bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental factors associated with general practitioner consultations for allergic rhinitis in London, England: a retrospective time series analysis
Authors: Todkill Dan , de Jesus Colon Gonzalez Felipe , Morbey Roger , Charlett Andre , Hajat Shakoor , Kovats Sari , Osborne Nicholas J , McInnes Rachel , Vardoulakis Sotiris , Exley Karen , Edeghere Obaghe , Smith Gillian , Elliot Alex J 
Published: December 2020

ObjectivesTo identify key predictors of general practitioner (GP) consultations for allergic rhinitis (AR) using meteorological and environmental data.DesignA retrospective, time series analysis of GP consultations for AR.SettingA large GP surveillance network of GP practices in the London area.ParticipantsThe study population was all persons who presented to general practices in London that report to the Public Health England GP in-hours syndromic surveillance system during the study period (3 April 2012 to 11 August 2014).Primary measureConsultations for AR (numbers of consultations).ResultsDuring the study period there were 186 401 GP consultations for AR. High grass and nettle pollen counts (combined) were associated with the highest increases in consultations (for the category 216-270 grains/m3, relative risk (RR) 3.33, 95% CI 2.69 to 4.12) followed by high tree (oak, birch and plane combined) pollen counts (for the category 260–325 grains/m3, RR 1.69, 95% CI 1.32 to 2.15) and average daily temperatures between 15°C and 20°C (RR 1.47, 95% CI 1.20 to 1.81). Higher levels of nitrogen dioxide (NO2) appeared to be associated with increased consultations (for the category 70–85 µg/m3, RR 1.33, 95% CI 1.03 to 1.71), but a significant effect was not found with ozone. Higher daily rainfall was associated with fewer consultations (15–20 mm/day; RR 0.812, 95% CI 0.674 to 0.980).ConclusionsChanges in grass, nettle or tree pollen counts, temperatures between 15°C and 20°C, and (to a lesser extent) NO2 concentrations were found to be associated with increased consultations for AR. Rainfall has a negative effect. In the context of climate change and continued exposures to environmental air pollution, intelligent use of these data will aid targeting public health messages and plan healthcare demand.
Effects of novel flash glucose monitoring system on glycaemic control in adult patients with type 1 diabetes mellitus: protocol of a multicentre randomised controlled trial
Authors: Zhou Yongwen , Deng Hongrong , Liu Hongxia , Yang Daizhi , Xu Wen , Yao Bin , Yan Jinhua , Weng Jianping 
Published: December 2020

IntroductionOptimal glycaemic control is beneficial to prevent and delay microvascular complications in patients with type 1 diabetes mellitus (T1DM). The benefits of flash glucose monitoring (FGM) have been proved among well-controlled adults with T1DM, but evidence for FGM in adults with T1DM who have suboptimal glycaemic control is limited. This study aims to evaluate the effect of FGM in suboptimally controlled adult patients with T1DM .Methods and analysisThis open-label, multicentre, randomised trial will be conducted at eight tertiary hospitals and recruit 104 adult participants (≥18 years old) with T1DM diagnosed for at least 1 year and with suboptimal glycaemic control (glycated haemoglobin (HbA1c) ranging from 7.0% to 10.0%). After a run-in period (baseline, 0–2 weeks), eligible participants will be randomised 1:1 to either use FGM or self-monitoring of blood glucose alone consequently for the next 24 weeks. At baseline, 12–14 weeks and 24–26 weeks, retrospective continuous glucose monitoring (CGM) systems will be used in both groups for device-related data collection. Biological metrics, including HbA1c, blood routine, lipid profiles, liver enzymes, questionnaires and adverse events, will be assessed at baseline, week 14 and week 26. All analyses will be conducted on the intent-to-treat population. Efficacy endpoint analyses will also be repeated on the per-protocol population. The primary outcome is the change of HbA1c from baseline to week 26. The secondary outcomes are the changes of CGM metrics, including time spent in range, time spent in target, time spent below range, time spent above range, SD, coefficient of variation, mean amplitude of glucose excursions, high or low blood glucose index, mean of daily differences, percentage of HbA1c in target (<7%), frequency of FGM use, total daily insulin dose and the scores of questionnaires including Diabetes Distress Scale, Hypoglycemia Fear Scale and European Quality of Life Scale.Ethics and disseminationThis study was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University in January 2017. Ethical approval has been obtained at all centres. All participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT03522870.
Scoping review protocol: the use of telemedicine in providing opioid agonist treatment and related psychosocial supports
Authors: Crowley Des , Homeniuk Robyn , Delargy Ide 
Published: December 2020

IntroductionThe global opioid-related disease burden is significant. Opioid agonist treatment (OAT) can be effective in reducing illicit opioid use and fatal overdose, and improving multiple health and social outcomes. Despite evidence for its effectiveness, there are significant deficits in OAT globally. COVID-19 has required rapid adaptation of remote models of healthcare. Telemedicine is not used routinely in OAT, and little is known about the current levels of use and effectiveness. The objective of this review is to describe models of telemedicine and their efficacy.Methods and analysisThis scoping review uses the review methodology described by Arksey and O’Malley and adapted by Levacet al. The search strategy developed by the medical librarian at the Irish College of General Practitioners in conjunction with the research team will involve five databases (PubMed, EMBASE, the Cochrane Library, PsycInfo and OpenGrey) and the hand searching of reference lists. A limited initial search of two databases will be completed to refine search terms, followed by a second comprehensive search using newly refined search terms of all databases and finally hand searching references of included studies. To be included, studies must report on remote ways of providing OAT (including assessment, induction and monitoring) or related psychosocial support; be published in English after 2010. Two researchers will independently screen titles, abstracts and full-text articles considered for inclusion. Data will be extracted onto an agreed template and will undergo a descriptive analysis of the contextual or process-oriented data and simple quantitative analysis using descriptive statistics.Ethics and disseminationResearch ethics approval is not required for this scoping review. The results of this scoping review will inform the development of a national remote model of OAT. The results will be published in peer-reviewed journals and presented at relevant conferences.
U(1) mixing and the weak gravity conjecture
Authors: Benakli Karim , Branchina Carlo , Lafforgue-Marmet Gaëtan 
Published: December 2020

AbstractTiny values for gauge couplings of dark photons allow to suppress their kinetic mixing with ordinary photons. We point out that the weak gravity conjecture predicts consequently low ultraviolet cut-offs where new degrees of freedom might appear. In particular, a mixing angle of $$\mathcal {O}(10^{-15})$$

O
(

10

-
15

)

, required in order to fit the excess reported by XENON1T, corresponds to new physics below $$\mathcal {O}(100)$$

O
(
100
)

TeV, thus accessible at a future circular collider. We show that possible realizations are provided by compactifications with six large extra dimensions and a string scale of order $$\mathcal {O}(100)$$

O
(
100
)

TeV.
Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC Resistant to Second-Line Antiandrogen Therapy
Authors: Lee Geun Taek , Nagaya Naoya , Desantis Jenny , Madura Kiran , Sabaawy Hatem E. , Kim Wun-Jae , Vaz Roy J. , Cruciani Gabriele , Kim Isaac Yi 
Published: December 2020

Abstract
Although second-line antiandrogen therapy (SAT) is the standard of care in men with castration-resistant prostate cancer (CRPC), resistance inevitably occurs. One major proposed mechanism of resistance to SAT involves the emergence of androgen receptor (AR) splice variant-7, AR-V7. Recently, we developed MTX-23 using the principle of proteolysis targeting chimera (PROTAC) to target both AR-V7 and AR-full length (AR-FL). MTX-23 has been designed to simultaneously bind AR's DNA binding domain (DBD) and the Von Hippel–Lindau (VHL) E3 ubiquitin ligase. Immunoblots demonstrated that MTX-23's degradation concentration 50% (DC50) for AR-V7 and AR-FL was 0.37 and 2 μmol/L, respectively. Further studies revealed that MTX-23 inhibited prostate cancer cellular proliferation and increased apoptosis only in androgen-responsive prostate cancer cells. The antiproliferative effect of MTX-23 was partially reversed when either AR-V7 or AR-FL was overexpressed and was completely abrogated when both were overexpressed. To assess the potential therapeutic value of MTX-23, we next generated 12 human prostate cancer cell lines that are resistant to the four FDA-approved SAT agents—abiraterone, enzalutamide, apalutamide, and darolutamide. When resistant cells were treated with MTX-23, decreased cellular proliferation and reduced tumor growth were observed both in vitro and in mice. These results collectively suggest that MTX-23 is a novel PROTAC small molecule that may be effective against SAT-resistant CRPC by degrading both AR-V7 and AR-FL.
Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer
Authors: Daher May , Rezvani Katayoun 
Published: December 2020

AbstractChimeric antigen receptor (CAR) engineering of T cells has revolutionized the field of cellular therapy for the treatment of cancer. Despite this success, autologous CAR-T cells have recognized limitations that have led to the investigation of other immune effector cells as candidates for CAR modification. Recently, natural killer (NK) cells have emerged as safe and effective platforms for CAR engineering. In this article, we review the advantages, challenges, and preclinical and clinical research advances in CAR NK cell engineering for cancer immunotherapy. We also briefly consider the feasibility and potential benefits of applying other immune effector cells as vehicles for CAR expression.Significance:CAR engineering can redirect the specificity of immune effector cells, converting them to a much more potent weapon to combat cancer cells. Expanding this strategy to immune effectors beyond conventional T lymphocytes could overcome some of the limitations of CAR T cells, paving the way for safer and more effective off-the-shelf cellular therapy products.
Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells
Authors: Drijvers Jefte M. , Gillis Jacob E. , Muijlwijk Tara , Nguyen Thao H. , Gaudiano Emily F. , Harris Isaac S. , LaFleur Martin W. , Ringel Alison E. , Yao Cong-Hui , Kurmi Kiran , Juneja Vikram R. , Trombley Justin D. , Haigis Marcia C. , Sharpe Arlene H. 
Published: December 2020

AbstractMetabolic constraints in the tumor microenvironment constitute a barrier to effective antitumor immunity and similarities in the metabolic properties of T cells and cancer cells impede the specific therapeutic targeting of metabolism in either population. To identify distinct metabolic vulnerabilities of CD8+ T cells and cancer cells, we developed a high-throughput in vitro pharmacologic screening platform and used it to measure the cell type–specific sensitivities of activated CD8+ T cells and B16 melanoma cells to a wide array of metabolic perturbations during antigen-specific killing of cancer cells by CD8+ T cells. We illustrated the applicability of this screening platform by showing that CD8+ T cells were more sensitive to ferroptosis induction by inhibitors of glutathione peroxidase 4 (GPX4) than B16 and MC38 cancer cells. Overexpression of ferroptosis suppressor protein 1 (FSP1) or cytosolic GPX4 yielded ferroptosis-resistant CD8+ T cells without compromising their function, while genetic deletion of the ferroptosis sensitivity–promoting enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) protected CD8+ T cells from ferroptosis but impaired antitumor CD8+ T-cell responses. Our screen also revealed high T cell–specific vulnerabilities for compounds targeting NAD+ metabolism or autophagy and endoplasmic reticulum (ER) stress pathways. We focused the current screening effort on metabolic agents. However, this in vitro screening platform may also be valuable for rapid testing of other types of compounds to identify regulators of antitumor CD8+ T-cell function and potential therapeutic targets.
Self-Expandable Nitinol Stents for the Treatment of Nonmalignant Deep Venous Obstruction
Authors: Sebastian Tim , Gnanapiragasam Suvetha , Spirk David , Engelberger Rolf Peter , Moeri Laura , Lodigiani Corrado , Kreuzpointner Robert , Barco Stefano , Kucher Nils 
Published: December 2020

Background:
Angioplasty with stent placement is a therapeutic option for patients with acute thrombotic, postthrombotic, and nonthrombotic obstruction of the iliofemoral veins or inferior vena cava. Previous studies of steel-alloy stents described variable patency rate across indications.

Methods:
The prospective Swiss Venous Stent Registry includes patients treated with self-expandable nitinol stents for deep venous obstruction. Routine follow-up visits include serial duplex ultrasound for stent patency assessment. The primary outcome was primary stent patency. The secondary outcome was venous thromboembolisms. We studied the rate of stent occlusion and potentially contributing factors.

Results:

We included 379 patients: 160 with acute thrombotic, 193 with postthrombotic, and 26 with nonthrombotic deep vein obstruction. The mean age was 46±18 years; 55% were women. The cumulative 3-year primary patency rate was 80.5% (95% CI, 73.0%–88.0%) for acute thrombotic, 59.2% (95% CI, 50.4%–68.0%) for postthrombotic, and 100% for nonthrombotic obstruction (log-rank,
P
<0.0001). Annualized rates of stent occlusion or venous thromboembolism were 7.8 (acute thrombotic), 15.0 (postthrombotic), and 0 (nonthrombotic) events/100 patient-years. In a multivariable Cox regression model, postthrombotic femoral veins at baseline (hazard ratio, 2.64 [95% CI, 1.53–4.56]) and the number of stents (hazard ratio, 1.22 [95% CI, 1.06–1.40]) were associated with stent occlusion after conditioning for age, sex, and clinically relevant factors.

Conclusions:
The rate of stent occlusion (patency loss) and venous thromboembolism varies substantially across indications, also with dedicated venous nitinol stents. Patients with postthrombotic femoral veins and those who received multiple stents were characterized by the highest risk.

Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT02433054.
Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage
Authors: Schatlo Bawarjan , Fung Christian , Stienen Martin N. , Fathi Ali R. , Fandino Javier , Smoll Nicolas R. , Zumofen Daniel , Daniel Roy Thomas , Burkhardt Jan-Karl , Bervini David , Marbacher Serge , Reinert Michael , D´Alonzo Donato , Ahlborn Peter , Mendes Pereira Vitor , Roethlisberger Michel , Seule Martin , Kerkeni Hassen , Remonda Luca , Weyerbrock Astrid , Woernle Kerstin , Venier Alice , Perren Fabienne , Sailer Martin , Robert Thomas , Rohde Veit , Schöni Daniel , Goldberg Johannes , Nevzati Edin , Diepers Michael , Gralla Jan , Z’Graggen Werner , Starnoni Daniele , Woernle Christoph , Maldaner Nicolai , Kulcsar Zsolt , Mostaguir Khaled , Maduri Rodolfo , Eisenring Christian , Bernays René , Ferrari Andrea , Dan-Ura Hiroki , Finkenstädt Sina , Gasche Yvan , Sarrafzadeh Asita , Jakob Stephan M. , Corniola Marco , Baumann Fabian , Regli Luca , Levivier Marc , Hildebrandt Gerhard , Landolt Hans , Mariani Luigi , Guzman Raphael , Beck Jürgen , Raabe Andreas , Keller Emanuela , Bijlenga Philippe , Schaller Karl 
Published: December 2020

Background and Purpose:
The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level.

Methods:
All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded.

Results:
We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0–2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3–5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year.

Conclusions:
The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03245866.
Intravenous Thrombolysis With Tenecteplase in Patients With Large Vessel Occlusions
Authors: Katsanos Aristeidis H. , Safouris Apostolos , Sarraj Amrou , Magoufis Georgios , Leker Ronen R. , Khatri Pooja , Cordonnier Charlotte , Leys Didier , Shoamanesh Ashkan , Ahmed Niaz , Alexandrov Andrei V. , Tsivgoulis Georgios 
Published: December 2020

Background and Purpose:
Accumulating evidence from randomized controlled clinical trials suggests that tenecteplase may represent an effective treatment alternative to alteplase for acute ischemic stroke. In the present systematic review and meta-analysis, we sought to compare the efficacy and safety outcomes of intravenous tenecteplase to intravenous alteplase administration for acute ischemic stroke patients with large vessel occlusions (LVOs).

Methods:
We searched MEDLINE (Medical Literature Analysis and Retrieval System Online) and Scopus for published randomized controlled clinical trials providing outcomes of acute ischemic stroke with confirmed LVO receiving intravenous thrombolysis with either tenecteplase at different doses or alteplase at a standard dose of 0.9 mg/kg. The primary outcome was the odds of modified Rankin Scale score of 0 to 2 at 3 months.

Results:

We included 4 randomized controlled clinical trials including a total of 433 patients. Patients with confirmed LVO receiving tenecteplase had higher odds of modified Rankin Scale scores of 0 to 2 (odds ratio, 2.06 [95% CI, 1.15–3.69]), successful recanalization (odds ratio, 3.05 [95% CI, 1.73–5.40]), and functional improvement defined as 1-point decrease across all modified Rankin Scale grades (common odds ratio, 1.84 [95% CI, 1.18–2.87]) at 3 months compared with patients with confirmed LVO receiving alteplase. There was little or no heterogeneity between the results provided from included studies regarding the aforementioned outcomes (I
2
≤20%). No difference in the outcomes of early neurological improvement, symptomatic intracranial hemorrhage, any intracranial hemorrhage, and the rates of modified Rankin Scale score 0 to 1 or all-cause mortality at 3 months was detected between patients with LVO receiving intravenous thrombolysis with either tenecteplase or alteplase.

Conclusions:
Acute ischemic stroke patients with LVO receiving intravenous thrombolysis with tenecteplase have significantly better recanalization and clinical outcomes compared with patients receiving intravenous alteplase.
Linoleic Acid Status in Cell Membranes Inversely Relates to the Prevalence of Symptomatic Carotid Artery Disease
Authors: Lázaro Iolanda , Cofán Montserrat , Amor Antonio J. , Ortega Emilio , Freitas-Simoes Tania-Marisa , Llull Laura , Amaro Sergio , Mestres Gaspar , Yugueros Xavier , Harris William S. , Riambau Vicente , Sala-Vila Aleix 
Published: December 2020

Background and Purpose:
The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease.

Methods:
We included patients with symptomatic (n=22) and asymptomatic (n=23) carotid artery disease. We determined all-C18:1 trans, linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), and the omega-3 index (sum of eicosapentaenoic [C20:5n3] and docosahexaenoic [C22:6n3] acids) in both red blood cells and carotid plaque phospholipids by gas-chromatography.

Results:

In a multivariate logistic regression analysis, we only observed a significant association for LA, whose red blood cell status was inversely related to symptomatic carotid artery disease (odds ratio, 0.116 [95% CI, 0.022–0.607],
P
=0.011, for each 1-SD increase). A similar result was observed for LA in carotid plaque phospholipids.

Conclusions:
Cell membrane enrichment in LA, which reflects its intake, was inversely related to symptomatic carotid disease. This increases evidence supporting a favorable role of dietary LA in vascular health.
Exploratory Discoveries from Eye-Tracking Tests of
Wertheimer’s Gestalt Patterns
Authors: Hu Xinran , Bačić Dinko 
Published: December 2020

Abstract
In this study, the authors use a novel eye-tracking technology to determine how viewing behavior complies with Wertheimer’s descriptions of Gestalt principles of similarity, proximity, continuation and closure. The results show that viewers respond predictably to most Gestalt principles and that there are nuances to note when it comes to better understanding the role of visual attention in the closure principle and competing principles. In addition, the results reveal a fundamental distinction between visual attention and visual perception. By grasping this critical difference between attention and perception, designers may become more successful in applying Gestalt principles to their design.
Mobile Communications Technologies in Tree Time: The Listening Wood
Authors: Lovett Leah , Hay Duncan , Hudson-Smith Andy , de Jode Martin 
Published: December 2020

Abstract
This article presents a practice-led investigation by a cross-disciplinary team of artists and computer scientists into the potential for mobile and digital communications technologies to engage visitors to London's Hampstead Heath with the histories of its veteran urban trees. Focusing on the application of Internet of Things (IoT) technologies within the arboreal environment for the digital poetic walk, The Listening Wood, it considers the reciprocal impact of “tree time” on the development of “slow tech.”