bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low skeletal muscle mass is associated with arterial stiffness in community-dwelling Chinese aged 45 years and older
Authors: Yang Mingzhe , Zhang Xuguang , Ding Zhenkai , Wang Feijie , Wang Yufang , Jiao Changya , Chen Jie-Hua 
Published: February 2020

AbstractBackgroundEvidence suggests that body composition has impact on arterial stiffness. However, evidence in Chinese are limited, and results remain controversial. The aim of our study is to investigate whether skeletal muscle mass is associated with arterial stiffness in Chinese community-dwelling men and women aged 45 years and older.MethodsIn this cross-sectional study, 20,477 participants (age range: 45–80 years, 68.8% women) were included in the analysis. Brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness was measured using a waveform device. Total muscle mass and muscle mass of arm, leg and trunk were measured by bioelectrical impedance analysis. Height and weight were measured and appendicular skeletal muscle mass index (ASMI) was calculated as appendicular skeletal muscle mass (sum of arm and leg muscle mass) divided by height square.ResultsAfter adjustment for age, body fat percentage, systolic blood pressure and diastolic blood pressure, ASMI was negatively associated with baPWV [β (SE) for men: − 0.208 (0.016),p < 0.0001; for women: − 0.245 (0.012),p < 0.0001]. High ASMI was a protective factor for the presence of arterial stiffness (defined as baPWV) [OR (95%CI) for men: 0.730 (0.682, 0.782),p < 0.0001; women: 0.634 (0.593, 0.677),p < 0.0001]. Similar associations were found between quantity of muscle mass (total and appendicular muscle mass, muscle mass of arm, leg and trunk) and arterial stiffness in men and women after further adjustment for height (allp < 0.0001).ConclusionLow skeletal muscle mass is associated with increased risk of arterial stiffness in Chinese community-dwelling adults aged 45 years and older.
The complex neurobiology of resilient functioning after childhood maltreatment
Authors: Ioannidis Konstantinos , Askelund Adrian Dahl , Kievit Rogier A. , van Harmelen Anne-Laura 
Published: February 2020

AbstractBackgroundChildhood maltreatment has been associated with significant impairment in social, emotional and behavioural functioning later in life. Nevertheless, some individuals who have experienced childhood maltreatment function better than expected given their circumstances.Main bodyHere, we provide an integrated understanding of the complex, interrelated mechanisms that facilitate such individual resilient functioning after childhood maltreatment. We aim to show that resilient functioning is not facilitated by any single ‘resilience biomarker’. Rather, resilient functioning after childhood maltreatment is a product of complex processes and influences across multiple levels, ranging from ‘bottom-up’ polygenetic influences, to ‘top-down’ supportive social influences. We highlight the complex nature of resilient functioning and suggest how future studies could embrace a complexity theory approach and investigate multiple levels of biological organisation and their temporal dynamics in a longitudinal or prospective manner. This would involve using methods and tools that allow the characterisation of resilient functioning trajectories, attractor states and multidimensional/multilevel assessments of functioning. Such an approach necessitates large, longitudinal studies on the neurobiological mechanisms of resilient functioning after childhood maltreatment that cut across and integrate multiple levels of explanation (i.e. genetics, endocrine and immune systems, brain structure and function, cognition and environmental factors) and their temporal interconnections.ConclusionWe conclude that a turn towards complexity is likely to foster collaboration and integration across fields. It is a promising avenue which may guide future studies aimed to promote resilience in those who have experienced childhood maltreatment.
Incremental value of three-dimensional echocardiography for evaluating left atrial function in patients with coronary slow flow phenomenon: a case control study
Authors: Li Jun , Wang Yonghuai , Zhao Cuiting , Zhu Qing , Li Guangyuan , Yang Jun , Jia Dalin , Ma Chunyan 
Published: February 2020

Abstract
Background
Coronary slow flow phenomenon (CSFP) involves the delayed opacification of the coronary distal vessel, in the absence of an obstructive lesion in the epicardial coronary artery during angiography. Since the link between left atrial (LA) function and decreased left ventricular function is still unclear, we evaluated LA function using real-time three-dimensional echocardiography (RT3DE) in patients with CSFP, and subsequently determined the incremental value of RT3DE.

Methods
This study enrolled 60 patients with CSFP and 45 control subjects. CSFP was diagnosed based on thrombolysis in myocardial infarction frame count (TFC). The LA phasic volume and function was evaluated by both two-dimensional echocardiography (2DE) and RT3DE.

Results
The LA maximal volume (Volmax), pre-systolic volume (Volp), and minimal volume (Volmin) increased, but LA total and active ejection fraction decreased in patients with CSFP. Based on our results, Volmax, Volp, Volmin, and LA total and active ejection fraction correlated with TFC, and with the number of arteries involved. The LA total ejection fraction by RT3DE was the only independent predictor for CSFP (odds ratio, 0.64 [95% confidence interval, 0.49–0.83]; P = 0.001). Also, the LA total ejection fraction by RT3DE demonstrated good predictive power for CSFP, with a cut-off value of 54.15% (area under curve, 0.85; sensitivity, 84%; specificity, 83%).

Conclusions
The LA reservoir and contractile function decreased in the patients with CSFP and correlated with coronary flow rate and with the number of arteries involved. The LA total ejection fraction by RT3DE can independently predict CSFP, and RT3DE demonstrated incremental value for evaluating LA phasic function in the patients with CSFP compared to 2DE.
Low-intensity ultrasound attenuates paw edema formation and decreases vascular permeability induced by carrageenan injection in rats
Authors: Kim Kil Hwan , Im Hyeon-Woo , Karmacharya Mrigendra Bir , Kim Sejong , Min Byoung-Hyun , Park So Ra , Choi Byung Hyune 
Published: February 2020

Abstract
Background
Therapeutic potential of low-intensity ultrasound (LIUS) has become evident in various musculoskeletal diseases. We have previously shown that LIUS has an inhibitory effect on local edema in various diseases including the arthritis and brain injury. In this study, we examined whether LIUS can attenuate paw edema formation vis-à-vis vascular permeability and inflammation in rats induced by carrageenan. LIUS with a frequency of 1 MHz and the intensities of 50, 100, or 200 mW/cm2 were exposed on rat paws for 10 min immediately after carrageenan injection.

Results
Carrageenan injection induced paw edema which was peaked at 6 h and gradually decreased nearly to the initial baseline value after 72 h. LIUS showed a significant reduction of paw edema formation at 2 and 6 h at all intensities tested. The highest reduction was observed at the intensity of 50 mW/cm2. Histological analyses confirmed that LIUS clearly decreased the carrageenan-induced swelling of interstitial space under the paw skin and infiltration of polymorphonuclear leukocytes. Moreover, Evans Blue extravasation analyses exhibited a significant decreases of vascular permeability by LIUS. Finally, immunohistochemical staining showed that expression of pro-inflammatory proteins, namely, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) induced by carrageenan injection was reduced back to the normal level after LIUS stimulation.

Conclusions
These results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis.
The eEF2 kinase-induced STAT3 inactivation inhibits lung cancer cell proliferation by phosphorylation of PKM2
Authors: Xiao Min , Xie Jianling , Wu Yu , Wang Genzhu , Qi Xin , Liu Zailiang , Wang Yuying , Wang Xuemin , Hoque Ashfaqul , Oakhill Jon , Proud Christopher G. , Li Jing 
Published: February 2020

Abstract
Background
Eukaryotic elongation factor-2 kinase (eEF2K) is a Ca 2+ /calmodulin (CaM)-dependent protein kinase that inhibits protein synthesis. However, the role of eEF2K in cancer development was reported paradoxically and remains to be elucidated.

Methods
Herein, A549 cells with eEF2K depletion or overexpression by stably transfected lentivirus plasmids were used in vitro and in vivo study. MTT and colony assays were used to detect cell proliferation and growth. Extracellular glucose and lactate concentration were measured using test kit. Immunoblot and co-immunoprecipitation assays were used to examine the molecular biology changes and molecular interaction in these cells. LC-MS/MS analysis and [γ- 32 P] ATP kinase assay were used to identify combining protein and phosphorylation site. Nude mice was utilized to study the correlation of eEF2K and tumor growth in vivo.

Results
We demonstrated that eEF2K inhibited lung cancer cells proliferation and affected the inhibitory effects of EGFR inhibitor gefitinib. Mechanistically, we showed that eEF2K formed a complex with PKM2 and STAT3, thereby phosphorylated PKM2 at T129, leading to reduced dimerization of PKM2. Subsequently, PKM2 impeded STAT3 phosphorylation and STAT3-dependent c-Myc expression. eEF2K depletion promoted the nuclear translocation of PKM2 and increased aerobic glycolysis reflected by increased lactate secretion and glucose.

Conclusions
Our findings define a novel mechanism underlying the regulation of cancer cell proliferation by eEF2K independent of its role in protein synthesis, disclosing the diverse roles of eEF2K in cell biology, which lays foundation for the development of new anticancer therapeutic strategies.
Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients
Authors:   Italian Melanoma Intergroup (I.M.I.), Ciccarese Giulia , Dalmasso Bruna , Bruno William , Queirolo Paola , Pastorino Lorenza , Andreotti Virginia , Spagnolo Francesco , Tanda Enrica , Ponti Giovanni , Massone Cesare , Drago Francesco , Parodi Aurora , Ghigliotti Giovanni , Pizzichetta Maria Antonietta , Ghiorzo Paola 
Published: February 2020

Abstract
Background
The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF−), including dermoscopic findings of melanomas and dysplastic nevi.

Methods
we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available.

Results
After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF−. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF−). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF− patients, whose most prevalent pattern was the multicomponent.

Conclusions
MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF− patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.
YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling
Authors: Zhou Qimin , Bauden Monika , Andersson Roland , Hu Dingyuan , Marko-Varga György , Xu Jianfeng , Sasor Agata , Dai Hua , Pawłowski Krzysztof , Said Hilmersson Katarzyna , Chen Xi , Ansari Daniel 
Published: February 2020

Abstract
Background
Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue.

Methods
YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP–TEAD interaction, including Super-TDU, Verteporfin and CA3.

Results
Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E−06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224–2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299–2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction.

Conclusions
Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.
A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation
Authors: Betjes Michiel G. H. , Langerak Anton W. , Klepper Mariska , Litjens Nicolle H. R. 
Published: February 2020

AbstractBackgroundEnd-stage renal disease is associated with premature ageing of the T cell immune system but inter-individual variation is substantial. The hypothesis was tested that advanced immunological T cell ageing assessed by peripheral T cell differentiation increases the long-term mortality risk after renal transplantation.ResultsCirculating T cells of 211 recipients of a kidney from a living donor were analyzed before and in the first year after transplantation. The number of CD31-positive naive T cells (as a marker for recent thymic emigrants) and the differentiation status of the memory T cells was assessed. Thirty recipients died during follow-up of at least 5 years. Absolute numbers of naive CD4+(living:258 cells/μl vs. deceased:101 cells/μl,p < 0.001) and naive CD8+T cells (living:97 cells/μl vs. deceased:37 cells/μl, p < 0.001) were significantly lower in the deceased group prior to transplantation. In a multivariate proportional hazard analysis the number of naive CD4+T cells remained associated with all-cause mortality (HR 0.98, CI 0.98–0.99,p < 0.001). The low number of naive T cells in the deceased patient group was primarily caused by a decrease in recent thymic emigrants (i.e. less CD31+naive T cells) indicating a lowered thymus function. In addition, the physiological age-related compensatory increase in CD31−naïve T cells was not observed. Within the first year after transplantation, the number and characteristics of naive T cells remained stable.ConclusionsA severe reduction in circulating naïve T cells because of a decrease in recent thymic emigrants is highly associated with all-cause mortality after renal transplantation.
Assessment of bilateral motor skills and visuospatial attention in children with perinatal stroke using a robotic object hitting task
Authors: Hawe Rachel L. , Kuczynski Andrea M. , Kirton Adam , Dukelow Sean P. 
Published: February 2020

Abstract
Background
While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention.

Methods
Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures.

Results
The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional (“unaffected”) arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21–32% of the variance in number of balls hit with the unaffected hand.

Conclusions
Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.
Drought and heat stress tolerance screening in wheat using computed tomography
Authors: Schmidt Jessica , Claussen Joelle , Wörlein Norbert , Eggert Anja , Fleury Delphine , Garnett Trevor , Gerth Stefan 
Published: February 2020

Abstract
Background
Improving abiotic stress tolerance in wheat requires large scale screening of yield components such as seed weight, seed number and single seed weight, all of which is very laborious, and a detailed analysis of seed morphology is time-consuming and visually often impossible. Computed tomography offers the opportunity for much faster and more accurate assessment of yield components.

Results
An X-ray computed tomographic analysis was carried out on 203 very diverse wheat accessions which have been exposed to either drought or combined drought and heat stress. Results demonstrated that our computed tomography pipeline was capable of evaluating grain set with an accuracy of 95–99%. Most accessions exposed to combined drought and heat stress developed smaller, shrivelled seeds with an increased seed surface. As expected, seed weight and seed number per ear as well as single seed size were significantly reduced under combined drought and heat compared to drought alone. Seed weight along the ear was significantly reduced at the top and bottom of the wheat spike.

Conclusions
We were able to establish a pipeline with a higher throughput with scanning times of 7 min per ear and accuracy than previous pipelines predicting a set of agronomical important seed traits and to visualize even more complex traits such as seed deformations. The pipeline presented here could be scaled up to use for high throughput, high resolution phenotyping of tens of thousands of heads, greatly accelerating breeding efforts to improve abiotic stress tolerance.
Evaluation of plan quality and robustness of IMPT and helical IMRT for cervical cancer
Authors: Shang Haijiao , Pu Yuehu , Wang Wei , Dai Zhitao , Jin Fu 
Published: February 2020

Abstract
Background
Both plan quality and robustness were investigated through comparing some dosimetric metrics between intensity modulated proton therapy (IMPT) and helical tomotherapy based intensity modulated radiotherapy (IMRT) for cervical cancer.

Methods
Both a spot-scanning robust (SRO) IMPT plan and a helical tomotherapy robust (TRO) IMRT plan were generated for each of 18 patients. In order to evaluate the quality of nominal plans without dose perturbations, planning scores (PS) on clinical target volume (CTV) and five organs at risk (OARs) based on clinical experience, and normal tissue complication probabilities (NTCP) of rectum and sigmoid were calculated based on Lyman-Kutcher-Burman (LKB) model. Dose volume histogram bands width (DVHBW) were calculated in 28 perturbed scenarios to evaluate plan robustness.

Results
Compared with TRO, the average scores of SRO nominal plans were higher in target metrics [V46.8Gy, V50Gy, Conformity and Homogeneity](16.5 vs. 15.1), and in OARs metrics (60.9 vs. 53.3), including bladder [V35,V45, Dmean,D2cc], rectum [V40,V45,D2cc,Dmax], bowel [V35,V40,V45, Dmax], sigmoid [V40,Dmax] and femoral heads [V30,Dmax]. Meanwhile, NTCP calculation showed that the toxicities of rectum and sigmoid in SRO were lower than those in TRO (rectum: 2.8% vs. 4.8%, p < 0.05; sigmoid: 5.2% vs. 5.7%, p < 0.05). DVHBW in target coverage for the SRO plan was smaller than that for the TRO plan (0.6% vs. 2.1%), which means that the SRO plan generated a more robust plan in target.

Conclusion
Better CTV coverage and OAR Sparing were obtained in SRO nominal plan. Based on NTCP calculation, SRO was expected to allow a small reduction in rectal toxicity. Furthermore, SRO generated a more robust plan in CTV target coverage.