bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidized cell-free DNA as a stress-signaling factor activating the chronic inflammatory process in patients with autism spectrum disorders
Authors: Shmarina Galina V. , Ershova Elizaveta S. , Simashkova Natalia V. , Nikitina Svetlana G. , Chudakova Julia M. , Veiko Natalia N. , Porokhovnik Lev N. , Basova Anna Y. , Shaposhnikova Antonina F. , Pukhalskaya Daria A. , Pisarev Vladimir M. , Korovina Natalia J. , Gorbachevskaya Natalia L. , Dolgikh Olga A. , Bogush Marina , Kutsev Sergey I. , Kostyuk Svetlana V. 
Published: July 2020

Abstract
Background
Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study’s aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients.

Methods
The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1β and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed.

Results
The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1β, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1β, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls.

Conclusions
It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.
Risk factors for iliopsoas impingement after total hip arthroplasty using a collared femoral prosthesis
Authors: Qiu Jiandi , Ke Xiurong , Chen Shanxi , Zhao Liben , Wu Fanghui , Yang Guojing , Zhang Lei 
Published: July 2020

Abstract
Background
The relationship between collar design of a femoral component and iliopsoas impingement (IPI) after total hip arthroplasty (THA) is still underrecognized. The purpose of our study was to determine the possible risk factors for IPI related to the femoral component, when using a collared femoral prosthesis.

Methods
A total of 196 consecutive THA patients (206 hips) using a collared femoral prosthesis were reviewed retrospectively after exclusion of the factors related to acetabular component and femoral head. The patients were divided into +IPI and −IPI group according to the presence of IPI. Radiological evaluations were performed including femoral morphology, stem positioning, and collar protrusion length (CPL). Multivariate regression analysis was performed to assess the risk factors for IPI.

Results
At a minimum follow-up of 1 year, IPI was observed in 15 hips (7.3%). Dorr type C proximal femur was found in nine hips (60%) in the +IPI group and in 28 hips in the −IPI group (14.7%, p < 0.001). The mean stem anteversion in the +IPI group was significantly greater than that in the −IPI group (19.1° vs. 15.2°, p < 0.001), as well as the mean CPL (2.6 mm vs. − 0.5 mm, p < 0.001). The increased stem anteversion (OR = 1.745, p = 0.001) and CPL (OR = 13.889, p = 0.001) were potential risk factors for IPI.

Conclusions
The incidence of IPI after THA is higher than expected when using a collared femoral prosthesis. Among the factors related to collared femoral prosthesis, excessively increased stem anteversion and prominent collar protrusion are independent predictors for IPI. In addition, high risk of IPI should be carefully considered in Dorr type C bone, despite that femoral morphology is not a predictive factor.

Level of evidence
Level IV, clinical cohort study
DT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas
Authors: He Yonghan , Koch Raphael , Budamagunta Vivekananda , Zhang Peiyi , Zhang Xuan , Khan Sajid , Thummuri Dinesh , Ortiz Yuma T. , Zhang Xin , Lv Dongwen , Wiegand Janet S. , Li Wen , Palmer Adam C. , Zheng Guangrong , Weinstock David M. , Zhou Daohong 
Published: July 2020

Abstract
Background
Patients with advanced T cell lymphomas (TCLs) have limited therapeutic options and poor outcomes in part because their TCLs evade apoptosis through upregulation of anti-apoptotic Bcl-2 proteins. Subsets of TCL cell lines, patient-derived xenografts (PDXs), and primary patient samples depend on Bcl-xL for survival. However, small molecule Bcl-xL inhibitors such as ABT263 have failed during clinical development due to on-target and dose-limiting thrombocytopenia.

Methods
We have developed DT2216, a proteolysis targeting chimera (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and shown that it has better anti-tumor activity but is less toxic to platelets compared to ABT263. Here, we examined the therapeutic potential of DT2216 for TCLs via testing its anti-TCL activity in vitro using MTS assay, immunoblotting, and flow cytometry and anti-TCL activity in vivo using TCL cell xenograft and PDX model in mice.

Results
The results showed that DT2216 selectively killed various Bcl-xL-dependent TCL cells including MyLa cells in vitro. In vivo, DT2216 alone was highly effective against MyLa TCL xenografts in mice without causing significant thrombocytopenia or other toxicity. Furthermore, DT2216 combined with ABT199 (a selective Bcl-2 inhibitor) synergistically reduced disease burden and improved survival in a TCL PDX mouse model dependent on both Bcl-2 and Bcl-xL.

Conclusions
These findings support the clinical testing of DT2216 in patients with Bcl-xL-dependent TCLs, both as a single agent and in rational combinations.
Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma
Authors: Liu Junhui , Gao Lun , Zhan Na , Xu Pengfei , Yang Ji’an , Yuan Fan’en , Xu Yang , Cai Qiang , Geng Rongxin , Chen Qianxue 
Published: July 2020

Abstract
Background
Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metabolism regulators and is overexpressed in glioma. However, relationship between hypoxia and FTL expression and its role in regulating EMT remains unclear.

Methods
Immunohistochemistry (IHC), western blot and public datasets were used to evaluate FTL level in glioma. Wound healing, transwell assays, CCK8, annexin V staining assay were used to measure migration, invasion, proliferation and apoptosis of glioma cells in vitro. Interaction between HIF1A and FTL was assessed by luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. Subcutaneous xenograft model was established to investigate in vivo growth.

Results
FTL expression was enriched in high grade glioma (HGG) and its expression significantly associated with IDH1/2 wildtype and unfavorable prognosis of glioma patients. FTL expression positively correlated with HIF1A in glioma tissues and obviously increased in U87 and U251 cells under hypoxia in a time-dependent manner. Mechanistically, HIF-1α regulates FTL expression by directly binding to HRE-3 in FTL promoter region. Furthermore, we found that knockdown FTL dramatically repressed EMT and reduced migration and invasion of glioma by regulating AKT/GSK3β/ β-catenin signaling both in vitro and in vivo. Moreover, our study found downregulation FTL decreased the survival rate and increased the apoptosis of glioma cells treated with temozolomide (TMZ). FTL expression segregated glioma patients who were treated with TMZ or with high MGMT promoter methylation into survival groups in TCGA dataset. Patients with methylated MGMT who had high FTL expression presented similar prognosis with patients with unmethylated MGMT.

Conclusion
Our study strongly suggested that hypoxia-inducible FTL was a regulator of EMT and acted not only as a prognostic marker but also a novel biomarker of response to TMZ in glioma.
The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial
Authors: Cioccari Luca , Luethi Nora , Bailey Michael , Shehabi Yahya , Howe Belinda , Messmer Anna S. , Proimos Helena K. , Peck Leah , Young Helen , Eastwood Glenn M. , Merz Tobias M. , Takala Jukka , Jakob Stephan M. , Bellomo Rinaldo ,   for the ANZICS Clinical Trials Group and the SPICE III Investigators, Shehabi Yahya , Arabi Yaseen , Bass Frances , Bellomo Rinaldo , Erickson Simon , Howe Belinda , Kadiman Suhaini , McArthur Colin , Murray Lynnette , Reade Michael , Seppelt Ian , Takala Jukka , Webb Steve A. , Wise Matthew P. , Shehabi Yahya , Howe Belinda , Bellomo Rinaldo , Arabi Yaseen M. , Bailey Michael J. , Bass Frances , Kadiman Suhaini , McArthur Colin , Murray Lynnette , Reade Michael , Seppelt Ian , Takala Jukka , Webb Steve A. , Wise Matthew P. , Bailey Michael J. , Howe Belinda D. , Murray Lynette , Singh Vanessa 
Published: July 2020

Abstract
Background
Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting.

Methods
In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4).

Results
Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio.

Conclusions
In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP.

Trial registration
The SPICE III trial was registered at ClinicalTrials.gov (NCT01728558).
Fractional modeling and control in a delayed predator-prey system: extended feedback scheme
Authors: Li Shuai , Huang Chengdai , Guo Shuli , Song Xinyu 
Published: July 2020

AbstractThis paper’s goal is to delve into the fractional modeling and bifurcation control for a predator-prey model with prey dispersal and gestation delay. First, the bifurcation criteria for the uncontrolled system are obtained by viewing gestation delay as a bifurcation parameter. It is revealed that gestation delay can induce periodic oscillations. Then, an extended feedback controller is deeply conceived to suppress Hopf bifurcation for the underlying system. The results reflect that the stability behaviors of the uncontrolled system are saliently enhanced by adjusting feedback gain and feedback delay if other coefficients are fixed. To protrude the correctness and excellent feature of our works, two simulation examples are eventually carried out.
Higher-dimensional physical models with multimemory indices: analytic solution and convergence analysis
Authors: Jaradat Imad , Alquran Marwan , Abdel-Muhsen Ruwa , Momani Shaher , Baleanu Dumitru 
Published: July 2020

AbstractThe purpose of this work is to analytically simulate the mutual impact for the existence of both temporal and spatial Caputo fractional derivative parameters in higher-dimensional physical models. For this purpose, we employ the γ̅-Maclaurin series along with an amendment of the power series technique. To supplement our idea, we present the necessary convergence analysis regarding the γ̅-Maclaurin series. As for the application side, we solved versions of the higher-dimensional heat and wave models with spatial and temporal Caputo fractional derivatives in terms of a rapidly convergent γ̅-Maclaurin series. The method performed extremely well, and the projections of the obtained solutions into the integer space are compatible with solutions available in the literature. Finally, the graphical analysis showed a possibility that the Caputo fractional derivatives reflect some memory characteristics.
Inference and prediction of malaria transmission dynamics using time series data
Authors: Shi Benyun , Lin Shan , Tan Qi , Cao Jie , Zhou Xiaohong , Xia Shang , Zhou Xiao-Nong , Liu Jiming 
Published: July 2020

Abstract
Background
Disease surveillance systems are essential for effective disease intervention and control by monitoring disease prevalence as time series. To evaluate the severity of an epidemic, statistical methods are widely used to forecast the trend, seasonality, and the possible number of infections of a disease. However, most statistical methods are limited in revealing the underlying dynamics of disease transmission, which may be affected by various impact factors, such as environmental, meteorological, and physiological factors. In this study, we focus on investigating malaria transmission dynamics based on time series data.

Methods
A data-driven nonlinear stochastic model is proposed to infer and predict the dynamics of malaria transmission based on the time series of prevalence data. Specifically, the dynamics of malaria transmission is modeled based on the notion of vectorial capacity (VCAP) and entomological inoculation rate (EIR). A particle Markov chain Monte Carlo (PMCMC) method is employed to estimate the model parameters. Accordingly, a one-step-ahead prediction method is proposed to project the number of future malaria infections. Finally, two case studies are carried out on the inference and prediction of Plasmodium vivax transmission in Tengchong and Longling, Yunnan province, China.

Results
The results show that the trained data-driven stochastic model can well fit the historical time series of P. vivax prevalence data in both counties from 2007 to 2010. Moreover, with well-trained model parameters, the proposed one-step-ahead prediction method can achieve better performances than that of the seasonal autoregressive integrated moving average model with respect to predicting the number of future malaria infections.

Conclusions
By involving dynamically changing impact factors, the proposed data-driven model together with the PMCMC method can successfully (i) depict the dynamics of malaria transmission, and (ii) achieve accurate one-step-ahead prediction about malaria infections. Such a data-driven method has the potential to investigate malaria transmission dynamics in other malaria-endemic countries/regions.
Inactivating mutations in genes encoding for components of the BAF/PBAF complex and immune-checkpoint inhibitor outcome
Authors: Courtet Kevin , Laizet Yec’han , Lucchesi Carlo , Bessede Alban , Italiano Antoine 
Published: July 2020

AbstractAlterations of genes encoding subunits of the BAF/PBAF complexes are among the most frequent gene aberrations in human cancer. Such alterations have been shown to have an impact on tumor microenvironnement and on the capacity of tumors to respond to immune-checkpoint inhibitors (ICI). We analysed the clinical and genetic data from 43,728 patients accessed through cBioportal. The mutational frequencies of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1 were 6.6%, 3,4, 3.4, 3.2, 4.1, and 1.2%, respectively. We then investigated the association between the presence of least one nonsynonymous somatic mutation of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, or SMARCB1 and overall survival of 1661 patients treated with an ICI. Across the entire cohort, patients with BAF/PBAF mutated tumors have a statistically significant improvement in overall survival (median overall survival: 28 months [95% CI 21.6–34.3] versus 15 months [95% CI 12.9–17.0], p < 0.0001). When tumor mutational burden was adjusted for a multivariable Cox regression analysis, BAF/PBAF gene mutations remained an independent prognostic factor for overall survival in patients treated ICI. Our results establish a relationship between mutations in key genes encoding for components of the BAF/PBAF complex and outcome of patients treated with ICI. Further studies are needed to elucidate the underlying mechanisms of this interaction.
The Impact of Health Consciousness on the Association Between Walking Durations and Mental Health Conditions After a Disaster: a Cross-Sectional Study
Authors: Utsumi Yusuke , Nemoto Harumi , Nakaya Naoki , Nakamura Tomohiro , Tsuchiya Naho , Narita Akira , Kogure Mana , Suzuki Tomomi , Seto Moe , Katayanagi Mitsuaki , Okuyama Junko , Sakuma Atsushi , Honda Nami , Sugawara Yumi , Kaye-Kauderer Halley , Takahashi Yuta , Kayama Akemi , Kakuto Yoshihisa , Kohzuki Masahiro , Hozawa Atsushi , Tsuji Ichiro , Tomita Hiroaki 
Published: July 2020

Abstract
Background
In communities affected by a disaster, walking can be a feasible form of physical exercise to improve physical and mental health conditions. However, there is limited evidence to support relationships between walking habits and mental health conditions in post-disaster settings. Cross-sectional epidemiological data obtained from a questionnaire survey (conducted in October 2017) of a community affected by the 2011 Great East Japan Earthquake (GEJE) was analyzed to evaluate the relationships.

Methods
Participants included individuals over 20 years of age (N = 718) from Shichigahama town in Miyagi prefecture, whose houses were significantly damaged by the GEJE. Their mental health conditions were assessed by the Kessler Psychological Distress Scale (K6), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Impact of Event Scale-Revised (IES-R). Additionally, the questionnaire asked the participants spent duration walking on average and their walking purpose by the following items: (1) longer than 60 min per day, (2) between 30 and 60 min per day, or (3) less than 30 min per day, and whether they walked to maintain healthy living habits (health-conscious walkers) or merely for transportation without considering health consequences (non-health-conscious walkers). These information and mental health indicators were analyzed using analysis of covariance (ANCOVA).

Results
Among the three walking duration groups of health-conscious walkers, there were significant differences in CES-D and K6 scores (p = 0.01 and p = 0.04), but not in IES-R scores, considering age, gender, and alcohol drinking habits as covariates. CES-D score was significantly higher among short walkers (p = 0.004). Among the three walking duration groups of non-health-conscious walkers, there were significant differences in avoidance symptoms, the subdomain of IES-R (p = 0.01), but not in CES-D, K6, and total IES-R scores, considering the variants.

Conclusion
Our study suggests that walking durations may positively affect mood, but not PTSR, only when walking is performed with the purpose of maintaining healthy living habits. Walking durations were negatively associated with avoidance symptoms among non-health-conscious walkers in the community affected by the GEJE, indicating that the disaster may have had a long-lasting impact on walking habits.
Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)
Authors: Grob Jean-Jacques , Gonzalez Rene , Basset-Seguin Nicole , Vornicova Olga , Schachter Jacob , Joshi Abhishek , Meyer Nicolas , Grange Florent , Piulats Josep M. , Bauman Jessica R. , Zhang Pingye , Gumuscu Burak , Swaby Ramona F. , Hughes Brett G. M. 
Published: July 2020

PURPOSE Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort—locally advanced and R/M—phase II KEYNOTE-629 study. PATIENTS AND METHODS Patients with R/M cSCC not amenable to surgery or radiation received pembrolizumab 200 mg every 3 weeks. The primary end point was objective response rate per RECIST v1.1. Secondary end points were duration of response, disease control rate, progression-free survival, overall survival, and safety. RESULTS At data cutoff (April 8, 2019), median follow-up of 105 enrolled patients in the R/M cohort was 11.4 months (range, 0.4 to 16.3 months). Objective response rate was 34.3% (95% CI, 25.3% to 44.2%; 4 complete responses, 32 partial responses), and disease control rate was 52.4% (95% CI, 42.4% to 62.2%). Median duration of response was not reached (range, 2.7 to 13.1+ months; ‘+’ refers to ongoing response at data cutoff). Median progression-free survival was 6.9 months (95% CI, 3.1 months to 8.5 months). Median overall survival was not reached (95% CI, 10.7 months to not reached). Treatment-related adverse events occurred in 66.7% of patients (n = 70), the most common of which were pruritus (n = 15; 14.3%), asthenia (n = 14; 13.3%), and fatigue (n = 13; 12.4%). Grade 3 to 5 treatment-related adverse events occurred in 5.7% (n = 6) of patients. One patient died of treatment-related cranial nerve neuropathy. CONCLUSION Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with R/M cSCC, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.