bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation and evolution of a magmatic system in the Indian passive margin: Insights from the Triassic Yumai Complex from the eastern Tethyan Himalaya
Authors: Wang Chao , Ding Lin , Wang Houqi , Cai Fulong , Wang Xiaodong , Zhang Liyun , Yue Yahui 
Published: September 2023

Abstract
The Indian passive margin has preserved several pulses of magmatism during and after the disassembly of Gondwana since the late Paleozoic, providing valuable insights into the long-term magmatic evolution of various passive margins, including the Indian passive margin. In the Yumai Complex, eastern Tethyan Himalaya, a pulse of Late Triassic alkaline volcanism (ca. 227–216 Ma) is evident. The Late Triassic volcanic rocks are mildly alkaline to tholeiitic basalts with minor ultrabasic rocks, similar in geochemistry to within-plate flood basalts. The TiO2 contents (1.46–3.38 wt%, mainly &gt;2 wt%), (La/Yb)N values (4.05–7.50), εNd (t) values (+4.86 to +6.98), and results from partial-melt modeling suggest that the basalts likely originated from garnet peridotite. Elemental and Sr-Nd systematics of magmatic rocks emplaced during the Triassic indicate oceanic island basalt (OIB) components in the magma source, interpreted as enriched mantle components rather than crustal contamination products. Spatiotemporal and geochemical patterns of magmatism reveal that the bulk compositions of the basalts changed from enriched OIB-like to depleted mid-ocean-ridge basalt (MORB)–like compositions. This phenomenon likely resulted from the evolving nature of the rifting basin, changing from a nascent continental setting to a mature ocean basin. The Triassic magmatism in the Tethyan Himalaya can be attributed to remnant lithospheric instability arising from the prolonged rifting of eastern Gondwana, leading to the formation of a magmatically passive margin.
Study protocol for NeuroCARE: a randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours
Authors: Forst Deborah Anne , Rhee John Y , Mesa Michelle Marie , Podgurski Alyx F , Strander Sumita Madhok , Datta Shibani , Kaslow-Zieve Emilia , Horick Nora K , Greer Joseph A , El-Jawahri Areej , Sannes Timothy S , Temel Jennifer S , Jacobs Jamie 
Published: September 2023

IntroductionCaregivers of patients with primary malignant brain tumours experience substantial psychological distress while caring for someone with a progressive, life-limiting neurological illness. However, there are few interventions aimed at addressing the psychosocial needs of this population. We developed and are testing a population-specific, evidence-based, telehealth intervention (NeuroCARE) to reduce anxiety symptoms and improve psychosocial functioning in this caregiver population.Methods and analysisThis study is a non-blinded, randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours receiving care at the Massachusetts General Hospital Cancer Center or Dana-Farber Cancer Institute. We will enrol 120 caregivers who screen positive for heightened anxiety. Participants will be randomised 1:1 to the NeuroCARE intervention or a usual care control condition. Caregivers assigned to NeuroCARE will complete six individual telehealth sessions with a trained behavioural health specialist over 12 weeks. Caregivers randomised to the control condition will receive usual care, including possible referral to social work or other appropriate resources. Participants will complete self-report questionnaires at baseline and 11 weeks and 16 weeks postrandomisation. The primary outcome is anxiety symptoms at 11 weeks among NeuroCARE participants, compared with usual care. Secondary outcomes include caregiver-reported depressive symptoms, quality of life, caregiver burden, caregiving self-efficacy, perceived coping skills and post-traumatic stress disorder symptoms. We also will explore potential mediators of the NeuroCARE effect on caregiver anxiety symptoms.Ethics and disseminationThe study is funded by a Career Development Award from Conquer Cancer, the American Society of Clinical Oncology Foundation (award number 2019CDA-7743456038) and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #19-250 V.10.1). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be presented at scientific meetings and in peer-reviewed journals.Trial registration numberNCT04109209
Protocol for the YORKSURe prospective multistage study testing the feasibility for early detection of bladder cancer in populations with high disease-specific mortality risk
Authors: Catto James WF , North Bernard , Goff Megan , Carter Abigail , Sleeth Michelle , Mandrik Olena , Chilcott Jim , Sasieni Peter , Cumberbatch Marcus G K 
Published: September 2023

IntroductionAround 25% of patients with bladder cancer (BCa) present with invasive disease. Non-randomised studies of population-based screening have suggested reductions in BCa-specific mortality are possible through earlier detection. The low prevalence of lethal disease in the general population means screening is not cost-effective and there is no consensus on the best strategy. Yorkshire has some of the highest mortality rates from BCa in England. We aim to test whether population screening in a region of high mortality risk will lead to a downward stage-migration of aggressive BCa, improved survival and is cost-effective.Methods and analysisYORKSURe is a tiered, randomised, multicohort study to test the feasibility of a large BCa screening randomised controlled trial. In three parallel cohorts, participants will self-test urine (at home) up to six times. Results are submitted via a mobile app or freephone. Those with a positive result will be invited for further investigation at community-based early detection clinics or within usual National Health Service (NHS) pathways. In Cohort 1, we will post self-testing kits to research engaged participants (n=2000) embedded within the Yorkshire Lung Screening Trial. In Cohort 2, we will post self-testing kits to 3000 invitees. Cohort 2 participants will be randomised between haematuria and glycosuria testing using a reveal/conceal design. In Cohort 3, we will post self-testing kits to 500 patients within the NHS pathway for investigation of haematuria. Our primary outcomes are rates of recruitment and randomisation, rates of positive test and acceptability of the design. The study is currently recruiting and scheduled to finish in June 2023.Ethics and disseminationThe study has received the following approvals: London Riverside Research Ethics Committee (22/LO/0018) and Health Research Authority Confidentiality Advisory Group (20/CAG/0009). Results will be made available to providers and researchers via publicly accessible scientific journals.Trial registration numberISRCTN34273159.
Socioeconomic disparities in the management and outcomes of acute myocardial infarction
Authors: Weight Nicholas , Moledina Saadiq , Volgman Annabelle Santos , Bagur Rodrigo , Wijeysundera Harindra C , Sun Louise Y , Chadi Alraies M , Rashid Muhammad , Kontopantelis Evangelos , Mamas Mamas A 
Published: September 2023

BackgroundPatients from lower socioeconomic status areas have poorer outcomes following acute myocardial infarction (AMI); however, how ethnicity modifies such socioeconomic disparities is unclear.MethodsUsing the UK Myocardial Ischaemia National Audit Project (MINAP) registry, we divided 370 064 patients with AMI into quintiles based on Index of Multiple Deprivation (IMD) score, comprising seven domains including income, health, employment and education. We compared white and ‘ethnic-minority’ patients, comprising Black, Asian and mixed ethnicity patients (as recorded in MINAP); further analyses compared the constituents of the ethnic-minority group. Logistic regression models examined the role of the IMD, ethnicity and their interaction on the odds of in-hospital mortality.ResultsMore patients from the most deprived quintile (Q5) were from ethnic-minority backgrounds (Q5; 15% vs Q1; 4%). In-hospital mortality (OR 1.10, 95% CI 1.01 to 1.19, p=0.025) and major adverse cardiovascular event (MACE) (OR 1.07, 95% CI 1.00 to 1.15, p=0.048) were more likely in Q5, and MACE was more likely in ethnic-minority patients (OR 1.40, 95% CI 1.00 to 1.95, p=0.048) versus white (OR 1.05, 95% CI 0.98 to 1.13, p=0.027) in Q5. In subgroup analyses, Black patients had the highest in-hospital mortality within the most affluent quintile (Q1) (Black: 0.079, 95% CI 0.046 to 0.112, p<0.001; White: 0.062, 95% CI 0.059 to 0.066, p<0.001), but not in Q5 (Black: 0.065, 95% CI 0.054 to 0.077, p<0.001; White: 0.065, 95% CI 0.061 to 0.069, p<0.001).ConclusionPatients with a higher deprivation score were more often from an ethnic-minority background, more likely to suffer in-hospital mortality or MACE when compared with the most affluent quintile, and this relationship was stronger in ethnic minorities compared with White patients.
Long-term cardiac follow-up of athletes infected with SARS-CoV-2 after resumption of elite-level sports
Authors: van Hattum Juliette C , Daems Joëlle J N , Verwijs Sjoerd M , Wismans Leonoor V , van Diepen Maarten A , Groenink Maarten , Boekholdt S Matthijs , Planken R Nils , van Randen Adrienne , Hirsch Alexander , Moen Maarten H , Pinto Yigal M , Wilde Arthur A M , Jørstad Harald T 
Published: September 2023

ObjectiveLongitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the highest level of sports and exercise.MethodsThis prospective controlled study included elite athletes from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise cohort. Athletes infected with SARS-CoV-2were offered structured, additional cardiovascular screenings, including cardiovascular MRI (CMR). We compared ventricular volumes and function, late gadolinium enhancement (LGE) and T1 relaxation times, between infected and non-infected elite athletes, and collected follow-up data on cardiac adverse events, ventricular arrhythmia burden and the cessation of sports careers.ResultsWe included 259 elite athletes (mean age 26±5 years; 40% women), of whom 123 were infected (9% cardiovascular symptoms) and 136 were controls. We found no differences in function and volumetric CMR parameters. Four infected athletes (3%) demonstrated LGE (one reversible), compared with none of the controls. During the 26.7 (±5.8) months follow-up, all four athletes resumed elite-level sports, without an increase in ventricular arrhythmias or adverse cardiac remodelling. None of the infected athletes reported new cardiac symptoms or events. The majority (n=118; 96%) still participated in elite-level sports; no sports careers were terminated due to SARS-CoV-2.ConclusionsThis prospective study demonstrates the safety of resuming elite-level sports after SARS-CoV-2 infection. The medium-term risks associated with SARS-CoV-2 infection and elite-level sports appear low, as the resumption of elite sports did not lead to detrimental cardiac effects or increases in clinical events, even in the four elite athletes with SARS-CoV-2 associated myocardial involvement.
Local blockade of tacrolimus promotes T-cell-mediated tumor regression in systemically immunosuppressed hosts
Authors: Veitch Margaret , Beaumont Kimberly , Pouwer Rebecca , Chew Hui Yi , Frazer Ian H , Soyer H Peter , Campbell Scott , Dymock Brian W , Harvey Andrew , Cock Terrie-Anne , Wells James W 
Published: September 2023

BackgroundImmunosuppressive drugs such as tacrolimus have revolutionized our ability to transplant organs between individuals. Tacrolimus acts systemically to suppress the activity of T-cells within and around transplanted organs. However, tacrolimus also suppresses T-cell function in the skin, contributing to a high incidence of skin cancer and associated mortality and morbidity in solid organ transplant recipients. Here, we aimed to identify a compound capable of re-establishing antitumor T-cell control in the skin despite the presence of tacrolimus.MethodsIn this study, we performed time-resolved fluorescence resonance energy transfer to identify molecules capable of antagonizing the interaction between tacrolimus and FKBP12. The capacity of these molecules to rescue mouse and human T-cell function in the presence of tacrolimus was determined in vitro, and the antitumor effect of the lead compound, Q-2361, was assessed in “regressor” models of skin cancer in immunosuppressed mice. Systemic CD8 T-cell depletion and analyses of intratumoral T-cell activation markers and effector molecule production were performed to determine the mechanism of tumor rejection. Pharmacokinetic studies of topically applied Q-2361 were performed to assess skin and systemic drug exposure.ResultsQ-2361 potently blocked the interaction between tacrolimus and FKBP12 and reversed the inhibition of the nuclear factor of activated T cells activation by tacrolimus following T-cell receptor engagement in human Jurkat cells. Q-2361 rescued T-cell function in the presence of tacrolimus, rapamycin, and everolimus. Intratumoral injection of Q-2361-induced tumor regression in mice systemically immune suppressed with tacrolimus. Mechanistically, Q-2361 treatment permitted T-cell activation, proliferation, and effector function within tumors. When CD8 T cells were depleted, Q-2361 could not induce tumor regression. A simple solution-based Q-2361 topical formulation achieved high and sustained residence in the skin with negligible drug in the blood.ConclusionsOur findings demonstrate that the local application of Q-2361 permits T-cells to become activated driving tumor rejection in the presence of tacrolimus. The data presented here suggests that topically applied Q-2361 has great potential for the reactivation of T-cells in the skin but not systemically, and therefore represents a promising strategy to prevent or treat skin malignancies in immunosuppressed organ transplant recipients.
Heart failure virtual consultation: caters for frailer, multimorbid and remote patients
Authors: Wong Bethany , McCambridge Joseph , Barrett Matthew , Ledwidge Mark , McCudden Lisa , Fawsitt Ronan , Gallagher Joseph J , McDonald Kenneth 
Published: September 2023

Background: The heart failure (HF) virtual consultation (VC) is an eHealth tool for delivery of peer-to-peer specialist advice to general practitioners (GPs) to discuss HF diagnosis/management. We aim to investigate the impact of the VC service on onward referral rate and quality of assessment by GPs, as well as assess VC patient characteristics; Clinical Frailty Score (CSF), age and morbidity.Methods: This prospective observational study collected VC data on: demographics, comorbidity, frailty, referral indication, the impact of VC on clinical care and the GP response to the question ‘what would you have done without the VC service’. We compared patient characteristics to a control population of patients attending the HF unit (HFU) (n=118).Reults: Between 2015 and 2021, 1681 VC cases were discussed. The majority of cases were discussed from remote areas (75%). Rediscussion cases increased from 0% to 34%. VC patients were older (76.2 (±11.3) vs 73.1 (±12.5) years, p<0.05), more frail (CSF=3.8 (±1.7) vs 3 (±1.6), p<0.01) and multimorbid (number of comorbidities=7.1 (±3.4) vs 3.8 (±1.9), p<0.001) compared with patients attending the HFU. Without the VC, 93% of cases would have been referred to face-to-face hospital services. Instead, VC resulted in only 9% of cases being referred to hospital services. The remainder of cases were managed by the VC service, in a shared GP-specialist approach. GP use of natriuretic peptide (NP) increased from 0% in 2015–2016 to 63% in 2021 and use of TTE increased from 0% in 2015–2016 to 69% by 2021.Conclusions: The VC service provides a platform for case discussion in particular for older, frailer patients and reduces onward hospital referrals. This may facilitate early diagnosis and management of suspected HF in the current era of long outpatient waiting times. The quality of community HF assessment improved as indicated by increased use of NP/TTE by GPs.
Tithonian mafic intrusions in north-central Newfoundland: link to Atlantic rifting?
Authors: Peace Alexander L. , Sandeman Hamish A.I. , Welford J. Kim , Dunning Gregory R. , Camacho Alfredo 
Published: September 2023

The small volume, Mesozoic alkali gabbro intrusions of the Budgell Harbour and Dildo Pond stocks and associated alkaline lamprophyre dykes in Notre Dame Bay in Newfoundland are an example of onshore magmatism that may be associated with North Atlantic Ocean opening. Chemical abrasion isotope dilution thermal ionization mass spectrometry U–Pb dating of zircon from Budgell Harbour Stock drill core samples yielded a weighted average 206Pb/238U age of 147.9 ± 0.5 Ma (95% confidence interval, mean square weighted deviation = 0.10). Five 40Ar/39Ar laser step-heating, single phlogopite grain analyses from the Budgell Harbour and Dildo Pond stocks, plus a lamprophyre dyke, yielded ages ranging from 146.3 ± 0.2 to 149.5 ± 0.5 Ma. The data demonstrate a ca. 148 Ma (Jurassic and Tithonian) alkaline magmatic event in Newfoundland, contemporaneous with rifting and offshore basin formation. These new age data and published determinations from magmatic rocks on conjugate margins and adjacent regions reveal long-lived episodic magmatism in the embryonic North Atlantic rift environment. We propose a new model whereby magmatism occurred in Notre Dame Bay at the convergence of older crustal-scale faults and localized Moho depth variations that may have triggered lithospheric mantle melting through isothermal, distal, and edge-driven upwelling related to regional extension.
Nested warped geometry in a non-flat braneworld scenario
Authors: Bhaumik Arko , SenGupta Soumitra 
Published: September 2023

AbstractWe generalize nested multiply warped braneworld models by incorporating non-zero brane curvature caused by an effective cosmological constant $$\Omega $$
Ω
induced on the 3-branes. Starting with the doubly warped model, we first analyze the case where the maximally warped brane is identified as the visible brane. For $$\Omega <0$$

Ω
<
0

, resolution of the gauge hierarchy problem imposes a small upper bound on $$|\Omega |$$

|
Ω
|

, and can possibly lead to positivity of all the 3-brane tensions. For $$\Omega >0$$

Ω
>
0

, the latter is not possible but the tuning of the cosmological constant to its tiny observed value is linked to the tuning of the extra dimensional moduli close to the inverse Planck length, justifying the original flat brane approximation. In both regimes, we study the dependence of the scale-clustering of the pair of TeV-branes on the brane cosmological constant and hence its potential role in generating a fermion mass hierarchy between these branes. Identifying the near-maximally warped brane as the visible brane instead opens up regions in the parameter space that allow positive 3-brane tensions for both anti de Sitter and de Sitter branes, subject to non-trivial constraints on the warping parameters. We conclude by generalizing the key results to arbitrary n-fold nested warped braneworlds.
Scaling dimension of Cooper pair operator from the black hole interior
Authors: Choun Yoon-Seok , Sin Sang-Jin 
Published: September 2023

AbstractWe have shown that in holographic superconductivity theory for 3+1 dimensional system, the scaling dimension of Cooper pair operator can be obtained as a quantized value if we request that the the scalar function describing the order parameter is finite inside the black hole as well as outside. This should be contrasted to the usual situation where we set the mass squared of the scalar by hand. Our method can be applied to any order parameters.
Minimum+1 (
s, t
)-cuts and Dual-edge Sensitivity Oracle
Authors: Baswana Surender , Bhanja Koustav , Pandey Abhyuday 
Published: September 2023

Let
G
be a directed multi-graph on
n
vertices and
m
edges with a designated source vertex
s
and a designated sink vertex
t
. We study the (
s,t
)-cuts of capacity minimum+1 and as an important application of them, we give a solution to the dual-edge sensitivity for (
s,t
)-mincuts—reporting an (
s,t
)-mincut upon failure or insertion of any pair of edges.

Picard and Queyranne [Mathematical Programming Studies, 13(1): 8–16 (1980)] showed that there exists a directed acyclic graph (DAG) that compactly stores all minimum (
s,t
)-cuts of
G
. This structure also acts as an oracle for the single-edge sensitivity of minimum (
s,t
)-cut. For undirected multi-graphs, Dinitz and Nutov [STOC, 509–518 (1995)] showed that there exists an 𝒪(
n
) size 2-level Cactus model that stores all global cuts of capacity minimum+1. However, for minimum+1 (
s,t
)-cuts, no such compact structure exists till date. We present the following structural and algorithmic results on minimum+1 (
s,t
)-cuts.

(1)

Structure:
There is an 𝒪(
m
) size 2-level DAG structure that stores all minimum+1
(s,t)
-cuts of
G
such that each minimum+1 (
s,t
)-cut appears as 3-transversal cut—it intersects any path in this structure at most thrice. We also show that there is an 𝒪(
mn
) size structure for storing and characterizing all minimum+1
(s,t)
-cuts in terms of 1-transversal cuts.

(2)

Data structure:
There exists an 𝒪(

n
2

) size data structure that, given a pair of vertices {u,v} that are not separated by an (
s,t
)-mincut, can determine in 𝒪(1) time if there exists a minimum+1 (
s,t
)-cut, say (
A,B
), such that
s,u ∊ A
and
v,t∊ B
; the corresponding cut can be reported in 𝒪(|
B
|) time.

(3)

Sensitivity oracle:
There exists an 𝒪(
n
2
) size data structure that solves the dual-edge sensitivity problem for
(s,t)
-mincuts. It takes 𝒪(1) time to report the capacity of a resulting
(s,t)
-mincut
(A,B)
and 𝒪(|
B
|) time to report the cut.

(4)

Lower bounds:
For the data structure problems addressed in results (2) and (3) above, we also provide a matching conditional lower bound. We establish a close relationship among three seemingly unrelated problems—all-pairs directed reachability problem, the dual-edge sensitivity problem for (
s,t
)-mincuts, and the problem of reporting the capacity of ({
x,y
}, {
u,v
})-mincut for any four vertices
x,y,u,v
in
G
. Assuming the Directed Reachability Hypothesis by Patrascu [SIAM J. Computing, 827–847 (2011)] and Goldstein et al. [WADS, 421–436 (2017)], this leads to

\(\tilde{\Omega }(n^2)\)

lower bounds on the space for the latter two problems.
Targeting the RNA-Binding Protein HuR in Cancer
Authors: Finan Jennifer M. , Sutton Thomas L. , Dixon Dan A. , Brody Jonathan R. 
Published: September 2023

Abstract
The RNA-binding protein human antigen R (HuR) is a well-established regulator of gene expression at the posttranscriptional level. Its dysregulation has been implicated in various human diseases, particularly cancer. In cancer, HuR is considered “active” when it shows increased subcellular localization in the cytoplasm, in addition to its normal nuclear localization. Cytoplasmic HuR plays a crucial role in stabilizing and enhancing the translation of prosurvival mRNAs that are involved in stress responses relevant to cancer progression, such as hypoxia, radiotherapy, and chemotherapy. In general, due to HuR's abundance and function in cancer cells compared with normal cells, it is an appealing target for oncology research. Exploiting the principles underlying HuR's role in tumorigenesis and resistance to stressors, targeting HuR has the potential for synergy with existing and novel oncologic therapies. This review aims to explore HuR's role in homeostasis and cancer pathophysiology, as well as current targeting strategies, which include silencing HuR expression, preventing its translocation and dimerization from the nucleus to the cytoplasm, and inhibiting mRNA binding. Furthermore, this review will discuss recent studies investigating the potential synergy between HuR inhibition and traditional chemotherapeutics.