cell should be analyzed at the electrode level, as the inherent properties of active materials might be changed in electrode preparation, including the calendaring process and real-operating environments.

Categorizing Monogenic Epilepsies by Genetic Mechanisms May Predict Efficacy of the Ketogenic Diet.

Background: The ketogenic diet (KD) is an effective treatment for epilepsy. In recent years, studies have shown favorable efficacy of KD in epilepsy from genetic disorders. In this study, we propose an approach to KD in monogenic epilepsy: we evaluate the utility of categorizing genetic variants based on rational associations with the known mechanisms of KD.

Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily.

Assessment of hydraulic and thermal properties of the Antarctic active layer: Insights from laboratory column experiments and inverse modeling.

To better understand the changes in the hydrologic cycle caused by global warming in Antarctica, it is crucial to improve our understanding of the groundwater flow system, which has received less attention despite its significance. Both hydraulic and thermal properties of the active layer, through which groundwater can flow during thawing seasons, are essential to quantify the groundwater flow system. However, there has been insufficient information on the Antarctic active layer.

Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss.

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence.

Geriatric risk model for older patients with diffuse large B-cell lymphoma (GERIAD): a prospective multicenter cohort study.

Background/aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI).

Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation.

In vitro atherosclerosis models are essential to evaluate therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput assays for therapeutic evaluation. Herein, we report an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA), including endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation.

Genetic ablation of synaptotagmin-9 alters tomosyn-1 function to increase insulin secretion from pancreatic β-cells improving glucose clearance.

Stimulus-coupled insulin secretion from the pancreatic islet β-cells involves the fusion of insulin granules to the plasma membrane (PM) via SNARE complex formation-a cellular process key for maintaining whole-body glucose homeostasis. Less is known about the role of endogenous inhibitors of SNARE complexes in insulin secretion. We show that an insulin granule protein synaptotagmin-9 (Syt9) deletion in mice increased glucose clearance and plasma insulin levels without affecting insulin action compared to the control mice.

Loss of Brain Angiogenesis Inhibitor-3 (BAI3) G-Protein Coupled Receptor in Mice Regulates Adaptive Thermogenesis by Enhancing Energy Expenditure.

Effective energy expenditure is critical for maintaining body weight (BW). However, underlying mechanisms contributing to increased BW remain unknown. We characterized the role of brain angiogenesis inhibitor-3 (BAI3/ADGRB3), an adhesion G-protein coupled receptor (aGPCR), in regulating BW.

Systemic Lymphadenopathic Mastocytosis with Eosinophilia.

Systemic mastocytosis is a neoplastic proliferation of mast cells that most frequently involves cutaneous sites. Mastocytosis involves various extracutaneous sites, but the lymph node is rare. We present an interesting image of systemic mastocytosis in the lymph node with marked eosinophilia.

Aberrant synaptophysin expression in classic Hodgkin lymphoma.

Background: Synaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has not yet been described. However, we experienced an index case of classic Hodgkin lymphoma with synaptophysin expression.

Experience with the ketogenic diet in premature neonates.

The ketogenic diet is a time-tested, potent, nonpharmacological treatment of epilepsy. However, the use of the ketogenic diet in premature neonates with epilepsy has not been previously reported. We share our experience with the use of ketogenic diet therapy in two premature neonates.

Revisiting the Classical Wide-Bandgap HOMO and Random Copolymers for Indoor Artificial Light Photovoltaics.

Organic indoor photovoltaics (IPVs) are attractive energy harvesting devices for low-power consumption electronic devices and the Internet of Things (IoTs) owing to their properties such as being lightweight, semitransparent, having multicoloring capability, and flexibility. It is important to match the absorption range of photoactive materials with the emission spectra of indoor light sources that have a visible range of 400-700 nm for IPVs to provide sustainable, high-power density. To this end, benzo[1,2-b:4,5-b']dithiophene-based homopolymer (PBDTT) is synthesized as a polymer donor, which is a classical material that has a wide bandgap with a deep highest occupied molecular orbitals (HOMO) level, and a series of random copolymers by incorporating thieno[3,4-c]pyrrole-4,6,-dione (TPD) as a weak electron acceptor unit in PBDTT.

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation.

Multicenter, phase II study of response-adapted lenalidomide-based therapy for transplant-ineligible patients with newly diagnosed multiple myeloma without high-risk features.

Lenalidomide and low-dose dexamethasone (Rd) are a standard treatment for older adults with multiple myeloma (MM). Lenalidomide monotherapy has rarely been evaluated for newly diagnosed transplant-ineligible MM patients. This multicenter phase II trial evaluated a response-adapted strategy for elderly patients with newly diagnosed MM without high-risk features.

Vibrio vulnificus induces the death of a major bacterial species in the mouse gut via cyclo-Phe-Pro.

Background: A foodborne pathogen, Vibrio vulnificus, encounters normal microflora inhabiting the gut environments prior to causing fatal septicemia or gastroenteritis and should overcome the barriers derived from the gut commensals for successful infection. Its interactions with gut commensals during the infection process, however, have not yet been understood. In the present study, the effect of V.

Ablation of Sam68 in adult mice increases thermogenesis and energy expenditure.

Genetic deletion of Src associated in mitosis of 68kDa (Sam68), a pleiotropic adaptor protein prevents high-fat diet-induced weight gain and insulin resistance. To clarify the role of Sam68 in energy metabolism in the adult stage, we generated an inducible Sam68 knockout mice. Knockout of Sam68 was induced at the age of 7-10 weeks, and then we examined the metabolic profiles of the mice.

Long-chain acyl-CoA synthetase-1 mediates the palmitic acid-induced inflammatory response in human aortic endothelial cells.

Saturated fatty acid (SFA) induces proinflammatory response through a Toll-like receptor (TLR)-mediated mechanism, which is associated with cardiometabolic diseases such as obesity, insulin resistance, and endothelial dysfunction. Consistent with this notion, TLR2 or TLR4 knockout mice are protected from obesity-induced proinflammatory response and endothelial dysfunction. Although SFA causes endothelial dysfunction through TLR-mediated signaling pathways, the mechanisms underlying SFA-stimulated inflammatory response are not completely understood.

Diurnal, metabolic and thermogenic alterations in a murine model of accelerated aging.

Senescence-Accelerated Mouse-Prone 8 (SAMP8) mice exhibit characteristics of premature aging, including hair loss, cognitive dysfunction, reduced physical activity, impaired metabolic homeostasis, cardiac dysfunction and reduced lifespan. Interestingly, circadian disruption can induce or augment many of these same pathologies. Moreover, previous studies have reported that SAMP8 mice exhibit abnormalities in circadian wheel-running behavior, indicating possible alterations in circadian clock function.

Metformin reduces saturated fatty acid-induced lipid accumulation and inflammatory response by restoration of autophagic flux in endothelial cells.

Autophagy, an integral part of the waste recycling process, plays an important role in cellular physiology and pathophysiology. Impaired autophagic flux causes ectopic lipid deposition, which is defined as the accumulation of lipids in non-adipose tissue. Ectopic lipid accumulation is observed in patients with cardiometabolic syndrome, including obesity, diabetes, insulin resistance, and cardiovascular complications.

A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders.

Targeting retinoid X receptor (RXR) has been proposed as one of the therapeutic strategies to treat individuals with metabolic syndrome, as RXR heterodimerizes with multiple nuclear receptors that regulate genes involved in metabolism. Despite numerous efforts, RXR ligands (rexinoids) have not been approved for clinical trials to treat metabolic syndrome due to the serious side effects such as hypertriglyceridemia and altered thyroid hormone axis. In this study, we demonstrate a novel rexinoid-like small molecule, UAB126, which has positive effects on metabolic syndrome without the known side effects of potent rexinoids.