bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Derived CCL5 Recruits Cancer-Associated Fibroblasts and Promotes Tumor Cell Proliferation in Esophageal Squamous Cell Carcinoma
Authors: Dunbar Karen J. , Karakasheva Tatiana A. , Tang Qiaosi , Efe Gizem , Lin Eric W. , Harris Michael , Sahu Varun , Sachdeva Uma M. , Hu Jianhua , Klein-Szanto Andres J. , Henick Brian , Diehl J. Alan , Nakagawa Hiroshi , Rustgi Anil K. 
Published: April 2023

Abstract

Cancer-associated fibroblasts (CAF) can promote tumor growth, metastasis, and therapeutic resistance in esophageal squamous cell carcinoma (ESCC), but the mechanisms of action remain elusive. Our objective was to identify secreted factor(s) that mediate the communication between CAFs and ESCC tumor cells with the aim of identifying potential druggable targets. Through unbiased cytokine arrays, we have identified CC motif chemokine ligand 5 (CCL5) as a secreted factor that is increased upon co-culture of ESCC cells and CAFs, which we replicated in esophageal adenocarcinoma (EAC) with CAFs. Loss of tumor-cell-derived CCL5 reduces ESCC cell proliferation in vitro and in vivo and we propose this is mediated, in part, by a reduction in ERK1/2 signaling. Loss of tumor-derived CCL5 reduces the percentage of CAFs recruited to xenograft tumors in vivo. CCL5 is a ligand for the CC motif receptor 5 (CCR5), for which a clinically approved inhibitor exists, namely Maraviroc. Maraviroc treatment reduced tumor volume, CAF recruitment, and ERK1/2 signaling in vivo, thus, mimicking the effects observed with genetic loss of CCL5. High CCL5 or CCR5 expression is associated with worse prognosis in low-grade esophageal carcinomas.

Implications:
These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5–CCR5 axis in ESCC.
MACdb: A Curated Knowledgebase for Metabolic Associations across Human Cancers
Authors: Sun Yanling , Zheng Xinchang , Wang Guoliang , Wang Yibo , Chen Xiaoning , Sun Jiani , Xiong Zhuang , Zhang Sisi , Wang Tianyi , Fan Zhuojing , Bu Congfan , Bao Yiming , Zhao Wenming 
Published: April 2023

Abstract

Cancer is one of the leading causes of human death. As metabolomics techniques become more and more widely used in cancer research, metabolites are increasingly recognized as crucial factors in both cancer diagnosis and treatment. In this study, we developed MACdb (https://ngdc.cncb.ac.cn/macdb), a curated knowledgebase to recruit the metabolic associations between metabolites and cancers. Unlike conventional data-driven resources, MACdb integrates cancer-metabolic knowledge from extensive publications, providing high quality metabolite associations and tools to support multiple research purposes. In the current implementation, MACdb has integrated 40,710 cancer-metabolite associations, covering 267 traits from 17 categories of cancers with high incidence or mortality, based entirely on manual curation from 1,127 studies reported in 462 publications (screened from 5,153 research papers). MACdb offers intuitive browsing functions to explore associations at multi-dimensions (metabolite, trait, study, and publication), and constructs knowledge graph to provide overall landscape among cancer, trait, and metabolite. Furthermore, NameToCid (map metabolite name to PubChem Cid) and Enrichment tools are developed to help users enrich the association of metabolites with various cancer types and traits.

Implication:
MACdb paves an informative and practical way to evaluate cancer-metabolite associations and has a great potential to help researchers identify key predictive metabolic markers in cancers.
Propensity-Matched Study of Early Cardiac Rehabilitation in Patients With Acute Decompensated Heart Failure
Authors: Enzan Nobuyuki , Matsushima Shouji , Kaku Hidetaka , Tohyama Takeshi , Nezu Tomoyuki , Higuchi Tae , Nagatomi Yuta , Fujino Takeo , Hashimoto Toru , Ide Tomomi , Tsutsui Hiroyuki 
Published: April 2023

Background:
The impact of early implementation of cardiac rehabilitation (CR) in heart failure (HF) patients remains to be elucidated. This study sought to determine whether CR during HF hospitalization could improve prognostic outcomes in patients with acute decompensated HF.

Methods:
We analyzed patients with HF enrolled in the JROADHF (Japanese Registry of Acute Decompensated Heart Failure) registry, a retrospective, multicenter, nationwide registry of patients hospitalized for acute decompensated HF. Eligible patients were divided into 2 groups according to CR during hospitalization. The primary outcome was a composite of cardiovascular death or rehospitalization due to cardiovascular event after discharge. The secondary outcomes were cardiovascular death and cardiovascular event rehospitalization.

Results:

Out of 10 473 eligible patients, 3210 patients underwent CR. Propensity score matching yielded 2804 pairs. Mean age was 77±12 years and 3127 (55.8%) were male. During a mean follow-up of 2.8 years, the CR group had lower incidence rates of the composite outcome (291 versus 327 events per 1000 patient-years; rate ratio, 0.890 [95% CI, 0.830–0.954];
P
=0.001) and rehospitalization due to cardiovascular event (262 versus 295 events per 1000 patient-years; rate ratio, 0.888 [95% CI, 0.825–0.956];
P
=0.002) than the no CR group. In-hospital CR was associated with an improvement in Barthel index for activities of daily living (
P
=0.002). Patients with very low Barthel index at admission were benefited by CR in comparison with patients with independent Barthel index (very low; hazard ratio, 0.834 [95% CI, 0.742–0.938]: independent; hazard ratio, 0.985 [95% CI, 0.891–1.088];
P
for interaction=0.035).

Conclusions:
CR implementation during hospitalization was associated with better long-term outcomes in patients with acute decompensated HF. These data support the need for a randomized, controlled, adequately powered trial to definitively test the role of early physical rehabilitation in hospitalized patients with HF.
Associations of Community and Individual Social Determinants of Health With Medication Adherence in Patients With Atrial Fibrillation: A Retrospective Cohort Study
Authors: Boyd Lisa M. , Colavecchia Anthony Carmine , Townsend Kevin A. , Kmitch Laura , Broder Leah , Hegeman‐Dingle Rozelle R. , Ateya Mohammad , Lattimer Alan , Bosch Ryan , Alvir Jose 
Published: April 2023

Background
Despite guideline‐recommended use of oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF), OAC medication adherence among patients with AF in the United States ranges from 47% to 82%. To characterize potential causes of nonadherence, we analyzed associations between community and individual social risk factors and OAC adherence for stroke prevention in AF.

Methods and Results
A retrospective cohort analysis of patients with AF was conducted using the IQVIA PharMetrics Plus claims data from January 2016 to June 2020, and 3‐digit ZIP code‐level social risk scores were calculated using American Community Survey and commercial data. Logistic regression models evaluated associations between community social determinants of health, community social risk scores for 5 domains (economic climate, food landscape, housing environment, transportation network, and health literacy), patient characteristics and comorbidities, and 2 adherence outcomes: persistence on OAC for 180 days and proportion of days covered ≥0.80 at 360 days. Of 28 779 patients with AF included in the study, 70.8% of patients were male, 94.6% were commercially insured, and the average patient age was 59.2 years. Multivariable regression found that greater health literacy risk was negatively associated with 180‐day persistence (odds ratio [OR]=0.80 [95% CI, 0.76–0.83]) and 360‐day proportion of days covered (OR, 0.81 [95% CI, 0.76–0.87]). Patient age and higher AF stroke risk score and AF bleeding risk scores were positively associated with both 180‐day persistence and 360‐day proportion of days covered.

Conclusions
Social risk domains, such as health literacy, may affect OAC adherence among patients with AF. Future studies should explore associations between social risk factors and nonadherence with greater geographic granularity.
The EVA Study: Early Vascular Aging in Women With History of Preeclampsia
Authors: Werlang Ana , Paquin Amélie , Coutinho Thais 
Published: April 2023

Background
Early vascular aging (EVA) is associated with higher risk of adverse cardiovascular events and can be estimated noninvasively by assessing arterial hemodynamics. Women with a history of preeclampsia have increased risk of cardiovascular disease, but underlying mechanisms are incompletely understood. We hypothesized that women with a history of preeclampsia display persistent arterial abnormalities and EVA in the postpartum period.

Methods and Results

We performed a comprehensive, noninvasive arterial hemodynamic evaluation in women with a history of preeclampsia (n=40) and age‐matched controls with previous normotensive pregnancies (n=40). We used validated methods integrating applanation tonometry with transthoracic echocardiography to obtain measures of aortic stiffness, steady and pulsatile arterial load, central blood pressure, and arterial wave reflections. Presence of EVA was defined as aortic stiffness higher than that predicted from reference values based on the participant's age and blood pressure. The association of preeclampsia with arterial hemodynamic variables was assessed with multivariable linear regression, and the association of severe preeclampsia with EVA was assessed with multivariable logistic regression, adjusted for confounders. We found that women with a history of preeclampsia had greater aortic stiffness, steady arterial load, central blood pressure, and arterial wave reflections when compared with controls. We observed a dose–response relationship, with the greatest abnormalities observed in subgroups with severe, preterm, or recurrent preeclampsia. Women with severe preeclampsia had 9.23 times greater odds of having EVA as compared with controls (95% CI, 1.67–51.06,
P
=0.011) and 7.87 greater odds of EVA as compared with women with nonsevere preeclampsia (95% CI, 1.29–47.77,
P
=0.025).

Conclusions
Our study comprehensively characterizes arterial hemodynamic abnormalities after preeclampsia and suggests that specific subgroups of women with a history of preeclampsia exhibit greater alterations in arterial hemodynamics related to arterial health. Our findings have important implications for understanding potential links between preeclampsia and cardiovascular events, and suggest women with severe, preterm, or recurrent preeclampsia as subgroups who may deserve intensification of efforts for prevention and early detection of cardiovascular disease.
Twenty‐Four‐Hour Ambulatory Blood Pressure Profile in Patients With Reflex Syncope and Matched Controls
Authors: Sharad Bashaaer , Rivasi Giulia , Hamrefors Viktor , Johansson Madeleine , Ungar Andrea , Sutton Richard , Brignole Michele , Parati Gianfranco , Fedorowski Artur 
Published: April 2023

Background
Ambulatory blood pressure (BP) monitoring has long been used to monitor BP in hypertension and lately emerged as a useful tool to detect hypotensive susceptibility in reflex syncope. However, hemodynamic characteristics in reflex syncope have not been sufficiently explored. The present study investigated the differences between ambulatory BP monitoring profiles associated with reflex syncope and normal population.

Methods and Results

This is an observational study comparing ambulatory BP monitoring data from 50 patients with reflex syncope and 100 controls without syncope, age‐ and sex‐matched 1:2. Mean 24‐hour systolic (SBP) and diastolic BP, pulse pressure (24‐hour PP), dipping status, and number of daytime SBP drops <90 to 100 mm Hg were analyzed. Variables associated with reflex syncope were investigated using multivariable logistic regression. Patients with reflex syncope displayed significantly lower 24‐hour SBP (112.9±12.6 versus 119.3±11.5 mm Hg,
P
=0.002), higher 24‐hour diastolic BP (85.2±9.6 versus 79.1±10.6 mm Hg,
P
<0.001), and markedly lower 24‐hour PP (27.7±7.6 versus 40.3±9.0 mm Hg,
P
<0.001) compared with controls. Daytime SBP drops <90 mm Hg were more prevalent in patients with syncope (44% versus 17%,
P
<0.001). Daytime SBP drops <90 mm Hg, 24‐hour PP <32 mm Hg, 24‐hour SBP ≤110 mm Hg, and 24‐hour diastolic BP ≥82 mm Hg were independently associated with reflex syncope, with 24‐hour PP <32 mm Hg achieving the highest sensitivity (80%) and specificity (86%).

Conclusions
Patients with reflex syncope have lower 24‐hour SBP but higher 24‐hour diastolic BP and more frequent daytime SBP drops <90 mm Hg than individuals without syncope. Our results support the presence of lower SBP and PP in reflex syncope and suggest a role for ambulatory BP monitoring in the diagnostic work‐up of this condition.
Characterization of the Mitochondrial Genetic Landscape in Abdominal Aortic Aneurysm
Authors: Vats Sakshi , Sundquist Kristina , Li Yanni , Wang Xiao , Hong Mun‐Gwan , Sundquist Jan , Zarrouk Moncef , Gottsäter Anders , Memon Ashfaque A. 
Published: April 2023

Background
Abdominal aortic aneurysm (AAA) is a vascular disease with a mortality rate of >80% if ruptured. Mitochondrial dysfunction has been previously implicated in AAA pathogenesis. In this study, we aimed to characterize the mitochondrial genetic landscape in AAA.

Methods and Results

Whole mitochondrial genome sequencing and bioinformatics analysis were performed in comorbidity matched 48 cases without AAA and 48 cases with AAA, objectively diagnosed, and selected from a cohort of 65‐year‐old men recruited for a screening program. We identified differential mutational landscapes in men with and without AAA, with errors in mitochondrial DNA replication or repair as potential sources. Heteroplasmic insertions and overall heteroplasmy of structural rearrangements were significantly elevated in AAA cases. Three heteroplasmic variants were associated with risk factors of AAA: leukocyte concentration, plasma glucose, and cholesterol levels, respectively. Interestingly, mutations were more prevalent in regulatory part of the mitochondria, the displacement loop region, in AAA as compared with controls (
P
value <0.05), especially in the conserved and critical mitochondrial extended termination‐associated sequence region. Moreover, we report a novel 24 bp mitochondrial DNA duplication present exclusively in cases with AAA (4%) and 75% of the unmatched AAA biopsies. Finally, the haplogroup cluster JTU was overrepresented in AAA and significantly associated with a positive family history of AAA (odds ratio, 2.9 [95% CI, 1.1–8.1]).

Conclusions
This is the first study investigating the mitochondrial genome in AAA, where important genetic alterations and haplogroups associated with AAA and clinical risk factors were identified. Our findings have the potential to fill in gaps in the missing genetic information on AAA.
Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study
Authors: Sandvig Heidi Vihovde , Aam Stina , Alme Katinka Nordheim , Askim Torunn , Beyer Mona K. , Ellekjær Hanne , Ihle-Hansen Hege , Lydersen Stian , Mollnes Tom Eirik , Munthe-Kaas Ragnhild , Næss Halvor , Saltvedt Ingvild , Seljeseth Yngve Müller , Thingstad Pernille , Wethal Torgeir , Knapskog Anne-Brita 
Published: April 2023

Background:
Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment.

Methods:
The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex.

Results:

We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (
P
<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (
P
<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (
P
<0.01).

Conclusions:
Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02650531.
Perfusion Imaging Mismatch Profiles in the Early Thrombectomy Window: A Single-Center Analysis
Authors: Schwarz Ghil , Agostoni Elio C. , Saliou Guillaume , Hajdu Steven David , Salerno Alexander , Dunet Vincent , Michel Patrik , Strambo Davide 
Published: April 2023

Background:
Little is known on the role of mismatch profile in patients undergoing early endovascular treatment (EVT). We aimed to describe pretreatment perfusion parameters and mismatch profiles in anterior circulation large vessel occlusion acute ischemic stroke undergoing EVT in the early time window and assess their association with time from stroke onset and outcomes.

Methods:

Retrospective single-center study, including early (<6 hours) EVT-treated large vessel occlusion acute ischemic stroke with baseline perfusion data, assessing perfusion parameters (ischemic core volume, mismatch volume and mismatch ratio) and mismatch profiles (favorable versus unfavorable, based on criteria adopted in EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial], SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment], DEFUSE 3 [Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3], and DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo] trials). We evaluated their association with time from stroke onset (r
s
[for parameters] or χ
2
for trend [for profiles]) and association with modified Rankin Scale score >2, symptomatic intracranial hemorrhage, and mortality (multivariate regression analyses [each parameter/profile entered into a separate logistic regression model, adjusted for baseline variables associated with each outcome in the univariate analysis at the
P
<0.1 level]).

Results:

Among 357 patients, unfavorable mismatch profiles ranged from 21% to 60%, depending on the criterion, and were not correlated with time from stroke onset (
P
=0.490). All individual perfusion parameters and unfavorable mismatch profiles were associated with poor functional outcome: ischemic core volume adjusted odds ratio (aOR), 1.49 ([95% CI, 1.13–1.97]
P
=0.005); penumbral volume aOR, 0.30 ([95% CI, 0.10–0.84]
P
=0.022); mismatch ratio aOR, 0.67 ([95% CI, 0.50–0.90]
P
=0.007); EXTEND-IA aOR, 2.61 ([95% CI, 1.23–5.51]
P
=0.012); SWIFT PRIME aOR, 2.50 ([95% CI, 1.30–4.57]
P
=0.006); DEFUSE 3 aOR, 2.28 ([95% CI, 1.14–4.57]
P
=0.020); and DAWN aOR, 4.19 ([95% CI, 2.13–8.26]
P
<0.001). EXTEND-IA and DEFUSE 3 unfavorable profiles were also independently associated with symptomatic intracranial hemorrhage (aOR, 3.82 [95% CI, 1.42–10.3];
P
=0.008 and aOR, 2.83 [95% CI, 1.09–7.36];
P
=0.033) and death (aOR, 3.26 [95% CI, 1.33–8.02];
P
=0.010 and aOR, 2.52 [95% CI, 1.10–5.82];
P
=0.030).

Conclusions:
Pretreatment perfusion parameters and mismatch profiles in early EVT-treated patients were not correlated with time from stroke onset but were independently associated with functional outcome. Mismatch assessment in the early time window may improve EVT patient selection, independently of onset-to-treatment time.
Optimizing network neuroscience computation of individual differences in human spontaneous brain activity for test-retest reliability
Authors: Jiang Chao , He Ye , Betzel Richard F. , Wang Yin-Shan , Xing Xiu-Xia , Zuo Xi-Nian 
Published: April 2023

Abstract
A rapidly emerging application of network neuroscience in neuroimaging studies has provided useful tools to understand individual differences in intrinsic brain function by mapping spontaneous brain activity, namely intrinsic functional network neuroscience (ifNN). However, the variability of methodologies applied across the ifNN studies—with respect to node definition, edge construction, and graph measurements—makes it difficult to directly compare findings and also challenging for end users to select the optimal strategies for mapping individual differences in brain networks. Here, we aim to provide a benchmark for best ifNN practices by systematically comparing the measurement reliability of individual differences under different ifNN analytical strategies using the test-retest design of the Human Connectome Project. The results uncovered four essential principles to guide ifNN studies: (1) use a whole brain parcellation to define network nodes, including subcortical and cerebellar regions; (2) construct functional networks using spontaneous brain activity in multiple slow bands; and (3) optimize topological economy of networks at individual level; and (4) characterize information flow with specific metrics of integration and segregation. We built an interactive online resource of reliability assessments for future ifNN (https://ibraindata.com/research/ifNN).
The Idea of a Good Life: Lessons from Confucius, Aristotle, Zhuangzi, and the Stoics
Authors: Wenzel Christian Helmut 
Published: April 2023

Abstract
In 1930, the British economist John Maynard Keynes predicted that by 2030 people would work only fifteen hours per week and enjoy more free time and leisure, that we would return to “principles of religion and traditional virtue,” declaring “love of money morbid, semi-criminal, and semi-pathological,” and that “we shall once more value ends above means.” But today, we do not see that this prophesy has proven true. Something must have gone wrong. We do not sufficiently know the distinction between needs and wants, absolute values and relative values, what a good life is, and how to live it. In this essay, I will present and discuss ideas from Confucius, Aristotle, Zhuangzi, and the Stoics that I think are deep and meaningful and can help us free ourselves from evolutionary programming and blind belief in economic and technological growth.
Gangster Zhi: Comedic Daoist Philosophical Practice
Authors: Moeller Hans-Georg 
Published: April 2023

Abstract
This paper argues that the Zhuangzi 《莊子》 represents a specific type of Daoist practical philosophy: It is medicinal or therapeutic and seeks to promote existential ease, often by means of humor. Part of its approach to practical philosophy consists in pointing out the impracticality of many early Chinese philosophical doctrines, and, especially, Confucian political and ethical teachings. To illustrate this understanding of the Zhuangzi, the narrative of Confucius’ visit to the legendary Gangster Zhi (dao zhi 盜跖) is analyzed in some detail.