bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epley manoeuvre for posterior semicircular canal benign paroxysmal positional vertigo in people with multiple sclerosis: protocol of a randomised controlled trial
Authors: García-Muñoz Cristina , Cortés-Vega María-Dolores , Hernández-Rodríguez Juan Carlos , Palomo-Carrión Rocio , Martín-Valero Rocío , Casuso-Holgado María Jesús 
Published: March 2021

IntroductionVestibular disorders in multiple sclerosis (MS) could have central or peripheral origin. Although the central aetiology is the most expected in MS, peripheral damage is also significant in this disease. The most prevalent effect of vestibular peripheral damage is benign paroxysmal positional vertigo (BPPV). Impairments of the posterior semicircular canals represent 60%–90% of cases of BPPV. The standard gold treatment for this syndrome is the Epley manoeuvre (EM), the effectiveness of which has been poorly studied in patients with MS. Only one retrospective research study and a case study have reported encouraging results for EM with regard to resolution of posterior semicircular canal BPPV. The aim of this future randomised controlled trial (RCT) is to assess the effectiveness of EM for BPPV in participants with MS compared with a sham manoeuvre.Methods and analysisThe current protocol describes an RCT with two-arm, parallel-group design. Randomisation, concealed allocation and double-blinding will be conducted to reduce possible bias. Participants and evaluators will be blinded to group allocation. At least 80 participants who meet all eligibility criteria will be recruited. Participants will have the EM or sham manoeuvre performed within the experimental or control group, respectively. The primary outcome of the study is changes in the Dix Hallpike test. The secondary outcome will be changes in self-perceived scales: Dizziness Handicap Inventory and Vestibular Disorders Activities of Daily Living Scale. The sample will be evaluated at baseline, immediately after the intervention and 48 hours postintervention.Ethics and disseminationThe study was approved by the Andalusian Review Board and Ethics Committee of Virgen Macarena-Virgen del Rocio Hospitals (ID 0107-N-20, 23 July 2020). The results of the research will be disseminated by the investigators to peer-reviewed journals.Trial registration numberNCT04578262.
Online Bridging Program for new international palliative medicine fellows: development and evaluation
Authors: Al-Mohawes Hanan , Amante Madelaine , Hannon Breffni , Zimmermann Camilla , Kaya Ebru , al-Awamer Ahmed 
Published: March 2021

ObjectivesInternational medical graduates (IMGs) who pursue additional training in another country may encounter unique challenges that compromise their learning experience. This paper describes the development of an Online Bridging Program in the Division of Palliative Care at the University Health Network Toronto and examines its effectiveness in improving IMGs’ readiness for Canadian fellowship training.MethodsThe annual Online Bridging Program was developed to help new IMGs transitioning to Canadian palliative fellowship using Kern’s framework for curriculum development. Following a needs assessment, eight online modules with weekly live sessions were developed and underwent external content validation and usability tests. After each iteration, the programme was improved based on participant feedback. Evaluation was conducted first through an online survey immediately on completion of the programme and then through qualitative interviews 6 months into the fellowship. The interviews were analysed using Braun and Clarke’s model for thematic analysis.ResultsNine IMGs participated in the Online Bridging Program from 2018 to 2020. All nine participated in the survey and eight in the interviews. Responses to the online survey were almost unanimously positive, suggesting its effectiveness in assisting the IMGs’ transitions into fellowship. The interviews revealed four major themes: the importance of combining online modules and live sessions, reducing the fellows’ anxiety and easing the transition into their new role, an improved overall learning experience and recognising online format limitations.ConclusionThe Online Bridging Program effectively eased IMG palliative medicine fellows’ transition into training and enhanced their learning experience.
Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry
Authors: Bertaina Maurizio , Nuñez-Gil Ivan J , Franchin Luca , Fernández Rozas Inmaculada , Arroyo-Espliguero Ramón , Viana-Llamas María C , Romero Rodolfo , Maroun Eid Charbel , Uribarri Aitor , Becerra-Muñoz Víctor Manuel , Huang Jia , Alfonso Emilio , Marmol-Mosquera Fernando , Ugo Fabrizio , Cerrato Enrico , Fernandez-Presa Lucia , Raposeiras Roubin Sergio , Feltes Guzman Gisela , Gonzalez Adelina , Abumayyaleh Mohammad , Fernandez-Ortiz Antonio , Macaya Carlos , Estrada Vicente 
Published: March 2021

BackgroundThe COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF).MethodsWe conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated.Results1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint.ConclusionNIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis.Trial registration numbersNCT04334291/EUPAS34399.
Dural venous system: angiographic technique and correlation with ex vivo investigations
Authors: Shapiro Maksim , Raz Eytan , Nossek Erez , Srivatanakul Kittipong , Walker Melanie , Mir Osman , Nelson Peter Kim 
Published: March 2021

BackgroundThe dural vasculature plays a key role in several important conditions, including dural fistulas and subdural collections. While in vivo investigations of intrinsic dural arterial angioarchitecture are rare, no angiographic studies of dural venous drainage exist to our knowledge.ObjectiveTo describe methods by which dural venous drainage might be visualized with current angiographic equipment and technique, and to correlate our results with existing ex vivo literature.MethodsDigital subtraction angiography and 3D angiography (rotational and Dyna CT) of dural neurovasculature were acquired in the context of subdural hematoma embolization and normal dura. Protocols for visualization of dural venous drainage were established, and findings correlated with ex vivo studies.ResultsMeningeal arteries supply both the skull and dura. Normal dural enhancement is accentuated by the presence of hypervascular membranes. Intrinsic meningeal veins/sinuses parallel outer layer arteries with well-known tram-tracking appearance. Dura adjacent to main arterial trunks drains via skull base foramina into the pterygopalatine venous plexus, or via emissary veins into the temporalis venous plexus. Dura near the sinuses drains into venous pouches adjacent to the sinus, before emptying into the sinus proper—possibly the same pouches implicated in the angioarchitecture of dural fistulas. Finally, posterior temporoparietal convexity dura, situated in a watershed-like region between middle and posterior meningeal territories, frequently empties into diploic and emissary veins of the skull. Wide variation in balance is expected between these three routes. Drainage patterns appear to correlate with venous embryologic investigations of Padget and ex vivo studies in adults.ConclusionsContinued attention to dural venous drainage may prove useful in the diagnosis and management of dural-based vascular diseases.
China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design
Authors: Liu Liping , Wang Yilong , Xie Xuewei , Liu Dacheng , Wang Aili , Wang Penglian , Shen Suwen , Zhong Chongke , Wei Yufei , Xu Tan , Pan Yuesong , Jiang Yong , Meng Xia , Wang David , Zhang Yonghong , He Jiang , Wang Yongjun 
Published: March 2021

BackgroundsIncreased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown.AimsWe aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke.DesignThe China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%–20% reduction within the first 24 hours, and achieving an average BP level of <140/90 mm Hg within 5 days. Patients in the delayed treatment group will discontinue any antihypertension medications for the first 7 days of randomisation, and will receive antihypertensive therapy achieving a BP goal of <140/90 mm Hg after 7 days.ConclusionThe CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke.Trial registration numberNCT03479554.
A new generation of sensors and monitoring tools to support climate-smart forestry practices
Authors: Torresan Chiara , Benito Garzón Marta , O’Grady Michael , Robson Thomas Matthew , Picchi Gianni , Panzacchi Pietro , Tomelleri Enrico , Smith Melanie , Marshall John , Wingate Lisa , Tognetti Roberto , Rustad Lindsey E. , Kneeshaw Dan 
Published: March 2021

Climate-smart forestry (CSF) is an emerging branch of sustainable adaptive forest management aimed at enhancing the potential of forests to adapt to and mitigate climate change. It relies on much higher data requirements than traditional forestry. These data requirements can be met by new devices that support continuous, in situ monitoring of forest conditions in real time. We propose a comprehensive network of sensors, i.e., a wireless sensor network (WSN), that can be part of a worldwide network of interconnected uniquely addressable objects, an Internet of Things (IoT), which can make data available in near real time to multiple stakeholders, including scientists, foresters, and forest managers, and may partially motivate citizens to participate in big data collection. The use of in situ sources of monitoring data as ground-truthed training data for remotely sensed data can boost forest monitoring by increasing the spatial and temporal scales of the monitoring, leading to a better understanding of forest processes and potential threats. Here, some of the key developments and applications of these sensors are outlined, together with guidelines for data management. Examples are given of their deployment to detect early warning signals (EWS) of ecosystem regime shifts in terms of forest productivity, health, and biodiversity. Analysis of the strategic use of these tools highlights the opportunities for engaging citizens and forest managers in this new generation of forest monitoring.
Study of the threshold anomaly effect in the reaction $$^{7}$$Li+$$^{208}$$Pb at energies around the Coulomb barrier
Authors: Vardaci E. , Rath P. K. , Mazzocco M. , Nitto A. Di , Rana G. La , Parascandolo C. , Pierroutsakou D. , Romoli M. , Boiano A. , Vanzanella A. , Cinausero M. , Prete G. , Gelli N. , Lucarelli F. , Mazzocchi C. , Commara M. La , Fortunato L. , Guglielmetti A. , Soramel F. , Stroe L. , Signorini C. 
Published: March 2021

AbstractThe elastic scattering in the reaction $$^{7}$$

7

Li+$$^{208}$$

208

Pb was investigated in the bombarding energy range from 25 to 39 MeV. The real and imaginary parts of the optical potential were analyzed by using a phenomenological potential. A dispersion relation analysis is presented in order to investigate the threshold anomaly effect. It is concluded that $$^{7}$$

7

Li has an intermediate behavior between the tightly bound nuclei such as $$^{16}$$

16

O and the loosely bound nuclei such as $$^{6}$$

6

Li where the lack of the threshold anomaly is unambiguously observed. Reaction cross sections are also extracted from the elastic scattering data and its comparison with the ones of other systems has been performed to draw hints on the effect of the breakup channel.
A spectroscopical study of H$$_{2}$$ emission in a simply magnetized toroidal plasma
Authors: Barni R. , Alex P. , Ghorbanpour E. , Riccardi C. 
Published: March 2021

Abstract
A noninvasive diagnostic technique relying on optical emission spectroscopy is used for studying plasma confined in a purely toroidal magnetic field. Visible emission lines of molecular hydrogen were specifically targeted. Bi-dimensional structures and poloidal plasma profiles were reconstructed from the emissivity distribution of hydrogen Fulcher system using a tomographic method. A few details concerning the methods employed to capture different emission viewlines, data reduction and tomographic reconstruction techniques are also addressed. We report also the first measurement of the excitation temperature of the $$\text {H}_2$$

H
2

[3c] level in the center of the plasma column, $$T_{\mathrm{exc}}=0.67 \pm 0.11$$

T
exc

=
0.67
±
0.11

eV.

Graphic Abstract
Review of The Theory of Quantum Information John Watrous
Authors: Fenner Stephen A. 
Published: March 2021

This is an extremely clear, carefully written book that covers the most important results in the sprawling field of quantum information. It is perfect for a reference, self-study, or a graduate course in quantum information. It makes no attempt to be broad or encyclopedic, but instead goes deep into the core topics. The definitions and theorems are all precisely worded, and (starting in Chapter 2) all results have complete proofs, making the book largely self-contained. The book focuses heavily on the mathematical results and nuts-and-bolts techniques underpinning current research, and as such gives the reader a thorough and flexible toolkit for proving new results. If you are just looking for a broad but cursory survey of the field, then this is probably not the book for you. If, however, you want a working knowledge of the core results and proof techniques of quantum information with an eye toward doing cutting-edge research in the field, then this book will be an indispensable addition to your library.
The mathematical theory of quantum information studies the ultimate abilities and limits of transmitting and processing information using the laws of quantum mechanics. It owes much of its motivation to classical information theory, which was largely developed by Claude Shannon in the mid 20th century, and to quantum mechanics itself (of course). It addresses basic questions like: how much information can be transmitted through quantum channels, noisy or otherwise, and how entanglement helps. The theory informs, and is informed by, its sister disciplines of quantum computation and quantum communication (which overlap with physics and computer science), although in some sense it is more fundamental. Though he occasionally mentions applications to these other areas, Watrous seats his book squarely in the realm of pure mathematics.
Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Breast Cancer in BRCA1 Mutation Carriers
Authors: Hu Li , Su Liming , Cheng Hainan , Mo Chunling , Ouyang Tao , Li Jinfeng , Wang Tianfeng , Fan Zhaoqing , Fan Tie , Lin Benyao , Zhang Jianguang , Xie Yuntao 
Published: March 2021

Abstract

The cell of origin and the development of breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)–positive breast cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from the breast cancer tissues and adjacent or prophylactic normal breast tissues from four BRCA1 mutation carriers and three noncarriers. Whole-exome sequencing was performed on breast tumors from the four BRCA1 mutation carriers; for validation, bulk RNA-seq was performed on adjacent normal breast tissues from eight additional BRCA1 mutation carriers and 14 noncarriers. Correlation analyses suggested that breast cancers in BRCA1 mutation carriers might originate from luminal cells. The aberrant luminal progenitor cells with impaired differentiation were significantly increased in normal breast tissues in BRCA1 mutation carriers compared with noncarriers. These observations were further validated by the bulk RNA-seq data from additional BRCA1 mutation carriers. These data suggest that the cell of origin of basal-like breast tumors (ERneg) in BRCA1 mutation carriers might be luminal progenitor cells. The expression of TP53 and BRCA1 was decreased in luminal progenitor cells from normal breast tissue in BRCA1 mutation carriers, which might trigger the basal/mesenchymal transition of luminal progenitors and might result in basal-like tumor development. Furthermore, ERhigh luminal tumors might originate from mature luminal cells. Our study provides in-depth evidence regarding the cells of origin of different breast cancer subtypes in BRCA1 mutation carriers.

Significance:
Single-cell RNA-seq data indicate that basal-like breast cancer (ERneg) might originate from luminal progenitors, and ERhigh luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers.
Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance
Authors: Zhang Xu , Maity Tapan K. , Ross Karen E. , Qi Yue , Cultraro Constance M. , Bahta Meriam , Pitts Stephanie , Keswani Meghana , Gao Shaojian , Nguyen Khoa Dang P. , Cowart Julie , Kirkali Fatos , Wu Cathy , Guha Udayan 
Published: March 2021

Abstract

Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial–mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both in vitro and in vivo. Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance.

Significance:
Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance.
Integrated Screens Identify CDK1 as a Therapeutic Target in Advanced Gastrointestinal Stromal Tumors
Authors: Lu Xiaojing , Pang Yuzhi , Cao Hui , Liu Xiaoxiao , Tu Lin , Shen Yanying , Jia Xiaona , Lee Jen-Chieh , Wang Yuexiang 
Published: March 2021

Abstract

Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. It is unclear whether there are other therapeutic targets in advanced GIST. Using genome-wide transcriptomic profiling of advanced versus early-stage GIST and CRISPR knockout functional screens, we demonstrate that CDK1 is frequently highly expressed in advanced GIST but not in early-stage GIST across three patient cohorts. High expression of CDK1 was associated with malignancy in GIST. CDK1 was critically required for advanced GIST, including imatinib-resistant GIST. CDK1 ablation led to robust proliferation inhibition. A mass spectrometry-based proteomics screen further revealed that AKT is a novel substrate of CDK1 kinase in GIST. CDK1 bound AKT and regulated its phosphorylation, thereby promoting GIST proliferation and progression. Importantly, a pharmacologic inhibitor of CDK1, RO-3306, disrupted GIST cell proliferation in CDK1 highly expressed GIST but not in CDK1-negative GIST cells and nontransformed fibroblast cells. Treatment with RO-3306 reduced tumor growth in both imatinib-resistant and imatinib-sensitive GIST xenograft mouse models. Our findings suggest that CDK1 represents a druggable therapeutic target in GIST and warrants further testing in clinical trials.

Significance:
These findings propose CDK1 as a novel cell-cycle–independent vulnerability in gastrointestinal stromal tumors, representing a new therapeutic opportunity for patients with advanced disease.