bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway
Authors: Yang Guojun , Yang Yixin , Tang Hong , Yang Kai 
Published: February 2020

AbstractCurrent studies have shown that the clock gene Period 1 (Per1) is downregulated in various tumors and plays an important role in promoting tumor progression. However, the biological functions and mechanism of Per1 in tumors remain largely unknown. In this study, 86 specimens of oral squamous cell carcinoma (OSCC) tissues and adjacent noncancerous tissues were collected to determine the Per1 expression level and the clinical significance of Per1 expression. Per1 was stably inhibited or overexpressed in OSCC cells to investigate its function and mechanism in vitro and in vivo. We found that Per1 was remarkably downregulated in OSCC and that low Per1 expression was significantly associated with TNM clinical stage and poor prognosis of OSCC patients. Per1 overexpression in SCC15 OSCC cells (Per1‐OE SCC15 cells) significantly promoted autophagy and apoptosis while inhibiting proliferation and the AKT/mTOR pathway. However, the results obtained in Per1‐silenced TSCCA OSCC cells were opposite those obtained in Per1‐OE SCC15 cells. After addition of the AKT activator SC79 to Per1‐OE SCC15 cells, the increased autophagy and apoptosis as well as decreased proliferation were remarkably rescued. Furthermore, increased apoptosis was significantly rescued in Per1‐OE SCC15 cells treated with the autophagy inhibitor autophinib. In vivo tumorigenicity assays also confirmed that Per1 overexpression suppressed tumor growth. Taken together, our findings demonstrate for the first time that Per1 promotes OSCC progression by inhibiting autophagy‐mediated cell apoptosis and enhancing cell proliferation in an AKT/mTOR pathway‐dependent manner, and Per1 could be used as a valuable therapeutic target for OSCC.
Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors
Authors: Kurimoto Chiaki , Inaba Hidefumi , Ariyasu Hiroyuki , Iwakura Hiroshi , Ueda Yoko , Uraki Shinsuke , Takeshima Ken , Furukawa Yasushi , Morita Shuhei , Yamamoto Yuki , Yamashita Shimpei , Katsuda Masahiro , Hayata Atsushi , Akamatsu Hiroaki , Jinnin Masatoshi , Hara Isao , Yamaue Hiroki , Akamizu Takashi 
Published: February 2020

AbstractImmune‐related adverse events (irAEs) are often seen during immune‐checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow‐up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty‐six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL‐1β, IL‐2, and GM‐CSF at baseline, and early decrease of IL‐8, G‐CSF, and MCP‐1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti‐PD‐1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre‐existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.
SPH3643: A novel cyclin‐dependent kinase 4/6 inhibitor with good anticancer efficacy and strong blood‐brain barrier permeability
Authors: Liao XueMei , Hong Yuan , Mao Yu , Chen Na , Wang Qian , Wang Zhe , Zhang LeDuo , Wang Li , Shi Chen , Shi WeiJun , Ge Hui , Li AnDi , Li Xin , Xia GuangXin , Liu YanJun 
Published: February 2020

AbstractThe cyclin‐dependent kinase (CDK)4/6‐cyclin D1‐Rb‐p16/ink4a pathway is responsible for regulating cell progression past the G1 restriction point during the cell cycle. The development of a majority of human tumors is associated with dysregulation of this pathway, resulting in increased cancer cell proliferation. Both CDK4 and CDK6, well‐validated cancer drug targets, function primarily as catalytic enzymes that mediate the phosphorylation of retinoblastoma protein (Rb). Here, we determined that SPH3643 is a novel potent antiproliferative agent that inhibits CDK4/6 kinase activity. In biochemical assays, SPH3643 showed more potent inhibition of both CDK4 and CDK6 than did 2 published CDK4/6 inhibitors, LY2835219 and palbociclib, and had better selectivity than LY2835219. Further in vitro study revealed that SPH3643 blocked Cdk/Rb signaling by inhibiting the phosphorylation of RbSer780 and arrested the MCF‐7 cancer cells at G0/G1 phase, resulting in marked inhibition of the proliferation of Rb‐positive cancer cell lines. In vivo SPH3643 treatment in mice bearing xenograft tumor models of breast cancer, colon cancer, acute myelocytic leukemia, and glioblastoma resulted in significant decreases in tumor growth. SPH3643 was able to particularly strongly inhibit glioblastoma (U87‐MG) cell growth in the brains of orthotopic carcinoma xenograft mice due to its high degree of intracerebral penetration and significant persistence in this setting. Together these results revealed that SPH3643 is a potent, orally active small‐molecule inhibitor of CDK4/6 with robust anticancer efficacy and a high degree of blood‐brain barrier permeability.
Omalizumab in the treatment of adult patients with mastocytosis: A systematic review
Authors: Jendoubi Fatma , Gaudenzio Nicolas , Gallini Adeline , Negretto Mathilde , Paul Carle , Bulai Livideanu Cristina 
Published: February 2020

Abstract BackgroundMastocytosis is associated with mast cell (MC) mediator‐related symptoms for which limited therapies are available.ObjectiveOur aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator‐related symptoms in adult patients with mastocytosis.ResultsWe identified one multi‐centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post‐honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients.Conclusions and Clinical RelevanceOmalizumab appears to prevent some life‐threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.
Making sense of places: Belonging among “unaccompanied” young migrants in kinship care in a Swedish suburb
Authors: Moberg Stephenson Maria , Källström Åsa 
Published: February 2020

AbstractFor young people who have migrated unaccompanied by parents or other legal guardians, it is important to feel a sense of belonging. However, belonging is not fixed to one place. This study aims to explore how young migrants in kinship care in a Swedish suburb describe what different places mean to them and what these descriptions can tell us about their sense of belonging. In this study, semi‐structured interviews with 11 young migrants between 16 and 21 years of age who took part in a mentoring programme are analysed by thematic analysis. Our analysis reveals that (a) the young people described four “levels” of place as meaningful in different ways—their kinship homes, the local community, the country they currently inhabit, and the world and that (b) it was through the interrelationships between these levels that their described sense of belonging emerged. To counterbalance young migrants' uncertain future, social interventions are needed that can help them to meet other people and get wider social networks in order to gain a sense of belonging in the new country.
Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy
Authors: Greco Anna , Goossens Remko , van Engelen Baziel , van der Maarel Silvère M. 
Published: February 2020

AbstractFacioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. DUX4 is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. Here we provide a review of the recent literature describing the progress in understanding the complex genetic and epigenetic architecture of FSHD, with a focus on one of the consequences that these epigenetic changes inflict, the DUX4‐induced immune deregulation cascade. Moreover, we review the latest therapeutic strategies, with particular attention to the potential of epigenetic correction of the FSHD locus.
Pain relief and improvement in quality of life with 10 kHz SCS therapy: Summary of clinical evidence
Authors: Sayed Dawood , Kallewaard Jan Willem , Rotte Anand , Jameson Jessica , Caraway David 
Published: February 2020

AbstractObjectiveChronic pain is a prevalent condition which has a significant effect on the lives of those it impacts. High‐frequency 10 kHz spinal cord stimulation (10 kHz SCS) has been shown to provide paresthesia‐free pain relief for a wide variety of pain indications. This article summarizes the current and emerging data as they relate to the clinical use of the therapy in various pain syndromes.MethodsA literature search was conducted using the PubMed electronic database using keywords related to 10 kHz SCS. The database was queried from 2013 to May 2019. Articles reporting clinical studies that included human subjects permanently treated with 10 kHz SCS (Senza® system) were included in the review. Recent and relevant conference proceedings known to the authors were also included.ResultsThe selected literature demonstrated significant evidence for the efficacy of 10 kHz SCS in treating chronic back and leg pain (CBLP), including a randomized, controlled trial as well as prospective and retrospective studies. One‐year follow‐up responder rates (pain relief ≥50%) ranged from 60% to 80%. Other studies and case series showed promising outcomes in specific conditions, including nonsurgical refractory back pain, neuropathic limb pain, complex regional pain syndrome, chronic widespread pain, chronic pelvic pain, and intractable headache. Subgroup analyses also pointed toward the potential of 10 kHz SCS being successful when low‐frequency SCS has failed. The vast majority of these studies reported improved quality of life (QOL) metrics and/or reduced opioid consumption.ConclusionsLevel I evidence already exists for the efficacy of 10 kHz SCS in treating CBLP, supported by real‐world clinical experience. Other studies demonstrate the potential of the therapy across a range of chronic pain etiologies, although larger confirmatory studies are recommended. Overall, the literature suggests that the therapy is associated with improved QOL as well as reduced opioid consumption.
Hidden risks in toys: A systematic review of pediatric toy contact dermatitis
Authors: Fenner Justine , Hadi Ali , Yeh Lindsey , Silverberg Nanette 
Published: February 2020

AbstractToys are a reflection of the compounds used frequently in manufacturing. Allergic contact dermatitis to potties, metal toys, and children's jewelry is well known, however, there is a broad range of skin risks in toys. With the objective to identify and publicize the associated risk of contact dermatitis in children's toys, we have searched the PubMed database from creation to September 9, 2019. Studies were eligible if they reported a new case of contact dermatitis secondary to interaction with a toy in patients from birth to 18 years of age. A toy was defined as something children interact with for entertainment during leisure time. In this review of the PubMed database we filtered by age and language which may have prevented us from detecting cases in adults that could be extrapolated to children. In addition, several articles were excluded based on title alone. A total of 1312 articles were identified and reviewed manually for inclusion criteria. Review of the articles found 25 original articles for consideration. Several toys were found to be associated with contact dermatitis. These included electronics, toy cars, costume jewelry, bicycles, sqwish balls, slime, Play‐Doh, and plasticine. Electronics such as video game controllers, cellphones, iPads, and computers were implicated. In conclusion, there is still an unmet need for observation of this segment of industry for labeling of contents and ongoing surveillance.
Season wise bike sharing demand analysis using random forest algorithm
Authors: V. E. Sathishkumar , Cho Yongyun 
Published: February 2020

AbstractRental bike sharing is an urban mobility model that is affordable and ecofriendly. The public bike sharing model is widely used in several cities across the world over the past decade. Because bike use is rising constantly, understanding the system demand in prediction is important to boost the operating system readiness. This article presents a prediction model to meet user demands and efficient operations for rental bikes using Random Forest (RF), which is a homogeneous ensemble method. The approach is carried out in Seoul, South Korea to predict the hourly use of rental bikes. RF is compared with Support Vector Machine with Radial Basis Function Kernel, k‐nearest neighbor and Classification and Regression Trees to verify RF supremacy in rental bike demand prediction. Performance Index measures the efficiency of RF compared to the other predictive models. Also, the variable importance analysis is performed to assess the most important characteristics during different seasons by creating a predictive model using RF for each season. The results show that the influence of variables changes depending on the seasons that suggest different operating conditions. RF models trained with yearly and seasonwise models show that bike sharing demand can be further improved by considering seasonal change.
Neural network prediction of bioleaching of metals from waste computer printed circuit boards using Levenberg‐Marquardt algorithm
Authors: Annamalai Mohan , Gurumurthy Kalaichelvan 
Published: February 2020

AbstractThe applicability of artificial neural network (ANN) to predict the bioleaching of metals using from computer printed circuit boards (CPCB) and the influence of process parameters were studied. The influence of process parameters initial pH (1.6‐2.4), pulp density (2%‐13%), and the initial volume of Inoculum (5%‐25%) were investigated on the rate of bioleaching of metals from CPCB. Network inputs were fed as initial pH, pulp density, and inoculum volume and with the extraction of Cu, Ag, and Au as output. The ANN was developed using the Levenberg‐Marquardt algorithm and trained for modeling and prediction. The most fitting architectures for Cu, Ag, and Au were [4‐5‐5‐2‐1], [4‐7‐5‐2‐1], [4‐7‐1‐1‐1] trained with Levenberg‐Marquardt algorithm, respectively. The R values were observed to be 0.996, 0.997, and 0.993 for Cu, Ag, and Au extraction predictions, respectively. The genetic algorithm model defined by ANN was used to achieve maximum extraction rates for Cu, Au, and Ag. The predicted data showed that there is a great capability of using ANN for the prediction of Cu, Ag, and Au extraction from CPCB through bioleaching process. Hence, the ANN model can be used to control the operational conditions for improved metals extraction through bioleaching.
L1 norm based pedestrian detection using video analytics technique
Authors: Selvaraj Anandamurugan , Selvaraj Jeeva , Maruthaiappan Sivabalakrishnan , Babu Gokulnath Chandra , Kumar Priyan Malarvizhi 
Published: February 2020

AbstractPedestrian detection from images of the visible spectrum is a high relevant area of research given its potential impact in the design of pedestrian protection systems. In general, detection is made with two different phases, feature extraction and classification. Also, features for detection of pedestrian are already are available such as optimal feature model. But still required is an improvement in detection by reducing the execution time and false positive. The proposed model has three different phases, that is, background subtraction, feature extraction, and classification. In spite of giving entire information into feature extraction, the system gives only a useful information (foreground image) by twin background model. Then the foreground image moves to the feature extraction and classifies the pedestrian. For feature extraction, histogram of orientation gradient (HOG) L1 normalization has been used. This will increase the detection accuracy and reduce the computation time of a process. In addition, false positive rate has been minimized.
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real‐world study
Authors: Iannitto Emilio , Romano Alessandra , Scalzulli Potito Rosario , Bonanno Vincenza , Scalone Renato , Chiarenza Annalisa , Pirosa Maria Cristina , Caruso Anastasia Laura , Minoia Carla , Mantuano Saverio , De Santis Gaetano , Salerno Marilena , Crescimanno Alessandra , Porretto Ferdinando , Li Gioi Felicina , Ricciuti Giuseppina , Greco Antonino , Pavone Enzo , Guarini Attilio , Tarantini Giuseppe , Mannina Donato , Consoli Ugo , Cascavilla Nicola , Di Raimondo Francesco , Musso Maurizio 
Published: February 2020

AbstractObjective and MethodsIn order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed.ResultsThe median number of previous treatments was 2 (1‐4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21‐day cycle. The median number of BvB cycles was 4 (2‐7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow‐up of 19 months (5‐47), median PFS was 18 months (95%CI: 23‐29), and the 2‐year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%).ConclusionOur real‐world results suggest that BvB is an effective third‐line rescue and bridge‐to‐transplant regimen for RR‐cHL patients.
Trait plasticity alters the range of possible coexistence conditions in a competition–colonisation trade‐off
Authors: Muthukrishnan Ranjan , Sullivan Lauren L. , Shaw Allison K. , Forester James D. 
Published: February 2020

AbstractMost of the classical theory on species coexistence has been based on species‐level competitive trade‐offs. However, it is becoming apparent that plant species display high levels of trait plasticity. The implications of this plasticity are almost completely unknown for most coexistence theory. Here, we model a competition–colonisation trade‐off and incorporate trait plasticity to evaluate its effects on coexistence. Our simulations show that the classic competition–colonisation trade‐off is highly sensitive to environmental circumstances, and coexistence only occurs in narrow ranges of conditions. The inclusion of plasticity, which allows shifts in competitive hierarchies across the landscape, leads to coexistence across a much broader range of competitive and environmental conditions including disturbance levels, the magnitude of competitive differences between species, and landscape spatial patterning. Plasticity also increases the number of species that persist in simulations of multispecies assemblages. Plasticity may generally increase the robustness of coexistence mechanisms and be an important component of scaling coexistence theory to higher diversity communities.