bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of cutaneous and uveal melanoma liver metastases
Authors: Hoefsmit Esmee P , Rozeman Elisa A , Van Trieu My , Dimitriadis Petros , Krijgsman Oscar , Conway Jordan W , Pires da Silva Ines , van der Wal Jacqueline E , Ketelaars Steven L C , Bresser Kaspar , Broeks Annegien , Kerkhoven Ron M , Reeves Jason W , Warren Sarah , Kvistborg Pia , Scolyer Richard A , Kapiteijn Ellen W , Peeper Daniel S , Long Georgina V , Schumacher Ton N M , Blank Christian U 
Published: December 2020

BackgroundThe profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB.MethodsTumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level.ResultsComparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases.ConclusionsWhile TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.
Creatine kinase during non-ST-segment elevation acute coronary syndromes is associated with major bleeding
Authors: Brewster Lizzy Maritza , Fernand Jim 
Published: December 2020

BackgroundIt was recently reported that highly elevated plasma activity of the ADP-scavenging enzyme creatine kinase (CK), to >10 times the upper reference limit (URL), is independently associated with fatal or non-fatal bleeding during treatment for ST-segment elevation myocardial infarction (OR 2.6 (95% CI, 1.8 to 2.7)/log CK increase). Evidence indicates that CK attenuates ADP-dependent platelet aggregation. This study investigates whether moderately elevated CK in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is associated with major bleeding.MethodsThe Thrombolysis In Myocardial Ischemia (TIMI) 3B trial compared recombinant tissue-type plasminogen activator (rt-PA) (35–80 mg) with placebo and early catheterisation with conservative management in patients with NSTE-ACS. Main outcomes of the current study are the independent association of peak plasma CK (CKmax) with adjudicated fatal or non-fatal major bleeding (primary) and with combined major bleeding, stroke and hospital death (secondary), with covariables including age, sex, body mass index, systolic blood pressure, creatinine and assignment to add-on rt-PA versus placebo. Discrimination was assessed with C-statistics.ResultsThe study included 1473 patients (66% men, 80% white, mean age 59 years, SE 0.3). CKmax ranged between 15 and 19 045 IU/L (mean (SE), 450 (24) IU/L; two times URL). Major bleeding occurred in 2.0% (mean age 65 (1.3) years; mean CKmax 1015 (319) IU/L; six times URL), and the combined outcome in 4.3% of the patients, adjusted OR per log CK increase, respectively, 3.1 (1.6 to 5.9) for major bleeding and 3.9 (2.5 to 6.1) for the combined outcome; C-index 0.8 for both outcomes. The association between CK and bleeding was independent of the use of thrombolytic therapy.DiscussionThe presented data add to the existing evidence that proportionate to its plasma activity, the ADP-binding enzyme CK is strongly and independently associated with non-fatal and fatal major bleeding during treatment for NSTE-ACS. CK might increase the accuracy of prediction models for major bleeding in patients with NSTE-ACS.Trial registration numberNCT00000472.
Traumatic abdominal wall hernias: a single-center case series of surgical management
Authors: Chow Kevin L , Omi Ellen C , Santaniello John , Lee Jane K , McElmeel David P , Thomas Yalaunda M , Cartolano Thomas J , Doherty James C , Smith-Singares Eduardo 
Published: December 2020

BackgroundTraumatic abdominal wall hernias (TAWHs) are a rare clinical entity that can be difficult to diagnose and manage. There is no consensus on management of TAWH due to its low incidence and complex concomitant injury patterns. We hereby present the largest single-center case series in the USA to characterize associated injury patterns, identify optimal strategies for hernia management, and determine outcomes.MethodsPatients who presented with a TAWH from blunt trauma requiring operative management were retrospectively identified over a 14-year period. Demographic data, Injury Severity Score (ISS), associated injuries, type of repair, durability of repair, and complications were collected, and descriptive statistics were calculated.ResultsFifteen patients were identified. The average age was 31±11 years, ISS 15±9, and body mass index 33.4±7.1 kg/m2. Mechanisms included falls (13%), motor vehicle collisions (60%), motorcycle accidents (20%), and pedestrian versus motor vehicle collisions (7%). The most commonly associated injuries included colonic injuries (53%), long bone fractures (47%), pelvic fractures (40%), and small bowel injuries (33%). Nineteen hernia repairs were performed: 6 underwent primary suture repair (32%) and 13 used mesh (68%). There were four recurrences. We could not find any significant relationship between contamination and mesh use or recurrence. There was one mortality related to sepsis.DiscussionTAWHs have an associated injury pattern involving fractures and abdominopelvic visceral injuries where a tailored approach is advisable. Without hollow viscous injuries and gross contamination, these hernias can be repaired safely with mesh in the acute setting. However, in patients with gross contamination or hemodynamic instability, the risk of recurrence with primary repair must be weighed against the risk of infection and prolonged surgery with mesh repair. In those cases, a delayed reconstruction in the elective setting may be optimal.
A new f(R) gravity model and properties of gravitational waves in it
Authors: Gogoi Dhruba Jyoti , Dev Goswami Umananda 
Published: December 2020

AbstractIn this paper, we have introduced a new f(R) gravity model as an attempt to have a model with more parametric control, so that the model can be used to explain the existing problems as well as to explore new directions in physics of gravity, by properly constraining it with recent observational data. Here basic aim is to study the properties of Gravitational Waves (GWs) in this new model. In f(R) gravity metric formalism, the model shows the existence of scalar degree of freedom as like other f(R) gravity models. Due to this reason, there is a scalar mode of polarization of GWs present in the theory. This polarization mode exists in a mixed state, of which one is transverse massless breathing mode with non-vanishing trace and the other is massive longitudinal mode. The longitudinal mode being massive, travels at speed less than the usual tensor modes found in General Relativity (GR). Moreover, for a better understanding of the model, we have studied the potential and mass of scalar graviton in both Jordan frame and Einstein frame. This model can pass the solar system tests and can explain primordial and present dark energy. Also, we have put constraints on the model. It is found that the correlation function for the third mode of polarization under certain mass scale predicted by the model agrees well with the recent data of Pulsar Timing Arrays. It seems that this new model would be useful in dealing with different existing issues in the areas of astrophysics and cosmology.
Traversable wormhole solutions in f(R) gravity via Karmarkar condition
Authors: Shamir M. Farasat , Fayyaz I. 
Published: December 2020

AbstractMotivated by recent proposals of possible wormhole shape functions, we construct a wormhole shape function by employing the Karmarkar condition for static traversable wormhole geometry. The proposed shape function generates wormhole geometry that connects two asymptotically flat regions of spacetime and satisfies the required conditions. Further, we discuss the embedding diagram in three-dimensional Euclidean space to present the wormhole configurations. The main feature of current study is to consider three well-known f(R) gravity models, namely exponential gravity model, Starobinsky gravity Model and Tsujikawa f(R) gravity model. Moreover, we investigate that our proposed shape function provides the wormhole solutions with less (or may be negligible) amount of exotic matter corresponding to the appropriate choice of f(R) gravity models and suitable values of free parameters. Interestingly, the solutions obtained for this shape function generate stable static spherically symmetric wormhole structure in the context of non-existence theorem in f(R) gravity. This may lead to a better analytical representation of wormhole solutions in other modified gravities for the suggested shape function.
How to form a wormhole
Authors: Dai De-Chang , Minic Djordje , Stojkovic Dejan 
Published: December 2020

AbstractWe provide a simple but very useful description of the process of wormhole formation. We place two massive objects in two parallel universes (modeled by two branes). Gravitational attraction between the objects competes with the resistance coming from the brane tension. For sufficiently strong attraction, the branes are deformed, objects touch and a wormhole is formed. Our calculations show that more massive and compact objects are more likely to fulfill the conditions for wormhole formation. This implies that we should be looking for wormholes either in the background of black holes and compact stars, or massive microscopic relics. Our formation mechanism applies equally well for a wormhole connecting two objects in the same universe.
RF deflecting cavity for fast radioactive ion beams
Authors: Kutsaev S. V. , Plastun A. S. , Agustsson R. , Bazin D. , Bultman N. , Ostroumov P. N. , Smirnov A. Y. , Taletski K. , Tarasov O. , Zegers R. G. T. 
Published: December 2020

AbstractThe Facility for Rare Isotope Beams (FRIB) will be a new scientific user facility that produces rare-isotope beams for experiments from the fragmentation of heavy ions at energies of 100–200 MeV/u. During the projectile fragmentation, the rare isotope of interest is produced along with many contaminants that need to be removed before the beam reaches detectors. At FRIB, this is accomplished with a magnetic projectile fragment separator. However, to achieve higher beam purity, in particular for proton-rich rare isotopes, additional purification is necessary. RadiaBeam in collaboration with Michigan State University (MSU) has designed a 20.125 MHz radiofrequency (RF) fragment separator capable of producing a 4 MV kick with 18 cm aperture in order to remove contaminant isotopes based on their time of flight. In this paper, we will discuss the RF and engineering design considerations of this separator cavity.
Optimal Strategies for Control of COVID-19: A Mathematical Perspective
Authors: Seidu Baba 
Published: December 2020

A deterministic ordinary differential equation model for SARS-CoV-2 is developed and analysed, taking into account the role of exposed, mildly symptomatic, and severely symptomatic persons in the spread of the disease. It is shown that in the absence of infective immigrants, the model has a locally asymptotically stable disease-free equilibrium whenever the basic reproduction number is below unity. In the absence of immigration of infective persons, the disease can be eradicated whenever

ℛ

0

<
1

. Specifically, if the controls

u

i

,

i
=
1,2,3,4

, are implemented to 100% efficiency, the disease dies away easily. It is shown that border closure (or at least screening) is indispensable in the fight against the spread of SARS-CoV-2. Simulation of optimal control of the model suggests that the most cost-effective strategy to combat SARS-CoV-2 is to reduce contact through use of nose masks and physical distancing.
Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel
Authors: Willis Jason , Lefterova Martina I. , Artyomenko Alexander , Kasi Pashtoon Murtaza , Nakamura Yoshiaki , Mody Kabir , Catenacci Daniel V.T. , Fakih Marwan , Barbacioru Catalin , Zhao Jing , Sikora Marcin , Fairclough Stephen R. , Lee Hyuk , Kim Kyoung-Mee , Kim Seung Tae , Kim Jinchul , Gavino Danielle , Benavides Manuel , Peled Nir , Nguyen Timmy , Cusnir Mike , Eskander Ramez N. , Azzi Georges , Yoshino Takayuki , Banks Kimberly C. , Raymond Victoria M. , Lanman Richard B. , Chudova Darya I. , Talasaz AmirAli , Kopetz Scott , Lee Jeeyun , Odegaard Justin I. 
Published: December 2020

AbstractPurpose:To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.Experimental Design:Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples. Clinical outcomes for 16 patients with cfDNA MSI-H gastric cancer treated with immunotherapy were evaluated.Results:cfDNA MSI evaluation was shown to have high specificity, precision, and sensitivity, with a limit of detection of 0.1% tumor content. In evaluable patients, cfDNA testing accurately detected 87% (71/82) of tissue MSI-H and 99.5% of tissue microsatellite stable (863/867) for an overall accuracy of 98.4% (934/949) and a positive predictive value of 95% (71/75). Concordance of cfDNA MSI with tissue PCR and next-generation sequencing was significantly higher than IHC. Prevalence of cfDNA MSI for major cancer types was consistent with those reported for tissue. Finally, robust clinical activity of immunotherapy treatment was seen in patients with advanced gastric cancer positive for MSI by cfDNA, with 63% (10/16) of patients achieving complete or partial remission with sustained clinical benefit.Conclusions:cfDNA-based MSI detection using Guardant360 is highly concordant with tissue-based testing, enabling highly accurate detection of MSI status concurrent with comprehensive genomic profiling and expanding access to immunotherapy for patients with advanced cancer for whom current testing practices are inadequate.See related commentary by Wang and Ajani, p. 6887
Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer
Authors: Nakajima Takako Eguchi , Kadowaki Shigenori , Minashi Keiko , Nishina Tomohiro , Yamanaka Takeharu , Hayashi Yuichiro , Izawa Naoki , Muro Kei , Hironaka Shuichi , Kajiwara Takeshi , Kawakami Yutaka 
Published: December 2020

Abstract

Purpose:
We conducted a phase I/II study to investigate the safety and efficacy of nivolumab with paclitaxel plus ramucirumab.

Patients and Methods:
Patients with advanced gastric cancer (AGC) refractory to first-line chemotherapy were included. Patients received nivolumab (3 mg/kg on days 1 and 15) combined with paclitaxel (80 mg/m2 on days 1, 8, and 15) and ramucirumab (8 mg/kg on days 1 and 15) every 4 weeks. After feasibility evaluation in six patients (phase I), 37 additional patients were enrolled in the phase II part with the primary endpoint of 6-month progression-free survival (PFS) rate with two-sided 80% confidence interval (CI). The combined positive score (CPS) was defined as the number of programmed death-ligand 1–positive cells divided by the total number of viable tumor cells multiplied by 100.

Results:
Forty-three patients were enrolled. Of these, 60.5% had CPS ≥ 1. Dose-limiting toxicities were observed in two patients, and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients experienced treatment-related adverse events (AEs) grade ≥3 and 14 (32.6%) patients experienced immune-related AEs grade ≥3. The overall response rate was 37.2% (95% CI, 23.0%–53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%–55.8%; P = 0.067). Median survival time was 13.1 months (95% CI, 8.0–16.6 months): 13.8 months (95% CI, 8.0–19.5 months) in patients with CPS ≥ 1 and 8.0 months (95% CI, 4.8–24.1 months) in patients with CPS &lt; 1.

Conclusions:
Nivolumab with paclitaxel plus ramucirumab demonstrated promising antitumor activity with manageable toxicities as second-line treatment for AGC.
Changes in Annual Extremes of Daily Temperature and Precipitation in CMIP6 Models
Authors: Li Chao , Zwiers Francis , Zhang Xuebin , Li Guilong , Sun Ying , Wehner Michael 
Published: December 2020

AbstractThis study presents an analysis of daily temperature and precipitation extremes with return periods ranging from 2 to 50 years in phase 6 of the Coupled Model Intercomparison Project (CMIP6) multimodel ensemble of simulations. Judged by similarity with reanalyses, the new-generation models simulate the present-day temperature and precipitation extremes reasonably well. In line with previous CMIP simulations, the new simulations continue to project a large-scale picture of more frequent and more intense hot temperature extremes and precipitation extremes and vanishing cold extremes under continued global warming. Changes in temperature extremes outpace changes in global annual mean surface air temperature (GSAT) over most landmasses, while changes in precipitation extremes follow changes in GSAT globally at roughly the Clausius–Clapeyron rate of ~7% °C−1. Changes in temperature and precipitation extremes normalized with respect to GSAT do not depend strongly on the choice of forcing scenario or model climate sensitivity, and do not vary strongly over time, but with notable regional variations. Over the majority of land regions, the projected intensity increases and relative frequency increases tend to be larger for more extreme hot temperature and precipitation events than for weaker events. To obtain robust estimates of these changes at local scales, large initial-condition ensemble simulations are needed. Appropriate spatial pooling of data from neighboring grid cells within individual simulations can, to some extent, reduce the needed ensemble size.
Intensified Impacts of Central Pacific ENSO on the Reversal of December and January Surface Air Temperature Anomaly over China since 1997
Authors: Li Hua , Fan Ke , He Shengping , Liu Yong , Yuan Xing , Wang Huijun 
Published: December 2020

AbstractThe reversal of surface air temperature anomalies (SATA) in winter brings a great challenge for short-term climate prediction, and the mechanisms are not well understood. This study found that the reversal of SATA between December and January over China could be demonstrated by the second leading mode of multivariate empirical orthogonal function analysis on the December–January SATA. It further reveals that the central Pacific El Niño–Southern Oscillation (CP ENSO) has contributed more influence on such a reversal of SATA since 1997. CP ENSO shows positive but weak correlations with SATA over China in both December and January during the pre-1996 period, whereas it shows significant negative and positive correlations with the SATA in December and January, respectively, during the post-1997 period. The CP ENSO–related circulations suggest that the change of the Siberian high has played an essential role in the reversal of SATA since 1997. The pattern of sea surface temperature anomalies associated with the CP ENSO leads to a westward-replaced Walker circulation that alters the local meridional circulation and, further, has impacted the Siberian high and SATA over China since 1997. Moreover, the seasonal northward march of the convergence zone from December to January causes a northward-replaced west branch of the Walker circulation in January compared with that in December. The west branch of the Walker circulation in December and January directly modulates local Hadley and Ferrel circulations and then causes contrasting Siberian high anomalies by inducing opposite vertical motion anomalies over Siberia. The reversal of SATA between December and January, therefore, has been more frequently observed over China since 1997. The abovementioned mechanisms are validated by the analysis at pentad time scales and confirmed by numerical simulations.
The Acceptability and Influencing Factors of an Internet-Based Tinnitus Multivariate Integrated Sound Therapy for Patients With Tinnitus
Authors: Lan Tianxiang , Zhao Fei , Xiong Binbin 
Published: December 2020

Objective: To explore the acceptability and influencing factors of an Internet-based Tinnitus Multivariate Integrated Sound Therapy (iT-MIST). The individually tailored sound therapy used narrowband noise centered on the patient’s tinnitus frequency in combination with natural sounds and relaxing music. Design: Patients with tinnitus were given a 1-week trial of iT-MIST. Semistructured interviews were then carried out and a thematic analysis used to analyze, identify, organize, and report factors discovered in the data. Study Sample: Semistructured interviews were carried out with 11 participants, 2 women and 9 men, mean age 39.82 years. Results: The first theme identified from patient interview analysis was their motivation to undertake and expectations of iT-MIST. Nearly half of the participants indicated that advice from the physician was considered very important and professional. Benefits acknowledged by most participants from their iT-MIST experience were accessibility, convenience, time- and cost-effectiveness, and emotional benefit. However, a few participants with poor understanding of tinnitus and iT-MIST showed a negative acceptability with doubtful thoughts and complaints about technical issues such as being easily interrupted by messages and phone calls. Conclusion: Patients with tinnitus in this study were not universally accepting of the iT-MIST therapy. Concerns about their tinnitus and ability to comply with doctor’s recommendations were the main influencing factors. Attitude or willingness to explore new therapies facilitated its use. Emotional benefits, for example, relaxation and comfort, were seen to sustain motivation, while doubtful thoughts and technical problems negatively affected acceptability.