bluuebunny/crossref_metadata_2025_split huggingface dataset:
FXR1-related congenital myopathy: expansion of the clinical and genetic spectrum
Authors: Mroczek Magdalena , Longman Cheryl , Farrugia Maria Elena , Kapetanovic Garcia Solange , Ardicli Didem , Topaloglu Haluk , Hernández-Laín Aurelio , Orhan Diclehan , Alikasifoglu Mehmet , Duff Jennifer , Specht Sabine , Nowak Kristen , Ravenscroft Gianina , Chao Katherine , Valivullah Zaheer , Donkervoort Sandra , Saade Dimah , Bönnemann Carsten , Straub Volker , Yoon Grace 
Published: April 2022

BackgroundBiallelic pathogenic variants inFXR1have recently been associated with two congenital myopathy phenotypes: a severe form associated with hypotonia, long bone fractures, respiratory insufficiency and infantile death, and a milder form characterised by proximal muscle weakness with survival into adulthood.ObjectiveWe report eight patients from four unrelated families with biallelic pathogenic variants in exon 15 ofFXR1.MethodsWhole exome sequencing was used to detect variants inFXR1.ResultsCommon clinical features were noted for all patients, which included proximal myopathy, normal serum creatine kinase levels and diffuse muscle atrophy with relative preservation of the quadriceps femoris muscle on muscle imaging. Additionally, some patients withFXR1-related myopathy had respiratory involvement and required bilevel positive airway pressure support. Muscle biopsy showed multi-minicores and type I fibre predominance with internalised nuclei.ConclusionFXR1-related congenital myopathy is an emerging entity that is clinically recognisable. Phenotypic variability associated with variants inFXR1can result from differences in variant location and type and is also observed between patients homozygous for the same variant, rendering specific genotype–phenotype correlations difficult. Our work broadens the phenotypic spectrum ofFXR1-related congenital myopathy.
Safety and efficacy of the eCLIPs bifurcation remodelling system for the treatment of wide necked bifurcation aneurysms: 1 year results from the European eCLIPs Safety, Feasibility, and Efficacy Study (EESIS)
Authors: de Vries Joost , Aquarius René , Sørensen Leif , Boogaarts Hieronymus D , Turowski Bernd , van Zwam Wim H , Marotta Thomas R , Bartels Ronald H M A 
Published: April 2022

BackgroundThe eCLIPs bifurcation remodelling system is a non-circumferential implant that bridges the neck from outside of a bifurcation aneurysm. The goal of the multicenter, post-marketing European eCLIPs Safety, FeasIbility, and Efficacy Study (EESIS), was to present the efficacy and safety results of the eCLIPs device after 365 days of follow-up.MethodsAll patients were to receive an eCLIPs in conjunction with coils. The study was conducted according to good clinical practices and included independent adjudication of safety and efficacy outcomes.ResultsTwenty patients were enrolled at four European centers. Mean age was 60 years (range 41–74) and aneurysms were located at the basilar tip (n=19) and carotid tip (n=1). Average aneurysm dome height was 6.0 mm (range 2.0–15.0). Mean neck length was 5.1 mm (range 2.6–8.5). The technical success rate was 90% (18 of 20). No major territorial strokes or deaths occurred between the index procedure and after 365 days of follow-up. Complete occlusion was achieved in 60% of patients (12 of 20 patients) and 67% of patients with an eCLIPs device (12 of 18) after 365 days of follow-up. Adequate occlusion (complete occlusion and neck remnant) was achieved in 80% of patients (16 of 20 patients) and 89% of patients with an eCLIPs device (16 of 18 patients) after 365 days of follow-up.ConclusionIn this small series, treatment with eCLIPs was feasible, safe, and efficacious, considering the challenging nature of the aneurysms.Trial registration numberClinicalTrials.govNCT02607501.
Head and neck cancer and asbestos exposure
Authors: Clin Bénédicte , Gramond Celine , Thaon Isabelle , Brochard Patrick , Delva Fleur , Chammings Soizick , Gislard Antoine , Laurent François , Paris Christophe , Lacourt Aude , Pairon Jean-Claude 
Published: April 2022

ObjectivesThe aim of this study was to analyse, within a French cohort of workers previously occupationally exposed to asbestos, incidence and mortality from various sites of head and neck cancers (larynx excluded) and to examine the potential link of these cancers with pleural plaques.MethodsA 10-year follow-up study was conducted in the 13 481 male subjects included in the cohort between October 2003 and December 2005. Asbestos exposure was assessed by industrial hygienist analysis of a standardised questionnaire. The final cumulative exposure index (CEI; in equivalent fibres.years/mL) for each subject was calculated as the sum of each employment period’s four-level CEI. The number of head and neck cancers recorded by the National Health Insurance fund was collected in order to conduct an incidence study. Complementary analysis was restricted to men who had performed at least one chest CT scan (N=4804). A mortality study was also conducted. We used a Cox model with age as the time axis variable adjusted for smoking, time since first exposure, CEI of exposure to asbestos and pleural plaques on CT scans.ResultsWe reported a significant dose–response relationship between CEI of exposure to asbestos and head and neck cancers after exclusion of laryngeal cancers, in the mortality study (HR 1.03, 95% CI (1.01 to 1.06) for an increase of 10 f.years/mL) and a close to significant dose–response relationship in the incidence study (HR 1.02, 95% CI (1.00 to 1.04) for an increase of 10 f.years/mL). No statistically significant association between pleural plaques and head and neck cancer incidence was observed.ConclusionsThis large-scale study suggests a relationship between asbestos exposure and head and neck cancers, after exclusion of laryngeal cancers, regardless of whether associated pleural plaques were present.
Repeat measures of DNA methylation in an inception cohort of firefighters
Authors: Goodrich Jaclyn M , Jung Alesia M , Furlong Melissa A , Beitel Shawn , Littau Sally , Gulotta John , Wallentine Darin , Burgess Jefferey L 
Published: April 2022

ObjectivesFirefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs).MethodsWe profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20–37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control.ResultsWe report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures.ConclusionsOverall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.
Rice protein suppresses 4-hydroxy-2-nonenal-induced inflammation owing to methionine availability
Authors: Wang Zhengxuan , Liang Mingcai , Li Hui , Liu Bingxiao , Yang Lin 
Published: April 2022

4-Hydroxy-2-nonenal (HNE) is one of the most important products of lipid peroxidation, which induces inflammation. To investigate the effects of rice protein (RP) on suppressing HNE-induced inflammation and the role of methionine in regulating the anti-inflammatory function of RP, Wistar rats (male, weighing 180–200 g) were either ad libitum fed a pellet diet with oral administration of methionine or ad libitum fed RP for 2 weeks. RP and methionine significantly reduced HNE levels and effectively suppressed the expressions of cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1β ( IL-1β) and IL-6, and inducible nitric oxide synthase. The anti-inflammatory action of RP was evident from the upregulation of IL-10 and glutathione S-transferase ( GST), which played a role in the detoxification of HNE. The results show that the molecular mechanism responsible for the anti-inflammatory function of RP is the inhibition of nuclear factor kappa B (NF-κB) activation by the downregulation of protein kinase B/phosphoinositide 3 kinase. Further, this study demonstrates that Met availability contributes to the suppression of HNE-induced inflammation through upregulating IL-10 and GST in rats fed RP. Novelty: RP suppresses HNE-induced inflammation. Methionine plays a role in upregulating IL-10 and GST. Methionine availability regulates the inhibition of NF-κB by RP.
Conserving wetlands in agroecosystems can sustain aerial insectivore productivity and survival
Authors: Berzins Lisha L. , Morrissey Christy A. , Howerter David W. , Clark Robert G. 
Published: April 2022

Agricultural intensification simplifies natural landscapes and frequently results in the loss of biodiversity. Wetlands are highly productive and may offset these losses, but the amount of wetland area needed to support declining avian species on farmland is unknown. Using an avian aerial insectivore, the Tree Swallow ( Tachycineta bicolor (Vieillot, 1808)), we tested whether a gradient of pond area (visible surface water in wetland basins within 500 m of nest boxes; range 0.2%–30% pond area) at cropland and grassland sites was related to aquatic insect biomass, reproductive success, and adult female or nestling body condition. Aquatic insect biomass was ∼2–8 times higher at the cropland sites with intermediate (5.2%) pond areas than at sites with the highest (15.6%) and lowest (0.2%) pond areas. Swallow clutch initiation date was ∼3–4 days earlier, and nestling body condition and model-predicted first-year survival were ∼10% higher among cropland sites with more pond area and were comparable to birds hatched at grassland sites. Loss of ponds due to agricultural drainage can reduce aquatic insect prey during the breeding season with apparent individual and demographic consequences for insectivorous birds. Overall, the results suggest that where wetlands are conserved, intensive croplands can sustain Tree Swallow populations.
Covariant formulation of f(Q) theory
Authors: Zhao Dehao 
Published: April 2022

AbstractIn Symmetric Teleparallel General Relativity, gravity is attributed to the non-metricity. The so-called “coincident gauge” is usually taken in this theory so that the affine connection vanishes and the metric is the only fundamental variable. This gauge choice was kept in many studies on the extensions of Symmetric Teleparallel General Relativity, such as the so-called f(Q) theory. In this paper, we point out that sometimes this gauge choice conflicts with the coordinate system we selected based on symmetry. To circumvent this problem, we formulate the f(Q) theory in a covariant way with which we can find suitable non-vanishing affine connection for a given metric. We also apply this method to two important cases: the static spherically symmetric spacetime and the homogeneous and isotropic expanding universe.
NSGA-II-Based Microchannel Structure Optimization Problem Study
Authors: Wang Linlin 
Published: April 2022

A multiobjective genetic algorithm is used to optimize the structure of circular concave cavities and microchannels. The objective functions of thermal resistance and pumping power are constructed by the response plane approximation method according to the simulation results, and then a mathematical model of multiobjective genetic optimization with the structural parameters of microchannels as variables is established. The Pareto optimized solution sets of thermal resistance and pumping power are calculated by the nondominated ranking genetic algorithm NSGA-II, and the comprehensive heat transfer performance is evaluated by the enhanced heat transfer factor. The results show that the multivariate statistical coefficients

R

2

of the thermal resistance and pumping power objective functions are 0.932 9 and 0.996 6, respectively, indicating the high accuracy of the fitted functions. The optimized channel structure (

e

1

=
0.036.8

mm

,

e

2

=
0.019.3

mm

) was used to achieve a more uniform temperature field distribution and better integrated heat transfer performance (enhanced heat transfer factor

η
=
1.23

). When the thermal resistance is larger or the pump work is larger, the comprehensive heat transfer effect is not as good as the working condition when the thermal resistance and pump work are more uniform.
A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors
Authors: Choudhury Atish D. , Higano Celestia S. , de Bono Johann S. , Cook Natalie , Rathkopf Dana E. , Wisinski Kari B. , Martin-Liberal Juan , Linch Mark , Heath Elisabeth I. , Baird Richard D. , García-Carbacho Javier , Quintela-Fandino Miguel , Barry Simon T. , de Bruin Elza C. , Colebrook Steve , Hawkins George , Klinowska Teresa , Maroj Brijesh , Moorthy Ganesh , Mortimer Peter G. , Moschetta Michele , Nikolaou Myria , Sainsbury Liz , Shapiro Geoffrey I. , Siu Lillian L. , Hansen Aaron R. 
Published: April 2022

Abstract

Purpose:
To characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), and assess preliminary efficacy in combination with abiraterone acetate or vistusertib.

Patients and Methods:
This phase I open-label study included patients with advanced solid tumors, particularly prostate cancer, triple-negative breast cancer, and squamous non–small cell lung cancer. The study comprised four arms: (i) AZD8186 monotherapy dose finding; (ii) monotherapy dose expansion; (iii) AZD8186/abiraterone acetate (with prednisone); and (iv) AZD8186/vistusertib. The primary endpoints were safety, tolerability, and identification of the RP2D of AZD8186 monotherapy and in combination. Secondary endpoints included pharmacokinetics (PK), pharmacodynamics, and tumor and prostate-specific antigen (PSA) responses.

Results:
In total, 161 patients were enrolled. AZD8186 was well tolerated across all study arms, the most common adverse events being gastrointestinal symptoms. In the monotherapy dose-finding arm, four patients experienced dose-limiting toxicities (mainly rash). AZD8186 doses of 60-mg twice daily [BID; 5 days on, 2 days off (5:2)] and 120-mg BID (continuous and 5:2 dosing) were taken into subsequent arms. The PKs of AZD8186 were dose proportional, without interactions with abiraterone acetate or vistusertib, and target inhibition was observed in plasma and tumor tissue. Monotherapy and combination therapy showed preliminary evidence of limited antitumor activity by imaging and, in prostate cancer, PSA reduction.

Conclusions:
AZD8186 monotherapy had an acceptable safety and tolerability profile, and combination with abiraterone acetate/prednisone or vistusertib was also tolerated. There was preliminary evidence of antitumor activity, meriting further exploration of AZD8186 in subsequent studies in PI3Kβ pathway–dependent cancers.
Tailored Sitting Tai Chi Program for Subacute Stroke Survivors: A Randomized Controlled Trial
Authors: Zhao Jie , Chau Janita Pak Chun , Chan Aileen Wai Kiu , Meng Qiang , Choi Kai Chow , Xiang Xiaoqi , Zhao Yali , He Rong , Li Qin 
Published: April 2022

Background:
The initiation of exercise during rehabilitation at the subacute stage could provide stroke survivors with an approach to recovery that capitalizes on unique physiological conditions and promotes spontaneous recovery. We aimed to examine the effects of a tailored sitting Tai Chi program on recovery outcomes among subacute stroke survivors.

Methods:
We conducted a 12-week assessor-blind randomized controlled trial in China. Subacute stroke survivor-caregiver dyads were recruited and randomly assigned to either the sitting Tai Chi group (n=80) or attention control group (n=80). Outcomes including upper limb function (Fugl-Meyer Assessment Upper Extremity & Wolf Motor Function Test), balance control (Berg Balance Scale), sitting balance control (Trunk Impairment Scale), depressive symptoms (Geriatric Depression Scale Short Form), shoulder range of motion, shoulder pain (ShoulderQ), activities of daily living (Modified Barthel Index), and quality of life (Stroke Specific Quality of Life Scale) were measured at baseline, in-process, immediately post, and 4-week postintervention.

Results:
Immediately postintervention, the sitting Tai Chi group (n=69) showed significant upper limb function improvement in the primary outcomes including the performance time (regression coefficient of the group-by-time interaction, B=–21.415 [95% CI, –31.000 to –11.831]) and functional ability (B=10.146 [95% CI, 4.886–15.406]) domains of the Wolf Motor Function Test, balance control (B, 4.972 [95% CI, 1.356–8.588]), and sitting balance control (B=4.397 [95% CI, 2.699–6.096]). Compared with the control group (n=65), improvements were also observed in secondary outcomes including depressive symptoms (B=–1.626 [95% CI, –2.304 to –0.948]), shoulder extension (B=4.518 [95% CI, 0.893–8.144]), activities of daily living (B=5.510 [95% CI, 0.450–10.569]), and quality of life (B=15.680 [95% CI, 7.255–24.105]).

Conclusions:
The results support the effectiveness of a tailored sitting Tai Chi program in improving recovery outcomes among subacute stroke survivors and provide additional knowledge to support the clinical implementation of such a program.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04138407.
UDapter: Typology-based Language Adapters for Multilingual Dependency Parsing and Sequence Labeling
Authors: Üstün Ahmet , Bisazza Arianna , Bouma Gosse , Noord Gertjan van 
Published: April 2022

Abstract
Recent advances in multilingual language modeling have brought the idea of a truly universal parser closer to reality. However, such models are still not immune to the “curse of multilinguality”: Cross-language interference and restrained model capacity remain major obstacles. To address this, we propose a novel language adaptation approach by introducing contextual language adapters to a multilingual parser. Contextual language adapters make it possible to learn adapters via language embeddings while sharing model parameters across languages based on contextual parameter generation. Moreover, our method allows for an easy but effective integration of existing linguistic typology features into the parsing model. Because not all typological features are available for every language, we further combine typological feature prediction with parsing in a multi-task model that achieves very competitive parsing performance without the need for an external prediction system for missing features.
The resulting parser, UDapter, can be used for dependency parsing as well as sequence labeling tasks such as POS tagging, morphological tagging, and NER. In dependency parsing, it outperforms strong monolingual and multilingual baselines on the majority of both high-resource and low-resource (zero-shot) languages, showing the success of the proposed adaptation approach. In sequence labeling tasks, our parser surpasses the baseline on high resource languages, and performs very competitively in a zero-shot setting. Our in-depth analyses show that adapter generation via typological features of languages is key to this success.1
Towards General Natural Language Understanding with Probabilistic
Worldbuilding
Authors: Saparov Abulhair , Mitchell Tom M. 
Published: April 2022

Abstract
We introduce the Probabilistic Worldbuilding Model (PWM), a new fully symbolic Bayesian model of semantic parsing and reasoning, as a first step in a research program toward more domain- and task-general NLU and AI. Humans create internal mental models of their observations that greatly aid in their ability to understand and reason about a large variety of problems. In PWM, the meanings of sentences, acquired facts about the world, and intermediate steps in reasoning are all expressed in a human-readable formal language, with the design goal of interpretability. PWM is Bayesian, designed specifically to be able to generalize to new domains and new tasks. We derive and implement an inference algorithm that reads sentences by parsing and abducing updates to its latent world model that capture the semantics of those sentences, and evaluate it on two out-of-domain question-answering datasets: (1) ProofWriter and (2) a new dataset we call FictionalGeoQA, designed to be more representative of real language but still simple enough to focus on evaluating reasoning ability, while being robust against heuristics. Our method outperforms baselines on both, thereby demonstrating its value as a proof-of-concept.
Data-driven Model Generalizability in Crosslinguistic Low-resource Morphological Segmentation
Authors: Liu Zoey , Prud’hommeaux Emily 
Published: April 2022

Abstract
Common designs of model evaluation typically focus on monolingual settings, where different models are compared according to their performance on a single data set that is assumed to be representative of all possible data for the task at hand. While this may be reasonable for a large data set, this assumption is difficult to maintain in low-resource scenarios, where artifacts of the data collection can yield data sets that are outliers, potentially making conclusions about model performance coincidental. To address these concerns, we investigate model generalizability in crosslinguistic low-resource scenarios. Using morphological segmentation as the test case, we compare three broad classes of models with different parameterizations, taking data from 11 languages across 6 language families. In each experimental setting, we evaluate all models on a first data set, then examine their performance consistency when introducing new randomly sampled data sets with the same size and when applying the trained models to unseen test sets of varying sizes. The results demonstrate that the extent of model generalization depends on the characteristics of the data set, and does not necessarily rely heavily on the data set size. Among the characteristics that we studied, the ratio of morpheme overlap and that of the average number of morphemes per word between the training and test sets are the two most prominent factors. Our findings suggest that future work should adopt random sampling to construct data sets with different sizes in order to make more responsible claims about model evaluation.