bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer
Authors: Yan Wei , Menjivar Rosa E. , Bonilla Monica E. , Steele Nina G. , Kemp Samantha B. , Du Wenting , Donahue Katelyn L. , Brown Kristee L. , Carpenter Eileen S. , Avritt Faith R. , Irizarry-Negron Valerie M. , Yang Sion , Burns William R. , Zhang Yaqing , Pasca di Magliano Marina , Bednar Filip 
Published: November 2023

Abstract
Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed to a high rate of early metastasis and low efficacy of current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies from our group and others have shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression in PDA. Here, we explored the role of Notch signaling, a key regulator of immune response, within the PDA microenvironment. We identified Notch pathway components in multiple immune cell types within human and mouse pancreatic cancer. TAMs, the most abundant immune cell population in the tumor microenvironment, expressed high levels of Notch receptors, with cognate ligands such as JAG1 expressed on tumor epithelial cells, endothelial cells, and fibroblasts. TAMs with activated Notch signaling expressed higher levels of immunosuppressive mediators, suggesting that Notch signaling plays a role in macrophage polarization within the PDA microenvironment. Genetic inhibition of Notch in myeloid cells led to reduced tumor size and decreased macrophage infiltration in an orthotopic PDA model. Combination of pharmacologic Notch inhibition with PD-1 blockade resulted in increased cytotoxic T-cell infiltration, tumor cell apoptosis, and smaller tumor size. Our work implicates macrophage Notch signaling in the establishment of immunosuppression and indicates that targeting the Notch pathway may improve the efficacy of immune-based therapies in patients with PDA.
Angiographic Severity of the Nonculprit Lesion and the Efficacy of Fractional Flow Reserve–Guided Complete Revascularization in Patients With AMI: FRAME-AMI Substudy
Authors: Seung Jaeho , Choo Eun Ho , Kim Chan Joon , Kim Hyun Kuk , Park Keun Ho , Lee Seung Hun , Kim Min Chul , Hong Young Joon , Ahn Sung Gyun , Doh Joon-Hyung , Lee Sang Yeub , Park Sang Don , Lee Hyun-Jong , Kang Min Gyu , Koh Jin-Sin , Cho Yun-Kyeong , Nam Chang-Wook , Koo Bon-Kwon , Lee Bong-Ki , Yun Kyeong Ho , Hong David , Joh Hyun Sung , Choi Ki Hong , Park Taek Kyu , Lee Joo Myung , Yang Jeong Hoon , Song Young Bin , Choi Seung-Hyuk , Gwon Hyeon-Cheol , Hahn Joo-Yong ,   the FRAME-AMI Investigators
Published: November 2023

BACKGROUND:
The benefit of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) for noninfarct-related artery (IRA) lesions with angiographically severe stenosis in patients with acute myocardial infarction is unclear.

METHODS:
Among 562 patients from the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infraction Related Artery Stenosis in Patients With Acute Myocardial Infarction) who were randomly allocated into either FFR-guided or angiography-guided PCI for non-IRA lesions, the current study evaluated the relationship between non-IRA stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI. The incidence of the primary end point (death, myocardial infarction, or repeat revascularization) was compared between FFR- and angiography-guided PCI according to non-IRA stenosis severity (QCA stenosis ≥70% or <70%).

RESULTS:

A total of 562 patients were assigned to FFR-guided (n=284) versus angiography-guided PCI (n=278). At a median follow-up of 3.5 years, the primary end point occurred in 14 of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patients with QCA stenosis ≥70% (8.5% versus 19.2%; hazard ratio, 0.41 [95% CI, 0.22–0.80];
P
=0.008), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiography-guided PCI among those with QCA stenosis <70% (3.9% versus 11.1%;
P
=0.315). There was no significant interaction between treatment strategy and non-IRA stenosis severity (
P
for interaction=0.636). FFR-guided PCI was associated with the reduction of death and myocardial infarction in both patients with QCA stenosis ≥70% (6.7% versus 15.1%;
P
=0.008) and those with QCA stenosis <70% (1.0% versus 9.6%;
P
=0.042) compared with angiography-guided PCI.

CONCLUSIONS:
In patients with acute myocardial infarction and multivessel disease, FFR-guided PCI tended to have a lower risk of primary end point than angiography-guided PCI regardless of non-IRA stenosis severity without significant interaction.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02715518.
Association Between Symptoms of Chronic Psychological Distress and Myocardial Ischemia Induced by Mental Stress in Patients With Coronary Artery Disease
Authors: Moazzami Kasra , Garcia Mariana , Sullivan Samaah , Lewis Tené T. , Bremner J. Douglas , Razavi Alexander C. , Shallenberger Lucy , Sun Yan V. , Raggi Paolo , Shah Amit J. , Quyyumi Arshed A. , Vaccarino Viola 
Published: November 2023

Background
Mental stress–induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease and is associated with a greater risk of future cardiovascular events. The association between chronic symptoms of psychological distress and mental stress–induced ischemia is not clear.

Methods and Results
We used a composite score of psychological distress derived from symptoms of depression, posttraumatic stress disorder, anxiety, anger, and perceived general stress. Participants underwent myocardial perfusion imaging with both mental (public speaking task) and conventional (exercise or pharmacological) stress testing. Overall, 142 (15.9%) patients experienced mental stress–induced myocardial ischemia. After adjusting for demographic factors, medical history, and medication use, patients in the highest tertile of psychological distress score had 35% higher odds of having mental stress–induced ischemia compared to those in the lowest tertile (odds ratio [OR], 1.35 [95% CI, 1.06–2.22]). Stratified analyses showed that the association between psychological distress score and mental stress–induced myocardial ischemia was significantly associated only within the subgroup of patients with a prior myocardial infraction, with patients with a prior myocardial infarction in the highest tertile having a 93% higher odds of developing myocardial ischemia with mental stress (95% CI, 1.07–3.60). There was no significant association between psychological distress and conventional stress–induced ischemia (OR, 1.19 [95% CI, 0.87–1.63]).

Conclusions
Among patients with a history of myocardial infarction, a higher level of psychosocial distress is associated with mental stress–induced myocardial ischemia but not with ischemia induced by a conventional stress test.
Association Between the Liver Fibrosis Markers and Scores, and Hemodynamic Congestion Assessed by Peripheral Venous Pressure in Patients With Acute Heart Failure
Authors: Nagao Kazuya , Maruichi‐Kawakami Shiori , Aida Kenji , Matsuto Kenichi , Imamoto Kazumasa , Yukawa Hiroshi , Kanazawa Takenori , Kobayashi Yohei , Takahashi Naoki , Ito Haruyasu , Hayashi Fujio , Inada Tsukasa 
Published: November 2023

Background
Peripheral venous pressure (PVP) has been shown to be a reliable surrogate for right atrial pressure in assessing congestion in patients with heart failure (HF). Liver fibrosis markers and scores can be useful in assessing organ injury in patients with acute HF. This study aimed to investigate the association of liver fibrosis markers and scores with PVP in patients with acute HF.

Methods and Results

The 7S domain of the collagen type IV N‐terminal propeptide (P4NP 7S), aspartate aminotransferase‐to‐platelet ratio index, fibrosis‐4, and nonalcoholic fatty liver disease fibrosis score were determined along with PVP measurements before discharge in 229 patients with acute HF. The strongest correlation with PVP was found for P4NP 7S (Pearson
r
=0.40). Patients with high P4NP 7S levels (≥median [6.2 ng/mL]) had an increased risk of cardiovascular death or HF hospitalization (adjusted hazard ratio [HR], 1.80 [95% CI, 1.09–3.04],
P
=0.02). The concomitant high PVP (≥mean [8 mm Hg])/high P4NP 7S group, in contrast to the high PVP/low P4NP 7S or low PVP/high P4NP 7S group, had a significant risk relative to the low PVP/low P4NP 7S group for cardiovascular death or HF hospitalization (adjusted HR, 2.63 [95% CI, 1.43–5.05],
P
=0.002). A sustained elevation in PVP for 1 month postdischarge was associated with a persistent increase in P4NP 7S.

Conclusions
The study demonstrated the relationship between the liver fibrosis marker P4NP 7S and congestion. PVP and P4NP 7S could be useful for assessing congestion‐related organ injury and predicting prognosis in patients with acute HF.
Right Heart Remodeling After Pulmonary Valve Replacement in Patients With Pulmonary Atresia or Critical Stenosis With Intact Ventricular Septum
Authors: Irwin Margaret , Reynolds Lindsey , Binney Geoffrey , Lipsitz Stuart , Ghelani Sunil J. , Harrild David M. , Baird Christopher W. , Geva Tal , Brown David W. 
Published: November 2023

Background
Patients with pulmonary atresia or critical pulmonary stenosis with intact ventricular septum (PA/IVS) and biventricular circulation may require pulmonary valve replacement (PVR). Right ventricular (RV) remodeling after PVR is well described in tetralogy of Fallot (TOF); we sought to investigate RV changes in PA/IVS using cardiac magnetic resonance imaging.

Methods and Results

A retrospective cohort of patients with PA/IVS who underwent PVR at Boston Children's Hospital from 1995 to 2021 with cardiac magnetic resonance imaging before and after PVR was matched 1:3 with patients with TOF by age at PVR. Median regression modeling was performed with post‐PVR indexed RV end‐diastolic volume as the primary outcome. A total of 20 patients with PA/IVS (cases) were matched with 60 patients with TOF (controls), with median age at PVR of 14 years. Pre‐PVR indexed RV end‐diastolic volume was similar between groups; cases had higher RV ejection fraction (51.4% versus 48.6%;
P
=0.03). Pre‐PVR RV free wall and left ventricular (LV) longitudinal strain were similar, although LV midcavity circumferential strain was decreased in cases (−15.6 versus −17.1;
P
=0.001). At a median of 2 years after PVR, indexed RV end‐diastolic volume was similarly reduced; cases continued to have higher RV ejection fraction (52.3% versus 46.9%;
P
=0.007) with less reduction in RV mass (Δ4.5 versus 9.6 g/m
2
;
P
=0.004). Post‐PVR, RV and LV longitudinal strain remained unchanged, and LV circumferential strain was similar, although lower in cases.

Conclusions
Compared with patients with TOF, patients with PA/IVS demonstrate similar RV remodeling after PVR, with lower reduction in RV mass and comparatively higher RV ejection fraction. Although no differences were detected in peak systolic RV or LV strain values, further investigation of diastolic parameters is needed.
Genome‐Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the
CETP
Gene
Authors: Yu Chenglong , Bakshi Andrew , Watts Gerald F. , Renton Alan E. , Fulton‐Howard Brian , Goate Alison M. , Natarajan Pradeep , Chasman Daniel I. , Robman Liubov , Woods Robyn L. , Guymer Robyn , Wolfe Rory , Thao Le Thi Phuong , McNeil John J. , Tonkin Andrew M. , Nicholls Stephen J. , Lacaze Paul 
Published: November 2023

Background
The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience.

Methods and Results

We performed a genome‐wide association study using a 10‐year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome‐wide association study of N=12 031 ASCVD event‐free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (
P
<5×10
−8
) and rs56156922 (
P
<10
−6
), in the
CETP
(cholesteryl ester transfer protein) gene. The
CETP
gene is a regulator of plasma high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified
CETP
variants (versus noncarriers) had higher plasma high‐density lipoprotein cholesterol levels, lower plasma low‐density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow‐up. Expression quantitative trait loci analysis predicted the identified
CETP
variants reduce
CETP
gene expression across various tissues. Previously reported associations between genetic
CETP
inhibition and increased risk of age‐related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available.

Conclusions

Common genetic variants in the
CETP
gene region are associated with cardiovascular resilience during aging.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01038583.
Longitudinal Changes in Health‐Related Quality of Life in Patients With Atrial Fibrillation
Authors: Foster‐Witassek Fabienne , Aebersold Helena , Aeschbacher Stefanie , Ammann Peter , Beer Jürg H. , Blozik Eva , Bonati Leo H. , Cattaneo Mattia , Coslovsky Michael , Felder Stefan , Moschovitis Giorgio , Müller Andreas , Netzer Seraina , Paladini Rebecca E. , Reichlin Tobias , Rodondi Nicolas , Stauber Annina , Sticherling Christian , Szucs Thomas , Conen David , Kühne Michael , Osswald Stefan , Serra‐Burriel Miquel , Schwenkglenks Matthias ,   the Swiss‐AF Investigators
Published: November 2023

Background
Optimizing health‐related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long‐term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics.

Methods and Results
We used 5‐year follow‐up data from the Swiss–Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL‐5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability‐weighted regressions. Effects of postbaseline clinical events were additionally assessed using time‐shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: “cardiovascular dominated,” “isolated symptomatic,” and “severely morbid without cardiovascular disease.” Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by −0.12 (95% CI, −0.18 to −0.06), −0.10 (95% CI, −0.13 to −0.08), and −0.06 (95% CI, −0.08 to −0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke.

Conclusions
In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure, stroke, and bleeding had only a temporary effect on HRQoL.
Use of Atrial Fibrillation Electrograms and T1/T2 Magnetic Resonance Imaging to Define the Progressive Nature of Molecular and Structural Remodeling: A New Paradigm Underlying the Emergence of Persistent Atrial Fibrillation
Authors: Rottmann Markus , Yoo Shin , Pfenniger Anna , Mikhailov Aleksei , Benefield Brandon , Johnson David A. , Zhang Wenwei , Ghosh Asish K. , Kim Daniel , Passman Rod , Knight Bradley P. , Lee Daniel C. , Arora Rishi 
Published: November 2023

Background
The temporal progression states of the molecular and structural substrate in atrial fibrillation (AF) are not well understood. We hypothesized that these can be detected by AF electrograms and magnetic resonance imaging parametric mapping.

Methods and Results

AF was induced in 43 dogs (25–35 kg, ≥1 year) by rapid atrial pacing (RAP) (3–33 weeks, 600 beats/min), and 4 controls were used. We performed high‐resolution epicardial mapping (UnEmap, 6 atrial regions, both atria, 130 electrodes, distance 2.5 mm) and analyzed electrogram cycle length, dominant frequency, organization index, and peak‐to‐peak bipolar voltage. Implantable telemetry recordings were used to quantify parasympathetic nerve activity over RAP time. Magnetic resonance imaging native T1, postcontrast T1, T2 mapping, and extracellular volume fraction were assessed (1.5T, Siemens) at baseline and AF. In explanted atrial tissue, DNA oxidative damage (8‐hydroxy‐2′‐deoxyguanosine staining) and percentage of fibrofatty tissue were quantified. Cycle length and organization index decreased (
R
=0.5,
P
<0.05; and
R
=0.5,
P
<0.05; respectively), and dominant frequency increased (
R
=0.3,
P
n.s.) until 80 days of RAP but not thereafter. In contrast, voltage continued to decrease throughout the duration of RAP (
R
=0.6,
P
<0.05). Parasympathetic nerve activity increased following RAP and plateaued at 80 days. Magnetic resonance imaging native T1 and T2 times increased with RAP days (
R
=0.5,
P
<0.05;
R
=0.6,
P
<0.05) in the posterior left atrium throughout RAP. Increased RAP days correlated with increasing 8‐hydroxy‐2′‐deoxyguanosine levels and with fibrosis percentage (
R
=0.5,
P
<0.05 for both).

Conclusions
A combination of AF electrogram characteristics and T1/T2 magnetic resonance imaging can detect early‐stage AF remodeling (autonomic remodeling, oxidative stress) and advanced AF remodeling due to oxidative stress and fibrosis.
The implications of Fe speciation for the humic substance stability of ternary Fe(III)–montmorillonite–humic substance systems
Authors: Lei Qinkai , Lv Yahui , Liu Chengshuai , Xu Wenpo , Hu Shujie , Chen Manjia , Bu Hongling , Li Junhui 
Published: November 2023

AbstractMineral–organic matter (OM) associations play an important role in determining the long-term retention of OM in soils. However, the retention mechanisms of OM in cation–mineral–OM systems remain unclear. Taking into account the dominance of montmorillonite (Mnt) in the soil of the temperate zone, we investigated the stability of humic substances (HSs) in the Fe(III)–Mnt–HS system using thermal analysis. The HS degradation started at ~387°C in the Fe(III)–Mnt–HS system, which was higher than that of the Fe(III)–HS system (290°C). The formed ferrihydrite (Fhy) mainly contributed to the enhanced labile OM retention through adsorption and/or co-precipitation, whereas Mnt inhibited the initial formation and subsequent transformation of Fhy, thus improving the stability of OM. These results suggest that the HS stability in Fe(III)–clay–HS systems depends on the Fe speciation affected by clay minerals, and this finding provides insights into OM–mineral interactions in temperate-zone soils.
Preparation of phase-change microcapsules with illite as a filler and their applications in foaming materials
Authors: Li Ming , Zhang Shuhua , Liu Weijun , Liu Binyan , Wang Yu 
Published: November 2023

AbstractTo solve the problem of the leakage of phase-change materials and expand the application of clay minerals in the field of phase-change materials, illite and paraffin wax were used for the first time as a new binary hybrid core material with silica as the wall material. Phase-change microcapsules were prepared using the sol–gel method and successfully applied in silicone rubber foams. Differential scanning calorimetry showed that the microcapsules had a melting temperature of 62.99°C and a latent heat capacity of 98.24 J g–1, indicating their good heat-storage capacity. Furthermore, the effectiveness of using illite as a filler for preventing paraffin leakage was demonstrated through 200 thermal cycling tests, which demonstrated a leakage rate of only 2.6% compared to 3.2% exhibited by microcapsules without illite.
Tiger attack at a Japanese safari park: a case report
Authors: Fujii Kouichi , Kikuchi Jin , Uchida Masatoshi , Machida Masanari , Tsuchiya Midori , Hayashi Kentaro , Maekawa Nana , Houzumi Hajime , Honda Arata , Wake Koji 
Published: November 2023

Abstract
Background
Big cat bites are highly lethal due to the enormous bite force of these animals. This article reviews the morphology of these types of injuries and key points of management through a survival case at a Japanese safari park.

Case presentation
We report the case of a 26-year-old female keeper who was attacked by a tiger. She was quickly transported to our university hospital by ambulance helicopter. The keeper was severely bitten on the head and face and had wounds all over her body. Craniofacial repair was performed by emergency surgery. She suffered mild facial nerve paralysis and trismus because of being bitten by the tiger and is currently recovering.

Conclusions
A multidisciplinary approach of the severe tiger bites successfully treated a young woman cosmetically and mentally. Animal farms and zoos that keep tigers should take strict measures to avoid direct confrontation with tigers.