bluuebunny/crossref_metadata_2025_split huggingface dataset:
KA‐104, a new multitargeted anticonvulsant with potent antinociceptive activity in preclinical models
Authors: Kamiński Krzysztof , Mogilski Szczepan , Abram Michał , Rapacz Anna , Latacz Gniewomir , Szulczyk Bartłomiej , Walczak Maria , Kuś Kamil , Matyjaszczyk Karolina , Kamiński Rafał M. 
Published: September 2020

AbstractObjectiveThe main objective of the present work was to assess the utility of KA‐104 as potential therapy for drug‐resistant seizures and neuropathic pain, and to characterize its druglike properties in a series of absorption, distribution, metabolism, excretion and toxicity (ADME‐Tox) studies. We also aimed to establish its mechanism of action in electrophysiological studies.MethodsThe activity of KA‐104 against drug‐resistant seizures was tested in the mouse 6‐Hz (44‐mA) model, whereas the antinociceptive activity was assessed with the capsaicin‐ and oxaliplatin‐induced pain models in mice. The patch‐clamp technique was used to study the influence of KA‐104 on fast voltage‐gated sodium currents in rat prefrontal cortex pyramidal neurons. The pharmacokinetic profile was determined after intraperitoneal (ip) injection in mice. The in vitro ADME‐Tox properties were studied by applying routine testing procedures.ResultsKA‐104 was effective in the 6‐Hz (44‐mA) model (median effective dose [ED50] = 73.2 mg/kg) and revealed high efficacy in capsaicin‐induced neurogenic pain as well as in oxaliplatin‐induced neuropathic pain in mice. Patch‐clamp technique showed that KA‐104 reversibly inhibits voltage‐gated sodium currents. KA‐104 was rapidly absorbed after the ip injection and showed relatively good penetration through the blood‐brain barrier. This molecule was also characterized by high passive permeability, moderate influence on CYP2C9, and negligible hepatotoxicity on HepG2 cells.SignificanceThe results reported herein indicate that KA‐104 is a new wide‐spectrum multitargeted anticonvulsant with favorable in vitro ADME‐Tox properties. Importantly, this compound may also prove to become an interesting and hopefully more effective therapeutic option for treatment of neuropathic pain.
Characterization of the microbiome in the infant diapered area: Insights from healthy and damaged skin
Authors: Teufel Amber , Howard Brian , Hu Ping , Carr Andrew N. 
Published: September 2020

AbstractIt has been recognized for nearly a century that human beings are inhabited by a remarkably dense and diverse microbial ecosystem, yet we are only just beginning to understand and appreciate the many roles that these microbes play in human health and development. Establishment of the microbiome begins at birth, but many previous studies on infant skin health have focused on Candida species. Little is known on the full microbial composition across different areas and even less is known on how these communities change during disease/inflammatory states. In this clinical study, infants were recruited during periods of diaper dermatitis (DD) and health to characterize the skin microbiome in these two states. Substantial shifts in the skin microbiome were observed across four sites in the diapered area (genitals, intertriginous, buttocks and perianal), as well as during periods of DD. As DD scores increased, there was a shift in relative abundance that demonstrated higher community percentages of faecal coliforms, such as Enterococcus, and lower percentages of Staphylococcus strains. In high‐rash samples, the predominant Staphylococcus species is S aureus, potentially implicating S aureus as a DD aetiological agent. This study provides new information related to the microbiome on infant skin in the diapered area and provides insights into the role of the microbiome in the development of DD.
Detection of anomalous episodes in urban Ozone maps
Authors: Cárdenas‐Montes Miguel 
Published: September 2020

AbstractIn addition to classification and regression, outlier detection has emerged as a relevant activity in deep learning. In comparison with previous approaches where the original features of the examples were used for separating the examples with high dissimilarity from the rest of the examples, deep learning can automatically extract useful features from raw data, thus removing the need for most of the feature engineering efforts usually required with classical machine learning approaches. This requires training the deep learning algorithm with labels identifying the examples or with numerical values. Although outlier detection in deep learning has been usually undertaken by training the algorithm with categorical labels—classifier—, it can also be performed by using the algorithm as regressor. Nowadays numerous urban areas have deployed a network of sensors for monitoring multiple variables about air quality. The measurements of these sensors can be treated individually—as time series—or collectively. Collectively, a variable monitored by a network of sensors can be transformed into a map. Maps can be used as images in machine learning algorithms—including computer vision algorithms—for outlier detection. The identification of anomalous episodes in air quality monitoring networks allows later processing this time period with finer‐grained scientific packages involving fluid dynamic and chemical evolution software, or the identification of malfunction stations. In this work, a Convolutional Neural Network is trained—as a regressor—using as input Ozone‐urban images generated from the Air Quality Monitoring Network of Madrid (Spain). The learned features are processed by Density‐based Spatial Clustering of Applications with Noise (DBSCAN) algorithm for identifying anomalous maps. Comparisons with other deep learning architectures are undertaken, for instance, autoencoders—undercomplete and denoizing—for learning salient features of the maps and later to use as input of DBSCAN. The proposed approach is able efficiently find maps with local anomalies compared to other approaches based on raw images or latent features extracted with autoencoders architectures with DBSCAN.
Escalation and Regulation of Emotional Arousal in Couples Predicts Relationship Satisfaction Concurrently and 25 Years Later
Authors: Weber Danielle M. , Fischer Melanie S. , Baucom Donald H. , Baucom Brian R. W. , Engl Joachim , Thurmaier Franz , Wojda Alexandra K. , Hahlweg Kurt 
Published: September 2020

Relationship distress and divorce are major risk factors for the development or exacerbation of psychopathology and psychosocial impairments. Given that heightened negative emotions within couples’ interactions may portend negative relationship outcomes, it is critical to understand how emotions unfold across a conversation and how partners may influence each other’s immediate emotional experiences. This study examined whether these regulatory dynamics within one interaction predicted relationship satisfaction concurrently and 25 years later. Vocally‐encoded emotional arousal (f0) was measured during couples’ (N = 25 couples) conversations about a relationship issue. Across different analytical strategies, results demonstrate that one partner’s f0dynamics had immediate and long‐term associations with the other partner’s satisfaction. Partners were less satisfied if the other partner (a) expressed higher f0overall and (b) escalated more in f0across the conversation. Yet, partners weremoresatisfied when their f0escalated across the conversation. Also, women specifically were more satisfied if their f0remained elevated longer before regulating back to their emotional baseline. Thus, higher f0was associated with higher satisfaction in thesamepartner, but associated with less satisfaction in theotherpartner—particularly when these emotions come from women. It may be that partners have to decide whether to prioritize expressing their emotions fully or limit expression in the service of their partner’s happiness. These findings challenge us to think of ways to address this “win–lose” scenario so that couples can balance both partners’ emotional needs and preserve relationship quality across the life span.
Metformin potentiates the chemotherapeutic effects of doxorubicin on 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5b] pyridine‐induced Mammary Carcinoma in rats
Authors: Salim Elsayed , El‐Sisi Alaa El‐Din , Sokar Samia , EL‐Sayad Magda , Moussa Ethar 
Published: September 2020

AbstractThis study was carried out to evaluate the antitumor activity of Metformin (Met) and its impending utility to potentiate the chemotherapeutic action of doxorubicin on 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5b]pyridine (PhIP)‐induced rat mammary carcinogenesis. Female Sprague –Dawley (SD) rats were divided into seven groups (n = 15 each). Mammary carcinogenesis was induced by the administration of PhIP at a dose of 75 mg/kg by gavage. Met treatment was 2 mg/ml in drinking water for 26 weeks started after the last PhIP dose. Doxorubicin (Dox) treatment started after one month of the last PhIP dose with a dose of 4 mg/kg, i.v. once per week for 4 weeks. Compared to the PhIP group, the latency period of tumors in the PhIP+Dox, PhIP+Met, and PhIP+Dox+Met groups were significantly increased and tumors’ incidences and multiplicities were significantly reduced. By immunohistochemistry, carcinomas from the combination treatment groups showed a significant decrease in the labeling indexes (LI%) of cellular proliferation and CD44 compared to the PhIP group while LI% for ERα was significantly decreased in all combination treatment groups compared to the PhIP‐administered group. Moreover, the quantitative mRNA expression of ERα was significantly decreased in mammary tumors from PhIP + Dox+Met combined group more than the PhIP + Dox group. However, mRNA expression of EGF was found significantly lower in all combination treatment groups compared to the PhIP group. These findings suggest that Metformin potentiate the antitumor efficacy of doxorubicin and had beneficial effects on PhIP‐induced mammary carcinogenesis through the prevention of cellular proliferation and mRNA expression of ERα and EGF.
Impacts of uncertain feedstock quality on the economic feasibility of fast pyrolysis biorefineries with blended feedstocks and decentralized preprocessing sites in the Southeastern United States
Authors: Lan Kai , Park Sunkyu , Kelley Stephen S. , English Burton C. , Yu Tun‐Hsiang E. , Larson James , Yao Yuan 
Published: September 2020

AbstractThis study performs techno‐economic analysis and Monte Carlo simulations (MCS) to explore the effects that variations in biomass feedstock quality have on the economic feasibility of fast pyrolysis biorefineries using decentralized preprocessing sites (i.e., depots that produce pellets). Two biomass resources in the Southeastern United States, that is, pine residues and switchgrass, were examined as feedstocks. A scenario analysis was conducted for an array of different combinations, including different pellet ash control levels, feedstock blending ratios, different biorefinery capacities, and different biorefinery on‐stream capacities, followed by a comparison with the traditional centralized system. MCS results show that, with depot preprocessing, variations in the feedstock moisture and feedstock ash content can be significantly reduced compared with a traditional centralized system. For a biorefinery operating at 100% of its designed capacity, the minimum fuel selling price (MFSP) of the decentralized system is $3.97–$4.39 per gallon gasoline equivalent (GGE) based on the mean value across all scenarios, whereas the mean MFSP for the traditional centralized system was $3.79–$4.12/GGE. To understand the potential benefits of highly flowable pellets in decreasing biorefinery downtime due to feedstock handling and plugging problems, this study also compares the MFSP of the decentralized system at 90% of its designed capacity with a traditional system at 80%. The analysis illustrates that using low ash pellets mixed with switchgrass and pine residues generates a more competitive MFSP. Specifically, for a biorefinery designed for 2,000 oven dry metric ton per day, running a blended pellet made from 75% switchgrass and 25% pine residues with 2% ash level, and operating at 90% of designed capacity could make an MFSP between $4.49 and $4.71/GGE. In contrast, a traditional centralized biorefinery operating at 80% of designed capacity marks an MFSP between $4.72 and $5.28.
Relationship between psychological pain and death anxiety with comprehensive geriatric assessment in older adults
Authors: Cavusoglu Cagatay , Ileri Ibrahim , Tuna Dogrul Rana , Ozsurekci Cemile , Caliskan Hatice , Cemal Kizilarslanoglu Muhammet , Goker Berna 
Published: September 2020

AimPsychological pain refers to the torment that results from adverse experiences, such as loneliness, guilt, frustration, hopelessness or loss. Psychological pain may impair physical and psychosocial functioning of older adults. Death anxiety is associated with cognitive function deterioration, change to social environment and increased risk of depression. This study investigated associations among components of comprehensive geriatric assessment (CGA), death anxiety and psychological pain.MethodsIn total, 100 patients aged ≥65 years were included in this study. Demographic characteristics and CGA test scores were examined. The Templer scale was used to evaluate death anxiety; the Psychache scale was used to evaluate psychological pain. Multivariate logistic regression analysis was performed to identify parameters independently associated with poor cognitive performance and death anxiety.ResultsThe patients' median age was 73 (65–92) years. Death anxiety was detected in 34% of patients. Psychological pain and death anxiety levels were significantly associated with Mini‐Mental State Examination, clock drawing test, Geriatric Depression Scale‐15 and Instrumental Activities of Daily Living (IADL) scores. Psychological pain levels were independently associated with cognitive performance. Finally, psychological pain and IADL scores were independently associated with death anxiety.ConclusionsDuring a CGA, practitioners should note that psychological pain and death anxiety may negatively affect cognitive function and IADL scores. Patients should be re‐evaluated, following suitable psychotherapeutic interventions. Geriatr Gerontol Int 2020; 20: 1056–1060..
Mobilizing betrayal: Black feminist pedagogy and Black women graduate student educators
Authors: James‐Gallaway ArCasia D. , Turner Francena F. L. 
Published: September 2020

AbstractThis article addresses Black women graduate students' educational labor in higher education teacher training programs. We ground this reflective account of our respective teaching praxis in the educational betrayal we endured as younger students, connecting it to our engagement of Black feminist pedagogy. We illustrate how this praxis empowered us as undergraduate educators to implement pedagogies of equity and justice. Employing a structured vignette analysis framework, we draw on a Black feminist paradigm and Black feminist autoethnography to examine field notes of our teaching praxis. These two field notes, one from Francena and one from ArCasia, demonstrate challenges that emerged in our instruction of mostly white undergraduates. Despite the precarious nature of our political and professional positions, we discuss why working toward an anti‐oppression praxis remains our ultimate pedagogical aim.
Real‐world efficacy of sofosbuvir plus velpatasvir therapy for patients with hepatitis C virus‐related decompensated cirrhosis
Authors: Ohya Kazuki , Imamura Michio , Teraoka Yuji , Morio Kei , Fujino Hatsue , Nakahara Takashi , Ono Atsushi , Murakami Eisuke , Kawaoka Tomokazu , Miki Daiki , Tsuge Masataka , Hiramatsu Akira , Aikata Hiroshi , Hayes C. Nelson , Mori Nami , Takaki Shintaro , Tsuji Keiji , Aisaka Yasuyuki , Ishitobi Tomokazu , Katamura Yoshio , Kodama Hideaki , Nabeshima Yoshitaka , Masaki Keiichi , Honda Yohji , Moriya Takashi , Kohno Hirotaka , Kohno Hiroshi , Chayama Kazuaki 
Published: September 2020

AimCombination therapy with sofosbuvir (SOF) plus velpatasvir (VEL) is approved for patients with hepatitis C virus (HCV)‐related decompensated cirrhosis. We analyzed the real‐world efficacy of SOF/VEL therapy.MethodsThirty‐three patients with HCV‐related decompensated cirrhosis (25 and eight patients with Child B and C, respectively) were treated with SOF/VEL for 12 weeks. The HCV non‐structural protein (NS)5A and NS5B drug resistance‐associated substitutions (RASs) were determined by direct sequencing.ResultThirty‐two of 33 patients completed the treatment, but the remaining patient discontinued the therapy during third week of the treatment due to aggravation of hepatic encephalopathy. Serum HCV‐RNA became negative during the treatment in all patients but relapsed after the end of therapy in five patients. In total, 28 out of 33 patients (85%) achieved sustained virological response 12 weeks following completion of treatment (SVR12). The SVR12 rate was 96% in patients with Child B, but significantly lower, at 50%, in patients with Child C (P < 0.05). In genotype 1b HCV‐infected patients, all eight patients without baseline NS5A RASs, but only three of seven patients with RASs, achieved SVR12. Multivariate analysis identified Child B (odds ratio, 35.8 for Child C; P = 0.045) as an independent predictor of SVR12. Median serum albumin levels significantly increased only in patients who achieved SVR12. Child–Pugh scores improved in 16 of 28 patients (57%) following achievement of SVR12.ConclusionThe effect of SOF/VEL therapy is lower for patients with Child C. Improvement of hepatic function is expected after viral eradication with SOF/VEL therapy in patients with decompensated cirrhosis.
Effect of wheat bran dietary fibre on the rheological properties of dough during fermentation and Chinese steamed bread quality
Authors: Ma Sen , Wang Zhen , Liu Ning , Zhou Peng , Bao Qingdan , Wang Xiaoxi 
Published: September 2020

SummaryThe effects of wheat bran dietary fibre (WBDF) on the rheological properties of dough during fermentation and quality of Chinese steamed bun (CSB) were investigated. The study revealed that with the increase of the content of WBDF, the dough extensibility and time at which gas starts to escape from the dough significantly decreased but the dough firmness significantly increased (P < 0.05). The elastic modulus and viscous modulus showed an upward trend, probably due to the increased molecular weight of the viscoelastic body resulting from the presence of WBDF. Additionally, by changing the quality of the gluten network, the specific volume and L* value significantly decreased from 2.52 to 1.31 mL g−1, and from 87 to 51, respectively, these adverse effects on CSBs could be moderated by the fermentation process.
Changes in lifestyle behaviours during the COVID‐19 confinement in Spanish children: A longitudinal analysis from the MUGI project
Authors: Medrano María , Cadenas‐Sanchez Cristina , Oses Maddi , Arenaza Lide , Amasene Maria , Labayen Idoia 
Published: September 2020

SummaryBackgroundHome confinement during the COVID‐19 pandemic could have affected lifestyle behaviours of children, however evidence about it is emerging and yet scarce.ObjectivesTo examine the effects of the COVID‐19 confinement on lifestyle behaviours in Spanish children, and to assess the influence of social vulnerabilities on changes in lifestyle behaviours.MethodsPhysical activity (PA), screen time, sleep time, adherence to the Mediterranean diet (KIDMED) and sociodemographic information were longitudinally assessed before (N = 291, 12.1 ± 2.4 years, 47.8% girls) and during the COVID‐19 confinement (N = 113, 12.0 ± 2.6 years, 48.7% girls) by online questionnaires.ResultsDuring the COVID‐19 confinement, PA (−91 ± 55 min/d, P < .001) and screen time (±2.6 h/d, P < .001) worsened, whereas the KIDMED score improved (0.5 ± 2.2 points, P < .02). The decrease of PA was higher in children with mother of non‐Spanish origin (−1.8 ± 0.2 vs −1.5 ± 0.1 h/d, P < .04) or with non‐university studies (−1.7 ± 0.1 vs −1.3 ± 0.1 h/d, P < .005) in comparison to their counterparts.ConclusionThis study evidence the negative impact of the COVID‐19 confinement on PA levels and sedentary behaviours of Spanish children. These findings should be taken into account to design and implement public health strategies for preserving children´s health during and after the pandemic, particularly, in children with social vulnerabilities.
TANK‐binding kinase 1 mediates osteoclast differentiation by regulating NF‐κB, MAPK and Akt signaling pathways
Authors: Lin Shuai , Zhao Xiao‐li , Wang Zhen 
Published: September 2020

AbstractTANK‐binding kinase 1 (TBK1) belongs to the noncanonical IκB kinase (IKK) family. The ubiquitously expressed protein is well known to play a pivotal role in innate immune response and inflammation. Although excessive inflammatory activities have been shown to affect osteoclast (OC) differentiation and function, direct relevance of TBK1 in bone turnover is not known. In this work, we specifically altered the TBK1 protein level by knocking down or overexpressing it without affecting its homologous protein IKKε expression, and demonstrated the effect of TBK1 on OC differentiation in bone marrow macrophages (BMMs) and RAW264.7 cells upon induction by receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL). TBK1 knockdown was found to markedly inhibit the OC differentiation and function, while TBK1 overexpression enhanced OC formation. Downregulation of TBK1 greatly suppressed RANKL‐induced gene expression of Mmp9, Atp6v0d2, Acp5, Ctsk andNfatc1 involved in the regulation of OC formation and function in both BMM and RAW264.7 cells. Mechanistic studies indicated that TBK1 affected the NF‐κB signaling pathway as well as mitogen‐activated protein kinases (MAPKs) and protein kinase B (Akt) activation during OC differentiation. Moreover, the protein level of TNF receptor‐associated factor 6 (TRAF6) was increased, and the interaction of TRAF6 with TBK1 was potentiated, by RANKL. Collectively, we provide direct evidence showing that TBK1 effectively mediates OC differentiation and function by regulating NF‐κB, MAPKs and Akt signals. A TBK1‐targeted therapeutic strategy may be useful for the treatment of bone‐related disorders.
Medical and surgical treatment of thyroid eye disease
Authors: Hall Anthony J. H. , Topliss Duncan J. 
Published: September 2020

AbstractThyroid eye disease is an autoimmune inflammatory disease strongly associated with thyroid disease, principally Graves disease. It can range from mild disease requiring observation or symptomatic treatments only, through to sight‐threatening disease requiring major drug therapy and orbital surgery. Severity is graded by the NOSPECS system and activity by the clinical activity score (CAS) to assist in treatment selection. Non‐surgical management can extend from observation alone to minor therapy such as oral selenium, then glucocorticoid therapy, cyclosporin, mycophenolate, rituximab, immunoglobulin, teprotumumab, and orbital radiotherapy. High‐dose intravenous methylprednisolone therapy is used in active vision‐threatening disease with early use of tarsorrhaphy and orbital decompression. Inactive but moderate to severe disease may be treated by orbital decompression, strabismus and eyelid surgery. Systematic assessment and management by both an endocrinologist and ophthalmologist to achieve and maintain euthyroidism and select and sequence treatments according to activity and severity of thyroid eye disease gives the best results for quality of life and vision.