bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications
Authors: Shi Fengqin , Li Ya , Han Rui , Fu Alan , Wang Ronghua , Nusbaum Olivia , Qin Qin , Chen Xinyi , Hou Li , Zhu Yong 
Published: January 2021

AbstractValerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb’s ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.
Clinical pattern of failure after a durable response to immune checkpoint inhibitors in non-small cell lung cancer patients
Authors: Heo Ja Yoon , Yoo Shin Hye , Suh Koung Jin , Kim Se Hyun , Kim Yu Jung , Ock Chan-Young , Kim Miso , Keam Bhumsuk , Kim Tae Min , Kim Dong-Wan , Heo Dae Seog , Lee Jong Seok 
Published: January 2021

AbstractAlthough immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5–21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
The consequences of COVID-19 on social interactions: an online study on face covering
Authors: Calbi Marta , Langiulli Nunzio , Ferroni Francesca , Montalti Martina , Kolesnikov Anna , Gallese Vittorio , Umiltà Maria Alessandra 
Published: January 2021

AbstractThe COVID-19 pandemic has dramatically changed the nature of our social interactions. In order to understand how protective equipment and distancing measures influence the ability to comprehend others’ emotions and, thus, to effectively interact with others, we carried out an online study across the Italian population during the first pandemic peak. Participants were shown static facial expressions (Angry, Happy and Neutral) covered by a sanitary mask or by a scarf. They were asked to evaluate the expressed emotions as well as to assess the degree to which one would adopt physical and social distancing measures for each stimulus. Results demonstrate that, despite the covering of the lower-face, participants correctly recognized the facial expressions of emotions with a polarizing effect on emotional valence ratings found in females. Noticeably, while females’ ratings for physical and social distancing were driven by the emotional content of the stimuli, males were influenced by the “covered” condition. The results also show the impact of the pandemic on anxiety and fear experienced by participants. Taken together, our results offer novel insights on the impact of the COVID-19 pandemic on social interactions, providing a deeper understanding of the way people react to different kinds of protective face covering.
Concomitant improvement in anti-saccade success rate and postural instability gait difficulty after rTMS treatment for Parkinson’s disease
Authors: Okada Ken-ichi , Takahira Mizuki , Mano Tomoo , Uga Taichi , Konaka Kuni , Hosomi Koichi , Saitoh Youichi 
Published: January 2021

AbstractParkinson’s disease (PD) is a progressive neurological disorder characterised by motor and non-motor deficits. Repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex at a high frequency (5 Hz or higher) is reported to be a potential treatment of PD. We aimed to assess the effect of rTMS on eye movement control in patients with PD in their ‘on’ state. We enrolled 14 patients with PD and assessed motor symptoms (Movement Disorder Society-Sponsored Unified Parkinson’s Disease Rating Scale; MDS-UPDRS) and eye movement performances (visually guided saccades, volitional anti-saccades, and small involuntary saccades during fixation) at baseline and after administering bilateral 10 Hz rTMS on leg region of the motor cortex. We confirmed that rTMS improved the MDS-UPDRS motor scores and found that rTMS improved the anti-saccade success rate, which requires adequate inhibition of the reflexive response. The improvement in anti-saccade success rate was correlated with that of the postural instability gait difficulty (PIGD) sub-scores of MDS-UPDRS and lower baseline Japanese version of the Montreal Cognitive Assessment scores. This result is consistent with previous findings that PIGD and inhibitory control deficits share common brain dysfunctions in PD. rTMS may alleviate dysfunctions of that circuit and have a clinical effect.
Cardiac hypoxic resistance and decreasing lactate during maximum apnea in elite breath hold divers
Authors: Kjeld Thomas , Møller Jakob , Fogh Kristian , Hansen Egon Godthaab , Arendrup Henrik Christian , Isbrand Anders Brenøe , Zerahn Bo , Højberg Jens , Ostenfeld Ellen , Thomsen Henrik , Gormsen Lars Christian , Carlsson Marcus 
Published: January 2021

AbstractBreath-hold divers (BHD) enduring apnea for more than 4 min are characterized by resistance to release of reactive oxygen species, reduced sensitivity to hypoxia, and low mitochondrial oxygen consumption in their skeletal muscles similar to northern elephant seals. The muscles and myocardium of harbor seals also exhibit metabolic adaptations including increased cardiac lactate-dehydrogenase-activity, exceeding their hypoxic limit. We hypothesized that the myocardium of BHD possesses similar adaptive mechanisms. During maximum apnea 15O-H2O-PET/CT (n = 6) revealed no myocardial perfusion deficits but increased myocardial blood flow (MBF). Cardiac MRI determined blood oxygen level dependence oxygenation (n = 8) after 4 min of apnea was unaltered compared to rest, whereas cine-MRI demonstrated increased left ventricular wall thickness (LVWT). Arterial blood gases were collected after warm-up and maximum apnea in a pool. At the end of the maximum pool apnea (5 min), arterial saturation decreased to 52%, and lactate decreased 20%. Our findings contrast with previous MR studies of BHD, that reported elevated cardiac troponins and decreased myocardial perfusion after 4 min of apnea. In conclusion, we demonstrated for the first time with 15O-H2O-PET/CT and MRI in elite BHD during maximum apnea, that MBF and LVWT increases while lactate decreases, indicating anaerobic/fat-based cardiac-metabolism similar to diving mammals.
A set of simple methods for detection and extraction of laminarinase
Authors: Koteshwara Ananthamurthy , Philip Nancy V. , Aranjani Jesil Mathew , Hariharapura Raghu Chandrashekhar , Volety Mallikarjuna Subrahmanyam 
Published: January 2021

AbstractA carefully designed ammonium sulfate precipitation will simplify extraction of proteins and is considered to be a gold standard among various precipitation methods. Therefore, optimization of ammonium sulfate precipitation can be an important functional step in protein purification. The presence of high amounts of ammonium sulphate precludes direct detection of many enzymatically active proteins including reducing sugar assays (e.g. Nelson-Somogyi, Reissig and 3,5-dinitrosalicylic acid methods) for assessing carbohydrases (e.g. laminarinase (β (1–3)-glucanohydrolase), cellulases and chitinases). In this study, a simple method was developed using laminarin infused agarose plate for the direct analysis of the ammonium sulphate precipitates from Streptomyces rimosus AFM-1. The developed method is simple and convenient that can give accurate results even in presence of ammonium sulfate in the crude precipitates. Laminarin is a translucent substrate requiring the use of a stain to visualize the zones of hydrolysis in a plate assay. A very low-cost and locally available fluorescent optical fabric brightener Tinopal CBS-X has been used as a stain to detect the zones of hydrolysis. We also report simple methods to prepare colloidal chitin and cell free supernatant in this manuscript.
Assessment of the biological potential of diaryltriazene-derived triazene compounds
Authors: Figueirêdo Patricia de Maria Silva , Sampaio Filho José Costa , Sodré Alzirene de Jesus Sales , de Castro Júnior José Ribamar , Gonçalves Ingrid Santos , Blasques Rodrigo Vieira , S. Correa Rodrigo , Lima Benedicto Augusto Vieira , dos Anjos Marques Larissa , Coutinho Denise Fernandes , de Azevedo dos Santos Ana Paula Silva , Luz Tássio Rômulo Silva Araújo , de Miranda Rita de Cassia Mendonça , dos Santos Julliana Ribeiro Alves , Doriguetto Antonio Carlos , Pividori María Isabel , Hörner Manfredo , Villis Paulo Cesar Mendes 
Published: January 2021

AbstractIn the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.
Development and characterization of patient-derived xenografts from non-small cell lung cancer brain metastases
Authors: Baschnagel Andrew M. , Kaushik Saakshi , Durmaz Arda , Goldstein Steve , Ong Irene M. , Abel Lindsey , Clark Paul A. , Gurel Zafer , Leal Ticiana , Buehler Darya , Iyer Gopal , Scott Jacob G. , Kimple Randall J. 
Published: January 2021

AbstractNon-small cell lung cancer (NSCLC) brain metastasis cell lines and in vivo models are not widely accessible. Herein we report on a direct-from patient-derived xenograft (PDX) model system of NSCLC brain metastases with genomic annotation useful for translational and mechanistic studies. Both heterotopic and orthotopic intracranial xenografts were established and RNA and DNA sequencing was performed on patient and matching tumors. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumors and PDXs. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples with more than more than 95% of variants detected being retained in the matched PDXs. PDXs demonstrated response to radiation, response to selumetinib in tumors harboringKRASG12C mutations and response to savolitinib in a tumor withMETexon 14 skipping mutation. Savolitinib also demonstrated in vivo radiation enhancement in our MET exon 14 mutated PDX. Early passage cell strains showed high consistency between patient and PDX tumors. Together, these data describe a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.
Non pharmacological high-intensity ultrasound treatment of human dermal fibroblasts to accelerate wound healing
Authors: Lee Jeong Yu , Min Dae-Jin , Kim Wanil , Bin Bum-Ho , Kim Kyuhan , Cho Eun-Gyung 
Published: January 2021

AbstractInspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-β. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.
Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry
Authors: Schmitz Timo , Thilo Christian , Linseisen Jakob , Heier Margit , Peters Annette , Kuch Bernhard , Meisinger Christa 
Published: January 2021

AbstractCalcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25–74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan–Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28–2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28–2500 days after the event (OR 1.53 [1.19–1.98]). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
Unhealthy life habits associated with self-induced vomiting and laxative misuse in Brazilian adolescents
Authors: de Souza Ana Luiza Gomes , de Almeida Alexandre Aparecido , Noll Priscilla Rayanne E. Silva , Noll Matias 
Published: January 2021

AbstractAdolescence is a stage in life characterized by important social, cognitive, and physical changes. Adolescents are vulnerable to various psychosocial disorders, including eating disorders. We aimed to investigate the association between unhealthy habits, sociodemographic characteristics, and the practice of self-induced vomiting or laxative misuse in a representative sample of Brazilian adolescent girls and boys. Data from 102,072 students who participated in the National Adolescent School-based Health Survey were analyzed using the dependent variable: presence or absence of self-induced vomiting and/or laxative misuse; independent variables: consumption of unhealthy and high-calorie food items, age during first sexual intercourse, and the use of tobacco, alcohol, and/or illicit drugs. Associations between exposure and outcome were estimated using Poisson’s regression models stratified by sex, and including region, school, age group, and mother's educational history as adjustment variables. Eating ultra-processed foods and age during first sexual intercourse were associated with self-induced vomiting and laxative misuse only for girls; all other variables (consuming unhealthy foods and using legal or illicit substances) were associated with these behaviors for both sexes after applying adjustment variables. Early interventions focusing on changing unhealthy behaviors may prevent development of eating disorders in adolescents. Our findings demonstrate a strong association of many unhealthy habits with laxative misuse and self-induced vomiting practices in Brazilian adolescents.
Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
Authors: Bo Chunrui , Zhang Huixue , Cao Yuze , Lu Xiaoyu , Zhang Cong , Li Shuang , Kong Xiaotong , Zhang Xiaoming , Bai Ming , Tian Kuo , Saitgareeva Aigul , Lyaysan Gaysina , Wang Jianjian , Ning Shangwei , Wang Lihua 
Published: January 2021

AbstractMyasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.
Social isolation enhances cued-reinstatement of sucrose and nicotine seeking, but this is reversed by a return to social housing
Authors: Mastrogiovanni Natalie A. , Wheeler Alice K. , Clemens Kelly J. 
Published: January 2021

AbstractPhysical or perceived (i.e. loneliness) social isolation is increasing in Western cultures. Unfortunately, social isolation is associated with a range of negative physical and mental health outcomes, including increased incidence of obesity and smoking. Here we monitored the impact of social isolation on a range of physical measures, and then tested whether social isolation in adult rats changes how reward-related stimuli motivate sucrose- or nicotine-seeking. Socially isolated rats showed elevated baseline CORT, gained significantly less weight across the study, were more active in response to a novel or familiar environment. Isolated rats also acquired nose-poking for a food pellet more rapidly, and showed increased susceptibility to cue-, but not reward-induced reinstatement. Notably, these effects are partially mitigated by a return to group housing, suggesting that they are not necessarily permanent, and that a return to a social setting can quickly reverse any deficits or changes associated with social isolation. This study advances our understanding of altered reward-processing in socially isolated individuals and reiterates the importance of socialisation in the treatment of disorders such as overeating and addiction.
Development and characterization of GR2E Golden rice introgression lines
Authors: Mallikarjuna Swamy B. P. , Marundan Severino , Samia Mercy , Ordonio Reynante L. , Rebong Democrito B. , Miranda Ronalyn , Alibuyog Anielyn , Rebong Anna Theresa , Tabil Ma. Angela , Suralta Roel R. , Alfonso Antonio A. , Biswas Partha Sarathi , Kader Md. Abdul , Reinke Russell F. , Boncodin Raul , MacKenzie Donald J. 
Published: January 2021

AbstractGolden Rice with β-carotene in the grain helps to address the problem of vitamin A deficiency. Prior to commercialize Golden Rice, several performance and regulatory checkpoints must be achieved. We report results of marker assisted backcross breeding of the GR2E trait into three popular rice varieties followed by a series of confined field tests of event GR2E introgression lines to assess their agronomic performance and carotenoid expression. Results from confined tests in the Philippines and Bangladesh have shown that GR2E introgression lines matched the performance of the recurrent parents for agronomic and yield performance, and the key components of grain quality. Moreover, no differences were observed in terms of pest and disease reaction. The best performing lines identified in each genetic background had significant amounts of carotenoids in the milled grains. These lines can supply 30–50% of the estimated average requirements of vitamin A.