bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modularity underlying the performance of unusual locomotor tasks inspired by developmental milestones
Authors: Hinnekens Elodie , Berret Bastien , Do Manh-Cuong , Teulier Caroline 
Published: December 2019

Motor behaviors are often hypothesized to be set up from the combination of a small number of modules encoded in the central nervous system. These modules are thought to combine such that a variety of motor tasks can be realized, from reproducible tasks such as walking to more unusual locomotor tasks that typically exhibit more step-by-step variability. We investigated the impact of step-by-step variability on the modular architecture of unusual tasks compared with walking. To this aim, 20 adults had to perform walking and two unusual modes of locomotion inspired by developmental milestones (cruising and crawling). Sixteen surface electromyography (EMG) signals were recorded to extract both spatial and temporal modules. Modules were extracted from both averaged and nonaveraged (i.e., single step) EMG signals to assess the significance of step-to-step variability when participants practiced such unusual locomotor tasks. The number of modules extracted from averaged data was similar across tasks, but a higher number of modules was required to reconstruct nonaveraged EMG data of the unusual tasks. Although certain walking modules were shared with cruising and crawling, task-specific modules were necessary to account for the muscle patterns underlying these unusual locomotion modes. These results highlight a more complex modularity (e.g., more modules) for cruising and crawling compared with walking, which was only apparent when the step-to-step variability of EMG patterns was considered. This suggests that considering nonaveraged data is relevant when muscle modularity is studied, especially in motor tasks with high variability as in motor development.NEW & NOTEWORTHY This study addresses the general question of modularity in locomotor control. We demonstrate for the first time the importance of intraindividual variability in the muscle modularity of unusual locomotor behaviors that exhibit greater step-by-step variability than standard walking. Crawling and cruising, the unusual locomotor modes considered, are based on a more complex modular organization than walking. More spatial and temporal modules, task specific or shared with walking modules, are needed to reconstruct muscle patterns.
Burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia in humans
Authors: Gousset S. , Mouraux A. , van den Broeke E. N. 
Published: December 2019

The aim of the present study was to compare the efficacy of burst-like conditioning electrical stimulation vs. continuous stimulation of cutaneous nociceptors for inducing increased pinprick sensitivity in the surrounding unstimulated skin (a phenomenon referred to as secondary hyperalgesia). In a first experiment ( n = 30), we compared the increase in mechanical pinprick sensitivity induced by 50-Hz burst-like stimulation ( n = 15) vs. 5-Hz continuous stimulation ( n = 15) while maintaining constant the total number of stimuli and the total duration of stimulation. We found a significantly greater increase in mechanical pinprick sensitivity in the surrounding unstimulated skin after 50-Hz burst-like stimulation compared with 5-Hz continuous stimulation ( P = 0.013, Cohen’s d = 0.970). Importantly, to control for the different frequency of stimulation, we compared in a second experiment ( n = 40) 5-Hz continuous stimulation ( n = 20) vs. 5-Hz burst-like stimulation ( n = 20), this time while keeping the total number of stimuli as well as the frequency of stimulation identical. Again, we found a significantly greater increase in pinprick sensitivity after 5-Hz burst-like stimulation compared with 5-Hz continuous stimulation ( P = 0.009, Cohen’s d = 0.868). To conclude, our data indicate that burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia. NEW & NOTEWORTHY Burst-like electrical conditioning stimulation of cutaneous nociceptors is more efficacious than continuous stimulation for inducing heterosynaptic facilitation of mechanical nociceptive input in humans.
Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians
Authors: Lu Yingchang , Kweon Sun-Seog , Cai Qiuyin , Tanikawa Chizu , Shu Xiao-Ou , Jia Wei-Hua , Xiang Yong-Bing , Huyghe Jeroen R. , Harrison Tabitha A. , Kim Jeongseon , Shin Aesun , Kim Dong-Hyun , Matsuo Keitaro , Jee Sun Ha , Guo Xingyi , Wen Wanqing , Shi Jiajun , Li Bingshan , Wang Nan , Shin Min-Ho , Li Hong-Lan , Ren Zefang , Oh Jae Hwan , Oze Isao , Ahn Yoon-Ok , Jung Keum Ji , Gao Jing , Gao Yu-Tang , Pan Zhi-Zhong , Kamatani Yoichiro , Chan Andrew T. , Gsur Andrea , Hampe Jochen , Le Marchand Loic , Li Li , Lindblom Annika , Moreno Victor , Newcomb Polly A. , Offit Kenneth , Pharoah Paul D.P. , van Duijnhoven Franzel J.B. , Van Guelpen Bethany , Vodicka Pavel , Weinstein Stephanie J. , Wolk Alicja , Wu Anna H. , Hsu Li , Zeng Yi-Xin , Long Jirong , Peters Ulrike , Matsuda Koichi , Zheng Wei 
Published: December 2019

Abstract

Background:
Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians.

Methods:
We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians.

Results:
An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10–8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08–1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10–3). Of the remaining 59 variants, 12 showed an association at P &lt; 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P &lt; 5 × 10−8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10−8; rs62558833, P = 7.5 × 10−8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS.

Conclusions:
In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously.

Impact:
Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
Whole Exome Sequencing of Highly Aggregated Lung Cancer Families Reveals Linked Loci for Increased Cancer Risk on Chromosomes 12q, 7p, and 4q
Authors: Musolf Anthony M. , Moiz Bilal A. , Sun Haiming , Pikielny Claudio W. , Bossé Yohan , Mandal Diptasri , de Andrade Mariza , Gaba Colette , Yang Ping , Li Yafang , You Ming , Govindan Ramaswamy , Wilson Richard K. , Kupert Elena Y. , Anderson Marshall W. , Schwartz Ann G. , Pinney Susan M. , Amos Christopher I. , Bailey-Wilson Joan E. 
Published: December 2019

Abstract

Background:
Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer.

Methods:
Parametric genetic linkage analysis was performed on these samples using two distinct analyses—the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were coded as affected.

Results:
The AAC analysis yielded a genome-wide significant result at rs61943670 in POLR3B at 12q23.3. POLR3B has been implicated somatically in lung cancer, but this germline finding is novel and is a significant expression quantitative trait locus in lung tissue. Interesting genome-wide suggestive haplotypes were also found within individual families, particularly near SSPO at 7p36.1 in one family and a large linked haplotype spanning 4q21.3-28.3 in a different family. The 4q haplotype contains potential causal rare variants in DSPP at 4q22.1 and PTPN13 at 4q21.3.

Conclusions:
Regions on 12q, 7p, and 4q are linked to increased cancer risk in highly aggregated lung cancer families, 12q across families and 7p and 4q within a single family. POLR3B, SSPO, DSPP, and PTPN13 are currently the best candidate genes.

Impact:
Functional work on these genes is planned for future studies and if confirmed would lead to potential biomarkers for risk in cancer.
High-Negative Anti–Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan
Authors: Inoue Manami , Sawada Norie , Goto Atsushi , Shimazu Taichi , Yamaji Taiki , Iwasaki Motoki , Tsugane Shoichiro 
Published: December 2019

Abstract

Background:
Serologic testing of anti–Helicobacter pylori antibody, together with testing of pepsinogen I and II, is now widely used to stratify groups at high risk of gastric cancer in Japan. Those with a negative anti–H. pylori IgG titer, especially “high-negative” (3–&lt;10 U/mL), are speculated to have higher risk of gastric cancer. We aimed to evaluate the association between a high-negative anti–H. pylori IgG titer and the long-term risk of gastric cancer in the Japan Public Health Center-based Prospective Study (JPHC Study) Cohort II.

Methods:
The study population consisted of 19,106 Japanese men and women who were followed from 1993 to 2013. A Cox proportional hazards model was used to assess the risk of gastric cancer for plasma anti–H. pylori IgG titers, together with the severity of atrophic gastritis by pepsinogen I and II levels. A total of 595 cases of gastric cancer occurred during an average of 18 years of follow-up.

Results:
Compared with those with a low-negative anti–H. pylori IgG titer (≤3 U/mL), subjects with a high-negative titer (3–&lt;10 U/mL) showed a significantly elevated risk of gastric cancer [HR = 2.81; 95% confidence interval (CI) = 1.62–4.89]. Among those with a high-negative titer, risk increase was observed under moderate or severe atrophic gastritis (HR = 18.73; 95% CI = 8.83–39.70).

Conclusions:
Our results suggest that those with a high-negative anti–H. pylori IgG titer and moderate and severe atrophic gastritis are at increased long-term risk of gastric cancer.

Impact:
Development of moderate or severe atrophic gastritis in subjects with high-negative anti–H. pylori IgG titer is suggested to increase risk of gastric cancer.
Clinical Application of Next-Generation Sequencing–Based Panel toBRAFWild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies
Authors: Park Changhee , Kim Miso , Kim Min Jung , Kim Hyeongmin , Ock Chan-Young , Keam Bhumsuk , Kim Tae Min , Kim Dong-Wan , Kim Jong-Il , Heo Dae Seog 
Published: December 2019

AbstractMolecular profiling with next-generation sequencing (NGS) has been applied in multiple solid cancers to discover potential therapeutic targets. Here, we describe the results of a clinical NGS panel in patients with advanced melanoma. Thirty-six tumor tissues from patients with BRAF wild-type melanoma at Seoul National University Hospital (SNUH; Seoul, Republic of Korea) were collected and deep-sequenced using the SNUH FIRST-Cancer NGS panel to assess single-nucleotide variants, small insertions/deletions, copy number variations, and structural variations to estimate tumor mutation burden (TMB). We discovered 106 oncogenic alterations and most of the patients (n = 33, 92%) harbored at least one oncogenic alteration, including 2 patients who were initially diagnosed as BRAF V600E–negative but were later confirmed to be positive. Altogether, 36 samples were classified into RAS/BRAF/NF1–mutant (n = 14, 39%) or triple wild-type (n = 22, 61%) melanoma subtypes. The estimated median TMB was 8.2 mutations per Mb, ranging from 0 to 146.67 mutations per Mb. Of the 36 patients, 25 (70%) had actionable alterations with currently developed drugs, and 7 (19.4%) were enrolled in clinical trials with an RAF inhibitor, multiple receptor tyrosine kinase inhibitor, and anti-programmed cell death-1 (PD-1) antibody. TMB tended to associate with progression-free survival (PFS) of treatment with anti-PD-1/PDL-1 antibody (HR, 0.96; 95% confidence interval, 0.92–1.00; P = 0.07). High-TMB (≥13) group was associated with longer PFS than the low-TMB group (median 34.0 vs. 11.0 weeks, P = 0.04). Overall, the clinical use of a NGS panel in patients with advanced melanoma shows association with clinical outcomes and several therapeutic strategies.
MAIT Cells Promote Tumor Initiation, Growth, and Metastases via Tumor MR1
Authors: Yan Juming , Allen Stacey , McDonald Elizabeth , Das Indrajit , Mak Jeffrey Y.W. , Liu Ligong , Fairlie David P. , Meehan Bronwyn S. , Chen Zhenjun , Corbett Alexandra J. , Varelias Antiopi , Smyth Mark J. , Teng Michele W.L. 
Published: December 2019

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that require MHC class I–related protein 1 (MR1) for their development. The role of MAIT cells in cancer is unclear, and to date no study has evaluated these cells in vivo in this context. Here, we demonstrated that tumor initiation, growth, and experimental lung metastasis were significantly reduced in Mr1−/− mice, compared with wild-type mice. The antitumor activity observed in Mr1−/− mice required natural killer (NK) and/or CD8+ T cells and IFNγ. Adoptive transfer of MAIT cells into Mr1−/− mice reversed metastasis reduction. Similarly, MR1-blocking antibodies decreased lung metastases and suppressed tumor growth. Following MR1 ligand exposure, some, but not all, mouse and human tumor cell lines upregulated MR1. Pretreatment of tumor cells with the stimulatory ligand 5-OP-RU or inhibitory ligand Ac-6-FP increased or decreased lung metastases, respectively. MR1-deleted tumors resulted in fewer metastases compared with parental tumor cells. MAIT cell suppression of NK-cell effector function was tumor-MR1–dependent and partially required IL17A. Our studies indicate that MAIT cells display tumor-promoting function by suppressing T and/or NK cells and that blocking MR1 may represent a new therapeutic strategy for cancer immunotherapy.

Significance:
Contradicting the perception that MAIT cells kill tumor cells, here MAIT cells promoted tumor initiation, growth, and metastasis. MR1-expressing tumor cells activated MAIT cells to reduce NK-cell effector function, partly in a host IL17A–dependent manner. MR1-blocking antibodies reduced tumor metastases and growth, and may represent a new class of cancer therapeutics.
This article is highlighted in the In This Issue feature, p. 1
Assessing the Representation of Phonological Rules by a Production Study of Non-Words in Coratino
Authors: Bucci Jonathan , Lorusso Paolo , Gerber Silvain , Grimaldi Mirko , Schwartz Jean-Luc 
Published: December 2019

AbstractPhonological regularities in a given language can be described as a set of formal rules applied to logical expressions (e.g., the value of a distinctive feature) or alternatively as distributional properties emerging from the phonetic substance. An indirect way to assess how phonology is represented in a speaker’s mind consists in testing how phonological regularities are transferred to non-words. This is the objective of this study, focusing on Coratino, a dialect from southern Italy spoken in the Apulia region. In Coratino, a complex process of vowel reduction operates, transforming the /i e ɛ u o ɔ a/ system for stressed vowels into a system with a smaller number of vowels for unstressed configurations, characterized by four major properties: (1) all word-initial vowels are maintained, even unstressed; (2) /a/ is never reduced, even unstressed; (3) unstressed vowels /i e ɛ u o ɔ/ are protected against reduction when they are adjacent to a consonant that shares articulation (labiality and velarity for /u o ɔ/ and palatality for /i e ɛ/); (4) when they are reduced, high vowels are reduced to /ɨ/ and mid vowels to /ə/. A production experiment was carried out on 19 speakers of Coratino to test whether these properties were displayed with non-words. The production data display a complex pattern which seems to imply both explicit/formal rules and distributional properties transferred statistically to non-words. Furthermore, the speakers appear to vary considerably in how they perform this task. Altogether, this suggests that both formal rules and distributional principles contribute to the encoding of Coratino phonology in the speaker’s mind.
The Effect of Body Mass Index on Outcome after Endovascular Treatment in Acute Ischemic Stroke Patients: A Post Hoc Analysis of the MR CLEAN Trial
Authors: Pirson France Anne Victoire , Hinsenveld Wouter H. , Staals Julie , de Greef Bianca T.A. , van Zwam Wim H. , Dippel Diederik W.J. , Vos Jan Albert , Schonewille Wouter J. , van Oostenbrugge Robert J. ,   on behalf of MR CLEAN investigators
Published: December 2019

<b><i>Background:</i></b> Though obesity is a well-known risk factor for vascular disease, the impact of obesity on stroke outcome has been disputed. Several studies have shown that obesity is associated with better functional outcome after stroke. Whether obesity influences the benefit of endovascular treatment (EVT) in stroke patients is unknown. We evaluated the association between body mass index (BMI) and outcome in acute ischemic stroke patients with large vessel ­occlusion (LVO), and assessed whether BMI affects the ­benefit of EVT. <b><i>Methods:</i></b> This is a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial (­ISRCTN10888758). BMI was used as a continuous and categorical variable, distinguishing underweight and normal weight (BMI &#x3c;25), overweight (BMI 25–30), and obesity (BMI ≥30). We used multivariable ordinal logistic regression analysis to estimate the association of BMI with functional outcome (shift analysis), assessed with modified Rankin Scale (mRs) at 90 days. The impact of BMI on EVT effect was tested by the use of a multiplicative interaction term. <b><i>Results:</i></b> Of 366 patients, 160 (44%) were underweight or normal weight, 145 (40%) overweight, and 61 (17%) were obese. In multivariable analysis with BMI as a continuous variable, we found a shift toward better functional outcome with higher BMI (mRS adjusted common OR 1.04; 95% CI 1.0–1.09), and mortality was inversely related to BMI (aOR 0.92; 95% CI 0.85–0.99). Safety analysis showed that higher BMI was associated with lower risk of stroke progression (aOR 0.92, 95% CI 0.87–0.99). Additional analysis showed no interaction between BMI and EVT effect on functional outcome, mortality, and other safety outcomes. <b><i>Conclusion:</i></b> Our study confirms the effect of obesity on outcome in acute ischemic stroke patients with LVO, meaning better functional outcome, lower mortality, and lower risk of stroke progression for patients with higher BMI. As we found no interaction between BMI and EVT effect, all BMI classes may expect the same benefit from EVT.
Apresentação do primeiro número da Revista Ingesta
Authors: Carneiro Henrique Soares 
Published: December 2019

A história da alimentação, das bebidas e das drogas se constitui como um campo de circunscrição temática e conceitual de elementos distintos, mas sobrepostos. Os estudos sobre comida, bebidas alcoólicas e outras drogas se inscreveram nas tentativas de analisar o cerne da vida cotidiana e que é também a matéria-prima da economia, ou seja, as práticas que podemos chamar de ingestões. Ingerir é assimilar no corpo produtos externos que se consubstanciam na própria carne constituindo assim o seu alimento reprodutor, mas também reguladores psicofisiológicos que desde as épocas mais arcaicas foram encontrados com a fermentação de matérias orgânicas e a riqueza psicoativa da flora. Por isso, denominamos essa revista que apresenta agora o seu primeiro número de Ingesta, ou seja, ingestões que esperamos sejam também digestivas e nutritivas. Temos, aqui, um cardápio amplo de temas que tratam de muitos aspectos, sob olhares quase sempre ancorados em pesquisas monográficas muito ricas que investigam manifestações peculiares de nossa relação com o que se come ou se bebe, como isso se faz, com quais significados e com que repercussões.
Association Between Hospital Teaching Status and Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Czarnecki Andrew , Qiu Feng , Koh Maria , Cheskes Sheldon , Dorian Paul , Scales Damon C. , Ko Dennis T. 
Published: December 2019

Background:
Controversy exists about how best to organize systems of care for patients with out-of-hospital cardiac arrest (OHCA), as little evidence exists to guide policy-makers. In Canada, teaching hospitals are mainly cardiac referral centers that are potentially well suited towards treating patients with OHCA. Our objective was to determine whether patients with OHCA are more likely to survive if they present to teaching hospitals.

Methods and Results:

We conducted a retrospective observational cohort study by linking several population-based administrative databases in Ontario, Canada. All patients >20 years old who arrived alive to hospital after OHCA between April 1, 2007, and March 31, 2014, were eligible for inclusion. Patients with ST-segment–elevation myocardial infarction were excluded. The primary outcome was survival at 30 days. To determine the association between teaching status and 30-day survival, logistic regression models were used to adjust for baseline differences in patient characteristics. Prespecified analysis was performed stratified by age: ≤65, 66 to 80, and >80 years old. A total of 25 346 patients were included: 5413 at teaching and 19 933 at nonteaching hospitals. Survival at 30 days was 13.9% in teaching and 11.0% (
P
<0.001) in nonteaching hospitals. Hospital teaching status was associated with a significantly higher adjusted odds of 30-day survival (odds ratio, 1.38 [95% CI, 1.14–1.67]). This improvement in survival was observed in younger patients (≤65 years: odds ratio, 1.41 [95% CI, 1.14–1.74]; 66 to 80 years: odds ratio,1.37 [95% CI, 1.13–1.67]), but there was no significant difference in the elderly (>80 years: odds ratio, 1.07 [95% CI, 0.79–1.44]).

Conclusions:
Patients with OHCA treated at teaching hospitals were more likely to survive to 30 days. These findings support current recommendations suggesting that treatment of these patients should be provided at specialized hospitals.