bluuebunny/crossref_metadata_2025_split huggingface dataset:
XRT-07. LATE-ONSET LYMPHOPENIA DURING CRANIOSPINAL RADIATION IS ASSOCIATED WITH AN INCREASED RISK OF TUMOR RECURRENCE IN NEWLY-DIAGNOSED PEDIATRIC MEDULLOBLASTOMA
Authors: Lindsay Holly , Scheurer Michael , Allam Anthony , McGovern Susan , Chintagumpala Murali , Paulino Arnold 
Published: June 2023

Abstract
A recent publication (PMID 33556478) demonstrated an increased risk of tumor recurrence in patients with newly-diagnosed pediatric medulloblastoma who have decreased lymphocyte counts early in their course of craniospinal radiation (CSI) (weeks 1 and 2). We set out to confirm this data in an independent population of pediatric patients with newly-diagnosed medulloblastoma. We analyzed 54 patients treated from 1997-2013. All patients that received radiation in or after 2007 received protons. Per standard of care, patients with clinically high-risk disease were treated with 36-39.6 Gy CSI while patients with standard-risk disease received 23.4 Gy. Total dose to the primary site of disease ranged from 54-55.8 Gy. The mean patient age at diagnosis was 8 years. 16/54 (30%) patients developed a recurrence at an average of 30.2 months after diagnosis. Lymphocyte counts were analyzed both as a continuous variable and as CTCAE v5.0 grades (grades 0-2 lymphopenia (ALC &gt;/=500) compared to grade 3 and 4 (ALC&lt;500/mm3)) using Cox regression. As expected, patients with M+ disease had increased risk of tumor recurrence (p=0.001). There was no correlation between risk of tumor recurrence and early lymphopenia (weeks 0-3 radiation). However, in both weeks 4 and 5 of radiation, decreases in ALC closely correlated with an increased risk of tumor recurrence (week 4 p=0.038, week 5 p=0.042). Similarly, patients with grade 3/4 lymphopenia at weeks 4 and 5 of radiation had an increased risk of tumor recurrence (week 4 p=0.040, week 5 p=0.008) compared to those with grade 0-2 lymphopenia. In summary, both M+ disease and lymphopenia during weeks 4 and 5 of radiation correlated with an increased risk of tumor recurrence in pediatric medulloblastoma.
TRLS-16. RAPID GENERATION OF EPENDYMOMA MOUSE MODELS FOR PRE-CLINICAL STUDIES
Authors: Ippagunta Siri , Emanus Erik , Bertrand Kelsey , Mack Stephen 
Published: June 2023

Abstract
Pediatric Ependymomas are the leading cause of cancer death among children & adolescents with the 5-year progression free survival (PFS)rate being &lt; 30%. Despite this poor prognosis there has been less success in development of targeted therapies. A major drawback in developing new therapeutics is lack of proper models of disease. Objective of out work has been to develop orthogonal models of various distinct groups of ependymoma to enable understanding of tumor microenvironment thus leading to strategies targeting potential therapeutic sites. In this regard we have developed two models of ZFTA-RELA Ependymoma: 1) In Utero Electroporation Model: DNA plasmids are transfected into developing forebrain, 2) Allograft Model: Primary tumor derived or in vitro transducer cells are allografted into various regions of brain. Further we have shown that these models molecularly resemble patient-derived tumors using RNA sequencing. Using these ZFTA-RELA mouse models we have shown that NSG mice (n=8/treatment group) treated with Selinexor (an XPO1 inhibitor) in combination with chemotherapy have lower tumor volumes by 40% as compared to vehicle or chemotherapy alone treated mice (P&lt;0.05). Furthermore the combination therapy treated mice have improved survival by 28 days as compared to vehicle mice. In conclusion, we have shown that our novel models of ependymomas not only closely resemble disease in patients, but can also be used to develop effective targeted therapies.
The Concept and Measurement of Legislative Backsliding
Authors: Sebők Miklós , Kiss Rebeka , Kovács Ádám 
Published: June 2023

Abstract
The article examines the concept of legislative backsliding and offers a measurement strategy for its empirical analysis. Legislative backsliding is defined as a move away from liberal democracy in four critical dimensions of legislative quality, its public policy; legal-constitutional-formal; procedural; and stability aspects. We operationalise each of these dimensions with their separate indices relying on components such as stakeholder consultations, time passed between bill introduction and passing the law as well as results of constitutional reviews. We use qualitative mini case studies from Hungary, widely considered from 2010 on to be a poster child for democratic backsliding, to illustrate the viability of the proposed measurement strategy. We find that laws which show deficiencies in terms of legislative quality exhibit them in not just but several dimensions. Based on the case studies we offer insights into scaling up the law-level analysis to the level of legislative cycles and show how the legislative quality index can be used to measure macro-level legislative backsliding.
Geminivirus C5 proteins mediate formation of virus complexes at plasmodesmata for viral intercellular movement
Authors: Zhao Siwen , Gong Pan , Liu Jie , Liu Hui , Lozano-Durán Rosa , Zhou Xueping , Li Fangfang 
Published: June 2023

Abstract
Movement proteins (MPs) encoded by plant viruses deliver viral genomes to plasmodesmata (PD) to ensure intracellular and intercellular transport. However, how the MPs encoded by monopartite geminiviruses are targeted to PD is obscure. Here, we demonstrate that the C5 protein of tomato yellow leaf curl virus (TYLCV) anchors to PD during the viral infection following trafficking from the nucleus along microfilaments in Nicotiana benthamiana. C5 could move between cells and partially complement the traffic of a movement-deficient turnip mosaic virus (TuMV) mutant (TuMV-GFP-P3N-PIPO-m1) into adjacent cells. The TYLCV-C5 null mutant (TYLCV-mC5) attenuates viral pathogenicity and decreases viral DNA and protein accumulation, and ectopic overexpression of C5 enhances viral DNA accumulation. Interaction assays between TYLCV-C5 and the other eight viral proteins described in TYLCV reveal that C5 associates with C2 in the nucleus and with V2 in the cytoplasm and at PD. The V2 protein is mainly localized in the nucleus and cytoplasmic granules when expressed alone; in contrast, V2 forms small punctate granules at PD when co-expressed with C5 or in TYLCV-infected cells. The interaction of V2 and C5 also facilitates their nuclear export. Furthermore, C5-mediated PD localization of V2 is conserved in two other geminiviruses. Therefore, this study solves a long-sought-after functional connection between PD and the geminivirus movement and improves our understanding of geminivirus-encoded MPs and their potential cellular and molecular mechanisms.
Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study
Authors: Ben-Joseph Rami H , Saad Ragy , Black Jed , Dabrowski Elizabeth C , Taylor Ben , Gallucci Sophia , Somers Virend K 
Published: June 2023

Abstract

Study Objectives
Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy.

Methods
A retrospective cohort study using IBM MarketScan administrative claims data (2014–2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]).

Conclusion
Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.
Single-session bilateral reduced-settings photodynamic therapy for bilateral chronic central serous chorioretinopathy
Authors: Pauleikhoff Laurenz J.B. , Diederen Roselie M.H. , Feenstra Helena , Schlingemann Reinier O. , van Dijk Elon H.C. , Boon Camiel J.F. 
Published: June 2023

Abstract

Purpose:
We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) that received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid (SRF)) and functional (best-corrected visual acuity (BCVA)) outcomes as well as safety.

Methods:
Patients that underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT) and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded pre- and post-treatment.

Results:
Fifty-five patients were included in this study. Sixty two out of 108 eyes (56%) showed a complete resolution of SRF at first follow-up, which increased to 73/110 (66%) at final follow-up. Mean LogMAR BCVA improved by -0.047 (p = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%), while ELM integrity increased from 22/30 (73%) to 29/30 (97%).

Conclusion:
cCSC patients with bilateral SRF at baseline showed significant anatomical and functional improvement after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted.
Accuracy of New Intraocular Lens Calculation Formulae in eyes undergoing Silicone Oil Removal/Pars Plana Vitrectomy-cataract surgery
Authors: Chen Xu , Zhao He , Xu Yufei , Qin Zuoxin , Ren Jiayun , Wang Lu , Wan Junli , Wang Ziran , Liu Bo , Wu Nan , Liu Xi , Liu Yong 
Published: June 2023

Abstract

Purpose:
To investigate the performance of novel intraocular lens (IOL) calculation formulae (Barrett Universal II [BUII], Emmetropia Verifying Optical [EVO], and Kane) and conventional formulae (Haigis, Hoffer Q, Holladay 1, and SRK/T) in patients who underwent pars plana vitrectomy (PPV) or silicone oil removal (SOR) combined with cataract surgery.

Methods:
In total, 301 eyes from 301 patients underwent PPV/SOR with concomitant cataract surgery were enrolled and divided into four groups according to preoperative diagnosis: silicone oil-filled eyes after PPV, epiretinal membrane, primary retinal detachment (RD), and macular hole.

Results:
BUII exhibited the smallest mean absolute error (MAE) (0.65 diopters [D]) and median absolute error (MedAE) (0.39 D) in total. In patients with RD, each formula exhibited the worst refractive outcomes in diverse vitreoretinal pathologies (P<.01), and no difference in accuracy between the seven formulas was observed (P=.075). For long eyes, the second linear (WK2) version of the Wang-Koch adjustment significantly reduced the MedAE for Holladay 1 and SRK/T (P<.001 and P=.019).

Conclusion:
In combined surgery, both new and conventional formulas using WK2 adjustment demonstrated satisfactory performance, with BUII exhibiting the best overall performance. However, in patients with RD, all seven formulas showed less favorable performance.
The UK Divide: Does having a Pembrolizumab-Chemotherapy option in head and neck cancer matter? Real-world experience of first-line palliative pembrolizumab monotherapy and pembrolizumab-chemotherapy combination in Scotland
Authors: Thapa Alekh , Cowell Anna , Peters Adam , Noble David J , James Allan , Lamb Carolynn , Grose Derek , Vohra Saurabh , Schipani Stefano , Mactier Karen , Mackenzie Joanna , Srinivasan Devraj , Laws Kirsten , Moleron Rafael , Niblock Paddy , Soh Feng Yi , Paterson Claire , Wilson Christina 
Published: June 2023

AbstractObjectivesThe Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma (HNSCC) in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence who approved monotherapy alone in England and Wales. We aimed to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma (HNSCC) in the palliative setting in Scotland.Materials and MethodsWe analysed the electronic records of patients who initiated pembrolizumab-containing treatment between 01/03/2020–30/09/2021. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DOR), disease control rate (DCR). Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival.ResultsOur cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to the KEYNOTE-048 study though our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease.For patients receiving monotherapy (n=76), 12-month and 24-month OS was 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n=15), 12-month OS was 60% (24-month OS had not yet been reached). Experiencing ≥1 irAE (versus no irAEs), of any grade, was associated with favourable OS and PFS for patients receiving monotherapy in both univariable log-rank analysis (median OS 17.4 months versus 8.6 months, respectively, P=0.0033; median PFS 10.9 months versus 3.0 months, respectively, P<0.0001) and multivariable analysis (Cox proportional hazards regression: OS HR: 0.31, P=0.0009; PFS HR: 0.17, P<0.0001).ConclusionOur real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing irAEs are generally a positive marker of PD-L1 inhibitor response.
Genomic insights into the 2022–2023Vibrio choleraeoutbreak in Malawi
Authors: Chaguza Chrispin , Chibwe Innocent , Chaima David , Musicha Patrick , Ndeketa Latif , Kasambara Watipaso , Mhango Chimwemwe , Mseka Upendo L. , Bitilinyu-Bangoh Joseph , Mvula Bernard , Kipandula Wakisa , Bonongwe Patrick , Munthali Richard J. , Ngwira Selemani , Mwendera Chikondi A. , Kalizang’oma Akuzike , Jambo Kondwani C. , Kambalame Dzinkambani , Kamng’ona Arox W. , Steele A Duncan , Chauma-Mwale Annie , Hungerford Daniel , Kagoli Matthew , Nyaga Martin M. , Dube Queen , French Neil , Msefula Chisomo L. , Cunliffe Nigel A. , Jere Khuzwayo C. 
Published: June 2023

AbstractMalawi is experiencing its deadliestVibrio cholerae(Vc) outbreak following devastating cyclones, with >58,000 cases and >1,700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022– 2023Vcoutbreak isolates. Our results demonstrate the predominance of ST69 seventh cholera pandemic El Tor (7PET) strains expressing O1 Ogawa (∼80%) serotype followed by Inaba (∼16%) and typical non-outbreak-associated non-O1/non-ST69 serotypes (∼4%). Phylogenetic reconstruction of the current and historicalVcisolates from Malawi, together with globalVcisolates, suggested the Malawi outbreak strains originated from Asia. The unique antimicrobial resistance and virulence profiles of the 2022–2023 isolates, notably the acquisition of ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage, which causedctxB3toctxB7genotype shift, support the importation hypothesis. These data suggest that the recent importation ofctxB7O1 strains, coupled with climatic changes, may explain the magnitude of the cholera outbreak in Malawi.
Deep-Learning Model for Personalized Prediction of Positive MRSA Culture Results Using Patient’s Time-Series Electronic Health Records
Authors: Nigo Masayuki , Rasmy Laila , Xie Ziqian , Kannadath Bijun Sai , Zhi Degui 
Published: June 2023

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a common bacterial cause of morbidity and mortality. Our deep-learning model (PyTorch_EHR) processes time-series structured electronic health record (EHR) data, including previous cultures and antimicrobial exposures, to predict the lab result of MRSA culture positivity over the next two weeks. After training and evaluation on data from 8,164 MRSA and 22,563 non-MRSA patient events from Memorial Hermann Hospital System, Houston, Texas, the PyTorch_EHR outperformed traditional machine learning methods logistic regression and light GBM (Area Under the Curve of Receiver Operating Curve [AUC]PyTorch_EHR=91.12%, AUCLR=85.91%, AUCLGBM=89.11%). External validation using the MIMIC-IV dataset of 393,713 patient events from a tertiary care center in Boston, Massachusetts, confirmed PyTorch_EHR’s accuracy (AUCPyTorch_EHR=85.50%, AUCLR=83.24%, AUCLGBM=82.48%). The model maintained its accuracy across most subgroup analyses based on infection type. The cumulative incidence curves based on our model successfully high-, medium-, and low-risk patients. This study demonstrates the potential of deep-learning models to predict the presence of MRSA-positive cultures to optimize MRSA antimicrobial therapy.
Lifespan of COVID-19 living guideline recommendations: a survival analysis
Authors: McFarlane Emma , Mercer Toby , Sharp Steve , Hunter Debra , Kelley Kate , Glen Fiona , Majeed Maria 
Published: June 2023

AbstractBackgroundNICE has maintained a portfolio of COVID-19 living guidelines since March 2020. Recommendations within these living guidelines are subject to continuous surveillance and updates in response to triggers. However, the lifespan of individual living guideline recommendations and features that may impact on whether a recommendation becomes out of date sooner, is unknown.ObjectivesThis study aimed to describe the length of time NICE COVID-19 living guideline recommendations have remained valid.MethodsAll guidelines within NICE’s COVID-19 portfolio were included to determine the lifespan of living guideline recommendations. Data were collected on all recommendations that had been developed, undergone surveillance or updated between 1 March 2020 and 31 August 2022. Information on initial publication date, decision to update, and update publication date was extracted. Updates were labelled as major changes in evidence synthesis or minor changes without a substantial change in evidence base. Any recommendation that had not been updated or withdrawn was censored. Survival analysis (Kaplan-Meier Curve) was carried out to determine the lifespan of recommendations.ResultsOverall, 26 COVID-19 living guidelines and 1182 recommendations were included in the analysis. Living recommendations had median survival time of 739 days (IQR: 332, 781). Based on recommendation type, intervention recommendations had a shorter survival time (354 days, IQR 312, 775) compared to diagnosis (368 days, IQR: 328, 795), patient experience (733 days, IQR: 345, 795) and service delivery (739 days, IQR: 643, 781). Within intervention type, pharmacological recommendations had shortest survival time versus non-pharmacological recommendations [335 days (IQR: 161, 775) vs 775 days (IQR: 354, 775)]. Updates were published an average of 29.12 days following a surveillance decision.ConclusionWithin living guidelines, some recommendations need to be updated sooner than others. This study outlines the value of a flexible responsive approach to surveillance within the living mode according to pace of change and expectation of update triggers.What is new?Key findingsWithin the context of a living guideline, some recommendations will become out of date sooner than others.What this adds to what was known?This study supports the concept of prioritising recommendations within a guideline to be living.What is the implication and what should change now?Guideline developers should consider which recommendations within a living guideline would have the most value in being maintained as living to optimise resources.
Assessment of fetal corpus callosum biometry by 3D super-resolution reconstructed T2-weighted MRI
Authors: Lamon Samuel , de Dumast Priscille , Dunet Vincent , Pomar Léo , Vial Yvan , Koob Mériam , Cuadra Meritxell Bach 
Published: June 2023

AbstractObjectiveTo assess the accuracy of corpus callosum (CC) and its sub-segments’ biometry by super-resolution (SR) 3-dimensional fetal brain MRI in comparison to measurements in 2-dimensional or 3-dimensional ultrasonography (US) and clinical low-resolution T2-weighted MRI sequences (T2WS).MethodWe performed fetal brain biometry of the overall length of the CC, the heights of its sub-segments and its area by two observers (one junior observer, obs1, and one senior pediatric neuroradiologist, obs2) in a cohort of 57 subjects (between 21 and 35 weeks of gestational age (GA), including 11 cases of partial agenesis of CC). Obs1 made measures on US, T2WS, and SR, and obs2 in T2WS and SR. Regression curves of CC biometry with GA were done. Statistical analysis of inter-modality (US vs. T2WS, US vs. SR, and T2WS vs SR) agreement for single observer (obs1) and inter-modality (US vs. T2WS, and US vs. SR) between observers (obs1 vs obs2) were also conducted.ResultsOur study shows a high concordance through GA of CC measurements performed by SR in comparison with US, with a higher agreement than biometry based on T2WS clinical acquisitions. For obs1, SR measurements are highly concordant to US (except for the genu and the CC length) and helps visualizing the splenium. For obs2, SR measurements are highly concordant to US, except for the rostrum and the CC length. Rostrum and Genu (forming the anterior callosum) are the subsegments with larger variability. Regression curves by SR overlay more accurately those from the literature (by US) for the CC length, the splenium and the body than T2WS.ConclusionSuper-resolution MRI could be used in the biometrical assessment of the CC, providing measurements close to US, except for the anterior part of the CC Thanks to its 3D-visualisation capacity and improved through plane spatial resolution, it allows to perform CC biometry more frequently than on T2WS.