Miracle-dz/UniFAR-FTUs huggingface dataset:
Children’s Greenness Exposure and IQ-Associated DNA Methylation: A Prospective Cohort Study

Epigenetics is known to be involved in regulatory pathways through which greenness exposure influences child development and health. We aimed to investigate the associations between residential surrounding greenness and DNA methylation changes in children, and further assessed the association between DNA methylation and children’s intelligence quotient (IQ) in a prospective cohort study. We identified cytosine-guanine dinucleotide sites (CpGs) associated with cognitive abilities from epigenome- and genome-wide association studies through a systematic literature review for candidate gene analysis. We estimated the residential surrounding greenness at age 2 using a geographic information system. DNA methylation was analyzed from whole blood using the HumanMethylationEPIC array in 59 children at age 2. We analyzed the association between greenness exposure and DNA methylation at age 2 at the selected CpGs using multivariable linear regression. We further investigated the relationship between DNA methylation and children’s IQ. We identified 8743 CpGs associated with cognitive ability based on the literature review. Among these CpGs, we found that 25 CpGs were significantly associated with greenness exposure at age 2, including cg26269038 (Bonferroni-corrected p ≤ 0.05) located in the body of SLC6A3, which encodes a dopamine transporter. DNA methylation at cg26269038 at age 2 was significantly associated with children’s performance IQ at age 6. Exposure to surrounding greenness was associated with cognitive ability-related DNA methylation changes, which was also associated with children’s IQ. Further studies are warranted to clarify the epigenetic pathways linking greenness exposure and neurocognitive function.
Evaluation of Wound Healing Activity of Salvianolic Acid B on In Vitro Experimental Model

Despite a wide range of bactericides and antiseptics, the treatment of chronic or complicated wounds is still a major challenge for modern medicine. Topical medications are the most sought-after new agents for use as treatment. The therapeutic concentration of their active substances is easy to achieve with the lowest possible burden on the patient’s body. This study assesses the effect of salvianolic acid B (Sal B) on the proliferation, migration, and production of collagen type III by fibroblasts, which are the most important processes in wound healing. The study was conducted on human gingival fibroblasts obtained from primary cell culture. The results showed that Sal B at a dose of 75 µg/mL increases the cell viability with significant stimulation of the cell migration as demonstrated in the wound healing assay, as well as an increase in the expression of collagen type III, which has great importance in the initial stages of wound scarring. The results obtained in the conducted studies and previous scientific reports on the antibacterial properties and low toxicity of Sal B indicate its high potential in wound healing.
Active dendrites enable strong but sparse inputs to determine orientation selectivity

Significance An active pyramidal cell model, constrained by physiological and anatomical data, was used to simulate dendritic integration in vivo. The model shows that small numbers of strong excitatory synapses can trigger dendritic Na+ and NMDA spikes. Moreover, only a few dendritic spikes are sufficient to drive a single output action potential. As a consequence, as few as 1% of the synaptic inputs to a neuron can determine the tuning of somatic output in vivo. These results suggest that dendritic spikes can help to make sensory representations more efficient and flexible: they require fewer connections to sustain them, and only a small number of connections need to be changed to encode a different stimulus and alter the response properties of a neuron. The dendrites of neocortical pyramidal neurons are excitable. However, it is unknown how synaptic inputs engage nonlinear dendritic mechanisms during sensory processing in vivo, and how they in turn influence action potential output. Here, we provide a quantitative account of the relationship between synaptic inputs, nonlinear dendritic events, and action potential output. We developed a detailed pyramidal neuron model constrained by in vivo dendritic recordings. We drive this model with realistic input patterns constrained by sensory responses measured in vivo and connectivity measured in vitro. We show mechanistically that under realistic conditions, dendritic Na+ and NMDA spikes are the major determinants of neuronal output in vivo. We demonstrate that these dendritic spikes can be triggered by a surprisingly small number of strong synaptic inputs, in some cases even by single synapses. We predict that dendritic excitability allows the 1% strongest synaptic inputs of a neuron to control the tuning of its output. Active dendrites therefore allow smaller subcircuits consisting of only a few strongly connected neurons to achieve selectivity for specific sensory features.
Early Intervention of Pulmonary Rehabilitation for Fibrotic Interstitial Lung Disease Is a Favorable Factor for Short-Term Improvement in Health-Related Quality of Life

Patients with fibrosing interstitial lung disease (FILD) have poor health-related quality of life (HRQOL). We analyzed predictors of short-term improvement of HRQOL after starting pulmonary rehabilitation (PR) in moderate to severe FILD patients. This study involved 28 consecutive patients with FILD (20 males, median age of 77.5 years), who participated in PR program of our hospital for >6 weeks. The St. George’s Respiratory Questionnaire (SGRQ) score and the 6-min walk distance (6MWD) were evaluated before and after PR, and the predictors of efficacy of PR were analyzed. The duration from diagnosis of FILD to start of PR showed a positive correlation with the increase in the SGRQ score, and the baseline SGRQ score showed a negative correlation with increase in the 6MWD. The FILD subtype, modified Medical Research Council score, and treatment history were not associated with the endpoints. According to the receiver operating characteristic curve (ROC) analyses, starting PR within 514 days after diagnosis of FILD was a significant favorable predictor of improvement in the SGRQ total score more than a minimal clinically important difference of 4. In this study, early intervention of PR and lower SGRQ score were associated with the favorable response to PR. PR for FILD should be initiated early before the disease becomes severe.
Evasion of the Host Immune Response by Betaherpesviruses

The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.
Glucose Regulation Beyond HbA1c in Type 2 Diabetes Treated With Insulin: Real-World Evidence From the DIALECT-2 Cohort

OBJECTIVE To investigate glucose variations associated with glycated hemoglobin (HbA1c) in insulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients included in Diabetes and Lifestyle Cohort Twente (DIALECT)-2 (n = 79) were grouped into three HbA1c categories: low, intermediate, and high (≤53, 54–62, and ≥63 mmol/mol or ≤7, 7.1–7.8, and ≥7.9%, respectively). Blood glucose time in range (TIR), time below range (TBR), time above range (TAR), glucose variability parameters, day and night duration, and frequency of TBR and TAR episodes were determined by continuous glucose monitoring (CGM) using the FreeStyle Libre sensor and compared between HbA1c categories. RESULTS CGM was performed for a median (interquartile range) of 10 (7–12) days/patient. TIR was not different for low and intermediate HbA1c categories (76.8% [68.3–88.2] vs. 76.0% [72.5.0–80.1]), whereas in the low category, TBR was higher and TAR lower (7.7% [2.4–19.1] vs. 0.7% [0.3–6.1] and 8.2% [5.7–17.6] vs. 20.4% [11.6–27.0], respectively; P < 0.05). Patients in the highest HbA1c category had lower TIR (52.7% [40.9–67.3]) and higher TAR (44.1% [27.8–57.0]) than the other HbA1c categories (P < 0.05), but did not have less TBR during the night. All patients had more (0.06 ± 0.06/h vs. 0.03 ± 0.03/h; P = 0.002) and longer (88.0 [45.0–195.5] vs. 53.4 [34.4–82.8] minutes; P < 0.001) TBR episodes during the night than during the day. CONCLUSIONS In this study, a high HbA1c did not reduce the occurrence of nocturnal hypoglycemia, and low HbA1c was not associated with the highest TIR. Optimal personalization of glycemic control requires the use of newer tools, including CGM-derived parameters.
Wild-Type and Mutant FUS Expression Reduce Proliferation and Neuronal Differentiation Properties of Neural Stem Progenitor Cells

Nervous system development involves proliferation and cell specification of progenitor cells into neurons and glial cells. Unveiling how this complex process is orchestrated under physiological conditions and deciphering the molecular and cellular changes leading to neurological diseases is mandatory. To date, great efforts have been aimed at identifying gene mutations associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the RNA/DNA binding protein Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) have been associated with motor neuron degeneration in rodents and humans. Furthermore, increased levels of the wild-type protein can promote neuronal cell death. Despite the well-established causal link between FUS mutations and ALS, its role in neural cells remains elusive. In order to shed new light on FUS functions we studied its role in the control of neural stem progenitor cell (NSPC) properties. Here, we report that human wild-type Fused in Sarcoma (WT FUS), exogenously expressed in mouse embryonic spinal cord-derived NSPCs, was localized in the nucleus, caused cell cycle arrest in G1 phase by affecting cell cycle regulator expression, and strongly reduced neuronal differentiation. Furthermore, the expression of the human mutant form of FUS (P525L-FUS), associated with early-onset ALS, drives the cells preferentially towards a glial lineage, strongly reducing the number of developing neurons. These results provide insight into the involvement of FUS in NSPC proliferation and differentiation into neurons and glia.
Effectiveness of Mind–Body Intervention for Inflammatory Conditions: Results from a 26-Week Randomized, Non-Blinded, Parallel-Group Trial

Biopsychosocial intervention has been suggested as a complementary treatment strategy for patients with chronic conditions. We compared the effect of a mind–body intervention (MBI), relative to treatment-as-usual (TAU) on WHO-5 Well-being Index during an intensive period of 12 weeks and follow-up at week 26 among patients with either psoriasis (PsO) or rheumatoid arthritis (RA). The MBI was based on the ‘Relaxation Response Resiliency Program’ and the ‘Open and Calm Program’, as well as ‘Mindfulness Based Stress Reduction’ (MBSR). The trial was randomized, management-as-usual, and controlled. Statistical analyses were based on the intention-to-treat population using repeated measures and mixed effects models (NCT03888261). We screened 39 potential participants, 35 of which (PsO, n = 20; RA, n = 15) met the eligibility criteria and were randomized: 17 in the MBI group and 18 in the TAU group. Attrition from the intervention program was 19%, with 65% of MBI patients and 71% of TAU patients completing the outcome assessments. After 12 weeks, a statistically significant difference in WHO-5 was observed between the groups (p = 0.019). However, according to the protocol, during the entire trial period, the average (least squares mean values) WHO-5 score was higher although not statistically significant in the MBI group (65.3) compared with the TAU group (59.1), corresponding to a between-group difference over 26 weeks of 6.15 (95% CI: −0.26 to 12.56; p = 0.060). All things considered, adding biopsychosocial intervention to clinical practice to patients with conditions, such as PsO and RA, could potentially improve health-related quality of life.
Applying Proteomics and Integrative “Omics” Strategies to Decipher the Chronic Kidney Disease-Related Atherosclerosis

Patients with chronic kidney disease (CKD) are at increased risk of atherosclerosis and premature mortality, mainly due to cardiovascular events. However, well-known risk factors, which promote “classical” atherosclerosis are alone insufficient to explain the high prevalence of atherosclerosis-related to CKD (CKD-A). The complexity of the molecular mechanisms underlying the acceleration of CKD-A is still to be defied. To obtain a holistic picture of these changes, comprehensive proteomic approaches have been developed including global protein profiling followed by functional bioinformatics analyses of dysregulated pathways. Furthermore, proteomics surveys in combination with other “omics” techniques, i.e., transcriptomics and metabolomics as well as physiological assays provide a solid ground for interpretation of observed phenomena in the context of disease pathology. This review discusses the comprehensive application of various “omics” approaches, with emphasis on proteomics, to tackle the molecular mechanisms underlying CKD-A progression. We summarize here the recent findings derived from global proteomic approaches and underline the potential of utilizing integrative systems biology, to gain a deeper insight into the pathogenesis of CKD-A and other disorders.
Actin Isovariant ACT7 Modulates Root Thermomorphogenesis by Altering Intracellular Auxin Homeostasis

High temperature stress is one of the most threatening abiotic stresses for plants limiting the crop productivity world-wide. Altered developmental responses of plants to moderate-high temperature has been shown to be linked to the intracellular auxin homeostasis regulated by both auxin biosynthesis and transport. Trafficking of the auxin carrier proteins plays a major role in maintaining the cellular auxin homeostasis. The intracellular trafficking largely relies on the cytoskeletal component, actin, which provides track for vesicle movement. Different classes of actin and the isovariants function in regulating various stages of plant development. Although high temperature alters the intracellular trafficking, the role of actin in this process remains obscure. Using isovariant specific vegetative class actin mutants, here we demonstrate that ACTIN 7 (ACT7) isovariant plays an important role in regulating the moderate-high temperature response in Arabidopsis root. Loss of ACT7, but not ACT8 resulted in increased inhibition of root elongation under prolonged moderate-high temperature. Consistently, kinematic analysis revealed a drastic reduction in cell production rate and cell elongation in act7-4 mutant under high temperature. Quantification of actin dynamicity reveals that prolonged moderate-high temperature modulates bundling along with orientation and parallelness of filamentous actin in act7-4 mutant. The hypersensitive response of act7-4 mutant was found to be linked to the altered intracellular auxin distribution, resulted from the reduced abundance of PIN-FORMED PIN1 and PIN2 efflux carriers. Collectively, these results suggest that vegetative class actin isovariant, ACT7 modulates the long-term moderate-high temperature response in Arabidopsis root.
Magnetism and Luminescence of a MOF with Linear Mn3 Nodes Derived from an Emissive Terthiophene-Based Imidazole Linker †

A new terthiophene-based imidazole luminophore 5,5’-(1H-thieno[3,4-d]imidazole-4,6-diyl)bis(thiophene-2-carboxylic acid) (TIBTCH2, 5) was synthesized in one step from previously reported 4,6-di(thiophen-2-yl)-1H-thieno[3,4-d]imidazole (DTTI, 4), and their photophysical properties were studied and compared accordingly. Under solvothermal conditions, reacting 5 with Mn(OAc)2 yielded a new three-dimensional metal-organic framework (MOF, 6) which was structurally defined by single-crystal X-ray diffraction. In 6, all Mn(II) ions octahedrally bind to carboxylate-O atoms to form a linear Mn3 secondary building unit (SBU) that contains three distinct coordination modes. Importantly, 6 exhibits dual functional properties of ligand-based emission and metal-based magnetic behaviors.
The Relationship among Community Environment, Behavior, Activity Ability, and Self-Rated Health of Older Adults: A Hierarchical and Multi-Dimensional Comparative Study

Although the community environment is a known determinant of older adults’ health, it is unclear about the logical relationships among the community environment, behavior, activity ability, and health of older adults, and the differences between the different age groups. This study used a two-stage sampling method to conduct a household survey of people over 60 years old living in Xinhua Street, Shanghai, China. In total, 2783 valid samples were obtained. Of these, 1256 were males and 1627 were females, with an average age of 71.1 years. The statistical method used in this study was the structural equation modeling method. The effects of the community environment and behavior on the activity ability and self-rated health of older adults are different, and the path of health influence of older adults is different in different age groups. Community environment has more wider effects on older adults’ self-rated health, while behavior, including walking behavior and neighbor contacts, have a more intensive effect on the activity ability of older adults. The community environment has a significant positive effect on the activity ability of the younger group but not on that of the older group, which instead was significantly affected by the neighbor contacts. Therefore, refined environmental governance and targeted improvement and resolution of different types of health problems among different groups of older persons will contribute to the overall health of older adults.
Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development

Co-crystal innovation is an opportunity in drug development for both scientists and industry. In line with the “green pharmacy” concept for obtaining safer methods and advanced pharmaceutical products, co-crystallization is one of the most promising approaches to find novel patent drugs, including non-steroidal anti-inflammatory drugs (NSAID). This kind of multi-component system improves previously poor physicochemical and mechanical properties through non-covalent interactions. Practically, there are many challenges to find commercially viable co-crystal drugs. The difficulty in selecting co-formers becomes the primary problem, followed by unexpected results, such as decreased solubility and dissolution, spring and parachute effect, microenvironment pH effects, changes in instability, and polymorphisms, which can occur during the co-crystal development. However, over time, NSAID co-crystals have been continuously updated regarding co-formers selection and methods development.
Attitudes towards Trusting Artificial Intelligence Insights and Factors to Prevent the Passive Adherence of GPs: A Pilot Study

Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals. However, they are imperfect by nature and misdiagnoses, if not correctly identified, can have consequences for patient care. In this paper, findings from an online survey are presented to understand the aptitude of GPs (n = 50) in appropriately trusting or not trusting the output of a fictitious AI-based decision support tool when assessing skin lesions, and to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results. The findings suggest that, when the AI was correct, the GPs’ ability to correctly diagnose a skin lesion significantly improved after receiving correct AI information, from 73.6% to 86.8% (X2 (1, N = 50) = 21.787, p < 0.001), with significant effects for both the benign (X2 (1, N = 50) = 21, p < 0.001) and malignant cases (X2 (1, N = 50) = 4.654, p = 0.031). However, when the AI provided erroneous information, only 10% of the GPs were able to correctly disagree with the indication of the AI in terms of diagnosis (d-AIW M: 0.12, SD: 0.37), and only 14% of participants were able to correctly decide the management plan despite the AI insights (d-AIW M:0.12, SD: 0.32). The analysis of the difference between groups in terms of individual characteristics suggested that GPs with domain knowledge in dermatology were better at rejecting the wrong insights from AI.
Human-Machine Shared Driving Control for Semi-Autonomous Vehicles Using Level of Cooperativeness †

This paper proposes a new haptic shared control concept between the human driver and the automation for lane keeping in semi-autonomous vehicles. Based on the principle of human-machine interaction during lane keeping, the level of cooperativeness for completion of driving task is introduced. Using the proposed human-machine cooperative status along with the driver workload, the required level of haptic authority is determined according to the driver’s performance characteristics. Then, a time-varying assistance factor is developed to modulate the assistance torque, which is designed from an integrated driver-in-the-loop vehicle model taking into account the yaw-slip dynamics, the steering dynamics, and the human driver dynamics. To deal with the time-varying nature of both the assistance factor and the vehicle speed involved in the driver-in-the-loop vehicle model, a new ℓ∞ linear parameter varying control technique is proposed. The predefined specifications of the driver-vehicle system are guaranteed using Lyapunov stability theory. The proposed haptic shared control method is validated under various driving tests conducted with high-fidelity simulations. Extensive performance evaluations are performed to highlight the effectiveness of the new method in terms of driver-automation conflict management.