bluuebunny/crossref_metadata_2025_split huggingface dataset:
FormulationAI: a novel web-based platform for drug formulation design driven by artificial intelligence
Authors: Dong Jie , Wu Zheng , Xu Huanle , Ouyang Defang 
Published: November 2023

Abstract
Today, pharmaceutical industry faces great pressure to employ more efficient and systematic ways in drug discovery and development process. However, conventional formulation studies still strongly rely on personal experiences by trial-and-error experiments, resulting in a labor-consuming, tedious and costly pipeline. Thus, it is highly required to develop intelligent and efficient methods for formulation development to keep pace with the progress of the pharmaceutical industry. Here, we developed a comprehensive web-based platform (FormulationAI) for in silico formulation design. First, the most comprehensive datasets of six widely used drug formulation systems in the pharmaceutical industry were collected over 10 years, including cyclodextrin formulation, solid dispersion, phospholipid complex, nanocrystals, self-emulsifying and liposome systems. Then, intelligent prediction and evaluation of 16 important properties from the six systems were investigated and implemented by systematic study and comparison of different AI algorithms and molecular representations. Finally, an efficient prediction platform was established and validated, which enables the formulation design just by inputting basic information of drugs and excipients. FormulationAI is the first freely available comprehensive web-based platform, which provides a powerful solution to assist the formulation design in pharmaceutical industry. It is available at https://formulationai.computpharm.org/.
Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder
Authors: Hu Yongbo , Li Shiyi , Li Jin , Zhao Youjin , Li Meiling , Cui Weigang , Peng Xiaolong , Dong Zaiquan , Zhang Lianqing , Xu Haizhen , Gao Li , Huang Xiaoqi , Kuang Weihong , Gong Qiyong , Liu Hesheng 
Published: November 2023

Abstract
The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.
Early growth response 1 as a podocyte injury marker in human glomerular diseases
Authors: Okabe Masahiro , Koike Kentaro , Yamamoto Izumi , Tsuboi Nobuo , Matsusaka Taiji , Yokoo Takashi 
Published: November 2023

ABSTRACT

Background
In human glomerular diseases, visualizing podocyte injury is desirable since podocytes do not regenerate and podocyte injury leads to podocyte loss. Herein, we investigated the utility of immunostaining for early growth response 1 (EGR1), which is expressed in injured podocytes from the early stages of injury in animal experiments, as a podocyte injury marker in human glomerular diseases.

Methods
This study included 102 patients with biopsy-proven glomerular diseases between 2018 and 2021. The proportion of EGR1 expression in podocytes (%EGR1pod) was analyzed in relation to clinical and histopathological features, including glomerular and urinary podocyte-specific markers.

Results
%EGR1pod correlated significantly with the urinary protein:creatinine ratio, urinary nephrin and podocin mRNA levels, and glomerular podocin staining (rho = 0.361, 0.514, 0.487 and –0.417, respectively; adjusted P = .002, &lt;.001, &lt;.001 and &lt;.001, respectively). Additionally, %EGR1pod correlated with cellular/fibrocellular crescents (rho = 0.479, adjusted P &lt;.001). %EGR1pod was high in patients with glomerulonephritis, such as immunoglobulin A nephropathy (IgAN), lupus nephritis and antineutrophil cytoplasmic antibody–associated glomerulonephritis, and in those with podocytopathies, such as membranous nephropathy and primary focal segmental glomerulosclerosis, while %EGR1pod was low in patients with minimal change disease. In a subgroup analysis of IgAN, %EGR1pod was higher in Oxford C1 patients than in C0 patients. However, unexpectedly, patients with higher %EGR1pod were more prone to attain proteinuria remission, suggesting that EGR1 in the context of IgAN reflects reversible early injury.

Conclusions
Our findings indicate that EGR1 is a promising potential marker for identifying active early podocyte injury in human glomerular diseases.
How Social Justice Shapes Youth Development: Centering Youth Voice across Shifts in Out-of-School Time
Authors: Osai Esohe R , Campbell Shanyce L , Greer James W 
Published: November 2023

Abstract
Out-of-school time (OST) has great significance as a youth development space that can support students’ exploration of social justice. Such opportunities for exploration are especially important in times of social distress and upheaval, such as those experienced during the school shutdowns and racial unrest associated with the global pandemic. Framed in a context of inequities for educationally marginalized youth, this qualitative case study provides a glimpse into the OST experiences of students before and after the onset of COVID-19. Authors explore navigating justice-related topics with youth in both an in-person and virtual format of the OST program. In addition to interviewing youth participants, the authors use a critical reflexivity approach to examine experiences facilitating OST spaces that serve youth of color. Findings point to the importance of youth-driven programming that centers youth voice and reimagines engagement for youth in OST programs. The discussion highlights implications for education and social work professionals in the service of social justice youth development outcomes.
Olive extract enriched with hydroxytyrosol improves cardiac and vascular function in patients with stable coronary artery disease: a double-blind, placebo-controlled trial
Authors: Katogiannis K , Ikonomidis I , Chania C , Tsoumani M , Brinia E , Pavlidis G , Thymis J , Tsilivarakis D , Kountouri A , Korakas E , Lambadiari V , Skaltsounis L , Tsetis I , Iliodromitis E K , Andreadou I 
Published: November 2023

Abstract

Aims
We investigated the effect of olive extract enriched with hydroxytyrosol, on vascular and myocardial function markers in patients with stable coronary artery disease (SCAD).

Methods
In a prospective, cross-over, double-blind, placebo-controlled, clinical trial, 30 patients with stable CAD were randomly assigned to an oral supplement containing olive oil extract enriched with hydroxytyrosol (OOHT) or placebo for one month and then were crossed over to the alternate treatment (placebo or OOHT for one more month). We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography d) Pulse Wave Velocity (PWV) e) oxidative/nitrosative stress and inflammatory biomarkers and blood lipids at baseline and after one month treatment.

Results
Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.81±0.35 vs 1.77±0.40 μm p=0.04 3.71±2.12 vs 6.51±2.31%, p&lt;0.001;2.37±0.40 vs 2.45±0.41, p=0.030 and 11.03±1.81 vs 11.78±2.34 m/sec, p=0.002), while there was no effect after placebo (p&gt;0.05). Compared to baseline, treatment with OOHT reduced malondialdehyde (MDA) a marker of lipid peroxidation (2.10±1.37 vs 1.69±0.83 mmol/lt, p=0.045), oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p&lt;0.05) in contrast to placebo. There was a parallel improvement of E’ of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p&lt;0.05) but not after placebo.

Conclusions
Olive extract enriched with hydroxytyrosol improves endothelial and arterial function likely by reducing oxidative and inflammatory burden leading to improved LV diastolic function after one month of treatment in patients with stable CAD.
Reduction in the risk of major adverse limb events with ezetimibe versus placebo in addition to statin therapy: insights from the IMPROVE IT trial
Authors: Bonaca M , Giugliano R P , Cannon C P , Park J G , Murphy S A , Creager M A , Braunwald E , Sabatine M S 
Published: November 2023

Abstract

Background/Introduction
Patients with peripheral artery disease (PAD) are at risk of developing progressive symptoms leading to revascularization as well as major adverse limb events such as critical limb ischemia and amputation. Recently, two trials of PCSK9 inhibitors, which lower both LDL-C and Lp(a) have demonstrated reductions in MALE and peripheral revascularization. Whether this benefit is present for other LDL-C lowering therapies has not been well described.

Purpose
To evaluate whether LDL-C lowering with ezetimibe reduces the risk of adverse limb events.

Methods
IMPROVE-IT randomized 18,144 patients with acute coronary syndrome (ACS), including 1,005 with PAD, to ezetimibe or placebo on top of statin and followed for a median of 6 years. Two vascular specialists blinded to treatment allocation independently reviewed all adverse events to categorize limb outcomes including critical limb ischemia (CLI), and related amputation as well as progressive symptoms leading to lower extremity revascularization (worsening PAD). Total limb outcomes over follow up were compared by treatment groups using negative binomial regression and relative risks (RR) are presented.

Results
A total of 397 patients had worsening symptoms (in 346 PAD patients) and 43 developed CLI (in 36 patients) during follow up. The risk of total PAD events (CLI or worsening symptoms) was lower with ezetimibe versus placebo (RR 0.77, 95% CI 0.62 – 0.96, p=0.018) with a consistent trend for both components (Figure Panel A). When evaluating the relationship of achieved LDL-C at 1-month post-randomization and the risk of first PAD event, there appeared to a linear relationship extending to an LDL-C less than 25 mg/dL (Figure Panel B).

Conclusion
Further lowering of LDL-C with ezetimibe on top of statin therapy in patients with ACS was associated with a lower risk of adverse limb events over long-term follow up including CLI and progressive disease leading to revascularization. These data support the importance of intensive lipid lowering therapies in improving limb outcomes in patients with atherosclerotic vascular disease. In addition, these data support LDL-C as a treatment target for optimizing outcomes in patients with peripheral artery disease.Figure Panel AFigure Panel B
Global epidemiology of lower-extremities artery disease in the 21st century (2000-2021): a systematic review and meta-analysis
Authors: Adou C , Magne J , Gazere N , Aboyans V 
Published: November 2023

Abstract

Objectives
The epidemiology of cardiovascular diseases and risk factors are evolving. In this meta-analysis our objectives were (1) to determine the prevalence of lower-extremities artery disease (LEAD) in the general population worldwide and by region in the 21st century and (2) to identify the risk factors associated with LEAD in the general population and by region in this period.

Methods
We performed a systematic literature review through PubMed, Cochrane, Scopus, Science Direct and Google Scholar databases, restricted to studies in general population performed between 01/2000 and 09/2021 on LEAD, defined by a low ankle brachial index (≤ 0.90). The Newcastle-Ottawa Scale was used to evaluate the quality of the articles before data extraction. A meta-analysis on the association of LEAD with cardiovascular risk factors was conducted. Due to high heterogeneity, random effect model was applied.

Results
Among 1418 references extracted, 42 articles (129,376 participants) were retained. Overall, the global prevalence in adults, mostly ≥ 40 years of age, was higher prevalence in women than in men (9.7%, 95%CI:6.4-13.0, vs. 7.9%, 95%CI:5.2-10.7) with an increase in prevalence with age in both genders (Figure). The highest prevalence was found in Europe (12.7%, 95%CI: 5.3-20.1) and the lowest in North America (5.6%, 95%CI: 2.5-8.6). Significant associations were found between LEAD and current tobacco smoking (odds-ratio (OR)=1.9, 95%CI:1.4-2.5) and past smoking (OR= 1.6, 95%CI:1.3-1.9) versus never smoking. Significant association was found between the prevalence of LEAD and diabetes (OR=2.3, 95%CI:2.0-2.8) with the strongest association in South-Center Asia (OR= 5.8, 95%CI:1.2-28.1). Hypertension was significantly associated with LEAD (OR=2.3, 95%CI: 1.9-2.8) and in particular in South America (OR=4.0, 95%CI:0.9-18.0). Finally, obesity and total cholesterol level (&gt;240 mg/dL) were also significantly associated with LEAD (OR=1.4, 95%CI:1.2-1.8 and OR=2.2, 95%CI:1.0 -5.3, respectively).

Conclusion
This meta-analysis highlights the high prevalence of LEAD with significant differences between men and women and the increasing importance of the metabolic syndrome in recent decades, with some variation by gender and global region.Prevalence of LEAD by age and gender
Restarting anticoagulation after chronic subdural hematoma neurosurgical evacuation: a prospective observationaL
Authors: Marchetti G , Bernardini F , Zoli M , Mazzatenta D 
Published: November 2023

Abstract

Introduction
Management of anticoagulation (AC) in patients with chronic subdural hematoma (cSDH) lacks evidences, with uncertainties regarding outcomes after neurosurgical intervention. In patients with atrial fibrillation the interruption of an anticoagulant therapy can be a risk of thromboembolic event within the first 90 days.

Purpose
We aimed to define safety and effectiveness of AC resumption in a single center cohort undergoing neurosurgical intervention for cSDH.

Methods
Consecutive patients undergoing neurosurgical intervention for evacuation of cSDH and taking anticoagulants due to atrial fibrillation were included and followed-up over time (3 to 30 months) to define evolution of cSDH thickness depending on AC restart. Secondary outcomes included: (i)ischemic stroke and major bleeding (including intracerebral hemorrhage, ICH), assessed at each visit, and (ii) recurrent cSDH needing neurosurgical re-intervention.

Results
Overall, we included 47 consecutive patients, mean age 82.5±7.8 years. Previous trauma emerged in 68% of cases. Patients received warfarin (n=30, 64%), low molecular weight heparin (LMWH, n=6, 13%) or direct oral anticoagulants (DOAC, n=11, 23%). Oral AC was stopped before neurosurgery (7.9±16.7 days before intervention), and 42 (89%) underwent AC reversal. Mean cSDH thickness was 2.3±0.6 cm, midline shift was detected in 94% of patients. All patients survived surgical procedure and completed a minimum of 3-month follow-up. Over a mean 8-month follow-up (range 3-29), cSDH thickness substantially decreased (baseline 2.3±0.6 cm vs follow-up 0.7±0.6 cm, p&lt;0.001). Restarting anticoagulation after chronic subdural hematoma neurosurgical evacuation: a prospective observational. Overall, 26 patients (55.3%) restarted AC, 15 with DOAC, 8 with warfarin, 3 with LMWH. Compared to no AC, AC resumption was not associated with changes in cSDH thickness (0.7±0.7 cm vs 0.9±0.6 cm, p=0.4) or modified Rankin scale at follow-up (2.6±1 vs 2±1.3, p=0.3). Four patients restarting AC had cSDH recurrence requiring re-intervention vs 0 in those avoiding AC (p=0.11); 3 of 4 were post-traumatic. No peri-interventional complications occurred. No ischemic stroke or major bleeding was detected during AC withdrawal.

Conclusions
The study has obviously limitations due to its preliminary nature. Even though, resumption of anticoagulation after neurosurgical intervention for cSDH seems safe, with no significant increase in recurrence rate and cSDH width over time. Longitudinal data from prospectively collected larger cohorts are needed to guide management.
Peripheral blood cell characteristics are independently related to major adverse cardiovascular events after carotid endarterectomy
Authors: Overmars M , Mekke J M , Van Solinge W W , De Jager S C A , Hulsbergen-Veelken C A R , Hoefer I E , De Kleijn D P V , De Borst G J , Van Der Laan S W , Haitjema S 
Published: November 2023

Abstract

Background
Patients who underwent carotid endarterectomy (CEA) still have a residual risk of 13% of developing a major adverse cardiovascular event (MACE) within 3 years. Inflammatory processes leading up to MACE are not fully understood. Therefore, we examined blood cell characteristics (BCCs), possibly reflecting inflammatory processes, in relation to MACE to identify BCCs that may contribute to an increased risk.

Methods
We analyzed 75 pretreatment BCCs from the Sapphire analyzer, and clinical data from the AtheroExpress biobank in relation to MACE after CEA using Random Survival Forests, and a Generalized Additive Survival Model. To understand biological mechanisms, we related the identified variables to intraplaque hemorrhage (IPH).

Results
Of 783 patients, 97 (12%) developed MACE within 3 years after CEA. Red blood cell distribution width (RDW) (HR 1.23 [1.02, 1.68], p = 0.022), CV of lymphocyte size (LACV) (HR 0.78 [0.63, 0.99], p = 0.043), neutrophil complexity of the intracellular structure (NIMN) (HR 0.80 [0.64, 0.98], p = 0.033), mean neutrophil size (NAMN) (HR 0.67 [0.55, 0.83], p &lt; 0.001), mean corpuscular volume (MCV) (HR 1.35 [1.09, 1.66], p = 0.005), eGFR (HR 0.65 [0.52, 0.80], p &lt; 0.001); and HDL (HR 0.62 [0.45, 0.85], p = 0.003) were related to MACE. NAMN was related to IPH (OR 0.83 [0.71 - 0.98], p = 0.02).

Conclusions
This is the first study to present a higher RDW and MCV and lower LACV, NIMN and NAMN as biomarkers reflecting inflammatory processes that may contribute to an increased risk of MACE after CEA.Variables associated with secondary MACE
Increased arterial stiffness in patients with ischemia and no obstructive coronary artery disease
Authors: Sakalidis A , Dimitriadis K , Leontsinis I , Dri E , Mantzouranis E , Bora M , Karanikola A E , Iliakis P , Vlachakis P , Siafi E , Beneki E , Tsioufis P , Manta E , Soulaidopoulos S , Tsioufis C 
Published: November 2023

Abstract

Introduction
Recent studies have shown that patients with angina pectoris and no obstructive coronary artery disease are a heterogeneous population with an elevated risk of major adverse cardiovascular events. The current literature lacks evidence regarding the possible association between arterial stiffness and coronary microvascular dysfunction (CMD).

Purpose
The aim of this study is to determine whether arterial stiffness is increased among patients with CMD compared to hypertensive control group.

Methods
We examined 25 patients [10 female, 40%, mean age: 60.7±9.6 years, mean office blood pressure (BP) : 141/88±17/9 mmHg] and 35 CMD patients (22 female, 63%, mean age : 62.4±4.9 years, average office BP: 129/79±15/10 mmHg). In the group of patients with chronic angina, CMD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. In addition, in all participants, arterial stiffness was assessed using aortic augmentation index (AIx), derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the radial artery.

Results
In the CMD group, mean CFR and IMR were 1.3±0.9 and 45.7±35, respectively. Out of the 35 CMD patients with abnormal CFR 12 of them (34%) had a normal value of IMR, indicating functional microvascular dysfunction. On the other hand, 23 patients (66%) had an abnormal IMR, indicating structural microvascular dysfunction. In CMD group compared to asymptomatic controls, AIx was found significantly higher (35.6±10.5 vs 25.1±12.1%, p=0.03). This difference in AIx between groups was found to be statistically significant after adjustment for age, gender and levels of BP (p&lt;0.05). Moreover, no significant differences were found in body mass index, renal function, history of dyslipidemia, diabetes mellitus and smoking status between the two groups (p=NS for all).

Conclusion
CMD patients are characterized by increased arterial stiffness in comparison with asymptomatic controls, independently of demographic and hemodynamic confounders. These results indicate that impairment of the microvasculature is associated with large artery stiffening. Thus, potential clinical benefit could be derived from specific therapies targeting AIx in patients with CMD.