bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emulating randomised clinical trials in relapsing-remitting multiple sclerosis with non-randomised real-world evidence: an application using data from the MSBase Registry
Authors: Signori Alessio , Ponzano Marta , Kalincik Tomas , Ozakbas Serkan , Horakova Dana , Kubala Havrdova Eva , Alroughani Raed , Patti Francesco , Kuhle Jens , Izquierdo Guillermo , Eichau Sara , Yamout Bassem , Khoury Samia Joseph , Karabudak Rana , Grammond Pierre , Duquette Pierre , Roos Izanne , Butzkueven Helmut , van der Walt Anneke , Sormani Maria Pia 
Published: January 2024

Background
To mimic as closely as possible a randomised controlled trial (RCT) and calibrate the real-world evidence (RWE) studies against a known treatment effect would be helpful to understand if RWE can support causal conclusions in selected circumstances. The aim was to emulate the TRANSFORMS trial comparing Fingolimod (FTY) versus intramuscular interferon β-1a (IFN) using observational data.

Methods
We extracted from the MSBase registry all the patients with relapsing-remitting multiple sclerosis (RRMS) collected in the period 2011–2021 who received IFN or FTY (0.5 mg) and with the same inclusion and exclusion criteria of the TRANSFORMS RCT. The primary endpoint was the annualised relapse rate (ARR) over 12 months. Patients were 1:1 propensity-score (PS) matched. Relapse-rate ratio (RR) was calculated by mean of a negative binomial regression.

Results
A total of 4376 patients with RRMS (1140 in IFN and 3236 in FTY) were selected. After PS, 856 patients in each group were matched. The ARR was 0.45 in IFN and 0.25 in FTY with a significant difference between the two groups (RR: 0.55, 95% CI: 0.45 to 0.68; p<0.001). The result of the emulation was very similar and fell within the 95% CI of that observed in the RCT (RR: 0.49, 95% CI: 0.37 to 0.64; p<0.001) with a standardised difference of 0.66 (p=0.51).

Conclusions
By applying the same inclusion and exclusion criteria used in the RCT and employing appropriate methodology, we successfully replicated the RCT results with only minor discrepancies. Also, even if the confounding bias cannot be fully eliminated, conducting a rigorous target trial emulation could still yield valuable insights for comparative effectiveness research.
Cost-effectiveness of stepwise provisional versus systematic dual stenting strategies in patients with distal bifurcation left main stem lesions: economic analysis of the EBC MAIN trial
Authors: Le Bras Alicia , Hildick-Smith David , Nze Ossima Arnaud , Supplisson Olivier , Egred Mohaned , Brunel Philippe , Banning Adrian P , Morice Marie-Claude , Durand-Zaleski Isabelle 
Published: January 2024

BackgroundIn patients with distal bifurcation left main stem lesions requiring intervention, the European Bifurcation Club Left Main Coronary Stent Study trial found a non-significant difference in major adverse cardiac events (MACEs, composite of all-cause death, non-fatal myocardial infarction and target lesion revascularisation) favouring the stepwise provisional strategy, compared with the systematic dual stenting.AimsTo estimate the 1-year cost-effectiveness of stepwise provisional versus systematic dual stenting strategies.MethodsCosts in France and the UK, and MACE were calculated in both groups to estimate the incremental cost-effectiveness ratio (ICER). Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the healthcare provider with a time horizon of 1 year.ResultsThe cost difference between the two groups was €−755 (€5700 in the stepwise provisional group and €6455 in the systematic dual stenting group, p value<0.01) in France and €−647 (€6728 and €7375, respectively, p value=0.08) in the UK. The point estimates for the ICERs found that stepwise provisional strategy was cost saving and improved outcomes with a probabilistic sensitivity analysis confirming dominance with an 80% probability.ConclusionThe stepwise provisional strategy at 1 year is dominant compared with the systematic dual stenting strategy on both economic and clinical outcomes.
Decision tree algorithm to predict mortality in incurable cancer: a new prognostic model
Authors: Souza-Silva Renata de , Calixto-Lima Larissa , Varea Maria Wiegert Emanuelly , de Oliveira Livia Costa 
Published: January 2024

ObjectivesTo develop and validate a new prognostic model to predict 90-day mortality in patients with incurable cancer.MethodsIn this prospective cohort study, patients with incurable cancer receiving palliative care (n = 1322) were randomly divided into two groups: development (n = 926, 70%) and validation (n = 396, 30%). A decision tree algorithm was used to develop a prognostic model with clinical variables. The accuracy and applicability of the proposed model were assessed by the C-statistic, calibration and receiver operating characteristic (ROC) curve.ResultsAlbumin (75.2%), C reactive protein (CRP) (47.7%) and Karnofsky Performance Status (KPS) ≥50% (26.5%) were the variables that most contributed to the classification power of the prognostic model, named Simple decision Tree algorithm for predicting mortality in patients with Incurable Cancer (acromion STIC). This was used to identify three groups of increasing risk of 90-day mortality: STIC-1 - low risk (probability of death: 0.30): albumin ≥3.6 g/dL, CRP <7.8 mg/dL and KPS ≥50%; STIC-2 - medium risk (probability of death: 0.66 to 0.69): albumin ≥3.6 g/dL, CRP <7.8 mg/dL and KPS <50%, or albumin ≥3.6 g/dL and CRP ≥7.8 mg/dL; STIC-3 - high risk (probability of death: 0.79): albumin <3.6 g/dL. In the validation dataset, good accuracy (C-statistic ≥0.71), Hosmer-Lemeshow p=0.12 and area under the ROC curve=0.707 were found.ConclusionsSTIC is a valid, practical tool for stratifying patients with incurable cancer into three risk groups for 90-day mortality.
Metabolic remodeling of visceral and subcutaneous white adipose tissue during reacclimation of rats after cold
Authors: Soskic Marta Budnar , Zakic Tamara , Korac Aleksandra , Korac Bato , Jankovic Aleksandra 
Published: January 2024

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1 °C) for 45 days and reacclimated to room temperature (RT, 22 ± 1 °C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes.
Influence of overconsolidation ratio on hydromechanical behaviour of unsaturated silty soil under various shearing rates
Authors: Wu Shengshen , Zhou Annan , Li Jie , Wu Bisheng 
Published: January 2024

Due to the limited land resources in major cities, reclamation becomes an optimal option to solve this issue, unsaturated soil is often involved in these projects, and the hydro-mechanical behaviour of this type of soil significantly are affected by the stress history and time effect. In this study, the overconsolidation ratio (OCR) effect of unsaturated silt under different shearing rates was studied through a series of constant water content tests. The specimens were under an effective confining pressure of 400 kPa. The samples were unloaded to 100 kPa, and 50 kPa to achieve different values of OCRs (4 and 8). The samples with different OCRs were then dried from saturated state to initial suction = 100, 200, and 300 kPa via axis-translation, and then sheared at three different rates. The results show that higher strain rates led to a higher degree of saturation during shearing under different OCRs. The shear strength increased with increasing shearing rates while the maximum deviator stress decreased when OCR decreased. Higher OCRs resulted in larger volume change during shearing; similar behaviour was observed for increasing rates.
Global phase space analysis for a class of single scalar field bouncing solutions in general relativity
Authors: Agrawal A. S. , Chakraborty Saikat , Mishra B. , Dutta Jibitesh , Khyllep Wompherdeiki 
Published: January 2024

AbstractWe carry out a compact phase space analysis of a non-canonical scalar field theory whose Lagrangian is of the form $$F(X)-V(\phi )$$

F
(
X
)
-
V
(
ϕ
)

within general relativity. In particular, we focus on a kinetic term of the form $$F(X)=\beta X^m$$

F

(
X
)

=
β

X
m

($$m\ne 1/2$$

m
≠
1
/
2

) with power-law potential $$V_0 \phi ^n$$

V
0

ϕ
n

and exponential potential $$V_0 e^{-\lambda \phi /M_{Pl}}$$

V
0

e

-
λ
ϕ
/

M

Pl

of the scalar field. The Cuscuton case $$m=1/2$$

m
=
1
/
2

where the scalar field is non-dynamical is left out of consideration. The main aim of this work is to investigate the genericity of nonsingular bounce in these models and to investigate the cosmic future of the bouncing cosmologies when they are generic. A global dynamical system formulation that is particularly suitable for investigating nonsingular bouncing cosmologies is used to carry out the analysis. We show that when $$F(X)=\beta X^m$$

F

(
X
)

=
β

X
m

($$\beta <0$$

β
<
0

), nonsingular bounce is generic for a power law potential $$V(\phi ) = V_0 \phi ^n$$

V

(
ϕ
)

=

V
0

ϕ
n

only within the parameter range $$\left\{ \frac{1}{2}<m<1,\,n<\frac{2\,m}{m-1}\right\} $$

1
2

<
m
<
1
,

n
<

2

m

m
-
1

and for an exponential potential $$V(\phi ) = V_0 e^{-\lambda \phi /M_{Pl}}$$

V

(
ϕ
)

=

V
0

e

-
λ
ϕ
/

M

Pl

only within the parameter range $$\left\{ \frac{1}{2}<m\le 1\right\} $$

1
2

<
m
≤
1

. Except in these cases, nonsingular bounce in these models is not generic due to the non-existence of global past or future attractors. Our analysis serves to show the importance of a global phase space analysis to address important questions about nonsingular bouncing solutions, an idea that may and must be adopted for such solutions even in other theories.
Abnormal states with unequal constituent masses
Authors: Karmanov V. A. 
Published: January 2024

AbstractThe Bethe–Salpeter equation for system of two oppositely charged particles not only reproduces the Coulomb spectrum, but, for enough large coupling constant $${\mathcal C}>\frac{\pi }{4}$$

C
>

π
4

, predicts additional levels not predicted by the Schrödinger equation. These relativistic states (called abnormal), in contrast to the normal ones, are dominated, for more than 90–99%, by Fock states involving the exchange particles—the photons, whereas contribution of two massive charged particles themselves is rather small (1–10%). Since the carrier of a large (positive) charge is a heavy ion, and the negative charge is provided by electron, the masses of two constituents are very different. It is shown that in a system with so different masses the abnormal states still exist. Moreover, the effect of unequal masses is attractive. The balance between photons and charged constituents is weakly sensitive to the mass ratio, so the photons still predominate.
Targeting the Epigenetic Reader ENL Inhibits Super-Enhancer–Driven Oncogenic Transcription and Synergizes with BET Inhibition to Suppress Tumor Progression
Authors: Chen Yongheng , Ying Ying , Ma Wenlong , Ma Hongchao , Shi Liang , Gao Xuefeng , Jia Min , Li Meiqi , Song Xiaoman , Kong Weixiao , Chen Wei , Zheng Xiangyi , Muluh Tobias Achu , Wang Xiaobin , Wang Maolin , Shu Xing-sheng 
Published: January 2024

Abstract

Epigenetic alterations at cis-regulatory elements (CRE) fine-tune transcriptional output. Epigenetic readers interact with CREs and can cooperate with other chromatin regulators to drive oncogene transcription. Here, we found that the YEATS domain-containing histone acetylation reader ENL (eleven–nineteen leukemia) acts as a key regulator of super-enhancers (SE), which are highly active distal CREs, across cancer types. ENL occupied the majority of SEs with substantially higher preference over typical enhancers, and the enrichment of ENL at SEs depended on its ability to bind acetylated histones. Rapid depletion of ENL by auxin-inducible degron tagging severely repressed the transcription of SE-controlled oncogenes, such as MYC, by inducing the decommissioning of their SEs, and restoring ENL protein expression largely reversed these effects. Additionally, ENL was indispensable for the rapid activation of SE-regulated immediate early genes in response to growth factor stimulation. Furthermore, ENL interacted with the histone chaperone FACT complex and was required for the deposition of FACT over CREs, which mediates nucleosome reorganization required for transcription initiation and elongation. Proper control of transcription by ENL and ENL-associated FACT was regulated by the histone reader BRD4. ENL was overexpressed in colorectal cancer and functionally contributed to colorectal cancer growth and metastasis. ENL degradation or inhibition synergized with BET inhibitors that target BRD4 in restraining colorectal cancer progression. These findings establish the essential role of epigenetic reader ENL in governing SE-driven oncogenic transcription and uncover the potential of ENL intervention to increase sensitivity to BET inhibition.

Significance:
ENL plays a key role in decoding epigenetic marks at highly active oncogenic super-enhancers and can be targeted in combination with BET inhibition as a promising synergistic strategy for optimizing cancer treatment.
Classification Algorithm to Distinguish Between Type 1 and Type 2 Myocardial Infarction in Administrative Claims Data
Authors: Wasfy Jason H. , Price Mary , Normand Sharon-Lise T. , Januzzi James L. , McCarthy Cian P. , Hsu John 
Published: January 2024

BACKGROUND:
Type 2 myocardial infarction (T2MI) and type 1 myocardial infarction (T1MI) differ with respect to demographics, comorbidities, treatments, and clinical outcomes. Reliable quality and outcomes assessment depends on the ability to distinguish between T1MI and T2MI in administrative claims data. As such, we aimed to develop a classification algorithm to distinguish between T1MI and T2MI that could be applied to claims data.

METHODS:

Using data for beneficiaries in a Medicare accountable care organization contract in a large health care system in New England, we examined the distribution of MI diagnosis codes between 2018 to 2021 and the patterns of care and coding for beneficiaries with a hospital discharge diagnosis
International Classification of Diseases
,
Tenth Revision
code for T2MI, compared with those for T1MI. We then assessed the probability that each hospitalization was for a T2MI versus T1MI and examined care occurring in 2017 before the introduction of the T2MI code.

RESULTS:
After application of inclusion and exclusion criteria, 7759 hospitalizations for myocardial infarction remained (46.5% T1MI and 53.5% T2MI; mean age, 79±10.3 years; 47% female). In the classification algorithm, female gender (odds ratio, 1.26 [95% CI, 1.11–1.44]), Black race relative to White race (odds ratio, 2.48 [95% CI, 1.76–3.48]), and diagnoses of COVID-19 (odds ratio, 1.74 [95% CI, 1.11–2.71]) or hypertensive emergency (odds ratio, 1.46 [95% CI, 1.00–2.14]) were associated with higher odds of the hospitalization being for T2MI versus T1MI. When applied to the testing sample, the C-statistic of the full model was 0.83. Comparison of classified T2MI and observed T2MI suggest the possibility of substantial misclassification both before and after the T2MI code.

CONCLUSIONS:
A simple classification algorithm appears to be able to differentiate between hospitalizations for T1MI and T2MI before and after the T2MI code was introduced. This could facilitate more accurate longitudinal assessments of acute myocardial infarction quality and outcomes.
High‐Intensity Interval Training Is Associated With Improved 10‐Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid‐Range Ejection Fraction
Authors: Hsu Chih‐Chin , Fu Tieh‐Cheng , Wang Chao‐Hung , Huang Ting‐Shuo , Cherng Wen‐Jin , Wang Jong‐Shyan 
Published: January 2024

Background
This study aimed to assess the left ventricular (LV) remodeling response and long‐term survival after high‐intensity interval training (HIIT) in patients with various heart failure (HF) phenotypes during a 10‐year longitudinal follow‐up.

Methods and Results

Among 214 patients with HF receiving guideline‐directed medical therapy, those who underwent an additional 36 sessions of aerobic exercise at alternating intensities of 80% and 40% peak oxygen consumption (

V
̇

$$ \dot{\mathrm{V}} $$

O
2peak
) were considered HIIT participants (n=96). Patients who did not undergo HIIT were considered participants receiving guideline‐directed medical therapy (n=118). Participants with LV ejection fraction (EF) <40%, ≥40% and <50%, and ≥50% were considered to have HF with reduced EF, HF with mid‐range EF, and HF with preserved EF, respectively.

V
̇

$$ \dot{\mathrm{V}} $$

O
2peak
, serial LV geometry, and time to death were recorded. In all included participants, 10‐year survival was better (
P
=0.015) for participants who underwent HIIT (80.3%) than for participants receiving guideline‐directed medical therapy (68.6%). An increased

V
̇

$$ \dot{\mathrm{V}} $$

O
2peak
, decreased minute ventilation carbon dioxide production slope, and reduced LV end‐diastolic diameter were protective factors against all‐cause mortality. Regarding 138 patients with HF with reduced EF (
P
=0.044) and 36 patients with HF with mid‐range EF (
P
=0.036), 10‐year survival was better for participants who underwent HIIT than for participants on guideline‐directed medical therapy. Causal mediation analysis showed a significant mediation path for LV end‐diastolic diameter on the association between HIIT and 10‐year mortality in all included patients with HF (
P
<0.001) and those with LV ejection fraction <50% (
P
=0.006). HIIT also had a significant direct association with 10‐year mortality in patients with HF with LV ejection fraction <50% (
P
=0.027) but not in those with LV ejection fraction ≥50% (n=40).

Conclusions
Reversal of LV remodeling after HIIT could be a significant mediating factor for 10‐year survival in patients with HF with reduced EF and those with HF with mid‐range EF.
High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging
Authors: Kotadia Irum D. , O'Dowling Robert , Aboagye Akosua , Crawley Richard J. , Bodagh Neil , Gharaviri Ali , O'Hare Daniel , Solis‐Lemus Jose Alonso , Roney Caroline H. , Sim Iain , Ramsey Deborah , Newby David , Chiribiri Amedeo , Plein Sven , Sztriha Laszlo , Scott Paul , Masci Pier‐Giorgio , Harrison James , Williams Michelle C. , Birns Jonathan , Somerville Peter , Bhalla Ajay , Niederer Steven , O'Neill Mark , Williams Steven E. 
Published: January 2024

Background
Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS.

Methods and Results
In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow‐up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2).

Conclusions
CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04555538.
Value and Variability of Pulse Shape Indicator for Estimating Mean Arterial Pressure in the Radial and Femoral Arteries
Authors: Jozwiak Mathieu , Millasseau Sandrine , Teboul Jean‐Louis , Lombardi Romain , Devanlay Raphaël , Umbdenstock Emilien , Morand Lucas , Dellamonica Jean , Chemla Denis 
Published: January 2024

Background
The form factor (FF) is a pulse shape indicator that corresponds to the fraction of pulse pressure added to diastolic blood pressure to estimate the time‐averaged mean arterial pressure (MAP). Our invasive study assessed the FF value and variability at the radial and femoral artery levels and evaluated the recommended fixed FF value of 0.33.

Methods and Results

Hemodynamically stable patients were prospectively included in 2 intensive care units. FF was documented at baseline and during dynamic maneuvers. A total of 632 patients (64±16 years of age, 66% men, MAP=81±14 mm Hg) were included. Among them, 355 (56%) had a radial catheter and 277 (44%) had a femoral catheter. The FF was 0.34±0.06. In multiple linear regression, FF was influenced by biological sex (
P
<0.0001) and heart rate (
P
=0.04) but not by height, weight, or catheter location. The radial FF was 0.35±0.06, whereas the femoral FF was 0.34±0.05 (
P
=0.08). Both radial and femoral FF were higher in women than in men (
P
<0.05). When using the 0.33 FF value to estimate MAP, the error was −0.4±4.0 mm Hg and −0.1±2.9 mm Hg at the radial and femoral level, respectively, and the MAP estimate still demonstrated high accuracy and good precision even after changes in norepinephrine dose, increase in positive end‐expiratory pressure level, fluid administration, or prone positioning (n=218).

Conclusions
Despite higher FF in women and despite interindividual variability in FF, using a fixed FF value of 0.33 yielded accurate and precise estimations of MAP. This finding has potential implications for blood pressure monitoring devices and the study of pulse wave amplification.