Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Diurnal Variations in Heart Rate: Potential Applications for Chronobiology and Cardiovascular Medicine

Circadian factors likely influence the occurrence, development, therapy, and prognosis of cardiovascular diseases (CVDs). To determine the association between the heart rate (HR) diurnal parameters and CVD risks, we designed an analytical strategy to detect diurnal rhythms of HR using longitudinal data collected by clinically used Holter monitors and wearable devices. By combining in-house developed algorithms with existing analytical tools, we obtained trough phase and nocturnal variation in HR for different purposes. The analytical strategy is robust and also sensitive enough to identify variations in HR rhythms influenced by multiple effectors such as jet lag, geological location and altitude, and age from total 211 volunteers. A total of 10,094 sets of 24-h Holter ECG data were analyzed by stepwise partial correlation to determine the critical points of HR trough phase and nocturnal variation. The following HR diurnal patterns correlate with high CVD risk: arrhythmic pattern, anti-phase pattern, rhythmic patterns with trough phase less than 0 (extremely advanced diurnal pattern) or more than 5 (extremely delayed diurnal pattern), and nocturnal variation less than 2.75 (extremely low) or more than 26 (extremely high). In addition, HR trough phases from wearable devices were nearly identical to those from 24-h Holter monitoring from 12 volunteers by linear correlation and Bland-Altman analysis. Our analytical system provides useful information to identify functional diurnal patterns and parameters by monitoring personalized, HR-based diurnal changes. These findings have important implications for understanding how a regular heart diurnal pattern benefits cardiac function and raising the possibility of non-pharmacological intervention against circadian related CVDs. With the rapid expansion of wearable devices, public cardiovascular health can be promoted if the analytical strategy is widely applied.
Effect of Topology and Geometric Structure on Collective Motion in the Vicsek Model

In this work, we explore how the emergence of collective motion in a system of particles is influenced by the structure of their domain. Using the Vicsek model to generate flocking, we simulate two-dimensional systems that are confined based on varying obstacle arrangements. The presence of obstacles alters the topological structure of the domain where collective motion occurs, which, in turn, alters the scaling behavior. We evaluate these trends by considering the scaling exponent and critical noise threshold for the Vicsek model, as well as the associated diffusion properties of the system. We show that obstacles tend to inhibit collective motion by forcing particles to traverse the system based on curved trajectories that reflect the domain topology. Our results highlight key challenges related to the development of a more comprehensive understanding of geometric structure's influence on collective behavior.
The Study of Biomechanics and Clinical Anatomy on a Novel Plate Designed for Posterolateral Tibial Plateau Fractures via Anterolateral Approach

There is no consensus about the optimal internal fixation selection for treatment of posterolateral tibial plateau fracture. This study described a novel plate through an anterolateral approach for posterolateral tibial plateau fractures (PTPFs). We evaluated the biomechanical performance of a novel plate and two conventional internal implants and investigated the anatomic feasibility of the novel plate. The fracture models were randomly assigned into six groups: Groups A–C were the model groups of posterolateral split fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. Groups D–E were the model groups of posterolateral depression fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. We evaluated the biomechanical performance of six model groups by the biomechanical testing and finite element analysis. Progressively increasing axial compressive loads were applied to each synthetic fracture model by using a customized indentor under 250–750 N loads. Meanwhile, we dissected 12 fresh frozen knee specimens and fixed them with the novel plate through the anterolateral approach. We recorded the adjacency of the novel plate to important anatomic structures. Biomechanical testing showed that the novel plate had the least displacement, followed by the posterior buttress plate, and the lateral plate had the most displacement in posterolateral split fracture. There was no significant difference in the displacement between the novel plate and the lateral plate at different loads in posterolateral depression fractures. And the posterior buttress plate showed the most displacement. In the finite element analysis, the maximum stress values of Groups A, B, and C were 383.76, 414.63, and 305.07 MPa under the load of 750 N, respectively. The maximum stress values of Groups D, E, and F were 474.28, 436.31, and 413.4 MPa under the load of 750 N, respectively. In the anatomic study, the placement of the novel plate had a low risk of damage to the important anatomic structures of knee posterolateral corner. The novel plate could be a great choice for the treatment of PTPFs due to better biomechanical performance and easy manipulation.
A Radiomics Approach to Assess High Risk Carotid Plaques: A Non-invasive Imaging Biomarker, Retrospective Study

Objective This study aimed to construct a radiomics-based MRI sequence from high-resolution magnetic resonance imaging (HRMRI), combined with clinical high-risk factors for non-invasive differentiation of the plaque of symptomatic patients from asyptomatic patients. Methods A total of 115 patients were retrospectively recruited. HRMRI was performed, and patients were diagnosed with symptomatic plaques (SPs) and asymptomatic plaques (ASPs). Patients were randomly divided into training and test groups in the ratio of 7:3. T2WI was used for segmentation and extraction of the texture features. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were employed for the optimized model. Radscore was applied to construct a diagnostic model considering the T2WI texture features and patient demography to assess the power in differentiating SPs and ASPs. Results SPs and ASPs were seen in 75 and 40 patients, respectively. Thirty texture features were selected by mRMR, and LASSO identified a radscore of 16 radiomics features as being related to plaque vulnerability. The radscore, consisting of eight texture features, showed a better diagnostic performance than clinical information, both in the training (area under the curve [AUC], 0.923 vs. 0.713) and test groups (AUC, 0.989 vs. 0.735). The combination model of texture and clinical information had the best performance in assessing lesion vulnerability in both the training (AUC, 0.926) and test groups (AUC, 0.898). Conclusion This study demonstrated that HRMRI texture features provide incremental value for carotid atherosclerotic risk assessment.
Elevated Serum Uric Acid Increases the Risk of Ischemic Stroke Recurrence and Its Inflammatory Mechanism in Older Adults

Background Serum uric acid (UA) has been reported to be associated with ischemic stroke and inflammation. However, whether or not UA is related to the recurrence of ischemic stroke, and whether inflammation plays a role in the relationship between them remain inconclusive. Objective We sought to explore the relationship between UA and the recurrence of ischemic stroke and to define the role of neutrophil-to-lymphocyte ratio (NLR) in the aforementioned relationship. Methods A total of 8,995 patients were included in this study. Basic information and blood samples were collected, and whether or not each participant experienced ischemic stroke recurrence within 3 years was documented. Patients were stratified into three groups according to their UA level, as follows: ≤ 266, 267–339, and ≥ 340 μmol/L. COX regression and restricted cubic spline regression models were used to evaluate the clinical correlation between UA and ischemic stroke recurrence, mediation analysis and interaction and joint analysis were used to evaluate the role of NLR in the association of UA and ischemic stroke recurrence, and sensitivity and subgroup analyses were performed to test the robustness of the data. Results Ischemic stroke recurrence was related to male sex, older age, higher UA level, higher NLR, hypertension, diabetes, and cardiovascular disease. Following adjustment for potential confounders, a high level of UA (≥ 340 μmol/L) increased the risk of recurrence by 92.6% in patients with previous ischemic stroke. We also found that NLR affects the association between UA and the recurrence of ischemic stroke in older adults, suggesting that patients with high NLR and high UA levels are at greater risk for ischemic stroke recurrence. Conclusion UA level is non-linearly associated with recurrence, and NLR has an additive interaction between UA and ischemic stroke recurrence.
The Resistance of Cancer Cells to Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, is Mediated by the ABCB1 Transporter

Palbociclib was approved by the United States Food and Drug Administration for use, in combination with letrozole, as a first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) postmenopausal metastatic breast cancer. However, recent studies show that palbociclib may be an inhibitor of the ABCB1 transporter, although this remains to be elucidated. Therefore, we conducted experiments to determine the interaction of palbociclib with the ABCB1 transporter. Our in vitro results indicated that the efficacy of palbociclib was significantly decreased in the ABCB1-overexpressing cell lines. Furthermore, the resistance of ABCB1-overexpressing cells to palbociclib was reversed by 3 μM of the ABCB1 inhibitor, verapamil. Moreover, the incubation of ABCB1-overexpressing KB-C2 and SW620/Ad300 cells with up to 5 μM of palbociclib for 72 h, significantly upregulated the protein expression of ABCB1. The incubation with 3 µM of palbociclib for 2h significantly increased the intracellular accumulation of [3H]-paclitaxel, a substrate of ABCB1, in ABCB1 overexpressing KB-C2 cells but not in the corresponding non-resistant parental KB-3-1 cell line. However, the incubation of KB-C2 cells with 3 μM of palbociclib for 72 h decreased the intracellular accumulation of [3H]-paclitaxel due to an increase in the expression of the ABCB1 protein. Palbociclib produced a concentration-dependent increase in the basal ATPase activity of the ABCB1 transporter (EC50 = 4.73 μM). Molecular docking data indicated that palbociclib had a high binding affinity for the ABCB1 transporter at the substrate binding site, suggesting that palbociclib may compete with other ABCB1 substrates for the substrate binding site of the ABCB1. Overall, our results indicate that palbociclib is a substrate for the ABCB1 transporter and that its in vitro anticancer efficacy is significantly decreased in cancer cells overexpressing the ABCB1.
Bioaccessibility and Antioxidant Capacity of Bioactive Compounds From Various Typologies of Canned Tomatoes

Tomato (Solanum lycopersicum L.) is one of the most consumed vegetables in the world; it contains high amounts of antioxidant phytochemicals and essential nutrients. Although it is commonly consumed fresh, more than 80% of its consumption derives from processed products. Since limited information on changes in the bioaccessibility of bioactive compounds during gastrointestinal digestion was reported, this current study aimed to monitor the antioxidant activity, total polyphenolic and carotenoid content, and bioaccessibility during in vitro gastrointestinal digestion of different typologies (n = 7) of canned tomatoes. A comprehensive evaluation of the polyphenolic profile of digested and not digested samples was ascertained by ultra-high-performance liquid chromatography combined with high-resolution Orbitrap mass spectrometry. The results highlighted a considerable content of rutin (1.191–9.516 mg/100 g), naringenin (0.359–1.452 mg/100 g), chlorogenic acid (1.857–11.236 mg/100 g), and lycopene (50.894–222.061 mg/kg) in the analyzed matrices. After in vitro gastrointestinal digestion, large variability, losses and low recovery were recorded. An appreciable percentage of rutin (30.7%), naringenin (29.6%), chlorogenic acid (25.8%), and lycopene (varied between 9.3 and 20%) remained bioaccessible after the in vitro gastrointestinal digestion. Our study could be a valid support to evaluate which content of bioactive compounds could be really bioaccessible to exercise beneficial effects on human health. Graphical Abstract
Increased Basal Ganglia Modulatory Effective Connectivity Observed in Resting-State fMRI in Individuals With Parkinson’s Disease

Alterations to interactions between networked brain regions underlie cognitive impairment in many neurodegenerative diseases, providing an important physiological link between brain structure and cognitive function. Previous attempts to characterize the effects of Parkinson’s disease (PD) on network functioning using resting-state functional magnetic resonance imaging (rs-fMRI), however, have yielded inconsistent and contradictory results. Potential problems with prior work arise in the specifics of how the area targeted by the diseases (the basal ganglia) interacts with other brain regions. Specifically, current computational models point to the fact that the basal ganglia contributions should be captured with modulatory (i.e., second-order) rather than direct (i.e., first-order) functional connectivity measures. Following this hypothesis, a principled but manageable large-scale brain architecture, the Common Model of Cognition, was used to identify differences in basal ganglia connectivity in PD by analyzing resting-state fMRI data from 111 participants (70 patients with PD; 41 healthy controls) using Dynamic Causal Modeling (DCM). Specifically, the functional connectivity of the basal ganglia was modeled as two second-level, modulatory connections that control projections from sensory cortices to the prefrontal cortex, and from the hippocampus and medial temporal lobe to the prefrontal cortex. We then examined group differences between patients with PD and healthy controls in estimated modulatory effective connectivity in these connections. The Modulatory variant of the Common Model of Cognition outperformed the Direct model across all subjects. It was also found that these second-level modulatory connections had higher estimates of effective connectivity in the PD group compared to the control group, and that differences in effective connectivity were observed for all direct connections between the PD and control groups.We make the case that accounting for modulatory effective connectivity better captures the effects of PD on network functioning and influences the interpretation of the directionality of the between-group results. Limitations include that the PD group was scanned on dopaminergic medication, results were derived from a reasonable but small number of individuals and the ratio of PD to healthy control participants was relatively unbalanced. Future research will examine if the observed effect holds for individuals with PD scanned off their typical dopaminergic medications.
Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function

Background Immune checkpoint inhibitors (ICI) are clinically active across multiple tumor types but the associated immune-related adverse events (irAEs) lead to treatment delays or discontinuation and negatively impact quality-of-life. Hypophysitis is often a permanent irAE that may affect multiple pituitary hormonal axes. Here we comprehensively characterize our institution’s clinical experience with ICI-induced hypophysitis and the associated patterns of pituitary function loss. Methods Patients with solid tumors, mostly melanoma and renal cell carcinoma (RCC), treated with ICI at Yale Cancer Center were prospectively enrolled from October 2016-May 2021. Demographics and clinical data were obtained from the medical record including type and timing of irAEs. Patients were included in this cohort if hypophysitis was diagnosed by pre-specified biochemical and clinical parameters. Results The overall incidence of hypophysitis was 69/490 (14%) in patients with melanoma (n=58, 84%), RCC (n=10,14%), and merkel cell carcinoma (n=1, 1%) who received ipilimumab plus nivolumab (77%; 53/69), anti-PD-(L)1 (17%; 12/69), or ipilimumab monotherapy (6%; 4/69). Of the 69 patients analyzed, median time to hypophysitis on combination ICI versus anti-PD-1 was 2.8 vs. 4.1 months. The incidence of hypophysitis in patients with melanoma was 25% (46/187) with ipilimumab plus nivolumab and 5% (7/129) with anti-PD-(L)1 compared to 9% (7/77) and 8% (3/37), respectively, in patients with RCC. Patients who developed hypophysitis on combination ICI had a higher rate of headache (p=0.05) and co-occurring irAEs (p=0.01) compared anti-PD-(L1)1 monotherapy. At a median follow-up of 2.2 years, 77% of patients were alive. Objective response rates to ICI in melanoma patients were higher than previously reported for unselected populations. Central hypothyroidism and hypogonadism were the most common pituitary axes affected after the adrenal axis. In select cases, there was evidence of spontaneous rebound in free testosterone levels after an initial decline. Conclusions We demonstrate a higher rate of ICI-induced hypophysitis than previously reported, which may be reflective of real-world practice due to increased awareness as experience with ICI has grown. In select cases, there was evidence of rebound in free testosterone and/or gonadotropins but not in adrenal axis hormones.
Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database

Objective To assess the effect of serum inorganic phosphate (Pi) on the prognosis of patients with sepsis. Methods A retrospective analysis of patients with sepsis selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database was performed. Sepsis was diagnosed according to the Third International Consensus Definition for sepsis and septic shock (Sepsis-3). The time-weighted values of the serum Pi measurements within the first 24 h of sepsis were analyzed. The association between serum Pi and in-hospital mortality was evaluated with a generalized linear model (log-binomial model). Results The analysis of 11,658 patients from six intensive care units (ICUs) showed a nearly linear correlation between serum Pi and in-hospital mortality in all patients with sepsis, especially in those with acute kidney injury (AKI). The increase of serum Pi was related to a higher risk of AKI, higher norepinephrine doses, ICU mortality, and in-hospital mortality. The generalized linear model showed that serum Pi was an independent predictor for in-hospital mortality in all patients with sepsis even within the normal range. The adjusted risk ratios (RRs) were also significant in subgroup analyses according to kidney function, gender, respiratory infection, vasopressor use, and Sequential Organ Failure Assessment (SOFA) score. Conclusion Higher levels of serum Pi, even within the normal range, were significantly associated with a higher risk of in-hospital mortality in patients with sepsis regardless of kidney function, gender, respiratory infection, vasopressor use, and SOFA score.
A Domain-General Developmental “Do-GooD” Network Model of Prosocial Cognition in Adolescence: A Systematic Review

Adolescence is a period of substantial neural and social development, and prosocial decisions are beneficial to personal well-being, the well-being of others, and the functioning of society. Advances in network neuroscience call for a systematic synthesis and reappraisal of prosocial neural correlates during adolescent development. In this systematic review, we aim to outline the progress made in this field, identify the similarities between study results, and propose a model for prosocial cognition in adolescents to young adults. A total of 25 articles were included in this review. After reviewing and synthesizing the literature, we propose a DOmain-General Developmental “Do-GooD” network model of prosocial cognition that aligns with the reviewed literature, accounts for development, and combines elements of the value-based decision-making model with distinct value contributions from the default mode network, salience network, and control network. We offer predictions to test the “Do-GooD” model and propose new future directions for studying prosocial behavior and its development during adolescence, which in turn may lead to improving education and the development of better health interventions for adolescents.
GC-MS Profile of Hua-Feng-Dan and RNA-Seq Analysis of Induced Adaptive Responses in the Liver

Background: Hua-Feng-Dan is a patent Chinese medicine for stroke recovery and various diseases. This study used GC-MS to profile its ingredients and RNA-Seq to analyze the induced adaptive response in the liver. Methods: Hua-Feng-Dan was subjected to steam distillation and solvent extraction, followed by GC-MS analysis. Mice were orally administered Hua-Feng-Dan and its “Guide drug” Yaomu for 7 days. Liver pathology was examined, and total RNA isolated for RNA-Seq, followed by bioinformatic analysis and quantitative real-time PCR (qPCR). Results: Forty-four volatile and fifty liposoluble components in Hua-Feng-Dan were profiled and analyzed by the NIST library and their concentrations quantified. The major components (>1%) in volatile (5) and liposoluble (10) were highlighted. Hua-Feng-Dan and Yaomu at hepatoprotective doses did not produce liver toxicity as evidenced by histopathology and serum enzyme activities. GO Enrichment revealed that Hua-Feng-Dan affected lipid homeostasis, protein folding, and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion, and PPAR signaling pathways. Differentially expressed genes (DEGs) were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced more DEGs than Yaomu. qPCR on selected genes largely verified RNA-Seq results. Ingenuity Pathways Analysis of the upstream regulator revealed activation of MAPK and adaptive responses by Hua-Feng-Dan, and Yaomu was less effective. Hua-Feng-Dan-induced DEGs were highly correlated with the Gene Expression Omnibus database of chemical-induced adaptive transcriptome changes in the liver. Conclusion: GC-MS primarily profiled volatile and liposoluble components in Hua-Feng-Dan. Hua-Feng-Dan at the hepatoprotective dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. The effects of Hua-Feng-Dan on liver transcriptome changes point toward induced adaptive responses to program the liver to produce hepatoprotective effects.