bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple risk score based on the China Acute Myocardial Infarction registry for predicting in-hospital mortality among patients with non-ST-segment elevation myocardial infarction: results of a prospective observational cohort study
Authors: Song Chenxi , Fu Rui , Li Sidong , Yang Jingang , Wang Yan , Xu Haiyan , Gao Xiaojin , Liu Jia , Liu Qianqian , Wang Chunyue , Dou Kefei , Yang Yuejin 
Published: September 2019

ObjectivesTo simplify our previous risk score for predicting the in-hospital mortality risk in patients with non-ST-segment elevation myocardial infarction (NSTEMI) by dropping laboratory data.DesignProspective cohort.SettingMulticentre, 108 hospitals across three levels in China.ParticipantsA total of 5775 patients with NSTEMI enrolled in the China Acute Myocardial Infarction (CAMI) registry.Primary outcome measuresIn-hospital mortality.ResultsThe simplified CAMI-NSTEMI (SCAMI-NSTEMI) score includes the following nine variables: age, body mass index, systolic blood pressure, Killip classification, cardiac arrest, ST-segment depression on ECG, smoking status, previous angina and previous percutaneous coronary intervention. Within both the derivation and validation cohorts, the SCAMI-NSTEMI score showed a good discrimination ability (C-statistics: 0.76 and 0.83, respectively); further, the SCAMI-NSTEMI score had a diagnostic performance superior to that of the Global Registry of Acute Coronary Events risk score (C-statistics: 0.78 and 0.73, respectively; p<0.0001 for comparison). The in-hospital mortality increased significantly across the different risk groups.ConclusionsThe SCAMI-NSTEMI score can serve as a useful tool facilitating rapid risk assessment among a broader spectrum of patients admitted owing to NSTEMI.Trial registration numberNCT01874691.
Does diabetes influence the probability of experiencing chronic low back pain? A population-based cohort study: the Nord-Trøndelag Health Study
Authors: Heuch Ingrid , Heuch Ivar , Hagen Knut , Sørgjerd Elin Pettersen , Åsvold Bjørn Olav , Zwart John-Anker 
Published: September 2019

ObjectiveLow back pain (LBP) is a major problem in modern society and it is important to study possible risk factors for this disorder. People with diabetes are often affected by LBP, but whether diabetes represents a risk factor for LBP has not been studied in detail. The aim of this study was to explore the association between diabetes and subsequent risk of chronic LBP.DesignAn 11-year follow-up study.SettingThe Nord-Trøndelag Health Study (HUNT2; 1995–1997) and HUNT3 (2006–2008) surveys of Nord-Trøndelag County in Norway.Main outcome measureChronic LBP, defined as LBP persisting at least 3 months continuously during the last year.ParticipantsA total of 18 972 persons without chronic LBP at baseline in HUNT2, and 6802 persons who reported chronic LBP at baseline in HUNT2.MethodsAssociations between diabetes and risk of chronic LBP among individuals aged 30–69 years were examined by generalised linear modelling.ResultsMen without chronic LBP at baseline showed a significant association between diabetes and risk of chronic LBP (relative risk (RR) 1.43, 95% CI 1.04 to 1.96, p=0.043). In women, no association was found (RR 1.01, 95% CI 0.69 to 1.48, p=0.98). No association could be established between diabetes and recurrence or persistence of chronic LBP after 11 years in either sex.ConclusionsMen with a diagnosis of diabetes may have a higher risk of subsequently experiencing chronic LBP.
Risk factors for head and neck cancer in the World Trade Center Health Program General Responder Cohort: results from a nested case–control study
Authors: Bover Manderski Michelle T , Black Kathleen , Udasin Iris G , Giuliano Anna R , Steinberg Michael B , Ohman Strickland Pamela , Black Taylor M , Dasaro Christopher R , Crane Michael , Harrison Denise , Moline Jacqueline , Luft Benjamin J , Passannante Marian R , Lucchini Roberto G , Todd Andrew C , Graber Judith M 
Published: September 2019

ObjectivesHead and neck cancers (HNCs) may be among the health consequences of involvement in the World Trade Center (WTC) response on and after 11 September 2001. We conducted a nested case–control study of WTC Health Program (WTCHP) general responders to examine the effects of WTC exposures and behavioural risk factors on HNC.MethodsWe enrolled 64 cases and 136 controls, matched on age, sex and race/ethnicity within risk sets. We assessed tobacco and alcohol use, sexual activity, and occupational exposures prior to, during and after WTC exposure until case diagnosis via questionnaire. We obtained WTC exposure information (duration (first to last day), total days and location of work) from the WTCHP General Responder Data Center. We assessed associations with HNC, and interaction among exposures, using conditional logistic regression.ResultsResponders in protective services versus other occupations had increased odds (OR: 2.51, 95% CI 1.09 to 5.82) of HNC. Among those in non-protective services occupations, arriving to the WTC effort on versus after 11 September 2001 was significantly associated with HNC (OR: 3.77, 95% CI 1.00 to 14.11). Duration of work was not significantly associated with HNC. Lifetime and post-WTC years of cigarette smoking and post-WTC number of sex partners were positively and significantly associated with HNC, while alcohol consumption was not.ConclusionsThese findings suggest opportunities for HNC risk factor mitigation (eg, smoking cessation, human papillomavirus vaccination) and contribute to a risk factor profile which may assist WTCHP clinicians with identifying high-risk responders and improve detection and treatment outcomes in this population.
Opacity dependence of elliptic flow in kinetic theory
Authors: Kurkela Aleksi , Wiedemann Urs Achim , Wu Bin 
Published: September 2019

Abstract
The observation of large azimuthal anisotropies $$v_n$$vn in the particle spectra of proton–proton (pp) and proton–nucleus (pA) collisions challenges fluid dynamic interpretations of $$v_n$$vn, as it remains unclear how small collision systems can hydrodynamize and to what extent hydrodynamization is needed to build up $$v_n$$vn. Here, we study in a simple kinetic theory how the same physics that leads to hydrodynamization in large systems represents itself in small systems. We observe that one third to one half of the elliptic flow signal seen in fully hydrodynamized systems can be built up in collisions that extend over only one mean free path $$l_\mathrm{mfp}$$lmfp and that do not hydrodynamize. This is qualitatively in line with observing a sizeable $$v_2$$v2 in pp collisions for which other characteristics of soft multi-particle production seem well-described in a free-streaming picture. We further expose a significant system size dependence in the accuracy of hybrid approaches that match kinetic theory to viscous fluid dynamics. The implications of these findings for a reliable extraction of shear viscosity are discussed.
Skeletal muscle mitochondrial function and exercise capacity are not impaired in mice with knockout of STAT3
Authors: Dent Jessica R. , Hetrick Byron , Tahvilian Shahriar , Sathe Abha , Greyslak Keenan , LaBarge Samuel A. , Svensson Kristoffer , McCurdy Carrie E. , Schenk Simon 
Published: September 2019

Signal transducer and activator of transcription 3 (STAT3) was recently found to be localized to mitochondria in a number of tissues and cell types, where it modulates oxidative phosphorylation via interactions with the electron transport proteins, complex I and complex II. Skeletal muscle is densely populated with mitochondria although whether STAT3 contributes to skeletal muscle oxidative capacity is unknown. In the present study, we sought to elucidate the contribution of STAT3 to mitochondrial and skeletal muscle function by studying mice with muscle-specific knockout of STAT3 (mKO). First, we developed a novel flow cytometry-based approach to confirm that STAT3 is present in skeletal muscle mitochondria. However, contrary to findings in other tissue types, complex I and complex II activity and maximal mitochondrial respiratory capacity in skeletal muscle were comparable between mKO mice and floxed/wild-type littermates. Moreover, there were no genotype differences in endurance exercise performance, skeletal muscle force-generating capacity, or the adaptive response of skeletal muscle to voluntary wheel running. Collectively, although we confirm the presence of STAT3 in skeletal muscle mitochondria, our data establish that STAT3 is dispensable for mitochondrial and physiological function in skeletal muscle.NEW & NOTEWORTHY Whether signal transducer and activator of transcription 3 (STAT3) can regulate the activity of complex I and II of the electron transport chain and mitochondrial oxidative capacity in skeletal muscle, as it can in other tissues, is unknown. By using a mouse model lacking STAT3 in muscle, we demonstrate that skeletal muscle mitochondrial and physiological function, both in vivo and ex vivo, is not impacted by the loss of STAT3.
Diffuse correlation spectroscopy and frequency-domain near-infrared spectroscopy for measuring microvascular blood flow in dynamically exercising human muscles
Authors: Quaresima Valentina , Farzam Parisa , Anderson Pamela , Farzam Parya Y. , Wiese Daniel , Carp Stefan A. , Ferrari Marco , Franceschini Maria Angela 
Published: September 2019

In the last 20 yr, near-infrared diffuse correlation spectroscopy (DCS) has been developed for providing a noninvasive estimate of microvascular blood flow (BF) as a BF index (BFi) in the human skin, muscle, breast, brain, and other tissue types. In this study, we proposed a new motion correction algorithm for DCS-derived BFi able to remove motion artifacts during cycling exercise. We tested this algorithm on DCS data collected during cycling exercise and demonstrated that DCS can be used to quantify muscle BFi during dynamic high-intensity exercise. In addition, we measured tissue regional oxygen metabolic rate (MRO2i) by combining frequency-domain multidistance near-infrared spectroscopy (FDNIRS) oximetry with DCS flow measures. Recreationally active subjects ( n = 12; 31 ± 8 yr, 183 ± 4 cm, 79 ± 10 kg) pedaled at 80–100 revolutions/min until volitional fatigue with a work rate increase of 30 W every 4 min. Exercise intensity was normalized in each subject to the cycling power peak (Wpeak). Both rectus femoris BFi and MRO2i increased from 15% up to 75% Wpeak and then plateaued to the end of the exercise. During the recovery at 30 W cycling power, BFi remained almost constant, whereas MRO2i started to decrease. The BFi/MRO2i plateau was associated with the rising of the lactate concentration, indicating the progressive involvement of the anaerobic metabolism. These findings further highlight the utility of DCS and FDNIRS oximetry as effective, reproducible, and noninvasive techniques to assess muscle BFi and MRO2i in real time during a dynamic exercise such as cycling. NEW & NOTEWORTHY To the best of our knowledge, this study is the first to demonstrate that diffuse correlation spectroscopy in combination with frequency-domain near-infrared spectroscopy can monitor human quadriceps microvascular blood flow and oxygen metabolism with high temporal resolution during a cycling exercise. The optically measured parameters confirm the expected relationship between blood flow, muscle oxidative metabolism, and lactate production during exercise.
Respiratory-related displacement of the trachea in obstructive sleep apnea
Authors: Tong Joshua , Jugé Lauriane , Burke Peter GR , Knapman Fiona , Eckert Danny J , Bilston Lynne E , Amatoury Jason 
Published: September 2019

Tracheal displacement is thought to be the primary mechanism by which changes in lung volume influence upper airway patency. Caudal tracheal displacement during inspiration may help preserve the integrity of the upper airway in response to increasing negative airway pressure by stretching and stiffening pharyngeal tissues. However, tracheal displacement has not been previously quantified in obstructive sleep apnea (OSA). Accordingly, we aimed to measure tracheal displacements in awake individuals with and without OSA. The upper head and neck of 34 participants [apnea-hypopnea index (AHI) = 2–74 events/h] were imaged in the midsagittal plane using dynamic magnetic resonance imaging (MRI) during supine awake quiet breathing. MRI data were analyzed to identify peak tracheal displacement and its timing relative to inspiration. Epiglottic pressure was measured separately for a subset of participants ( n = 30) during similar experimental conditions. Nadir epiglottic pressure and its timing relative to inspiration were quantified. Peak tracheal displacement ranged from 1.0–9.6 mm, with a median (25th–75th percentile) of 2.3 (1.7–3.5) mm, and occurred at 89 (78–99)% of inspiratory time. Peak tracheal displacement increased with increasing OSA severity (AHI) ( R2 = 0.28, P = 0.013) and increasing negative nadir epiglottic pressure ( R2 = 0.47, P = 0.023). Relative inspiratory timing of peak tracheal displacement also correlated with OSA severity, with peak displacement occurring earlier in inspiration with increasing AHI ( R2 = 0.36, P = 0.002). Tracheal displacements during quiet breathing are larger in individuals with more severe OSA and tend to reach peak displacement earlier in the inspiratory cycle. Increased tracheal displacement may contribute to maintenance of upper airway patency during wakefulness in OSA, particularly in those with severe disease. NEW & NOTEWORTHY Tracheal displacement is thought to play an important role in stabilizing the upper airway by stretching/stiffening the pharyngeal musculature. Using dynamic magnetic resonance imaging, this study shows that caudal tracheal displacement is more pronounced during inspiration in obstructive sleep apnea (OSA) compared with healthy individuals. Softer pharyngeal muscles and greater inspiratory forces in OSA may underpin greater tracheal excursion. These findings suggest that tracheal displacement may contribute to maintenance of pharyngeal patency during wakefulness in OSA.
Consistent expression pattern of myogenic regulatory factors in whole muscle and isolated human muscle satellite cells after eccentric contractions in humans
Authors: Nederveen Joshua P. , Fortino Stephen A. , Baker Jeff M. , Snijders Tim , Joanisse Sophie , McGlory Chris , McKay Bryon R. , Kumbhare Dinesh , Parise Gianni 
Published: September 2019

Skeletal muscle satellite cells (SC) play an important role in muscle repair following injury. The regulation of SC activity is governed by myogenic regulatory factors (MRF), including MyoD, Myf5, myogenin, and MRF4. The mRNA expression of these MRF in humans following muscle damage has been predominately measured in whole muscle homogenates. Whether the temporal expression of MRF in a whole muscle homogenate reflects SC-specific expression of MRF remains largely unknown. Sixteen young men (23.1 ± 1.0 yr) performed 300 unilateral eccentric contractions (180°/s) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis were taken before (Pre) and 48 h postexercise. Fluorescence-activated cell sorting analysis was utilized to purify NCAM+muscle SC from the whole muscle homogenate. Forty-eight hours post-eccentric exercise, MyoD, Myf5, and myogenin mRNA expression were increased in the whole muscle homogenate (~1.4-, ~4.0-, ~1.7-fold, respectively, P < 0.05) and in isolated SC (~19.3-, ~17.5-, ~58.9-fold, respectively, P < 0.05). MRF4 mRNA expression was not increased 48 h postexercise in the whole muscle homogenate ( P > 0.05) or in isolated SC ( P > 0.05). In conclusion, our results suggest that the directional changes in mRNA expression of the MRF in a whole muscle homogenate in response to acute eccentric exercise reflects that observed in isolated muscle SC.NEW & NOTEWORTHY The myogenic program is controlled via transcription factors referred to as myogenic regulatory factors (MRF). Previous studies have derived MRF expression from whole muscle homogenates, but little work has examined whether the mRNA expression of these transcripts reflects the pattern of expression in the actual population of satellite cells (SC). We report that MRF expression from an enriched SC population reflects the directional pattern of expression from skeletal muscle biopsy samples following eccentric contractions.
Drug Sensitivity Prediction Models Reveal a Link between DNA Repair Defects and Poor Prognosis in HNSCC
Authors: Essers Paul B.M. , van der Heijden Martijn , Verhagen Caroline V.M. , Ploeg Emily M. , de Roest Reinout H. , Leemans C. René , Brakenhoff Ruud H. , van den Brekel Michiel W.M. , Bartelink Harry , Verheij Marcel , Vens Conchita 
Published: September 2019

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by the frequent manifestation of DNA crosslink repair defects. We established novel expression-based DNA repair defect markers to determine the clinical impact of such repair defects. Using hypersensitivity to the DNA crosslinking agents, mitomycin C and olaparib, as proxies for functional DNA repair defects in a panel of 25 HNSCC cell lines, we applied machine learning to define gene expression models that predict repair defects. The expression profiles established predicted hypersensitivity to DNA-damaging agents and were associated with mutations in crosslink repair genes, as well as downregulation of DNA damage response and repair genes, in two independent datasets. The prognostic value of the repair defect prediction profiles was assessed in two retrospective cohorts with a total of 180 patients with advanced HPV-negative HNSCC, who were treated with cisplatin-based chemoradiotherapy. DNA repair defects, as predicted by the profiles, were associated with poor outcome in both patient cohorts. The poor prognosis association was particularly strong in normoxic tumor samples and was linked to an increased risk of distant metastasis. In vitro, only crosslink repair–defective HNSCC cell lines are highly migratory and invasive. This phenotype could also be induced in cells by inhibiting rad51 in repair competent and reduced by DNA-PK inhibition. In conclusion, DNA crosslink repair prediction expression profiles reveal a poor prognosis association in HNSCC.

Significance:
This study uses innovative machine learning-based approaches to derive models that predict the effect of DNA repair defects on treatment outcome in HNSCC.
Response to Anti-EGFR Therapy in Patients with BRAF non-V600–Mutant Metastatic Colorectal Cancer
Authors: Yaeger Rona , Kotani Daisuke , Mondaca Sebastián , Parikh Aparna R. , Bando Hideaki , Van Seventer Emily E. , Taniguchi Hiroya , Zhao HuiYong , Thant Claire N. , de Stanchina Elisa , Rosen Neal , Corcoran Ryan B. , Yoshino Takayuki , Yao Zhan , Ebi Hiromichi 
Published: September 2019

Abstract

Purpose:
While mutations in BRAF in metastatic colorectal cancer (mCRC) most commonly occur at the V600 amino acid, with the advent of next-generation sequencing, non-V600 BRAF mutations are increasingly identified in clinical practice. It is unclear whether these mutants, like BRAF V600E, confer resistance to anti-EGFR therapy.

Experimental Design:
We conducted a multicenter pooled analysis of consecutive patients with non-V600 BRAF-mutated mCRCs identified between 2010 and 2017. Non-V600 BRAF mutations were divided into functional classes based on signaling mechanism and kinase activity: activating and RAS-independent (class 2) or kinase-impaired and RAS-dependent (class 3).

Results:
Forty patients with oncogenic non-V600 BRAF–mutant mCRC received anti-EGFR antibody treatment [n = 12 (30%) class 2 and n = 28 (70%) class 3]. No significant differences in clinical characteristics were observed by mutation class. In contrast, while only 1 of 12 patients with class 2 BRAF mCRC responded, 14 of 28 patients with class 3 BRAF responded to anti-EGFR therapy (response rate, 8% and 50%, respectively, P = 0.02). Specifically, in first- or second-line, 1 of 6 (17%) patients with class 2 and 7 of 9 (78%) patients with class 3 BRAF mutants responded (P = 0.04). In third- or later-line, none of 6 patients with class 2 and 7 of 19 (37%) patients with class 3 BRAF mutants responded (P = 0.14).

Conclusions:
Response to EGFR antibody treatment in mCRCs with class 2 BRAF mutants is rare, while a large portion of CRCs with class 3 BRAF mutants respond. Patients with colorectal cancer with class 3 BRAF mutations should be considered for anti-EGFR antibody treatment.
See related commentary by Fontana and Valeri, p. 6896
Model Informed Drug Development: Novel Oncology Agents are Lost in Translation
Authors: Mayawala Kapil , de Alwis Dinesh P. , Sachs Jeffrey R. 
Published: September 2019

Abstract
Excitement around and investment in oncology drug development are at unprecedented levels. To maximize the health impact and productivity of this research and development investment, quantitative modeling should impact key decisions in early clinical oncology including Go/No-Go decisions based on early clinical data, and dose selection for late stage studies.
See related article by Bottino et al., p. 6633
Ovarian Primary and Metastatic Tumors Suppressed by Survivin Knockout or a Novel Survivin Inhibitor
Authors: Zhao Guannan , Wang Qinghui , Wu Zhongzhi , Tian Xinchun , Yan Huan , Wang Baojin , Dong Peixin , Watari Hidemichi , Pfeffer Lawrence M. , Guo Yuqi , Li Wei , Yue Junming 
Published: September 2019

AbstractSurvivin, a member of the inhibitor of apoptosis family, is upregulated in multiple cancers including ovarian cancer, but is rarely detectable in normal tissues. We previously reported that survivin promoted epithelial-to-mesenchymal transition (EMT) in ovarian cancer cells, suggesting that survivin may contribute to ovarian tumor metastasis and chemoresistance. In this study, we tested whether knockout or pharmacologic inhibition of survivin overcomes chemoresistance and suppresses tumor metastasis. The genetic loss of survivin suppressed tumor metastasis in an orthotopic ovarian cancer mouse model. To pharmacologically test the role of survivin on ovarian tumor metastasis, we treated chemo-resistant ovarian cancer cells with a selective survivin inhibitor, MX106, and found that MX106 effectively overcame chemoresistance in vitro. MX106 inhibited cell migration and invasion by attenuating the TGFβ pathway and inhibiting EMT in ovarian cancer cells. To evaluate the efficacy of MX106 in inhibiting ovarian tumor metastasis, we treated an orthotopic ovarian cancer mouse model with MX106, and found that MX106 efficiently inhibited primary tumor growth in ovaries and metastasis in multiple peritoneal organs as compared with vehicle-treated control mice. Our data demonstrate that inhibition of survivin using either genetic knockout or a novel inhibitor MX106 suppresses primary ovarian tumor growth and metastasis, supporting that targeting survivin could be an effective therapeutic approach in ovarian cancer.