Stereotactic Radiosurgery Practice Patterns for Brain Metastases in the United States: A National Survey

Background: Stereotactic radiosurgery (SRS) has emerged as an important modality for the treatment of intracranial metastases. There are currently few established guidelines delineating indications for SRS use and fewer still regarding plan evaluation in the treat- ment of multiple brain metastases. Methods: An 18 question electronic survey was distributed to radiation oncologists at National Cancer Institute (NCI) designated cancer centers in the US (60). Centers without radiation oncologists were excluded. Physicians who indicated that they do not prescribe SRS were excluded from the remaining survey questions. Sign test and Chi-square test were used to determine if responses differed significantly from random distribution. Results: 116 of the 697 radiation oncologists surveyed completed the questionnaire, representing 51 institutions. 62% reported treating patients with brain metastases using SRS. Radiation oncologists prescribing SRS most commonly treat CNS (66.2%) and lung (49.3%) malignancies. SRS was used more frequently for \u3c10 brain metastases (73.7%; p\u3c.0001) and whole brain radiation therapy (WBRT) for \u3e10 brain metastases (82.5%; p\u3c.0001). The maximum number of lesions physicians were willing to treat with SRS without WBRT was 1-4 (40.4%) and 5-10 (42.4%) (p\u3c.0001 compared to 11-15, 16-20 and no limit). The most important criteria for choosing SRS or WBRT were number of lesions (p\u3c.0001) and performance status (p=.016). The most common margin for SRS was 0 mm (49.1%; p=.0021). The most common dose constraints other than critical structure was conformity index (84.2%) and brain V12 (61.4%). The LINAC was the most common treatment modality (54.4%) and mono-isocenter technique for multiple brain metastases was commonly used (43.9%; p=.23). Most departments do not have a policy for brain metastases treatment (64.9%; p=.024). Conclusions: This is one of the first national surveys assessing the use of SRS for brain metastases in clinical practice. These data highlight some clinical considerations for physicians treating brain metastases with SRS. Summary: This is among the first national surveys to assess the use of SRS for brain metastases in clinical practice. Specifically, radiation oncologist reported increasingly using SRS instead of WBRT for treating \u3c10 metastases, with the LINAC being the most common modality. Further, treatment parameters considered the most important included 0 mm margins, conformity index, brain V12, and mono- isocenter technique for multiple brain metastases. These results may provide context regarding the use of SRS for brain metastases in clinical practice

A Context-Aware Computational Approach for Measuring Vocal Entrainment in Dyadic Conversations

Vocal entrainment is a social adaptation mechanism in human interaction, knowledge of which can offer useful insights to an individual's cognitive-behavioral characteristics. We propose a context-aware approach for measuring vocal entrainment in dyadic conversations. We use conformers(a combination of convolutional network and transformer) for capturing both short-term and long-term conversational context to model entrainment patterns in interactions across different domains. Specifically we use cross-subject attention layers to learn intra- as well as inter-personal signals from dyadic conversations. We first validate the proposed method based on classification experiments to distinguish between real(consistent) and fake(inconsistent/shuffled) conversations. Experimental results on interactions involving individuals with Autism Spectrum Disorder also show evidence of a statistically-significant association between the introduced entrainment measure and clinical scores relevant to symptoms, including across gender and age groups

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Sleep state classification using power spectral density and residual neural network with multichannel EEG signals.

This paper proposes a classification framework for automatic sleep stage detection in both male and female human subjects by analyzing the electroencephalogram (EEG) data of polysomnography (PSG) recorded for three regions of the human brain, i.e., the pre-frontal, central, and occipital lobes. Without considering any artifact removal approach, the residual neural network (ResNet) architecture is used to automatically learn the distinctive features of different sleep stages from the power spectral density (PSD) of the raw EEG data. The residual block of the ResNet learns the intrinsic features of different sleep stages from the EEG data while avoiding the vanishing gradient problem. The proposed approach is validated using the sleep dataset of the Dreams database, which comprises of EEG signals for 20 healthy human subjects, 16 female and 4 male. Our experimental results demonstrate the effectiveness of the ResNet based approach in identifying different sleep stages in both female and male subjects compared to state-of-the-art methods with classification accuracies of 87.8% and 83.7%, respectively

Complete mitochondrial genome of saw-jawed monocle bream Scolopsis ciliata and its phylogenetic relationship in genus Scolopsis

The complete mitochondrial genome of the saw-jawed monocle bream, Scolopsis ciliata was deter�mined by the next generation sequencing (NGS) technique. The circular mitogenome of S. ciliata (16,733 bp) encoded the canonical 37 genes including 13 proteins, 22 tRNA genes, 2 rRNAs (12S rRNA and 16S rRNA), and two non-coding regions; the origin of light strand replication (OL) and the putative control region (D-Loop). The gene arrangement of the S. ciliata mitogenome was identical to its rela�tive, Scolopsis vosmeri. Phylogenetic analysis based on the full mitochondrial genome sequences showed that S. ciliata is most closely related to S. vosmeri with 83% nucleotide sequence identity. The mitogenome information of S. ciliata would be the useful information to understand the evolutional relationship of fishes in genus Scolopsi

Budaya dan kesannya ke atas perbelanjaan belia Melayu Kuala Lumpur

Perbelanjaan merupakan hasil daripada aktiviti berbelanja yang dilakukan untuk memenuhi keperluan seharian. Namun demikian, ketika berbelanja terdapat beberapa faktor yang menyebabkan perbelanjaan bagi satu-satu keperluan berbeza mengikut individu. Kajian ini dijalankan pertamanya adalah untuk mengenalpasti adakah nilai-nilai budaya yang dikaji mewakili unsur budaya, apakah jenis keperluan yang diutamakan ketika berbelanja dan sejauhmanakah budaya mempengaruhi perbelanjaan keperluan tersebut. Untuk melaksanakan kajian ini, kaedah persampelan bertujuan (purposive sampling) dan bola salji (snowball sampling) telah dijalankan ke atas 522 orang belia di Kuala Lumpur. Sampel yang terpilih melibatkan beberapa kriteria iaitu bekerjaya, kaum Melayu, berumur antara 20-39 tahun, serta tinggal dan bekerja di Kuala Lumpur. Bagi mencapai objektif kajian ini, satu set borang soal selidik telah diedarkan ke atas 522 orang responden dan data yang diperoleh kemudiannya dianalisis dengan menggunakan Structural Equation Modelling (SEM) dengan program Analysis of Momentum Structure (AMOS) versi 24. Hasil kajian yang diperolehi menunjukkan bahawa faktor nilai budaya yang diuji sememangnya mempengaruhi perbelanjaan golongan belia Melayu bandar secara signifikan. Belia Melayu bandar didapati menghayati nilai berjimat dan masih mengutamakan keperluan keluarga dengan baik, di samping masih mengamalkan nilai-nilai tradisional masyarakat Melayu walaupun berdepan dengan budaya bandaran. Dapatan kajian yang ditonjolkan secara keseluruhannya memperlihatkan, latar belakang budaya yang dihayati akan membentuk pola perbelanjaan seseorang individu itu sendiri. Maka, dapat dibuktikan bahawa dengan perbelanjaan yang pelbagai meliputi diri sendiri serta masyarakat di sekeliling tidak diabaikan apabila menghayati nilai budaya yang menjadi pegangan hidup walaupun sedang menetap di kawasan bandar. Hasil kajian ini dapat membantu memahami gaya berbelanja yang diamalkan oleh golongan belia Melayu khususnya yang menetap di bandar yang seterusnya dapat dijadikan panduan oleh pihak yang berkaitan untuk memberi bantuan secara bersasar, sesuai dengan keperluan demi kelangsungan hidup mereka

In silico analysis of the antigenic properties of iron-regulated proteins against neisseria meningitides

Neisseria meningitidis is a commensal pathogen that causes infectious cerebrospinal disease in people of all ages. The multivariate role of six disease-causing polysaccharide serotypes is found to play a crucial role in developing vaccines (or general treatment strategies) to treat this emerging pathogen. Iron is a crucial transition metal for N. meningitidis. Proteomic analysis data could be valuable for vaccine design. Here, we conduct a comparative study using computational bioinformatic tools to identify the most effective iron-regulated outer membrane proteins (OMPs) as immunogenic targets for a potential vaccine against N. meningitidis. The basic properties of N. meningitidis OMPs are explored for flexibility, solubility, hydrophilicity, beta-turns, and overall antigenic probability. Results of our study suggest that iron-regulated OMPs are flexible and soluble in water with high densities of conformational B-cell epitopes. As such, they can be recommended as a novel candidate for a vaccine against N. meningitidis both in vitro and in vivo

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy

The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy

Simple, Rapid and Cost-Effective Method for High Quality Nucleic Acids Extraction from Different Strains of Botryococcus braunii

This study deals with an effective nucleic acids extraction method from various strains of Botryococcus braunii which possesses an extensive extracellular matrix. A method combining freeze/thaw and bead-beating with heterogeneous diameter of silica/zirconia beads was optimized to isolate DNA and RNA from microalgae, especially from B. braunii. Eukaryotic Microalgal Nucleic Acids Extraction (EMNE) method developed in this study showed at least 300 times higher DNA yield in all strains of B. braunii with high integrity and 50 times reduced working volume compared to commercially available DNA extraction kits. High quality RNA was also extracted using this method and more than two times the yield compared to existing methods. Real-time experiments confirmed the quality and quantity of the input DNA and RNA extracted using EMNE method. The method was also applied to other eukaryotic microalgae, such as diatoms, Chlamydomonas sp., Chlorella sp., and Scenedesmus sp. resulting in higher efficiencies. Cost-effectiveness analysis of DNA extraction by various methods revealed that EMNE method was superior to commercial kits and other reported methods by >15%. This method would immensely contribute to area of microalgal genomics

Type 2 diabetes genetic association database manually curated for the study design and odds ratio

<p>Abstract</p> <p>Background</p> <p>The prevalence of type 2 diabetes has reached epidemic proportions worldwide, and the incidence of life-threatening complications of diabetes through continued exposure of tissues to high glucose levels is increasing. Advances in genotyping technology have increased the scale and accuracy of the genotype data so that an association genetic study has expanded enormously. Consequently, it is difficult to search the published association data efficiently, and several databases on the association results have been constructed, but these databases have their limitations to researchers: some providing only genome-wide association data, some not focused on the association but more on the integrative data, and some are not user-friendly. In this study, a user-friend database of type 2 diabetes genetic association of manually curated information was constructed.</p> <p>Description</p> <p>The list of publications used in this study was collected from the HuGE Navigator, which is an online database of published genome epidemiology literature. Because type 2 diabetes genetic association database (T2DGADB) aims to provide specialized information on the genetic risk factors involved in the development of type 2 diabetes, 701 of the 1,771 publications in the type 2 Diabetes case-control study for the development of the disease were extracted.</p> <p>Conclusions</p> <p>In the database, the association results were grouped as either positive or negative. The gene and SNP names were replaced with gene symbols and rsSNP numbers, the association p-values were determined manually, and the results are displayed by graphs and tables. In addition, the study design in publications, such as the population type and size are described. This database can be used for research purposes, such as an association and functional study of type 2 diabetes related genes, and as a primary genetic resource to construct a diabetes risk test in the preparation of personalized medicine in the future.</p