bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population modeling to inform management and recovery efforts for lake sturgeon, Acipenser fulvescens
Authors: Vaugeois Maxime , Venturelli Paul A. , Hummel Stephanie L. , Forbes Valery E. 
Published: January 2022

Abstract
Lake sturgeon (Acipenser fulvescens) populations have significantly declined across their historic range, in large part due to anthropogenic impacts that have likely been exacerbated by the life-history traits of this slow-growing and long-lived species. We developed a population model to explore how Contaminants of Emerging Concern (CECs) impact lake sturgeon populations. We explored how different physiological modes of action (pMoAs) of CECs impacted population abundance and recovery and how different simulated management actions could enable recovery. We first estimated the impacts on population abundance and recovery by comparing the trajectory of an unexposed population to a population that had been exposed to a CEC with a specific pMoA after the end of the exposure. We then predicted how different management actions would impact population recovery by comparing the trajectories of an unexposed population to an exposed population for which a management action started at a fixed time without discontinuation of the exposure. Our results predicted that the individual-level pMoA of CECs has an important impact on population-level effects because different stressor's pMoA impacts the life-history traits of sturgeon differently. For example, the feeding and reproduction pMoAs caused the strongest and weakest population declines, respectively. For the same reason, pMoA also impacted recovery. For example, recovery was delayed when the pMoA was growth, maintenance, or feeding, but it was immediate when the pMoA was reproduction. We found that management actions that increased the egg survival rate or the stocking of fingerlings resulted in faster and stronger recovery than management actions that increased the juvenile or adult survival rate. This result occurred because the first two management actions immediately impacted recruitment, whereas the impact was delayed for the last two. Finally, there was greater potential for recovery when management action targeted eggs and fingerlings because these life stages have lower natural survival rates. Integr Environ Assess Manag 2022;18:1597–1608. © 2022 Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by US Government employees and their work is in the public domain in the USA.
KEY POINTS
The individual-level physiological mode of action of a stressor is important to forecast its effects at the population level and select the most appropriate management strategy. Management actions that increased egg survival rate or the stocking of fingerlings resulted in faster and stronger recovery than management actions that increased juvenile or adult survival rate. There is a greater potential for recovery when management actions target eggs and fingerlings because these life stages have lower natural survival rates.
Phase Ib study of combinations of avadomide (CC‐122), CC‐223, CC‐292, and rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma
Authors: Ribrag Vincent , Chavez Julio C. , Boccomini Carola , Kaplan Jason , Chandler Jason C. , Santoro Armando , Corradini Paolo , Flinn Ian W. , Advani Ranjana , Cassier Philippe A. , Sangha Randeep , Kenkre Vaishalee P. , Isufi Iris , Uttamsingh Shailaja , Hagner Patrick R. , Gandhi Anita K. , Shen Frank , Michelliza Sophie , Haeske Harald , Hege Kristen , Pourdehnad Michael , Kuruvilla John 
Published: January 2022

AbstractThere is a need for additional treatment options for patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) who do not benefit from available therapies. We examined combinations of the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC‐122), the selective, ATP‐competitive mammalian target of rapamycin kinase inhibitor CC‐223, and the potent, selective, covalent Bruton tyrosine kinase inhibitor CC‐292 in patients with relapsed/refractory (R/R) DLBCL.In the multicenter, phase Ib CC‐122‐DLBCL‐001 study (NCT02031419), the dose‐escalation portion explored combinations of CC‐122, CC‐223, and CC‐292 administered as doublets or triplets with rituximab in patients with chemorefractory DLBCL. Primary endpoints were safety, tolerability, and dose‐limiting toxicities; additional endpoints included pharmacokinetics, pharmacodynamics, biomarkers, and preliminary efficacy.As of December 1, 2017, 106 patients were enrolled across four cohorts. The median age was 65 years (range 24–84 years), and patients had a median of 3 (range 1–10) prior to regimens. A total of 101 patients (95.3%) discontinued, most commonly due to disease progression (49.1%). The most common any‐grade adverse events (AEs) across treatment arms were gastrointestinal and hematologic; the most common grade 3/4 AEs were hematologic. CC‐122 was well tolerated, with no unexpected safety concerns. Preliminary efficacy was observed in three of four treatment arms. CC‐122 plus rituximab was considered suitable for dose expansion, whereas CC‐223 and CC‐292 combinations were associated with enhanced toxicity and/or insufficient improvement in responses.CC‐122 plus rituximab was well tolerated, with preliminary antitumor activity in patients with R/R DLBCL. This innovative study demonstrates the feasibility of assessing the tolerability and preliminary efficacy of novel combinations utilizing a multi‐arm dose‐finding design.
Impact of locus of care on outcomes in adolescents and young adults with osteosarcoma and Ewing sarcoma treated at pediatric versus adult cancer centers: An IMPACT cohort study
Authors: Mortazavi Mohammadreza , Baxter Nancy N. , Gupta Sumit , Gupta Abha A. , Lau Cindy , Nagamuthu Chenthila , Nathan Paul C. 
Published: January 2022

AbstractBackgroundLocation of cancer care (LOC; pediatric vs. adult center) impacts outcomes in adolescents and young adults (AYA) with some cancer types. Data on the impact of LOC on survival in AYA with osteosarcoma (OSS) and Ewing sarcoma (EWS) are limitedObjectivesTo compare differences in demographics, disease/treatment characteristics, and survival in a population‐based cohort of AYA with OSS or EWS treated at pediatric versus adult centersMethodsThe Initiative to Maximize Progress in Adolescent Cancer Therapy (IMPACT) cohort captured demographic, disease, and treatment data for all AYA (15–21 years old) diagnosed with OSS and EWS in Ontario, Canada between 1992 and 2012. Patients were linked to provincial administrative health care databases. Outcomes were compared between patients treated in pediatric versus adult centers.ResultsOne hundred thirty‐seven AYA were diagnosed with OSS (LOC: 47 pediatric, 90 adult) and 84 with EWS (38 pediatric, 46 adult). AYA treated at pediatric centers were more likely to be enrolled in a clinical trial (OSS 55% vs. 1%, p < .001; EWS 53% vs. 2%, p < .001) and received higher cumulative chemotherapy doses. Five‐year event‐free survival (EFS ± standard error) in OSS and EWS were 47% ± 4% and 43% ± 5%, respectively. In multivariable analysis, the impact of LOC (pediatric vs. adult center) on EFS in OSS (adjusted hazard ratio [HR] 1.15, 95% confidence interval [CI]: 0.58–2.27, p = .69) and EWS (adjusted HR 1.82, 95% CI: 0.97–3.43, p = .06) was not statistically significant.ConclusionDespite disparities in trial participation and chemotherapy doses, outcomes did not differ by LOC suggesting that AYA with bone tumors can be treated at either pediatric or adult centers.
Access to early‐phase clinical trials for children with relapsed and refractory neuroblastoma: A multicentre international study
Authors: Cortes Marta , Carceller Fernando , Rubio‐San‐Simón Alba , Vaidya Sucheta J. , Bautista Francisco , Moreno Lucas 
Published: January 2022

AbstractObjectivesNeuroblastoma is the most common extracranial tumour in children, and prognosis for refractory and relapsed disease is still poor. Early‐phase clinical trials play a pivotal role in the development of novel drugs. Ensuring adequate recruitment is crucial. The primary aim was to determine the rate of participation trials for children with refractory/relapsed neuroblastoma in two of the largest drug development European institutions.MethodsData from patients diagnosed with refractory/relapsed neuroblastoma between January 2012 and December 2018 at the two institutions were collected and analysed.ResultsOverall, 48 patients were included. A total of 31 (65%) refractory/relapsed cases were enrolled in early‐phase trials. The main reasons for not participating in clinical trials included not fulfilling eligibility criteria prior to consent (12/17, 70%) and screening failure (2/17, 12%). Median time on trial was 4.3 months (range 0.6–13.4). Most common cause for trial discontinuation was disease progression (67.7%). Median overall survival was longer in refractory (28 months, 95% CI: 20.9–40.2) than in relapsed patients (14 months, 95% CI: 8.1–20.1) (p = .034).ConclusionsAlthough two thirds of children with refractory/relapsed neuroblastoma were enrolled in early‐phase trials, recruitment rates can still be improved. The main cause for not participating on trials was not fulfilling eligibility criteria prior to consent, mainly due to performance status and short life expectancy. This study highlights the hurdles to access to innovative therapies for children with relapsed/refractory neuroblastomas, and identifies key areas of development to improve recruitment to early‐phase trials.
Generation and reactivity of phenylhydroxycarbenes in solution
Authors: Keul Felix , Mardyukov Artur , Schreiner Peter R. 
Published: January 2022

AbstractWe provide evidence for the first successful generation of phenylhydroxycarbene and 4‐trifluoromethylphenylhydroxycarbene in solution. The carbene tautomers of the corresponding benzaldehyde derivatives had been prepared under cryogenic matrix‐isolation conditions before but their reactivity, apart from a prototypical quantum mechanical tunneling [1,2]‐H‐shift reaction, had not been studied. Here our strategy is to employ suitable carbene precursors for the McFadyen–Stevens reaction, to generate the parent and the para‐CF3‐substituted phenylhydroxycarbenes, and to react them with benzaldehyde or acetone in a highly facile, allowed six‐electron carbonyl‐ene reaction toward the corresponding α‐hydroxy ketones. Our findings are supported by computations at the DLPNO‐CCSD(T)/cc‐pVQZ//B3LYP/def2‐TZVP level of theory.
Optimal terminal‐velocity‐control guidance for intercepting non‐cooperative maneuvering quadcopter
Authors: Tao Hong , Lin Defu , He Shaoming , Song Tao , Jin Ren 
Published: January 2022

AbstractThis paper proposes a three‐dimensional optimal terminal velocity control guidance for multicopter intercepting maneuvering drone with equal maneuverability level. We investigate a novel multi‐rate extended Kalman filter‐based approach to estimate target's velocity and acceleration by fusing the measurements of onboard machine vision algorithm, electro‐optical pod, and inertial navigation system. The estimated target information is helpfully incorporated into the formulation of relative kinematics, based on which the guidance problem is naturally decoupled and optimal control theory can be directly leveraged to obtain the analytical solution. The key aspect of the proposed law lies in its low maneuverability requirement due to the inclusion of target information. The working principle and characteristics of the guidance command are theoretically analyzed to support our findings. Both numerical simulations and flight experiments are performed to validate the proposed approach and demonstrate its advantages.
Anti-inflammatory and Immunomodulatory Therapies in Atherosclerosis
Authors: Deroissart Justine , Porsch Florentina , Koller Thomas , Binder Christoph J. 
Published: January 2022

AbstractHypercholesterolemia is a major risk factor in atherosclerosis development and lipid-lowering drugs (i.e., statins) remain the treatment of choice. Despite effective reduction of LDL cholesterol in patients, a residual cardiovascular risk persists in some individuals, highlighting the need for further therapeutic intervention. Recently, the CANTOS trial paved the way toward the development of specific therapies targeting inflammation, a key feature in atherosclerosis progression. The pre-existence of multiple drugs modulating both innate and adaptive immune responses has significantly accelerated the number of translational studies applying these drugs to atherosclerosis. Additional preclinical research has led to the discovery of new therapeutic targets, offering promising perspectives for the treatment and prevention of atherosclerosis. Currently, both drugs with selective targeting and broad unspecific anti-inflammatory effects have been tested. In this chapter, we aim to give an overview of current advances in immunomodulatory treatment approaches for atherosclerotic cardiovascular diseases.
Lipidomics in Biomarker Research
Authors: Hornemann Thorsten 
Published: January 2022

AbstractLipids are natural substances found in all living organisms and involved in many biological functions. Imbalances in the lipid metabolism are linked to various diseases such as obesity, diabetes, or cardiovascular disease. Lipids comprise thousands of chemically distinct species making them a challenge to analyze because of their great structural diversity.Thanks to the technological improvements in the fields of chromatography, high-resolution mass spectrometry, and bioinformatics over the last years, it is now possible to perform global lipidomics analyses, allowing the concomitant detection, identification, and relative quantification of hundreds of lipid species. This review shall provide an insight into a general lipidomics workflow and its application in metabolic biomarker research.
Large N external-field quantum electrodynamics
Authors: Karbstein Felix 
Published: January 2022

Abstract
We advocate the study of external-field quantum electrodynamics with N charged particle flavors. Our main focus is on the Heisenberg-Euler effective action for this theory in the large N limit which receives contributions from all loop orders. The contributions beyond one loop stem from one-particle reducible diagrams. We show that specifically in constant electromagnetic fields the latter are generated by the one-loop Heisenberg-Euler effective Lagrangian. Hence, in this case the large N Heisenberg-Euler effective action can be determined explicitly at any desired loop order. We demonstrate that further analytical insights are possible for electric-and magnetic-like field configurations characterized by the vanishing of one of the secular invariants of the electromagnetic field and work out the all-orders strong field limit of the theory.
Spin(7) orientifolds and 2d $$ \mathcal{N} $$ = (0, 1) triality
Authors: Franco Sebastián , Mininno Alessandro , Uranga Ángel M. , Yu Xingyang 
Published: January 2022

Abstract
We present a new, geometric perspective on the recently proposed triality of 2d $$ \mathcal{N} $$
N
= (0, 1) gauge theories, based on its engineering in terms of D1-branes probing Spin(7) orientifolds. In this context, triality translates into the fact that multiple gauge theories correspond to the same underlying orientifold. We show how Spin(7) orientifolds based on a particular involution, which we call the universal involution, give rise to precisely the original version of $$ \mathcal{N} $$
N
= (0, 1) triality. Interestingly, our work also shows that the space of possibilities is significantly richer. Indeed, general Spin(7) orientifolds extend triality to theories that can be regarded as consisting of coupled $$ \mathcal{N} $$
N
= (0, 2) and (0, 1) sectors. The geometric construction of 2d gauge theories in terms of D1-branes at singularities therefore leads to extensions of triality that interpolate between the pure $$ \mathcal{N} $$
N
= (0, 2) and (0, 1) cases.
Kibble mechanism for electroweak magnetic monopoles and magnetic fields
Authors: Patel Teerthal , Vachaspati Tanmay 
Published: January 2022

Abstract
The vacuum manifold of the standard electroweak model is a three-sphere when one considers homogeneous Higgs field configurations. For inhomogeneous configurations we argue that the vacuum manifold is the Hopf fibered three sphere and that this viewpoint leads to general criteria to detect electroweak monopoles and Z-strings. We extend the Kibble mechanism to study the formation of electroweak monopoles and strings during electroweak symmetry breaking. The distribution of magnetic monopoles produces magnetic fields that have a spectrum Bλ ∝ λ−2, where λ is a smearing length scale. Even as the magnetic monopoles annihilate due to the confining Z-strings, the magnetic field evolves with the turbulent plasma and may be relevant for cosmological observations.
Moderately suppressed dimension-five proton decay in a flipped SU(5) model
Authors: Haba Naoyuki , Yamada Toshifumi 
Published: January 2022

Abstract
We study colored Higgsino-mediated proton decay (dimension-five proton decay) in a model based on the flipped SU(5) GUT. In the model, the GUT-breaking 10, $$ \overline{\mathbf{10}} $$

10
¯

fields have a GUT-scale mass term and gain VEVs through higher-dimensional operators, which induces an effective mass term between the color triplets in the 5, $$ \overline{\mathbf{5}} $$

5
¯

Higgs fields that is not much smaller than the GUT scale. This model structure gives rise to observable dimension-five proton decay, and at the same time achieves moderate suppression on dimension-five proton decay that softens the tension with the current bound on Γ(p → K+$$ \overline{\nu} $$

ν
¯

). We investigate the flavor dependence of the Wilson coefficients of the operators relevant to dimension-five proton decay, by relating them with diagonalized Yukawa couplings and CKM matrix components in MSSM, utilizing the fact that the GUT Yukawa couplings are in one-to-one correspondence with the MSSM Yukawa couplings in flipped models. Then we numerically evaluate the Wilson coefficients, and predict the distributions of the ratios of the partial widths of various proton decay modes.
Prime Time for Artificial Intelligence in Interventional Radiology
Authors: Seah Jarrel , Boeken Tom , Sapoval Marc , Goh Gerard S. 
Published: January 2022

AbstractMachine learning techniques, also known as artificial intelligence (AI), is about to dramatically change workflow and diagnostic capabilities in diagnostic radiology. The interest in AI in Interventional Radiology is rapidly gathering pace. With this early interest in AI in procedural medicine, IR could lead the way to AI research and clinical applications for all interventional medical fields. This review will address an overview of machine learning, radiomics and AI in the field of interventional radiology, enumerating the possible applications of such techniques, while also describing techniques to overcome the challenge of limited data when applying these techniques in interventional radiology. Lastly, this review will address common errors in research in this field and suggest pathways for those interested in learning and becoming involved about AI.
Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas
Authors: Schrader Anne M. R. , de Groen Ruben A. L. , Willemze Rein , Jansen Patty M. , Quint Koen D. , van Wezel Tom , van Eijk Ronald , Ruano Dina , Tensen Cornelis P. , Hauben Esther , Woei-A-Jin F. J. S. H. , Busschots Anne M. , van den Berg Anke , Diepstra Arjan , Vermeer Maarten H. , Vermaat Joost S. P. 
Published: January 2022

Abstract
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.
Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens
Authors: Kalló Imre , Omrani Azar , Meye Frank J. , de Jong Han , Liposits Zsolt , Adan Roger A. H. 
Published: January 2022

AbstractOrexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.