bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer
Authors: Xia Wei-Xiong , Lv Xing , Liang Hu , Liu Guo-Ying , Sun Rui , Zeng Qi , Li Si-Wei , Mo Hao-Yuan , Han Fei , Luo Dong-Hua , Liu Qing , Shi Meng-Yun , Ye Yan-Fang , Yang Jing , Ke Liang-Ru , Qiang Meng-Yun , Qiu Wen-Ze , Yu Ya-Hui , Liu Kui-Yuan , Huang Xin-Jun , Li Wang-Zhong , Lv Shu-Hui , Cai Zhuo-Chen , Miao Jing-Jing , Guo Ling , Chen Ming-Yuan , Cao Ka-Jia , Wang Lin , Zhao Chong , Huang Pei-Yu , Chen Qiu-Yan , Hua Yi-Jun , Tang Lin-Quan , Qian Chao-Nan , Mai Hai-Qiang , Guo Xiang , Xiang Yan-Qun 
Published: June 2021

Abstract

Purpose:
Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen.

Patients and Methods:
This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin.

Results:
A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of −0.2% (95% confidence interval, −6.3 to 5.9; Pnoninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3–4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039).

Conclusions:
Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.
Phase I, First-in-Human Study of the Probody Therapeutic CX-2029 in Adults with Advanced Solid Tumor Malignancies
Authors: Johnson Melissa , El-Khoueiry Anthony , Hafez Navid , Lakhani Nehal , Mamdani Hirva , Rodon Jordi , Sanborn Rachel E. , Garcia-Corbacho Javier , Boni Valentina , Stroh Mark , Hannah Alison L. , Wang Song , Castro Henry , Spira Alexander 
Published: June 2021

Abstract

Purpose:
PROCLAIM-CX-2029 is a phase I first-in-human study of CX-2029, a Probody–drug conjugate targeting CD71 (transferrin receptor 1) in adults with advanced solid tumors. Although the transferrin receptor is highly expressed across multiple tumor types, it has not been considered a target for antibody–drug conjugates (ADCs) due to its broad expression on normal cells. CX-2029 is a masked form of a proprietary anti-CD71 antibody conjugated to monomethyl auristatin E, designed to be unmasked in the tumor microenvironment by tumor-associated proteases, therefore limiting off-tumor toxicity and creating a therapeutic window for this previously undruggable target.

Patients and Methods:
This was a dose-escalation, multicenter trial to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. The primary endpoint was to determine the maximum tolerated dose (MTD) and cycle 1 dose-limiting toxicity (DLT). CX-2029 was administered i.v. every 3 weeks.

Results:
Forty-five patients were enrolled in eight dose levels. No DLTs were reported in the dose escalation through 4 mg/kg. At 5 mg/kg, there were two DLTs (febrile neutropenia and pancytopenia). Following expansion of the 4 mg/kg dose to six patients, two additional DLTs were observed (infusion-related reaction and neutropenia/anemia). Both the 4 and 5 mg/kg doses were declared above the maximum tolerated dose. The recommended phase II dose is 3 mg/kg. The most common dose-dependent hematologic toxicities were anemia and neutropenia. Confirmed partial responses were observed in three patients, all with squamous histologies.

Conclusions:
The Probody therapeutic platform enables targeting CD71, a previously undruggable ADC target, at tolerable doses associated with clinical activity.
See related commentary by Oberoi and Garralda, p. 4459
Deepenz: prediction of enzyme classification by deep learning
Authors: Chehili Hamza , Eddine Aliouane Salah , Bendahmane Abdelhafedh , Abdelhafid Hamidechi Mohamed 
Published: June 2021

<span>Previously, the classification of enzymes was carried out by traditional heuritic methods, however, due to the rapid increase in the number of enzymes being discovered, new methods aimed to classify them are required. Their goal is to increase the speed of processing and to improve the accuracy of predictions. The Purpose of this work is to develop an approach that predicts the enzymes’ classification. This approach is based on two axes of artificial intelligence (AI): natural language processing (NLP) and deep learning (DL). The results obtained in the tests show the effectiveness of this approach. The combination of these two tools give a model with a great capacity to extract knowledge from enzyme data to predict and classify them. The proposed model learns through intensive training by exploiting enzyme sequences. This work highlights the contribution of this approach to improve the precision of enzyme classification.</span>
ISODATA SOPC-FPGA implementation of image segmentation using NIOS-II processor
Authors: Fayçal Radjah , Lahcene Ziet , Nabil Benoudjit 
Published: June 2021

<p>This paper presents an FPGA image segmentation-binarization system based on<em> </em>Iterative Self Organizing DATA <em>(ISODATA)</em> threshold using histogram analysis for embedded systems. The histogram module computes pixels levels statistics which are used by the ISODATA algorithm module to determine the segmentation threshold. In our case, this threshold binarizes a gray-scale image into two values 0 or 255. The prototype of the complete system uses an ALTERA CYCLONE-II DE2 kit with a lot of component and interfaces, such as the SD-CARD reader or a camera to read the image to be segmented, the FPGA which will implement the intellectual property (IP) core calculation with the NIOS processor, the VGA interface to view the results, and possibly of the ETHERNET interface for data transfer via internet. The use of FPGA contains the ISODATA, histogram, NIOS processor and others custom altera IPs hardware modules greatly improves processing speed and allows the binarization application to be embedded on a single chip. For the project elaboration, we have used QUARTUS-II software for the hardware development part with VHDL description, SOPC-builder or QSYS for the integration of NIOS-system, and NIOS-II-STB-ECLIPSE for the software program with eclipse c++ langage.</p><p> </p>
An improved quasi-Newton equation on the quasi-Newton methods for unconstrained optimizations
Authors: Hassan Basim Abbas , Muangchoo Kanikar , Alfarag Fadhil , Ibrahim Abdulkarim Hassan , Bala Abubakar Auwal 
Published: June 2021

<span><span>Quasi-Newton methods are a class of numerical methods for </span>solving the problem of unconstrained optimization. To improve the overall efficiency of resulting algorithms, we use the quasi-Newton methods which is interesting for quasi-Newton equation. In this manuscript, we present a modified BFGS update formula based on the new quasi-Newton equation, which give a new search direction for solving unconstrained optimizations proplems. We analyse the convergence rate of quasi-Newton method under some mild condition. Numerical experiments are conducted to demonstrate the efficiency of new methods using some test problems. The results indicates that the proposed method is competitive compared to the BFGS methods as it yielded fewer iteration and fewer function evaluations.</span>
Health-Related Quality of Life and Angina in Fractional Flow Reserve- Versus Angiography-Guided Coronary Artery Bypass Grafting: FARGO Trial (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization)
Authors: Thuesen Anne Langhoff , Riber Lars Peter , Veien Karsten Tange , Christiansen Evald Høj , Jensen Svend Eggert , Modrau Ivy , Andreasen Jan Jesper , Borregaard Britt , Junker Anders , Mortensen Poul Erik , Jensen Lisette Okkels 
Published: June 2021

Background:
In coronary artery bypass grafting (CABG), the use of fractional flow reserve (FFR) is insufficiently investigated. Stenosis assessment usually relies on visual estimates of lesion severity. This study evaluated health-related quality of life (HRQoL) and angina after FFR- versus angiography-guided CABG.

Methods:
One hundred patients referred for CABG were randomized to FFR- or angiography-guided CABG. In the FFR group, lesions with FFR>0.80 were deferred, while the surgeon was blinded to the FFR values in the angiography group. Before and 6 months after CABG, HRQoL was assessed by the health state classifier EQ-5D of the EuroQoL 5-level instrument and angina status based on the Canadian Cardiovascular Society classification system were registered.

Results:

Six-month angiography included FFR evaluations of deferred lesions. In total, completed EQ-5D of the EuroQoL 5-level instrument questionnaires were available in 86 patients (43 in the FFR versus 43 in the angiography-guided group). HRQoL was significantly improved and angina significantly decreased from baseline to 6 months after CABG with no difference between the randomization groups. Graft failure rates and clinical outcomes were similar in both groups. Patients with graft failure or FFR<0.80 of the previous deferred lesions had significantly lower visual analogue scale scores (78.7±14.2 versus 86.8±14.7,
P
=0.004) and more angina compared with patients without graft failure or FFR≥0.80 at 6-month follow-up.

Conclusions:
FFR- versus angiography-guided CABG demonstrated similar improvements in HRQoL and angina 6 months after CABG. Graft failure or low FFR in deferred lesions were associated with low HRQoL and angina.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02477371
Invoking Humans in Roman-Era Oaths: Emotional Relations and Divine Ambiguity
Authors: Blidstein Moshe 
Published: June 2021

Abstract
This article examines Roman-era oaths invoking nondeities, especially persons. It argues that rather than invoking quasi-deities or persons to be punished by the gods in case of perjury, as usually understood in the past, these invocations could have two concurrent functions: honoring the invoked persons and affirming a statement. Though such invocations had limited legal power, they were commonly practiced throughout the period, as demonstrated in various textual genres, including Latin poetry and rhetoric, texts of the Second Sophistic, Jewish rabbinical writings, and 5th-century Christian sermons. Furthermore, nondivine invocations were frequently combined and mingled with divine invocations, with only theologically inclined authors attempting to define them clearly as a separate category. This interpretation has significance for understanding some equivocal oaths, such as the oath by the emperor, as well as for our perception of oaths in general as a speech act with functions going beyond the affirmation of a statement.
Effect of Augmentative Technology on Communication and Quality of Life After Tracheostomy or Total Laryngectomy
Authors: Haring Catherine T. , Farlow Janice L. , Leginza Marie , Vance Kaitlin , Blakely Anna , Lyden Teresa , Hoesli Rebecca C. , Neal Molly E. Heft , Brenner Michael J. , Hogikyan Norman D. , Morrison Robert J. , Casper Keith A. 
Published: June 2021

ObjectiveSurgical procedures that render patients acutely aphonic can cause them to experience significant anxiety and distress. We queried patient perceptions after tracheostomy or laryngectomy and investigated whether introducing augmentative technology was associated with improvement in patient‐reported outcomes.MethodsParticipants included hospitalized patients who acutely lost the ability to speak due to tracheostomy or total laryngectomy from April 2018 to December 2019. We distributed questions regarding the patient communication experience and relevant questions from the validated V‐RQOL questionnaire (Voice‐Related Quality of Life). Patients were offered a tablet with the electronic communication application Verbally. Pre‐ and postintervention groups were compared with chi‐square analyses.ResultsSurveys were completed by 35 patients (n = 18, preintervention; n = 17, postintervention). Prior to using augmentative technology, 89% of patients who were aphonic reported difficulty communicating, specifically noting breathing or suctioning (56%), treatment and discharge plans (78%), or immediate needs, such as pain and using the bathroom (39%). Communication difficulties caused anxiety (55%), depression (44%), or frustration (62%), and 92% of patients were interested in using an electronic communication device. Patients reported less trouble communicating after the intervention versus before (53% vs 89%, P =. 03), including less difficulty communicating about treatment or discharge plans (35% vs 78%, P <. 01). V‐RQOL scores were unchanged.DiscussionAcute loss of phonation arising from surgery can be highly distressing for patients, and use of augmentative technology may alleviate some of these challenges by improving communication. Further studies are needed to identify what additional strategies may improve overall well‐being.Implications for PracticeElectronic communication devices may benefit patients with acute aphonia.
A Simple Screw-Type Wrap-Around Retainer
Authors: Korath Akin Kulangara , Jude Charles , Hattarki Rohan 
Published: June 2021

Retainers are used after orthodontic correction to maintain the teeth in the new position while allowing remodeling of the surrounding tissue. Begg’s wrap-around retainers are the most commonly used retainers after orthodontic correction for providing stability to the achieved orthodontic correction. It is not always possible for the patient to visit the orthodontist periodically, especially during situations like pandemics. This new design of Begg’sretainer has been modified with the addition of expansion screws for self-activation, thus reducing the need for the patient to visit the orthodontist for activation of the retainer.
Intravenous Acetaminophen Overdose in an Infant With Toxicokinetic Data
Authors: Trebach Joshua , Mahonski Sarah G. , Melchert Kristina , Howland Mary Ann , Chiang William K. 
Published: June 2021

The toxicokinetics of pediatric intravenous (IV) acetaminophen (APAP) in overdose is not well described and few case reports with serial APAP concentrations allowing for calculations of half-life exist. Here, we report toxicokinetic data from a case of an unintentional IV APAP overdose in a 12-month-old male who was treated with NAC. Case Report: A 12-month-old (former 24 week gestational age), 8.7 kg male was hospitalized after an uneventful colostomy reversal. In the postoperative unit, the patient unintentionally received 1000 mg IV (114.9 mg/kg) acetaminophen instead of the intended 100 mg IV. Serial acetaminophen concentrations were drawn. The patient received IV Nacetylcysteine and ultimately had no adverse outcomes. Discussion: This case report adds to the existing literature regarding toxicokinetics of IV APAP in infants. Our patient had a calculated ke of 0.263 h-1, correlating with a half-life of 2.63 hours. Based on current available data, the half-life of IV APAP in infants varies (2.6 to 4.9 hours). The reason for this variation is unknown and further research is needed in this area.
Acupuncture for post-stroke cognitive impairment: a systematic review and meta-analysis
Authors: Kuang Xu , Fan Wenjuan , Hu Jiawei , Wu Liqun , Yi Wei , Lu Liming , Xu Nenggui 
Published: June 2021

Objectives: The aim of this study was to evaluate the effectiveness and safety of acupuncture for the treatment of post-stroke cognitive impairment (PSCI). Methods: The Cochrane Library, Embase, Medline, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical (VIP), Wanfang, and Chinese Biological Medicine (CBM) databases were electronically searched from their inception to 10 April 2019. The Montreal Cognitive Assessment (MoCA) scale and Mini-Mental State Examination (MMSE) scale were used as outcomes to assess effectiveness with respect to cognitive function. Assessment of risk of bias (ROB) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment were performed by two reviewers independently. Data were analyzed using Review Manager (RevMan) 5.3. Results: A total of 28 trials with 2144 participants were included in the qualitative synthesis and meta-analysis. Four of the 28 trials (14%) were assessed as being at overall low ROB, 24 of the 28 trials (86%) were assessed as having overall high ROB. The quality of evidence for both MoCA and MMSE were deemed to be very low by the GRADE criteria. Results indicated that acupuncture groups may be benefiting more than non-acupuncture groups with respect to variation of MoCA scores (merged mean difference (MMD): 2.66, 95% confidence interval (CI): 2.18 to 3.13, p < 0.00001; heterogeneity: χ2 = 35.52, p = 0.0007, I2 = 63%), and the heterogeneity decreased in both subgroup analysis and sensitivity analysis. In addition, acupuncture groups might be benefiting more than non-acupuncture groups in terms of changes in MMSE score (MMD = 2.97, 95% CI = 2.13 to 3.80, p < 0.00001; heterogeneity: χ2 = 269.75; p < 0.00001; I2 = 92%), and the heterogeneity decreased in subgroup analysis. Only one RCT addressed adverse events, and the symptoms were mild and did not affect treatment and evaluation. Conclusion: Acupuncture could be effective and safe for PSCI. Nevertheless, the results should be interpreted cautiously due to the high ROB of included trials and very low quality of evidence for assessed outcomes.
Association between Polygenic Risk Scores for ADHD and Asthma: A Birth Cohort Investigation
Authors: Leffa Douglas Teixeira , Horta Bernardo , Barros Fernando C. , Menezes Ana M. B. , Martins-Silva Thais , Hutz Mara Helena , Bau Claiton Henrique Dotto , Grevet Eugenio Horacio , Rohde Luis Augusto , Tovo-Rodrigues Luciana 
Published: June 2021

Objective: Shared genetic mechanisms have been hypothesized to explain the comorbidity between ADHD and asthma. To evaluate their genetic overlap, we relied on data from the 1982 Pelotas birth cohort to test the association between polygenic risk scores (PRSs) for ADHD (ADHD-PRSs) and asthma, and PRSs for asthma (asthma-PRSs) and ADHD. Method: We analyzed data collected at birth, 2, 22, and 30 years from 3,574 individuals. Results: Subjects with ADHD had increased risk of having asthma (OR 1.92, 95% CI 1.01–3.66). The association was stronger for females. Our results showed no evidence of association between ADHD-PRSs and asthma or asthma-PRSs and ADHD. However, an exploratory analysis suggested that adult ADHD might be genetically associated with asthma. Conclusion: Our results do not support a shared genetic background between both conditions. Findings should be viewed in light of important limitations, particularly the sample size and the self-reported asthma diagnosis. Studies in larger datasets are required to better explore the genetic overlap between adult ADHD and asthma.
Anaplasma phagocytophilum in domestic cats from Germany, Austria and Switzerland and clinical/laboratory findings in 18 PCR-positive cats (2008–2020)
Authors: Schäfer Ingo , Kohn Barbara , Müller Elisabeth 
Published: June 2021

Objectives Anaplasma phagocytophilum is considered the most significant rickettsial pathogen affecting cats. The organism is transmitted by ticks of the species Ixodes ricinus in Central Europe and can cause granulocytic anaplasmosis in pets, wildlife and humans. The aims of this study were to assess the frequency of positive test results for A phagocytophilum in cats in Germany, Austria and Switzerland, as well as to evaluate clinical and laboratory findings in cats with positive PCR results. Methods This study included the results of direct (PCR) and indirect detection methods (immunofluorescence antibody tests [IFAT]) requested by veterinarians in Germany, Austria and Switzerland between 2008 and 2020 from the LABOKLIN laboratory (Bad Kissingen, Germany). The veterinarians treating the PCR-positive cats were contacted by telephone to enquire about their clinical signs, laboratory findings, management and outcomes. Results In total, 244/1636 cats (15%) tested positive by direct (PCR: n = 27/725 [4%]) and/or indirect detection methods (IFAT: n = 221/956 [23%]). In 18/26 cats with PCR results positive for A phagocytophilum, additional information about clinical signs, laboratory findings, treatment and outcome was obtained. Of these 18 cats, five had comorbidities independent of their infection with A phagocytophilum. The most common clinical signs in PCR-positive cats (total/without comorbidities) were lethargy (83%/92%), fever (83%/85%) and thrombocytopenia (61%/62%). Overall, more than half (57%) of the cats with and without comorbidities recovered clinically. Conclusions and relevance Infections with A phagocytophilum should be considered as differential diagnoses in cats with tick infestation, lethargy, fever and thrombocytopenia. The clinical signs and laboratory findings are consistent with published case reports in cats. Ectoparasite prophylaxis in cats is recommended throughout the entire year.