bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of psychiatric disorders and all-cause mortality with belimumab therapy in patients with systemic lupus erythematosus: a meta-analysis of randomised controlled trials
Authors: Xie Wenhui , Huang Hong , Zhan Siyan , Zhang Zhuoli 
Published: October 2021

ObjectivesTo evaluate the risk of psychiatric disorders and all-cause mortality associated with belimumab therapy in patients with SLE.MethodsA literature search of four electronic bibliographic databases, including PubMed, EMBASE, Scopus and Cochrane databases, was conducted for randomised controlled trials (RCTs) reporting adverse reactions between belimumab and placebo. OR and 95% CI were calculated using the Mantel-Haenszel method with fixed-effects or random-effects model, depending on the heterogeneity test.ResultsIn total, 11 eligible RCTs including 8824 patients with SLE were randomised into belimumab (5160 patients with 5552 patient-years) and placebo (3664 patients with 3985 patient-years) groups, respectively. Overall, no increased risk was identified with belimumab therapy at all dosages compared with placebo in patients with SLE regarding all psychiatric disorders (OR 0.89, 95% CI 0.64 to 1.23, I2=58%) and all-cause mortality (OR 1.10, 95% CI 0.64 to 1.89, I2=0%). The subgroup analysis of psychiatric disorders also revealed no statistically elevated risks in serious psychiatric disorders (OR 1.15, 95% CI 0.77 to 1.70, I2=47%), non-serious psychiatric disorders (OR 0.83, 95% CI 0.60 to 1.16, I2=52%), suicidal ideation or behaviour (OR 0.87, 95% CI 0.57 to 1.33, I2=0%), and depression (OR 1.29, 95% CI 0.90 to 1.85, I2=15%). Secondary analysis restricting belimumab at approved dose of 10 mg/kg only yielded similar results.ConclusionBelimumab therapy overall does not increase psychiatric events and all-cause mortality risks, whereas the results from Belimumab Assessment of Safety in SLE Study are suggestive of increased risk of psychiatric adverse events with belimumab exposure. Consequently, post-marketing data are needed to ascertain its psychiatric safety, especially serious mental disorders.
Picoradiant tiltmeter and direct ground tilt measurements at the Sos Enattos site
Authors: Allocca Annalisa , Avino Saverio , Calloni Enrico , Caprara Sergio , Carpinelli Massimo , D’Urso Domenico , De Laurentis Martina , De Rosa Rosario , Errico L. , Gagliardi G. , Grilli Marco , Mangano Valentina , Marsella Maria , Naticchioni Luca , Pasqualetti Antonio , Pepe Gianpiero , Perciballi Maurizio , Pesenti Luca , Puppo Paola , Rapagnani Piero , Ricci Fulvio , Rosa Luigi , Rovelli Carlo , Rozza Davide , Ruggi P. , Saini Naurang L. , Sequino Valeria , Sipala Valeria , Stornaiuolo Daniela , Tafuri Francesco 
Published: October 2021

AbstractWe report the tilt sensitivity reached by the ARCHIMEDES tiltmeter in the 2–20 Hz frequency region, where seismic noise is expected to give an important limitation to the sensitivity in the next future Gravitational Waves detection, particularly through Newtonian noise. The tilt noise level $$\tilde{\theta }(f)$$

θ
~

(
f
)

is about $$10^{-12} \mathrm{rad}/\sqrt{\mathrm{Hz}}$$

10

-
12

rad
/

Hz

in most of the band, reaching the minimum of $$\tilde{\theta } = 7\cdot 10^{-13} \mathrm{rad}/\sqrt{\mathrm{Hz}}$$

θ
~

=
7
·

10

-
13

rad
/

Hz

around 9 Hz. The tiltmeter is a beam balance with a 0.5 m suspended arm and interferometric optical readout, working in closed loop. The results have been obtained by a direct measurement of the ground tilt at the Sos Enattos site (Sardinia, Italy). This sensitivity is a requirement to use the tiltmeter as part of an effective Newtonian noise reduction system for present Gravitational Waves detectors, and also confirms that Sos Enattos is among the quietest sites in the world, suitable to host the third-generation Gravitational Waves detector Einstein Telescope.
IR challenges and the machine detector interface at FCC-ee
Authors: Boscolo Manuela , Burkhardt Helmut , Oide Katsunobu , Sullivan Michael K. 
Published: October 2021

AbstractThe FCC-ee, with its unprecedented luminosity goal and high energy reach, creates challenges and requires solutions to many issues in order to produce a realistic design for the complex machine detector interface. The interaction region design for the FCC-ee adopts the crab-waist collision scheme and proposes an elegant local chromaticity correction system. An asymmetric layout of nearby dipoles suppresses the critical energy of synchrotron radiation incoming to the detector at the interaction point to a maximum value of 100 keV. The main challenge of the FCC-ee machine detector interface design is to combine the many conflicting accelerator and 2 T detector constraints, aiming for the optimal trade-off choices that simultaneously allow for a best machine performance in terms of integrated luminosity and data taking efficiency. Much of the success of the FCC-ee will be related to the interaction region design, as a result of the ingredients coming from areas of accelerator physics, mechanical engineering and detector optimization.
Multi-itinerary optimization as cloud service
Authors: Cristian Alexandru , Marshall Luke , Negrea Mihai , Stoichescu Flavius , Cao Peiwei , Menache Ishai 
Published: October 2021

In this paper, we describe multi-itinerary optimization (MIO)---a novel Bing Maps service that automates the process of building itineraries for multiple agents while optimizing their routes to minimize travel time or distance. MIO can be used by organizations with a fleet of vehicles and drivers, mobile salesforce, or a team of personnel in the field, to maximize workforce efficiency. It supports a variety of constraints, such as service time windows, duration, priority, pickup and delivery dependencies, and vehicle capacity. MIO also considers traffic conditions between locations, resulting in algorithmic challenges at multiple levels (e.g., calculating time-dependent travel-time distance matrices at scale and scheduling services for multiple agents).
To support an end-to-end cloud service with turnaround times of a few seconds, our algorithm design targets a sweet spot between accuracy and performance. Toward that end, we build a scalable approach based on the ALNS metaheuristic. Our experiments show that accounting for traffic significantly improves solution quality: MIO finds efficient routes that avoid late arrivals, whereas traffic-agnostic approaches result in a 15% increase in the combined travel time and the lateness of an arrival. Furthermore, our approach generates itineraries with substantially higher quality than a cutting-edge heuristic (LKH), with faster running times for large instances.
DNA Methylation Profiles of Ovarian Clear Cell Carcinoma
Authors: Cunningham Julie M. , Winham Stacey J. , Wang Chen , Weiglt Britta , Fu Zhuxuan , Armasu Sebastian M. , McCauley Bryan M. , Brand Alison H. , Chiew Yoke-Eng , Elishaev Esther , Gourley Charlie , Kennedy Catherine J. , Laslavic Angela , Lester Jenny , Piskorz Anna , Sekowska Magdalena , Brenton James D. , Churchman Michael , DeFazio Anna , Drapkin Ronny , Elias Kevin M. , Huntsman David G. , Karlan Beth Y. , Köbel Martin , Konner Jason , Lawrenson Kate , Papaemmanuil Elli , Bolton Kelly L. , Modugno Francesmary , Goode Ellen L. 
Published: October 2021

Abstract

Background:
Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC.

Methods:
We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways.

Results:
Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 (N = 137), Cluster 1 cases (N = 134) presented at a more advanced stage, were less likely to be of Asian ancestry, and tended to have poorer outcomes including macroscopic residual disease following primary debulking surgery (P &lt; 0.10). Subset analyses of targeted tumor sequencing and IHC data revealed that Cluster 1 tumors showed TP53 mutation and abnormal p53 expression, and Cluster 2 tumors showed aneuploidy and ARID1A/PIK3CA mutation (P &lt; 0.05). Cluster-defining CpGs included 1,388 CpGs residing within 200 bp of the transcription start sites of 977 genes; 38% of these genes (N = 369 genes) were differentially expressed across cluster in transcriptomic subset analysis (P &lt; 10−4). Differentially expressed genes were enriched for six immune-related pathways, including IFNα and IFNγ responses (P &lt; 10−6).

Conclusions:
DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways.

Impact:
This work serves as a foundation for integrative analyses that better understand the complex biology of OCCC in an effort to improve potential for development of targeted therapeutics.
FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions
Authors: Ivey-Miranda Juan B. , Stewart Brendan , Cox Zachary L. , McCallum Wendy , Maulion Christopher , Gleason Olyvia , Meegan Grace , Amatruda Jonathan G. , Moreno-Villagomez Julieta , Mahoney Devin , Turner Jeffrey M. , Wilson F. Perry , Estrella Michelle M. , Shlipak Michael G. , Rao Veena S. , Testani Jeffrey M. 
Published: October 2021

Background:
Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors.

Methods:
One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics.

Results:

FGF-23 was associated with several metrics of disease severity such as higher home loop diuretic dose and NT-proBNP (N-terminal pro-B-type natriuretic peptide), and lower estimated glomerular filtration rate, serum chloride, and serum albumin. Multivariable analysis demonstrated no statistically significant association between FGF-23 and sodium avidity measured by fractional excretion of sodium, or proximal or distal tubular sodium reabsorption, either before diuretic administration or at peak diuresis (
P
≥0.11 for all). Likewise, FGF-23 was not independently associated with parameters of diuretic resistance (diuretic excretion, cumulative urine and sodium output, and loop diuretic efficiency [
P
≥0.33 for all]) or neurohormonal activation (plasma or urine renin [
P
≥0.36 for all]). Moreover, the upper boundary of the 95% CI of all the partial correlations were ≤0.30, supporting the lack of meaningful correlations. FGF-23 was not associated with mortality in multivariable analysis (
P
=0.44).

Conclusions:
FGF-23 was not meaningfully associated with any cardiorenal parameter in patients with heart failure. While our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal interactions.
Changing Demographics, Temporal Trends in Waitlist, and Posttransplant Outcomes After Heart Transplantation in the United States: Analysis of the UNOS Database 1991–2019
Authors: Akintoye Emmanuel , Alvarez Paulino , Shin Doosup , Egbe Alexander , Panos Anthony , Sellke Frank , Briasoulis Alexandros 
Published: October 2021

Background:
We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States.

Methods:
Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991–January 1999; Era 2=January 1999–July 2006; Era 3=July 2006–October 2018; and Era 4=October 2018–March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era.

Results:

Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65–0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58–0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%–17.1%), and length-of-stay (14–17days),
P
<0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively).

Conclusions:
There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.
Evaluating the Economic Impacts of Improvements to the High-Resolution Rapid Refresh (HRRR) Numerical Weather Prediction Model
Authors: Turner David D. , Cutler Harvey , Shields Martin , Hill Rebecca , Hartman Brad , Hu Yuchen , Lu Tao , Jeon Hwayoung 
Published: October 2021

Abstract
Forecasts from numerical weather prediction (NWP) models play a critical role in many sectors of the U.S. economy. Improvements to operational NWP model forecasts are generally assumed to provide significant economic savings through better decision-making. But is this true? Since 2014, several new versions of the High-Resolution Rapid Refresh (HRRR) model were released into operation within the National Weather Service. Practically, forecasts have an economic impact only if they lead to a different action than what would be taken under an alternative information set. And in many sectors, these decisions only need to be considered during certain weather conditions. We estimate the economic impacts of improvements made to the HRRR, using 12-h wind, precipitation, and temperature forecasts in several cases where they can have “economically meaningful” behavioral consequences. We examine three different components of the U.S. economy where such information matters: 1) better integration of wind energy resources into the electric grid, 2) increased worker output due to better precipitation forecasts that allow workers to arrive to their jobs on time, and 3) better decisions by agricultural producers in preparing for freezing conditions. These applications demonstrate some of the challenges in ascertaining the economic impacts of improved weather forecasts, including highlighting key assumptions that must be made to make the problem tractable. For these sectors, we demonstrate that there was a marked economic gain for the United States between HRRR versions 1 and 2 and a smaller, but still appreciable economic gain between versions 2 and 3.
A Geostationary Lightning Pseudo-Observation Generator Utilizing Low-Frequency Ground-Based Lightning Observations
Authors: Erdmann Felix , Caumont Olivier , Defer Eric 
Published: October 2021

Abstract
Coincident Geostationary Lightning Mapper (GLM) and National Lightning Detection Network (NLDN) observations are used to build a generator of realistic lightning optical signal in the perspective to simulate Lightning Imager (LI) signal from European NLDN-like observations. Characteristics of GLM and NLDN flashes are used to train different machine-learning (ML) models, which predict simulated pseudo-GLM flash extent, flash duration, and event number per flash (targets) from several NLDN flash characteristics. Comparing statistics of observed GLM targets and simulated pseudo-GLM targets, the most suitable ML-based target generators are identified. The simulated targets are then further processed to obtain pseudo-GLM events and flash-scale products. In the perspective of lightning data assimilation, flash extent density (FED) is derived from both observed and simulated GLM data. The best generators simulate accumulated hourly FED sums with a bias of 2% to the observation while cumulated absolute differences remain of about 22%. A visual comparison reveals that hourly simulated FED features local maxima at the similar geolocations as the FED derived from GLM observations. However, the simulated FED often exceeds the observed FED in regions of convective cores and high flash rates. The accumulated hourly area with FED > 0 flashes per 5 km × 5 km pixel simulated by some pseudo-GLM generators differs by only 7%–8% from the observed values. The recommended generator uses a linear support vector regressor (linSVR) to create pseudo-GLM FED. It provides the best balance between target simulation, hourly FED sum, and hourly electrified area.
Are We Prepared for Precision Public Health? An Examination of Genomics Content in Graduate Public Health Programs
Authors: Niemchick Karen L. , Goerge Ally , Ponte Amy H. 
Published: October 2021

Objective With the completion of the Human Genome Project and swift development of genomic technologies, public health practitioners can use these advancements to more precisely target disease interventions to populations at risk. To integrate these innovations into better health outcomes, public health professionals need to have at least a basic understanding of genomics within various disciplines of public health. This descriptive study focused on the current level of genomics content in accredited master of public health (MPH) programs in the United States. Methods We conducted an internet search on all 171 Council on Education for Public Health (CEPH)–accredited MPH programs in the United States for genomics content in required and elective courses using the search terms “genetics,” “genomics,” and “molecular.” Results Of the 171 CEPH-accredited MPH programs examined, 52 (30.4%) schools and programs in 34 states offered some type of genomics education. Thirty-five (20.5%) schools and programs had a course in genetic epidemiology, 29 (16.9%) had a course in genetic biostatistics or bioinformatics, and 17 (9.9%) had a course in general public health genomics. The remaining 119 offered no course with a focus on genetics or genomics. In addition, some electives or specifically focused courses related to genomics were offered. Conclusion We found inadequate training in public health genomics for MPH students. To realize the promise of precision public health and to increase the understanding of genomics among the public health workforce, MPH programs need to find ways to integrate genomics education into their curricula.
Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies
Authors: Booler Helen S. , Lejeune Typhaine , Sorden Steven , Gruebbel Margarita M. , Schafer Kenneth A. , Short Brian , Farman Cindy , Ramos Meg Ferrell , Bennet Bindu , Yekkala Krishna , Atzpodien Elke-Astrid , Turner Oliver C. , Brassard Jaqueline , Foley George 
Published: October 2021

A Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee conducted a technical and scientific review of current practices relating to the fixation, trimming, and sectioning of the nonrodent eye to identify key points and species-specific anatomical landmarks to consider when preparing and evaluating eyes of rabbits, dogs, minipigs, and nonhuman primates from ocular and general toxicity studies. The topics addressed in this Points to Consider article include determination of situations when more comprehensive evaluation of the globe and/or associated extraocular tissues should be implemented (expanded ocular sampling), and what constitutes expanded ocular sampling. In addition, this manuscript highlights the practical aspects of fixing, trimming, and sectioning the eye to ensure adequate histopathological evaluation of all major ocular structures, including the cone-dense areas (visual streak/macula/fovea) of the retina for rabbits, dogs, minipigs, and nonhuman primates, which is a current regulatory expectation for ocular toxicity studies. [Box: see text]
Association Between Excessive Joint Laxity and a Wider Hill-Sachs Lesion in Anterior Shoulder Instability
Authors: Lim Joon-Ryul , Lee Hyung-Min , Yoon Tae-Hwan , Lee Hwan-Mo , Chun Yong-Min 
Published: October 2021

Background: Excessive general joint laxity, a negative prognostic factor in joint instability, has not been studied to determine its relationship with bipolar bone loss in anterior shoulder instability. Purpose/Hypothesis: This study aimed to investigate the characteristics of bipolar bone defects in the presence of excessive joint laxity and the clinical outcomes based on the on-track/off-track theory. We hypothesized that (1) patients with excessive joint laxity might have less significant bipolar bone defects compared with those without excessive joint laxity and (2) no significant difference would be found in the clinical outcomes, including recurrence rate. Study Design: Cohort study; Level of evidence, 3. Methods: This study included 81 patients who had undergone arthroscopic Bankart repair, with (group L; n = 33) or without (group N; n = 48) excessive joint laxity. The presence of excessive joint laxity was defined as a score of ≥4 using Beighton and Horan criteria preoperatively. Bipolar bone lesions were assessed using preoperative 3-dimensional computed tomography. Additional remplissage was performed for cases with off-track or positive engagement test in borderline on-track lesions. The functional outcomes at the 2-year follow-up were assessed using the recurrence rate, Subjective Shoulder Value, Rowe score, University of California Los Angeles shoulder score, active range of motion, and the sports/recreation activity level. Results: No significant difference was found in the glenoid bone defect between groups (14.1%, group L; 14.4%, group N). Off-track lesions were identified in 39.4% (13/33) of group L and 14.6% (7/48) of group N ( P = .011). The mean Hill-Sachs interval to glenoid track ratio was 83.1% in group L and 75.2% in group N ( P = .021). Additional remplissage procedures were more frequently performed in group L (48.5%; 16/33) than in group N (16.7%; 8/48) ( P = .002). However, no significant difference was observed in the shoulder functional scores and recurrence rates between the groups. Conclusion: Patients with anterior shoulder instability and excessive joint laxity had significantly wider Hill-Sachs lesions and more off-track lesions than did those with normal joint laxity despite the lack of a significant difference in the glenoid bone defect. However, these differences in the Hill-Sachs lesion were not related to differences in the functional outcomes between the groups.