A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916

Exploring Chickpea Germplasm Diversity for Broadening the Genetic Base Utilizing Genomic Resourses

Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes improve the cropping environment by replenishing the soil nitrogen content. Chickpeas are the second most significant staple legume food crop worldwide behind dry bean which contains 17%–24% protein, 41%–51% carbohydrate, and other important essential minerals, vitamins, dietary fiber, folate, β-carotene, anti-oxidants, micronutrients (phosphorus, calcium, magnesium, iron, and zinc) as well as linoleic and oleic unsaturated fatty acids. Despite these advantages, legumes are far behind cereals in terms of genetic improvement mainly due to far less effort, the bottlenecks of the narrow genetic base, and several biotic and abiotic factors in the scenario of changing climatic conditions. Measures are now called for beyond conventional breeding practices to strategically broadening of narrow genetic base utilizing chickpea wild relatives and improvement of cultivars through advanced breeding approaches with a focus on high yield productivity, biotic and abiotic stresses including climate resilience, and enhanced nutritional values. Desirable donors having such multiple traits have been identified using core and mini core collections from the cultivated gene pool and wild relatives of Chickpea. Several methods have been developed to address cross-species fertilization obstacles and to aid in inter-specific hybridization and introgression of the target gene sequences from wild Cicer species. Additionally, recent advances in “Omics” sciences along with high-throughput and precise phenotyping tools have made it easier to identify genes that regulate traits of interest. Next-generation sequencing technologies, whole-genome sequencing, transcriptomics, and differential genes expression profiling along with a plethora of novel techniques like single nucleotide polymorphism exploiting high-density genotyping by sequencing assays, simple sequence repeat markers, diversity array technology platform, and whole-genome re-sequencing technique led to the identification and development of QTLs and high-density trait mapping of the global chickpea germplasm. These altogether have helped in broadening the narrow genetic base of chickpeas

Prediction of buffalo bull fertility on the basis of sperm motion traits, viability, membrane integrity, heat shock protein (HSP70) expression and fertility associated antigen (FAA)

The present study was conducted on 20 buffalo bulls to predict the fertility on the basis of: (a) Computer assisted semen analysis (CASA) based sperm motion traits, (b) viability, (c) membrane integrity, (d) expression for HSP70, and (e) assessment of fertility associated antigen (FAA). Six frozen semen straws from each buffalo bulls were analyzed for sperm motion traits, viz. individual motility, progressive motility, average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), amplitude of lateral head deviation (ALH), beat cross frequency (BCF), straightness (STR), linearity (LIN) and sperm size. Viability and hypoosmotic swelling tests (HOST) were also conducted. Heat shock protein 70 (HSP70) expression and quantification was conducted using a real time PCR. Fertility associated antigen (FAA) was assessed in fresh semen from buffalo bulls using test. Fertility trial was conducted on 250 normal cycling buffaloes following estrus synchronization with GnRH-PGF- GnRH protocol. It was concluded that buffalo bull fertility could be best predicted on the basis of sperm motion traits (VCL, VAP, VSL, ALH, LIN), motility, viability, HOST and HSP70 expression. However, FAA assessment in fresh semen did not indicate fertility

Photodegradation of organic pollutants RhB dye using UV simulated sunlight on ceria based TiO2 nanomaterials for antibacterial applications

To photo-catalytically degrade RhB dye using solar irradiation, CeO2 doped TiO2 nanocomposites were synthesized hydrothermally at 700 °C for 9 hrs. All emission spectra showed a prominent band centered at 442 nm that was attributed to oxygen related defects in the CeO2-TiO2 nanocrystals. Two sharp absorption bands at 1418 cm−1 and 3323 cm−1 were attributed to the deformation and stretching vibration, and bending vibration of the OH group of water physisorbed to TiO2, respectively. The photocatalytic activities of Ce-TiO2 nanocrystals were investigated through the degradation of RhB under UV and UV+ visible light over a period of 8 hrs. After 8 hrs, the most intense absorption peak at 579 nm disappeared under the highest photocatalytic activity and 99.89% of RhB degraded under solar irradiation. Visible light-activated TiO2 could be prepared from metal-ion incorporation, reduction of TiO2, non-metal doping or sensitizing of TiO2 using dyes. Studying the antibacterial activity of Ce-TiO2 nanocrystals against E. coli revealed significant activity when 10 μg was used, suggesting that it can be used as an antibacterial agent. Its effectiveness is likely related to its strong oxidation activity and superhydrophilicity. This study also discusses the mechanism of heterogeneous photocatalysis in the presence of TiO2

Alliance of Genome Resources Portal: unified model organism research platform

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource

Alliance of Genome Resources Portal: unified model organism research platform

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource

The effect of cognitive fatigue on prefrontal cortex correlates of neuromuscular fatigue in older women

BACKGROUND: As the population of adults aged 65 and above is rapidly growing, it is crucial to identify physical and cognitive limitations pertaining to daily living. Cognitive fatigue has shown to adversely impact neuromuscular function in younger adults, however its impact on neuromuscular fatigue, and associated brain function changes, in older adults is not well understood. The aim of the study was to examine the impact of cognitive fatigue on neuromuscular fatigue and associated prefrontal cortex (PFC) activation patterns in older women. METHODS: Eleven older (75.82 (7.4) years) females attended two sessions and performed intermittent handgrip exercises at 30 % maximum voluntary contraction (MVC) until voluntary exhaustion after a 60-min control (watching documentary) and 60-min cognitive fatigue (performing Stroop Color Word and 1-Back tests) condition. Dependent measures included endurance time, strength loss, PFC activity (measured using fNIRS), force fluctuations, muscle activity, cardiovascular responses, and perceived discomfort. RESULTS: Participants perceived greater cognitive fatigue after the 60-min cognitive fatigue condition when compared to the control condition. While neuromuscular fatigue outcomes (i.e., endurance time, strength loss, perceived discomfort), force fluctuations, and muscle activity were similar across both the control and cognitive fatigue conditions, greater decrements in PFC activity during neuromuscular fatigue development after the cognitive fatigue condition were observed when compared to the control condition. CONCLUSION: Despite similar neuromuscular outcomes, cognitive fatigue was associated with blunted PFC activation during the handgrip fatiguing exercise that may be indicative of neural adaptation with aging in an effort to maintain motor performance. Examining the relationship between cognitive fatigue and neuromuscular output by imaging other motor-related brain regions are needed to provide a better understanding of age-related compensatory adaptations to perform daily tasks that involve some levels of cognitive demand and physical exercise, especially when older adults experience them sequentially