bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinician estimates of prognosis: accuracy and impact—a retrospective inpatient hospice study
Authors: Tavabie Simon , Hargreaves Anya , Tookman Adrian , Stone Patrick 
Published: December 2021

ObjectiveTo evaluate the accuracy and impact of clinicians’ estimates of prognosis (CEP) in patients referred for hospice inpatient care.MethodsRetrospective review of 12 months’ referrals to a London hospice unit. Data extracted included date of referral, admission and death and CEP.ResultsN=383. Mean age 72 years (range 24–101). CEP accuracy: Median survival where CEP was ‘days’ (n=141) was 7 days (0–164); CEP ‘weeks’ (n=167) was 14 days (1–538); CEP ‘months’ (n=75) was 32 days (2–507). Kaplan-Meier survival curves showed significant difference between CEP of ‘months’ and ‘weeks’ (p<0.0001); ‘months’ and ‘days’ (p<0.0001); but not ‘days’ and ‘weeks’ (p=0.1). CEP impact: admission waiting time increased with increasing CEP: CEP ‘days’ (n=105) median 1 day (0–14); CEP ‘weeks’ (n=154) median 2 days (0–46); CEP ‘months’ (n=69) median 3 days (0–46). No significant difference was demonstrated in the number of discharge planning conversations between groups (0.9/patient).ConclusionsCEP was accurate in over half of the cases but did not adequately discriminate between those with prognoses of days or weeks. CEP may affect the prioritisation given to patients by hospices. Inaccurate CEP on referral forms may influence other aspects of care; however, further research is needed.
Association between the number of endotracheal intubation attempts and rates of adverse events in a paediatric emergency department
Authors: Abid Edir S , Miller Kelsey A , Monuteaux Michael C , Nagler Joshua 
Published: December 2021

BackgroundChallenges in emergent airway management in children can affect intubation success. It is unknown if number of endotracheal intubation attempts is associated with rates of adverse events in the paediatric ED setting.ObjectiveWe sought to (1) Identify rates of intubation-related adverse events, (2) Evaluate the association between the number of intubation attempts and adverse events in a paediatric ED, and (3) Determine the effect of videolaryngoscopy on these associations.Design and methodsWe performed a retrospective observational study of patients who underwent endotracheal intubation in a paediatric ED in the USA between January 2004 and December 2018. Data on patient-related, provider-related and procedure-related characteristics were obtained from a quality assurance database and the health record. Our primary outcome was frequency of intubation-related adverse events, categorised as major and minor. The number of intubation attempts was trichotomised to 1, 2, and 3 or greater. Multivariable logistic regression models were used to determine the relationship between the number of intubation attempts and odds of adverse events, adjusting for demographic and clinical factors.ResultsDuring the study period, 628 patients were intubated in the ED. The overall rate of adverse events was 39%. Hypoxia (19%) was the most common major event and mainstem intubation (15%) the most common minor event. 72% patients were successfully intubated on the first attempt. With two intubation attempts, the adjusted odds of any adverse event were 3.26 (95% CI 2.11 to 5.03) and with ≥3 attempts the odds were 4.59 (95% CI 2.23 to 9.46). Odds similarly increased in analyses of both major and minor adverse events. This association was consistent for both traditional and videolaryngoscopy.ConclusionIncreasing number of endotracheal intubation attempts was associated with higher odds of adverse events. Efforts to optimise first attempt success in children undergoing intubation may mitigate this risk and improve clinical outcomes.
Phenotypic spectrum and clinical course of single large-scale mitochondrial DNA deletion disease in the paediatric population: a multicentre study
Authors: Björkman Kristoffer , Vissing John , Østergaard Elsebet , Bindoff Laurence A , de Coo Irenaeus F M , Engvall Martin , Hikmat Omar , Isohanni Pirjo , Kollberg Gittan , Lindberg Christopher , Majamaa Kari , Naess Karin , Uusimaa Johanna , Tulinius Mar , Darin Niklas 
Published: December 2021

BackgroundLarge-scale mitochondrial DNA deletions (LMD) are a common genetic cause of mitochondrial disease and give rise to a wide range of clinical features. Lack of longitudinal data means the natural history remains unclear. This study was undertaken to describe the clinical spectrum in a large cohort of patients with paediatric disease onset.MethodsA retrospective multicentre study was performed in patients with clinical onset <16 years of age, diagnosed and followed in seven European mitochondrial disease centres.ResultsA total of 80 patients were included. The average age at disease onset and at last examination was 10 and 31 years, respectively. The median time from disease onset to death was 11.5 years. Pearson syndrome was present in 21%, Kearns-Sayre syndrome spectrum disorder in 50% and progressive external ophthalmoplegia in 29% of patients. Haematological abnormalities were the hallmark of the disease in preschool children, while the most common presentations in older patients were ptosis and external ophthalmoplegia. Skeletal muscle involvement was found in 65% and exercise intolerance in 25% of the patients. Central nervous system involvement was frequent, with variable presence of ataxia (40%), cognitive involvement (36%) and stroke-like episodes (9%). Other common features were pigmentary retinopathy (46%), short stature (42%), hearing impairment (39%), cardiac disease (39%), diabetes mellitus (25%) and renal disease (19%).ConclusionOur study provides new insights into the phenotypic spectrum of childhood-onset, LMD-associated syndromes. We found a wider spectrum of more prevalent multisystem involvement compared with previous studies, most likely related to a longer time of follow-up.
Evaluation of direct-to-angiography suite (DTAS) and conventional clinical pathways in stroke care: a simulation study
Authors: Bastani Mehrad , White Timothy G , Martinez Gabriela , Ohara Joseph , Sangha Kinpritma , Gribko Michele , Katz Jeffrey M , Woo Henry H , Boltyenkov Artem T , Wang Jason , Rula Elizabeth , Naidich Jason J , Sanelli Pina C 
Published: December 2021

BackgroundRapid time to reperfusion is essential to minimize morbidity and mortality in acute ischemic stroke due to large vessel occlusion (LVO). We aimed to evaluate the workflow times when utilizing a direct-to-angiography suite (DTAS) pathway for patients with suspected stroke presenting at a comprehensive stroke center compared with a conventional CT pathway.MethodsWe developed a discrete-event simulation (DES) model to evaluate DTAS workflow timelines compared with a conventional CT pathway, varying the admission NIHSS score treatment eligibility criteria. Model parameters were estimated based on 2 year observational data from our institution. Sensitivity analyses of simulation parameters were performed to assess the impact of patient volume and baseline utilization of angiography suites on workflow times utilizing DTAS.ResultsSimulation modeling of stroke patients (SimStroke) demonstrated door-to-reperfusion time savings of 0.2–3.5 min (p=0.05) for a range of DTAS eligibility criteria (ie, last known well to arrival <6 hours and National Institutes of Health Stroke Scale ≥6–11), when compared with the conventional stroke care pathway. Sensitivity analyses revealed that DTAS time savings is highly dependent on baseline utilization of angiography suites.ConclusionsThe results of the SimStroke model showed comparable time intervals for door-to-reperfusion for DTAS compared with a conventional stroke care pathway. However, the DTAS pathway was very sensitive to baseline angiography suite utilization, with even a 10% increase eliminating the advantages of DTAS compared with the conventional pathway. Given the minimal time savings modeled here, further investigation of implementing the DTAS pathway in clinical care is warranted.
Evaluation of a laboratory-developed multiplex real-time PCR assay for diagnosis of syphilis, herpes and chancroid genital ulcers in four public health laboratories in the USA
Authors: Koralur Munegowda , Chen Cheng Y , Pillay Allan , White Brunie , Pettus Kevin , Chi Kai-Hua , Stringer Joey , Aroh Chukwuemika , Dasu Trivikram , Bhattacharyya Sanjib , Perkins Keith , Chen Jenny , Riner Diana , Soehnlen Marty , Cao Weiping , Gaynor Anne M , Kersh Ellen N 
Published: December 2021

ObjectiveTo evaluate the field performance of a multiplex PCR (M-PCR) assay for detection of herpes simplex virus (HSV)-1 and HSV-2, Treponema pallidum (T. pallidum) and Haemophilus ducreyi (H. ducreyi) in genital ulcer disease (GUD) specimens.MethodsGUD M-PCR was performed on 186 remnant specimens, previously collected for HSV testing, by four public health laboratories (PHLs) and the Laboratory Reference and Research Branch (LRRB) at the Centers for Disease Control and Prevention. The results from the PHLs were compared with those of LRRB, which served as the reference testing method, and percentage agreement was calculated.ResultsHSV was detected in 31 of 52 (59.6%), 20 of 40 (50%), 43 of 44 (97.7%) and 19 of 50 (38.0%) specimens from PHL1, PHL2, PHL3 and PHL4, respectively. There were seven discrepant results for HSV, and the overall percent agreement between the PHLs and the LRRB was 94%–100%, with a kappa value of 0.922, which demonstrates high agreement. T. pallidum was identified in 7 of 51 (13.7%) specimens from PHL1 with 94.1% agreement and in 2 of 40 (5.0%) specimens from PHL2 with 100% agreement. The LRRB identified three additional T. pallidum-positive specimens from PHL1. The kappa value (0.849) for T. pallidum testing suggests good agreement. Consistent with the LRRB results, no T. pallidum was detected in specimens from PHL3 and PHL4, and H. ducreyi was not detected at any of the study sites.ConclusionsThe GUD M-PCR assay performed well in four independent PHLs and 12 suspected syphilis cases were identified in this study. The M-PCR assay could provide improved diagnostic options for GUD infections in state and local PHLs.
A model to predict adherence to antiretroviral therapy among people living with HIV
Authors: Chen Hui , Long Rusi , Hu Tian , Chen Yaqi , Wang Rongxi , Liu Yujie , Liu Shangbin , Xu Chen , Yu Xiaoyue , Chang Ruijie , Wang Huwen , Zhang Kechun , Hu Fan , Cai Yong 
Published: December 2021

ObjectivesSuboptimal adherence to antiretroviral therapy (ART) dramatically hampers the achievement of the UNAIDS HIV treatment targets. This study aimed to develop a theory-informed predictive model for ART adherence based on data from Chinese.MethodsA cross-sectional study was conducted in Shenzhen, China, in December 2020. Participants were recruited through snowball sampling, completing a survey that included sociodemographic characteristics, HIV clinical information, Information-Motivation-Behavioural Skills (IMB) constructs and adherence to ART. CD4 counts and HIV viral load were extracted from medical records. A model to predict ART adherence was developed from a multivariable logistic regression with significant predictors selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. To evaluate the performance of the model, we tested the discriminatory capacity using the concordance index (C-index) and calibration accuracy using the Hosmer and Lemeshow test.ResultsThe average age of the 651 people living with HIV (PLHIV) in the training group was 34.1±8.4 years, with 20.1% reporting suboptimal adherence. The mean age of the 276 PLHIV in the validation group was 33.9±8.2 years, and the prevalence of poor adherence was 22.1%. The suboptimal adherence model incorporates five predictors: education level, alcohol use, side effects, objective abilities and self-efficacy. Constructed by those predictors, the model showed a C-index of 0.739 (95% CI 0.703 to 0.772) in internal validation, which was confirmed be 0.717 via bootstrapping validation and remained modest in temporal validation (C-index 0.676). The calibration capacity was acceptable both in the training and in the validation groups (p>0.05).ConclusionsOur model accurately estimates ART adherence behaviours. The prediction tool can help identify individuals at greater risk for poor adherence and guide tailored interventions to optimise adherence.
Examination of the association between state tobacco control spending and the demand for electronic cigarettes by high school students
Authors: Tauras John , Diaz Megan C , Schillo Barbara , Vallone Donna 
Published: December 2021

BackgroundWhile much is known about the influence of tobacco control spending on the demand for conventional cigarettes, little is known about the effects of tobacco control spending on the demand for electronic cigarettes (e-cigarettes). This study provides the first evidence on the association between state tobacco control spending and high school student vaping in the USA.MethodsWe used data from the 2015 through 2019 National Youth Risk Behavior Surveys to estimate vaping prevalence and vaping intensity demand equations. We employed logistic regressions to estimate the vaping prevalence equations and generalised linear models with log-link and gamma distribution to estimate the vaping intensity equations.ResultsWe found evidence that funding for state tobacco control programmes had a significant negative association with both vaping prevalence and vaping intensity among high school students in the USA. Our results indicate that a 50% increase in state spending on tobacco control during the time of the surveys would have been associated with a 7.46% lower high school student vaping prevalence rate than what was observed.ConclusionsThere has been a dramatic increase in e-cigarette use by adolescents and young adults in the USA. The rapid rise in e-cigarette use has been a significant source of public policy concern for many states. The results of this study strongly suggest that increased spending on tobacco control programmes will reduce the number of high school students who vape and will decrease the number of days vaping products are used by high school students. These findings should be extremely valuable to policymakers interested in curbing the youth vaping epidemic in the USA.
Two-year optical site characterization for the Pacific Ocean Neutrino Experiment (P-ONE) in the Cascadia Basin
Authors: Bailly Nicolai , Bedard Jeannette , Böhmer Michael , Bosma Jeff , Brussow Dirk , Cheng Jonathan , Clark Ken , Croteau Beckey , Danninger Matthias , De Leo Fabio , Deis Nathan , Ens Matthew , Fox Rowan , Fruck Christian , Gärtner Andreas , Gernhäuser Roman , Ghuman Dilraj , Grant Darren , He Helen , Henningsen Felix , Holzapfel Kilian , Hotte Ryan , Jenkyns Reyna , Johnson Hamish , Katil Akanksha , Kopper Claudio , Krauss Carsten B. , Kulin Ian , Leismüller Klaus , Leys Sally , Lin Tony , Macoun Paul , Man Matthew , McElroy Thomas , Meighen-Berger Stephan , Michel Jan , Moore Roger , Morley Mike , Papp Laszlo , Pirenne Benoit , Qiu Tom , Rankin Mark , Rea Immacolata Carmen , Resconi Elisa , Round Adrian , Ruskey Albert , Rutley Ryan , Spannfellner Christian , Stacho Jakub , Timmerman Ross , Tomlin Meghan , Tradewell Matt , Traxler Michael , Uganecz Matt , Wagner Seann , Yañez Juan Pablo , Zheng Yinsong 
Published: December 2021

AbstractThe STRings for Absorption length in Water (STRAW) are the first in a series of pathfinders for the Pacific Ocean Neutrino Experiment (P-ONE), a future large-scale neutrino telescope in the north-eastern Pacific Ocean. STRAW consists of two $$150\,\mathrm {m}$$

150

m

long mooring lines instrumented with optical emitters and detectors. The pathfinder is designed to measure the attenuation length of the water and perform a long-term assessment of the optical background at the future P-ONE site. After 2 years of continuous operation, measurements from STRAW show an optical attenuation length of about 28 m at $$450\,\mathrm {nm}$$

450

nm

. Additionally, the data allow a study of the ambient undersea background. The overall optical environment reported here is comparable to other deep-water neutrino telescopes and qualifies the site for the deployment of P-ONE.
A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture
Authors: Chakrabarty Sanjiban , Quiros-Solano William F. , Kuijten Maayke M.P. , Haspels Ben , Mallya Sandeep , Lo Calvin Shun Yu , Othman Amr , Silvestri Cinzia , van de Stolpe Anja , Gaio Nikolas , Odijk Hanny , van de Ven Marieke , de Ridder Corrina M.A. , van Weerden Wytske M. , Jonkers Jos , Dekker Ronald , Taneja Nitika , Kanaar Roland , van Gent Dik C. 
Published: December 2021

AbstractOptimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies.Significance:The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.
Abdominopelvic FLASH Irradiation Improves PD-1 Immune Checkpoint Inhibition in Preclinical Models of Ovarian Cancer
Authors: Eggold Joshua T. , Chow Stephanie , Melemenidis Stavros , Wang Jinghui , Natarajan Suchitra , Loo Phoebe E. , Manjappa Rakesh , Viswanathan Vignesh , Kidd Elizabeth A. , Engleman Edgar , Dorigo Oliver , Loo Billy W. , Rankin Erinn B. 
Published: December 2021

Abstract
Treatment of advanced ovarian cancer using PD-1/PD-L1 immune checkpoint blockade shows promise; however, current clinical trials are limited by modest response rates. Radiotherapy has been shown to synergize with PD-1/PD-L1 blockade in some cancers but has not been utilized in advanced ovarian cancer due to toxicity associated with conventional abdominopelvic irradiation. Ultrahigh-dose rate (FLASH) irradiation has emerged as a strategy to reduce radiation-induced toxicity, however, the immunomodulatory properties of FLASH irradiation remain unknown. Here, we demonstrate that single high-dose abdominopelvic FLASH irradiation promoted intestinal regeneration and maintained tumor control in a preclinical mouse model of ovarian cancer. Reduced tumor burden in conventional and FLASH-treated mice was associated with an early decrease in intratumoral regulatory T cells and a late increase in cytolytic CD8+ T cells. Compared with conventional irradiation, FLASH irradiation increased intratumoral T-cell infiltration at early timepoints. Moreover, FLASH irradiation maintained the ability to increase intratumoral CD8+ T-cell infiltration and enhance the efficacy of αPD-1 therapy in preclinical models of ovarian cancer. These data highlight the potential for FLASH irradiation to improve the therapeutic efficacy of checkpoint inhibition in the treatment of ovarian cancer.
Unspliced XBP1 Counteracts β-Catenin to Inhibit Vascular Calcification
Authors: Yang Liu , Dai Rongbo , Wu Hao , Cai Zeyu , Xie Nan , Zhang Xu , Shen Yicong , Gong Ze , Jia Yiting , Yu Fang , Zhao Ying , Lin Pinglan , Ye Chaoyang , Hu Yanhua , Fu Yi , Xu Qingbo , Li Zhiqing , Kong Wei 
Published: December 2021

Background:
Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the XBP1u (unspliced XBP1) and XBP1s (spliced XBP1) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear.

Methods:
We aim to investigate the role of XBP1u in vascular calcification. XBP1u protein levels were reduced in high phosphate–induced calcified vascular smooth muscle cells, calcified aortas from mice with adenine diet-induced chronic renal failure, and calcified radial arteries from patients with chronic renal failure.

Results:
Inhibition of XBP1u rather than XBP1s upregulated in the expression of the osteogenic markers Runx2 (runt-related transcription factor 2) and Msx2 (msh homeobox 2), and exacerbated high phosphate–induced vascular smooth muscle cell calcification, as verified by calcium deposition and Alizarin red S staining. In contrast, XBP1u overexpression in high phosphate–induced vascular smooth muscle cells significantly inhibited osteogenic differentiation and calcification. Consistently, smooth muscle cell–specific XBP1 deficiency in mice markedly aggravated the adenine diet- and 5/6 nephrectomy-induced vascular calcification compared with that in the control littermates. Further interactome analysis revealed that XBP1u is bound directly to β-catenin, a key regulator of vascular calcification, via amino acid (aa) 205-230 in its C-terminal degradation domain. XBP1u interacted with β-catenin to promote its ubiquitin-proteasomal degradation and thus inhibited β-catenin/TCF (T-cell factor)-mediated Runx2 and Msx2 transcription. Knockdown of β-catenin abolished the effect of XBP1u deficiency on vascular smooth muscle cell calcification, suggesting a β-catenin-mediated mechanism. Moreover, the degradation of β-catenin promoted by XBP1u was independent of GSK-3β (glycogen synthase kinase 3β)–involved destruction complex.

Conclusions:
Our study identified XBP1u as a novel endogenous inhibitor of vascular calcification by counteracting β-catenin and promoting its ubiquitin-proteasomal degradation, which represents a new regulatory pathway of β-catenin and a promising target for vascular calcification treatment.