bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual oral multifocal epithelial hyperplasia in an adult African‐American lung transplant patient
Authors: Chompunud Na Ayudhya Chalatip , Alawi Faizan , Akintoye Sunday O. 
Published: October 2020

AbstractOral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65‐year‐old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV‐related precancerous lesions.
Investigating Small Modular Reactor's Design Limits for Its Flexible Operation With Photovoltaic Generation in Microcommunities
Authors: Joshi Kalpesh , Poudel Bikash , Gokaraju Ramakrishna (Rama) 
Published: October 2020

Abstract
Use of flexible and dispatchable generation from the small modular reactors (SMRs) in combination with the nondispatchable generation from renewable energy systems (RES) can be an effective alternative to pursue the mandate of replacing the fossil-fuel based electricity with the carbon-neutral energy systems in the remote microcommunities. This paper evaluates the feasibility of SMRs' flexible operations in microcommunities with the photovoltaic (PV) generation as a case study. Considering the design limits of SMRs for (a) the range of net change in electrical power output and (b) the ramp rates of net change in turbine power, a power system study is conducted to cover the three aspects of flexible operations, namely: (1) Planned load-following, (2) Unplanned load-following, and (3) Frequency regulation. A generic governor model in power system simulator for engineering (PSS/E), a power system transmission and planning software, is adapted to incorporate the operating limits of the reactor for the dynamic simulation. The multitimescale approach, combining (a) steady-state time-series power flow analysis and (b) dynamic simulations with high-resolution solar irradiation datasets, is proposed to assess the implications of SMR's design limits. The results obtained on an existing remote feeder with three sets of operating limits—namely, the conventional, advanced and extreme limits of ramp rates juxtapose the SMRs' performance, given the challenging operating conditions with PV generation in remote locations. The results indicate that the SMR under study can accommodate the highest permissible PV penetration obtained by the hosting capacity analysis of the feeder under the clear sky conditions. However, dynamic simulations with the extreme PV variabilities show that the PV penetration level should be further limited so that the maximum deviations in SMR power levels stay within 40% of its rated capacity. SMR provides adequate frequency support for the PV penetration of up to 50% of the feeder maximum demand in this study.
Neutronic Analysis of the European Sodium Fast Reactor: Part I—Fresh Core Results
Authors: Fridman Emil , Álvarez Velarde Francisco , Romojaro Otero Pablo , Tsige-Tamirat Haileyesus , Jiménez Carrascosa Antonio , García Herranz Nuria , Bernard Franck , Gregg Robert , Davies Una , Krepel Jiri , Massara Simone , Poumerouly Sandra , Girardi Enrico , Mikityuk Konstantin 
Published: October 2020

Abstract
In the framework of the Horizon 2020 project ESFR-SMART (2017-2021), the European Sodium Fast Reactor (ESFR) core was updated through a safety-related modification and optimization of the core design from the earlier FP7 CP-ESFR project (2009-2013). This study is dedicated to neutronic analyses of the improved ESFR core design. The conducted work is reported in two parts. Part I deals with the evaluation of the safety-related neutronic parameters of the fresh Beginning-of-Life (BOL) core carried out by 8 organizations using both continuous energy Monte Carlo and deterministic computer codes. In addition to the neutronics characterization of the core, a special emphasis was put on the calibration and verification of the computational tools involved in the analyses. Part II is devoted to once-through and realistic batch-wise burnup calculations aiming at the establishing of the equilibrium core state, which will later serve as a basis for detailed safety analyses.
Association between corneal refractive surgery and the prevalence of glaucoma: Korea National Health and Nutrition Examination Survey 2010–2012
Authors: Song Jae Shin , Lee Young Bok , Kim Ji-Ah , Lee Eun Ji , Kim Hyunjoong 
Published: October 2020

AimTo determine the relationship between corneal refractive surgery and the prevalence of glaucoma in the Korean population.MethodsData were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES), a population-based cross-sectional study using a complex, stratified, multistage, probability-cluster survey. This study included 604 eyes that had undergone myopic corneal refractive surgery, and 3389 control eyes without a history of any ocular surgery and having a spherical equivalent (SE) <−3.00 D, obtained from the KNHANES database for the years 2010–2012. Glaucoma diagnosis was based on the International Society of Geographical and Epidemiological Ophthalmology criteria. The association between a history of corneal refractive surgery and the prevalence of glaucoma was analysed using logistic regression analysis, after adjusting for potential confounding factors.ResultsGlaucoma prevalence did not differ between eyes that had and had not undergone corneal refractive surgery (p=0.675). After adjusting for age, sex, SE, and intraocular pressure, multivariate logistic regression analysis found that corneal refractive surgery was significantly associated with an increased risk of glaucoma (OR 9.14, p=0.002; 95% CI 2.22 to 37.69). Subgroup analysis that only included control eyes with a refraction cut-off <−3.70 D found that corneal refractive surgery was not significantly associated with glaucoma.ConclusionsHistory of corneal refractive surgery was associated with a higher prevalence of glaucoma in the Korean population. However, this association was not observed in eyes with a higher degree of myopia.
Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)
Authors: Agarwal Anup , Mukherjee Aparna , Kumar Gunjan , Chatterjee Pranab , Bhatnagar Tarun , Malhotra Pankaj 
Published: October 2020

AbstractObjectiveTo investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India.DesignOpen label, parallel arm, phase II, multicentre, randomised controlled trial.Setting39 public and private hospitals across India.Participants464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm).InterventionsParticipants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study.Main outcome measureComposite of progression to severe disease (PaO2/FiO2<100 mm Hg) or all cause mortality at 28 days post-enrolment.ResultsProgression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval −0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54).ConclusionConvalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19.Trial registrationClinical Trial Registry of India CTRI/2020/04/024775.
Oregon’s approach to leveraging system-level data to guide a social determinants of health-informed approach to children’s healthcare
Authors: Reuland Colleen P , Collins Jon , Chiang Lydia , Stewart Valerie , Cochran Aaron C , Coon Christopher W , Shinde Deepti , Hargunani Dana 
Published: October 2020

Background
Children’s health and healthcare use are impacted by both medical conditions and social factors, such as their home and community environment. As healthcare systems manage a pediatric population, information about these factors is crucial to providing quality care coordination.

Methods
The authors developed a novel methodology combining medical complexity (using the Pediatric Medical Complexity Algorithm) and social complexity (using available family social factors known to impact a child’s health and healthcare use) to create a new health complexity model at both the population-level and individual-level. System-level data from Oregon’s Medicaid Management Information Systems and Integrated Client Services database was analysed, examining claims data and service utilization, to calculate the health complexity of children enrolled in Medicaid/Child Health Insurance Program (CHIP) across Oregon.

Results
Of the 390 582 children ages 0 to 17 enrolled in Medicaid/CHIP in Oregon from July 2015 to June 2016, 83.4% (n=325 900) had some level of medical and/or social complexity and 22.1% (n=85 839) had health complexity (both medical and social complexity). Statistically significant (p<0.05) differences in health complexity were observed among attributed patients by Oregon’s 16 Coordinated Care Organizations, as well as by a child’s age, county of residence and race/ethnicity.

Conclusions
Given the high proportion of children with health complexity, these findings demonstrate that a large number of Medicaid/CHIP-insured children could benefit from targeted care coordination and differential resource allocation. Reports have been shared with state, county and health system leaders to drive work across the state. This paper describes the collaborative process necessary for other states considering similar work.
Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients
Authors: Machiels Jean-Pascal , Gomez-Roca Carlos , Michot Jean-Marie , Zamarin Dmitriy , Mitchell Tara , Catala Gaetan , Eberst Lauriane , Jacob Wolfgang , Jegg Anna-Maria , Cannarile Michael A , Watson Carl , Babitzki Galina , Korski Konstanty , Klaman Irina , Teixeira Priscila , Hoves Sabine , Ries Carola , Meneses-Lorente Georgina , Michielin Francesca , Christen Randolph , Rüttinger Dominik , Weisser Martin , Delord Jean-Pierre , Cassier Philippe 
Published: October 2020

BackgroundThis phase Ib study evaluated the safety, clinical activity, pharmacokinetics, and pharmacodynamics (PD) of emactuzumab (anti-colony stimulating factor 1 receptor monoclonal antibody (mAb)) in combination with selicrelumab (agonistic cluster of differentiation 40 mAb) in patients with advanced solid tumors.MethodsBoth emactuzumab and selicrelumab were administered intravenously every 3 weeks and doses were concomitantly escalated (emactuzumab: 500 to 1000 mg flat; selicrelumab: 2 to 16 mg flat). Dose escalation was conducted using the product of independent beta probabilities dose-escalation design. PD analyzes were performed on peripheral blood samples and tumor/skin biopsies at baseline and on treatment. Clinical activity was evaluated using investigator-based and Response Evaluation Criteria In Solid Tumors V.1.1-based tumor assessments.ResultsThree dose-limiting toxicities (all infusion-related reactions (IRRs)) were observed at 8, 12 and 16 mg of selicrelumab together with 1000 mg of emactuzumab. The maximum tolerated dose was not reached at the predefined top doses of emactuzumab (1000 mg) and selicrelumab (16 mg). The most common adverse events were IRRs (75.7%), fatigue (54.1%), facial edema (37.8%), and increase in aspartate aminotransferase and creatinine phosphokinase (35.1% both). PD analyzes demonstrated an increase of Ki67+-activated CD8+ T cells accompanied by a decrease of B cells and the reduction of CD14Dim CD16bright monocytes in peripheral blood. The best objective clinical response was stable disease in 40.5% of patients.ConclusionEmactuzumab in combination with selicrelumab demonstrated a manageable safety profile and evidence of PD activity but did not translate into objective clinical responses.Trialregistration numberNCT02760797.
Balancing COVID-19 preparedness and ‘business as usual’ in hospitals: lessons from executives in China, Norway and the UK
Authors: Ikram Umar , Ren Hui , Shields-Zeeman Laura , Frich Jan , Northam Jones Daniel , Wu Jiong , Kuang Ming , Liu Yuanli , Ma Jing 
Published: October 2020

BackgroundDuring the first wave of COVID-19 pandemic, hospitals were forced to cancel or postpone non-COVID-19 care. With new outbreaks emerging, hospitals are now figuring out how to balance preparedness for future COVID-19 waves with their elective and regular services. This report discusses how four hospital systems deal with these dual responsibilities in China, Norway and the UK.ReflectionsBased on the experiences and combined reflections of hospital executives, we have formulated five strategic and leadership lessons for hospitals as they manage these dual responsibilities. (1) Redesign organisation to separate COVID-19 and non-COVID-19 services both within and across hospitals. (2) Expand virtual care strategies to improve access. (3) Use data-driven models to allocate resources across COVID-19 and non-COVID-19 units. (4) Invest in programmes to promote frontline staff well-being. (5) Secure financial support to continue to deliver on the dual responsibilities.ConclusionThe COVID-19 pandemic gives rise to leadership challenges that have fuelled organisational change and new approaches to healthcare delivery. Leading hospitals during the pandemic is a balancing act—providing care for both patients with COVID-19 and non-COVID-19, while at the same time preparing for the next waves of the pandemic.
Improved $$(g-2)_\mu $$ measurements and supersymmetry
Authors: Chakraborti Manimala , Heinemeyer Sven , Saha Ipsita 
Published: October 2020

AbstractThe electroweak (EW) sector of the Minimal Supersymmetric Standard Model (MSSM) can account for variety of experimental data. The lighest supersymmetric particle (LSP), which we take as the lightest neutralino, $${\tilde{\chi }}_{1}^0$$

χ
~

1

0

, can account for the observed Dark Matter (DM) content of the universe via coannihilation with the next-to-LSP (NLSP), while being in agreement with negative results from Direct Detection (DD) experiments. Owing to relatively small production cross-sections a comparably light EW sector of the MSSM is also in agreement with the unsuccessful searches at the LHC. Most importantly, the EW sector of the MSSM can account for the persistent $$3-4\,\sigma $$

3
-
4

σ

discrepancy between the experimental result for the anomalous magnetic moment of the muon, $$(g-2)_\mu $$

(
g
-
2
)

μ

, and its Standard Model (SM) prediction. Under the assumption that the $${\tilde{\chi }}_{1}^0$$

χ
~

1

0

provides the full DM relic abundance we first analyze which mass ranges of neutralinos, charginos and scalar leptons are in agreement with all experimental data, including relevant LHC searches. We find an upper limit of $$\sim 600 \,\, \mathrm {GeV}$$

∼
600

GeV

for the LSP and NLSP masses. In a second step we assume that the new result of the Run 1 of the “MUON G-2” collaboration at Fermilab yields a precision comparable to the existing experimental result with the same central value. We analyze the potential impact of the combination of the Run 1 data with the existing $$(g-2)_\mu $$

(
g
-
2
)

μ

data on the allowed MSSM parameter space. We find that in this case the upper limits on the LSP and NLSP masses are substantially reduced by roughly $$100 \,\, \mathrm {GeV}$$

100

GeV

. This would yield improved upper limits on these masses of $$\sim 500 \,\, \mathrm {GeV}$$

∼
500

GeV

. In this way, a clear target could be set for future LHC EW searches, as well as for future high-energy $$e^+e^-$$

e
+

e
-

colliders, such as the ILC or CLIC.
Specific entropy as a clock for the evolutionary quantization of the isotropic Universe
Authors: Campolongo Andrea , Montani Giovanni 
Published: October 2020

AbstractIn this paper, we analyze the dynamics of an isotropic closed Universe in presence of a cosmological constant term and we compare its behavior in the standard Wheeler–DeWitt equation approach with the one when a Lagrangian fluid is considered in the spirit of the Kuchar–Brown paradigm. In particular, we compare the tunnelling of the Universe from the classically forbidden region to the allowed one, showing that considering a time evolution deeply influences the nature of the model. In fact, we show that in the presence of the Lagrangian fluid, the cosmological singularity is restored both in the classical and the quantum regime. However, in the quantum regime the singularity is probabilistically suppressed for some energy eigenvalues and in the case the latter is equal to zero one recovers the standard WDW case. Finally, we introduce a cut-off physics feature in the Minisuperspace by considering a Polymer quantum mechanical approach limiting our attention to the semi-classical dynamics mainly (the quantum treatment is inhibited by the non-local nature of the Hamiltonian operator). We show that the singularity is again removed, like in the fluid-free model, and a bouncing cosmology emerges so that the present model could mimic a cyclic cosmology.
Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase
Authors: Xiao Ling , Salem Joe-Elie , Clauss Sebastian , Hanley Alan , Bapat Aneesh , Hulsmans Maarten , Iwamoto Yoshiko , Wojtkiewicz Gregory , Cetinbas Murat , Schloss Maximilian J. , Tedeschi Justin , Lebrun-Vignes Bénédicte , Lundby Alicia , Sadreyev Ruslan I. , Moslehi Javid , Nahrendorf Matthias , Ellinor Patrick T. , Milan David J 
Published: October 2020

Background:
Ibrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood.

Methods:
We performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF. Chemoproteomic analysis of cardiac lysates identified candidate ibrutinib targets, which were further evaluated in genetic mouse models and additional pharmacological experiments. The pharmacovigilance database, VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of AF.

Results:

We demonstrate that treatment of mice with ibrutinib for 4 weeks results in inducible AF, left atrial enlargement, myocardial fibrosis, and inflammation. This effect was reproduced in mice lacking Bruton tyrosine kinase, but not in mice treated with 4 weeks of acalabrutinib, a more specific Bruton tyrosine kinase inhibitor, demonstrating that AF is an off-target side effect. Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving CSK (C-terminal Src kinase) as the strongest candidate for ibrutinib-induced AF. Cardiac-specific Csk knockout in mice led to increased AF, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment. Disproportionality analyses in VigiBase confirmed increased reporting of AF associated with kinase inhibitors blocking Csk versus non-Csk inhibitors, with a reporting odds ratio of 8.0 (95% CI, 7.3–8.7;
P
<0.0001).

Conclusions:
These data identify Csk inhibition as the mechanism through which ibrutinib leads to AF.

Registration:

URL:
https://ww.clinicaltrials.gov
; Unique identifier: NCT03530215.
Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function
Authors: Zannad Faiez , Ferreira João Pedro , Pocock Stuart J. , Zeller Cordula , Anker Stefan D. , Butler Javed , Filippatos Gerasimos , Hauske Sibylle Jenny , Brueckmann Martina , Pfarr Egon , Schnee Janet , Wanner Christoph , Packer Milton 
Published: October 2020

Background:
In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin reduced cardiovascular death or heart failure (HF) hospitalization and total HF hospitalizations, and slowed the progressive decline in kidney function in patients with HF and a reduced ejection fraction, with and without diabetes. We aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.

Methods:

In this prespecified analysis, patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m
2
or albumin-to-creatine ratio >300 mg/g). The primary and key secondary outcomes were: (1) a composite of cardiovascular death or HF hospitalization (primary outcome); (2) total HF hospitalizations; and (3) eGFR slope. The direct impact on kidney events was investigated by a prespecified composite kidney outcome (defined as a sustained profound decline in eGFR, chronic dialysis, or transplant). The median follow-up was 16 months.

Results:

Of 3730 patients who were randomized to empagliflozin or placebo, 1978 (53%) had CKD. Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: hazard ratio (HR)=0.78 (95% CI, 0.65–0.93) and HR=0.72 (95% CI, 0.58–0.90), respectively (interaction
P
=0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23–1.98) ml/min/1.73 m
2
/yr in patients with CKD and by 2.41 (1.49–3.32) ml/min/1.73 m
2
/yr in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95% CI, 0.31–0.91) and HR=0.46 (95% CI, 0.22–0.99), respectively. The effect of empagliflozin on the primary composite outcome and key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73 m
2
. Empagliflozin was well tolerated in CKD patients.

Conclusions:
In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03057977.