bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells
Authors: Danilova Anna , Misyurin Vsevolod , Novik Aleksei , Girdyuk Dmitry , Avdonkina Natalia , Nekhaeva Tatiana , Emelyanova Natalia , Pipia Nino , Misyurin Andrey , Baldueva Irina 
Published: February 2020

Abstract
Background
Autologous dendritic cells (DC) loaded with tumor-associated antigens (TAAs) are a promising approach for anticancer immunotherapy. Polyantigen lysates appear to be an excellent source of TAAs for loading onto the patient’s dendritic cells. Cancer/testis antigens (CTA) are expressed by a wide range of tumors, but are minimally expressed on normal tissues, and could serve as a universal target for immunotherapy. However, CTA expression levels can vary significantly in patients with the same tumor type. We proposed that patients who do not respond to DC-based therapy may have distinct features of the CTA expression profile on tumor cells.

Patients and methods
We compared the gene expression of the principal families CTA in 22 melanoma and 27 soft tissue and bone sarcomas cell lines (STBS), received from patients and used for DC vaccine preparation.

Results
The majority (47 of 49, 95.9%) cell lines showed CTA gene activity. The incidence of gene expression of GAGE, NYESO1, MAGEA1, PRAME’s was significantly different (adj. p < 0.05) between melanoma and sarcoma cell lines. The expression of the SCP1 gene was detected neither in melanoma cells nor in the STBS cells. Clustering by the gene expression profile revealed four different expression patterns. We found three main patterns types: hyperexpression of multiple CTA, hyperexpression of one CTA with almost no expression of others, and no expression of CTA. All clusters types exist in melanoma and sarcoma cell lines. We observed dependence of killing efficacy from the PRAME (rho = 0.940, adj. p < 0.01) expression during real-time monitoring with the xCELLigence system of the interaction between melanoma or sarcoma cells with the T-lymphocytes activated by the lysate of selected allogenous melanoma cell lines with high expression of CTA.

Conclusion
Our results demonstrate that one can use lysates from allogeneic melanoma cell lines as a source of CTA for DC load during the production of anticancer vaccines for the STBS treatment. Patterns of CTA expression should be evaluated as biomarkers of response in prospective clinical trials.
Impulsive stochastic fractional differential equations driven by fractional Brownian motion
Authors: Abouagwa Mahmoud , Cheng Feifei , Li Ji 
Published: February 2020

AbstractIn this research, we study the existence and uniqueness results for a new class of stochastic fractional differential equations with impulses driven by a standard Brownian motion and an independent fractional Brownian motion with Hurst index $1/2< H<1$1/2<H<1 under a non-Lipschitz condition with the Lipschitz one as a particular case. Our analysis depends on an approximation scheme of Carathéodory type. Some previous results are improved and extended.
Thermodynamic and ecological preselection of synthetic fuel intermediates from biogas at farm sites
Authors: Peters Ralf , Decker Maximilian , Eggemann Lea , Schemme Steffen , Schorn Felix , Breuer Janos Lucian , Weiske Stefan , Pasel Joachim , Samsun Remzi Can , Stolten Detlef 
Published: February 2020

AbstractBackgroundSynthetic fuels based on renewable hydrogen and CO2are a currently highly discussed piece of the puzzle to defossilize the transport sector. In this regard, CO2can play a positive role in shaping a sustainable future. Large potentials are available as a product of biogas production, however occurring in small scales and in thin spatial distributions. This work aims to evaluate suitable synthetic fuel products to be produced at farm sites.MethodsA thermodynamic analysis to assess the energetic efficiency of synthesis pathways and a qualitative assessment of product handling issues is carried out.ResultsRegarding the technical and safety-related advantages in storage, liquid products are the superior option for fuel production at decentralized sites. Due to the economy of scale, multi-stage synthesis processes lose economic performance with rising complexity. A method was shown which covers a principle sketch of all necessary reaction, separation steps, and all compression and heat exchanger units. The figures showed that methanol and butanol are the most suitable candidates in contrast to OME3-5for implementation in existing transportation and fuel systems. These results were underpin by a Gibbs energy analysis.ConclusionsAs long as safety regulations are met and the farm can guarantee safe storage and transport, farm-site production for all intermediates can be realized technically. Ultimately, this work points out that the process must be kept as simple as possible, favoring methanol production at farm site and its further processing to more complicated fuels in large units for several fuel pathways.
The physiology of movement
Authors: Goossens Steven , Wybouw Nicky , Van Leeuwen Thomas , Bonte Dries 
Published: February 2020

AbstractMovement, from foraging to migration, is known to be under the influence of the environment. The translation of environmental cues to individual movement decision making is determined by an individual’s internal state and anticipated to balance costs and benefits. General body condition, metabolic and hormonal physiology mechanistically underpin this internal state. These physiological determinants are tightly, and often genetically linked with each other and hence central to a mechanistic understanding of movement. We here synthesise the available evidence of the physiological drivers and signatures of movement and review (1) how physiological state as measured in its most coarse way by body condition correlates with movement decisions during foraging, migration and dispersal, (2) how hormonal changes underlie changes in these movement strategies and (3) how these can be linked to molecular pathways.We reveale that a high body condition facilitates the efficiency of routine foraging, dispersal and migration. Dispersal decision making is, however, in some cases stimulated by a decreased individual condition. Many of the biotic and abiotic stressors that induce movement initiate a physiological cascade in vertebrates through the production of stress hormones. Movement is therefore associated with hormone levels in vertebrates but also insects, often in interaction with factors related to body or social condition. The underlying molecular and physiological mechanisms are currently studied in few model species, and show –in congruence with our insights on the role of body condition- a central role of energy metabolism during glycolysis, and the coupling with timing processes during migration. Molecular insights into the physiological basis of movement remain, however, highly refractory. We finalise this review with a critical reflection on the importance of these physiological feedbacks for a better mechanistic understanding of movement and its effects on ecological dynamics at all levels of biological organization.
Electroencephalography-based neurofeedback as treatment for post-traumatic stress disorder: A systematic review and meta-analysis
Authors: Steingrimsson Steinn , Bilonic Gorana , Ekelund Ann-Catrin , Larson Tomas , Stadig Ida , Svensson Mikael , Vukovic Iris Sarajlic , Wartenberg Constanze , Wrede Olof , Bernhardsson Susanne 
Published: February 2020

Abstract

Background
Post-traumatic stress disorder (PTSD) is debilitating for patients and society. There are a number of treatment methods albeit not all patients respond to these and an interesting method using electroencephalography-based neurofeedback (EEG-NF) has become more prominent in recent years. This systematic review aimed to assess whether EEG-NF, compared with sham NF, other treatment, or no treatment, is effective for PTSD. Primary outcomes were self-harm, PTSD symptoms, level of functioning and health-related quality of life.

Methods
Systematic literature searches for randomized controlled trials (RCTs) were conducted in six databases. Random effects meta-analysis was performed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Results
Four RCTs were included (123 participants). Suicidal thoughts were significantly reduced after EEG-NF compared with a waiting list in a small study. PTSD symptoms were assessed in all studies with different instruments. Results were consistently in favor of EEG-NF with large effect sizes (standardized mean difference −2.30 (95% confidence interval: −4.37 to −0.24). One study reported significantly improved level of executive functioning and one study a reduction in use of psychotropic medication. Complications were scarcely reported. Certainty of evidence was assessed as very low for the four assessed outcomes.

Conclusions
Based on four RCTs, with several study limitations and imprecision, it is uncertain whether EEG-NF reduces suicidal thoughts, PTSD symptoms, medication use, or improves function. Although all studies showed promising results, further studies are needed to increase the certainty of evidence.
Pemetrexed plus erlotinib as a salvage treatment in high EGFR-expressing metastatic colorectal cancer patients following failure of standard chemotherapy: A phase II single-arm prospective study.
Authors: Byeon Seonggyu , Kim Seung Tae , Hong Jung Yong , Lee Jeeyun , Park Joon Oh , Lim Ho-Yeong , Kang Won Ki , Park Young Suk 
Published: February 2020

104 Background: We conducted a single-arm, phase II study to evaluate the combination of pemetrexed and erlotinib as a salvage treatment in high EGFR-expressing (2+ or 3 on immunohistochemistry (IHC)) metastatic colorectal cancer (CRC) patients who failed to show a benefit after standard chemotherapy. Methods: We investigated pemetrexed and erlotinib (pemetrexed 500 mg/m2 on Day 1 and erlotinib 100 mg/m2 on Days 1–21) as a salvage treatment, given every three weeks, until disease progression or intolerable toxicity. The primary outcome was overall response rate (RR). Results: From May 2017 to April 2018, 29 metastatic CRC patients with high EGFR expression who previously received the standard therapies were enrolled into this trial. The regimen was well tolerated. Skin rash, vomiting, fatigue, and anorexia were common toxic effects but were mostly manageable and controllable side effects of only grades 1 or 2. In intent-to-treat analysis, three partial responses (PRs) were observed in enrolled patients, revealing an overall RR of 10.3%. This value supported the statistical hypothesis of this study. Fifteen patients had stable disease and the disease control rate (DCR) was 62.1%. All three patients who achieved a PR had an expression of EGFR 3+ in a tumor. Among eight patients with a tumor expressing an EGFR value of 3+, the RR and DCR were 37.5% and 75.0%, respectively. Conclusions: This phase II trial using pemetrexed and erlotinib in metastatic CRC with high EGFR expression met the primary endpoint of tumor response. Clinical trial information: NCT03086538.
Clinical impact of primary tumor location in patients with metastatic colorectal cancer (mCRC) treated with regorafenib or trifluridine/tipiracil as later-line.
Authors: Nakajima Hiromichi , Fukuoka Shota , Moriwaki Toshikazu , Masuishi Toshiki , Takashima Atsuo , Kumekawa Yosuke , Kajiwara Takeshi , Yamazaki Kentaro , Komoda Masato , Makiyama Akitaka , Denda Tadamichi , Hatachi Yukimasa , Suto Takeshi , Sugimoto Naotoshi , Enomoto Masanobu , Ishikawa Toshiaki , Kashiwada Tomomi , Oki Eiji , Gosho Masahiko , Shimada Yasuhiro 
Published: February 2020

105 Background: In the recent years, primary tumor location (PTL) is considered as an important prognostic and predictive factor in first-line treatment of mCRC. Although regorafenib (REG) and trifluridine/tipiracil (TFTD) have been available recently, the prognostic value of PTL in later-line with these agents is not well understood. TFTD improved survival regardless of PTL in the RECOURSE trial, while REG did not show survival benefit in the patients (pts) with rectal cancer in the CORRECT trial. Methods: We retrospectively evaluated pts with mCRC who were registered in a multicenter observational study (the REGOTAS study). The main inclusion criteria were ECOG PS of 0–2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF and anti-EGFR therapy (if KRAS wild type), and no prior use of REG and TFTD. The impact of PTL on overall survival (OS) were evaluated using Cox proportional hazards models based on baseline characteristics and propensity score matching. Results: A total of 550 pts (223 pts in the REG group, 327 pts in the TFTD group; 122 pts in the right-sided, 428 pts in the left-sided) were included in this study. Although the right-sided pts was significantly shorter OS compared with the left-sided pts by univariate analysis (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.63-0.99, P = 0.04), multivariate analysis revealed that PTL was not an independent prognostic factor (HR 0.88, 95% CI 0.69-1.1, P = 0.26). The similar results were obtained in each treatment group. In subgroup analysis according to PTL, OS were comparable between REG and TFTD groups regardless of PTL (HR 0.93, 95% CI 0.62-1.39 in the right-sided; HR 1.08, 95% CI 0.83-1.39 in the left-sided [excluding rectum]; and HR 1.01, 95% CI 0.62-1.62 in the rectal cancer pts). These results were similar in sensitivity analysis using propensity score-matching. Conclusions: In the present study, PTL is not a prognostic factor in patient with mCRC treated with either REG or TFTD as later-line. No difference in OS was observed between REG and TFTD groups irrespective of PTL.
The clinical significance of simple endoscopic scoring of patients with rectal cancer after concurrent chemoradiotherapy.
Authors: Kim Jae Hyun , Park Seun Ja 
Published: February 2020

109 Background: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an effective treatment option for patients with rectal cancer. In this study, we investigated the clinical efficacy of simple endoscopic scoring of patients with rectal cancer after CCRT. Methods: Between July 2008 and October 2015, medical records including endoscopic imaging from 41 patients with rectal cancer who received CCRT were retrospectively reviewed. Two expert gastroenterologists reviewed the endoscopic images and assigned scores from 0–3 according to post-CCRT findings. The scoring criteria were as follows: 0 = scar without marginal elevation; 1 = clean-based ulcer without marginal elevation; 2 = clean-based ulcer with marginal elevation; 3 = non-clean-based ulcer. We evaluated image scores to predict long-term outcomes using Kaplan-Meier curves and Cox regression models. Results: The median follow-up duration was 55 months (interquartile range: 35–76). Patients with a low score (≤2) had a 17.2% recurrence rate, whereas patients with a high score (3) had a 50.0% recurrence rate. Patients with a low score had longer disease-free survival (DFS) than those with a high score in log-rank test (p = 0.026). In multivariate Cox regression analysis, a high score was a significant predictor of poor DFS in patients with rectal cancer after CCRT treatment (hazard ratio = 4.89, 95% confidence interval: 1.11–21.50, p = 0.036). Conclusions: This simple endoscopic scoring approach is helpful for predicting prognosis of patients with rectal cancer after treatment with CCRT.
PD-1 blockade combined with COX inhibitor in patients with MSI-H/dMMR or high TMB, advanced or metastatic colorectal cancer (PCOX study).
Authors: Wu Zehua , Hu Huabin , Zhang Jianwei , Cai Yue , Xie Xiaoyu , Ling Jiayu , Li Weiwei , Deng Yanhong 
Published: February 2020

111 Background: MSI-H/dMMR and POLE mutation had been proven to be predictive of response to PD-1 blockade in metastatic colorectal cancer. However, reported response rates are often < 50%. Several preclinical studies reported COX inhibitor improve antigen presentation and T-cell infiltration in tumors. We investigated the efficacy of PD-1 blockade combined with COX inhibitor in colorectal cancer patients with MSI-H/dMMR or POLE mutation. Methods: PCOX was a prospective, single arm, phase II study. Patients with MSI-H/dMMR or POLE mutation advanced or metastatic colorectal cancer received PD-1 blockade (pembrolizumab 200mg, q3w; or BAT 1306 100mg, q3w; or nivolumab 3mg per kilogram, q2w) plus COX inhibitor (celebrex 400mg or aspirin 200mg, p.o. qd). The primary endpoint was ORR, secondary endpoints included PFS, OS and safety. Results: Totally 24 patients were enrolled. 14(58.3%) patients were female. Median age was 41.5-years-old. Among 24 patients, 5(20.8%) patients were chemotherapy-naïve, 11(45.8%) patients had first line chemotherapy failed and 8(33.3%) patients had at least second lines chemotherapy failed. 22 patients were MSI-H/dMMR and 2 patients were with POLE mutation. At a median follow-up of 14.5 months, the ORR was 83.3% (20/24), including 5 patients achieved CR (3 pCR and 2 cCR). 3 patients achieved SD and 1 patient was PD. Median PFS and OS was not yet reached. One-year PFS rates was 80.7% (95%CI, 63.5%-97.9%). One-year survival rates was 91.3% (95%CI, 79.7%-100%). The reported treatment-related adverse events were listed in table below. Conclusions: The combination of PD-1 blockade plus COX inhibitor was associated with higher response rates in advanced or metastatic colorectal cancer patients with MSI-H/dMMR or POLE mutation than anti-PD-1 alone as historical controls. Clinical trial information: NCT03638297. [Table: see text][Table: see text]
The treatment strategy of the second-line chemotherapy for metastatic colorectal cancer (mCRC) patients (pts) with early progression in the first-line chemotherapy with bevacizumab (BEV), BEV beyond progression (BBP), or non-BBP.
Authors: Kawakami Takeshi , Yamamoto Shun , Mitani Seiichiro , Esaki Taito , Tsuji Yasushi , Izawa Naoki , Kawakami Kentaro , Yamamoto Yoshiyuki , Makiyama Akitaka , Yamazaki Kentaro , Masuishi Toshiki , Nakajima Takako Eguchi , Okuda Hiroyuki , Moriwaki Toshikazu , Boku Narikazu 
Published: February 2020

113 Background: BBP has been recognized as one of the standard 2nd-line treatment strategy for pts with mCRC based on the ML18147 trial. However, this trial excluded pts with disease progression < 3 months in the 1st-line BEV-containing chemotherapy. Methods: The subjects were mCRC pts who received the 2nd-line chemotherapy after experiencing disease progression < 100 days in the 1st-line BEV-containing chemotherapy between Apr 2010 and Dec 2016. This multi-institutional retrospective study compared the efficacy and safety between the 2nd-line chemotherapy with BEV (BBP) and without BEV (non-BBP), adjusting ECOG PS, WBC, ALP, number of metastatic sites, RAS status, and sidedness using Cox proportional hazard model. Results: 61 pts were evaluated. Patients' backgrounds were numerically different between BBP (n = 36) and non-BBP (n = 25), such as PS (0-1/2≤/unknown: 89/8/3 and 56/40/4%) and RASstatus (wild/mutant/unknown: 28/56/16 and 76/16/8%). There were no significant differences in age (median: 59 and 57), sex (male/female: 53/47 and 32/68%), tumor location (right/left: 44/56 and 40/60%), disease status (stage IV/recurrence: 67/33 and 84/16%), number of metastatic sites (1/2≤: 33/67 and 20/80%), the 1st-line regimens (oxaliplatin-based/irinotecan-based: 83/17 and 96/4%) between two arms. The 2nd-line chemotherapy regimens with EGFR antibody-containing/cytotoxic alone were 64/36% in non-BBP, respectively. The response rates were 5.9 and 8.7% in BBP and non-BBP. Median PFS were 3.7 and 2.8 months (HR 0.83, 95%CI 0.49-1.41, p = 0.486; adjusted HR 0.97, 95%CI 0.48-1.96, p = 0.932), respectively. The proportions of pts who received subsequent chemotherapy were 58 and 32% (p = 0.068). Median OS were 7.6 and 5.4 months (HR 0.70, 95%CI 0.41-1.19, p = 0.193; adjusted HR 0.65, 95%CI 0.34-1.25, p = 0.195). Common grade 3-4 adverse events (AEs) were neutropenia (11/24%) and anemia (3/16%), and other AEs were similar between two arms. Conclusions: The 2nd-line chemotherapy for pts with early progression in the 1st-line BEV-containing chemotherapy showed poor outcomes regardless of strategy.
Efficacy and safety of regorafenib in combination with chemotherapy as second-line therapy in patients with metastatic colorectal cancer: A network meta-analysis.
Authors: Xie Xiaoyu , Zhang Jianwei , Hu Huabin , Cai Yue , Wu Zehua , Ling Jiayu , Li Weiwei , Deng Yanhong 
Published: February 2020

115 Background: Recent studies have shown efficacy of chemotherapy (CTX) in combination with different biological agents including regorafenib (REG) in second-line treatment of metastatic colorectal cancer (mCRC). As there is no evidence on the relative efficacy and safety of REG as compared to other biological agents in combination with CTX, we evaluated the same in this network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) comparing efficacy and safety of biological agents + CTX against CTX alone as second-line treatment of mCRC were retrieved from PubMed, EMBASE and Cochrane databases. Progression free survival (PFS) was the primary outcome, while objective response rate (ORR), overall survival (OS) and safety were secondary outcomes. Outcomes were compared by random/mixed-effects NMA using Bayesian (R software, Gemtc package) and frequentist (R software, netmeta package) approaches. Results: Twelve RCTs comparing 9 different treatment regimens with a total of 6805 patients were included for analysis. Hazard ratios (HR)/ odds ratio (OR)/ relative risk (RR) and 95% confidence intervals (CI) for PFS, ORR and grade> 3 adverse events (AE) of selected comparisons from the results of the NMA are shown in table. Conclusions: REG combined with CTX might be a potential alternative to conventional therapeutic options and could be considered as the best option for treating KRAS and BRAF mutated mCRC patients. Future RCTs are needed to confirm our results. [Table: see text]