bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of remote consulting for patients and neurologists during the COVID-19 pandemic in Scotland
Authors: Stavrou Maria , Lioutas Eva , Lioutas Joanna , Davenport Richard J 
Published: November 2021

BackgroundRemote consulting is an emerging model in managing chronic neurological conditions and has been widely implemented during the COVID-19 pandemic. The objective of this national survey was to investigate the initial experiences of remote consulting for neurologists and patients with established neurological conditions under follow-up during the first COVID-19 phase.MethodsIn collaboration with the Scottish Association of Neurological Sciences and the Neurological Alliance of Scotland, we conducted a web-based survey of neurologists and patients between October and November 2020.FindingsData was available for 62 neurologists and 201 patients. The consensus among neurologists was that remote consulting is a satisfactory way of delivering healthcare in selected groups of patients. For practical and technical reasons, there was preference for phone over video consultations (phone 63% vs video 33%, p=0.003). The prevailing opinion among clinicians was that considerable training interventions for remote consultation skills are required (‘yes’ 63% vs ‘no’ 37%, p=0.009) to improve clinician consultation skills and successfully embed this new model of care.Most patients perceived remote consultations as safe, effective and convenient, with 89% of patients being satisfied with their remote consultation experience. Although traditional face-to-face consultations were the favoured way of interaction for 62% of patients, a significant proportion preferred that some of their future consultations be remote.InterpretationAlthough not a replacement for face-to-face consultations, this survey illustrates that remote consulting can be an acceptable adjunct to traditional face-to-face consultations for doctors and patients. More research is required to identify overall safety and applicability.
Quality improvement project to decrease unnecessary investigations in infants with bronchiolitis in Cork University Hospital
Authors: Jansen Lizeri , Meyer Gideon-Phil , Curtin Glenn , Lynch Bryan , O’Brien Rory 
Published: November 2021

BackgroundBronchiolitis is a common reason for infants to present to the emergency department (ED). Clear evidence-based guidelines exist that recommend against routine radiological and laboratory investigations in this cohort. Despite this, preintervention audit showed that children below 12 months of age with bronchiolitis in the ED during November 2018–January 2019 were receiving unnecessary investigations. Our aim was to improve patient care by decreasing unnecessary investigations in bronchiolitis infants.MethodsBaseline assessment comprised a preintervention audit of children less than 12 months of age with a diagnosis of bronchiolitis that presented to ED during November 2018–January 2019. The outcome measure was average weekly hospital length of stay (LOS), process measures were average weekly chest X-ray (CXR) and laboratory investigation rate. The balancing measure was the average weekly representation rate.InterventionA multimodal intervention was implemented comprising a locally agreed flowchart enhanced by regular feedback on performance using run charts and in-person sessions.ResultsA postintervention audit of November 2019–January 2020 was undertaken. There was a 57% reduction in the mean average weekly CXR rate (from 25% to 11%, p value 0.009974 significant at p<0.05); there was an improvement by 56% in the mean average weekly laboratory investigation rate (from 29% to 13%, p value 0.005475, significant at p<0.05) in the preintervention and postintervention periods, respectively. The mean average weekly representations remained at 4% preintervention and postintervention (p value 0.737). There was no significant difference in hospital LOS (from 25.3 hours to 20.7 hours, p value 0.270549).ConclusionAn evidence-based protocol improved physicians’ ability in diagnosing and managing infants with bronchiolitis. This led to a reduction in unnecessary and potential harmful investigations, thereby improving patient quality of care. This improvement will contribute to decreased healthcare cost and appropriate use of resources during the high-pressured winter period.
Association of sleep apnoea risk and aortic enlargement in Marfan syndrome
Authors: Sowho Mudiaga , MacCarrick Gretchen , Dietz Harry , Jun Jonathan , Schwartz Alan R , Neptune Enid R 
Published: November 2021

BackgroundMarfan syndrome (MFS) is a connective tissue disorder characterised by complex aortic pathology and a high prevalence of obstructive sleep apnoea (OSA). OSA produces intrathoracic transmural stresses that may accelerate aortic injury. The current study was designed to examine the associations between OSA risk and markers of aortic enlargement in MFS.MethodConsecutive patients with MFS were recruited at Johns Hopkins if they completed a STOP-BANG survey. Composite survey scores were categorised into those with low OSA risk (STOP-BANG <3) and high OSA risk (STOP-BANG ≥3). Participants’ aortic data were collated to ascertain aortic root diameter, dilatation and prior aortic root replacement. Regression analyses were used to examine associations between OSA risk strata and these aortic parameters.ResultsOf the 89 participants studied, 28% had a high OSA risk and 32% had aortic grafts. Persons with high OSA risk had greater aortic root diameter (mm) (ß=4.13, SE=1.81, p=0.027) and aortic root dilatation (ß=2.80, SE=1.34, p=0.046) compared with those with low OSA risk . In addition, the odds of prior aortic root replacement was three times greater in those with high OSA risk compared with those with low OSA risk.ConclusionIn MFS, high OSA risk is associated with aortic enlargement and a threefold increased risk of having had prior aortic root replacement. These findings invite further exploration of the relationship between OSA and aortic disease in MFS, and studies to clarify whether targeted interventions for OSA might mitigate aortic disease progression in MFS.Registration numberIRB00157483.
Integrating patients with chronic respiratory disease and heart failure into a combined breathlessness rehabilitation programme: a service redesign and pilot evaluation
Authors: Chaplin Emma , Ward Sarah , Daynes Enya , Bourne Claire LA , Stenson Amy , Watt Amye , Gardiner Nikki , Houchen-Wolloff Linzy , Singh Sally J 
Published: November 2021

IntroductionThe successful integration of patients with chronic heart failure (CHF) into a traditional pulmonary rehabilitation (PR) programme has previously been reported. Our aim was to reconfigure both our cardiac rehabilitation (CR) and PR services to enable us to deliver a symptom-based programme—breathlessness rehabilitation (BR), for patients with a primary symptom of breathlessness irrespective of the index diagnosis, or comorbid disease.MethodsAfter a service redesign process, patients attended a two times per week, group-based, tailored exercise and education programme for 6 weeks, delivered by CR and PR staff. The classes included both aerobic and resistance exercises and an overarching generic education programme alongside disease-specific components. Home programmes were reviewed at each session to facilitate progress and influence changes in exercise behaviour beyond the supervised programme. Generic clinical outcome measures were performed pre and post BR.Staff focus groups were conducted to identify barriers and facilitators and explore staff perceptions.Results272 patients (n=193 chronic respiratory disease (CRD) and n=79 CHF) were assessed and enrolled into BR (153 men, mean (SD) age 68.8 (12.7) years, body mass index 28.8 (7.3), Medical Research Council 3 (IQR 2–4), New York Heart Association 2 (IQR 2–3)). 164 patients completed the programme. Statistically significant improvements were seen in both exercise capacity (incremental shuttle walking test: mean change 47.4 m; endurance shuttle walking test: mean change 310.7 s) and quadriceps strength (quadriceps maximal voluntary contraction: mean change 3.7 kg) (p≤0.0001) alongside a statistically significant reduction in dyspnoea (chronic respiratory questionnaire/chronic heart questionnaire - self reported - dyspnoea: mean change 0.4) and anxiety and depression scores (Hospital Anxiety and Depression Scale (HADS) - anxiety: −1.6; HADS - depression: −1.3) (p≤0.0001).Qualitative staff focus groups identified three subthemes: collaboration and integration, service quality and future challenges.DiscussionOverall the service redesign indicates the feasibility for staff and individuals with CRD and CHF to integrate into a breathlessness programme. Early data suggests clinical effectiveness. Given the significance of comorbid disease it is an approach that warrants further consideration.
Detection of COX-2 in liquid biopsy of patients with prostate cancer
Authors: Pereira Vanessa Silva , Alves Beatriz da Costa Aguiar , Waisberg Jaques , Fonseca Fernando , Gehrke Flavia 
Published: November 2021

AimsTo determine the profile ofCOX-2gene expression in patients with prostate cancer attended at the ABC University Health Center outpatient clinic and correlate the results with patients’ anatomopathological examinations. Prostate cancer is the sixth most common type of cancer worldwide and the second in Brazil.COX-2expression is associated with an unfavourable prognosis.Methods15.0 mL of peripheral blood were collected from 24 patients and 25 healthy men. RNA extraction was performed using the QIAamp RNA Blood Mini Kit. Complementary DNA synthesis was performed using SuperScript II RNAse Reverse Transcriptase. Quantitative real-time PCR was performed with specificCOX-2oligonucleotides and the endogenousGAPDHgene.ResultsThe mean age of the patients was 69 years old. The Gleason scoring system showed 37.5% of patients with Gleason 6 (slow growth, low risk), 45.8% with Gleason 7 (intermediate risk) and 16.7% with Gleason 8 or 9 (risk of high-grade cancer). The medianCOX-2expression in the study group was 0.97, while in the control group it was 0.11 (p<0.045).ConclusionsPatients with prostate cancer showed higherCOX-2expression at diagnosis compared with the control group. SinceCOX-2detection associated with prostate-specific antigen dosage shows promise as a biomarker for diagnosis and prognosis in patients with prostate cancer, further research is required to confirm these findings.
Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial
Authors: Hua Yijun , You Rui , Wang Zhiqiang , Huang Peiyu , Lin Mei , Ouyang Yanfeng , Xie Yulong , Zou Xiong , Liu Youping , Duan Chongyang , Liu Yonglong , Gu Chenmei , Liu Rongzeng , Yang Qi , Jiang Rou , Zhang Mengxia , Ding Xi , Chen Siyuan , Lin Chao , Sun Rui , Chen Mingyuan 
Published: November 2021

BackgroundToripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1. We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC).MethodsWe conducted a single-arm, phase II trial with patients with rNPC who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate at 3 months post radiotherapy. The secondary endpoints included safety profiles, progression-free survival (PFS).ResultsBetween May 2019 and January 2020, a total of 25 patients with rNPC were enrolled (18 men (72.0%) and 7 women (28.0%); median (IQR) age, 49.0 (43.5–52.5) years). With a median (IQR) follow-up duration of 14.6 months (13.1–16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month PFS was 91.8% (95% CI 91.7% to 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine kinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively.ConclusionsToripalimab combined with IMRT was tolerable and showed promising antitumor activity in patients with rNPC.Trial registration numberNCT03854838.
Fc-comprising scDb-based trivalent, bispecific T-cell engagers for selective killing of HER3-expressing cancer cells independent of cytokine release
Authors: Aschmoneit Nadine , Kühl Lennart , Seifert Oliver , Kontermann Roland E 
Published: November 2021

BackgroundBispecific T-cell engagers are an established therapeutic strategy for the treatment of hematologic malignancies but face several challenges when it comes to their application for the treatment of solid tumors, including on-target off-tumor adverse events. Employing an avidity-mediated specificity gain by introducing an additional binding moiety for the tumor-associated antigen can be achieved using formats with a 2+1 stoichiometry.MethodsBesides biochemical characterization and validation of target cell binding to cancer cells with different HER3 expression, we used in vitro co-culture assays with human peripheral blood mononuclear cells (PBMCs) and HER3-expressing target cells to determine T-cell activation, T-cell proliferation and PBMC-mediated cancer cell lysis of HER3-positive cell lines by the trivalent, bispecific antibodies.ResultsIn this study, we developed trivalent, bispecific antibodies comprising a silenced Fc region for T-cell retargeting to HER3-expressing tumor cells, combining a bivalent single-chain diabody (scDb) fused to a first heterodimerizing Fc chain with either an Fab or scFv fused to a second heterodimerizing Fc chain. All these HER3-targeting T-cell engagers comprising two binding sites for HER3 and one binding site for CD3 mediated target cell killing. However, format and orientation of binding sites influenced efficacy of target cell binding, target cell-dependent T-cell activation and T-cell-mediated target cell killing. Beneficial effects were seen when the CD3 binding site was located in the scDb moiety. These molecules showed efficient killing of medium HER3-expressing cancer cells with very low induction of cytokine release, while sparing target cells with low or undetectable HER3 expression.ConclusionOur study demonstrates that these trivalent, bispecific antibodies represent formats with superior interdomain spacing resulting in efficient target cell killing and a potential advantageous safety profile due to very low cytokine release.
External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland
Authors: Simpson Colin R , Robertson Chris , Kerr Steven , Shi Ting , Vasileiou Eleftheria , Moore Emily , McCowan Colin , Agrawal Utkarsh , Docherty Annemarie , Mulholland Rachel , Murray Josie , Ritchie Lewis Duthie , McMenamin Jim , Hippisley-Cox Julia , Sheikh Aziz 
Published: November 2021

BackgroundThe QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland.MethodsWe established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020.ResultsOur dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell’s C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell’s C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively.ConclusionsVersion 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.
Clinical Epidemiological Characteristics and Risk Factors for Severe Bronchiolitis Caused by Respiratory Syncytial Virus in Vietnamese Children
Authors: Nguyen Sang Ngoc , Nguyen Thuy Ngoc Thi , Vu Lam Tung , Nguyen Thap Duc 
Published: November 2021

Introduction. Bronchiolitis is the most prevalent cause of hospitalization in infants under the age of 12 months. The disease is caused by respiratory syncytial virus (RSV) infection, which can cause breathing difficulties and respiratory failure. Therefore, it is necessary to discover the risk factors of severe bronchiolitis to diagnose and treat promptly. This study is aimed at describing the epidemiological characteristics and clinical features of acute bronchiolitis caused by RSV and assessing the related factors to severe acute bronchiolitis in studied patients. Methods. A descriptive cross-sectional study was carried out in Haiphong Children’s Hospital, Haiphong, Vietnam, for one year, from October 1, 2016, to September 30, 2017. All bronchiolitis

admissions
<
2

years

were included. Results. 377 children were evaluated, including 261 boys and 116 girls; children under 6 months accounted for the highest proportion (57%), and 47 (12.5%) of all patients had severe disease. Wheezing was the main reason to be taken to the hospital 261 (69.2%). Clinical symptoms of acute bronchiolitis such as cough, tachypnea, and runny nose were found in all patients. Bronchiolitis cases increased in the winter-spring season, and the highest registered number of patients was 42 in March. Image of bronchiolitis on chest X-ray was found in all patients, and air trapping lung was found in 124 (32.9%) patients. The risk factors included age (≤6 months), low birth weight, preterm birth, nonbreastfeeding for the first six months, early weaning, and exposition to cigarette smoke increased the severe disease (

p
<
0.05

). Conclusion. The number of hospitalized infants with bronchiolitis caused by RSV has an upward trend during the winter-spring season (from October to March). This study confirms that age, preterm birth, breastfeeding under 6 months, history of exposure to cigarette smoking, low birth weight, having sibling(s) under five years old going to kindergarten, history of undergoing cesarean section, history of mechanical ventilation, poor living condition, and maternal education are 10 risk factors of severe bronchiolitis caused by RSV.
Collagen Linearization within Tumors
Authors: Barcus Craig E. , Longmore Gregory D. 
Published: November 2021

Abstract
It is now well appreciated that the tumor microenvironment (TME) surrounding primary tumors impacts tumor growth, progression (invasion and migration), and response to therapy. Broadly speaking, the TME is composed of cells (immune cells, activated fibroblasts, adipocytes, endothelial cells), acellular extracellular matrix (ECM), and cytokines or growth factors, some of which are bound or tethered to the ECM proteins. All these compartments undergo significant changes during tumor development and progression. Changes to the ECM, in particular, can dramatically influence cancer biology. This has stimulated the development of therapies that directly reverse or prevent the structural changes in the TME ECM that facilitate cancer progression. But to do so, in a rational manner, we need to understand how structural changes to tumor ECM arise, are remodeled, and function to facilitate tumor cell invasion and migration that give rise to metastatic disease, which is the main cause of cancer-related deaths. In this issue of Cancer Research, Janjanam and colleagues show that the ratio of WISP1/WISP2 in tumors is critical for ECM collagen fiber linearization and important for metastasis. WISP2 binds ECM collagen directly and can inhibit WISP1-mediated collagen linearization. These new results offer a new approach for targeting the altered collagen ECM in tumors by preventing or reversing collagen linearization.
See related article by Janjanam et al., p. 5666
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Authors: Kilian Michael , Friedrich Mirco , Sanghvi Khwab , Green Edward , Pusch Stefan , Kawauchi Daisuke , Löwer Martin , Sonner Jana K. , Krämer Christopher , Zaman Julia , Jung Stefanie , Breckwoldt Michael O. , Willimsky Gerald , Eichmüller Stefan B. , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael , Bunse Lukas 
Published: November 2021

AbstractPurpose:Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy.Experimental Design:Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intraventricular TCR-transgenic T-cell therapy was assessed in a newly developed glioma model in MHC-humanized mice induced by CRISPR-based delivery of tumor suppressor–targeting guide RNAs.Results:We identify recurrent capicua transcriptional repressor (CIC) inactivating hotspot mutations at position 215 CICR215W/Q as immunogenic MHC class II (MHCII)-restricted neoepitopes. Vaccination of MHC-humanized mice resulted in the generation of robust MHCII-restricted mutation-specific T-cell responses against CICR215W/Q. Adoptive intraventricular transfer of CICR215W-specific TCR-transgenic T cells exert antitumor responses against CICR215W-expressing syngeneic gliomas.Conclusions:The integration of immunocompetent MHC-humanized orthotopic glioma models in the discovery of shared immunogenic glioma neoepitopes facilitates the identification and preclinical testing of human leukocyte antigen (HLA)-restricted neoepitope-specific TCRs for locoregional TCR-transgenic T-cell adoptive therapy.