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Context: A winged scapula (WS) is associated with faulty posture caused by weakness of the serratus anterior (SA), which mainly acts as a scapular stabilizer muscle. It is important to accurately assess and train the SA muscle with a focus on scapula stabilizers during musculoskeletal rehabilitation of individuals with a WS., Objective: The authors examined muscle activity in the SA and pectoralis major (PM), upper trapezius (UT), and anterior deltoid (AD) as well as shoulder protraction strength during isometric shoulder protraction in individuals with and without a WS., Design: Cross-sectional study., Setting: A clinical biomechanics laboratory., Participants: In total, 27 males with no shoulder, neck, or upper-extremity pain participated., Main Outcome Measures: Isometric shoulder protraction strength was collected and surface electromyography used to measure the activity of the SA, PM, UT, and AD muscles and selective SA activity ratio to other shoulder muscles., Results: Electromyography activity of the SA muscle and shoulder protraction strength were significantly lower in individuals with a WS compared with the non-WS group (P < .05). In contrast, PM muscle activity and the PM-to-SA, UT-to-SA, and AD-to-SA ratios were significantly greater in individuals with a WS than in individuals without winging (P < .05)., Conclusions: Isometric shoulder protraction for measuring SA strength in individuals with a WS should focus on isolated muscle activity of the SA, and SA strengthening exercises are important for individuals with a WS.

The Chinstrap (Pygoscelis antarcticus) and Gentoo (P. papua) penguins are distributed throughout Antarctica and the sub-Antarctic islands. In this study, high-quality de novo assemblies of blood transcriptomes from these penguins were generated using the Illumina MiSeq platform. A total of 22.2 and 21.8 raw reads were obtained from Chinstrap and Gentoo penguins, respectively. These reads were assembled using the Oases assembly platform and resulted in 26,036 and 21,854 contigs with N50 values of 929 and 933 base pairs, respectively. Functional gene annotations through pathway analyses of the Gene Ontology, EuKaryotic Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were performed for each blood transcriptome, resulting in a similar compositional order between the two transcriptomes. Ortholog comparisons with previously published transcriptomes from the Adélie (P. adeliae) and Emperor (Aptenodytes forsteri) penguins revealed that a high proportion of the four penguins' transcriptomes had significant sequence homology. Because blood and tissues of penguins have been used to monitor pollution in Antarctica, immune parameters in blood could be important indicators for understanding the health status of penguins and other Antarctic animals. In the blood transcriptomes, KEGG analyses detected many essential genes involved in the major innate immunity pathways, which are key metabolic pathways for maintaining homeostasis against exogenous infections or toxins. Blood transcriptome studies such as this may be useful for checking the immune and health status of penguins without sacrifice.

Icefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.

Movement disorders, such as Parkinson's disease, dystonia, tic disorder, and attention-deficit/hyperactivity disorder (ADHD) are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements. As the assessment of most movement disorders depends on subjective rating scales and clinical observations, the objective quantification of activity remains a challenging area. The purpose of our study was to verify whether an impulse radio ultra-wideband (IR-UWB) radar sensor technique is useful for an objective measurement of activity. Thus, we proposed an activity measurement algorithm and quantitative activity indicators for clinical assistance, based on IR-UWB radar sensors. The received signals of the sensor are sufficiently sensitive to measure heart rate, and multiple sensors can be used together to track the positions of people. To measure activity using these two features, we divided movement into two categories. For verification, we divided these into several scenarios, depending on the amount of activity, and compared with an actigraphy sensor to confirm the clinical feasibility of the proposed indicators. The experimental environment is similar to the environment of the comprehensive attention test (CAT), but with the inclusion of the IR-UWB radar. The experiment was carried out, according to a predefined scenario. Experiments demonstrate that the proposed indicators can measure movement quantitatively, and can be used as a quantified index to clinically record and compare patient activity. Therefore, this study suggests the possibility of clinical application of radar sensors for standardized diagnosis.

The purplish Washington clam (Saxidomus purpuratus) in the family Veneridae is distributed widely along the intertidal zones of northeast Asia and is increasingly being utilized as a commercially important food resource. Bivalves maintain homeostasis by regulating their food intake and digestion, innate immunity, and biotransformation in a mollusk-specific organ, the digestive gland. To understand digestive gland-specific pathways, we generated a high-quality de novo assembly of the digestive gland transcriptome of this clam using the Illumina Miseq platform. A total of 9.9 million raw reads were obtained and assembled using the Oases assembly platform, resulting in 27,358 contigs with an N50 of 433 bp. Functional gene annotations were performed using Gene Ontology, Eukaryotic Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In the transcriptome, many crucial genes involved in innate immunity and digestion metabolism were detected. A number of enzymes associated with drug metabolism were annotated, as much as that identified from the whole transcriptome of the Pacific oyster Crassostrea gigas. We provide valuable sequence information of S. purpuratus to predict functional understandings of the bivalve-specific digestive gland. This resource will be valuable for researchers comparing gene compositions and their expression levels in the digestive glands of bivalves.

Objectives: We aimed to compare preterm, neurodevelopmentally disordered and healthy full-term children., Methods: We enrolled 47 children who were born preterm, 40 neurodevelopmentally disordered children, and 80 healthy children as control participants, in order to assess the cognitive functioning and the risk of behavioral problems at the age of 5. Children were assessed using the Korean Wechsler Preschool and Primary Scale of Intelligence-4th edition (K-WPPSI-IV), the Child Behavior Checklist (CBCL), and the Temperament and Character Inventory (TCI)., Results: The mean K-WPPSI-IV score of the preterm group was 87.19±17.36, which was significantly higher than that of the neurodevelopmental disorder group (69.98±28.63; p<0.001) but lower than that of the control group (107.74±14.21; p<0.001). The cumulative CBCL scores of the preterm children were not significantly different from those of the control group. Additionally, the TCI scores for reward dependence of the preterm children were higher than those of the control group., Conclusion: The cognitive performance of preterm infants was lower than that of healthy full-term infants at the age of 5, and there was an association between slower growth and decreased cognitive ability., Competing Interests: Conflicts of Interest The authors have no financial conflicts of interest, (Copyright: © Journal of the Korean Academy of Child and Adolescent Psychiatry.)

Purpose: Although the DTaP and Tdap vaccines used to prevent pertussis have been used for a long time, there is no standard method for measuring pertussis antigens. Therefore, this preliminary study was conducted to develop an enzyme-linked immunosorbent assay method using an animal model for measuring antibodies against pertussis toxin, the most important pertussis pathogenic antigen, in the sera of vaccinated mice., Materials and Methods: Bordetella pertussis Tohama phase I was cultured for 24-30 hours, and then pertussis toxin was purified from the culture medium by chromatography. Purified pertussis toxin was diluted in phosphate-buffered saline-coating buffer, and 100 µL of diluted pertussis toxin was added to each well and reacted at room temperature for 4 hours. Positive serum was diluted to 1/1,250-1/80,000 and negative serum was diluted to 1/50 to determine the coating concentration with the optimal signal/noise ratio. Optimal test conditions were confirmed from the dilution factors of the secondary antibody and streptavidin horseradish peroxidase (SA-HRP)., Results: Optimal conditions were as follows: 4 µg/mL for coating antigen; 1/40,000 for secondary antibody; and 1/1,000 for the SA-HRP dilution factor. Comparison of the sera obtained from mice treated with a developing vaccine and commercial vaccine with National Institute for Biological Standard and Control standard serum under the established conditions showed the following results: 1,300.62, 534.94, and 34.85, respectively., Conclusion: The method developed in this study is suitable for measuring anti-pertussis toxin antibodies and may be applicable for clinical sample analysis or indirect diagnosis of pertussis.

Background: During maximal isometric protraction, it is important to determine the optimal resistance intensity in subjects with a winged scapula, for inducing isolated activity of the serratus anterior against the pectoralis major, which is activated as a synergistic muscle. The aim of the present study was to determine electromyographic activities of the serratus anterior and pectoralis major muscles during isometric shoulder protraction at different levels in subjects with and without a winged scapula., Methods: Thirty male subjects performed isometric shoulder protraction in a sitting position at different resistance intensity levels (100%, 80%, and 60% of maximal protraction strength). Surface electromyographic data of the serratus anterior and pectoralis major muscles were gathered simultaneously using fixed instrumentation to measure isometric shoulder protraction., Findings: Muscle activity of the serratus anterior in subjects without a winged scapula was significantly greater than that of subjects with a winged scapula across all three conditions, whereas muscle activity of the pectoralis major was lower in subjects without a winged scapula. In addition, winged scapula muscle activity corresponding to maximal protraction was significantly greater than that in the submaximal condition., Interpretation: In a clinical setting, submaximal resistance can be more optimal than maximal effort during isometric shoulder protraction in individuals with a winged scapula., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in patients who received ≤1 line of therapy for advanced BTC was conducted after determination of the maximum tolerated dose in this Phase 1 trial. Patients received binimetinib 60 mg twice daily. The primary objectives were to characterize the safety profile and pharmacokinetics of binimetinib in advanced BTC. Secondary objectives included assessment of clinical efficacy, changes in weight and lean body mass, and pharmacodynamic effects. Tumor samples were assessed for mutations in relevant genes. Results Twenty-eight patients received binimetinib. Common adverse events (AEs) were mild, with rash (82%) and nausea (54%) being most common. Two patients experienced grade 4 AEs, one generalized edema and the other pulmonary embolism. The pharmacokinetics in this patient population were consistent with those previously reported (Bendell JC et al., Br J Cancer 2017;116:575-583). Twelve patients (43%) experienced stable disease and two had objective responses (1 complete response, 1 partial response) per Response Evaluation Criteria in Solid Tumors and stable metabolic disease by positron emission tomography/computed tomography. Most patients (18/25; 72%) did not have KRAS, BRAF, NRAS, PI3KCA, or PTEN mutations, nor was there correlation between mutation status and response. The average non-fluid weight gain was 1.3% for lean muscle and 4.7% for adipose tissue. Conclusion Binimetinib was well tolerated and showed promising evidence of activity in patients with BTC. Correlative studies suggested the potential for binimetinib to promote muscle gain in patients with BTC.

Background/purpose: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity., Methods: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine. Moreover, comparative assessment was made by performing the same evaluations with a commercially available tri-component DTaP vaccine as the positive control., Results: Both groups showed significantly increased levels of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin, and the levels of interferon-γ and interleukin-10 were significantly increased after two doses of vaccination. Furthermore, since cross cell-mediated immune reactivity between the two vaccines was detected, the possibility of interchangeability was indirectly suggested. Although the positive control group showed significantly higher titers in antibody responses for filamentous hemagglutinin and pertactin compared to the experimental group, anti-pertussis toxin antibody titers of the two groups were not significantly different and the protective efficacy against the clinical and reference strains was maintained in both groups for 18 weeks., Conclusion: The results showed inferior immunogenicity of the new DTaP vaccine compared to a commercial vaccine despite comparable cellular immunity and protective efficacy. Some efforts are necessary for improving immunogenicity against filamentous hemagglutinin and pertactin before conducting human clinical trials., (Copyright © 2017. Published by Elsevier B.V.)

Purpose: FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown., Patients and Methods: Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher's exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis., Results: Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS., Conclusion: CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.

Background: The common long-arm octopus (Octopus minor) is found in mudflats of subtidal zones and faces numerous environmental challenges. The ability to adapt its morphology and behavioral repertoire to diverse environmental conditions makes the species a promising model for understanding genomic adaptation and evolution in cephalopods., Findings: The final genome assembly of O. minor is 5.09 Gb, with a contig N50 size of 197 kb and longest size of 3.027 Mb, from a total of 419 Gb raw reads generated using the Pacific Biosciences RS II platform. We identified 30,010 genes; 44.43% of the genome is composed of repeat elements. The genome-wide phylogenetic tree indicated the divergence time between O. minor and Octopus bimaculoides was estimated to be 43 million years ago based on single-copy orthologous genes. In total, 178 gene families are expanded in O. minor in the 14 bilaterian species., Conclusions: We found that the O. minor genome was larger than that of closely related O. bimaculoides, and this difference could be explained by enlarged introns and recently diversified transposable elements. The high-quality O. minor genome assembly provides a valuable resource for understanding octopus genome evolution and the molecular basis of adaptations to mudflats.

Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted., Competing Interests: J.M.B. owns purchased stock of Array BioPharma, Arqule Inc., Clovis Oncology, Intercept Pharmaceuticals, and Seattle Genetics. M.J.B. owns purchased stock of Intercept Pharmaceuticals. The remaining authors declare no competing interests.

Despite recent advancements in therapeutic options for advanced hepatobiliary cancers, there remains an unmet need for innovative systemic treatments. Immunotherapy has shown an ability to provide prolonged clinical benefit, but this benefit remains limited to a small subset of patients. Numerous ongoing endeavors are investigating novel immunotherapy concepts. Immunotherapies that have demonstrated clinical efficacy in hepatobiliary cancers include PD-1 inhibitor therapy and CTLA-4 inhibitor therapy. Novel immunotherapy concepts include targeting emerging checkpoint proteins, bispecific T-cell engagers, combinatorial trials with checkpoint inhibitors, oncolytic virotherapy and chimeric antigen receptor T cells. The goal for these new treatment strategies is to achieve a meaningful expansion of patients deriving prolonged clinical benefit from immunotherapy.

Objective: To evaluate if there is a difference in gait pattern when applying two different shapes of energy storing prosthetic feet for trainstibial amputation we conducted a comparative study. Energy storing prosthetic feet for transtibial amputation are increasing in use, but there are few studies that evaluate the effects of the shape of energy storing feet on gait patterns., Methods: Ten unilateral transtibial amputees were recruited. Two different shapes of dynamic response feet were applied to each subject either 1C30 Trias or 1C60 Triton. The main differences between the two are a split forefoot and the presence of a heel wedge. Spatiotemporal, kinematic, and kinetic data was obtained through gait analysis. Differences between intact and prosthetic side and differences between the two prosthetics were assessed., Results: On a side to side comparison, cadence asymmetry with 1C30 Trias was observed. Ankle plantarflexion at the end of stance and ankle supination at the onset of preswing was smaller with both prosthetic feet compared to the intact side. Other spatiotemporal, kinematic, and kinetic data showed no significant differences in a side to side comparison. In a comparison between the two prosthetics, stance and swing ratio and ankle dorsiflexion through mid-stance was closer to normal with 1C60 Triton than 1C30 Trias. Other spatiotemporal, kinematic, and kinetic data showed no statistically significant differences between prosthetics., Conclusion: Both energy storing feet implants showed symmetric gait in unilateral transtibial amputees who are functionally independent in daily living. And 1C60 Triton showed closer to normal gait patterns than 1C30 Trias in our study.

Although several biomarkers can be used to distinguish cholangiocarcinoma (CCA) from healthy controls, differentiating the disease from benign biliary disease (BBD) or pancreatic cancer (PC) is a challenge. CCA biomarkers are associated with low specificity or have not been validated in relation to the biological effects of CCA. In this study, we quantitatively analyzed 15 biliary bile acids in CCA (n = 30), BBD (n = 57) and PC (n = 17) patients and discovered glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) as specific CCA biomarkers. Firstly, we showed that the average concentration of total biliary bile acids in CCA patients was quantitatively less than in other patient groups. In addition, the average composition ratio of primary bile acids and conjugated bile acids in CCA patients was the highest in all patient groups. The average composition ratio of GCA (35.6%) in CCA patients was significantly higher than in other patient groups. Conversely, the average composition ratio of TCDCA (13.8%) in CCA patients was significantly lower in all patient groups. To verify the biological effects of GCA and TCDCA, we analyzed the gene expression of bile acid receptors associated with the development of CCA in a CCA cell line. The gene expression of transmembrane G protein coupled receptor (TGR5) and sphingosine 1-phosphate receptor 2 (S1PR2) in CCA cells treated with GCA was 8.6-fold and 3.4-fold higher compared with control (untreated with bile acids), respectively. Gene expression of TGR5 and S1PR2 in TCDCA-treated cells was not significantly different from the control. Taken together, our study identified GCA and TCDCA as phenotype-specific biomarkers for CCA.

Biophysical cues can improve the direct reprogramming of fibroblasts into neurons that can be used for therapeutic purposes. However, the effects of a three-dimensional (3D) environment on direct neuronal reprogramming remain unexplored. Here, we show that brain extracellular matrix (BEM) decellularized from human brain tissue facilitates the plasmid-transfection-based direct conversion of primary mouse embryonic fibroblasts into induced neuronal (iN) cells. We first show that two-dimensional (2D) surfaces modified with BEM significantly increase the generation efficiency of iN cells and enhance neuronal transdifferentiation and maturation. Moreover, in an animal model of ischaemic stroke, iN cells generated on the BEM substrates and transplanted into the brain led to significant improvements in locomotive behaviours. We also show that compared with the 2D BEM substrates, 3D BEM hydrogels recapitulating brain-like microenvironments further promote neuronal conversion and potentiate the functional recovery of the animals. Our findings suggest that 3D microenvironments can boost nonviral direct reprogramming for the generation of therapeutic neuronal cells.

Background and Purpose: The development and implementation of effective interventions to prevent falls in older adults is a public health priority. The purpose of this study was to compare the efficacy of a new practice model, incorporating Shubert's evidence-based fall prevention recommendations, with the usual ambulatory physical therapy (PT) at Rusk Rehabilitation, to decrease fall risk among older adults living in the community. The hypotheses were (1) the proposed program would decrease participants' fall risk, (2) it would be more effective than our usual PT, and (3) the addition of 4 consults after discharge would improve compliance with a home exercise program., Methods: This was a randomized controlled trial. Sixty-nine participants who were independent community dwellers, were 65 years or older, had difficulty walking or complaints of instability, and had 1 or more risk of falls were randomly assigned into a usual care group (UCG, n = 43) or an experimental group (EG, n = 26). Both groups received PT 2 times per week for 30 minutes for 10 to 32 visits. The UCG received the usual PT delivered at Rusk. The EG was instructed in a moderate- to high-intensity home exercise program designed after completing the mini-Balance Evaluation Systems Test to assist with exercise prescription. The EG was educated on performing a recommended dosage of exercise over 6 months using a diary. The EG received 4 additional 30-minute consults every 2 to 4 weeks postdischarge to reinforce compliance. Self-report of number of falls, number of minutes of exercise per week, and performance on outcome measures (Timed Up and Go, 5-times sit-to-stand, Berg Balance Scale, and Activity Balance Confidence Scale) were monitored at evaluation, 2, 4, and 6 months., Results and Discussion: Thirty-five participants completed the study (UCG n = 22; EG n = 13). Both groups were similar at baseline on outcome measures and number of visits. Random effect model analyses demonstrated that both groups made significant reductions in fall risk over 6 months as identified by performance on outcome measures. However, the EG improved significantly more compared with the UCG over time (P < .05). Linear regression analyses showed that the EG exercised significantly more compared with the UCG at all times (P < .05). The EG exceeded the target of 115 min/wk of exercise (154 minutes, standard deviation [SD] 68.5; 170 minutes, SD 96.8; and 143 minutes, SD 68.5) at 2, 4, and 6 months, respectively. This study demonstrated that the experimental program is effective in decreasing fall risk in community-dwelling older adults and is more effective than our usual care. Moreover, it suggests that the overall experimental protocol may offer an effective strategy to foster adherence to an exercise program without the increasing number of visits., Conclusion: This study supports the efficacy of the experimental program in decreasing fall risk and being more effective than our usual care, as well as fostering greater compliance with an exercise regimen. It provides some preliminary evidence to support Shubert's recommendation on exercise prescription for fall prevention.

As shown during the 2009 pandemic H1N1 (A(H1N1)pdm09) outbreak, egg-based influenza vaccine production technology is insufficient to meet global demands during an influenza pandemic. Therefore, there is a need to adapt cell culture-derived vaccine technology using suspended cell lines for more rapid and larger-scale vaccine production. In this study, we attempted to generate a high-growth influenza vaccine strain in MDCK cells using an A/Puerto/8/1934 (H1N1) vaccine seed strain. Following 48 serial passages with four rounds of virus plaque purification in MDCK cells, we were able to select several MDCK-adapted plaques that could grow over 10⁸ PFU/ml. Genetic characterization revealed that these viruses mainly had amino acid substitutions in internal genes and exhibited higher polymerase activities. By using a series of Rg viruses, we demonstrated the essential residues of each gene and identified a set of high-growth strains in MDCK cells (PB1 D153N , M1 A137T , and NS1 N176S ). In addition, we confirmed that in the context of the high-growth A/PR/8/34 backbone, A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2), and A/environment/Korea/deltaW150/2006 (H5N1) also showed significantly enhanced growth properties (more than 10⁷ PFU/ml) in both attached- and suspended-MDCK cells compared with each representative virus and the original PR8 vaccine strain. Taken together, this study demonstrates the feasibility of a cell culture-derived approach to produce seed viruses for influenza vaccines that are cheap and can be grown promptly and vigorously as a substitute for egg-based vaccines. Thus, our results suggest that MDCK cell-based vaccine production is a feasible option for producing large-scale vaccines in case of pandemic outbreaks.

Pancreatic adenocarcinoma is typically refractory to conventional treatments and associated with poor prognosis. While therapeutic advances over the past several years have improved patient outcomes, the observed benefits have been modest at best, highlighting the need for continued development of alternate treatment strategies. The tumor microenvironment has been identified as being integral to oncogenesis through its direct effect on cellular pathway communication, immune inhibition, and promoting chemo-resistance. A more in depth understanding of the biology of the disease, in addition with our ability to develop more effective novel therapies have led to ongoing studies that are investigating several promising treatment options in this disease. Herein, we highlight and review the therapeutic landscape in pancreatic adenocarcinoma.

Two bipolar host materials, 8-(9 H -carbazol-9-yl)-5-(pyridin-2-yl)-5 H -pyrido[3,2- b ]indole (CzCbPy) and 5-(6-(9 H -carbazol-9-yl)pyridin-2-yl)-8-(9 H -carbazol-9-yl)-5 H -pyrido[3,2- b ]indole (2CzCbPy), were synthesized for deep blue thermally activated delayed fluorescence organic light emitting diodes (TADF OLEDs). Both CzCbPy and 2CzCbPy hosts possess bipolar characteristic with high polarity, which results in high delayed photoluminescence quantum yields by reducing the energy gap between singlet and triplet states of TADF materials. In addition, these hosts have high enough triplet energies of 3.05 eV to transfer exciton energy to a deep blue TADF emitter. A deep blue TADF OLED fabricated with a CzCbPy host exhibited high external quantum efficiency of 22.9% and low efficiency roll-off (19.2% at 1000 cd m -2 )., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Treatment with cisplatin and gemcitabine demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1,000 mg/m 2 /min) and cisplatin 20 mg/m 2 on days 1 and 15 of every 28-day cycle. Patients received treatment until time of progression, death, or discontinuation due to intolerance. Collected data included demographics, clinico-pathologic features, toxicities, and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). The study included 107 evaluable pts with unresectable ABTC who received the biweekly regimen. Sites of tumor included gallbladder (21.5%), ampullary (3.7%), and bile duct (74.8%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade ≥3 adverse events included neutropenia (11%), fatigue (10%), and thrombocytopenia (6.4%). Biweekly FDR GC in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many patients. Further prospective trials should consider evaluating the role of biweekly GC regimen in ABTC, including a potentially more favorable platform in novel experimental strategies., (© 2017 UICC.)

Objective: Many treatment techniques have been used for refractory lumbar facet joint pain; however, their efficacy has been controversial. In this study, we investigated the clinical efficacy and safety of intra-articular pulsed radiofrequency for the treatment of refractory lumbar facet joint pain in patients with low back pain., Methods: Twenty patients with refractory lumbar facet joint pain were recruited, and each patient was treated via intra-articular pulsed radiofrequency. The treatment effects were measured with a numerical rating scale, and the technical accuracy of intra-articular pulsed radiofrequency treatment was evaluated independently by 2 radiologists. Any adverse events or complications also were checked., Results: We performed intra-articular pulsed radiofrequency treatment at 48 levels of the lumbar facet joints in 20 patients (5 men and 15 women; mean age, 64.50 ± 10.65 years) with refractory lumbar facet joint pain. Pain scores were significantly reduced at 1 month, 3 months, and 6 months after treatment (P < 0.05). The face validity revealed good intraarticular pulsed radiofrequency results in all 20 patients, without any serious adverse effects., Conclusions: Treatment using intra-articular pulsed radiofrequency is an alternative to other techniques in patients with refractory lumbar facet joint pain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Highly efficient deep blue fluorescent material and various thermally activated delayed fluorescent (TADF) blue sensitization materials were synthesized for fluorescent deep blue organic light-emitting diodes (OLEDs). These materials were designed and selected by considering efficient energy transfer conditions (i.e., spectral overlap and quantum efficiency) between sensitizer and acceptor. Energy transfer process from TADF host sensitizers to deep blue fluorescent emitter has been investigated by measuring the energy transfer rate. Measured energy transfer rate was to be 1.24 × 10 10 s -1 (mol/dm 3 ) -1 for a prompt decay of fluorescence and 2.61 × 10 8 s -1 (mol/dm 3 ) -1 for delayed fluorescence, which demonstrated the efficient energy transfer. Indeed, highly efficient deep blue fluorescent OLEDs boosted by the TADF host-sensitization process were successfully fabricated. The maximum external quantum efficiency was 19.0% with color coordinates of (0.14, 0.15) and 15.5% with color coordinates of (0.15, 0.11) in the different host system. The efficiency roll-off characteristic and device operating lifetime were also improved by this efficient sensitization process.

Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement. There are additional biomarkers that merit further exploration in hepatobiliary cancers including FGF19, ERRFI1, TERT, BAP1, BRAF, CDKN2A, tumor mutational burden and ERBB2 (HER2/neu). Development of new and innovative therapies would help address the unmet need for effective systemic therapies in advanced and metastatic hepatobiliary cancers.

Tuna cooking drip (TCD) is a protein rich by-product of canned tuna processing that is typically discarded. In this study, the immune-enhancing activities of TCD and its enzymatic hydrolysate (EH-TCD) were investigated by intraperitoneally administering Balb/c male mice with TCD and EH-TCD for 2 weeks. This administration resulted in an increase in the weight of the spleen and thymus (200-800 mg/kg) and enhanced the proliferation rates of splenocytes (200-800 mg/kg). TCD and EH-TCD significantly increased the production of immunostimulatory cytokines (interleukin-10 and interleukin-2). In addition, TCD and EH-TCD increased serum IgG1 and IgG2a levels in a concentration-dependent manner. Particularly, EH-TCD had a greater immune-enhancing effect than TCD. These results suggest that TCD and EH-TCD exert immune-enhancing effects through an IgG antibody response and T cell activation, and EH-TCD can be used as an immunostimulatory agent., Competing Interests: Compliance with ethical standardsThe authors declare no conflict of interest.

Introduction: Patients with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant chemotherapy (CT) per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcomes in patients who did and did not receive adjuvant CT., Materials and Methods: We used a prospectively collected database for patients treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence, patient characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using the χ or Fisher exact test., Results: Between August 2005 and July 2011, 110 patients were identified and 71 patients had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor stage, and pathologic complete response between the 2 patient groups. Although patient characteristics showed a difference in age (median age 54.3 vs. 62 y, P=0.01) and advanced pathologic nodal status (43% vs. 19%, P=0.02), there was a significant difference in OS. Median OS was 72.6 months with CT versus 36.4 months without CT (P=0.0003). Median time to recurrence has not yet been reached., Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for patients across the spectrum of stage II and III rectal cancer.

Background: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC., Methods: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS)., Results: Five studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47-0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS., Conclusions: Combination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single-agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine-based chemotherapy regimens. Cancer 2017;123:4680-4686. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

The tumor stroma in pancreatic adenocarcinoma is recognized as an integral component in tumorigenesis through its effects on cell signaling, immunosuppression and inhibitory effect on therapeutic agents. Promising preclinical activity has been observed with novel therapeutic agents that target the tumor microenvironment and represent one of many potential treatment strategies of interest in this disease. Herein, we will highlight and review therapeutic novel agents aimed at tumor stroma in pancreas cancer.

The bacterial toxin-antitoxin MazEF system in the tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis is activated under unfavorable conditions, including starvation, antibiotic exposure, and oxidative stress. This system contains the ribonucleolytic enzyme MazF and has emerged as a promising drug target for TB treatments targeting the latent stage of M. tuberculosis infection and reportedly mediates a cell death process via a peptide called extracellular death factor (EDF). Although it is well established that the increase in EDF-mediated toxicity of MazF drives a cell-killing phenomenon, the molecular details are poorly understood. Moreover, the divergence in sequences among reported EDFs suggests that each bacterial species has a unique EDF. To address these open questions, we report here the structures of MazF4 and MazEF4 complexes from M. tuberculosis , representing the first MazEF structures from this organism. We found that MazF4 possesses a negatively charged MazE4-binding pocket in contrast to the positively charged MazE-binding pockets in homologous MazEF complex structures from other bacteria. Moreover, using NMR spectroscopy and biochemical assays, we unraveled the molecular interactions of MazF4 with its RNA substrate and with a new EDF homolog originating from M. tuberculosis The EDF homolog discovered here possesses a positively charged residue at the C terminus, making this EDF distinct from previously reported EDFs. Overall, our results suggest that M. tuberculosis evolved a unique MazF and EDF and that the distinctive EDF sequence could serve as a starting point for designing new anti-tuberculosis drugs. We therefore conclude that this study might contribute to the development of a new line of anti-tuberculosis agents., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

The Antarctic bathydraconid dragonfish, Parachaenichthys charcoti, is an Antarctic notothenioid teleost endemic to the Southern Ocean. The Southern Ocean has cooled to -1.8ºC over the past 30 million years, and the seawater had retained this cold temperature and isolated oceanic environment because of the Antarctic Circumpolar Current. Notothenioids dominate Antarctic fish, making up 90% of the biomass, and all notothenioids have undergone molecular and ecological diversification to survive in this cold environment. Therefore, they are considered an attractive Antarctic fish model for evolutionary and ancestral genomic studies. Bathydraconidae is a speciose family of the Notothenioidei, the dominant taxonomic component of Antarctic teleosts. To understand the process of evolution of Antarctic fish, we select a typical Antarctic bathydraconid dragonfish, P. charcoti. Here, we have sequenced, de novo assembled, and annotated a comprehensive genome from P. charcoti. The draft genome of P. charcoti is 709 Mb in size. The N50 contig length is 6145 bp, and its N50 scaffold length 178 362 kb. The genome of P. charcoti is predicted to contain 32 712 genes, 18 455 of which have been assigned preliminary functions. A total of 8951 orthologous groups common to 7 species of fish were identified, while 333 genes were identified in P. charcoti only; 2519 orthologous groups were also identified in both P. charcoti and N. coriiceps, another Antarctic fish. Four gene ontology terms were statistically overrepresented among the 333 genes unique to P. charcoti, according to gene ontology enrichment analysis. The draft P. charcoti genome will broaden our understanding of the evolution of Antarctic fish in their extreme environment. It will provide a basis for further investigating the unusual characteristics of Antarctic fishes., (© The Author 2017. Published by Oxford University Press.)

Background: Biliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. BRCA2 mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) BRCA mutations. Therefore, it is important to define the clinical characteristics of GL/somatic BRCA1/2 variants in CCA patients., Materials and Methods: We performed a multicenter retrospective analysis of CCA patients diagnosed between January 2000 and December 2013 with GL or somatic variants in BRCA1/2 genes detected by GL mutations testing and/or by tumor next generation sequencing. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures, and systemic chemotherapy or radiation were extracted from patients' records., Results: Overall, 18 cases were identified: 5 carriers of GL BRCA1/2 mutations (4 BRCA2 ; 1 BRCA1 ) and 13 harboring somatic variations (7 BRCA1 ; 6 BRCA2 ). Mean age at diagnosis was 60, SD ± 10 years (range 36-75 years), with male and female prevalence rates of 61.2% and 38.8%, respectively. Stage at diagnosis was I ( n  = 4), II ( n  = 3), III ( n  = 3), and IV ( n  = 8). Six patients had extrahepatic CCA and the rest intrahepatic CCA. Thirteen patients received platinum-based therapy and four were treated with poly ADP ribose polymerase inhibitors, of whom one experienced sustained disease response with a progression-free survival of 42.6 months. Median overall survival from diagnosis for patients with stage I/II in this study was 40.3 months (95% confidence interval [CI], 6.73-108.15) and with stages III/IV was 25 months (95% CI, 15.23-40.57)., Conclusion: BRCA-associated CCA is uncommon. This multicenter retrospective study provides a thorough clinical analysis of a BRCA-associated CCA cohort, which can serve as a benchmark for future development and design of expanded analyses and clinical trials., Implications for Practice: BRCA-associated CCA is uncommon but a very important subtype of hepatic malignancies, due to its rising prevalence. Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in BRCA1/2 genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies. Thus this study, first of its kind, provides a basis for future multi-centered analyses in larger cohorts, as well as clinical trials. Additionally, this study emphasizes the importance of both germline and somatic genotyping for all CCA patients., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Competing Interests: Conflict of interest statement: Tanios Bekaii-Saab has received consultant fees from Celgene (advisory role) Summit, New Jersey, USA.

Background: Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model., Methods: Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice., Results: Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range., Conclusions: A murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine.

Biliary cancers (BCs) are a diverse group of tumors that arise from the bile duct epithelium and are divided into cholangiocarcinomas of the intrahepatic and extrahepatic cholangiocarcinoma (EHCC) and cancer of the gallbladder. Despite improvements in treatment and diagnosis, BCs are often diagnosed at an advanced stage and associated with poor prognosis and limited treatment options. Recent discoveries have allowed us to have a better understanding of the genomic diversity in BC, and identify genes that are likely contributing to its pathogenesis, proliferation and treatment resistance. Additionally, these advances have allowed us to reason that each anatomic group within BC behave as distinct diseases, with differences in prognosis and outcomes. Based on this knowledge, recent advances have allowed us to identify actionable mutations that form rational therapeutic targets with novel agents, where their relevance will be better understood through the completion of prospective clinical trials., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Biliary tract cancer (BTC) is a heterogeneous group of cancers, which is composed of intrahepatic cholangiocarcinoma (ICCA), extrahepatic cholangiocarcinoma (ECCA), gallbladder cancers and ampullary carcinomas. While all anatomic subgroups are treated uniformly, our understanding about the pathogenesis has allowed us to reason that each group represents a clinically and genetically diverse disease. The majority of patients present with locally advanced or metastatic disease, where the standard treatment is combination systemic cytotoxic chemotherapy with gemcitabine and cisplatin. While most receive a clinical benefit from chemotherapy, patients eventually progress where no standardized therapies are available in the refractory setting. With the use of next generation sequencing, we have come to understand that ICCA is a diverse genomic disease with many actionable alterations that may serve as potential therapeutic targets. Further studies investigating the role of novel targeted agents (as a single agent or with combination chemotherapy) will hopefully provide additional treatment options for this highly lethal disease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background/purpose: A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine., Methods: Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored., Results: A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups., Conclusion: The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus., (Copyright © 2015. Published by Elsevier B.V.)

Severe plastic deformation (SPD) has recently been advanced as the main process for fabricating bulk ultrafine grained or nanocrystalline metallic materials, which present much higher strength and better bio-compatibility than coarse-grained counterparts. Medical devices, such as aneurysm clips and dental implants, require high mechanical and biological performance (e.g., stiffness, yield strength, fatigue resistance, and bio-compatibility). These requirements match well the characteristics of SPD-processed materials. Typical aneurysm clips are made of a commercial Ti-6Al-4V alloy, which has higher yield strength than Ti. In this work, Ti and Ti-6Al-4V workpieces were processed by high-pressure torsion (HPT) to enhance their mechanical properties. Tensile tests and hardness tests were performed to evaluate their mechanical properties, and their microstructure was investigated. The hardness and yield stress of the HPT-processed Ti are comparable to those of the initial Ti-6Al-4V due to significantly refined microstructure. Finite element analyses for evaluating the opening performance of a specific geometry of the YASARGIL aneurysm clip were carried out using mechanical properties of the initial and HPT-processed Ti and Ti-6Al-4V. These results indicate that SPD-processed Ti could be a good candidate to substitute for Ti-6Al-4V in aneurysm clips., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy.

Objective: The aim of this study was to identify a transcriptomic signature that could be used to classify subjects with autism spectrum disorder (ASD) compared to controls on the basis of blood gene expression profiles. The gene expression profiles could ultimately be used as diagnostic biomarkers for ASD., Methods: We used the published microarray data (GSE26415) from the Gene Expression Omnibus database, which included 21 young adults with ASD and 21 age- and sex-matched unaffected controls. Nineteen differentially expressed probes were identified from a training dataset (n=26, 13 ASD cases and 13 controls) using the limma package in R language (adjusted p value ＜0.05) and were further analyzed in a test dataset (n=16, 8 ASD cases and 8 controls) using machine learning algorithms., Results: Hierarchical cluster analysis showed that subjects with ASD were relatively well-discriminated from controls. Based on the support vector machine and K-nearest neighbors analysis, validation of 19-DE probes with a test dataset resulted in an overall class prediction accuracy of 93.8% as well as a sensitivity and specificity of 100% and 87.5%, respectively., Conclusion: The results of our exploratory study suggest that the gene expression profiles identified from the peripheral blood samples of young adults with ASD can be used to identify a biological signature for ASD. Further study using a larger cohort and more homogeneous datasets is required to improve the diagnostic accuracy.

Background: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy., Methods: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities., Results: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9-13 months] and 5.4 months (95% CI 4.1-7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group., Conclusions: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We identified two antimicrobial peptides (AMPs) with similarity to moronecidin in Antarctic fishes. The characteristics of both AMPs were determined using moronecidin as a control. Moronecidin, which was first isolated from hybrid striped bass, is highly salt-resistant, and possesses broad-spectrum activity against various microbes. The moronecidin-like peptide from Notothenia coriiceps exhibited a narrower spectrum of activity and a higher salt sensitivity than moronecidin. The AMP from Parachaenichthys charcoti exhibited similar antimicrobial activity to moronecidin, and similar salt sensitivity. In an experiment to identify toxic effects, both of the moronecidin-like peptides from the Antarctic fishes exhibited lower hemolytic activity than moronecidin. In spite of its low toxicity, the AMP from N. coriiceps is unlikely to be considered as a candidate for antibiotic development, owing to its narrow spectrum of activity and high salt sensitivity. In contrast, the high salt resistance and broad-spectrum activity of the AMP from P. charcoti could be more advantageous for clinical use than moronecidin, since it could kill bacteria under physiological conditions with low toxicity. A further comparison of these two AMPs from Antarctic fishes with other AMPs could help to reduce the toxicity of AMPs for clinical use., Competing Interests: The authors have declared that no competing interests exist.

Bathynellacea (Crustacea, Syncarida, Parabathynellidae) are subterranean aquatic crustaceans that typically inhabit freshwater interstitial spaces (e.g., groundwater) and are occasionally found in caves and even hot springs. In this study, we sequenced the whole transcriptome of Allobathynella bangokensis using RNA-seq. De novo sequence assembly produced 74,866 contigs including 28,934 BLAST hits. Overall, the gene sequences were most similar to those of the waterflea Daphnia pulex. In the A. bangokensis transcriptome, no opsin or related sequences were identified, and no contig aligned to the crustacean visual opsins and non-visual opsins (i.e. arthropsins, peropsins, and melaopsins), suggesting potential regressive adaptation to the dark environment. However, A. bangokensis expressed conserved gene family sets, such as heat shock proteins and those related to key innate immunity pathways and antioxidant defense systems, at the transcriptional level, suggesting that this species has evolved adaptations involving molecular mechanisms of homeostasis. The transcriptomic information of A. bangokensis will be useful for investigating molecular adaptations and response mechanisms to subterranean environmental conditions., Competing Interests: The authors have declared that no competing interests exist.

Background: The Antarctic intertidal zone is continuously subjected to extremely fluctuating biotic and abiotic stressors. The West Antarctic Peninsula is the most rapidly warming region on Earth. Organisms living in Antarctic intertidal pools are therefore interesting for research into evolutionary adaptation to extreme environments and the effects of climate change., Findings: We report the whole genome sequence of the Antarctic-endemic harpacticoid copepod Tigriopus kingsejongensi . The 37 Gb raw DNA sequence was generated using the Illumina Miseq platform. Libraries were prepared with 65-fold coverage and a total length of 295 Mb. The final assembly consists of 48 368 contigs with an N50 contig length of 17.5 kb, and 27 823 scaffolds with an N50 contig length of 159.2 kb. A total of 12 772 coding genes were inferred using the MAKER annotation pipeline. Comparative genome analysis revealed that T. kingsejongensis -specific genes are enriched in transport and metabolism processes. Furthermore, rapidly evolving genes related to energy metabolism showed positive selection signatures., Conclusions: The T. kingsejongensis genome provides an interesting example of an evolutionary strategy for Antarctic cold adaptation, and offers new genetic insights into Antarctic intertidal biota., (© The Author 2017. Published by Oxford University Press.)