bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma
Authors: Cubillos-Zapata Carolina , Martínez-García Miguel Ángel , Díaz-García Elena , Jaureguizar Ana , Campos-Rodríguez Francisco , Sánchez-de-la-Torre Manuel , Nagore Eduardo , Martorell-Calatayud Antonio , Blasco Luis Hernández , Pastor Esther , Abad-Capa Jorge , Montserrat Josep María , Cabriada-Nuño Valentín , Cano-Pumarega Irene , Corral-Peñafiel Jaime , Arias Eva , Mediano Olga , Somoza-González María , Dalmau-Arias Joan , Almendros Isaac , Farré Ramón , López-Collazo Eduardo , Gozal David , García-Río Francisco 
Published: September 2020

AbstractActive transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.
A protein-coated micro-sucker patch inspired by octopus for adhesion in wet conditions
Authors: Meloni Gabriella , Tricinci Omar , Degl’Innocenti Andrea , Mazzolai Barbara 
Published: September 2020

AbstractIn medical robotics, micromanipulation becomes particularly challenging in the presence of blood and secretions. Nature offers many examples of adhesion strategies, which can be divided into two macro-categories: morphological adjustments and chemical adaptations. This paper analyzes how two successful specializations from different marine animals can converge into a single biomedical device usable in moist environments. Taking inspiration from the morphology of the octopus sucker and the chemistry of mussel secretions, we developed a protein-coated octopus-inspired micro-sucker device that retains in moist conditions about half of the adhesion it shows in dry environments. From a robotic perspective, this study emphasizes the advantages of taking inspiration from specialized natural solutions to optimize standard robotic designs.
A modified protocol of Capture-C allows affordable and flexible high-resolution promoter interactome analysis
Authors: Golov Arkadiy K. , Abashkin Dmitrii A. , Kondratyev Nikolay V. , Razin Sergey V. , Gavrilov Alexey A. , Golimbet Vera E. 
Published: September 2020

AbstractLarge-scale epigenomic projects have mapped hundreds of thousands of potential regulatory sites in the human genome, but only a small proportion of these elements are proximal to transcription start sites. It is believed that the majority of these sequences are remote promoter-activating genomic sites scattered within several hundreds of kilobases from their cognate promoters and referred to as enhancers. It is still unclear what principles, aside from relative closeness in the linear genome, determine which promoter(s) is controlled by a given enhancer; however, this understanding is of great fundamental and clinical relevance. In recent years, C-methods (chromosome conformation capture-based methods) have become a powerful tool for the identification of enhancer–promoter spatial contacts that, in most cases, reflect their functional link. Here, we describe a new hybridisation-based promoter Capture-C protocol that makes use of biotinylated dsDNA probes generated by PCR from a custom pool of long oligonucleotides. The described protocol allows high-resolution promoter interactome description, providing a flexible and cost-effective alternative to the existing promoter Capture-C modifications. Based on the obtained data, we propose several tips on probe design that could potentially improve the results of future experiments.
Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array
Authors: Jiman Ahmad A. , Ratze David C. , Welle Elissa J. , Patel Paras R. , Richie Julianna M. , Bottorff Elizabeth C. , Seymour John P. , Chestek Cynthia A. , Bruns Tim M. 
Published: September 2020

AbstractAutonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8–9 µm in diameter, 150–250 µm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1–91.7 µV and signal-to-noise ratios of 2.0–8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7–4.4 m/s) and efferent (0.7–8.8 m/s) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.
Conditional effects of gaze on automatic imitation: the role of autistic traits
Authors: Trilla Irene , Wnendt Hannah , Dziobek Isabel 
Published: September 2020

AbstractEstablishing direct gaze has been shown to enhance the tendency to automatically imitate the other person’s actions, an effect that seems to be reduced in autism. Most previous studies, however, used experimental tasks that may have confounded the measurement of automatic imitation with spatial compatibility effects. This calls into question whether gaze cues regulate automatic imitation, or instead affect domain-general processes of response inhibition. Using a task that disentangled imitative from spatial compatibility effects, the current study re-examined the role of autistic traits on the modulation of automatic imitation by direct and averted gaze cues. While our results do not provide evidence for an overall significant influence of gaze on neither automatic imitation nor spatial compatibility, autistic traits were predictive of a reduced inhibition of imitative behaviour following averted gaze. Nonetheless, exploratory analyses suggested that the observed modulation by autistic traits may actually be better explained by the effects of concomitant social anxiety symptoms. In addition, the ethnicity of the imitated agent was identified as another potential modulator of the gaze effects on automatic imitation. Overall, our findings highlight the contextual nature of automatic imitation, but call for a reconsideration of the role of gaze on imitative behaviour.
A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014
Authors: Nishimura Yoshito , Harada Ko , Koyama Toshihiro , Hagiya Hideharu , Otsuka Fumio 
Published: September 2020

AbstractIn the era of hyper-ageing, Creutzfeldt–Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005–2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4–5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7–8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.
Injectable pre-cultured tissue modules catalyze the formation of extensive functional microvasculature in vivo
Authors: Friend Nicole E. , Rioja Ana Y. , Kong Yen P. , Beamish Jeffrey A. , Hong Xiaowei , Habif Julia C. , Bezenah Jonathan R. , Deng Cheri X. , Stegemann Jan P. , Putnam Andrew J. 
Published: September 2020

AbstractRevascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds. Here, we developed cell-laden fibrin microbeads that can be pre-cultured to form primitive vascular networks within the modular structures. These microbeads can be delivered in a minimally invasive manner and form functional microvasculature in vivo. Microbeads containing endothelial cells and stromal fibroblasts were pre-cultured for 3 days in vitro and then injected within a fibrin matrix into subcutaneous pockets on the dorsal flanks of SCID mice. Vessels deployed from these pre-cultured microbeads formed functional connections to host vasculature within 3 days and exhibited extensive, mature vessel coverage after 7 days in vivo. Cellular microbeads showed vascularization potential comparable to bulk cellular hydrogels in this pilot study. Furthermore, our findings highlight some potentially advantageous characteristics of pre-cultured microbeads, such as volume preservation and vascular network distribution, which may be beneficial for treating ischemic diseases.
Stability and robustness of asymptotic autocatalytic systems
Authors: Yun-Cárcamo Sohyoun , Carrasco Sebastián , Rogan José , Correa-Burrows Paulina , Valdivia Juan Alejandro 
Published: September 2020

AbstractHere, we address the consequences of the extension in the space of a simple model of a system that is closed to efficient causation: the (M,R)-system model. To do so, we use a diffusion term to describe the collective motion of the nutrients’ concentration across the compartmentalized space that defines the organism. We show that the non-trivial stable steady state remains despite such generalization, as long as the system is small enough to deal with the transport of the precursors to feed the entire protocell and dispose of a sufficient concentration of it in its surroundings. Such consideration explains the emergence of a bifurcation with two parameters that we characterize. Finally, we show that the robustness of the system under catastrophic losses of catalysts also remains, preserving the original’s model character.
Higher visit-to-visit total cholesterol variability is associated with lower cognitive function among middle-aged and elderly Chinese men
Authors: Hua Jianian , Qiao Yanan , Ke Chaofu , Shen Yueping 
Published: September 2020

AbstractTo examine the prospective associations between total cholesterol (TC) variability and cognitive function in a large sample of Chinese participants aged 45 years and above. A total of 6,377 people who participated in the China Health and Retirement Longitudinal Study (CHARLS) were included. TC variability was defined as the intra-individual standard deviation over two blood tests in CHARLS 2011 and 2015 (Wave 1 and Wave 3). Cognitive function was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status (TICS). Multivariate linear regression models (MRLMs) and generalized estimating equation (GEE) were used to investigate associations between TC variability and cognitive scores. After adjusting for potential confounders, male participants with higher visit-to-visit TC variability showed lower global cognition scores (β = − 0.71, P < 0.001). After further adjustment for baseline cognition, the association remained statistically significant (β = − 0.68, P < 0.001). The domains with declines were focused on episodic memory (β = − 0.22, P = 0.026) and TICS (β = − 0.44, P = 0.004). However, these associations were not found in women (β = − 0.10, P = 0.623). For men, the rates of decline in global cognition increased by 0.14 (β = − 0.14, P = 0.009) units per year while TC variability increased by 1 mmol/L. For males, higher visit-to-visit TC variability correlated with lower cognitive function and an increased rate of decreases in memory. More attention should be paid to cognitive decline in males with high TC variability, and particularly, on decreases in memory, calculation, attention and orientation.
Osmolytes dynamically regulate mutant Huntingtin aggregation and CREB function in Huntington’s disease cell models
Authors: Aravindan Shreyaas , Chen Samantha , Choudhry Hannaan , Molfetta Celine , Chen Kuang Yu , Liu Alice Y. C. 
Published: September 2020

AbstractOsmolytes are organic solutes that change the protein folding landscape shifting the equilibrium towards the folded state. Herein, we use osmolytes to probe the structuring and aggregation of the intrinsically disordered mutant Huntingtin (mHtt) vis-a-vis the pathogenicity of mHtt on transcription factor function and cell survival. Using an inducible PC12 cell model of Huntington’s disease (HD), we show that stabilizing polyol osmolytes drive the aggregation of Htt103QExon1-EGFP from a diffuse ensemble into inclusion bodies (IBs), whereas the destabilizing osmolyte urea does not. This effect of stabilizing osmolytes is innate, generic, countered by urea, and unaffected by HSP70 and HSC70 knockdown. A qualitatively similar result of osmolyte-induced mHtt IB formation is observed in a conditionally immortalized striatal neuron model of HD, and IB formation correlates with improved survival under stress. Increased expression of diffuse mHtt sequesters the CREB transcription factor to repress CREB-reporter gene activity. This repression is mitigated either by stabilizing osmolytes, which deplete diffuse mHtt or by urea, which negates protein–protein interaction. Our results show that stabilizing polyol osmolytes promote mHtt aggregation, alleviate CREB dysfunction, and promote survival under stress to support the hypothesis that lower molecular weight entities of disease protein are relevant pathogenic species in neurodegeneration.
The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPP+-treated SH-SY5Y cells
Authors: Zhong Yanmin , Li Xin , Du Xixun , Bi Mingxia , Ma Fengtong , Xie Junxia , Jiang Hong 
Published: September 2020

AbstractAbnormal iron accumulation caused by elevated levels of divalent metal transporter 1 (DMT1) contributes to progressive neurodegeneration in Parkinson's disease (PD). Parkin is a E3 ubiquitin ligase for the ubiquitination of DMT1. S-nitrosylated parkin (SNO-parkin) is commonly observed in PD. However, the effects of S-nitrosylation on the E3 ubiquitin ligase activity of parkin for the ubiquitination of DMT1 in PD are largely unknown. To elucidate the role of S-nitrosylated parkin and DMT1 in PD, SH-SY5Y cells were transfected with parkin, being treated with S-nitrosoglutathione (GSNO) and 1-methyl-4-phenylpyridinium (MPP+). The results showed increased levels of oxidized nitric oxide (NO) and S-nitrosylated parkin after the treatment of GSNO and MPP+ in parkin-transfected cells. Consistently, increased levels of DMT1, iron uptake and cell viability were observed. Interestingly, inhibition of S-nitrosylated parkin reduced the level of DMT1. Further, S-nitrosylation of parkin significantly inhibited the ubiquitination of DMT1. When HEK293T cells were transfected with plasmid of parkin with single site mutation (Cys241A, Cys260A, Cys323A), ubiquitination of DMT1 was also inhibited. However, the cells cotransfected with plasmids containing all three mutations, GSNO treatment did not affect the ubiquitination of DMT1. The expression of SNO-parkin and DMT1 protein in substantia nigra increased significantly gradually after 2 h, 4 h and 24 h with MPTP injection. These results indicate that the S-nitrosylation of parkin inhibits its E3 ubiquitin ligase activity for the ubiquitination of DMT1, which contributes to iron accumulation and degenerative process in PD. Targeted S-nitrosylation could provide a potential therapeutic strategy against PD.
Optokinetic stimulation induces vertical vergence, possibly through a non-visual pathway
Authors: Wibble Tobias , Pansell Tony 
Published: September 2020

AbstractVertical vergence is generally associated with one of three mechanisms: vestibular activation during a head tilt, induced by vertical visual disparity, or as a by-product of ocular torsion. However, vertical vergence can also be induced by seemingly unrelated visual conditions, such as optokinetic rotations. This study aims to investigate the effect of vision on this latter form of vertical vergence. Eight subjects (4m/4f) viewed a visual scene in head erect position in two different viewing conditions (monocular and binocular). The scene, containing white lines angled at 45° against a black background, was projected at an eye-screen distance of 2 m, and rotated 28° at an acceleration of 56°/s2. Eye movements were recorded using a Chronos Eye-Tracker, and eye occlusions were carried out by placing an infrared-translucent cover in front of the left eye during monocular viewing. Results revealed vergence amplitudes during binocular viewing to be significantly lower than those seen for monocular conditions (p = 0.003), while torsion remained unaffected. This indicates that vertical vergence to optokinetic stimulation, though visually induced, is visually suppressed during binocular viewing. Considering that vertical vergence is generally viewed as a vestibular signal, the findings may reflect a visually induced activation of a vestibular pathway.
Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy
Authors: Yamashita Satoshi , Hattori Naoko , Fujii Satoshi , Yamaguchi Takeshi , Takahashi Masato , Hozumi Yasuo , Kogawa Takahiro , El-Omar Omar , Liu Yu-Yu , Arai Nobuaki , Mori Akiko , Higashimoto Hiroko , Ushijima Toshikazu , Mukai Hirofumi 
Published: September 2020

AbstractHER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, Infinium 450 K, and expression microarray, respectively, and 15 genes were identified as differentially expressed and eight genomic regions as differentially methylated between cancer samples with and without pCR. In a validation set (n = 47), one gene showed differential expression, and one region had differential methylation. Further, in the re-validation set (n = 55), all new samples, only HSD17B4 methylation was significantly different. The HSD17B4 methylation was at the transcriptional start site of its major variant, and was associated with its silencing. HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line. A combination of estrogen receptor-negative status and HSD17B4 methylation showed a positive predictive value of 80.0%. During HER2-directed neoadjuvant therapy, HSD17B4 methylation was the most reliable marker to monitor response to the therapy. These results showed that HSD17B4 methylation is a candidate predictive and response marker of HER2-positive breast cancer to HER2-directed therapy.
Relationship between domains of physical activity and cardiac autonomic modulation in adults: a cross-sectional study
Authors: Tebar William R. , Ritti-Dias Raphael M. , Mota Jorge , Farah Breno Q. , Saraiva Bruna T. C. , Damato Tatiana M. M. , Delfino Leandro D. , Aguilar Beatriz A. S. , dos Santos Amanda B. , Silva Stefany C. B. , Vanderlei Luiz Carlos M. , Christofaro Diego G. D. 
Published: September 2020

AbstractThis study aimed to analyze the relationship of physical activity in different domains with cardiac autonomic modulation in adults. A sample of 252 adults was randomly selected, with mean age of 42.1 (± 16.5) years, being 58% of women. Cardiac autonomic modulation was assessed through indexes of heart rate variability in time (SDNN, RMSSD) and frequency (LF, HF) domains for linear method, and by Poincaré plot for non-linear method (SD1, SD2 components). Domains of PA (occupation, sport, leisure time/commuting, and total) were assessed by Baecke’s questionnaire. Variables of age, gender, socioeconomic status (questionnaire) and body mass index (objectively measures) were covariates. Occupational PA was positively related to LF (β = 2.39, 95% CI 0.24; 4.54), sports PA was positively related to SDNN (β = 3.26, 95% CI 0.18; 7.05), RMSSD (β = 4.07, 95% CI 0.31; 7.85), and SD1 (β = 2.85, 95% CI 0.11; 5.81), and leisure time/commuting PA was positively related to SDNN (β = 3.36, 95% CI 0.28; 6.70) and RMSSD (β = 3.53, 95% CI 0.46; 7.52) indexes. Total PA was related to RMSSD (β = 1.70, 95% CI 0.04; 3.72). Sports, leisure time/commuting, and total PA were related to higher parasympathetic modulation, while occupational PA was related to higher sympathetic modulation to the heart in adults.