bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keep It Green for Generations to Come: Trail Running Events and the Impact on the Environment
Authors: Grafnetterova Nikola 
Published: May 2022

Trail running events, which are a form of adventure sport tourism, have been growing in popularity. However, with the influx of trail users, concerns prevail about the impact of these events on the natural environment. In general, sport and nature have a bidirectional relationship, and one cannot exist without the other. Therefore, for sport to remain an integral part of people’s lives and be preserved for future generations, it is imperative that all sport stakeholders, inclusive of patrons of sport and those managing it, accept their ethical responsibility toward nature and find ways to become more environmentally friendly. As such, it is important to educate future leaders of the sport industry about the importance of environmental sustainability and stewardship. Subsequently, this case allows students to (a) examine the relationship between sport and the environment, (b) reflect on how values shape the sport industry, (c) practice ethical decision making, (d) develop a code of conduct for a sport organization, and (e) craft a personal “leadership philosophy” statement.
Predicting Group II pulmonary hypertension: diagnostic accuracy of the H2FPEF and OPTICS scores in Scotland
Authors: Stubbs Harrison , MacLellan Alexander , McGettrick Michael , Jani Bhautesh , Brewis Melanie , Church Colin , Johnson Martin 
Published: May 2022

ObjectiveGroup II pulmonary hypertension (PH) can be challenging to distinguish from Group I PH without proceeding to right heart catheterisation (RHC). The diagnostic accuracy of the H2FPEF and OPTICS scores was investigated in Scotland.MethodsPatients were included in the study if they were referred to the Scottish Pulmonary Vascular Unit between 2016 and 2020 and subsequently diagnosed with Group II PH or Group I PH which was either idiopathic, heritable or pulmonary veno-occlusive disease. The established cut offs for the H2FPEF and for the OPTICS scores were applied retrospectively to predict the presence of Group II PH. The diagnosis from the scores were compared with the MDT consensus diagnosis following RHC.Results107 patients with Group I PH and 86 patients with Group II PH were included. Retrospective application of the OPTICS score demonstrated that pretest scoring would detect 28% of cases with Group II PH yet at the cost of misdiagnosing 4% of patients with Group I as Group II PH (specificity 0.96). The H2FPEF score had a far greater sensitivity (0.70) yet reduced specificity (0.91), leading to misdiagnosis of 9% of Group I PH cases.ConclusionWhile the specificity of these scores was high, the lack of perfect specificity limits their utility as it results in missed patients with Group I PH. As a consequence, they cannot replace RHC as the means of diagnosing the aetiology of PH in their current form. The scores may still be used to support clinical judgement or to indicate the advisability for further provocative testing at RHC.
Impact of multicarbohydrase and phytase on apparent and standardized digestibility, energy, and nutrient balance in broilers fed sunflower meal
Authors: Araujo Robert Guaracy Aparecido Cardoso , Vela Connie Gallardo , Sartori José Roberto , Neto Messias Alves da Trindade 
Published: May 2022

The apparent total tract digestibility (ATTD) (trial 1) and the apparent (AID) and standardized (SID) ileal digestibility of the amino acids (AAs) (trial 2) in sunflower meal (SM) were evaluated with the addition of exogenous multicarbohydrase (MC) and phytase (Phy). A total of 80 28-day-old broilers were allotted in a completely randomized design to receive treatments up to 35 days of age. A 2 × 2 factorial design was used to determine the enzyme effects, on the ATTD of dry matter, nitrogen, calcium, phosphorus, and fibre, energy use, and the AID and SID of AA, in five replicate cages. Synergic effect was identified between MC and Phy on the ATTD of minerals and fibre. The same benefit occurred with the isolated inclusion of MC on the ATTD of dry matter, nitrogen, and energy of SM. The effects of enzyme inclusion on the AID and SID of AAs in SM, established by comparing the means, suggested a higher effect to the addition of MC + Phy combibation. Supplementation of MC or combination with MC and Phy was a viable alternative to increase the ATTD of nutrients and energy. The addition MC + Phy higher AID and SID of AA from SM.
Contributions of S-, P-, and D-wave resonances to the quasi-two-body decays $$B^{0}_{s} \rightarrow \psi (3686,3770)K \pi $$ in the perturbative QCD approach
Authors: Liu Wen , Yu Xian-Qiao 
Published: May 2022

AbstractBased on the perturbative quantum chromodynamics (pQCD) approach and the quasi-two-body approximation, we have studied the three-body decays $$B^{0}_{s}\rightarrow \psi (3686,3770)K \pi $$

B
s
0

→
ψ

(
3686
,
3770
)

K
π

, which include the contributions of the intermediate resonances $$\overline{K }^{*}_{0}(1430)^{0}$$

K
¯

0

∗

(
1430
)

0

, $$\overline{K }^{*}(892)^{0}$$

K
¯

∗

(
892
)

0

, $$\overline{K }^{*}(1410)^{0}$$

K
¯

∗

(
1410
)

0

, $$\overline{K }^{*}(1680)^{0}$$

K
¯

∗

(
1680
)

0

, and $$\overline{K }^{*}_{2}(1430)^{0}$$

K
¯

2

∗

(
1430
)

0

. The time-like form factors corresponding to the distribution amplitudes of the S-, P-, and D-wave of the kaon–pion pair were adopted in parameterized form, and describe the interactions between $$K $$
K
and $$\pi $$
π
in the resonance region. First, the decays $$B^{0}_{s}\rightarrow \psi (2S,1D)K ^{-}\pi ^{+}$$

B
s
0

→
ψ

(
2
S
,
1
D
)

K
-

π
+

were calculated, followed by the calculation of the branching ratios of the decays $$B^{0}_{s}\rightarrow \psi (3686,3770)K ^{-}\pi ^{+}$$

B
s
0

→
ψ

(
3686
,
3770
)

K
-

π
+

using the 2S–1D mixing scheme. In addition, the pQCD predictions for the decays $$B^{0}_{s}\rightarrow \psi (2S,1D)K \pi $$

B
s
0

→
ψ

(
2
S
,
1
D
)

K
π

and $$B^{0}_{s}\rightarrow \psi (3686,3770)K \pi $$

B
s
0

→
ψ

(
3686
,
3770
)

K
π

were obtained using the narrow-width approximation relation given by the Clebsch–Gordan coefficients. Our work shows that the $$\overline{K }^{*}(892)^{0}$$

K
¯

∗

(
892
)

0

resonance is the main contributor to the total decay, and the branching ratio and the longitudinal polarization fraction of the $$\psi (2S)\overline{K }^{*}(892)^{0}$$

ψ

(
2
S
)

K
¯

∗

(
892
)

0

decay mode agree well with the currently available data within errors. Furthermore, the theoretical predictions of the $$\psi (2S)$$

ψ
(
2
S
)

and $$\psi (3686)$$

ψ
(
3686
)

decay modes are very close, indicating that they can be regarded as the same meson state. Finally, the pQCD predictions for branching ratios of decays $$B^{0}_{s}\rightarrow \psi (3686,3770)K \pi $$

B
s
0

→
ψ

(
3686
,
3770
)

K
π

are of the order of $$10^{-5}$$

10

-
5

and $$10^{-6}$$

10

-
6

, respectively, which can be verified using the ongoing LHCb and Belle II experiments.
Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials
Authors: Bellmunt Joaquim , de Wit Ronald , Fradet Yves , Climent Miguel A. , Petrylak Daniel P. , Lee Jae-Lyun , Fong Lawrence , Necchi Andrea , Sternberg Cora N. , O'Donnell Peter H. , Powles Thomas , Plimack Elizabeth R. , Bajorin Dean F. , Balar Arjun V. , Castellano Daniel , Choueiri Toni K. , Culine Stephane , Gerritsen Winald , Gurney Howard , Quinn David I. , Vuky Jacqueline , Vogelzang Nicholas J. , Cristescu Razvan , Lunceford Jared , Saadatpour Assieh , Loboda Andrey , Ma Junshui , Rajasagi Mohini , Godwin James Luke , Homet Moreno Blanca , Grivas Petros 
Published: May 2022

Abstract

Purpose:
In an exploratory analysis, we investigated the association between programmed death ligand 1 (PD-L1), tumor mutational burden (TMB), T-cell–inflamed gene expression profile (TcellinfGEP), and stromal signature with outcomes of pembrolizumab in urothelial carcinoma (UC).

Patients and Methods:
Patients with advanced UC received first-line pembrolizumab 200 mg every 3 weeks in the single-arm phase II KEYNOTE-052 trial (NCT02335424) and salvage pembrolizumab 200 mg every 3 weeks or chemotherapy (paclitaxel/docetaxel/vinflunine) in the randomized phase III KEYNOTE-045 trial (NCT02256436). The association of each biomarker (continuous variable) with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic regression (ORR) and Cox PH (PFS, OS), adjusted for ECOG PS; nominal P values were calculated without multiplicity adjustment (one-sided, pembrolizumab; two-sided, chemotherapy). Significance was prespecified at α = 0.05.

Results:
In KEYNOTE-052, PD-L1, TMB, and TcellinfGEP were significantly associated with improved outcomes; stromal signature was significantly associated with worse outcomes. In KEYNOTE-045, although findings for TMB and TcellinfGEP with pembrolizumab were consistent with those of KEYNOTE-052, PD-L1 was not significantly associated with improved outcomes, nor was stromal signature associated with worse outcomes with pembrolizumab; chemotherapy was not associated with outcomes in a consistent manner for any of the biomarkers. Hazard ratio (HR) estimates at prespecified cutoffs showed an advantage for pembrolizumab versus chemotherapy regardless of PD-L1 or TMB, with a trend toward lower HRs in the combined positive score ≥10 and the TMB ≥175 mutation/exome subgroup. For TcellinfGEP, PFS and OS HRs were lower in the TcellinfGEP-nonlow subgroup regardless of treatment.

Conclusions:
Multiple biomarkers characterizing the tumor microenvironment may help predict response to pembrolizumab monotherapy in UC, and potential clinical utility of these biomarkers may be context-dependent.
Circulating Tumor DNA Is Associated with Response and Survival in Patients with Advanced Leiomyosarcoma
Authors: Madanat-Harjuoja Laura M. , Klega Kelly , Lu Yao , Shulman David S. , Thorner Aaron R. , Nag Anwesha , Tap William D. , Reinke Denise K. , Diller Lisa , Ballman Karla V. , George Suzanne , Crompton Brian D. 
Published: May 2022

Abstract

Purpose:
We sought to determine whether the detection of circulating tumor DNA (ctDNA) in samples of patients undergoing chemotherapy for advanced leiomyosarcoma (LMS) is associated with objective response or survival.

Experimental Design:
Using ultra–low-passage whole-genome sequencing (ULP-WGS) of plasma cell-free DNA from patients treated on a prospective clinical trial, we tested whether detection of ctDNA evaluated prior to the start of therapy and after two cycles of chemotherapy was associated with treatment response and outcome. Associations between detection of ctDNA and pathologic measures of disease burden were evaluated.

Results:
We found that ctDNA was detectable by ULP-WGS in 49% patients prior to treatment and in 24.6% patients after two cycles of chemotherapy. Detection of pretreatment ctDNA was significantly associated with a lower overall survival [HR, 1.55; 95% confidence interval (CI), 1.03–2.31; P = 0.03] and a significantly lower likelihood of objective response [odds ratio (OR), 0.21; 95% CI, 0.06–0.59; P = 0.005]. After two cycles of chemotherapy, patients who continued to have detectable levels of ctDNA experienced a significantly worse overall survival (HR, 1.77; 95% CI, 1–3.14; P = 0.05) and were unlikely to experience an objective response (OR, 0.05; 95% CI, 0–0.39; P = 0.001).

Conclusions:
Our results demonstrate that detection of ctDNA is associated with outcome and objective response to chemotherapy in patients with advanced LMS. These results suggest that liquid biopsy assays could be used to inform treatment decisions by recognizing patients who are likely and unlikely to benefit from chemotherapy.
See related commentary by Kasper and Wilky, p. 2480
Revisiting Intracavitary Immunotherapy of Cancer
Authors: Aranda Fernando , Eguren-Santamaria Iñaki , Bella Ángela , Berraondo Pedro , Melero Ignacio 
Published: May 2022

AbstractOvarian cancer is often limited to the peritoneal cavity in the form of peritoneal carcinomatosis. Peritoneal spreading offers the opportunity for locoregional delivery of combinations of immunotherapy agents, maximizing bioavailability while potentially reducing systemic exposure and side effects.See related article by Orr et al., p. 2038
Ceramide Kinase Inhibition Drives Ferroptosis and Sensitivity to Cisplatin in Mutant KRAS Lung Cancer by Dysregulating VDAC-Mediated Mitochondria Function
Authors: Vu Ngoc T. , Kim Minjung , Stephenson Daniel J. , MacKnight H. Patrick , Chalfant Charles E. 
Published: May 2022

Abstract

Ceramide kinase (CERK) is the mammalian lipid kinase from which the bioactive sphingolipid, ceramide-1-phosphate (C1P), is derived. CERK has been implicated in several promalignant phenotypes with little known as to mechanistic underpinnings. In this study, the mechanism of how CERK inhibition decreases cell survival in mutant (Mut) KRAS non–small cell lung cancer (NSCLC), a major lung cancer subtype, was revealed. Specifically, NSCLC cells possessing a KRAS mutation were more responsive to inhibition, downregulation, and genetic ablation of CERK compared with those with wild-type (WT) KRAS regarding a reduction in cell survival. Inhibition of CERK induced ferroptosis in Mut KRAS NSCLC cells, which required elevating VDAC-regulated mitochondria membrane potential (MMP) and the generation of cellular reactive oxygen species (ROS). Importantly, through modulation of VDAC, CERK inhibition synergized with the first-line NSCLC treatment, cisplatin, in reducing cell survival and in vivo tumor growth. Further mechanistic studies indicated that CERK inhibition affected MMP and cell survival by limiting AKT activation and translocation to mitochondria, and thus, blocking VDAC phosphorylation and tubulin recruitment.

Implications:
Our findings depict how CERK inhibition may serve as a new key point in combination therapeutic strategy for NSCLC, specifically precision therapeutics targeting NSCLC possessing a KRAS mutation.
Uncanny Beauty: Aesthetics of Companionship, Love, and Sex Robots
Authors: Euron Paolo 
Published: May 2022

Abstract
In the last few years there has been a lively debate on humanoid robots interacting with humans in fields where human appearance and likeness may be essential. The debate has been bolstered by advancing AI technologies as well as increasing economic interest and public attention. The feasibility, inevitability, or ethical opportunity of companionship, love, and sex robots has been discussed. I propose a philosophical and cultural approach, applying the strategies of aesthetics and literary theory to the field of artificial beings, in order to understand reasons, use, limits, and possibilities expressed by the technology applied to companionship, love, and sex robots in the contemporary cultural and social context. In dealing with aesthetics, I will state how cognitive, biological, and ethical aspects are involved, how beauty is relatable to a robot’s physical appearance, and how the aesthetics of artificial beings may offer new existential experiences.
The Ocean Boundary Layer beneath Larsen C Ice Shelf: Insights from Large-Eddy Simulations with a Near-Wall Model
Authors: Vreugdenhil Catherine A. , Taylor John R. , Davis Peter E. D. , Nicholls Keith W. , Holland Paul R. , Jenkins Adrian 
Published: May 2022

Abstract
The melt rate of Antarctic ice shelves is of key importance for rising sea levels and future climate scenarios. Recent observations beneath Larsen C Ice Shelf revealed an ocean boundary layer that was highly turbulent and raised questions on the effect of these rich flow dynamics on the ocean heat transfer and the ice shelf melt rate. Directly motivated by the field observations, we have conducted large-eddy simulations (LES) to further examine the ocean boundary layer beneath Larsen C Ice Shelf. The LES was initialized with uniform temperature and salinity (T–S) and included a realistic tidal cycle and a small basal slope. A new parameterization based on previous work was applied at the top boundary to model near-wall turbulence and basal melting. The resulting vertical T–S profiles, melt rate, and friction velocity matched well with the Larsen C Ice Shelf observations. The instantaneous melt rate varied strongly with the tidal cycle, with faster flow increasing the turbulence and mixing of heat toward the ice base. An Ekman layer formed beneath the ice base and, due to the strong vertical shear of the current, Ekman rolls appeared in the mixed layer and stratified region (depth ≈ 20–60 m). In an additional high-resolution simulation (conducted with a smaller domain) the Ekman rolls were associated with increased turbulent kinetic energy, but a relatively small vertical heat flux. Our results will help with interpreting field observations and parameterizing the ocean-driven basal melting of ice shelves.
Creating a Communication Framework for FACETs: How Probabilistic Hazard Information Affected Warning Operations in NOAA’s Hazardous Weather Testbed
Authors: Trujillo-Falcón Joseph E. , Reedy Justin , Klockow-McClain Kimberly E. , Berry Kodi L. , Stumpf Gregory J. , Bates Alyssa V. , LaDue James G. 
Published: May 2022

Abstract
Scientists at NOAA are testing a new tool that allows forecasters to communicate estimated probabilities of severe hazards (tornadoes, severe wind, and hail) as part of the Forecasting a Continuum of Environmental Threats (FACETs) framework. In this study, we employ the embedded systems theory (EST)—a communication framework that analyzes small group workplace practices as products of group, organizational, and local dynamics—to understand how probabilistic hazard information (PHI) is produced and negotiated among multiple NWS weather forecast offices in an experimental setting. Gathering feedback from NWS meteorologists who participated in the 2020 Hazard Services (HS)-PHI Interoffice Collaboration experiment, we explored implications of local and interoffice collaboration while using this experimental tool. By using a qualitative thematic analysis, it was found that differing probability thresholds, forecasting styles, social dynamics, and workload will be social factors that developers should consider as they bring PHI toward operational readiness. Warning operations in this new paradigm were also implemented into the EST model to create a communication ecosystem for future weather hazard communication research.

Significance Statement
Meteorologists are currently exploring how to use probabilities to communicate life-saving information. From tornadoes to hail, a new type of probabilistic hazard information could fundamentally change the way that NWS meteorologists collaborate with one another when issuing weather products, especially near and along the boundaries of County Warning Areas. To explore potential collaboration challenges and solutions, we applied a communication framework and explored perceptions that NWS meteorologists had while using this new tool in an experimental setting. NWS meteorologists expressed that differing ways of communicating hazard information between each office, along with forecasting styles and workload, would change the way they go about producing critical hazard information to the public.
Evaluating real-world treatment patterns and outcomes of mantle cell lymphoma
Authors: Narkhede Mayur , Goyal Gaurav , Shea Lauren , Mehta Amit , Giri Smith 
Published: May 2022

Abstract
Mantle cell lymphoma (MCL) is considered incurable with the available chemoimmunotherapy approaches, and therefore, newer effective targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors are increasingly used in MCL as chronic suppressive therapy, especially in the elderly. We aimed to describe the treatment patterns in MCL at different lines of therapy with a focus on BTK inhibitor use and compare outcomes with known prognostic factors using a nationwide Flatiron Health electronic health record–derived de-identified database. We analyzed patient-level data from the period of 2011 to 2021. In this study of 4336 patients with MCL, we found that bendamustine plus rituximab chemotherapy was the most commonly used frontline regimen (42%). Maintenance rituximab or consolidative autologous stem cell transplant (ASCT) was administered to 31% of all patients. Also, for patients who received ASCT as consolidation therapy, only 34% subsequently received rituximab maintenance. BTK inhibitors were the most preferred agents in second or later lines of therapy (n = 933, 57%), followed by bortezomib, lenalidomide, and venetoclax, respectively. Among patients treated with BTK inhibitors, the median real-world overall survival (rwOS) was 35 months (95% confidence interval [CI], 27-50), 24 months (95% CI, 22-30), and 18 months (95% CI, 14-21) for first line, second line, and third or later line of therapy, respectively. Patients with a deletion 17p/TP53 mutation and blastoid variant MCL had poor outcomes; however, BTK inhibitors appeared to mitigate the negative influence of del17p/TP53-mutated MCL with a hazard ratio of 1.17 (95% CI, 0.88-1.55) on multivariable analysis.
Quality of breeding value predictions from longitudinal analyses, with application to residual feed intake in pigs
Authors: David Ingrid , Ricard Anne , Huynh-Tran Van-Hung , Dekkers Jack C. M. , Gilbert Hélène 
Published: May 2022

AbstractBackgroundAn important goal in animal breeding is to improve longitudinal traits. The objective of this study was to explore for longitudinal residual feed intake (RFI) data, which estimated breeding value (EBV), or combination of EBV, to use in a breeding program. Linear combinations of EBV (summarized breeding values, SBV) or phenotypes (summarized phenotypes) derived from the eigenvectors of the genetic covariance matrix over time were considered, and the linear regression method (LR method) was used to facilitate the evaluation of their prediction accuracy.ResultsWeekly feed intake, average daily gain, metabolic body weight, and backfat thickness measured on 2435 growing French Large White pigs over a 10-week period were analysed using a random regression model. In this population, the 544 dams of the phenotyped animals were genotyped. These dams did not have own phenotypes. The quality of the predictions of SBV and breeding values from summarized phenotypes of these females was evaluated. On average, predictions of SBV at the time of selection were unbiased, slightly over-dispersed and less accurate than those obtained with additional phenotypic information. The use of genomic information did not improve the quality of predictions. The use of summarized instead of longitudinal phenotypes resulted in predictions of breeding values of similar quality.ConclusionsFor practical selection on longitudinal data, the results obtained with this specific design suggest that the use of summarized phenotypes could facilitate routine genetic evaluation of longitudinal traits.