bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adding Base-Excision Repair Inhibitor TRC102 to Standard Pemetrexed–Platinum–Radiation in Patients with Advanced Nonsquamous Non–Small Cell Lung Cancer: Results of a Phase I Trial
Authors: Biswas Tithi , Dowlati Afshin , Kunos Charles A. , Pink John J. , Oleinick Nancy L. , Malik Shakun , Fu Pingfu , Cao Shufen , Bruno Debora S. , Bajor David L. , Patel Monaliben , Gerson Stanton L. , Machtay Mitchell 
Published: November 2021

Abstract

Purpose:
TRC102, a small-molecule base-excision repair inhibitor, potentiates the cytotoxicity of pemetrexed and reverses resistance by binding to chemotherapy-induced abasic sites in DNA. We conducted a phase I clinical trial combining pemetrexed and TRC102 with cisplatin–radiation in stage III nonsquamous non–small cell lung cancer (NS-NSCLC).

Patients and Methods:
Fifteen patients were enrolled from 2015 to 2019. The primary objective was to determine the dose-limiting toxicity and maximum tolerated dose of TRC102 in combination with pemetrexed, cisplatin, and radiotherapy. Secondary objectives were to assess toxicity, tumor response, and progression-free survival at 6 months. Based on our preclinical experiments, pemetrexed–TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated in the second cycle. After completion, two additional cycles of pemetrexed–cisplatin were given. Toxicities were assessed using NCI CTACAE versions 4/5.

Results:
The median age was 69 years (45–79) with the median follow-up of 25.7 months (range, 7.9–47.4). No dose-limiting toxicities and no grade 5 toxicity were seen. Hematologic and gastrointestinal toxicities were the most common side effects. No clinical radiation pneumonitis was seen. Of 15 evaluable patients, three had complete response (20%), and 12 had partial response (80%). The 6-month progression-free survival was 80%, and the 2-year overall survival was 83%.

Conclusions:
Pemetrexed–TRC102 combined with cisplatin/radiotherapy in NS-NSCLC is safe and well tolerated. The recommended phase II dose is 200 mg TRC102 along with cisplatin–pemetrexed. No additional safety signal was seen beyond the expected CRT risks. A phase II trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen, is warranted.
Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03
Authors: Sheng Xinan , Chen Haige , Hu Bin , Yao Xudong , Liu Ziling , Yao Xin , Guo Hongqian , Hu Yi , Ji Zhigang , Luo Hong , Shi Benkang , Liu Jiyan , Wu Jin , Zhou FangJian , He Zhisong , Fan Jinhai , Wang Weifeng , Feng Hui , Yao Sheng , Keegan Patricia , Huang Yiran , Guo Jun 
Published: November 2021

Abstract

Purpose:
Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC.

Patients and Methods:
Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated.

Results:
Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS), and overall survival (OS) were 19.7 months [95% confidence interval (CI): 13.9–not estimable], 2.3 months (95% CI, 1.8–3.6), and 14.4 months (95% CI, 9.3–23.1), respectively. Both PD-L1+ and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1− patients (42% vs. 17%, P = 0.002) and TMB-low patients (48% vs. 22%, P = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, P &lt; 0.001) and OS (not reached versus 10.0 months, P = 0.018) than the TMB-low group.

Conclusions:
Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.
A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non–Small Cell Lung Cancer: a Multicenter Phase I/II Study
Authors: Zhou Qing , Wu Lin , Hu Pei , An Tongtong , Zhou Jianying , Zhang Li , Liu Xiao-Qing , Luo Feng , Zheng Xin , Cheng Ying , Yang Nong , Li Junling , Feng Jifeng , Han Baohui , Song Yong , Wang Kai , Zhang Li , Fang Jian , Zhao Hong , Shu Yongqian , Lin Xiao-Yan , Chen Zhihong , Gan Bin , Xu Wan-Hong , Tang Wei , Zhang Xiaoying , Yang Jin-Ji , Xu Xiao , Wu Yi-Long 
Published: November 2021

Abstract

Purpose:
To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non–small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II.

Patients and Methods:
This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II.

Results:
The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43–129). Among 209 response–evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2–59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9–92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1–9.2) and 7.5 months (95% CI: 6.0–8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4–not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related.

Conclusions:
Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.
Robust recognition technique for handwritten Kannada character recognition using capsule networks
Authors: Rani N. Shobha , N. Manohar , M. Hariprasad , B. R. Pushpa 
Published: November 2021

<p>Automated reading of handwritten Kannada documents is highly challenging due to the presence of vowels, consonants and its modifiers. The variable nature of handwriting styles aggravates the complexity of machine based reading of handwritten vowels and consonants. In this paper, our investigation is inclined towards design of a deep convolution network with capsule and routing layers to efficiently recognize Kannada handwritten characters. Capsule network architecture is built of an input layer, two convolution layers, primary capsule, routing capsule layers followed by tri-level dense convolution layer and an output layer. For experimentation, datasets are collected from more than 100 users for creation of training data samples of about 7769 comprising of 49 classes. Test samples of all the 49 classes are again collected separately from 3 to 5 users creating a total of 245 samples for novel patterns. It is inferred from performance evaluation; a loss of 0.66% is obtained in the classification process and for 43 classes precision of 100% is achieved with an accuracy of 99%. An average accuracy of 95% is achieved for all remaining 6 classes with an average precision of 89%.</p>
Smart system for maintaining aquascape environment using internet of things based light and temperature controller
Authors: Hutabarat Daniel Patricko , Susanto Rudy , Prasetya Bryan , Linando Barry , Senanayake Senanayake Mudiyanselage Namal 
Published: November 2021

<span>The purpose of this research is to create a smart system based on internet of things (IoT) application for a plant aquarium. This smart system helps users to maintain the environment's parameters of the plant aquarium. In this study, the parameters to be controlled by the system are light intensity and temperature. The hardware used to develop this system is the ESP32 as the microcontroller, BH1750FVI as the light sensor, high power led (HPL) light-emitting diodes (LED) lamp as the light source, DS18B20 as temperature sensor, the heater, and the 220 VAC fan that is used to raise and lower the temperature. In this study also developed an application that is used by the user to provide input to the system. The developed application is then installed on the user's smartphone and used to connect the user to the system via the internet. The ease of adding and removing devices used on the system is a capability that is also being developed in this smart system. The developed system can produce light intensity with accuracy rate of 96% and always manage to keep the temperature within the predetermined range.</span>
Cross-Border Surrogacy Before the European Court of Human Rights: Analysis of Valdís Fjölnisdóttir And Others v Iceland
Authors: Bracken Lydia 
Published: November 2021

Abstract
The recent case of Valdís Fjölnisdóttir and Others v Iceland adds to the emerging ECtHR jurisprudence on cross-border surrogacy. It reinforces principles established in previous cases and, in doing so, clarifies the scope of the child’s rights under Article 8 ECHR, and hence clarifies the scope of the obligations placed on Member States in cases of cross-border surrogacy. At the same time, consideration of Valdís Fjölnisdóttir reveals significant omissions in the approach adopted by the ECtHR as regards consideration of the rights of the child. In this way, aspects of Valdís Fjölnisdóttir confuse, rather than clarify, the scope of the child’s Article 8 ECHR rights in cases of cross-border surrogacy. This article examines the Valdís Fjölnisdóttir judgment with a view to identifying emerging principles, as well as contradictions, in the developing body of jurisprudence relating to cross-border surrogacy.
Effect of KLF17 overexpression on epithelial–mesenchymal transition of gastric cancer cells
Authors: Li Shaoyi , Li Yong , Tan Bibo , An Zhaojie 
Published: November 2021

Objective To investigate Krüppel-like factor 17 ( KLF17) expression in normal and gastric cancer tissues and cell lines. Methods Levels of KLF17 mRNA and protein in GES-1 normal gastric mucosal cells, and NCI-N87, SGC-7901, BGC-823 and HGC-27 gastric cancer cells were analysed by quantitative polymerase chain reaction (qPCR) and western blot. Differences in KLF17 expression between gastric cancer and adjacent tissues were analysed by qPCR and immunohistochemistry. Invasion/migration effects of KLF17 overexpression in BGC-823 and HGC-27 cells were analysed by wound-healing and Transwell chamber assays. Changes in expression of KLF17 and epithelial–mesenchymal transition (EMT)-related genes (matrix metalloproteinase [MMP]-9, vimentin and E-cadherin) were analysed in BGC-823 and HGC-27 cells before and after transfection using qPCR and western blot. Transforming growth factor (TGF)-β1, Smad family member (Smad)2/3 and phosphorylated-Smad2/3 levels in BGC-823 and HGC-27 cells were assessed by qPCR and western blot. Results KLF17 expression was lower in gastric cancer versus adjacent tissues, and in gastric cancer cell lines versus GES-1 normal gastric mucosal cells, and was positively correlated with degree of cancer-cell differentiation. Wound-healing and Transwell assays showed decreased migration and invasion ability of BGC-823 and HGC-27 cells transfected to overexpress KLF17. KLF17 overexpression was associated with decreased MMP-9 and vimentin in BGC-823 and HGC-27 cancer cells, and increased KLF17 and E-cadherin. KLF17 overexpression also resulted in decreased levels of TGF-β1 and p-Smad2/3 in BGC-823 and HGC-27 cancer cells. Conclusion KLF17 is poorly expressed in gastric cancer tissues and cell lines. KLF17 overexpression might inhibit EMT via the TGF-β/Smad pathway, thereby reducing gastric cancer cell invasion and migration. Therefore, KLF17 may become a novel target for treating gastric cancer.
Impact of a Behavioral Sleep Intervention in Adolescents With ADHD: Feasibility, Acceptability, and Preliminary Effectiveness From a Pilot Open Trial
Authors: Becker Stephen P. , Duraccio Kara M. , Sidol Craig A. , Fershtman Chaya E. M. , Byars Kelly C. , Harvey Allison G. 
Published: November 2021

Objective: An open trial tested the feasibility, acceptability, and preliminary effectiveness of a behavioral sleep intervention in adolescents with ADHD. Method: Fourteen adolescents (ages 13–17 years; 50% male) with ADHD and co-occurring sleep problems received the cognitive-behavioral-based Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C). Adolescent, parent, and teacher ratings, actigraphy, and daily sleep diaries were collected at pre-intervention, post-intervention, and 3-month follow-up. Results: Adolescents experienced moderate to large improvements in sleep, mental health symptoms, and daily life executive functioning from pre-treatment to post-treatment, and improvements were generally maintained at 3 months. Pre-intervention, 71.4% of adolescents were classified as poor sleepers and this was reduced to 21.4% and 28.6% at post-treatment and follow-up, respectively. Conclusion: This study provides strong preliminary evidence that TranS-C improves sleep and associated outcomes in adolescents with ADHD and co-occurring sleep problems. A randomized controlled trial is needed to rigorously test the efficacy of TranS-C in this population.
Determination of pain experienced by children during intravenous bolus treatments and its causes
Authors: Alaca Asli , Yildirim Sari Hatice 
Published: November 2021

Objective: The present study aimed to determine the pain experienced by children during intravenous bolus treatment and to identify what causes it. Method: In the first stage of the study, the first 40 observations were performed by two researchers. The study was continued by a single observer after the Kappa test was performed. In this study, 101 drug treatments were administered by intravenous bolus in patients aged between 1 month and 6 years. The pain experienced during treatment was assessed using pain scales according to the age group the patient was in. Results: Pain was observed in 63.4% ( n = 64) of the treatments. There was a significant relationship between the type of medication administered and pain experienced during drug administration. There was also a significant correlation between the age of the children and their pain experiences. Given the location of the catheter, there was no significant difference among the children who experienced pain during intravenous treatment. Conclusion: Intravenous drug therapy may cause pain in children. To minimize such pain, it is recommended to determine the drugs that cause pain during intravenous treatment and to develop application protocols to minimize pain caused by these drugs.
The Prevalence of Post-Traumatic Stress Disorder in Birth Parents in Child Protection Services: Systematic Review and Meta-analysis
Authors: Suomi Aino , Bolton Annalese , Pasalich Dave 
Published: November 2021

Background Birth parents of children in the statutory child protection system have disproportionally high rates of trauma exposure and mental health problems, however, little is known about the extent to which this population display symptoms of Post-Traumatic Stress Disorder (PTSD) or Complex PTSD. This study provides a systematic review and meta-analysis of the PTSD rates in parent samples involved in the child protection services. Method Articles were identified by searching PSYCINFO, Medline, CINAHL, and PILOTS. The search included terminology pertaining to parents, trauma, and child protective services and we included all peer-reviewed articles that reported a valid measure of PTSD and child protection service involvement. Results Fifteen studies were included in the review with a combined prevalence estimate for PTSD based on 11 studies ( n = 4871) was 26.0% (95% CI 20.0–32.0%) for mothers, and estimate based on three studies ( n = 2606) was 13.0% (95% CI 7.0%–18.0%) for fathers and 23.0% (95% CI 17.0–29.0) for all parents based on 7848 responses. Four studies that did not report prevalence rates, reported sample mean scores for PTSD that were consistently higher than in general population. Factors associated with parents’ PTSD symptoms included mental health co-morbidities, victimization of physical and sexual violence, and perpetration of child abuse. Conclusion There are high rates of PTSD in parents involved in the protective system, thus more targeted efforts are needed to identify and adequately address trauma symptoms of parents as part of child protection interventions.
Circ_0039411 promotes papillary thyroid carcinoma development through mediating the miR-423-5p/SOX4 signaling
Authors: Wen Xiaohui , Du Jingyan , Wang Xun 
Published: November 2021

Background Papillary thyroid carcinoma is the most frequent histological subtype of thyroid cancer with a high incidence. We aimed to explore the function of circular RNA_0039411 (circ_0039411) and its associated mechanism in papillary thyroid carcinoma progression. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine the expression of RNA and protein, respectively. The colony formation ability, migration, invasion, and apoptosis were analyzed by colony formation assay, transwell migration assay, transwell invasion assay, and flow cytometry. Cell glycolytic metabolism was analyzed using fluorescence-based glucose assay kit and fluorescence-based lactate assay kit. Dual-luciferase reporter assay and RNA-Pull-Down Assay were performed to validate the binding between microRNA-423-5p (miR-423-5p) and circ_0039411 or SRY-box transcription factor 4 (SOX4). The xenograft tumor model was used to assess the role of circ_0039411 in the tumor growth in vivo. Results Circ_0039411 was highly expressed in papillary thyroid carcinoma tissues and cell lines compared with adjacent normal tissues and NTHY-ORI3.1 cells. Circ_0039411 interference suppressed the colony formation ability, migration, invasion, and glycolysis but promoted the apoptosis of papillary thyroid carcinoma cells. MiR-423-5p was a target of circ_0039411 in papillary thyroid carcinoma cells. Circ_0039411 knockdown-mediated effects in papillary thyroid carcinoma cells were largely overturned by the silence of miR-423-5p. MiR-423-5p bound to the 3′ untranslated region (3′UTR) of SOX4. SOX4 overexpression largely reversed circ_0039411 silencing-mediated effects in papillary thyroid carcinoma cells. Circ_0039411 positively regulated SOX4 expression by sponging miR-423-5p in papillary thyroid carcinoma cells. Circ_0039411 silencing notably suppressed the growth of xenograft tumors in vivo. Conclusion Circ_0039411 promoted the malignant behaviors of papillary thyroid carcinoma cells partly depending on the regulation of the miR-423-5p/SOX4 axis.
Occupation-based intervention in therapy for upper limb musculoskeletal conditions: A systematic review
Authors: Visser Elreen , de Klerk Susan , Jacobs-Nzuzi Khuabi Lee-Ann , Joubert Marleen 
Published: November 2021

Introduction Using meaningful activities as a treatment modality is characteristic of occupation-based intervention (OBI). The benefits of OBI have been described, but not the effectiveness thereof. The aim of this review was to assess the effectiveness of OBI in relation to the type, commencement, duration and outcomes as reported in literature. Methods A comprehensive search of electronic databases was conducted, including EBSCOHost, PubMed, Cochrane Register for Controlled Trials, Web of Science, OTSeeker, PEDro and Google Scholar. Search terms included ‘occupation-based’, ‘occupation-centered’, ‘intervention’, ‘upper limb’ and ‘outcome measures’. Studies including OBI for neurological or paediatric cases were excluded. Results Twelve studies met the inclusion criteria. Using the PEDro scale, three of the studies, all randomised controlled trials (RCTs), were viewed as high quality, one of fair and one of poor quality. Due to the heterogeneity of the studies, a meta-analysis was not possible, and a narrative synthesis is presented. Five studies used interviewing together with the Canadian Occupational Performance Measure (COPM) to determine the client’s occupational profile when choosing meaningful activities. The commencement and duration of OBI varied amongst the studies, and a variety of outcome measures were used to determine the effectiveness of OBI. Discussion OBI used together with biomechanical approaches shows promising effectiveness. Outcome measures such as the COPM and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) that measure activity and participation, should be employed in client-centered practice. More robust scientific evidence regarding the effectiveness of OBI is needed.
The Role of Hounsfield Unit in Intraoperative Endplate Violation and Delayed Cage Subsidence with Oblique Lateral Interbody Fusion
Authors: Wu Hao , Cheung Jason Pui Yin , Zhang Teng , Shan Zhi , Zhang Xuyang , Liu Junhui , Fan Shunwu , Zhao Fengdong 
Published: November 2021

Study Design Retrospective clinical case series. Objectives To investigate the risk factors for intraoperative endplate violations and delayed cage subsidence after oblique lateral interbody fusion (OLIF) surgery. Secondly, to examine whether low Hounsfield unit (HU) values at different regions of the endplate are associated with intraoperative endplate violation or delayed cage subsidence. Methods 61 patients (aged 65.1 ± 9.5 years; 107 segments) who underwent OLIF with or without posterior instrumentation from May 2015 to April 2019 were retrospectively studied. Intraoperative endplate violation was measured on sagittal reconstructed computerized tomography (CT) images immediate postoperatively, while delayed cage subsidence was evaluated using lateral radiographs and defined at 1-month follow-up or later. Demographic information and clinical parameters such as age, body mass index, bone mineral density, number of surgical levels, cage dimension, disc height restoration, visual analogue scale (VAS), and HU at different regions of the endplate were obtained. Results Total postoperative cage subsidence was identified in 45 surgical levels (42.0%) in 26 patients (42.6%) up till postoperative 1-year follow-up. Low HU value at the ipsilateral epiphyseal ring was an independent risk factor for intraoperative endplate violation ( P = .008) with a cut-off value of 326.21 HUs. Low HU values at the central endplate had a significant correlation with delayed cage subsidence in stand-alone cases ( P = .013) with a cut-off value of 296.42 HUs. VAS scores were not different at 1 week postoperatively in cases with or without intraoperative endplate violation (3.12 ± .73 vs 2.89 ± .72, P = .166) and showed no difference at 1 year with or without delayed cage subsidence (1.95 ± .60 vs 2.26 ± .85, P = .173). Conclusions Intraoperative endplate violation and delayed cage subsidence are not uncommon with OLIF surgery. HUs of the endplate are good predictors for intraoperative endplate violation and cage subsidence since they can represent the regional bone quality of the endplate in contact with the implant. VAS improvements were not affected by intraoperative endplate violation or delayed cage subsidence at 1-year follow-up. Level of Evidence Level III.