bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving patient-provider communication about chronic pain: development and feasibility testing of a shared decision-making tool
Authors: Col Nananda , Hull Stephen , Springmann Vicky , Ngo Long , Merritt Ernie , Gold Susan , Sprintz Michael , Genova Noel , Nesin Noah , Tierman Brenda , Sanfilippo Frank , Entel Richard , Pbert Lori 
Published: October 2020

Abstract
Background
Chronic pain has emerged as a disease in itself, affecting a growing number of people. Effective patient-provider communication is central to good pain management because pain can only be understood from the patient’s perspective. We aimed to develop a user-centered tool to improve patient-provider communication about chronic pain and assess its feasibility in real-world settings in preparation for further evaluation and distribution.

Methods
To identify and prioritize patient treatment goals for chronic pain, strategies to improve patient-provider communication about chronic pain, and facilitate implementation of the tool, we conducted nominal group technique meetings and card sorting with patients with chronic pain and experienced providers (n = 12). These findings informed the design of the PainAPP tool. Usability and beta-testing with patients (n = 38) and their providers refined the tool and assessed its feasibility, acceptability, and preliminary impact.

Results
Formative work revealed that patients felt neither respected nor trusted by their providers and focused on transforming providers’ negative attitudes towards them, whereas providers focused on gathering patient information. PainAPP incorporated areas prioritized by patients and providers: assessing patient treatment goals and preferences, functional abilities and pain, and providing patients tailored education and an overall summary that patients can share with providers.
Beta-testing involved 38 patients and their providers. Half of PainAPP users shared their summaries with their providers. Patients rated PainAPP highly in all areas. All users would recommend it to others with chronic pain; nearly all trusted the information and said it helped them think about my treatment goals (94%), understand my chronic pain (82%), make the most of my next doctor’s visit (82%), and not want to use opioids (73%). Beta-testing revealed challenges delivering the tool and summary report to patients and providers in a timely manner and obtaining provider feedback.

Conclusions
PainAPP appears feasible for use, but further adaptation and testing is needed to assess its impact on patients and providers.

Trial registration
This study was approved by the University of New England Independent Review Board for the Protection of Human Subjects in Research (012616–019) and was registered with ClinicalTrials.gov (protocol ID: NCT03425266) prior to enrollment. The trial was prospectively registered and was approved on February 7, 2018.
Physiological and biomechanical comparison of overground, treadmill, and ergometer handrim wheelchair propulsion in able-bodied subjects under standardized conditions
Authors: de Klerk Rick , Velhorst Vera , Veeger Dirkjan , van der Woude Lucas H. V. , Vegter Riemer J. K. 
Published: October 2020

AbstractBackgroundHandrim wheelchair propulsion is often assessed in the laboratory on treadmills (TM) or ergometers (WE), under the assumption that they relate to regular overground (OG) propulsion. However, little is known about the agreement of data obtained from TM, WE, and OG propulsion under standardized conditions. The current study aimed to standardize velocity and power output among these three modalities to consequently compare obtained physiological and biomechanical outcome parameters.MethodsSeventeen able-bodied participants performed two submaximal practice sessions before taking part in a measurement session consisting of 3 × 4 min of submaximal wheelchair propulsion in each of the different modalities. Power output and speed for TM and WE propulsion were matched with OG propulsion, making them (mechanically) as equal as possible. Physiological data and propulsion kinetics were recorded with a spirometer and a 3D measurement wheel, respectively.ResultsAgreement among conditions was moderate to good for most outcome variables. However, heart rate was significantly higher in OG propulsion than in the TM condition. Push time and contact angle were smaller and fraction of effective force was higher on the WE when compared to OG/TM propulsion. Participants used a larger cycle time and more negative work per cycle in the OG condition. A continuous analysis using statistical parametric mapping showed a lower torque profile in the start of the push phase for TM propulsion versus OG/WE propulsion. Total force was higher during the start of the push phase for the OG conditions when compared to TM/WE propulsion.ConclusionsPhysiological and biomechanical outcomes in general are similar, but possible differences between modalities exist, even after controlling for power output using conventional techniques. Further efforts towards increasing the ecological validity of lab-based equipment is advised and the possible impact of these differences -if at all- in (clinical) practice should be evaluated.
Comparative investigation of different telemetric methods for measuring intracranial pressure: a prospective pilot study
Authors: Rot S. , Dweek M. , Gutowski P. , Goelz L. , Meier U. , Lemcke J. 
Published: October 2020

Abstract
Objectives
Measurement of intracranial pressure (ICP) plays an important role in long-term monitoring and neuro-intensive treatment of patients with a cerebral shunt. Currently, only two complete telemetric implants with different technical features are available worldwide. This prospective pilot study aims to examine patients who had both probes implanted at overlapping times for clinical reasons and represents the first in vivo comparison of both measurement methods.

Materials and methods
Patients with a primary subarachnoid hemorrhage or a spontaneous intracerebral hemorrhage with ventricular hemorrhage who had received a telemetric ICP probe (Raumedic® NEUROVENT®-P-tel) were included in the study. Conventional external ventricular drainages (EVD) and ventriculoperitoneal shunts with a telemetric ICP probe (Miethke Sensor Reservoir) were implanted in patients with hydrocephalus who required CSF (cerebrospinal fluid) drainage. Absolute ICP values from all systems were obtained. Due to the overlapping implantation time, parallel ICP measurements were performed via two devices simultaneously. ICP measurements via the sensor reservoir were repeated after 3 and 9 months. Differences between the absolute ICP values measured via the NEUROVENT®-P-tel probe, the Miethke sensor reservoir®, and the EVD were analyzed.

Results
Seventeen patients were included in the present study between 2016 and 2018. 63% of all patients were male. In 11 patients the ICP measurements were followed up with both devices for 3 months. ICP measurements of the sensor reservoir showed corresponding trends in 9 cases compared to ICP measurement via the telemetry probe or EVD. Difference in absolute ICP values ranged between 14.5 mmHg and 0.0 mmHg. The average difference of the absolute ICP values in 8 cases was ≤ 3.5 mmHg.

Conclusion
ICP measurements with both systems continuously showed synchronous absolute ICP values, however absolute values of ICP measurement with the different systems did not match.
Evaluation of OAR dose sparing and plan robustness of beam-specific PTV in lung cancer IMRT treatment
Authors: Chang Yu , Xiao Feng , Quan Hong , Yang Zhiyong 
Published: October 2020

Abstract
Purpose
Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Here, we proposed a margin concept that takes into consideration the beam direction, thereby generating a beam-specific planning target volume (BSPTV) on a beam entrance view. The total merged BSPTV was considered a target for optimization. We investigated the impact of this novel approach for lung intensity-modulated radiotherapy (IMRT) treatment, and compared the treatment plans generated using BSPTV with general PTV.

Methods and materials
We generated the BSPTV by expanding the CTV perpendicularly to the incident beam direction using the 2D version of van Herk’s margin concept. The BSPTV and general PTV margin were analyzed using digital phantom simulation. Fifteen lung cancer patients were used in the planning study. First, all patient targets were performed with the CTV projection area analysis to select the suitable beam angles. Then, BSPTV was generated according to the selected beam angles. IMRT plans were optimized with the general PTV and BSPTV as the target volumes, respectively. The dosimetry metrics were calculated and evaluated between these two plans. The plan robustness of both plans for setup uncertainties was evaluated using worst-case analysis.

Results
Both general PTV and BSPTV plans satisfied the CTV coverage. In addition, the BSPTV plans improved the sparing of high doses to target-surrounding lung tissues compared to the general PTV plans. Both Dmean of Ring PTV and Ring BSPTV were significantly lower in BSPTV plans (38.89 Gy and 39.43 Gy) compared to the general PTV plans (40.27 Gy and 40.68 Gy). The V20, V5, and mean lung dose of the affected lung were significant lower in BSPTV plans (16.20%, 28.75% and 8.93 Gy) compared to general PTV plans (16.69%, 29.22% and 9.18 Gy). In uncertainty scenarios, about 80% of target coverage was achieved for both general PTV and BSPTV plans.

Conclusions
The results suggested that plan robustness can be guaranteed in both the BSPTV and general PTV plans. However, the BSPTV plan spared normal tissues, such as the lungs, significantly better compared to the general PTV plans.
The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
Authors: Ma Liying , Bian Xing , Lin Wenchu 
Published: October 2020

AbstractBackgroundSmall cell lung cancer (SCLC) is a deadly neuroendocrine tumor with limited therapeutic options. Recent data suggest that histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K) pathway play essential roles in SCLC cell proliferation and survival.MethodsThe inhibition of the PI3K signaling and HDAC activity by CUDC-907 was analyzed by western blotting. The effect of CUDC-907 on olaparib-induced DNA damage response was assessed by western blotting and Immunofluorescence staining. The cytotoxicity of CUDC-907 alone or in combination with olaparib in a panel of SCLC cell lines were evaluated by the CellTiter-Glo Luminescent Cell Viability Assay and flow cytometry. The in vivo effects of CUDC-907 and olaparib alone or in combination were examined using a patient-derived xenografts (PDX) model of SCLC.ResultsCUDC-907 treatment downregulated MYC paralogs and FoxM1, induced G1 cell-cycle arrest, and impaired DNA double-strand break (DSB) repair capacity in SCLC cells, which produced a potent antiproliferative effect. Furthermore, we showed that CUDC-907 treatment enhanced the therapeutic efficacy of PARP inhibitor olaparib in SCLC cellular models and a PDX model. Mechanistic investigations demonstrated that CUDC-907 synergized with olaparib through the blockade of DSB repair pathways and downregulation of MYC paralogs and FoxM1.ConclusionsOur study uncovers that dual PI3K and HDAC inhibition by CUDC-907 exerts significant single-agent activity and strong synergistic effects with PARP inhibitor olaparib in SCLC, which thus provides a rational combination treatment strategy for SCLC clinical investigation.
Description of Emergency Medical Services, treatment of cardiac arrest patients and cardiac arrest registries in Europe
Authors: Tjelmeland Ingvild B. M. , Masterson Siobhan , Herlitz Johan , Wnent Jan , Bossaert Leo , Rosell-Ortiz Fernando , Alm-Kruse Kristin , Bein Berthold , Lilja Gisela , Gräsner Jan-Thorsten ,   on behalf of GL2020 Epidemiology group and participating countries, Gräsner Jan-Thorsten , Bein Berthold , Bossaert Leo , Böttiger Bernd W. , Herlitz Johan , Lefering Rolf , Lilja Gisela , Masterson Siobhan , Rosell-Ortiz Fernando , Perkins Gavin D. , Wnent Jan , Akin Sule , Alihodzic Hajriz , Baert Valentine , Blom Marieke , Booth Scott , Burkart Roman , Bywater Dave , Kamishi Drilon , Baubin Michael , Birkun Alexei , Cebula Grzegorz , Cimpoiesu Diana , Christopher Giordimaina , Clarens Carlo , Correia Vitor Hugo Gouveia , Höskuldsson Hlynur , Ioannides Marios , Krikscionaitiene Asta , Leckey Stephanie , Lippert Freddy , Markota Andrej , Mols Pierre , Nagy Eniko , Nikolao Nikolaos , Rosell-Ortiz Fernando , Raffay Violetta , Salo Ari , Semeraro Federico , Trenkler Stefan , Truhlář Anatolij , Quinn Martin 
Published: October 2020

Abstract
Background
Variation in the incidence, survival rate and factors associated with survival after cardiac arrest in Europe is reported. Some studies have tried to fill the knowledge gap regarding the epidemiology of out-of-hospital cardiac arrest in Europe but were unable to identify reasons for the reported differences. Therefore, the purpose of this study was to describe European Emergency Medical Systems, particularly from the perspective of country and ambulance service characteristics, cardiac arrest identification, dispatch, treatment, and monitoring.

Methods
An online questionnaire with 51 questions about ambulance and dispatch characteristics, on-scene management of cardiac arrest and the availability and dataset in cardiac arrest registries, was sent to all national coordinators who participated in the European Registry of Cardiac Arrest studies. In addition, individual invitations were sent to the remaining European countries.

Results
Participants from 28 European countries responded to the questionnaire. Results were combined with official information on population density. Overall, the number of Emergency Medical Service missions, level of training of personnel, availability of Helicopter Emergency Medical Services and the involvement of first responders varied across and within countries. There were similarities in team training, availability of key resuscitation equipment and permission for ongoing performance of cardiopulmonary resuscitation during transported. The quality of reporting to cardiac arrest registries varied, as well as the data availability in the registries.

Conclusions
Throughout Europe there are important differences in Emergency Medical Service systems and the response to out-of-hospital cardiac arrest. Explaining these differences is complicated due to significant variation in how variables are reported to and used in registries.
New pencil graphite electrodes for potentiometric determination of fexofenadine hydrochloride and montelukast sodium in their pure, synthetic mixtures, and combined dosage form
Authors: Nashed Dania , Noureldin Imad , Sakur Amir Alhaj 
Published: October 2020

AbstractThis paper introduces the first electrochemical approach for the determination of Fexofenadine hydrochloride and Montelukast sodium as a combined form by constructing three new graphite electrodes coated with a polymeric membrane. The first electrode was constructed using ammonium molybdate reagent as an ion pair with fexofenadine cation for the determination of Fexofenadine drug, the second electrode was constructed using cobalt nitrate as an ion pair with montelukast anion for the determination of Montelukast drug, the third electrode was prepared by incorporating the two previously mentioned ion pairs in the same graphite sensor, which makes this sensor sensitive to each Fexofenadine and Montelukast drug. The coating material was a polymeric film comprises of Poly Vinyl Chloride (PVC), Di-butyl phthalate as a plasticizer (DBP), ion pairs of drugs with previously mentioned reagents. The electrodes showed a Nernstian response with a mean calibration graph slopes of [59.227, 28.430, (59.048, 28,643)] mv.decade−1 for the three pencil electrodes respectively, with detection limits 0.025 μM for Fexofenadine and 0.019 μM for Montelukast drug which makes this method outperforms the reported method for the determination of this combination. The electrodes work effectively over pH range (2–4.5) for Fexofenadine hydrochloride and (5–9.5) for Montelukast sodium. The influence of the proposed interfering species was negligible as shown by selectivity coefficient values. The effectiveness of the electrodes continued in a period of time (45–69) days. The suggested sensors demonstrated useful analytical features for the determination of both drugs in bulk powder, in laboratory prepared mixtures and their combined dosage form. We have validated the method following ICH protocol, and we have reached very significant results in terms of the linearity, accuracy, selectivity, and precision of the method.
Molecular detection of Rickettsia in fleas from micromammals in Chile
Authors: Moreno-Salas Lucila , Espinoza-Carniglia Mario , Lizama-Schmeisser Nicol , Torres-Fuentes Luis Gonzalo , Silva-de La Fuente María Carolina , Lareschi Marcela , González-Acuña Daniel 
Published: October 2020

Abstract
Background
Rickettsial diseases are considered important in public health due to their dispersal capacity determined by the particular characteristics of their reservoirs and/or vectors. Among the latter, fleas play an important role, since the vast majority of species parasitize wild and invasive rodents, so their detection is relevant to be able to monitor potential emerging diseases. The aim of this study was to detect, characterize, and compare Rickettsia spp. from the fleas of micromammals in areas with different human population densities in Chile.

Methods
The presence of Rickettsia spp. was evaluated by standard polymerase chain reaction (PCR) and sequencing in 1315 fleas collected from 1512 micromammals in 29 locations, with different human population densities in Chile. A generalized linear model (GLM) was used to identify the variables that may explain Rickettsia prevalence in fleas.

Results
DNA of Rickettsia spp. was identified in 13.2% (174 of 1315) of fleas tested. Fifteen flea species were found to be Rickettsia-positive. The prevalence of Rickettsia spp. was higher in winter, semi-arid region and natural areas, and the infection levels in fleas varied between species of flea. The prevalence of Rickettsia among flea species ranged between 0–35.1%. Areas of lower human density showed the highest prevalence of Rickettsia. The phylogenetic tree showed two well-differentiated clades with Rickettsia bellii positioned as basal in one clade. The second clade was subdivided into two subclades of species related to Rickettsia of the spotted fever group.

Conclusions
To our knowledge, this is the first report of the occurrence and molecular characterization of Rickettsia spp. in 15 flea species of micromammals in Chile. In this study, fleas were detected carrying Rickettsia DNA with zoonotic potential, mainly in villages and natural areas of Chile. Considering that there are differences in the prevalence of Rickettsia in fleas associated with different factors, more investigations are needed to further understand the ecology of Rickettsia in fleas and their implications for human health.
Blocking of efflux transporters in rats improves translational validation of brain radioligands
Authors: Shalgunov Vladimir , Xiong Mengfei , L’Estrade Elina T. , Raval Nakul R. , Andersen Ida V. , Edgar Fraser G. , Speth Nikolaj R. , Baerentzen Simone L. , Hansen Hanne D. , Donovan Lene L. , Nasser Arafat , Peitersen Siv T. , Kjaer Andreas , Knudsen Gitte M. , Syvänen Stina , Palner Mikael , Herth Matthias M. 
Published: October 2020

Abstract
Background
Positron emission tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation of PET tracers is often conducted in rodents due to the accessibility of disease models as well as economic considerations. Compared to larger species, rodents display a higher expression and/or activity of efflux transporters such as the P-glycoprotein (P-gp). Low brain uptake could, therefore, be species-specific and uptake in rodents not be predictive for that in humans. We hypothesized that a better prediction from rodent data could be achieved when a tracer is evaluated under P-gp inhibition. Consequently, we compared the performance of eight neuroreceptor tracers in rats with and without P-gp inhibition including a specific binding blockade. This data set was then used to predict the binding of these eight tracers in pigs.

Methods
PET tracers targeting serotonin 5-HT2A receptors ([18F]MH.MZ, [18F]Altanserin, [11C]Cimbi-36, [11C]Pimavanserin), serotonin 5-HT7 receptors ([11C]Cimbi-701, [11C]Cimbi-717 and [11C]BA-10) and dopamine D2/3 receptors ([18F]Fallypride) were used in the study. The brain uptake and target-specific binding of these PET radiotracers were evaluated in rats with and without inhibition of P-gp. Rat data were subsequently compared to the results obtained in pigs.

Results
Without P-gp inhibition, the amount of target-specific binding in the rat brain was sufficient to justify further translation for three out of eight evaluated tracers. With P-gp inhibition, results for five out of eight tracers justified further translation. The performance in pigs could correctly be predicted for six out of eight tracers when rat data obtained under P-gp inhibition were used, compared to four out of eight tracers without P-gp inhibition.

Conclusions
P-gp strongly affects the uptake of PET tracers in rodents, but false prediction outcomes can be reduced by evaluating a tracer under P-gp inhibition.
Inducible expression of heat shock protein 20 protects airway epithelial cells against oxidative injury involving the Nrf2-NQO-1 pathway
Authors: Bao Aihua , Ma Aying , Zhang Hui , Qiao Lihua , Ben Suqin , Zhou Xin , Zhang Min 
Published: October 2020

Abstract
Background
Heat shock protein (HSP) 20 is a molecular chaperone that exerts multiple protective functions in various kinds of tissues. However, the expression of HSP20 and its specific functions in airway epithelial cells (AECs) remain elusive.

Results
In current study, we first confirmed the inducible expression of HSP20 in mouse AECs and in a human bronchial epithelial cell line BEAS-2B cells, under different oxidant stressors. Then by establishing a HSP20-abundant mouse model with repeated low-level-ozone exposures and stimulating this model with a single high-level ozone exposure, we found that the HSP20 abundance along with its enhanced phosphorylation potentially contributed to the alleviation of oxidative injuries, evidenced by the decreases in the bodyweight reduction, the BAL neutrophil accumulation, the AECs shedding, and the BAL concentrations of albumin and E-cadherin. The biological function of HSP20 and its molecular mechanisms were further investigated in BEAS-2B cells that were transfected with HSP20-, unphosphorylatable HSP20(Ala) or empty vector plasmids prior to the stimulation of H2O2, of which its oxidant capacity has been proved to be similar with those of ozone in an air–liquid culture system. We found that the H2O2-induced intracellular ROS level and the early cell apoptosis were attenuated in the HSP20- but not HSP20(Ala)- transfected cells. The intracellular expression of NQO-1 (mRNA and protein) and the intranuclear content of Nrf2 were significantly increased in the HSP20- transfected cells but not in the HSP20(Ala)- and empty vector-transfected cells after the stimulation of H2O2.

Conclusions
The inducible expression of HSP20 in AECs by oxidative stress exerts protective roles against oxidative damages, which may involve the activation of the Nrf2-NQO-1 pathway.