bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary artery calcium progression after coronary artery bypass grafting surgery
Authors: Abazid Rami M , Romsa Jonathan G , Akincioglu Cigdem , Warrington James C , Bureau Yves , Kiaii Bob , Vezina William C 
Published: June 2021

ObjectivesAccelerated atherosclerosis is a well-established phenomenon after coronary artery bypass grafting surgery (CABG). In this study, we analysed coronary artery calcium (CCS) progression after CABG.MethodsWe retrospectively measured the CCS Agatston score (AS), volume score (VS) and mass score (MS) of 39 patients before and after CABG. The annualised CCS change and annualised CCS percent change of each coronary artery, coronary artery segments proximal and distal to anastomosis were analysed.ResultsMean age at the time of the surgery was 59.8±8.5 years. Follow-up period between the first and second CT scans was 6.7±2.8 (range, 1.1–12.8) years. Annualised CCS percent change (AS, VS and MS) of the coronary segments proximal-to-anastomosis did not differ from that of the non-grafted coronary arteries as follow: segments proximal-to-anastomosis: median (Q1–Q3) 12.8 (5.0–37.4), 13.7 (6.1–41.1) and 14.9 (5.4–53.7), left main coronary artery 12.6 (7.4–43.8), 22.0 (8.1–44.4) and 18.2 (7.3–57.4), non-grafted left circumflex artery: 13.5 (4.4–38.1), 10.5 (2.9–45.2) and 11.5 (7.1–47.9) and non-grafted right coronary artery: 31.4 (14.4–74.5), 25.2 (16.7–62.0) and 31.3 (23.8–85.6), respectively. Likewise, annualised percent change (AS, VS and MS) was similar between the native coronary arteries. Multivariate regression analysis showed that diabetes mellitus was the only predictor of annualised percent progression of the total CCS of >15% (HR, 8.12; 95% CI, 1.05 to 26.6; p=0.04).ConclusionThe CCS post-CABG did not follow an accelerated progression process. Among coronary artery disease risk factors, diabetes mellitus is the only predictor of annualised CCS percent progression of >15% post-CABG.
CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?
Authors: Miggelbrink Alexandra M. , Jackson Joshua D. , Lorrey Selena J. , Srinivasan Ethan S. , Waibl-Polania Jessica , Wilkinson Daniel S. , Fecci Peter E. 
Published: June 2021

AbstractIn chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.
Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening
Authors: Lalazar Gadi , Requena David , Ramos-Espiritu Lavoisier , Ng Denise , Bhola Patrick D. , de Jong Ype P. , Wang Ruisi , Narayan Nicole J.C. , Shebl Bassem , Levin Solomon , Michailidis Eleftherios , Kabbani Mohammad , Vercauteren Koen O.A. , Hurley Arlene M. , Farber Benjamin A. , Hammond William J. , Saltsman James A. , Weinberg Ethan M. , Glickman J. Fraser , Lyons Barbara A. , Ellison Jessica , Schadde Erik , Hertl Martin , Leiting Jennifer L. , Truty Mark J. , Smoot Rory L. , Tierney Faith , Kato Tomoaki , Wendel Hans-Guido , LaQuaglia Michael P. , Rice Charles M. , Letai Anthony , Coffino Philip , Torbenson Michael S. , Ortiz Michael V. , Simon Sanford M. 
Published: June 2021

Abstract

To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable.

Significance:
Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor.
This article is highlighted in the In This Issue feature, p. 2355
Characterizing the Complexities of Neutrophils with Suppressive Properties
Authors: Cassatella Marco Antonio 
Published: June 2021

Abstract
Several not-yet fully described neutrophil populations exerting either antitumor or suppressive/protumor functions may appear in the circulation of patients with cancer and/or infiltrate tumor tissues. In this issue, Emmons and colleagues provide new information on how complement-dependent “activation” of normal mature neutrophils renders the cells able to inhibit T-cell responsiveness in vitro. The data highlight the complexities of understanding the biology of neutrophil-mediated T-cell suppression.
See related article by Emmons et al., p. 790.
Electrophysiological Characteristics of Intra‐Atrial Reentrant Tachycardia in Adult Congenital Heart Disease: Implications for Catheter Ablation
Authors: Kahle Ann‐Kathrin , Gallotti Roberto G. , Alken Fares‐Alexander , Meyer Christian , Moore Jeremy P. 
Published: June 2021

Background
Ultra‐high‐density mapping enables detailed mechanistic analysis of atrial reentrant tachycardia but has yet to be used to assess circuit conduction velocity (CV) patterns in adults with congenital heart disease.

Methods and Results

Circuit pathways and central isthmus CVs were calculated from consecutive ultra‐high‐density isochronal maps at 2 tertiary centers over a 3‐year period. Circuits using anatomic versus surgical obstacles were considered separately and pathway length <50th percentile identified small circuits. CV analysis was used to derive a novel index for prediction of postablation conduction block. A total of 136 supraventricular tachycardias were studied (60% intra‐atrial reentrant, 14% multiple loop). Circuits with anatomic versus surgical obstacles featured longer pathway length (119 mm; interquartile range [IQR], 80–150 versus 78 mm; IQR, 63–95;
P
<0.001), faster central isthmus CV (0.1 m/s; IQR, 0.06–0.25 versus 0.07 m/s; IQR, 0.05–0.10;
P
=0.016), faster non‐isthmus CV (0.52 m/s; IQR, 0.33–0.71 versus 0.38 m/s; IQR, 0.27–0.46;
P
=0.009), and fewer slow isochrones (4; IQR, 2.3–6.8 versus 6; IQR 5–7;
P
=0.008). Both central isthmus (
R
2
=0.45;
P
<0.001) and non‐isthmus CV (
R
2
=0.71;
P
<0.001) correlated with pathway length, whereas central isthmus CV <0.15 m/s was ubiquitous for small circuits. Non‐isthmus CV in tachycardia correlated with CV during block validation (
R
2
=0.94;
P
<0.001) and a validation map to tachycardia conduction time ratio >85% predicted isthmus block in all cases. Over >1 year of follow‐up, arrhythmia‐free survival was better for homogeneous CV patterns (90% versus 57%;
P
=0.04).

Conclusions
Ultra‐high‐density mapping‐guided CV analysis distinguishes atrial reentrant patterns in adults with congenital heart disease with surgical obstacles producing slower and smaller circuits. Very slow central isthmus CV may be essential for atrial tachycardia maintenance in small circuits, and non‐isthmus conduction time in tachycardia appears to be useful for rapid assessment of postablation conduction block.
Revisiting Moore’s Anti-Skeptical Argument in “Proof of an External World”
Authors: Stratman Christopher 
Published: June 2021

Abstract
This paper argues that we should reject G. E. Moore’s anti-skeptical argument as it is presented in “Proof of an External World.” However, the reason I offer is different from traditional objections. A proper understanding of Moore’s “proof” requires paying attention to an important distinction between two forms of skepticism. I call these Ontological Skepticism and Epistemic Skepticism. The former is skepticism about the ontological status of fundamental reality, while the latter is skepticism about our empirical knowledge. Philosophers often assume that Moore’s response to “external world skepticism” deals exclusively with the former, not the latter. But this is a mistake. I shall argue that Moore’s anti-skeptical argument targets an ontological form of skepticism. Thus, the conclusion is an ontological claim about fundamental reality, while the premises are epistemic claims. If this is correct, then the conclusion outstrips the scope of its premises and proves too much.
A New k-Distribution Scheme for Clear-Sky Radiative Transfer Calculations in Earth’s Atmosphere. Part II: Solar (Shortwave) Heating due to H2O and CO2
Authors: Chou Ming-Dah , Lee Kyu-Tae , Zo Il-Sung , Lee Wei-Liang , Shiu Chein-Jung , Jee Joon-Bum 
Published: June 2021

AbstractA new k-distribution scheme without the assumption of the correlation between the absorption coefficients at different pressures is developed for solar heating due to water vapor and CO2. Grouping of spectral points is based on the observation that radiation at spectral points with a large absorption coefficient is quickly absorbed to heat the stratosphere, and the heating below is attributable to the absorption of the solar radiation at the remaining spectral points. By grouping the spectral points with a large absorption coefficient at low pressures, the range of the absorption coefficient of the remaining spectral points is narrowed, and the k-distribution approximation can be accurately applied to compute solar heating in both the stratosphere and troposphere. Grouping of the spectral points is based on the absorption coefficient at a couple of reference pressures where heating is significant. With a total number of 52 spectral groups in the water vapor and CO2 bands, fluxes and heating rates were calculated for various solar zenith angles in some typical and sampled atmospheres in diverse climatic regimes and seasons. The maximum heating rate difference between the k-distribution and line-by-line calculations is < 0.09 K day-1 for water vapor, and < 0.2 K day-1 for CO2. The difference in the surface radiation is ~ 1.4 W m-2 for water vapor and 0.6 W m-2 for CO2, while it could increase to 2.6 W m-2 due to overlapping absorption. These results can be improved by increasing the number of spectral groups at the expense of computational economy.
Projected sea-level changes in the marginal seas near China based on dynamical downscaling
Authors: Jin Yi , Zhang Xuebin , Church John A. , Bao Xianwen 
Published: June 2021

AbstractProjections of future sea-level changes are usually based on global climate models (GCMs). However, the changes in shallow coastal regions, like the marginal seas near China, cannot be fully resolved in GCMs. To improve regional sea-level simulations, a high-resolution (~8 km) regional ocean model is set up for the marginal seas near China for both the historical (1994-2015) and future (2079-2100) periods under representative concentration pathways (RCPs) 4.5 and 8.5. The historical ocean simulations are evaluated at different spatiotemporal scales, and the model is then integrated for the future period, driven by projected monthly climatological climate change signals from 8 GCMs individually via both surface and open boundary conditions. The downscaled ocean changes derived by comparing historical and future experiments reveal greater spatial details than those from GCMs, e.g., a low dynamic sea level (DSL) centre of -0.15 m in the middle of the South China Sea (SCS). As a novel test, the downscaled results driven by the ensemble mean forcings are almost identical with the ensemble average results from individually downscaled cases. Forcing of the DSL change and increased cyclonic circulation in the SCS are dominated by the climate change signals from the Pacific, while the DSL change in the East China marginal seas is caused by both local atmosphere forcing and signals from the Pacific. The method of downscaling developed in this study is a useful modelling protocol for adaptation and mitigation planning for future oceanic climate changes.
Variable Nordic Seas inflow linked to shifts in North Atlantic circulation
Authors: Asbjørnsen Helene , Johnson Helen L. , Årthun Marius 
Published: June 2021

AbstractThe inflow across the Iceland-Scotland Ridge determines the amount of heat supplied to the Nordic Seas from the subpolar North Atlantic (SPNA). Consequently, variable inflow properties and volume transport at the ridge influence marine ecosystems and sea ice extent further north. Here, we identify the upstream pathways of the Nordic Seas inflow, and assess the mechanisms responsible for interannual inflow variability. Using an eddy-permitting ocean model hindcast and a Lagrangian analysis tool, numerical particles are released at the ridge during 1986-2015 and tracked backward in time. We find an inflow that is well-mixed in terms of its properties, where 64% comes from the subtropics and 26% has a subpolar or Arctic origin. The local instantaneous response to the NAO is important for the overall transport of both subtropical and Arctic-origin waters at the ridge. In the years before reaching the ridge, the subtropical particles are influenced by atmospheric circulation anomalies in the gyre boundary region and over the SPNA, forcing shifts in the North Atlantic Current (NAC) and the subpolar front. An equatorward shifted NAC and westward shifted subpolar front correspond to a warmer, more saline inflow. Atmospheric circulation anomalies over the SPNA also affect the amount of Arctic-origin water re-routed from the Labrador Current toward the Nordic Seas. A high transport of Arctic-origin water is associated with a colder, fresher inflow across the Iceland-Scotland Ridge. The results thus demonstrate the importance of gyre dynamics and wind forcing in affecting the Nordic Seas inflow properties and volume transport.
Episodic versus Chronic Dizziness: An Analysis of Predictive Factors
Authors: Formeister Eric J. , Chae Ricky , Wong Emily , Chiao Whitney , Pasquesi Lauren , Sharon Jeffrey D. 
Published: June 2021

Objectives: To elucidate differences in demographic and clinical characteristics between patients with episodic and chronic dizziness. Methods: A cross-sectional, observational study of 217 adults referred for dizziness at 1 tertiary center was undertaken. Subjects were split into a chronic dizziness group (>15 dizzy days per month) and an episodic dizziness group (<15 dizzy days per month). Results: 217 adults (average age, 53.7 years; 56.7% female) participated. One-third (n = 74) met criteria for chronic dizziness. Dizziness handicap inventory (DHI) scores were significantly higher in those with chronic dizziness compared to those with episodic dizziness (53.9 vs 40.7; P < .001). Comorbid depression and anxiety were more prevalent in those with chronic dizziness (44.6% and 47.3% vs 37.8% and 35.7%, respectively; P > .05). Abnormal vestibular testing and abnormal imaging studies did not differ significantly between the 2 groups. Ménière’s disease and BPPV were significantly more common among those with episodic dizziness, while the prevalence of vestibular migraine did not differ according to chronicity of symptoms. A multivariate regression that included age, sex, DHI, history of anxiety and/or depression, associated symptoms, and dizziness triggers was able to account for 15% of the variance in the chronicity of dizziness (pseudo- R2 = 0.15; P < .001). Conclusions: Those who suffer from chronic dizziness have significantly higher DHI and high comorbid rates of depression and anxiety than those with episodic dizziness. Our findings show that factors other than diagnosis alone are important in the chronification of dizziness, an observation that could help improve on multimodal treatment options for this group of patients.
A Simple Method for Simulating Dementia Onset and Death within an Existing Demographic Model
Authors: Rutter Carolyn M. , Edochie Ifeanyi , Friedman Esther M. , Slaughter Mary E. , Weden Margaret M. 
Published: June 2021

Background Dementia is a common disease that has an impact on both the affected individual and family members who provide caregiving. Simulation models can assist in setting policy that anticipates public health needs by predicting the demand for and availability of care. Objective We developed a relatively simple method for simulating the onset of dementia that can be used in combination with an existing microsimulation model. Methods We started with Socsim, a demographic microsimulation model that simulates a population with family kinship networks. We simulated dementia in the Socsim population by simulating the number of individuals diagnosed with dementia in their lifetime and the ages of onset and death from dementia for each of these dementia cases. We then matched dementia cases to the simulated population based on age at death, so for each individual, we simulate whether they develop dementia and, if so, their age at onset. This approach simulates dementia onset but does not alter the demographic model’s simulated age of death. Results We selected model dementia parameters so that the combined Socsim-Dementia model reproduces published dementia prevalence rates and survival times after diagnosis. Conclusions Adding simulation of dementia to a kinship network model enables prediction of the availability of family caregivers for people with dementia under a range of different assumptions about future fertility, mortality, and dementia risk. We demonstrated how to add simulation of dementia onset and death to an existing microsimulation model to obtain a method for predicting dementia prevalence in the context of another more detailed model. The approach we developed can be generalized to simulate other progressive health conditions that affect mortality.
Transcatheter arterial embolization of iatrogenic massive arterioportal fistula in the liver
Authors: Okumura Kenichiro , Kobayashi Satoshi , Ogi Takahiro , Sugiura Takumi , Zhang Yu , Kanatani Mao , Yoneda Norihide , Kitao Azusa , Kozaka Kazuto , Gabata Toshifumi , Koda Wataru 
Published: June 2021

Background Massive arterioportal fistula (APF) is naturally irreversible and can induce portal hypertension and portal vein thrombosis (PVT), worsening survival outcomes. Purpose To evaluate the clinical course and details of transarterial embolization (TAE) procedures for massive APF. Material and Methods This retrospective single-center observational study evaluated the time until embolization after puncture, imaging, embolization methods, and laboratory data of 10 consecutive patients who were diagnosed with massive APF after puncture and underwent TAE at our hospital from 1 April 2012 to 30 September 2019. Results Out of 10 cases, eight demonstrated a simple type and the other two cases a complex network type on the digital subtraction angiography pattern of massive APF. In two simple-type cases for which re-embolization was required, other subsegmental branches were embolized. The two cases showing a complex network type had been embolized via not only the subsegmental branch, but also the extrahepatic and multiple subsegmental branches. Child–Pugh scores were improved in eight of the ten cases. PVT was seen in six cases before embolization, but disappeared after embolization in all cases, despite the fact that three cases had not received anticoagulant therapy. Six cases had digestive varices before embolization, suggesting portal hypertension, and two of the six cases with esophageal varices and one with gastric varices decreased after embolization. Conclusion TAE for massive APF contributed to the improvement of hepatic reserve, the disappearance of PVT, and the improvement of portal hypertension; however, embolization of multiple branches may still be required in some cases.
Creating an entrepreneurial learning environment for entrepreneurship education in HE: The educator’s perspective
Authors: Ilonen Sanna 
Published: June 2021

This paper focuses on entrepreneurship educators as creators of an entrepreneurial learning environment in entrepreneurship education. Entrepreneurship education research has concentrated mainly on the subjects of education (i.e. the students) or on the content of learning, leaving individuals with a critical role in entrepreneurship education – the educators – without sufficient attention. In response, the research question for this study is: how do entrepreneurship educators create entrepreneurial learning environments in entrepreneurship education within higher education? The qualitative study draws on the principles of Vosniadou et al. concerning active learning environments by concentrating on interviews with entrepreneurship educators and documentary data. An entrepreneurial learning environment can be defined as a self-regulatory, co-created learning setting in which entrepreneurship students from different backgrounds learn in teams, as the findings suggest that educators emphasise adjustable co-creation within a ‘given’ format involving individuals with complementary skills working in teams. The study contributes to fulfilment of the identified need to understand the educator’s perspective, and to share the know-how and educational experiences of entrepreneurship educators. Practitioners can use the findings as a concrete tool for the creation of an entrepreneurial learning environment. They can learn from, adopt and develop the practices discussed when designing learning environments for their entrepreneurship students.