bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 chimeric costimulatory receptor improves the efficacy of CAR-T cells for PD-L1-positive solid tumors and reduces toxicity in vivo
Authors: Liao Qibin , Mao Yunyu , He Huan , Ding Xiangqing , Zhang Xiaoyan , Xu Jianqing 
Published: November 2020

AbstractBackgroundOn-target off-tumor toxicity impedes the clinical application of chimeric antigen receptor-modified T cells (CAR-T cells) in the treatment of solid tumors. Previous reports proved that the combinatorial antigen recognition strategy could improve the safety profile of CAR-T cells by targeting two different tumor-associated antigens (TAAs), one as a CAR-T targeted antigen and the other as a chimeric costimulatory receptor (CCR) ligand. The programmed death-ligand 1 (PD-L1, also known as B7-H1) is preferentially overexpressed on multiple tumors, it will be highly interesting to explore the potential of PD-L1 as a universal target for designing CCR.MethodsA novel dual-targeted CAR, which is composed of first-generation CD19/HER2 CAR with CD3ζ signaling domain and PD-L1 CCR containing the CD28 costimulatory domain, was constructed and delivered into T cells by pseudotyped lentivirus. The cytokine release, cytotoxicity and proliferation of dual-targeted CAR-T cells were tested in vitro, and their safety and therapeutic efficacy were evaluated using a human tumor xenograft mouse model in vivo.ResultsThe dual-targeted CAR-T cells exerted a similar cytotoxic activity against CD19/HER2+tumor cells with or without PD-L1 in vitro, however, enhanced cytokine releases and improved proliferative capacity were only observed in the presence of both CD19/HER2 and PD-L1. Importantly, the dual-targeted CAR-T cells displayed no cytotoxicity against PD-L1+cells alone in the absence of tumor antigen CD19/HER2. In addition, the dual-targeted CAR-T cells preferably destroyed tumor xenografts bearing both CD19/HER2 and PD-L1,but spared only antigen-positive tumor xenografts without PD-L1 in vivo. Furthermore, PD-L1 CCR also improved the antitumor efficacy of the low-affinity HER2 CAR-T cells against PD-L1+tumors expressing high levels of HER2.ConclusionOur observations demonstrated that PD-L1 could be used as a universal target antigen for designing CCR, and the dual-targeted CAR-T cells equipped with PD-L1 CCR could be used to reduce the risk of on-target off-tumor toxicity while retaining their potent antitumor efficacy in the treatment of PD-L1+solid tumors.
Evaluation of temperature rise in the pulp during various IPR techniques—an in vivo study
Authors: Banga Kiran , Arora Nitin , Kannan Sridhar , Singh Ashish Kumar , Malhotra Abhita 
Published: November 2020

Abstract

Background
Non-extraction treatment protocol has gained a lot of popularity over extraction for orthodontic treatment. Interproximal enamel reduction is one such method that makes it possible to do orthodontic treatment without extractions. This procedure, which can be done by various techniques, leads to a rise in the temperature of the pulp of the teeth. Previously, studies have been done which have evaluated the temperature changes inside the pulp chamber of extracted teeth, during interproximal enamel reduction. However, no documented literature exists that has evaluated these changes in the live pulp of the teeth whilst interproximal enamel reduction (IPR) is being performed. Therefore, this study aimed to evaluate the temperature changes inside the live pulp of the teeth during various interproximal enamel reduction techniques in vivo.

Aims
Evaluation of temperature rise in the pulp during various interproximal enamel reduction techniques, done in vivo.

Material and method
The study was performed on patients for whom extraction of premolars had been advised for their orthodontic treatment. Fifty-one premolar teeth were randomly divided into three groups of IPR, i.e. using airotor and bur, handheld metal strip and orthodontic IPR kit (oscillating system). IPR was performed on the mesial and distal sides after access opening, temperature change was recorded during IPR and the readings were compared. The Shapiro-Wilk test was utilized for checking whether the data satisfied the requirement of normal distribution.

Results
The highest temperature rise was seen in group 1 in which interproximal enamel reduction was performed using airotor and bur. The minimum temperature rise was observed in group 2 in which interproximal enamel reduction was done using the handheld metal strip, whereas the temperature rise observed in group 3, in which interproximal enamel reduction was done using IPR kit, was between the range of group 1 and group 3. The temperature change was in the following order—group 1 (2.08 °C) > group 3 (1.22 °C) > group 2 (0.52 °C).

Conclusion
None of the methods used to perform interproximal enamel reduction caused a temperature increase more than 5.5 °C, beyond which pulp necrosis may occur. Therefore, all three methods used in the study for IPR were found to be safe.
3D printing technology and internet of things prototyping in family practice: building pulse oximeters during COVID-19 pandemic
Authors: Capobussi Matteo , Moja Lorenzo 
Published: November 2020

Abstract
Family doctors can have an active role in identifying significant population needs and solutions. During the COVID-19 epidemic, patient home monitoring with pulse oximetry has been a key aspect of care of patients. However, pandemics bring shortage of medical equipment such as pulse oximeters. Through the local maker community, in a matter of days four “smart” pulse oximeters were built. Following Internet of Things principles, the prototypes were programmed to transmit real-time data through Wi-Fi directly to the doctors. Each pulse oximeter served a family doctor during the pandemic. In this article we describe the process that led to the production of the technology and provide detailed instructions, which have also been shared in maker-oriented websites. Dissemination can potentially lead to additional small-scale productions, limiting future shortages.
Intravital imaging of orthotopic and ectopic bone
Authors: Hashimoto Kunihiko , Kaito Takashi , Kikuta Junichi , Ishii Masaru 
Published: November 2020

Abstract
Bone homeostasis is dynamically regulated by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Visualizing and evaluating the dynamics of bone cells in vivo remain difficult using conventional technologies, including histomorphometry and imaging analysis. Over the past two decades, multiphoton microscopy, which can penetrate thick specimens, has been utilized in the field of biological imaging. Using this innovative technique, the in vivo dynamic motion of bone metabolism-related cells and their interactions has been revealed. In this review, we summarize previous approaches used for bone imaging and provide an overview of current bone tissue imaging methods using multiphoton excitation microscopy.
Radiofrequency catheter ablation of ventricular tachycardia in pediatric patients
Authors: Park Woo Young , Song Mi Kyoung , Kim Gi Beom , Lee Sang Yun , Kwon Hye Won , Bae Eun Jung 
Published: November 2020

Abstract

Background
Radiofrequency catheter ablation (RFCA) has been accepted as an efficient therapy for tachycardia, and substantial improvement in the outcomes of RFCA in pediatric patients has been seen. However, there is not enough data on the clinical outcomes of RFCA for ventricular tachycardia (VT) in pediatric patients. The objective of this study was to elucidate the efficacy and safety of RFCA for VT in pediatric patients.

Methods
We performed a retrospective study involving 35 consecutive pediatric VT ablation procedures in 28 patients at a single institution.

Results
The median age at ablation was 14.0 years (range 6.9–19.2 years). There were 24 patients with a structurally normal heart and four patients with congenital heart disease (CHD). The left ventricular posteroseptal area was the most common site of VT origin (22/28, 78.6%). However, there was an unusual case of VT which involved a papillary muscle as its origin. Acute success was achieved in 30 (85.7%) of 35 procedures. The recurrence rate after successful RFCA was 14.2% (5/35) at a median follow-up of 6.7 years (range 1.0–16.7 years). There were five procedural failures due to the inability to induce VT for complete mapping. Ultimately, long-term success was achieved in 27 patients (96.4%) after repeated procedures and no major complications occurred. Long-term success was associated with VT inducibility (p =  < 0.001).

Conclusions
Difficulty in inducing VT for precise mapping was a significant obstacle to successful RFCA. RFCA was identified as safe and effective therapy to eliminate VT in the selected pediatric VT patients.
Disease modifying treatment trials in Parkinson’s disease: how to balance expectations and interests of patients, physicians and industry partners?
Authors: Berg D. , Eggert K. , Haslinger B. , Kassubek J. , Mollenhauer B. , Reetz K. , Rogge A. , Schaeffer E. , Tönges L. , Zeuner K. E. 
Published: November 2020

Abstract

Background
The advent of therapeutic strategies designed to modify the disease course in Parkinson’s disease has raised great expectations in the currently conducted clinical trials. However, we see ethical challenges in the cooperation of industry and clinical partners, specifically evident in the way recruitment is performed.
We here discuss the different positions and challenges of all involved to set the stage for a study and recruitment culture taking into account the expectations of all: (i) patients and their caregivers, ready to take the considerable burden of clinical trials in hope for the development of disease-modifying treatments; (ii) physicians and study nurses, obligated to the patients’ well-being and benefit who accompany and supervise patients closely as basis for the performance of elaborate clinical trials (iii) industrial partners, investing years of efforts and finances to develop new treatments.

Conclusions
We conclude that the current competitive race for enrollment in clinical studies in PD is challenging the primary goal to ensure patients’ benefit and formulate requests to the industrial partners to encounter these concerns.
Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma
Authors: Kim In Ae , Hur Jae Young , Kim Hee Joung , Park Jung Hoon , Hwang Jae Joon , Lee Song Am , Lee Seung Eun , Kim Wan Seop , Lee Kye Young 
Published: November 2020

Abstract
Background
Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence.

Methods
Tissues from 230 patients with resected stage I–II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan–Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model.

Results
Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02). Conclusions: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.
Effect of Carbon Dots on Supercapacitor Performance of Carbon Nanohorn/Conducting Polymer Composites
Authors: Chang Chia Chi , Geleta Tesfaye Abebe , Imae Toyoko 
Published: November 2020

Abstract
Conducting composites consisting of carbon nanohorn (CNH), carbon dots (C-dots) and polyaniline (PA) or polypyrrole (PP) have been synthesized via in-situ polymerization and evaluated for performance as electrode materials for supercapacitors. The addition of C-dots to composites of CNH and conducting polymer showed a superior influence on supercapacitance properties in comparison with composites without C-dots. Incidentally, the specific capacitance was 1206 F/g and 538 F/g at a scan rate of 5 mV/s for composites of CNH with PA and PP, respectively, with addition of C-dots. These values were 1.6 and 2.3 times higher than values for composites without C-dots. Moreover, composites with C-dots exhibited high capacitance retention (94 and 93%, respectively). Thus, these results indicate that the addition of C-dots to composites of CNH with conducting polymers provides a significant enhancing effect as promising electrode materials for energy storage devices with high capacitance and stability.
The varying openness of digital open science tools
Authors: Bezuidenhout Louise , Havemann Johanna 
Published: November 2020

Background: Digital tools that support open science practices play a key role in the seamless accumulation, archiving and dissemination of scholarly data, outcomes and conclusions. Despite their integration into open science practices, the providence and design of these digital tools are rarely explicitly scrutinized. This means that influential factors, such as the funding models of the parent organizations, their geographic location, and the dependency on digital infrastructures are rarely considered. Suggestions from literature and anecdotal evidence already draw attention to the impact of these factors, and raise the question of whether the open science ecosystem can realise the aspiration to become a truly “unlimited digital commons” in its current structure. Methods: In an online research approach, we compiled and analysed the geolocation, terms and conditions as well as funding models of 242 digital tools increasingly being used by researchers in various disciplines. Results: Our findings indicate that design decisions and restrictions are biased towards researchers in North American and European scholarly communities. In order to make the future open science ecosystem inclusive and operable for researchers in all world regions including Africa, Latin America, Asia and Oceania, those should be actively included in design decision processes. Conclusions: Digital open science tools carry the promise of enabling collaboration across disciplines, world regions and language groups through responsive design. We therefore encourage long term funding mechanisms and ethnically as well as culturally inclusive approaches serving local prerequisites and conditions to tool design and construction allowing a globally connected digital research infrastructure to evolve in a regionally balanced manner.
Insulin safety: what is all the fuss about?
Authors: Cartwright Anne 
Published: November 2020

Errors in the prescribing, dispensing and administration of insulin can cause serious harm. Anne Cartwright raises awareness of the risks In 2010 National Patient Safety Alerts produced a rapid response report ‘Safer Use of Insulin’ in response to an increasing number of medication incidents leading to severe harm or death as a result of errors with insulin therapy. In 2017 the World Health Organization launched a global initiative to reduce avoidable medication error by 50% over 5 years. This article aims to raise awareness of the risks of insulin therapy, the common mistakes that can be made in the prescribing, dispensing and administration of insulin, and to inform health professionals who are involved in caring for people on insulin therapy how to reduce the risk of potential harm.
Analysing the variation in volume and nature of trauma presentations during COVID-19 lockdown in Ireland
Authors: Fahy Stephen , Moore Joss , Kelly Michael , Flannery Olivia , Kenny Paddy 
Published: November 2020

Aims Europe has found itself at the epicentre of the COVID-19 pandemic. Naturally, this has placed added strain onto healthcare systems internationally. It was feared that the impact of the COVID-19 pandemic could overrun the Irish healthcare system. As such, the Irish government opted to introduce a national lockdown on the 27 March 2020 in an attempt to stem the flow of admissions to hospitals. Similar lockdowns in the UK and New Zealand have resulted in reduced emergency department presentations and trauma admissions. The aim of this study is to assess the effect of the national lockdown on trauma presentations to a model-3 hospital in Dublin, Ireland. Methods A retrospective study was conducted. All emergency department presentations between 27 March 2019 to 27 April 2020 and 27 March 2020 to 27 April 2020 were cross-referenced against the National Integrated Medical Imaging System-Picture Archiving Communication System (NIMIS-PACS) radiology system to identify those with radiologically proven skeletal trauma. These patients were grouped according to sex, age, discharge outcome, mechanism of injury, and injury location. Results A 21% decrease in radiologically proven trauma was observed on comparison with the same time-period last year. Additionally, a 40% reduction in trauma admissions was observed during the COVID-19 lockdown. A 60% reduction in sports-related injuries and road traffic accident-related injuries was noted during the national lockdown. However, a 17% increase was observed in patients sustaining trauma because of domestic accidents. Conclusion Variation was observed in both the volume and nature of trauma presentations during the COVID-19 lockdown. As would be expected, a reduction was seen in the number of injuries resulting from outdoor activities. Interestingly, increased rates of domestic injuries were seen during this period which could represent an unintended consequence of the prolonged period of lockdown. Cite this article: Bone Joint Open 2020;1-6:261–266.
Trauma and orthopaedic team members’ mental health during the COVID-19 pandemic
Authors: Thakrar Amit , Raheem Ali , Chui Karen , Karam Edward , Wickramarachchi Lilanthi , Chin Kuen 
Published: November 2020

Aims Healthcare systems have been rapidly restructured to meet COVID-19 demand. Clinicians are working to novel clinical guidelines, treating new patient cohorts and working in unfamiliar environments. Trauma and orthopaedics (T&O) has experienced cancellation of routine clinics and operating, with redistribution of the workload and human resources. To date, no studies have evaluated the mental health impact of these changes on the T&O workforce. We report the results of a novel survey on the impact of the pandemic on the mental health of our orthopaedic workforce and the contributory factors. Methods A 20-question survey-based cross-sectional study of orthopaedic team members was conducted during the COVID-19 pandemic. The primary objective was to identify the impact of the pandemic on mental health in the form of major depressive disorder (MDD) and general anxiety disorder (GAD). The survey incorporated the patient health questionnaire (PHQ-2), which is validated for screening of MDD, and the generalized anxiety disorder questionnaire (GAD-2), which is validated for screening of GAD. Results There were 62 respondents (18 females and 44 males). As compared to the general population, we noted a greater estimated prevalence of GAD (17.7% vs 5.9%, p = 0.0009297) and MDD (19.4% vs 3.3%, p = 0.0000007731). The prevalence of MDD symptoms was greatest among senior house officers (SHOs) (p = 0.02216). Female respondents scored higher for symptoms of MDD (p = 0.03583) and GAD (p = 0.0001086). Those identifying as ‘Black, African, Caribbean or Black British’ displayed a higher prevalence of GAD symptoms (p = 0.001575) and felt least supported at work (p = 0.001341). Conclusion Our study, in the first of its kind, shows a significant prevalence of GAD and MDD in the workforce. We found that SHOs, females and those of Black, African, Caribbean, or Black British origin were disproportionately affected. Action should be taken to help prevent adverse mental health outcomes for our colleagues during the pandemic. Cite this article: Bone Joint Open 2020;1-6:316–325.
The arithmetic HKA (aHKA) predicts the constitutional alignment of the arthritic knee compared to the normal contralateral knee
Authors: MacDessi Samuel J , Griffiths-Jones William , Harris Ian A , Bellemans Johan , Chen Darren B 
Published: November 2020

Aims An algorithm to determine the constitutional alignment of the lower limb once arthritic deformity has occurred would be of value when undertaking kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to determine if the arithmetic hip-knee-ankle angle (aHKA) algorithm could estimate the constitutional alignment of the lower limb following development of significant arthritis. Methods A matched-pairs radiological study was undertaken comparing the aHKA of an osteoarthritic knee (aHKA-OA) with the mechanical HKA of the contralateral normal knee (mHKA-N). Patients with Grade 3 or 4 Kellgren-Lawrence tibiofemoral osteoarthritis in an arthritic knee undergoing TKA and Grade 0 or 1 osteoarthritis in the contralateral normal knee were included. The aHKA algorithm subtracts the lateral distal femoral angle (LDFA) from the medial proximal tibial angle (MPTA) measured on standing long leg radiographs. The primary outcome was the mean of the paired differences in the aHKA-OA and mHKA-N. Secondary outcomes included comparison of sex-based differences and capacity of the aHKA to determine the constitutional alignment based on degree of deformity. Results A total of 51 radiographs met the inclusion criteria. There was no significant difference between aHKA-OA and mHKA-N, with a mean angular difference of −0.4° (95% SE −0.8° to 0.1°; p = 0.16). There was no significant sex-based difference when comparing aHKA-OA and mHKA-N (mean difference 0.8°; p = 0.11). Knees with deformities of more than 8° had a greater mean difference between aHKA-OA and mHKA-N (1.3°) than those with lesser deformities (-0.1°; p = 0.009). Conclusion This study supports the arithmetic HKA algorithm for prediction of the constitutional alignment once arthritis has developed. The algorithm has similar accuracy between sexes and greater accuracy with lesser degrees of deformity. Cite this article: Bone Joint Open 2020;1-7:339–345.