bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamics of Pre-Operative PD1 Checkpoint Blockade and Receptor Activator of NFkB Ligand (RANKL) Inhibition in Non-Small Cell Lung Cancer (NSCLC): study protocol for a multicentre open-label phase 1B/2 translational trial (POPCORN)
Authors: Ahern Elizabeth Stephanie , Cubitt Annette , Ballard Emma , Teng Michele W. L. , Dougall William C. , Smyth Mark J. , Godbolt David , Naidoo Rishendran , Goldrick Amanda , Hughes Brett G. M. 
Published: July 2019

Abstract
Background

Neoadjuvant immunotherapy targeting the immune checkpoint programmed death-1 (PD-1) is under investigation in various tumour settings including non-small-cell lung cancer (NSCLC). Preclinical models demonstrate the superior power of immunotherapy given in the neoadjuvant (pre-operative) compared with adjuvant (post-operative) setting to eradicate metastatic disease and induce long-lasting antigen-specific immunity. Novel effective immunotherapy combinations are widely sought in the oncology field, targeting non-redundant mechanisms of immune evasion. A promising combination partner with anti-PD1 in NSCLC is denosumab, a monoclonal antibody blocking Receptor Activator of NF-κB Ligand (RANKL). In preclinical cancer models, and a large retrospective case series in NSCLC, anti-cancer activity of combination immune checkpoint inhibition (ICI) and denosumab has been reported. Furthermore, clinical trials of ICI and denosumab are underway in advanced melanoma and clear-cell renal cell carcinoma. However, the mechanism of action of combination anti-PD1 and anti-RANKL is poorly defined.

Methods

This open-label multicentre trial will randomise by minimisation 30 patients with resectable stage IA (primary > 2cm) to IIIA NSCLC to a neoadjuvant treatment regime of either two doses of nivolumab (3 mg/kg every 2 weeks) or two doses of nivolumab (same regimen) plus denosumab (120 mg every 2 weeks, following nivolumab). Each treatment arm is of equal size, and be approximately balanced with respect to histology (squamous vs. non-squamous) and clinical stage (I-II vs IIIA). All patients will receive surgery for their tumour two weeks after the final dose of neoadjuvant therapy. The primary outcome will be translational research to define the tumour-immune correlates of combination therapy compared with monotherapy. Key secondary outcomes will include a comparison of rates of the following between each arm: toxicity, response (pathological and radiological), and microscopically complete resection.

Discussion

The POPCORN study provides a unique platform for translational research to determine the mechanism of action of a novel proposed combination immunotherapy for cancer.

Trial registration

Prospectively registered on Australian New Zealand Clinical Trials Registry (ACTRN12618001121257) on 06/07/2018.
1D-3D coupling investigation of hydraulic transient for power-supply failure of centrifugal pump-pipe system
Authors: Li Xiaoqin , Tang Xuelin , Zhu Min , Shi Xiaoyan 
Published: July 2019

Abstract
In the pumping station, the main feedwater system and the reactor system of nuclear power plant, power-supply failure causes strong hydraulic transients. One-dimensional method of characteristics (1D-MOC) is used to calculate the transient process in the pipeline system while three-dimensional (3D) computational fluid dynamics is employed to analyze the turbulent flows inside the pump and to obtain the performance parameters of the pump, and the data exchanges on the boundary conditions of the shared interface between 1D and 3D domains are updated based on the MpCCI platform. Based on the equation of motion of the pump motion parts, the relationship between the external characteristics and the internal flow field in the pump is further investigated because the dynamic behavior of the pump and the detailed fluid field evolutions inside the pump are captured during the transition process, and the transient flow rate, rotating speed, and pressure inside the impeller are comprehensively investigated. Meanwhile, compared with the data gained by experiment and traditional 1D-MOC, the relative errors of rotating speed and the flow rate obtained by 1D-3D coupling method are smaller than those by 1D-MOC. Furthermore, the influences of the main coupling parameters and coupling modes on the calculation results are analyzed, and the cause of the deviation is further explained.
Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity
Authors: Bhagyawant Sameer Suresh , Narvekar Dakshita Tanaji , Gupta Neha , Bhadkaria Amita , Gautam Ajay Kumar , Srivastava Nidhi 
Published: July 2019

Background:
Diabetes and hypertension are the major health concern and alleged to be
of epidemic proportions. This has made it a numero uno subject at various levels of investigation.
Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it
specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays
an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure
attracts special interest of the scientific community. Chickpea is a food legume and seeds contain
carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto
been elucidated.

Methods:
Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant,
ACE-I inhibitory and anti-diabetic characteristic.

Results:
Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral
anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are
compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent
manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose
having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene
bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole
(BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43
± 1.20 µg/ml compared to captopril.

Conclusion:
Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory
for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic
molecule. The biological effects of chickpea lectin display potential for reducing the parameters
of medically debilitating conditions. These characteristics however needs to be established
under in vivo systems too viz. animals through to humans.
The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis
Authors: Wu Yuangang , Lu Xiaoxi , Shen Bin , Zeng Yi 
Published: July 2019

Background:
Osteoarthritis (OA) is a disease characterized by progressive degeneration,
joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have
shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism
may be an effective way to reduce OA.

Objective:
The purpose of this review was to investigate the recent progress of miRNA, long noncoding
RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of
this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA.

Methods:
The following electronic databases were searched, including PubMed, EMBASE, Web of
Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA
in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular
matrix.

Results and Discussion:
With the development of technology, miRNA, lncRNA, and circRNA have
been found in many diseases. More importantly, recent studies have found that RNA interacts with
RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various
pathological processes of OA, thus becoming a potential therapy for OA.

Conclusion:
In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence
and development of OA and as a new target for gene therapy.
Changes in Clinical Markers During A Short-Term Transfer Program of Adult Cystic Fibrosis Patients from Pediatric to Adult Care
Authors: Welsner Matthias , Sutharsan Sivagurunathan , Taube Christian , Olivier Margarete , Mellies Uwe , Stehling Florian 
Published: July 2019

Background:Transition from child-oriented to adult-oriented health care in Cystic Fibrosis (CF) has become more important over recent decades as the survival of people with this disease has increased. The transition process usually begins in adolescence, with full transfer completed in early adulthood.Objective:This study investigated the impact of a short-term transfer program on clinical markers in an adult CF cohort still being managed by pediatricians.Methods:Clinically relevant data from the year before (T-1), the time of Transfer (T) and the year after the transfer (T+1) were analysed retrospectively.Results:39 patients (median age 29.0 years; 64% male) were transferred between February and December 2016. Lung function had declined significantly in the year before transfer (in % predicted: Forced Expiratory Volume in 1 second (FEV), 62.8vs.57.7,p<0.05; Forced Vital Capacity (FVC), 79.9vs.71.1,p<0.05), but remained stable in the year after transfer (in % predicted: FEV: 56.3; FVC 68.2). BMI was stable over the whole observational period. There was no relevant change in chronic lung infection withP. aeruginosa, Methicillin-Resistant Staphylococcus aureus (MRSA) andBurkholderiasp. during the observation period. The number of patient contacts increased significantly in the year after versus the year before transfer (inpatient: 1.51vs.2.51,p<0.05; outpatient: 2.67vs.3.41,p<0.05).Conclusions:Our data show that, within the framework of a structured transfer process, it is possible to transfer a large number of adult CF patients, outside a classic transition program, from a pediatric to an adult CF center in a short period of time, without any relevant changes in clinical markers and, stability.
A Review of the Traffic Accidents and Related Practices Worldwide
Authors: Mohammed Ali Ahmed , Ambak Kamarudin , Mosa Ahmed Mancy , Syamsunur Deprizon 
Published: July 2019

A traffic accident, a traffic collision or crash occurs when a vehicle collides with another vehicle, pedestrian, animal, road barriers, or any stationary obstruction such as a tree or a utility pole. Traffic collisions may result in injury, death, vehicle damage and possession damage. Motor vehicle collisions cause death and disability as well as a financial burden. Traffic accidents cause many losses especially of human life, property damages, and loss of resources. Indeed, even in strife influenced countries such as Afghanistan, Libya, Pakistan, and Yemen, road traffic remains the most common cause of fatal injuries, causing between two and eight times more fatalities than war and lawful mediation. The World Health Organization (WHO) 2013 assessed the traffic casualty rate in the Eastern Mediterranean Region (EMR) to be the second most elevated rate universally after the African Region and extending a few other countries in the region. The aim of this paper was to enrich the global highway safety knowledge by revealing the catastrophic impact of traffic accidents on the economy of the societies and the safety of the common worldwide.
Minocycline Inhibits the Enhanced Antidromic Stimulation-induced Sensitization of C-Fibers Following Intradermal Capsaicin Injection
Authors: Gong Kerui , Lin Qing 
Published: July 2019

Background:
Our previous studies indicated that retrograde signaling initiating from the spinal cord was mediated by the plasticity of Dorsal Root Ganglion (DRG) neurons. Both retrograde signaling and neuronal plasticity contributed to neurogenic inflammation, which were modulated by the activity of Satellite Glial Cells (SGCs). Thus, we want to know whether retrograde signaling is involved in the hypersensitivity of nociceptive afferents, and whether this process is affected by the plasticity of DRG neurons and glia.

Objective:
The study aims to examine if retrograde signaling can induce hypersensitivity of primary afferent nociceptors and if hypersensitivity involves glial modulation.

Methods:
Antidromic Electrical Stimulation (ES) of dorsal roots was used to mimic retrograde signaling activity. C- primary nociceptive afferent activity was recorded for testing the effect of antidromic ES. In a separate group, intradermal capsaicin injection to the ipsilateral hindpaw was used to prime DRG nociceptive neurons. For the third group, a glial inhibitor, minocycline, was pre-administered to test glial modulation in this process.

Results:
Antidromic ES sensitized the responses of C-fibers to nociceptive mechanical stimuli. For rats subjected to intradermal capsaicin injection, C fibers experienced more drastic sensitization induced by antidromic ES, shown as a greater response and longer duration, implying that sensitization correlates with the activation of DRG neurons.
Minocycline pretreatment significantly blocked the priming effect of capsaicin on C-fiber sensitization induced by antidromic ES, indicating the involvement of SGCs in DRG neuronal sensitization.

Conclusion:
Retrograde signaling may be one of the important mechanisms in neurogenic inflammation-mediated nociception, and this process is subjected to satellite glial modulation.
Spare Rib and Underwater Livecams
Authors: Brant Clare 
Published: July 2019

https://www.bl.uk/spare-rib Digital citizens of the future may have sorted a gender politics which works for everybody. A utopian hope, yes; in case not, and in any case, I would want them to know that in the 1960s, 70s and 80s, there was a worldwide women’s movement full of daring thinkers and brave activists. So often history is written by the victors; web resources at least prolong the availability of alternative versions. What’s known as second wave feminism worked largely through print and word of mouth, but is now partially recuperable through podcasts, oral history and digital archives. Spare Ribe was a polemical, practical monthly magazine published in Britain from 1972 to 1993. It’s available again, newly digitised at the British Library. Underwater Livecams. I like to imagine that future netizens will know more about the oceans than we do. But they should know that some of their predecessors are passionately curious about life underwater, and that there were webcams which livestreamed from depths no human had seen before.
Association of Online Learning Behavior and Learning Outcomes for Medical Students: Large-Scale Usage Data Analysis
Authors: Bientzle Martina , Hircin Emrah , Kimmerle Joachim , Knipfer Christian , Smeets Ralf , Gaudin Robert , Holtz Peter 
Published: July 2019

Background
Digital learning environments have become very common in the training of medical professionals, and students often use such platforms for exam preparation. Multiple choice questions (MCQs) are a common format in medical exams and are used by students to prepare for said exams.

Objective
We aimed to examine whether particular learning activities contributed more strongly than others to users’ exam performance.

Methods
We analyzed data from users of an online platform that provides learning materials for medical students in preparation for their final exams. We analyzed whether the number of learning cards viewed and the number of MCQs taken were positively related to learning outcomes. We also examined whether viewing learning cards or answering MCQs was more effective. Finally, we tested whether taking individual notes predicted learning outcomes, and whether taking notes had an effect after controlling for the effects of learning cards and MCQs. Our analyses from the online platform Amboss are based on user activity data, which supplied the number of learning cards studied and test questions answered. We also included the number of notes from each of those 23,633 users who had studied at least 200 learning cards and had answered at least 1000 test exam questions in the 180 days before their state exam. The activity data for this analysis was collected retrospectively, using Amboss archival usage data from April 2014 to April 2017. Learning outcomes were measured using the final state exam scores that were calculated by using the answers voluntarily entered by the participants.

Results
We found correlations between the number of cards studied (r=.22; P<.001) and the number of test questions that had been answered (r=.23; P<.001) with the percentage of correct answers in the learners’ medical exams. The number of test questions answered still yielded a significant effect, even after controlling for the number of learning cards studied using a hierarchical regression analysis (β=.14; P<.001; ΔR2=.017; P<.001). We found a negative interaction between the number of learning cards and MCQs, indicating that users with high scores for learning cards and MCQs had the highest exam scores. Those 8040 participants who had taken at least one note had a higher percentage of correct answers (80.94%; SD=7.44) than those who had not taken any notes (78.73%; SD=7.80; t23631=20.95; P<.001). In a stepwise regression, the number of notes the participants had taken predicted the percentage of correct answers over and above the effect of the number of learning cards studied and of the number of test questions entered in step one (β=.06; P<.001; ΔR2=.004; P<.001).

Conclusions
These results show that online learning platforms are particularly helpful whenever learners engage in active elaboration in learning material, such as by answering MCQs or taking notes.
A Systematic Framework for Analyzing Patient-Generated Narrative Data: Protocol for a Content Analysis
Authors: Zolnoori Maryam , Balls-Berry Joyce E , Brockman Tabetha A , Patten Christi A , Huang Ming , Yao Lixia 
Published: July 2019

BackgroundPatient narrative data in online health care forums (communities) are receiving increasing attention from the scientific community for implementing patient-centered care. Natural language processing (NLP) methods are gaining more and more attention because of the enormous data volume. However, state-of-the-art NLP still cannot meet the need of high-resolution analysis of patients’ narratives. Manual qualitative analysis still plays a pivotal role in answering complicated research questions from analyzing patient narratives.ObjectiveThis study aimed to develop a systematic framework for qualitative analysis of patient-generated narratives in online health care forums.MethodsOur systematic framework consists of 4 phases: (1) data collection, (2) data preparation, (3) content analysis, and (4) interpretation of the results. Data collection and data preparation phases are constructed based on text mining methods for identifying appropriate online health forums for data collection, differentiating posts of patients from other stakeholders, protecting patients’ privacy, sampling, and choosing the unit of analysis. Content analysis phase is built on the framework method, which facilitates and accelerates the identification of patterns and themes by an interdisciplinary research team. In the end, the focus of interpretation of the results phase is to measure the data quality and interpret the findings regarding the dimensions and aspects of patients’ experiences and concerns in their original contexts.ResultsWe demonstrated the usability of the proposed systematic framework using 2 case studies: one on determining factors affecting patients’ attitudes toward antidepressants and another on identifying the disease management strategies in patient with diabetes facing financial difficulties. The framework provides a clear step-by-step process for systematic content analysis of patient narratives and produces high-quality structured results that can be used for describing patterns or regularities in patients’ experiences, generating and testing hypotheses, and identifying areas of improvement in the health care systems.ConclusionsThe systematic framework is a rigorous and standardized method for qualitative analysis of patient narratives. Findings obtained through such a process indicate authentic dimensions and aspects of patient experiences and shed light on patients’ concerns, needs, preferences, and values, which are the core of patient-centered care.International Registered Report Identifier (IRRID)RR1-10.2196/13914
Effectiveness of a Walking Program Involving the Hybrid Assistive Limb Robotic Exoskeleton Suit for Improving Walking Ability in Stroke Patients: Protocol for a Randomized Controlled Trial
Authors: Tsurushima Hideo , Mizukami Masafumi , Yoshikawa Kenichi , Ueno Tomoyuki , Hada Yasushi , Gosho Masahiko , Kohno Yutaka , Hashimoto Koichi , Iizumi Yuichi , Kikuchi Toshihiro , Matsumura Akira ,   Hit2016 Study Group
Published: July 2019

Background
Gait disturbance often occurs in stroke survivors. Recovery of walking function is challenging, as some gait disturbance due to hemiparesis often remains even after rehabilitation therapy, presenting a major obstacle towards regaining activities-of-daily-living performance and achieving social reintegration.

Objective
This study aims to clarify the effectiveness of a walking program involving the wearable Hybrid Assistive Limb (HAL-TS01) robotic exoskeleton for improving walking ability in stroke patients with hemiparesis and stagnant recovery despite ongoing rehabilitation.

Methods
This is a multicenter, randomized, parallel-group, controlled study (HAL group, n=27; control group, n=27). The study period includes preintervention observation (until stagnant recovery), intervention (HAL-based walking therapy or conventional rehabilitation; 5 weeks), and postintervention observation (2 weeks). Following provision of informed consent and primary registration, the patients undergo conventional rehabilitation for preintervention observation, during which the recovery of walking ability is monitored to identify patients with stagnant recovery (based on weekly assessments using the 10-meter maximum walking speed [MWS] test). Patients with an MWS of 30-60 m/minute and insufficient weekly improvement in MWS undergo secondary registration and are randomly assigned to undergo HAL-based walking therapy (HAL group) or conventional rehabilitation (control group). The primary outcome is the change in MWS from baseline to the end of the 5-week intervention.

Results
This study began in November 2016 and is being conducted at 15 participating facilities in Japan.

Conclusions
Assessments of walking ability vary greatly and it is difficult to define the threshold for significant differences. To reduce such variability, our study involves conducting conventional rehabilitation to the point of saturation before starting the intervention. Stagnation in the recovery of walking ability despite conventional rehabilitation highlights the limits of current medical care. The present study may bring evidence that HAL-based therapy can overcome such limitations and induce added recovery of walking ability, which would promote the use of HAL technology in the clinical setting.

Trial Registration
UMIN Clinical Trials Registry UMIN000024805; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028545