bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
Authors: Ellingsen Espen Basmo , Aamdal Elin , Guren Tormod , Lilleby Wolfgang , Brunsvig Paal F , Mangsbo Sara M , Aamdal Steinar , Hovig Eivind , Mensali Nadia , Gaudernack Gustav , Inderberg Else Marit 
Published: May 2022

BackgroundTherapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response. Three phase I/IIa clinical trials covering malignant melanoma, non-small cell lung cancer, and prostate cancer have been completed, with patients in follow-up for up to 8 years.Methods52 patients were enrolled across the three trials. UV1 was given as monotherapy in the lung cancer trial and concurrent with combined androgen blockade in the prostate cancer trial. In the melanoma study, patients initiated ipilimumab treatment 1 week after the first vaccine dose. Patients were followed for UV1-specific immune responses at frequent intervals during vaccination, and every 6 months for up to 8 years in a follow-up period. Phenotypic and functional characterizations were performed on patient-derived vaccine-specific T cell responses.ResultsIn total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen.ConclusionLong-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer.
Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39
Authors: Tiwari-Heckler Shilpa , Lee Ghee Rye , Harbison James , Ledderose Carola , Csizmadia Eva , Melton David , Zhang Quanzhi , Junger Wolfgang , Chen Guanqing , Hauser Carl J , Otterbein Leo E , Longhi Maria Serena , Robson Simon Christopher 
Published: May 2022

RationaleThe increased mortality and morbidity seen in critically injured patients appears associated with systemic inflammatory response syndrome (SIRS) and immune dysfunction, which ultimately predisposes to infection. Mitochondria released by injury could generate danger molecules, for example, ATP, which in turn would be rapidly scavenged by ectonucleotidases, expressed on regulatory immune cells.ObjectiveTo determine the association between circulating mitochondria, purinergic signalling and immune dysfunction after trauma.MethodsWe tested the impact of hepatocyte-derived free mitochondria on blood-derived and lung-derived CD8 T cells in vitro and in experimental mouse models in vivo. In parallel, immune phenotypic analyses were conducted on blood-derived CD8 T cells obtained from trauma patients.ResultsIsolated intact mitochondria are functional and generate ATP ex vivo. Extracellular mitochondria perturb CD8+T cells in co-culture, inducing select features of immune exhaustion in vitro. These effects are modulated by scavenging ATP, modelled by addition of apyrase in vitro. Injection of intact mitochondria into recipient mice markedly upregulates the ectonucleotidase CD39, and other immune checkpoint markers in circulating CD8+T cells. We note that mice injected with mitochondria, prior to instilling bacteria into the lung, exhibit more severe lung injury, characterised by elevated neutrophil influx and by changes in CD8+T cell cytotoxic capacity. Importantly, the development of SIRS in injured humans, is likewise associated with disordered purinergic signalling and CD8 T cell dysfunction.ConclusionThese studies in experimental models and in a cohort of trauma patients reveal important associations between extracellular mitochondria, aberrant purinergic signalling and immune dysfunction. These pathogenic factors with immune exhaustion are linked to SIRS and could be targeted therapeutically.
Calculations of GDR parameters for deformed nuclei using LogitBoost classifier and artificial neural network
Authors: Üncü Yiğit Ali , Danışman Taner , Özdoğan Hasan 
Published: May 2022

Photo-nuclear interactions are important for investigating fundamental nuclear physics phenomena. The photo-absorption cross-section energy curve displays a wide resonance called giant dipole resonance (GDR) until 30 MeV. First, spherical and deformed nuclei have been determined by using LogitBoost classifier, and then GDR parameters for deformed nuclei have been estimated by using an artificial neural network (ANN) via Levenberg–Marquardt algorithm which has been selected for the training section. In the last step, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] reaction cross-sections have been computed by using GDR parameters obtained ANN estimations. The mean square error, root mean square error, and [Formula: see text] are evaluated as the best performance of ANN estimates. Photo-neutron cross-section results have been compared with experimental data from the literature. Consequently, it has been found that ANN algorithms can be used to determine the GDR parameters for deformed nuclei in the lack of experimental data of photo-absorption reaction.
What Distinguishes MJO Events Associated with Atmospheric Rivers?
Authors: Toride Kinya , Hakim Gregory J. 
Published: May 2022

Abstract
Atmospheric rivers (ARs) are long and narrow bands of intense water vapor transport that often induce heavy precipitation and flooding along the west coast of North America. Previous studies demonstrate that the Madden–Julian oscillation (MJO) contributes to the predictability of AR activity on a subseasonal time scale. However, individual AR responses vary widely following the same phase of MJO. Here we investigate 96 MJO events following phase 3 (convection over the Indian Ocean) and analyze the differences between events that brought large-scale ARs to the entire Pacific Northwest coastal region and those that did not. The MJO events with ARs tend to stay longer at phase 3 than those without ARs. We use linear regression to isolate the extratropical signals linearly related to the MJO and explore how the residual fields differ between the two groups. The linearly dependent signal shows slow-moving planetary-scale water vapor transport across the North Pacific. The residual field exhibits a contrasting extratropical low-frequency (>10 days) pattern in the Gulf of Alaska resembling the Pacific–North American (PNA) pattern: a trough for events with ARs and a ridge for events without ARs. This low-frequency variability alters the Pacific waveguide such that, for MJO events with ARs, baroclinic waves are directed into the Pacific Northwest with an orientation that favors anomalous positive IVT. For MJO events without ARs, the ridge strengthens large-scale anticyclonic flow over the North Pacific and prevents moisture access to the Pacific Northwest.
The Roles of Westward-Propagating Waves and the QBO in Limiting MJO Propagation
Authors: Huang Kai , Pegion Kathleen 
Published: May 2022

Abstract
A recent study categorized the Madden–Julian oscillation (MJO) during boreal winter season into four types called stand, jump, slow, and fast MJO. This study focuses on the stand and jump MJO. Based on whether their convection penetrates the Maritime Continent (MC), stand and jump MJOs are seen as non-penetrating (NP) MJOs, while the other two are seen as eastward-penetrating (EP) MJOs. Results reveal the relative roles of the westward-propagating wave (WPW), as well as the QBO and ENSO, in limiting MJO propagation. Lack of the premoistening over the southern sea surface of the MC stops NP MJO from penetrating the MC. The active convection of the WPWs hinders the descending branch of the NP MJO circulation and therefore leads to the insufficient meridional advective moistening over the southern sea surface of the MC. The independent convection over the Pacific for jump MJOs is influenced by a combined effect of the QBO and ENSO. The tropopause instability induced by the MJO is found to significantly decouple from its convection over the Pacific in westerly QBO (QBOW) winters more than in easterly QBO (QBOE) winters. For jump MJOs, the independent convection over the central Pacific comes from local WPWs whose amplification and further development into deep convection are correlated to jump the MJOs’ decoupled tropopause instability. For stand MJOs, however, the seasonal-mean La Niña–like cool SST anomalies weaken the WPW activity over the central Pacific and confine WPWs within the western Pacific. Therefore, the decoupled tropopause instability of stand MJOs is out phase of WPWs and fails to induce an independent convection over the central Pacific.
Centennial Annual Rainfall Pattern Changes Show an Increasing Trend with Higher Variation over Northern Australia
Authors: He Jie , Feng Puyu , Wang Bin , Zhuang Wei , Zhang Yongqiang , Liu De Li , Cleverly Jamie , Huete Alfredo , Yu Qiang 
Published: May 2022

Abstract
Global warming and anthropogenic activities have imposed noticeable impacts on rainfall pattern changes at both spatial and temporal scales in recent decades. Systematic diagnosis of rainfall pattern changes is urgently needed at spatiotemporal scales for a deeper understanding of how climate change produces variations in rainfall patterns. The objective of this study was to identify rainfall pattern changes systematically under climate change at a subcontinental scale along a rainfall gradient ranging from 1800 to 200 mm yr−1 by analyzing centennial rainfall data covering 230 sites from 1910 to 2017 in the Northern Territory of Australia. Rainfall pattern changes were characterized by considering aspects of trends and periodicity of annual rainfall, abrupt changes, rainfall distribution, and extreme rainfall events. Our results illustrated that rainfall patterns in northern Australia have changed significantly compared with the early period of the twentieth century. Specifically, 1) a significant increasing trend in annual precipitation associated with greater variation in recent decades was observed over the entire study area, 2) temporal variations represented a mean rainfall periodicity of 27 years over wet to dry regions, 3) an abrupt change of annual rainfall amount occurred consistently in both humid and arid regions during the 1966–75 period, and 4) partitioned long-term time series of rainfall demonstrated a wetter rainfall distribution trend across coastal to inland areas that was associated with more frequent extreme rainfall events in recent decades. The findings of this study could facilitate further studies on the mechanisms of climate change that influence rainfall pattern changes.

Significance Statement
Characterizing long-term rainfall pattern changes under different rainfall conditions is important to understand the impacts of climate change. We conducted diagnosis of centennial rainfall pattern changes across wet to dry regions in northern Australia and found that rainfall patterns have noticeably changed in recent decades. The entire region has a consistent increasing trend of annual rainfall with higher variation. Meanwhile, the main shifting period of rainfall pattern was during 1966–75. Although annual rainfall seems to become wetter with an increasing trend, more frequent extreme rainfall events should also be noticed for assessing the impacts of climate changes. The findings support further study to understand long-term rainfall pattern changes under climate change.
Evaluation of the WRF-Lake Model in the Large Dimictic Reservoir: Comparisons with Field Data and Another Water Temperature Model
Authors: Guo Shibo , Wang Fushan , Zhu Dejun , Ni Guangheng , Chen Yongcan 
Published: May 2022

Abstract
The WRF-lake, as a one-dimensional (1D) lake model popularly used for coupling with the Weather Research and Forecasting (WRF) system and modeling lake–atmosphere interactions, does not consider the heat exchange caused by inflow–outflow, which is an important characteristic of large reservoirs and can affect the energy budget and reservoir–atmosphere interactions. We evaluated the WRF-lake model by applying it at a large dimictic reservoir, Miyun Reservoir, in northern China. The results show that the WRF-lake model, though ignoring inflow–outflow, yields good surface water temperature simulation through reasonable parameterization. The Minlake model, as a better physically based model in reservoirs, was used to test the effect of inflow–outflow, including heat carried by inflow–outflow water exchange and water level change on the 1D model’s performance. The effect of heat carried by inflow–outflow is mainly in summer, negatively correlated with hydraulic residence time and positively correlated with temperature difference between inflow and outflow. For a reservoir with hydraulic residence time of 3 years and temperature difference between inflow and outflow about 10°C in summer, the heat carried by inflow–outflow is far less than the heat exchange through the surface (<2%) and therefore has little influence on total energy balance. The effect of water level change is mainly on latent heat and sensible heat in unit area, rather than outgoing longwave radiation. Though influencing the temperature in deep layers, the water level change does not have a significant impact on the surface temperature.

Significance Statement
The purpose of this study is to evaluate the applicability of WRF-lake, an important submodule of the Weather Research and Forecasting (WRF) system, in the large dimictic reservoir. This is important because WRF-lake does not consider the effect of inflow–outflow and water level change, which are important characteristics of large reservoirs and can affect the heat budget and reservoir–atmosphere interactions. The applicability of WRF-lake in large reservoirs with frequent inflow–outflow and water level change is widely concerned but has never been discussed in previous studies. Our research explored the applicability of WRF-lake in the large dimictic reservoir and discussed the effect of inflow–outflow and water level change quantitively.
Rain Impacts on the Surface Atmosphere and Upper Ocean in the Central Equatorial Pacific
Authors: Whitt Daniel B. 
Published: May 2022

Abstract
The impacts of rainy days (>24 mm) on the physics of the surface atmosphere and upper ocean are characterized in the central Pacific Ocean (140°–170°W) on the equator, where deep-cycle turbulence substantially influences the sea surface temperature and air–sea heat flux on diurnal and longer time scales. Here, rainfall is relatively weak on average (1–3 mm day−1), and enough rain to substantially alter the diurnal cycle of upper-ocean buoyancy only occurs on the order of once in 100 days, albeit more frequently to the west and during El Niño and boreal winter. Rainy days are associated with multiple systematic changes in the surface atmosphere, but the freshwater and the reduction in daily downwelling shortwave radiation (by ∼50 W m−2) are codominant and drive systematic changes in the ocean during and the day after the rainy day. These two drivers explain ensemble average reductions in the upper-ocean salinity (−0.12 psu at 1 m) and temperature (−0.16°C at 1 m) and increases in buoyancy (+0.0005 m s−2 at 1 m), which are typically confined to a shallow fresh/warm mixing layer on the order of 10 m thick in the daytime. At deeper depths, the intrinsic ocean temperature, salinity, and velocity variability make it challenging to extract an ensemble average response to rainy days in observations, but some examples from observations and large-eddy simulations suggest that rainfall can significantly reduce the vertical extent and heat flux in the deep-cycle turbulence, although the bulk energetics and buoyancy flux of the turbulence are not necessarily modified by rain.

Significance Statement
Rain significantly impacts social and ecological systems in many ways that are readily apparent in populated areas, but the impacts of rain over the ocean are not as well known. In this paper, sustained in situ observations over decades and highly resolved numerical simulations of ocean turbulence during a few rain events are used to characterize the impacts of rainy days on the surface–atmosphere and upper-ocean physics in the center of action of El Niño in the central equatorial Pacific. These results contribute to broader efforts to observe, understand, and accurately model the surface atmosphere, the upper ocean, and air–sea interaction in the central Pacific and thereby improve long-range weather and climate observations and predictions.
Lower Rates of Unplanned Conversion to Open in Robotic Approach to Esophagectomy for Cancer
Authors: Silva Jack P. , Putnam Luke R. , Wu Jessica , Ding Li , Samakar Kamran , Abel Stuart , Nguyen James D. , Dobrowolsky Adrian B. , Bildzukewicz Nikolai A. , Lipham John C. 
Published: May 2022

Background Minimally invasive approaches to esophagectomy have gained popularity worldwide; however, unplanned conversion to an open approach is not uncommon. This study sought to investigate risk factors associated with converting to an open approach and to evaluate outcomes following conversion. Methods Patients undergoing minimally invasive esophagectomy (MIE) for cancer were identified using the 2016-2019 Procedure Targeted NSQIP Database. Multivariable, stepwise logistic regression analysis was performed to investigate factors associated with unplanned conversion to open esophagectomy. Propensity-matched comparison of robotic (RAMIE) to traditional MIE was performed. Results A total of 1347 patients were included; 140 patients (10%) underwent conversion to open. Morbid obesity, diabetes, hypertension, American Society of Anesthesiologists class, and squamous cell carcinoma were associated with a higher likelihood of conversion. A robotic approach was associated with a lower likelihood of conversion to open (OR .57, 95% CI 0.32-.99). On multivariable analysis, squamous cell carcinoma pathology was the only variable independently associated with higher odds of conversion (OR 2.66, 95% CI 1.02-6.98). Propensity-matched comparison of RAMIE vs MIE showed no significant difference in conversion rate (6.5% vs 9.1%, P = .298), morbidity, or mortality. Discussion A robotic approach to esophagectomy was associated with a lower likelihood of unplanned conversion to open, and patients who were converted to open experienced worse outcomes. Future studies should aim to determine why a robotic esophagectomy approach may lead to fewer open conversions as it may be an underappreciated benefit of this newest operative approach.
Anger Is All the Rage: A Theoretical Analysis of Anger Within Emotional Ecology to Foster Growth and Political Change
Authors: Heilman Elizabeth E. 
Published: May 2022

Background and Purpose: Anger is implicated in nearly every social pathology, from war to bullying to child abuse. Yet, it is also the spark of reform for nearly every positive social movement, from civil rights to labor rights to handicapped rights. This article examines how anger has been understood and misunderstood across different discursive spaces in society, research, and education to offer a peace-promoting, emotional ecology theory of anger to foster emotional growth and political change. Research Design: This article employs theoretical research, which is a logical exploration of a system of beliefs and assumption to increase understanding, develop new theory, and explore implications. Findings: Anger is reconceptualized as a crucial emotional and political experience rooted in the emotional ecologies and histories of family, school, and society. Three distinctive features characterize it: An ethical response, an emotional response, and an action response. Five steps to anger resolution follow from this analysis including: mindfulness, compassion, insight, action, and a therapeutic response (or MCIAT). Recommendations: Future studies on anger should span developmental stages and include ways anger intersects with curricula, emotional experience and intellectual understanding. Teachers, social workers, and therapists must work together to address the emotional and political aspects of anger in education. Addressing our most painful and angering global challenges in all their complexity requires full integration of the personal, educational, civic, and therapeutic dimensions of emotional ecology and this worthy enterprise should inspire interdisciplinary dialogue and future research.