bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invisible and displaced dark matter signatures at Belle II
Authors: Duerr Michael , Ferber Torben , Hearty Christopher , Kahlhoefer Felix , Schmidt-Hoberg Kai , Tunney Patrick 
Published: February 2020

Abstract
Many dark matter models generically predict invisible and displaced signatures at Belle II, but even striking events may be missed by the currently implemented search programme because of inefficient trigger algorithms. Of particular interest are final states with a single photon accompanied by missing energy and a displaced pair of electrons, muons, or hadrons. We argue that a displaced vertex trigger will be essential to achieve optimal sensitivity at Belle II. To illustrate this point, we study a simple but well-motivated model of thermal inelastic dark matter in which this signature naturally occurs and show that otherwise inaccessible regions of parameter space can be tested with such a search. We also evaluate the sensitivity of single-photon searches at BaBar and Belle II to this model and provide detailed calculations of the relic density target.
Complexity in the presence of a boundary
Authors: Braccia Paolo , Cotrone Aldo L. , Tonni Erik 
Published: February 2020

Abstract
The effects of a boundary on the circuit complexity are studied in two dimensional theories. The analysis is performed in the holographic realization of a conformal field theory with a boundary by employing different proposals for the dual of the complexity, including the “Complexity = Volume” (CV) and “Complexity = Action” (CA) prescriptions, and in the harmonic chain with Dirichlet boundary conditions. In all the cases considered except for CA, the boundary introduces a subleading logarithmic divergence in the expansion of the complexity as the UV cutoff vanishes. Holographic subregion complexity is also explored in the CV case, finding that it can change discontinuously under continuous variations of the configuration of the subregion.
The Chiral Anomaly of the Free Fermion in Functorial Field Theory
Authors: Ludewig Matthias , Roos Saskia 
Published: February 2020

AbstractWhen trying to cast the free fermion in the framework of functorial field theory, itschiral anomalymanifests in the fact that it assigns the determinant of the Dirac operator to a top-dimensional closed spin manifold, which is not a number as expected, but an element of a complex line. In functorial field theory language, this means that the theory istwisted, which gives rise to ananomaly theory. In this paper, we give a detailed construction of this anomaly theory, as a functor that sends manifolds to infinite-dimensional Clifford algebras and bordisms to bimodules.
The glucose-lowering effects of α-glucosidase inhibitor require a bile acid signal in mice
Authors: Qiu Yixuan , Shen Linyan , Fu Lihong , Yang Jie , Cui Canqi , Li Tingting , Li Xuelin , Fu Chenyang , Gao Xianfu , Wang Weiqing , Ning Guang , Gu Yanyun 
Published: February 2020

Abstract
Aims/hypothesis
Bile-acid (BA) signalling is crucial in metabolism homeostasis and has recently been found to mediate the therapeutic effects of glucose-lowering treatments, including α-glucosidase inhibitor (AGI). However, the underlying mechanisms are yet to be clarified. We hypothesised that BA signalling may be required for the glucose-lowering effects and metabolic benefits of AGI.

Methods
Leptin receptor (Lepr)-knockout (KO) db/db mice and high-fat high-sucrose (HFHS)-fed Fxr (also known as Nr1h4)-KO mice were treated with AGI. Metabolic phenotypes and BA signalling in different compartments, including the liver, gut and endocrine pancreas, were evaluated. BA pool profiles were analysed by mass spectrometry. The islet transcription profile was assayed by RNA sequencing. The gut microbiome were assayed by 16S ribosomal RNA gene sequencing.

Results
AGI lowered microbial BA levels in BA pools of different compartments in the body, and increased gut BA reabsorption in both db/db and HFHS-fed mouse models via altering the gut microbiome. The AGI-induced changes in BA signalling (including increased activation of farnesoid X receptor [FXR] in the liver and inhibition of FXR in the ileum) echoed the alterations in BA pool size and composition in different organs. In Fxr-KO mice, the glucose- and lipid-lowering effects of AGI were partially abrogated, possibly due to the Fxr-dependent effects of AGI on decelerating beta cell replication, alleviating insulin hypersecretion and improving hepatic lipid and glucose metabolism.

Conclusions/interpretation
By regulating microbial BA metabolism, AGI elicited diverse changes in BA pool composition in different host compartments to orchestrate BA signalling in the whole body. The AGI-induced changes in BA signalling may be partly required for its glucose-lowering effects. Our study, hence, sheds light on the promising potential of regulating microbial BA and host FXR signalling for the treatment of type 2 diabetes.

Data availability
Sequencing data are available from the BioProject Database (accession no. PRJNA600345; www.ncbi.nlm.nih.gov/bioproject/600345).
Prospects and challenges of multi-omics data integration in toxicology
Authors: Canzler Sebastian , Schor Jana , Busch Wibke , Schubert Kristin , Rolle-Kampczyk Ulrike E. , Seitz Hervé , Kamp Hennicke , von Bergen Martin , Buesen Roland , Hackermüller Jörg 
Published: February 2020

AbstractExposure of cells or organisms to chemicals can trigger a series of effects at the regulatory pathway level, which involve changes of levels, interactions, and feedback loops of biomolecules of different types. A single-omics technique, e.g., transcriptomics, will detect biomolecules of one type and thus can only capture changes in a small subset of the biological cascade. Therefore, although applying single-omics analyses can lead to the identification of biomarkers for certain exposures, they cannot provide a systemic understanding of toxicity pathways or adverse outcome pathways. Integration of multiple omics data sets promises a substantial improvement in detecting this pathway response to a toxicant, by an increase of information as such and especially by a systemic understanding. Here, we report the findings of a thorough evaluation of the prospects and challenges of multi-omics data integration in toxicological research. We review the availability of such data, discuss options for experimental design, evaluate methods for integration and analysis of multi-omics data, discuss best practices, and identify knowledge gaps. Re-analyzing published data, we demonstrate that multi-omics data integration can considerably improve the confidence in detecting a pathway response. Finally, we argue that more data need to be generated from studies with a multi-omics-focused design, to define which omics layers contribute most to the identification of a pathway response to a toxicant.
Vestibular-guided visual search
Authors: Smith Laura , Gkioka Annita , Wilkinson David 
Published: February 2020

AbstractThe amnesic symptoms that accompany vestibular dysfunction point to a functional relationship between the vestibular and visual memory systems. However, little is known about the underpinning cognitive processes. As a starting point, we sought evidence for a type of cross-modal interaction commonly observed between other sensory modalities in which the identification of a target (in this case, visual) is facilitated if earlier coupled to a unique, temporally coincident stimulus from another sensory domain (in this case, vestibular). Participants first performed a visual detection task in which stimuli appeared at random locations within a computerised grid. Unknown to participants, the onset of one particular stimulus was accompanied by a brief, sub-sensory pulse of galvanic vestibular stimulation (GVS). Across two visual search experiments, both old and new targets were identified faster when presented in the grid location at which the GVS-paired visual stimulus had appeared in the earlier detection task. This location advantage appeared to be based on relative rather than absolute spatial co-ordinates since the effect held when the search grid was rotated 90°. Together these findings indicate that when individuals return to a familiar visual scene (here, a 2D grid), visual judgements are facilitated when targets appear at a location previously associated with a unique, task-irrelevant vestibular cue. This novel case of multisensory interplay has broader implications for understanding how vestibular signals inform cognitive processes and helps constrain the growing therapeutic application of GVS.
Burden of fractures in France: incidence and severity by age, gender, and site in 2016
Authors: Bouyer Benjamin , Leroy Fanny , Rudant Jérémie , Weill Alain , Coste Joël 
Published: February 2020

Abstract
Purpose
Fractures are common events, but the exact incidence and severity of fractures have not been clearly determined for most anatomical sites. We estimated the incidence and severity of fractures in France regardless of the anatomical site.

Methods
Observational cross-sectional study in France in 2016 based on the national health data system. All incident fractures in patients 20 years and older were included. We determined the anatomical fracture site (12 sites) and the severity using a 4-point scale (outpatient care, hospitalization, surgery, and in-hospital death).

Results
We identified 562,094 incident fractures, predominantly occurring in women (319,858: 56.9%); with a mean age of 63.6 years, and an exponential increase after the age of 70 years. Distal upper limb (172,591: 30.7%), distal lower limb (84,602: 15.1%), and femoral neck (78,766: 14.0%) accounted for more than one-half of all fractures. Sex and age of onset distributions varied widely according to fracture sites, with earlier onset for distal lower limb fractures (mean age: 54.2 years) and distal upper limb fractures (mean age: 55.2 years) with a men predominance for skull fractures. Only 105,165 (18.7%) fractures were treated on an outpatient basis; 11,913 (2.1%) in-hospital deaths occurred in patients with a mean age of 79.5 years. High mortality was observed for skull (12.9%), rib (4.9%), and femoral fractures (femoral neck 4.3% and proximal lower limb 4.2%).

Conclusion
We estimated the incidence of fractures in France by sex and anatomical site. We also showed that fractures remain common and serious life events, especially in older people.
Compared with matched controls, patients with postoperative atrial fibrillation (POAF) have increased long-term AF after CABG, and POAF is further associated with increased ischemic stroke, heart failure and mortality even after adjustment for AF
Authors: Thorén Emma , Wernroth Mona-Lisa , Christersson Christina , Grinnemo Karl-Henrik , Jidéus Lena , Ståhle Elisabeth 
Published: February 2020

Abstract
Objective
To analyze (1) associations between postoperative atrial fibrillation (POAF) after CABG and long-term cardiovascular outcome, (2) whether associations were influenced by AF during follow-up, and (3) if morbidities associated with POAF contribute to mortality.

Methods
An observational cohort study of 7145 in-hospital survivors after isolated CABG (1996–2012), with preoperative sinus rhythm and without AF history. Incidence of AF was compared with matched controls. Time-updated covariates were used to adjust for POAF-related morbidities during follow-up, including AF.

Results
Thirty-one percent of patients developed POAF. Median follow-up was 9.8 years. POAF patients had increased AF compared with matched controls (HR 3.03; 95% CI 2.66–3.49), while AF occurrence in non-POAF patients was similar to controls (1.00; 0.89–1.13). The observed AF increase among POAF patients compared with controls persisted over time (> 10 years 2.73; 2.13–3.51). Conversely, the non-POAF cohort showed no AF increase beyond the first postoperative year. Further, POAF was associated with long-term AF (adjusted HR 3.20; 95% CI 2.73–3.76), ischemic stroke (1.23; 1.06–1.42), heart failure (1.44; 1.27–1.63), overall mortality (1.21; 1.11–1.32), cardiac mortality (1.35; 1.18–1.54), and cerebrovascular mortality (1.54; 1.17–2.02). These associations remained after adjustment for AF during follow-up. Adjustment for other POAF-associated morbidities weakened the association between POAF and overall mortality, which became non-significant.

Conclusions
Patients with POAF after CABG had three times the incidence of long-term AF compared with both non-POAF patients and matched controls. POAF was associated with long-term ischemic stroke, heart failure, and corresponding mortality even after adjustment for AF during follow-up. The increased overall mortality was partly explained by morbidities associated with POAF.

Graphic abstract
Candidate gene screen for potential interaction partners and regulatory targets of the Hox gene labial in the spider Parasteatoda tepidariorum
Authors: Schomburg Christoph , Turetzek Natascha , Prpic Nikola-Michael 
Published: February 2020

AbstractThe Hox genelabial(lab) governs the formation of the tritocerebral head segment in insects and spiders. However, the morphology that results fromlabaction is very different in the two groups. In insects, the tritocerebral segment (intercalary segment) is reduced and lacks appendages, whereas in spiders the corresponding segment (pedipalpal segment) is a proper segment including a pair of appendages (pedipalps). It is likely that this difference betweenlabaction in insects and spiders is mediated by regulatory targets or interacting partners oflab. However, only a few such genes are known in insects and none in spiders. We have conducted a candidate gene screen in the spiderParasteatoda tepidariorumusing as candidatesDrosophila melanogastergenes known to (potentially) interact withlabor to be expressed in the intercalary segment. We have studied 75P. tepidariorumgenes (including previously published and duplicated genes). Only 3 of these (proboscipedia-A(pb-A) and two paralogs ofextradenticle(exd)) showed differential expression between leg and pedipalp. The low success rate points to a weakness of the candidate gene approach when it is applied to lineage specific organs. The spider pedipalp has no counterpart in insects, and therefore relying on insect data apparently cannot identify larger numbers of factors implicated in its specification and formation. We argue that in these cases a de novo approach to gene discovery might be superior to the candidate gene approach.
Peri-operative chemotherapy for resectable colorectal lung metastasis: a systematic review and meta-analysis
Authors: Li Yuting , Qin You 
Published: February 2020

Abstract
Purpose
Several studies have evaluated surgical resection of pulmonary metastases as a standard treatment option for colorectal cancer (CRC) patients with resectable pulmonary metastases. However, the role of peri-operative chemotherapy after complete resection of pulmonary metastases from CRC patients is still controversial. This systematic review and meta-analysis is aimed to investigate the clinical efficacy of peri-operative chemotherapy after resection of CRC pulmonary metastases.

Methods
PubMed, the Cochrane Library databases, and Embase were searched for studies evaluating the effect of peri-operative chemotherapy on the survival of patients with CRC after pulmonary metastasectomy. The hazard ratio (HR) was used for analyzing overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS).

Results
Eight studies were included in the final analysis. The outcome showed that peri-operative chemotherapy had a significant favourable effect on OS (HR 0.83, 95% CI 0.75–0.92, p < 0.05) and PFS/RFS/DFS (HR 0.67, 95% CI 0.53–0.86, p < 0.05) in patients who received pulmonary metastasectomy. Multivariate analysis also validated this result (OS: HR 0.56, 95% CI 0.36–0.86, p < 0.05; PFS/RFS/DFS: HR 0.64, 95% CI 0.46–0.87, p < 0.05). There was a significant benefit in peri-operative group on OS and PFS/RFS/DFS in studies with R0 resection of pulmonary metastases (OS: HR 0.72, 95% CI 0.53–0.97, p < 0.05; PFS/RFS/DFS: HR 0.72, 95% CI 0.54–0.95, p < 0.05) and metachronous pulmonary metastases (OS: HR 0.40, 95% CI 0.22–0.75, p < 0.05; PFS/RFS/DFS: HR 0.67, 95% CI 0.49–0.92, p < 0.05).

Conclusion
Our meta-analysis demonstrated a significant difference in favor of peri-operative chemotherapy in CRC patients who underwent resection of pulmonary metastases. More clinical data and studies are needed to validate the findings of our study.
New HER2-negative breast cancer subtype responsive to anti-HER2 therapy identified
Authors: MacNeil Ian A. , Burns David J. , Rich Benjamin E. , Soltani Sajjad M. , Kharbush Samantha , Osterhaus Nicole G. , Sullivan Brian F. , Hawkins Douglas M. , Pietruska Jodie R. , Laing Lance G. 
Published: February 2020

Abstract
Purpose
HER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient’s live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies.

Methods
The CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2−/HSFs+).

Results
HER2−/HSFs+ breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+ and HER2− cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI = 17–32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2−/HSFs+ patient population.

Conclusions
The CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+ population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20–25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.
Reliability of a radiation-free, noninvasive and computer-assisted assessment of the spine in children with cerebral palsy
Authors: Ruthard Kristina , Raabe-Oetker Anke , Ruthard Johannes , Oppermann Thomas , Duran Ibrahim , Schönau Eckhard 
Published: February 2020

AbstractPurposeThe radiation-free, noninvasive and computer-assisted Spinal Mouse®(SM) is a reliable and valid measuring instrument for functional analysis of the pediatric spine. The aim of this study was to examine the intra-rater reliability of the SM measurements in children with cerebral palsy (CP) and to investigate differences after a 1 week of the rehabilitation program.MethodsA total of 168 SM investigations in the sagittal plane and frontal plane at three measurement times from a sample of 28 children (n = 10 girls, age 9.7 ± 3.1 years) with CP were eligible for evaluation. For the verification of reliability, the measurement results from the first and second measurement times (t1,t2) were used at intervals of 1 day. In addition, differences after the rehabilitation program the patients underwent (t3) were evaluated using the measurement results of the first and third measurements (5-day interval).ResultsThe results show good to excellent intra-rater reliability for the SM measurements, both in the sagittal and in the frontal plane (ICC values = 0.69–0.99). Furthermore, significant changes may occur after only 1 week of therapeutic intervention for total spinal inclination (t1: 12.82 ± 5.40,t3: 11.11 ± 5.60,p = 0.014, Cohen’sd = 0.43) and spine length (t1: 401.75 ± 69.05,t3: 409.25 ± 63.58,p = 0.030, Cohen’sd = 0.43).ConclusionsSM can be used to generate reliable values for functional analysis of the spine in children with CP. Furthermore, significant posture differences can be demonstrated by therapeutic interventions, especially in the spine inclination (Inc) and spine length (SL).Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.
Challenges of neuropathic pain: focus on diabetic neuropathy
Authors: Rosenberger Daniela C. , Blechschmidt Vivian , Timmerman Hans , Wolff André , Treede Rolf-Detlef 
Published: February 2020

AbstractNeuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.