bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses
Authors: Friedman Claire F , Spencer Christine , Cabanski Christopher R , Panageas Katherine S , Wells Daniel K , Ribas Antoni , Tawbi Hussein , Tsai Katy , Postow Michael , Shoushtari Alexander , Chapman Paul , Karakunnel Joyson , Bucktrout Samantha , Gherardini Pier , Hollmann Travis J , Chen Richard O , Callahan Margaret , LaVallee Theresa , Ibrahim Ramy , Wolchok Jedd 
Published: January 2022

BackgroundThere are no validated biomarkers that can aid clinicians in selecting who would best benefit from anticytotoxic T lymphocyte-associated antigen 4 monotherapy versus combination checkpoint blockade in patients with advanced melanoma who have progressive disease after programmed death 1 (PD-1) blockade.MethodsWe conducted a randomized multicenter phase II trial in patients with advanced melanoma. Patients were randomly assigned to receive either 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab or 3 mg/kg of ipilimumab every 3 weeks for up to four doses. Patients were stratified by histological subtype and prior response to PD-1 therapy. The primary clinical objective was overall response rate by week 18. Translational biomarker analyses were conducted in patients with blood and tissue samples.ResultsObjective responses were seen in 5 of 9 patients in the ipilimumab arm and 2 of 10 patients in the ipilimumab+nivolumab arm; disease control rates (DCRs) (66.7% vs 60.0%) and rates of grade 3–4 adverse events (56% vs 50%) were comparable between arms. In a pooled analysis, patients with clinical benefit (CB), defined as Response Evaluation Criteria in Solid Tumors response or progression-free for 6 months, showed increased circulating CD4+ T cells with higher polyfunctionality and interferon gamma production following treatment. Tumor profiling revealed enrichment of NRAS mutations and activation of transcriptional programs associated with innate and adaptive immunity in patients with CB.ConclusionsIn patients with advanced melanoma that previously progressed on PD-1 blockade, objective responses were seen in both arms, with comparable DCRs. Findings from biomarker analyses provided hypothesis-generating signals for validation in future studies of larger patient cohorts.Trial registration numberNCT02731729.
Economic evaluation of intravenous alteplase for stroke with the time of onset between 4.5 and 9 hours
Authors: Chen Jigang , Liang Xin , Tong Xin , Han Mingyang , Ji Linjin , Zhao Songfeng , Hu Zhiqiang , Liu Aihua 
Published: January 2022

BackgroundA clinical trial proved the clinical effectiveness of perfusion imaging-guided intravenous thrombolysis with alteplase for patients with acute ischemic stroke (AIS) with the time of onset between 4.5 and 9 hours. This study aimed to assess the lifetime cost-effectiveness of alteplase versus placebo from the perspective of Chinese and United States (US) healthcare payers.MethodsA decision-analytic model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) associated with alteplase or placebo. Model inputs were extracted from published sources. Incremental costs, incremental QALYs, and incremental cost-effectiveness ratio (ICER) were calculated to evaluate the base-case scenario. One-way and probabilistic sensitivity analysis were performed to evaluate uncertainty in the results.ResultsIn China, alteplase yielded an additional lifetime QALY of 0.126 with an additional cost of Chinese Yuan (¥) ¥9552 compared with placebo, and the ICER was ¥83 950 (US$12 157)/QALY. In the US, alteplase had a higher QALY (difference: 0.193) with a lower cost (difference: US$−2024) compared with placebo. In probabilistic sensitivity analyses, alteplase had a 42.54% to 78.3% probability of being cost-effective compared with placebo in China when the willingness-to-pay (WTP) threshold ranged from ¥72 447/QALY to ¥217 341/QALY. In the US, alteplase had a 93.47% to 93.57% probability of being cost-effective under the WTP threshold of US$100 000/QALY to US$150 000/QALY. These findings remained robust under one-way sensitivity analysis.ConclusionFor patients with AIS with a time of onset between 4.5 and 9 hours, perfusion imaging-guided intravenous alteplase was likely to be cost-effective in China and was cost-effective in the US when compared with placebo.
Massless fermions in spatially flat FLRW space-times
Authors: Cotăescu Ion I. 
Published: January 2022

AbstractThe propagation of the packets of left-handed plane wave solutions of the massless Dirac equation is studied in spatially flat Friedmann–Lemaître–Robertson–Walker (FLRW) space-times. Assuming that the observations are performed in physical frames with Painlevé–Gullstrand coordinates, the current and energy–momentum tensor are derived, emphasising their severe decay and moderate dispersion during propagation. As the wave packets move along null geodesics, interesting effects are produced by the apparent or event horizons.
Application of superstatistical analysis on fluctuant surface shear in particle-laden turbulence boundary layer
Authors: Li Guang , He Wei , Yang Bo , Yu Hongxiang , Huang Ning , Herrmann Hans J. , Zhang Jie 
Published: January 2022

Abstract
We report on an application of superstatistics to particle-laden turbulent flow. Four flush-mounted hot-film wall shear sensors were used to record the fluctuations of the wall shear stress in sand-laden flow. By comparing the scaling exponent in sand-free with that in sand-laden flows, we found that the sand-laden flow is more intermittent. By applying the superstatistics analysis to the friction velocity, we found that the large time scale is smaller when the flow is sand-laden. The probability density of a fluctuating energy dissipation rate measured in sand-laden flow follows a log-normal distribution with higher variances than for sand-free flow. The variance of this dissipation rate is a power law of the corresponding time scale. The prediction based on the superstatistics model is consistent with our structure function exponents $$\zeta _n$$

ζ
n

for sand-free flow. Nevertheless, it overestimates $$\zeta _n$$

ζ
n

for sand-laden flow, especially at higher Reynolds numbers.

Graphic abstract
How to increase the physics output per MW.h for FCC-ee?
Authors: Shatilov D. 
Published: January 2022

AbstractThe efficiency of colliders for physics is largely determined by their luminosity, while most of the energy consumed by high-energy e$$^+$$

+

e$$^-$$

-

colliders is proportional to the total beam current. Thus, the energy efficiency is mainly determined by the specific luminosity that needs to be maximized. One of the most effective ways to achieve this is by using the Crab waist collision scheme, which implies a large Piwinski angle (LPA). A distinctive feature of the FCC-ee is the great influence of beamstrahlung (radiation in the field of an opposite bunch) on beam dynamics. At low energies, this manifests itself in a significant increase in the energy spread and bunch length, at high energies, in a limitation of the beam lifetime. The collision of intense bunches with LPA and beamstrahlung can also lead to various kinds of instabilities limiting the luminosity. Here, we discuss the main aspects to consider when optimizing the parameters of the FCC-ee collider at different energies and explain the choice of basic parameters such as RF voltage, lattice functions at IP, bunch intensity, etc. We will also pay attention to open issues requiring further study and identify some key points for the next phase of this project.
Hyper-Gaussian regularized Whittaker–Kotel’nikov–Shannon sampling series
Authors: Chen Liang , Wang Yang , Zhang Haizhang 
Published: January 2022

The reconstruction of a bandlimited function from its finite sample data is fundamental in signal analysis. It is well known that oversampling of a bandlimited function leads to exponential convergence in its reconstruction. A simple and efficient Gaussian regularized Shannon sampling formula has been proposed in G. W. Wei [Quasi wavelets and quasi interpolating wavelets, Chem. Phys. Lett. 296 (1998) 215–222] with such an exponential convergence ability. We show that all hyper-Gaussian regularized formulas share this desired property. The analysis is built on estimates on the Fourier transform of the hyper-Gaussian functions. We also establish error bounds for the reconstruction of derivatives of a univariate bandlimited function, and for multivariate bandlimited functions.
About this title - Lamprophyres, Lamproites and Related Rocks: Tracers to Supercontinent Cycles and Metallogenesis
Authors: Krmíček L. , Chalapathi Rao N. V. 
Published: January 2022

Paleoproterozoic to Cenozoic lamprophyres, lamproites and related rock types (e.g., orangeites, kimberlites) are volatile-rich mafic magmatic rocks with a unique potential for the investigation of processes affecting mantle reservoirs. They originated from primary mantle-derived melts that intruded both cratons and off-craton regions, which were parts of former supercontinents – Columbia, Rodinia and Gondwana–Pangea. Well-known for hosting economic minerals and elements such as diamonds, base metals, gold and platinum-group elements, they are also significant for our understanding of deep-mantle processes, such as mantle metasomatism and mantle plume–lithosphere interactions, as well as large-scale geodynamic processes, such as subduction-related tectonics, and supercontinent amalgamation and break-up.
This book aims to provide a timely overview of the state-of-the-art and recent advances as achieved by various research groups around the world. Mineralogical, geochemical, geochronological and isotope analyses are used to decipher the complex petrogenesis and metallogenesis of these extraordinary rocks, and unravel a complete history of tectonic events related to individual supercontinent cycles.
Immune-Guided Therapy of COVID-19
Authors: Ferraccioli Gianfranco , Gremese Elisa , Goletti Delia , Petrone Linda , Cantini Fabrizio , Ugel Stefano , Canè Stefania , Bronte Vincenzo 
Published: January 2022

Abstract
Vaccination has been a game changer in our efforts to address the coronavirus disease 2019 (COVID-19) pandemic. However, the disease might still represent a clinical crisis for several more years, in part because of the inevitable emergence of variants capable of evading the preexisting immunity. Drugs affecting viral spread will help curtail transmission, but therapeutics are needed to treat the more severe cases requiring hospitalization. A deep analysis of the evolving immune landscape of COVID-19 suggests that understanding the molecular bases of the distinct clinical stages is paramount if we are to limit the burden of inflammation, which can lead to death in frail individuals, according to age, sex, and comorbidities. Different phases can be defined using immune biomarkers and need specific therapeutic approaches, tailored to the underlying immune contexture.
Autologous CD34+ Stem Cell Therapy Increases Coronary Flow Reserve and Reduces Angina in Patients With Coronary Microvascular Dysfunction
Authors: Henry Timothy D. , Bairey Merz C. Noel , Wei Janet , Corban Michel T. , Quesada Odayme , Joung Sandy , Kotynski Christine L. , Wang Jian , Lewis Michelle , Schumacher Ann M. , Bartel Ronnda L. , Takagi Hiroshi , Shah Vishal , Lee Anna , Sietsema William K. , Losordo Douglas W. , Lerman Amir 
Published: January 2022

Background:
Coronary microvascular dysfunction results in angina and adverse outcomes in patients with evidence of ischemia and nonobstructive coronary artery disease; however, no specific therapy exists. CD34+ cell therapy increases microvasculature in preclinical models and improves symptoms, exercise tolerance, and mortality in refractory angina patients with obstructive coronary artery disease. The objective of this research was to evaluate the safety, tolerability, and efficacy of intracoronary CD34+ cell therapy in patients with coronary microvascular dysfunction.

Methods:
We conducted a 2-center, 20-participant trial of autologous CD34+ cell therapy (protocol CLBS16-P01; NCT03508609) in patients with ischemia and nonobstructive coronary artery disease with persistent angina and coronary flow reserve ≤2.5. Efficacy measures included coronary flow reserve, angina frequency, Canadian Cardiovascular Society angina class, Seattle Angina Questionnaire, SF-36, and modified Bruce exercise treadmill test obtained at baseline and 6 months after treatment. Autologous CD34+ cells (CLBS16) were mobilized by administration of granulocyte-colony stimulating factor 5µg/kg/day for 5 days and collected by leukapheresis. Participants received a single intracoronary left anterior descending infusion of isolated CD34+ cells in medium that enhances cell function.

Results:

Coronary flow reserve improved from 2.08±0.32 at baseline to 2.68±0.79 at 6 months after treatment (
P
<0.005). Angina frequency decreased (
P
<0.004), Canadian Cardiovascular Society class improved (
P
<0.001), and quality of life improved as assessed by the Seattle Angina Questionnaire (
P
≤0.03, all scales) and SF-36 (
P
≤0.04, all scales). There were no cell-related serious adverse events.

Conclusions:
In this pilot clinical trial of microvascular angina, patients with ischemia and nonobstructive coronary artery disease receiving intracoronary infusion of CD34+ cell therapy had higher coronary flow reserve, less severe angina, and better quality of life at 6 months. The current study supports a potential therapeutic role for CD34+ cells in patients with microvascular angina.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03508609.
Towards a Semiotics of Chinese Characters
Authors: Ting Liang 
Published: January 2022

Abstract
This article aims to describe the synchronic system of Chinese characters by investigating its cognitive trait of signs. Unlike alphabetic writing systems in which letters represent sounds, Chinese characters convey their meaning in part through images, which makes its synchronic system unique and requires a reconfiguration of the Saussurean framework of signifier and signified. I argue that the Chinese system is instead comprised of three components: pattern, meaning, and formation. Through a close investigation of the historical development of the Chinese character system and drawing on Peirce’s classification of the sign, I propose a threefold adaptation of Saussure’s semiology to Chinese that challenges the arbitrary relationship between signifier and signified, reconfigures the signifier from sound-image to visual character pattern, and proposes a morphological view that takes account of aesthetic principles in the generation and function of meaning.
Updraft Maintenance and Axisymmetrization during Secondary Eyewall Formation in a Model Simulation of Hurricane Matthew (2016)
Authors: Yu Chau-Lam , Didlake Anthony C. , Zhang Fuqing 
Published: January 2022

Abstract
As a follow-on to a previous study on secondary eyewall formation (SEF) in a simulation of Hurricane Matthew (2016), this study investigates the emergence and maintenance of an asymmetric rainband updraft region that leads to an SEF event. Under moderate deep-layer environmental wind shear, the storm develops a quasi-stationary rainband complex with intense, persistent updrafts in its left-of-shear, downwind end. Using a budget of equivalent potential temperature θE, it is demonstrated that the maintenance of the left-of-shear updraft is aided by a mesoscale cold pool induced by rainband stratiform cooling which interacts with the storm’s moist envelope of high-θE air. An extended period of destabilization occurs through differential horizontal advection of θE in the boundary layer, which continuously replenishes the moist instability that would otherwise be depleted by the updrafts. The initial lifting of the updraft is found to be the result of buoyancy advection resulting from the density contrast between the surface cold pool and the inner-core high-θE air. A potential vorticity (PV) budget analysis shows that these left-of-shear updrafts generate low- to midlevel PV through diabatic heating and boundary layer processes, which shapes the local PV enhancement and propagates cyclonically downwind. Meanwhile, in the mid- to upper levels, eddy PV flux convergence and PV generation continue to occur in the stratiform precipitation extending downwind into the upshear quadrants, which substantially increases the azimuthal mean PV at the radius of the developing secondary eyewall and marks the occurrence of the axisymmetrization process.
Characteristics of Wind-Generated Near-Inertial Waves in the Southeast Indian Ocean
Authors: Cyriac Ajitha , Phillips Helen E. , Bindoff Nathaniel L. , Feng Ming 
Published: January 2022

Abstract
This study presents the characteristics and spatiotemporal structure of near-inertial waves and their interaction with Leeuwin Current eddies in the eastern south Indian Ocean as observed by Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats. The floats sampled the upper ocean during July–October 2013 with a frequency of eight profiles per day down to 1200 m. Near-inertial waves (NIWs) are found to be the dominant signal in the frequency spectra. Complex demodulation is used to estimate the amplitude and phase of the NIWs from the velocity profiles. The NIW energy propagated from the base of the mixed layer downward into the ocean interior, following beam characteristics of linear wave theory. We visually identified a total of 15 near-inertial internal wave packets from the wave amplitudes and phases with a mean vertical wavelength of 89 ± 63 m, a mean horizontal wavelength of 69 ± 85 km, a mean horizontal group velocity of 3 ± 2 cm s−1, and a mean vertical group velocity of 9 ± 7 m day−1. A strong near-inertial packet with a kinetic energy of 20–30 J m−3 found propagating below 700 m suggests that the NIWs can contribute to deep ocean mixing. A blue shift of 10%–15% in the energy spectrum of the NIWs is observed in the upper 1200 m as the floats move toward the equator. The impacts of mesoscale eddies on the characteristics and propagation of the observed NIWs are also investigated. The elevated near-inertial shear variance in anticyclonic eddies suggests trapping of NIWs near the surface. Cyclonic eddies, in contrast, were associated with weak near-inertial shear variance in the upper 400 m.
Bias Correction of Mixed Distributions of Temperature with Strong Diurnal Signal
Authors: Haider Muhammad Rezaul , Peña Malaquias , Anagnostou Emmanouil 
Published: January 2022

Abstract
The performance of first-moment and full-distribution bias-correction methods of monthly temperature distributions for seasonal prediction is analyzed by comparing two approaches: the standard all-in-data procedure and the 6-hourly stratification of data. Five models are applied to remove the systematic errors of the CFSv2 forecasts of temperature for the rainy season in the Ethiopian Blue Nile River basin domain. Using deterministic evaluation measures, it is found that the stratification marginally increases the forecast skill especially in regions where the data distribution of temperature is prominently multimodal. The improvement may be attributed to a split of the mixed distribution into a set of unimodal distributions. A necessary condition for this splitting into unimodal distributions is that the amplitude of the diurnal cycle be larger than the interannual variability in the sample. The maximum improvement of stratification is achieved by the first-moment correction model.

Significance Statement
This paper evaluates bias-correction methods of monthly forecast distributions of temperature to improve seasonal forecast skill. It is found that marginal skill is gained when bias correction of the diurnal cycle is performed. This paper contributes to the discussion on the value of subdaily model output data.
Evaluation of three different rapid card tests for the detection of hepatitis B surface antigen
Authors: Gupta Akshita , Ramachandran Krithiga , Paul Diptanu , Gupta Ekta 
Published: January 2022

Rapid diagnostic card tests are crucial steps on the road to hepatitis B elimination and should be incorporated into diagnostic algorithms. However, all commercial rapid diagnostic card tests are not equal and require evaluation before clinical use. Thus, we aimed to compare the performance characteristics of three different rapid diagnostic card tests with chemiluminescence-based assay (CLIA) for the detection of hepatitis B surface antigen. We concluded rapid diagnostic card tests can be used to identify patients with high signal/cut-off ratio on CLIA, but patients with signal/cut-off ratio <200 may be missed. Rapid diagnostic card tests may help pave the way for decentralised testing, but should be used only after evaluation in the community.
Mortality and complications following total aortic arch replacement: 14 years’ experience
Authors: Sanphasitvong Vutthipong , Wongkornrat Wanchai , Jantarawan Teerawoot , Khongchu Nachasa , Slisatkorn Worawong 
Published: January 2022

Background Open total arch replacement is one of the most challenging procedures in cardiothoracic surgery and is the gold standard treatment for aortic arch pathology. Total arch replacement is associated with high rates of mortality and neurological morbidity. Using 14 years of data, we studied postoperative, in-hospital mortality, major complications, and examined associated risk factors. Materials and method Medical records of patients who underwent open, total arch replacement surgery at Siriraj Hospital from 2006 to December 2019 were reviewed. Demographic data, clinical factors, preoperative status, intraoperative data, and postoperative data were analyzed. Result A total of 330 patients were included and 36 (10.9%) died in the hospital. More than one concomitant operation (odds ratio (OR) 5.16, p < 0.001) and emergency operation (OR 3.45, p = 0.003) were risk factors for in-hospital mortality. Major postoperative morbidity occurred in 124 (37.7%) patients (124 of 329). Emergency operation (OR 2.88, p <0.001), preoperative creatinine clearance < 60 ml/ min/ 1.73 m2 (OR 2.04, p = 0.004), and aortic cross-clamp time > 180 min (OR 1.75, p = 0.022) were risk factors for major postsurgical complications. Conclusion In-hospital mortality after total arch replacement was 10.9% compared to international reports. Emergency operation was a major risk factor for both mortality and major complications. More than one concomitant operation, especially coronary artery bypass graft, more than doubled the risk of major complications.