Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial

Iron deficiency in pregnancy is a major public health problem that causes maternal complications. The objective of this randomized, controlled trial was to examine the bioavailability, efficacy, and safety of oral ferrous bisglycinate plus folinic acid supplementation in pregnant women with iron deficiency. Subjects (12–16 weeks of gestation, n = 120) were randomly allocated to receive oral iron as ferrous bisglycinate (equiv. iron 24 mg) in supplement form with folinic acid and multivitamins (test group, n = 60) or as ferrous fumarate (equiv. iron 66 mg iron, control group, n = 60) after breakfast daily. Iron absorption was assessed by measuring fasted serum iron levels at 1 and 2 h immediately after supplementation. Hematological biomarkers and iron status were assessed before intervention, and at 3 and 6 months. Side effects were monitored throughout the intervention. A significant increase in serum iron was seen in both groups (p < 0.001) during the bioavailability assessment; however, the test group increases were comparatively higher than the control values at each timepoint (p < 0.001). Similarly, both test and control groups demonstrated a statistically significant increases in hemoglobin (Hb) (p < 0.001), erythrocytes (p < 0.001), reticulocytes (p < 0.001), mean corpuscular volume (MCV) (p < 0.001), mean corpuscular hemoglobin (MCH) (p < 0.001), mean corpuscular hemoglobin concentration (MCHC) (p < 0.001), % transferrin saturation (p < 0.001), and ferritin (p < 0.001) at 3 and 6 months after supplementation. However, in all cases, the test group increases were numerically larger than the control group increases at each timepoint. The test intervention was also associated with significantly fewer reports of nausea, abdominal pain, bloating, constipation, or metallic taste (p < 0.001). In conclusion, ferrous bisglycinate with folinic acid as a multivitamin nutraceutical format is comparable to standard ferrous fumarate for the clinical management of iron deficiency during pregnancy, with comparatively better absorption, tolerability, and efficacy and with a lower elemental iron dosage.
Multivariate Analysis of the Predicted Probability of Smoking Behavior of Foster Care Minors: Results of a Study from Romania

Background: There are a multitude of factors that influence smoking status, and minors from the social protection system are a vulnerable category in terms of smoking. Methods: The objective of this research was to assess the degree of smoking dependence and to identify potential predictors of smoking status in foster care teenagers. Smoker status was confirmed by dosing CO in the exhaled air, and the degree of dependence was assessed using the Fagerström score. We performed a multivariate logistic regression analysis. Results: From the 275 foster care minors, 22.5% were current smokers. Exhaled CO was not influenced by general demographic factors, was associated with the frequency of smoking, and was positively correlated with the estimated number of cigarettes consumed daily and with the Fagerström score. The calculated probability of being a smoker was less than 20.4% in 75% of nonsmokers, whereas 75% of actual smokers had a predicted probability higher than 30.3%. Conclusions: In addition to age, gender, social environment, previous exposure to secondhand smoking, and residential type of foster care system, the expressed opinions regarding the health effects of tobacco use were associated with smoking in foster care teenagers.
Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) protects against focal cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome activation

Abstract Context Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown. Objective This study explores the potential mechanisms of Xingxiong injection in vivo or in vitro. Materials and methods Sprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection. Results Xingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1β (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression. Conclusions Xingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.
Online Video Teletherapy Treatment of Obsessive-Compulsive Disorder Using Exposure and Response Prevention: Clinical Outcomes From a Retrospective Longitudinal Observational Study

Background Exposure and response prevention, a type of cognitive-behavioral therapy, is an effective first-line treatment for obsessive-compulsive disorder (OCD). Despite extensive evidence of the efficacy of exposure and response prevention (ERP) from clinical studies and in real-world samples, it is still underused as a treatment. This is likely due to the limits to access to care that include the availability of adequately trained therapists, as well as geographical location, time, and cost barriers. To address these, NOCD created a digital behavioral health treatment for OCD using ERP delivered via video teletherapy and with technology-assisted elements including app-based therapy tools and between-session therapist messaging. Objective We examined treatment outcomes in a large naturalistic sample of 3552 adults with a primary OCD diagnosis who received NOCD treatment. Methods The treatment model consisted of twice-weekly, live, face-to-face video teletherapy ERP for 3 weeks, followed by 6 weeks of once-weekly brief video teletherapy check-ins for 30 minutes. Assessments were conducted at baseline, at midpoint after completion of 3 weeks of twice-weekly sessions, and at the end of 6 weeks of brief check-ins (endpoint). Longitudinal assessments were also obtained at 3, 6, 9, and 12 months after endpoint. Results Treatment resulted in clinically and statistically significant improvements, with a 43.4% mean reduction in obsessive-compulsive symptoms (g=1.0; 95% CI 0.93 to 1.03) and a 62.9% response rate. Treatment also resulted in a 44.2% mean reduction in depression, a 47.8% mean reduction in anxiety, and a 37.3% mean reduction in stress symptoms. Quality of life improved by a mean of 22.7%. Reduction in OCD symptoms and response rates were similar for those with mild, moderate, or severe symptoms. The mean duration of treatment was 11.5 (SD 4.0) weeks, and the mean total therapist time was 10.6 (SD 1.1) hours. Improvements were maintained at 3, 6, 9, and 12 months. Conclusions In this sample, representing the largest reported treated cohort of patients with OCD to date, video teletherapy treatment demonstrated effectiveness in reducing obsessive-compulsive and comorbid symptoms and improved quality of life. Further, it achieved meaningful results in less than half the total therapist time compared with standard once-weekly outpatient treatment, an efficiency that represents substantial monetary and time savings. The effect size was large and similar to studies of in-person ERP. This technology-assisted remote treatment is readily accessible for patients, offering an advancement in the field in the dissemination of effective evidence-based care for OCD.
Changes in Glial Support of the Hippocampus during the Development of an Alzheimer’s Disease-like Pathology and Their Correction by Mitochondria-Targeted Antioxidant SkQ1

Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alzheimer’s disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD-like pathology. Using immunohistochemistry, we showed that the early stage of the pathology is accompanied by a lower intensity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell-specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti-AD effects of prolonged supplementation with mitochondria-targeted antioxidant SkQ1. The antioxidant did not affect neurogenesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated-cell density. In summary, both astrocytes and microglia are more vulnerable to AD-associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti-inflammatory effect and is a promising modality for AD prevention and treatment.
Application of 3D Gel Dosimetry as a Quality Assurance Tool in Functional Leksell Gamma Knife Radiosurgery

Highly precise dose delivery to the target (tumor or cancerous tissue) is a key point when brain diseases are treated applying recent stereotactic techniques: intensity-modulated, image-guided radiotherapy, volumetric modulated arc therapy, Gamma knife radiosurgery. The doses in one single shot may vary between tens and hundreds of Gy and cause significant cell/tissue/organ damages. This indicates the need for implementation of quality assurance (QA) measures which are realized performing treatment dose verification with more than one calibrated quality assurance method or tool, especially when functional radiosurgery with a high dose (up to 40 Gy in our case) shall be delivered to the target using small 4 mm collimator. Application of two dosimetry methods: radiochromic film dosimetry using RTQA2 and EBT3 films and dose gel dosimetry using modified nPAG polymer gels for quality assurance purposes in stereotactic radiosurgery treatments using Leksell Gamma Knife© Icon™ facility is discussed in this paper. It is shown that due to their polymerization ability upon irradiation nPAG gels might be potentially used as a quality assurance tool in Gamma knife radiosurgery: they indicate well pronounced linear dose response in hypo-fractionated (up to 10 Gy) dose range and are sensitive enough to irradiation dose changes with a high (at least 0.2 mm) spatial resolution. Dose assessment sensitivity of gels depends on parameters of a dose evaluation method (optical or magnetic resonance imaging), however, is similar to this estimated using film dosimetry, which is set as a standard dosimetry method for dose verification in radiotherapy.
Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis

Simple Summary Human epidermal growth factor receptor 2 (HER2)-positive breast cancer causes more aggressive progression of disease and poorer outcomes for patients. HER2-targeted medicines used as neoadjuvant systemic therapy could improve clinical outcomes in early-stage or locally advanced breast cancer patients. The purpose of this systematic review and network meta-analysis was to identify the neoadjuvant anti-HER2 therapy with the best balance between efficacy and safety. We found that trastuzumab emtansine + pertuzumab + chemotherapy had a high pathologic complete response with a low risk of adverse events compared to other neoadjuvant anti-HER2 regimens, while the pertuzumab + trastuzumab + chemotherapy regimen showed the highest disease-free survival. However, further trial data on neoadjuvant regimens with trastuzumab emtansine are needed to confirm these findings. Abstract This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety. Methods: A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments. Results: Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32–0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE. Conclusions: The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings.
Septins Provide Microenvironment Sensing and Cortical Actomyosin Partitioning in Motile Amoeboid T Lymphocytes

The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For amoeboid motility, lymphocytes do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape and steric interactions with the microenvironment. However, the exact mechanism of amoeboid motility remains elusive. Here we report that septins shape T cells for amoeboid motility. Specifically, septins form F-actin and alpha-actinin-rich cortical rings at the sites of cortex-indenting collisions of T cells with the extracellular matrix. Cortical rings compartmentalize cells into chains of spherical segments that are spatially conformed to the available lumens, forming transient ‘hourglass’-shaped steric locks onto the surrounding collagen fibers. The steric lock facilitates pressure-driven peristaltic propulsion of cytosolic content by individually contracting cell segments. Our results demonstrate that septins provide microenvironment-guided partitioning of actomyosin contractility and steric pivots for amoeboid motility of T cells in tissue-like microenvironments. GLOSSARY Steric interactions - interactions by the means of their spatial collision dependent on objects’ shapes. Steric guidance - cell navigation within crowded 3D environments, determined by the available passages around and between steric hindrances. Peristaltic treadmilling - locomotion mode by the means of a repeated sequence of polarized cell cortex extension, stabilization, and retraction, accompanied by translocation of nucleus and cytoplasm via circumferential cortex contractility. Significance Statement T cells can be highly motile, searching for cognate antigens or better yet targets in chimeric antigen receptor therapy settings. However, mechanisms of motility remain elusive for T cells migrating in structurally and biochemically diverse tissues. Here we address one pivotal question of basic and clinical immunology - How T cells achieve the ‘all-terrain’ motility? Here we decipher and report septin-based T cell motility in a 3D tissue-like environment. Specifically, we show that septins facilitate cell morphological responsiveness to the steric obstacles, i.e., collagen fiber-wise partitioning of actomyosin cortex contractility and cell-obstacle steric interactions. These responses coordinate peristaltic propulsion of the lymphocyte’s cytosolic content along its individually contracting cell segments, forming the obstacle-avoiding motility, i.e., circumnavigation, shared across various tested lymphocytes.
Human Augmentation Technologies for Employee Well-Being: A Research and Development Agenda

The COVID-19 pandemic has changed the style of work. In adapting to the changing work environment, human augmentation technologies (HAT) can provide employees with new options to support their work. However, the agenda for research and development of HAT for the new normal is still unclear. In this study, we set two research questions: (i) what type of technology demand has emerged among employees due to the COVID-19 pandemic; and (ii) what is the nature of job satisfaction experienced by employees during the COVID-19 pandemic? This study aims to clarify the technology demand and job satisfaction of employees during the COVID-19 pandemic. We analyzed data from in-depth interviews with employees based on a grounded theory approach to answer the research questions and proposed an agenda for the research and development of HAT to enhance employees’ well-being in this new normal based on the crosspoint of technology demand and job satisfaction. The theoretical contribution of this study is the development of models of technology demand and job satisfaction of employees during the COVID-19 pandemic. The practical contribution is the development of a crosspoint framework to enable the development of HAT to support work while considering their impact on employees’ well-being.
The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

Preeclampsia is a pregnancy-specific disease which is characterized by abnormal placentation, endothelial dysfunction, and systemic inflammation. Several studies have shown that the maternal immune system, which is crucial for maintaining the pregnancy by ensuring maternal-fetal-tolerance, is disrupted in preeclamptic patients. Besides different immune cells, immune checkpoint molecules such as the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1 system) and the T-cell immunoglobulin and mucin domain-containing protein 3/Galectin-9 (TIM-3/Gal-9 system) are key players in upholding the balance between pro-inflammatory and anti-inflammatory signals. Therefore, a clear understanding about the role of these immune checkpoint molecules in preeclampsia is essential. This review discusses the role of these two immune checkpoint systems in pregnancy and their alterations in preeclampsia.
Neuron–Microglia Contact-Dependent Mechanisms Attenuate Methamphetamine-Induced Microglia Reactivity and Enhance Neuronal Plasticity

Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP3R2-Ca2+-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.
Structure and Characteristics of Plant-Frugivore Network in an Urban Park: A Case Study in Nanjing Botanical Garden Mem. Sun Yat-Sen

Interaction between animals and plants is an important way to maintain terrestrial biodiversity and ecosystem function, but little is known about the structure of reciprocal networks between fruit plants and frugivore birds in urban habitats. To explore the characteristics of the plant–frugivore network and network roles of species, we observed the fruit ripening phenology of 21 species of fruit plants and the interactions between these plants and 39 species of frugivore birds during the whole year in a large urban park. Then, we assessed the characteristics of the total plant–frugivore and seasonal networks, and analyzed the network roles of species and the relationship between their network roles and ecological traits. Fruit ripened mainly in autumn and winter, and interaction connections in the two seasons contributed 39.68% and 44.83% to the total network, respectively. The specialization (H2′), connectance (C), nestedness, and interaction evenness (eH2) of the network were lower in autumn and winter, while the interaction diversity was higher. Compared with the networks (N = 1000) generated by the null model, the observed network exhibited higher nestedness and interaction diversity (E2) and lower specialization (H2′), connectance (C), and interaction evenness (eH2). A correlation analysis combining ecological traits and network roles showed that plants with black fruit had higher effective partners and partner diversity, while other traits of plants and birds were not significantly correlated with their network parameters. The important plants (N = 6) and birds (N = 3) contributed to 71.78% and 67.55% of the total network connection, they were mainly evergreen plants with black and red drupes and omnivorous generalist birds with medium and large sizes. Our research highlighted the seasonal differences in urban plant–frugivore network and the value of important species in maintaining network structures and providing ecosystem services.