bluuebunny/crossref_metadata_2025 huggingface dataset:
Widespread co-occurrence of multiple ploidy levels in fragile ferns (Cystopteris fragilis complex; Cystopteridaceae) probably stems from similar ecology of cytotypes, their efficient dispersal and inter-ploidy hybridization
Authors: Hanušová Kristýna , Čertner Martin , Urfus Tomáš , Koutecký Petr , Košnar Jiří , Rothfels Carl J , Jarolímová Vlasta , Ptáček Jan , Ekrt Libor
Published: November 2018

Background and Aims

Polyploidy has played an important role in the evolution of ferns. However, the dearth of data on cytotype diversity, cytotype distribution patterns and ecology in ferns is striking in comparison with angiosperms and prevents an assessment of whether cytotype coexistence and its mechanisms show similar patterns in both plant groups. Here, an attempt to fill this gap was made using the ploidy-variable and widely distributed Cystopteris fragilis complex.

Methods

Flow cytometry was used to assess DNA ploidy level and monoploid genome size (Cx value) of 5518 C. fragilis individuals from 449 populations collected over most of the species’ global distributional range, supplemented with data from 405 individuals representing other related species from the complex. Ecological preferences of C. fragilis tetraploids and hexaploids were compared using field-recorded parameters and database-extracted climate data.

Key Results

Altogether, five different ploidy levels (2x, 4x, 5x, 6x, 8x) were detected and three species exhibited intraspecific ploidy-level variation: C. fragilis, C. alpina and C. diaphana. Two predominant C. fragilis cytotypes, tetraploids and hexaploids, co-occur over most of Europe in a diffuse, mosaic-like pattern. Within this contact zone, 40 % of populations were mixed-ploidy and most also contained pentaploid hybrids. Environmental conditions had only a limited effect on the distribution of cytotypes. Differences were found in the Cx value of tetraploids and hexaploids: between-cytotype divergence was higher in uniform-ploidy than in mixed-ploidy populations.

Conclusions

High ploidy-level diversity and widespread cytotype coexistence in the C. fragilis complex match the well-documented patterns in some angiosperms. While ploidy coexistence in C. fragilis is not driven by environmental factors, it could be facilitated by the perennial life-form of the species, its reproductive modes and efficient wind dispersal of spores. Independent origins of hexaploids and/or inter-ploidy gene flow may be expected in mixed-ploidy populations according to Cx value comparisons.
BGSA: a bit-parallel global sequence alignment toolkit for multi-core and many-core architectures
Authors: Zhang Jikai , Lan Haidong , Chan Yuandong , Shang Yuan , Schmidt Bertil , Liu Weiguo
Published: November 2018

Motivation

Modern bioinformatics tools for analyzing large-scale NGS datasets often need to include fast implementations of core sequence alignment algorithms in order to achieve reasonable execution times. We address this need by presenting the BGSA toolkit for optimized implementations of popular bit-parallel global pairwise alignment algorithms on modern microprocessors.

Results

BGSA outperforms Edlib, SeqAn and BitPAl for pairwise edit distance computations and Parasail, SeqAn and BitPAl when using more general scoring schemes for pairwise alignments of a batch of sequence reads on both standard multi-core CPUs and Xeon Phi many-core CPUs. Furthermore, banded edit distance performance of BGSA on a Xeon Phi-7210 outperforms the highly optimized NVBio implementation on a Titan X GPU for the seed verification stage of a read mapper by a factor of 4.4.

Availability and implementation

BGSA is open-source and available at https://github.com/sdu-hpcl/BGSA.

Supplementary information

Supplementary data are available at Bioinformatics online.
G4HunterApps
Authors: Lacroix Laurent
Published: November 2018

Motivation

In order to help G4Hunter users and make it more accessible, I have developed a set of small applications within the Shiny/R framework.

Results

Each application fulfils simple tasks ranging from computing the G4Hunter score for a sequence or a list of sequence to extracting sequences with a G4Hunter score above a threshold for a sequence up to 5 Mb or a list of short sequences. The application can be installed either on the user computer within Rstudio or on a Rstudio server.

Availability and implementation

The source code for the ShinyApps is available on GitHub (https://github.com/LacroixLaurent).
Identification of master regulator genes of UV response and their implications for skin carcinogenesis
Authors: Shen Yao , Chan Gabriel , Xie Michael , Zeng Wangyong , Liu Liang
Published: November 2018

Solar UV radiation is a major environmental risk factor for skin cancer. Despite decades of robust and meritorious investigation, our understanding of the mechanisms underlying UV-induced skin carcinogenesis remain incomplete. We previously performed comprehensive transcriptomic profiling in human keratinocytes following exposure to different UV radiation conditions to generate UV-specific gene expression signatures. In this study, we utilized Virtual Inference of Protein Activity by Enriched Regulon (VIPER), a robust systems biology tool, on UV-specific skin cell gene signatures to identify master regulators (MRs) of UV-induced transcriptomic changes. We identified multiple prominent candidate UV MRs, including forkhead box M1 (FOXM1), thyroid hormone receptor interactor 13 and DNA isomerase II alpha, which play important roles in cell cycle regulation and genome stability. MR protein activity was either activated or suppressed by UV in normal keratinocytes. Intriguingly, many of the UV-suppressed MRs were activated in human skin squamous cell carcinomas (SCCs), highlighting their importance in skin cancer development. We further demonstrated that selective inhibition of FOXM1, whose activity was elevated in SCC cells, was detrimental to SCC cell survival. Taken together, our study uncovered novel UV MRs that can be explored as new therapeutic targets for future skin cancer treatment.
Referral of patients for fractional flow reserve using quantitative flow ratio
Authors: Smit Jeff M , Koning Gerhard , van Rosendael Alexander R , El Mahdiui Mohammed , Mertens Bart J , Schalij Martin J , Jukema J Wouter , Delgado Victoria , Reiber Johan H C , Bax Jeroen J , Scholte Arthur J
Published: November 2018

Aims

Quantitative flow ratio (QFR) is a recently developed technique to calculate fractional flow reserve (FFR) based on 3D quantitative coronary angiography and computational fluid dynamics, obviating the need for a pressure-wire and hyperaemia induction. QFR might be used to guide patient selection for FFR and subsequent percutaneous coronary intervention (PCI) referral in hospitals not capable to perform FFR and PCI. We aimed to investigate the feasibility to use QFR to appropriately select patients for FFR referral.

Methods and results

Patients who underwent invasive coronary angiography in a hospital where FFR and PCI could not be performed and were referred to our hospital for invasive FFR measurement, were included. Angiogram images from the referring hospitals were retrospectively collected for QFR analysis. Based on QFR cut-off values of 0.77 and 0.86, our patient cohort was reclassified to ‘no referral’ (QFR ≥0.86), referral for ‘FFR’ (QFR 0.78–0.85), or ‘direct PCI’ (QFR ≤0.77). In total, 290 patients were included. Overall accuracy of QFR to detect an invasive FFR of ≤0.80 was 86%. Based on a QFR cut-off value of 0.86, a 50% reduction in patient referral for FFR could be obtained, while only 5% of these patients had an invasive FFR of ≤0.80 (thus, these patients were incorrectly reclassified to the ‘no referral’ group). Furthermore, 22% of the patients that still need to be referred could undergo direct PCI, based on a QFR cut-off value of 0.77.

Conclusion

QFR is feasible to use for the selection of patients for FFR referral.
Advance care planning for patients with cancer in the palliative phase in Dutch general practices
Authors: Ermers Daisy J M , van Bussel Karin J H , Perry Marieke , Engels Yvonne , Schers Henk J
Published: November 2018

Background

Advance care planning (ACP) is a crucial element of palliative care. It improves the quality of end-of-life care and reduces aggressive and needless life-prolonging medical interventions. However, little is known about its application in daily practice. This study aims to examine the application of ACP for patients with cancer in general practice.

Methods

We performed a retrospective cohort study in 11 general practices in the Netherlands. Electronic patient records (EPRs) of deceased patients with colorectal or lung cancer were analysed. Data on ACP documentation, correspondence between medical specialist and GP, and health care use in the last year of life were extracted.

Results

Records of 163 deceased patients were analysed. In 74% of the records, one or more ACP items were registered. GPs especially documented patients’ preferences for euthanasia (58%), palliative sedation (46%) and preferred place of death (26%). Per patient, GPs received on average six letters from medical specialists. These letters mainly contained information regarding medical treatment and rarely ACP items. In the last year of life, patients contacted the GP over 30 times, and 51% visited the emergency department at least once, of whom 54% in the last month.

Conclusions

Registration of ACP items in GPs’ EPRs appeared to be limited. ACP elements were rarely subject of communication between primary and secondary care, which may impact the continuity of patient care during the last year of life. More emphasis on registration of ACP items and better exchange of information regarding patients’ preferences are needed.
Climate sensitivities and uncertainties in food-web pathways supporting larval bluefin tuna in subtropical oligotrophic oceans
Authors: Landry Michael R , Beckley Lynnath E , Muhling Barbara A
Published: November 2018

Compared with high-latitude seas, the ecological implications of climate change for top consumers in subtropical regions are poorly understood. One critical area of knowledge deficiency is the nature of food-web connections to larvae during their vulnerable time in the plankton. Bluefin tuna (BFT) are highly migratory temperate species whose early life stages are spent in ultra-oligotrophic subtropical waters. Dietary studies of BFT larvae provide evidence of prey-limited growth coupled with strong selection for specific prey types—cladocerans and poecilostomatoid copepods—whose paradoxical or poorly resolved trophic characteristics do not fit the conventional understanding of open-ocean food-web structure and flows. Current knowledge consequently leaves many uncertainties in climate change effects, including the possibility that increased nitrogen fixation by Trichodesmium spp. might enhance resiliency of BFT larvae, despite a projected overall decline in system productivity. To advance understanding and future predictions, the complementary perspectives of oceanographers and fisheries researchers need to come together in studies that focus on the trophic pathways most relevant to fish larvae, the factors that drive variability in spawning regions, and their effects on larval feeding, growth, and survival.
Wearing Off Response to OnabotulinumtoxinA in Chronic Migraine: Analysis in a Series of 193 Patients
Authors: Quintas Sonia , García-Azorín David , Heredia Patricia , Talavera Blanca , Gago-Veiga Ana Beatriz , Guerrero Ángel L
Published: November 2018

Objective

Long-term real-life studies have supported a cumulative effect of OnabotulinumtoxinA (OnabotA) for the prophylactic treatment of chronic migraine (CM) during consecutive cycles, and individual adaptations have been described to improve clinical response.

Methods

This was a cohort longitudinal retrospective study of consecutive adult patients from the Headache Unit of the Hospital Clínico Universitario de Valladolid and the Hospital Universitario de La Princesa (Madrid) on OnabotA treatment for chronic migraine from May 2012 to December 2017. All patients were followed for 24 weeks. Full-length response to OnabotA was defined as ≥50% reduction in headache days for at least 12 weeks, and wearing off response was defined as a clinical response but with duration shorter than 10 weeks. We have analyzed the incidence and clinical predictors of this wearing off response.

Results

A total of 193 patients were included, of whom 91 (47.1%) were considered full-length responders and 45 (23.3%) wearing off responders. No statistically significant clinical predictors (including demographic variables and baseline headache characteristics) of full-length response or wearing off response were detected in our study. An increase in dose during the second treatment cycle was attempted in 68.9% of the wearing off patients, achieving a longer duration of response of up to 12 weeks in 74.2%.

Conclusions

Wearing off response to OnabotA during the first treatment cycle is not uncommon in patients with CM. Increasing the dose in subsequent cycles could improve clinical response, but further multicenter long-term studies are needed to establish predictors and solutions to this problem.
Governance under the Gun: Spillover Effects of Hedge Fund Activism*
Authors: Gantchev Nickolay , Gredil Oleg R , Jotikasthira Chotibhak
Published: November 2018

Hedge fund activism is associated with improvements in the governance and performance of targeted firms. In this article, we show that these positive effects of activism reach beyond the targets, as nontargeted peers make similar improvements under the threat of activism. Peers with higher threat perception, as measured by director connections to past targets, are more likely to increase leverage and payout, decrease capital expenditures and cash, and improve return on assets and asset turnover. As a result, their valuations improve, and their probability of being targeted declines. Our results are not explained by time-varying industry conditions or competition effects whereby improved targets force their product market rivals to become more competitive.
A SIMPLIFIED METHOD FOR THE WATER-EQUIVALENT DIAMETER CALCULATION TO ESTIMATE PATIENT DOSE IN CT EXAMINATIONS
Authors: Anam Choirul , Arif Idam , Haryanto Freddy , Widita Rena , Lestari Fauzia P , Adi Kusworo , Dougherty Geoff
Published: November 2018

We proposed and evaluated a water-equivalent diameter calculation without using a region of interest (ROI), (Dw,t) and compared it with the results of using a ROI fitted to the patient border (Dw,f). Evaluations were carried out on thoracic and head CT images. We found that the difference between Dw,t and Dw,f was within 5% for all images in the head region, and most images were within 5% (27 of the 30 patients, 90%) in the thoracic region. We also proposed a method to automatically detect and eliminate the patient table (or head support) from images and evaluated the water-equivalent diameter values after the table had been removed (Dw,nt). This method was able to recognize and remove the patient table from all images used. By removing the table, the water-equivalent diameter (Dw,nt) became more accurate and the difference from Dw,f was within 5% for all images (head and thoracic images).
The Effect of ICU Diaries on Psychological Outcomes and Quality of Life of Survivors of Critical Illness and Their Relatives: A Systematic Review and Meta-Analysis
Authors: McIlroy Philippa A. , King Rebecca S. , Garrouste-Orgeas Maité , Tabah Alexis , Ramanan Mahesh
Published: November 2018

Objectives:

To evaluate the effect of ICU diaries on posttraumatic stress disorder symptoms in ICU survivors and their relatives. Secondary objectives were to determine the effect on anxiety, depression, and health-related quality of life in patients and their relatives.

Data Sources:

We searched online databases, trial registries, and references of relevant articles.

Study Selection:

Studies were included if there was an ICU diary intervention group which was compared with a group without a diary.

Data Extraction:

Titles, abstracts, and full-text articles were reviewed independently by two authors. Data was abstracted using a structured template.

Data Synthesis:

Our search identified 1,790 articles and retained eight studies for inclusion in the analysis. Pooled results found no significant reduction in patients’ posttraumatic stress disorder symptoms with ICU diaries (risk ratio, 0.75 [0.3–1.73]; p = 0.5; n = 3 studies); however, there was a significant improvement in patients’ anxiety (risk ratio, 0.32 [0.12, 0.86]; p = 0.02; n = 2 studies) and depression (risk ratio, 0.39 [0.17–0.87]; p = 0.02; n = 2 studies) symptoms. Two studies reported significant improvement in posttraumatic stress disorder symptoms of relatives of ICU survivors; however, these results could not be pooled due to reporting differences. One study reported no significant improvement in either anxiety (risk ratio, 0.94; 95% [0.66–1.33]; p = 0.72) or depression (risk ratio, 0.98; 95% [0.5–1.9]; p = 0.95) in relatives. There was a significant improvement in health-related quality of life of patients with a mean increase in the Short Form-36 general health score by 11.46 (95% CI, 5.87–17.05; p ≤ 0.0001; n = 2 studies). No studies addressed health-related quality of life of relatives.

Conclusions:

ICU diaries decrease anxiety and depression and improve health-related quality of life, but not posttraumatic stress disorder among ICU survivors and may result in less posttraumatic stress disorder among relatives of ICU patients. Multicenter trials with larger sample sizes are necessary to confirm these findings.
Melanoma Explorer: a web application to allow easy reanalysis of publicly available and clinically annotated melanoma omics data sets
Authors: Strbenac Dario , Wang Kevin , Wang Xinyue , Dong Jiamin , Mann Graham J. , Mueller Samuel , Yang Jean Y.H.
Published: November 2018

Validating newly discovered biomarkers in large, publicly available data sets is often difficult and requires specialized computer programming skills. Melanoma Explorer is a web application that enables easy interrogation of melanoma omics data sets that are freely available in online data repositories with a point-and-click interface. Two use cases are demonstrated. First, the relationship of lysozyme mRNA expression is shown to be prognostic in two independent gene expression microarray data sets. Second, a figure from a journal article showing the relationship of tumour thickness and miR-382 abundance is reproduced. Melanoma Explorer is demonstrated to be a useful tool for reproducing results of published studies and providing additional evidence for biomarkers in independent data sets.
Epidemiology of cutaneous melanoma and melanoma in situ: a 10-year nationwide retrospective cohort study in South Korea
Authors: Soh Byung Woo , Kim You Chan , Choi Jee Woong
Published: November 2018

Numerous studies on the epidemiology of cutaneous melanoma (CM) have been reported for Caucasians, but rarely for Asian populations including Korea. The aim of this study was to investigate the epidemiology of CM and melanoma in situ (MIS) in the Korean population. We investigated a nationally representative sample cohort of over one million Koreans for patients diagnosed with CM and MIS. Annual and overall incidence rates, as well as the survival rate of CM during the study period (2004–2013), were estimated. Demographic factors associated with survival rates and other clinical features of CM and MIS were evaluated and compared with an age-matched, sex-matched, and income level-matched control group. The overall incidence was 1.09 (95% confidence interval, 0.87–1.41) per 100 000 person-years, which was low compared with Caucasians. The incidence rate had increased by 1.07-fold yearly during the 10-year follow-up period (P < 0.001). Five-year and 10-year survival rates of the melanoma patient group were 85.5 and 66.2%, respectively, and were also lower than those of the Caucasian population. The most frequently involved site was the lower limb, followed by the head and neck. Old age and diabetes were associated with an increased risk of melanoma-specific death, whereas surgical excision was a factor associated with decreased overall and melanoma-specific death rates irrespective of the stage of CM. Our data provide a better understanding of the characteristics of CM, especially in the Korean population, and warrant further study into the association between CM and other comorbid conditions.
Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts
Authors: Tang Tina , Brownstein Seymour , Chen Henry , Jordan David R. , Iacob Codrin E. , Blanco Paula , Farmer James
Published: November 2018

Purpose:

Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as “intratarsal epidermal inclusion cysts” or “epidermoid cysts.” It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis.

Methods:

A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant).

Results:

Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each).

Conclusions:

These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.
Mini-Open Surgical Fasciotomy for Chronic Exertional Compartment Syndrome of the Forearm in Professional Motorcycling Adolescents
Authors: Schiavi Paolo , Gondolini Giorgio , Gandolfi Cecilia Eugenia , Guardoli Luca , Vaienti Enrico , Zasa Michele
Published: November 2018

Objective:

Evaluate treatment and outcome of mini-open fasciotomy (MOF) in a population of adolescent motorcycling racers affected by forearm chronic exertional compartment syndrome (CECS).

Design:

Prospective case series.

Setting:

University hospital/private practice.

Patients:

Nine professional motorcycling adolescents were diagnosed with forearm CECS. All were treated with MOF between 2007 and 2012 and followed for a minimum of 5 years (range 5–10 years). Age, sex, body mass index, laterality, and profession were recorded.

Interventions:

A MOF to obtain decompression of all compartments was performed in all patients.

Main outcome measures:

Visual analog scale; a subjective scale to measure strength; and Quick-DASH functional scores. Time to resume full riding capacities as the short-term evaluation.

Results:

A significant decrease in visual analog scale (P < 0.001) and Quick-DASH (P < 0.001) scores was observed in the first 3 months, stabilizing during follow-up (P = 0.521; P = 0.217). Average time to return to sport was 2.8 ± 1 week. No symptom recurrence was reported, but one patient suffered a minor complication. There were no cases of infection, hematoma, or peripheral nerve injury.

Conclusions:

We assess that MOF can be a valid alternative for the treatment of forearm CECS in adolescent competitive motorcycling racers, as demonstrated by the good success rate and minimal incidence of complications during follow-up.

Level of Evidence:

IV, case series.
Probiotic Yogurt for the Prevention of Antibiotic-associated Diarrhea in Adults
Authors: Velasco María , Requena Teresa , Delgado-Iribarren Alberto , Peláez Carmen , Guijarro Carlos
Published: November 2018

Goal:

To evaluate the effect of yogurt supplemented with probiotic bacteria on the prevention of antibiotic-associated diarrhea (AAD) in hospitalized patients.

Background:

Diarrhea following antibiotic administration is a frequent clinical problem. The usefulness of probiotics for the prevention of AAD in the hospitalized adult population remains unclear.

Study:

A randomized, double-blind, placebo-controlled clinical trial was conducted in hospitalized patients who started antibiotic treatment. Patients were randomized (2:2:1) to receive a daily amount of 200 mL of placebo-yogurt (Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus), 200 mL of probiotic yogurt (previous plus Lactobacillus acidophilus La-5, Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus casei subsp. casei Lc-01 or no yogurt (unblinded control) within 48 hours of beginning the antibiotic therapy and up to 5 days after stopping the antibiotic. Patients were followed up with for 1 month to determine occurrence of diarrhea.

Results:

We included 314 patients, mean age 76 years. The rate of diarrhea was 23.0% in the probiotic group versus 17.6% in the placebo group, absolute risk reduction −5.35% (95% confidence interval, −15.4% to 4.7%; P=0.30). Rate of diarrhea was similar in the unblinded external control and in the blinded study groups combined (20.9% vs. 20.2% respectively; P=0.91). There was no difference in the duration of diarrhea, maximum number of bowel movements or prolonged admission because of diarrhea among the groups. All-cause mortality did not differ between groups.

Conclusions:

The combined probiotic strains LA-5, BB-12, and LC-01 do not have an effect in the prevention of AAD in hospitalized patients.
The Model to Estimate Survival in Ambulatory Hepatocellular Carcinoma Patients Aids in the Decision for TACE Retreatment
Authors: Cho Young Youn , Yu Su Jong , Yoo Jung-Ju , Lee Minjong , Lee Dong Hyeon , Cho Yuri , Yoon Kyoung Wan , Cho Eun Ju , Lee Jeong-Hoon , Kim Yoon Jun , Yoon Jung-Hwan
Published: November 2018

Background/Aims:

Transarterial chemoembolization (TACE) is a major therapeutic modality for patients with unresectable hepatocellular carcinoma, which needs repeated treatments. Model to Estimate Survival in Ambulatory Hepatocellular carcinoma patients (MESIAH) was recently developed as a model for predicting survival. We aimed to develop a novel index for TACE retreatment using MESIAH scores.

Patients and Methods:

From 2005 to 2008, 783 patients with hepatocellular carcinoma who had undergone 1 previous TACE procedure were enrolled. We calculated their pre-TACE and post-TACE-MESIAH and calculated the MESIAH ratio by dividing the post-TACE by pre-TACE score. The discriminatory abilities of the MESIAH ratio and post-TACE-MESIAH were compared with ART and ABCR scores.

Results:

Among 783 patients, 355 (45.3%) received a second TACE (test set), and 195 (24.9%) patients received a third TACE treatment (validation set). In the test set, patients with a MESIAH ratio <0.9 obtained longer overall survival than patients with a MESIAH ratio ≥0.9 [26.0 vs. 9.0 mo, respectively; hazard ratio 1.66 (1.29-2.14)], and patients with a post-TACE-MESIAH<4.5 showed longer overall survival than patients with a post-TACE-MESIAH≥4.5 [38.0 vs. 7.0 mo, respectively; hazard ratio, 3.17 (2.45-4.09)]. The post-TACE-MESIAH [C-index 0.663 (0.628-0.697)] was better than the ART [C-index 0.596 (0.554-0.638)] and ABCR scores [C-index 0.576 (0.536-0.617)] at estimating prognosis. Our results were confirmed by the validation set.

Conclusions:

A MESIAH score ≥4.5 after TACE identifies patients with a poor prognosis. Randomized studies are needed to establish whether additional TACE may affect survival.
Current First-line Therapy for Ovarian Cancer: A Comprehensive Review
Authors: Pierce Stuart R. , Clark Leslie H.
Published: November 2018

Importance

Ovarian, fallopian tube, and primary peritoneal cancers constitute the deadliest gynecologic malignancies. After primary cytoreductive surgery, there are several standard first-line cytotoxic treatments for providers to consider. Newer molecular targeted therapies are becoming more common and may have a role as first-line therapy in the future.

Objective

This article provides an evidence-based review of all approved standard therapies for first-line treatment of advanced-stage, high-grade serous ovarian cancer. Treatment schedules, dose modifications, and drug substitutions are reviewed. Ongoing trials and pending approvals for newer molecular therapies are discussed.

Evidence Acquisition

A comprehensive primary literature review was performed using MEDLINE, the Cochrane Collaborative Database, and PubMed. Guidelines from the National Comprehensive Cancer Network and the Society for Gynecologic Oncology were also reviewed.

Results

Seven different approved first-line regimens for high-grade serous ovarian cancer are available based on literature review. These vary in route of administration, dose intensity, drug combinations, and treatment schedules. Molecular targeted therapies, including antiangiogenic drugs and poly(ADP-ribose) polymerase inhibitors, have also been studied in multiple randomized controlled trials in the first-line setting.

Conclusions and Relevance

Cytotoxic regimens remain the foundation of first-line treatment for high-grade serous ovarian cancer. Choosing which regimen is best for a patient depends on both patient and disease factors. Molecular therapies in first-line treatment are a promising and exciting possibility, with regulatory approval pending.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to compare the 7 approved up-front cytotoxic regimens for high-grade serous ovarian cancer; choose a regimen based on patient and disease factors; and distinguish 3 molecular therapies that are in clinical trials that may be incorporated into up-front therapy.
Telementoring Demonstration in Craniofacial Surgery With HoloLens, Skype, and Three-Layer Facial Models
Authors: Mitsuno Daisuke , Hirota Yuka , Akamatsu Jun , Kino Hiromi , Okamoto Toyoko , Ueda Koichi
Published: November 2018

Background:

Telementoring is the technology for providing surgical instruction from a remote place via a network. To demonstrate the use of telementoring in craniofacial surgery, Skype and a mixed reality device HoloLens were adopted, and 3-layer facial models had been developed.

Methods:

A resident in hospital A used the model surgery under remote guidance by a mentor surgeon in hospital B 4 times on different dates. The straight-line between hospitals A and B is 250 km. The mentor gave the resident guidance via Skype and HoloLens, communicating by voice, and video of the surgical field, and providing reference data.

Results:

There was no delay in voice communication and a delay of <0.5 seconds in the video. The resident was able to confirm the main landmarks of the surgical field and to grasp the situation without problems. The mentor could send appropriate instructions by voice, could point out a specific part by telestration function, and could draw lines on the 2-dimentional images pasted on the operator's field of vision.

Discussion:

With the use of HoloLens, Skype, and the 3-layer models, it was possible to demonstrate telementoring. The risk of personal information leakage due to data interception seems to be very low because its data communication is encrypted with advanced encryption standard.

Conclusion:

This telementoring system has various advantages and many improvable aspects in the field of craniofacial surgery.
Personal Computer-Based Cephalometric Landmark Detection With Deep Learning, Using Cephalograms on the Internet
Authors: Nishimoto Soh , Sotsuka Yohei , Kawai Kenichiro , Ishise Hisako , Kakibuchi Masao
Published: November 2018

Background:

Cephalometric analysis has long been, and still is one of the most important tools in evaluating craniomaxillofacial skeletal profile. To perform this, manual tracing of x-ray film and plotting landmarks have been required. This procedure is time-consuming and demands expertise. In these days, computerized cephalometric systems have been introduced; however, tracing and plotting still have to be done on the monitor display. Artificial intelligence is developing rapidly. Deep learning is one of the most evolving areas in artificial intelligence. The authors made an automated landmark predicting system, based on a deep learning neural network.

Methods:

On a personal desktop computer, a convolutional network was built for regression analysis of cephalometric landmarks’ coordinate values. Lateral cephalogram images were gathered through the internet and 219 images were obtained. Ten skeletal cephalometric landmarks were manually plotted and coordinate values of them were listed. The images were randomly divided into 153 training images and 66 testing images. Training images were expanded 51 folds. The network was trained with the expanded training images. With the testing images, landmarks were predicted by the network. Prediction errors from manually plotted points were evaluated.

Results:

Average and median prediction errors were 17.02 and 16.22 pixels. Angles and lengths in cephalometric analysis, predicted by the neural network, were not statistically different from those calculated from manually plotted points.

Conclusion:

Despite the variety of image quality, using cephalogram images on the internet is a feasible approach for landmark prediction.
Approaches for Excision of Intramasseteric Nodules
Authors: Aizawa Tetsushi , Kubo Satoshi , Azuma Ryuichi , Kiyosawa Tomoharu
Published: November 2018

Developmental lesions, including benign or malignant tumors, rarely arise in the masseteric region. This retrospective study was performed to evaluate the adequacy of different surgical approaches in a series of patients with lesions in the masseteric region. The surgical methods, postoperative complications, pathological diagnosis, and aesthetic outcome were compared in 4 patients who underwent excision of intramasseteric mass lesions. A flap was elevated in 3 patients and direct incisional resection was performed in 1 patient. Two patients underwent incisional biopsy to exclude malignancy before the total excision was performed. The final diagnosis was hemangioma in 3 patients and schwannoma in 1 patient. All patients were satisfied with the aesthetic results and there were no major complications. In conclusion, surgery with skin flap elevation was concluded to be the best approach based on overall assessment of technical considerations, complications, and the cosmetic outcome. However, the surgeon should not hesitate to perform direct incisional biopsy when malignancy needs to be excluded.
ICTV Virus Taxonomy Profile: Nodaviridae
Authors: Sahul Hameed A. S. , Ninawe A. S. , Nakai T. , Chi S. C. , Johnson K. L. ,   ICTV Report Consortium
Published: November 2018

The family Nodaviridae includes two genera, Alphanodavirus and Betanodavirus. The family name derives from the Japanese village of Nodamura where Nodamura virus was first isolated from Culex tritaeniorhynchus mosquitoes. Virions are non-enveloped and spherical in shape with icosahedral symmetry (T=3) and diameters ranging from 25 to 33 nm. The genome consists of two molecules of single-stranded positive-sense RNA: RNA1 and RNA2. The virion capsid consists of 180 protein subunits arranged on a T=3 surface lattice. Alphanodaviruses infect insects, whereas betanodaviruses are pathogens of fish. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Nodaviridae, which is available at www.ictv.global/report/nodaviridae.
A factorial cluster-randomised controlled trial combining home-environmental and early child development interventions to improve child health and development: rationale, trial design and baseline findings
Authors: Hartinger Stella M , Nuño Nestor , Hattendorf Jan , Verastegui Hector , Ortiz Mariela , Mäusezahl Daniel
Published: November 2018

Background

Exposure to unhealthy environments and poor cognitive development are the main risk factors that affect children’s health and wellbeing in low- and middle-income countries. Interventions that simultaneously address several risk factors at the household level have great potential to reduce these negative effects. We present the design and baseline findings of a cluster-randomised controlled trial to evaluate the impact of an integrated home-environmental intervention package and an early child development programme to improve diarrhoea, acute respiratory infections and childhood developmental outcomes in children under 36 months of age living in resource-limited rural Andean Peru.

Methods

We collected baseline data on children’s developmental performance, health status and demography as well as microbial contamination in drinking water. In a sub-sample of households, we measured indoor and personal 24-hour air concentration levels of carbon monoxide (CO) and fine particulate matter (PM2.5).

Results

We recruited and randomised 317 children from 40 community-clusters to four study arms. At baseline, all arms had similar health and demographic characteristics, and the developmental status of children was comparable between arms. The analysis revealed that more than 25% of mothers completed primary education, a large proportion of children were stunted and diarrhoea prevalence was above 18%. Fifty-two percent of drinking water samples tested positive for thermo-tolerant coliforms and the occurrence ofE.coliwas evenly distributed between arms. The mean levels of kitchen PM2.5and CO concentrations were 213 μg/m3and 4.8 ppm, respectively.

Conclusions

The trial arms are balanced with respect to most baseline characteristics, such as household air and water pollution, and child development. These results ensure the possible estimation of the trial effectiveness. This trial will yield valuable information for assessing synergic, rational and cost-effective benefits of the combination of home-based interventions.

Trial registration

retrospectively registered on 15thJanuary 2018. SRCTN reference: 26548981
Correlation of Remodeling Brain and Phenotype Behavior in the Comorbidity of the Chronic Obstructive Pulmonary Disease and Acute Cerebral Ischemia in Animal Model
Authors: Plekhova Natalia G. , Geltser Boris I. , Zinoviev Sergey V. , Zayats Yulia V.
Published: November 2018

Cognitive impairment is one of the most common features in patients with COPD, and is associated with COPD severity and comorbidities. Development of relevant models of respiratory-cerebrovascular comorbidity in human diseases is an important task of experimental medicine. The purpose of the research consisted in determination of the morphological criteria brain condition and their correlation with behavioral phenotype of animals in the experimental comorbidity of the chronic obstructive pulmonary disease (COPD) and acute cerebral ischemia (ACI). Modeling of COPD on the basis of the combination of inducers, reproducing a proteoclastic degradation of lung tissue and systemic inflammation, and modeling of ACI by the suture middle cerebral artery occlusion with to mimic ischemia condition were used. Comparative histological study of the brain, neurological and behavioral phenotype of animals was conducted. It has been shown that in case of COPD and ACI comorbidity, formation of neurogliovascular microstructural complexes in brain is more pronounced than at animals with isolated form of disease, which was indicative of active adaptive transformation of neocortex. Significant disturbance of neurological and behavioral status of animals under the conditions of COPD and ACI comorbidity was correlated with the structural changes in the microvascular layer and neurons of brain. This study provides new insights about formation of neurogliovascular complexes with altered quantitative ratio in the vessels that was indicative of the presence of pericellular and perivascular edemas of the brain, and correlating of the these changes with the behavior of animals.
Ribosomal stress-induced senescence as a novel pro-senescence strategy for p16 positive basal-like breast cancer
Authors: Moore Madeleine , Gammon Luke , Dreger Sally , Koh James , Garbe James C , Stampfer Martha R , Philpott Michael , Jones Louise , Bishop Cleo L
Published: November 2018

Re-engaging the senescent programme represents an attractive yet underexplored strategy for cancer therapy, particularly for those tumour subtypes where targeted agents are limited or unavailable. Here, we identify a specific subset of ribosomal proteins as novel pro-senescence therapeutic targets for a highly aggressive subtype of breast cancer, p16 positive basal-like breast cancer. Mechanistically, ribosomal stress-induced senescence generates a stable cell cycle arrest, is dependent on endogenous p16 triggering a resensitisation to the p16/RB tumour suppressor axis, followed by establishment of a senescence-associated secretory phenotype, and is independent of DNA damage. Conversely, ribosomal protein knockdown in a p16 negative breast cancer model results in caspase-mediated apoptosis. Importantly, individual ribosomal protein loss is well tolerated by a panel of normal human cells. We demonstrate a reciprocal feedback loop between loss of RPS3A and RPS7 at both the transcriptional and post-transcriptional level during ribosomal stress-induced senescence. Further, our ribosomal hits are co-ordinately dysregulated in breast cancer, with elevated expression associated with a poor prognosis. Clinical relevance is demonstrated in tissue microarrays, and a RPS3AHIGHRPS7HIGHsignature is associated with an earlier disease onset and synergises with p16 to further worsen patient outcome. We conclude that dysregulation of ribosomal proteins constitutes a cancer cell-specific mechanism of senescence evasion and that engaging ribosomal stress-induced senescence may be relevant for future pro-senescence therapies.
Topological phase transitions in functional brain networks
Authors: Santos Fernando A. N. , Raposo Ernesto P. , Coutinho-Filho Maurício D. , Copelli Mauro , Stam Cornelis J. , Douw Linda
Published: November 2018

Functional brain networks are often constructed by quantifying correlations among brain regions. Their topological structure includes nodes, edges, triangles and even higher-dimensional objects. Topological data analysis (TDA) is the emerging framework to process datasets under this perspective. In parallel, topology has proven essential for understanding fundamental questions in physics. Here we report the discovery of topological phase transitions in functional brain networks by merging concepts from TDA, topology, geometry, physics, and network theory. We show that topological phase transitions occur when the Euler entropy has a singularity, which remarkably coincides with the emergence of multidimensional topological holes in the brain network. Our results suggest that a major alteration in the pattern of brain correlations can modify the signature of such transitions, and may point to suboptimal brain functioning. Due to the universal character of phase transitions and noise robustness of TDA, our findings open perspectives towards establishing reliable topological and geometrical biomarkers of individual and group differences in functional brain network organization.
Neural envelope tracking as a measure of speech understanding in cochlear implant users
Authors: Verschueren Eline , Somers Ben , Francart Tom
Published: November 2018

The speech envelope is essential for speech understanding and can be reconstructed from the electroencephalogram (EEG) recorded while listening to running speech. This so-called neural envelope tracking has been shown to relate to speech understanding in normal hearing listeners, but has barely been investigated in persons wearing cochlear implants (CI). We investigated the relation between speech understanding and neural envelope tracking in CI users.

EEG was recorded in 8 CI users while they listened to a story. Speech understanding was varied by changing the intensity of the presented speech. The speech envelope was reconstructed from the EEG using a linear decoder and then correlated with the envelope of the speech stimulus as a measure of neural envelope tracking which was compared to actual speech understanding.

This study showed that neural envelope tracking increased with increasing speech understanding in every participant. Furthermore behaviorally measured speech understanding was correlated with participant specific neural envelope tracking results indicating the potential of neural envelope tracking as an objective measure of speech understanding in CI users. This could enable objective and automatic fitting of CIs and pave the way towards closed-loop CIs that adjust continuously and automatically to individual CI users.
Association of brain age with smoking, alcohol consumption, and genetic variants
Authors: Ning Kaida , Zhao Lu , Matloff Will , Sun Fengzhu , Toga Arthur W.
Published: November 2018

The association of the degree of aging based on the whole-brain anatomical characteristics, or brain age, with smoking, alcohol consumption, and individual genetic variants is unclear. Here, we investigated these associations through analyzing data collected for UK Biobank subjects with an age range of 45 to 79 years old. We first trained a statistical model for obtaining relative brain age (RBA), a metric describing a subject’s brain age relative to peers, based on a randomly selected training set subjects (n=2,679). We then applied this model to the evaluation set subjects (n=6,252) and further tested the association of RBA with tobacco smoking, alcohol consumption, and 529,098 genetic variants. We found that daily or almost daily consumption of smoking or alcohol was significantly associated with increased RBA (P<0.05). Interestingly, there was no significant difference of RBA among subjects who smoked occasionally, only tried once or twice, or abstained from smoking. Further, there was no significant difference of RBA among subjects who consumed alcohol 1 to 3 times a month, at special occasions only, or abstained from alcohol consumption. Among the subjects who smoked on most or all days and did not abstain from alcohol drinking, RBA increased by 0.021 years for each addition pack-year of smoking (P<0.05) and by 0.014 years for each additional gram of alcohol consumed (P<0.05). We did not identify individual genetic variation significantly associate with RBA. Further exploration of genetic variation-brain aging association is warranted, where our current genetic association statistics may serve as prior knowledge.
Emotion Schemas are Embedded in the Human Visual System
Authors: Kragel Philip A. , Reddan Marianne , LaBar Kevin S. , Wager Tor D.
Published: November 2018

Theorists have suggested that emotions are canonical responses to situations ancestrally linked to survival. If so, then emotions may be afforded by features of the sensory environment. However, few computationally explicit models describe how combinations of stimulus features evoke different emotions. Here we develop a convolutional neural network that accurately decodes images into 11 distinct emotion categories. We validate the model using over 25,000 images and movies and show that image content is sufficient to predict the category and valence of human emotion ratings. In two fMRI studies, we demonstrate that patterns of human visual cortex activity encode emotion category-related model output and can decode multiple categories of emotional experience. These results suggest that rich, category-specific emotion representations are embedded within the human visual system.