bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does A Longer Waiting Period After Neoadjuvant Radio-chemotherapy Improve the Oncological Prognosis of Rectal Cancer?
Authors: Lefèvre Jérémie H. , Mineur Laurent , Cachanado Marine , Denost Quentin , Rouanet Philippe , de Chaisemartin Cécile , Meunier Bernard , Mehrdad Jafari , Cotte Eddy , Desrame Jérome , Karoui Mehdi , Benoist Stéphane , Kirzin Sylvain , Berger Anne , Panis Yves , Piessen Guillaume , Saudemont Alain , Prudhomme Michel , Peschaud Frédérique , Dubois Anne , Loriau Jérome , Tuech Jean-Jacques , Meurette Guillaume , Lupinacci Renato , Goasguen Nicolas , Creavin Ben , Simon Tabassome , Parc Yann 
Published: September 2019

Objective:
The aim of this study was to report the 3-year survival results of the GRECCAR-6 trial.

Summary Background Data:
Current data on the effect of an extended interval between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0) is controversial. Furthermore, its effect on oncological outcomes is unknown.

Methods:
The GRECCAR-6 trial was a phase III, multicenter, randomized, open-label, parallel-group, controlled trial. Patients with cT3/T4 or TxN+ tumors of the mid or lower rectum who had received RCT (45–50 Gy with 5-fluorouracil or capecitabine) were included and randomized into a 7- or 11-week waiting period. Primary endpoint was the pCR rate. Secondary endpoints were 3-year overall (OS), disease-free survival (DFS), and recurrence rates.

Results:
A total of 265 patients from 24 participating centers were enrolled. A total of 253 patients underwent a mesorectal excision. Overall pCR rate was 17% (43/253). Mean follow-up from surgical resection was 32 ± 8 months. Twenty-four deaths occurred with an 89% OS at 3 years. DFS was 68.7% at 3 years (75 recurrences). Three-year local and distant recurrences were 7.9% and 23.8%, respectively. The randomization group had no impact on the 3-year OS (P = 0.8868) or DFS (P = 0.9409). Distant (P = 0.7432) and local (P = 0.3944) recurrences were also not influenced by the waiting period. DFS was independently influenced by 3 factors: circumferential radial margin (CRM) ≤1 mm [hazard ratio (HR) = 2.03; 95% confidence interval (CI), 1.17–3.51], ypT3-T4 (HR = 2.69; 95% CI, 1.19–6.08) and positive lymph nodes (HR = 3.62; 95% CI, 1.89–6.91).

Conclusion:
Extending the waiting period by 4 weeks following RCT has no influence on the oncological outcomes of T3/T4 rectal cancers.
Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy
Authors: Schröder Wolfgang , Raptis Dimitri A. , Schmidt Henner M. , Gisbertz Suzanne S. , Moons Johnny , Asti Emanuele , Luyer Misha D. P. , Hölscher Arnulf H. , Schneider Paul M. , van Berge Henegouwen Mark I. , Nafteux Philippe , Nilsson Magnus , Räsanen Jari , Palazzo Francesco , Mercer Stuart , Bonavina Luigi , Nieuwenhuijzen Grard A. P. , Wijjnhoven Bas P. L. , Pattyn Piet , Grimminger Peter P. , Bruns Christiane J. , Gutschow Christian A. 
Published: September 2019

Objective:
The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity.

Background:
ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated.

Patients and Methods:
Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI).

Results:
Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0–36] vs 29 [IQR 0–40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE.

Conclusion:
Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.
Interrater Agreement Between Critical Care Providers for Background Classification and Seizure Detection After Implementation of Amplitude-Integrated Electroencephalography in Neonates, Infants, and Children
Authors: Bourgoin Pierre , Barrault Victoire , Loron Gauthier , Roger Alexandre , Bataille Emmanuelle , Leclair-Visonneau Laurène , Joram Nicolas , Chenouard Alexis 
Published: September 2019

Purposes:
Amplitude-integrated EEG (aEEG) has been widely developed in neonatal intensive care unit, but few studies focused on pediatric intensive care unit. Furthermore, reliability of aEEG under real-life conditions is unknown.

Methods:
Participants were nurses from a 12-bed pediatric intensive care unit in a referral university hospital in France. Amplitude EEG was implemented after standardized training, including e-learning course, individual feedback and bedside teaching concerning monitoring installation, background classification patterns recognition, artefact analysis, and seizure detection. The primary judgment criterion was the agreement (Cohen Kappa) between nurses and aEEG experts for the detection of abnormal aEEG traces (moderately or severely altered background pattern according to Hellström–Westas classification and/or seizure activity).

Results:
During the study period, 196 consecutives traces from 79 patients were analyzed by 51 nurses. According to expert's classification, 53% of traces were abnormal, including 17.5% of severely abnormal traces (severely altered traces and/or seizure activity) and 14% exhibiting seizure activity. Moderate agreement between experts and nurses was found for detection of any abnormal trace (k = 0.53; 95% confidence interval [CI]: 0.39–0.67). Substantial agreement was found for severely altered traces (k = 0.71; 95% CI: 0.57–0.85). Finally, fair agreement was found for seizure detection (irrespective of background classification, k = 0.40; 95% CI: 0.25–0.54).

Conclusions:
These results suggest that aEEG monitoring may be implemented in routine nursing care in pediatric intensive care unit. Further training courses are needed to enhance nurses' skill in detecting seizures activity at the bedside.
Information and genetic counselling for psychiatric risks in children with rare genomic disorders
Authors: Cuthbert Andrew , Challenger Aimee , Hall Jeremy , van den Bree Marianne BM 
Published: September 2019

AbstractPurposeGenomic medicine has transformed the diagnosis of neurodevelopmental disorders. Evidence of increased psychiatric comorbidity associated with genomic copy number and single nucleotide variants (CNV and SNV) may not be fully considered when providing genetic counselling. We explored parents’ experiences of genetics services and how they obtained information concerning psychiatric manifestations.MethodsParents of children diagnosed with genomic variants completed an online survey exploring, (i) how they experienced the genetic diagnosis, and (ii) how they acquired information about psychiatric, developmental and physical manifestations.ResultsTwo-hundred and 86 respondents completed the survey. Thirty percent were unsatisfied with receiving genetic diagnoses. Satisfaction was predicted if communication was by geneticists (p = 0.004); provided face-to-face (p = 0.003); clearly explained (p < 0.001); and accompanied by support (p = 0.017). Parents obtained psychiatric information from non-professional sources more often than developmental (ϕ 0.26, p < 0.001) and physical manifestations (ϕ 0.21, p = 0.003), which mostly came from health professionals. Information from support organisations was more helpful than from geneticists (odds ratio [OR] 21.0, 95% CI 5.1 – 86.8, p < 0.001); paediatricians (OR 11.0, 1.4 – 85.2, p = 0.004); and internet sites (OR 15.5, 3.7 – 64.8, p < 0.001).ConclusionA paucity of professional information about psychiatric risks after genetic diagnosis may impede early diagnosis and intervention for children with high genotypic risks. Planned integration of genomic testing into mainstream services should include genetic counselling training to address the full spectrum of developmental, physical and psychiatric manifestations and timely provision of high-quality information.
Futility of combining griseofulvin and terbinafine in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
Authors: Singh Sanjay , Anchan Vinayak N , Raheja Radhika 
Published: September 2019

AbstractBackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine plus griseofulvin versus terbinafine alone in tinea corporis, tinea cruris and tinea faciei in a randomized pragmatic open trial.MethodsOne hundred and thirty two microscopy confirmed patients were randomly allocated (ratio 1:1) to two groups, terbinafine (T) and terbinafine plus griseofulvin (T+G). Doses given were as follows: T, oral terbinafine (6 mg/kg/day, maximum 500 mg/day, once daily); T+G, terbinafine (as above) plus oral griseofulvin (children [<18 years] 10 mg/kg/day, adults [18 years or more] 10 mg/kg/day, but not <500 mg and not >1000 mg per day, in two divided doses). Patients were treated for 8 weeks or cure, whichever occurred earlier.ResultsAt 4 weeks, none of the patients were cured in both groups. At 6 weeks, 1(1.5%) and 4 (6.1%) patients were cured in T and T+G groups, respectively (P=0.417). At 8 weeks, 17 (25.8%) and 19 (28.8%) patients were cured in T and T+G groups, respectively (P=0.845). For cure rate at 8 weeks, number needed to treat (NNT) for T+G (versus T), was 33.ConclusionsAddition of griseofulvin to terbinafine does not increase effectiveness of terbinafine in current epidemic of altered dermatophytosis in India.
Three-Compartment Model of CAR T-cell Immunotherapy
Authors: de Jesus Rodrigues Brendon , Barros Luciana R. Carvalho , Almeida Regina C. 
Published: September 2019

AbstractImmunotherapy has gained great momentum with chimeric antigen receptor T-cell (CAR T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens to increase tumor elimination efficiency. Improved CAR T cell immunotherapy requires a better understanding of the interplay between CAR T cell doses and tumor burden, administration protocol, toxicity, resistance to immunotherapy, among other features. We developed a three-compartment mathematical model to describe tumor response to CAR T cell immunotherapy in immunodeficient mouse models. It encompasses interactions between tumor cells, effector and long-term memory CAR T cells such as tumor induced immunosuppression effects, conversion of memory T cells into effector T cells in the presence of tumor cells, and individual specificities considered as uncertainties in the parameters of the model. The model was able to represent two different immunotherapy scenarios with different CAR receptors and tumor targets reported in the literature. Further in silico studies considering different dosing quantities and tumor burden showed that the proposed model can represent the three possible therapy outcomes: tumor elimination, equilibrium, and escape. We found that therapy effectiveness may also depend on small variations in the parameter values, regarded as intrinsic individual specificities, as T cell proliferation capacity, as well as immunosuppressive tumor microenvironment factors. These issues may significantly reduce the chance of tumor elimination. In this way, the developed model provides potential use for assessing different CAR T cell protocols and associated efficacy without further in vivo experiments.
Dynamics of genetic code evolution: The emergence of universality
Authors: Argyriadis John-Antonio , He Yang-Hui , Jejjala Vishnu , Minic Djordje 
Published: September 2019

AbstractWe study the dynamics of genetic code evolution. The algorithm of Vetsigian et al. [1] provides a solution that is both optimal and universal. We reproduce and analyze the algorithm as a dynamical system. All the parameters used in the model are varied to assess their impact on achieving universality. We show that by allowing specific parameters to vary with time, the algorithm converges much faster to a universal solution. Finally, we study automorphisms of the genetic code arising due to this model. We use this to examine the scaling of the solutions in order to understand the origin of universality and find that there is a direct link to mutation rate.
United States wildlife and wildlife product imports from 2000-2014
Authors: Eskew Evan A. , White Allison M. , Ross Noam , Smith Kristine M. , Smith Katherine F. , Rodríguez Jon Paul , Zambrana-Torrelio Carlos , Karesh William B. , Daszak Peter 
Published: September 2019

AbstractThe global wildlife trade network is a massive system that has been shown to threaten biodiversity conservation, introduce non-native species and pathogens, and cause chronic animal welfare concerns. Despite its scale and impact, comprehensive characterization of the global wildlife trade is hampered by data that are limited in their temporal or taxonomic scope and detail. To help fill this gap, we present data on 15 years of the importation of wildlife and their derived products into the United States (2000-2014), originally collected by the United States Fish and Wildlife Service. We curated and cleaned the data and added taxonomic information to improve data usability. These data include > 2 million wildlife or wildlife product shipments, representing > 60 biological classes and > 3.2 billion live organisms. These data will be broadly useful to both scientists and policymakers seeking to better understand the volume, sources, biological composition, and potential risks of the global wildlife trade.
Pancreatic Islets Communicate With the Brain via Vagal Sensory Neurons
Authors: Makhmutova Madina , Weitz Jonathan , Tamayo Alejandro , Pereira Elizabeth , Almaça Joana , Rodriguez-Diaz Rayner , Caicedo Alejandro 
Published: September 2019

SUMMARYDepleting visceral sensory nerves affects pancreatic islet function, glucose metabolism and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. Here we show that the pancreatic islet is innervated by vagal sensory axons expressing substance P, calcitonin-gene related peptide, and serotonin receptor 5HT3R. Vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. These neurons respond to chemical but not mechanical stimulation of the pancreas. By recording activity from nodose neurons in vivo and from sensory axons in living pancreas slices, we show that sensory nerves respond to serotonin secreted from stimulated beta cells. Serotonin is co-released with insulin and therefore conveys information about the secretory state of beta cells via vagal afferent nerves. Our study thus establishes that pancreatic islets communicate with the brain using the neural route and identifies serotonin signaling as a peripheral transduction mechanism.
Large single-locus effects for maturation timing are mediated via body condition in Atlantic salmon
Authors: Debes Paul V , Piavchenko Nikolai , Ruokolainen Annukka , Ovaskainen Outi , Moustakas-Verho Jacqueline E , Parre Noora , Aykanat Tutku , Erkinaro Jaakko , Primmer Craig R 
Published: September 2019

AbstractMaturation timing is a pivotal life-history trait balancing probabilities between mortality and reproduction. Environmental vs. genetic contributions to traits associated with maturation initiation, such as growth and body condition, remain uncertain because of difficulties in determining causality. In Atlantic salmon, maturation timing associates with a large-effect locus around vgll3, but how this locus affects maturation remains unknown. We combined controlled breeding with common-garden experimentation at two temperatures and show that vgll3 effects on maturation of males express primarily via body condition, which we demonstrate in the males’ non-maturing female relatives, thus avoiding reverse causality. Between homozygous vgll3 genotypes, maturation probability differed several folds and female condition differed 2% in both temperature environments. Vgll3 effects explained 25 and 16% of maturation probability heritability and 15 and 6% of female condition heritability, in the warm and cold environment, respectively. Non-significant vgll3 effects on female length were antagonistic to those on condition but of equal proportional size. When controlling for vgll3 effects, genetic correlations changed antagonistically between both maturation and condition vs. growth, suggesting vgll3 as a resource-allocation locus. The results support large vgll3 maturation effects being mediated via environmentally stable body condition effects, enabling rapid co-evolution between the life-history traits.
Unusual genome expansion and transcription suppression in ectomycorrhizal Tricholoma matsutake by repetitive insertions of transposable elements
Authors: Min Byoungnam , Yoon Hyeokjun , Park Julius , Oh Youn-Lee , Kong Won-Sik , Kim Jong-Guk , Choi In-Geol 
Published: September 2019

AbstractGenome sequence of Tricholoma matsutake was revealed as the one of the large fungal genomes published up to date at 189.0 Mbp with 15,305 predicted genes. The unusual size of this fungal genome contained frequent colonization of transposable elements (TEs) occupying more than half of the entire genome. We identified that 702 genes were surrounded by TEs and 83.2% of those genes were never transcribed at any development stage. This observation corroborated that the insertion of transposable elements alters the transcription of the genes neighboring TEs.Repeat-induced point mutation such as C to T hypermutation with a bias over ’CpG’ dinucleotides was also recognized in this genome, representing a typical defense mechanism against TEs during evolution. Many transcription factor genes were activated in both primordia and fruiting body, which indicates that many regulatory processes are shared during developmental stages. Small secreted protein genes (<300 aa) were dominantly transcribed in hyphae, where symbiotic interactions occur with hosts. Comparative analysis with 37 Agaricomycetes genomes revealed that IstB-like domain (PF01695) was conserved in taxonomically diverse mycorrhizal genomes, where the T. matsutake genome contained four copies of this domain. Three of the IstB-like genes were overexpressed in hyphae. In the CAZyme analysis, reduced CAZyme genes were found as other ectomycorrhizal genomes including a lot of loss of glycoside hydrolase genes. Also, auxiliary activity genes were dominantly transcribed in primordia. The T. matsutake genome sequence provides insight into the large genome size and clues to understand unusual fungal genome expansion.
Seasonal influenza circulation patterns and projections for September 2019 to September 2020
Authors: Bedford Trevor , Huddleston John , Potter Barney , Neher Richard A. 
Published: September 2019

AbstractThis report details current seasonal influenza circulation patterns as of August 2019 and makes projections up to September 2020 to coincide with selection of the 2020 Southern Hemisphere vaccine strain. This is not meant as a comprehensive report, but is instead intended as particular observations that we’ve made that may be of relevance. Please also note that observed patterns reflect the GISAID database and may not be entirely representative of underlying dynamics. All analyses are based on the nextflu/nextstrain pipeline [1,2] with continual updates posted to nextstrain.org/flu. A/H3N2: A/H3N2 viruses continue to show substantial diversity in HA sequences with a deep split between 3c3.A and 3c2.A1b viruses. The most notable recent developments are the rapid rise of clade A1b/137F – a subclade of A1b/135K – in China and Bangladesh and clade A1b/197R – a subclade of A1b/131K – which dominates the ongoing season in Australia. Our models predict that A1b/137F and A1b/197R will be the dominant clades next year with A1b/197R accounting for most circulation. There is, however, large uncertainty in the true extent of A1b/137F circulation. A/H1N1pdm: The S183P substitution has risen to near fixation. The most successful subclade carrying this mutation is 183P-5 which has essentially replaced competing variants. A variant with substitutions 129D/185I is at 60% prevalence globally, while a second variant with substitution 130N is at 50% in North America and ~10% elsewhere. Substitutions at site 156 to D or K have arisen sporadically and result in loss of recognition by antisera raised against viruses with asparagine at position 156. Despite the large antigenic effect, viruses with mutations at site 156 don’t seem to spread. Beyond variants at site 156, little to no antigenic evolution is evident in assays with ferret antisera. B/Vic: Antigenically drifted deletion variants at HA1 sites 162, 163 and 164 are now dominating global circulation and have all but taken over. The double deletion variant V1A.1 had previously been circulating at high frequency in the Americas. However, over the course of 2009, the triple deletion variant V1A.3 has increased in frequency globally and is now dominating in all geographic regions. Importantly, V1A.1 and V1A.3 variants appear antigenically distinct by HI assays with 4-8 fold reductions in log2 titer in both directions. B/Yam: B/Yam has not circulated in large numbers since the Northern Hemisphere season 2017/2018 and displays relatively little amino acid variation in HA or antigenic diversity. Amino acid variants at sites 229 and 232 have begun to circulate and population is now split between 229D/232D, 229N/232D and 229D/232N variants. These variants show little sign of antigenic difference in HI assays.
Quantitative analysis of the ubiquitin-proteasome system under proteolytic and folding stressors
Authors: Work Jeremy J. , Brandman Onn 
Published: September 2019

AbstractAging, disease, and environmental stressors are associated with failures in the ubiquitin-proteasome system (UPS), yet a quantitative understanding of how stressors affect the proteome and how the UPS responds is lacking. Here we assessed UPS performance and adaptability in yeast under stressors using quantitative measurements of misfolded substrate stability and stress-dependent UPS regulation by the transcription factor Rpn4. We found that impairing degradation rates (proteolytic stress) and generating misfolded proteins (folding stress) elicited distinct effects on the proteome and on UPS adaptation. Folding stressors stabilized proteins via aggregation rather than overburdening the proteasome, as occurred under proteolytic stress. Still, the UPS productively adapted to both stressors using separate mechanisms: proteolytic stressors caused Rpn4 stabilization while folding stressors increasedRPN4transcription. In some cases, adaptation completely prevented loss of UPS substrate degradation. Our work reveals the distinct effects of proteotoxic stressors and the versatility of cells in adapting the UPS.