Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of a Remote Real-Time Monitoring System for Multiple Physiological Parameters Based on Smartphone

Background Utilization of the widely used wearable sensor and smartphone technology for remote monitoring represents a healthcare breakthrough. This study aims to design a remote real-time monitoring system for multiple physiological parameters (electrocardiogram, heart rate, respiratory rate, blood oxygen saturation, and temperature) based on smartphones, considering high performance, autoalarm generation, warning transmission, and security through more than one method. Methods Data on monitoring parameters were acquired by the integrated circuits of wearable sensors and collected by an Arduino Mega 250 R3. The collected data were transmitted via a Wi-Fi interface to a smartphone. A patient application was developed to analyze, process, and display the data in numerical and graphical forms. The abnormality threshold values of parameters were identified and analyzed to generate an autoalarm in the system and transmitted with data to a doctor application via a third-generation (3G) mobile network and Wi-Fi. The performance of the proposed system was verified and evaluated. The proposed system was designed to meet main (sensing, processing, displaying, real-time transmission, autoalarm generation, and threshold value identification) and auxiliary requirements (compatibility, comfort, low power consumption and cost, small size, and suitability for ambulatory applications). Results System performance is reliable, with a sufficient average accuracy measurement (99.26%). The system demonstrates an average time delay of 14 s in transmitting data to a doctor application via Wi-Fi compared with an average time of 68 s via a 3G mobile network. The proposed system achieves low power consumption against time (4 h 21 m 30 s) and the main and auxiliary requirements for remotely monitoring multiple parameters simultaneously with secure data. Conclusions The proposed system can offer economic benefits for remotely monitoring patients living alone or in rural areas, thereby improving medical services, if manufactured in large quantities.
Delayed Rectifier K+-Channel Is a Novel Therapeutic Target for Interstitial Renal Fibrosis in Rats with Unilateral Ureteral Obstruction

Background Delayed rectifier K+-channel, Kv1.3, is most predominantly expressed in T-lymphocytes and macrophages. In such leukocytes, Kv1.3-channels play pivotal roles in the activation and proliferation of cells, promoting cellular immunity. Since leukocyte-derived cytokines stimulate fibroblasts to produce collagen fibers in inflamed kidneys, Kv1.3-channels expressed in leukocytes would contribute to the progression of tubulointerstitial renal fibrosis. Methods Male Sprague-Dawley rats that underwent unilateral ureteral obstruction (UUO) were used at 1, 2, or 3 weeks after the operation. We examined the histological features of the kidneys and the leukocyte expression of Kv1.3-channels. We also examined the therapeutic effects of a selective channel inhibitor, margatoxin, on the progression of renal fibrosis and the proliferation of leukocytes within the cortical interstitium. Results In rat kidneys with UUO, progression of renal fibrosis and the infiltration of leukocytes became most prominent at 3 weeks after the operation, when Kv1.3-channels were overexpressed in proliferating leukocytes. In the cortical interstitium of margatoxin-treated UUO rat kidneys, immunohistochemistry revealed reduced expression of fibrosis markers. Additionally, margatoxin significantly decreased the numbers of leukocytes and suppressed their proliferation. Conclusions This study clearly demonstrated that the numbers of T-lymphocytes and macrophages were markedly increased in UUO rat kidneys with longer postobstructive days. The overexpression of Kv1.3-channels in leukocytes was thought to be responsible for the proliferation of these cells and the progression of renal fibrosis. This study strongly suggested the therapeutic usefulness of targeting lymphocyte Kv1.3-channels in the treatment of renal fibrosis.
Shear Stress Promotes Arterial Endothelium-Oriented Differentiation of Mouse-Induced Pluripotent Stem Cells

Establishment of a functional vascular network, which is required in tissue repair and regeneration, needs large-scale production of specific arterial or venous endothelial cells (ECs) from stem cells. Previous in vitro studies by us and others revealed that shear stress induces EC differentiation of bone marrow-derived mesenchymal stem cells and embryonic stem cells. In this study, we focused on the impact of different magnitudes of shear stress on the differentiation of mouse-induced pluripotent stem cells (iPSCs) towards arterial or venous ECs. When iPSCs were exposed to shear stress (5, 10, and 15 dyne/cm2) with 50 ng/mL vascular endothelial growth factor and 10 ng/mL fibroblast growth factor, the expression levels of the general EC markers and the arterial markers increased, and the stress amplitude of 10 dyne/cm2 could be regarded as a proper promoter, whereas the venous and lymphatic markers had little or no expression. Further, shear stress caused cells to align parallel to the direction of the flow, induced cells forming functional tubes, and increased the secretion of nitric oxide. In addition, Notch1 was significantly upregulated, and the Notch ligand Delta-like 4 was activated in response to shear stress, while inhibition of Notch signaling by DAPT remarkably abolished the shear stress-induced arterial epithelium differentiation. Taken together, our results indicate that exposure to appropriate shear stress facilitated the differentiation of mouse iPSCs towards arterial ECs via Notch signaling pathways, which have potential applications for both disease modeling and regenerative medicine.
Recurrent hypotension induced by sacubitril/valsartan in cardiomyopathy secondary to Duchenne muscular dystrophy: A case report

BACKGROUND Duchenne muscular dystrophy (DMD), which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome, is the most common type of neuromuscular disorder in pediatrics. Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years. Cardiac muscle is frequently affected in DMD patients, which leads to a high burden of cardiomyopathy and heart failure. In the era of improved respiratory care, cardiac deaths are becoming the major cause of mortality in DMD patients. CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo. He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years. He was prescribed diuretics and digoxin at the outpatient clinic; however, his symptoms did not resolve. Sacubitril/valsartan was added 1 mo prior to presentation, but he experienced recurrent episodes of palpitations. The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm, and he was then hospitalized. Hypotension was found following the administration of sacubitril/valsartan tablets; he could not tolerate even a small dose, always developing tachyarrhythmia. His symptoms were relieved after discontinuing sacubitril/valsartan, and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin. Atrial tachycardia spontaneously converted in this patient, and his symptoms attenuated in the following 6 mo, without palpitation episodes. CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.
Epigenome-wide association of father’s smoking with offspring DNA methylation: a hypothesis-generating study

Abstract Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers’ smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11–54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006–0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR) < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers’ smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers’ exposures might persistently modify their future offspring’s epigenome.
Association between Hyperreflective Foci on Spectral-Domain Optical Coherence Tomography and Early Recurrence of Diabetic Macular Edema after Intravitreal Dexamethasone Implantation

Purpose To investigate the associations between hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) and early recurrence of macular edema after intravitreal dexamethasone (DEX) implantation in eyes with refractory diabetic macular edema (DME) to bevacizumab. Methods Medical records of patients with refractory DME to bevacizumab, who underwent intravitreal DEX implantation and 12-month follow-up, were reviewed. Eyes in which central subfield thickness (CST) increased over 50 μm at 3 months compared with the first month after intravitreal DEX implantation were categorized into the early recurrence group, and the others were categorized into the late recurrence group. Best-corrected visual acuity (BCVA), CST, and number of HRF on SD-OCT were analyzed. Results Twenty-nine eyes of 26 patients (16 eyes in the early recurrence group and 13 eyes in the late recurrence group) were included in this study. The numbers of HRF in entire retina, inner retina, and outer retina at baseline in the early recurrence group (11.38 ± 3.07 in entire retina, 5.44 ± 1.50 in inner retina, 5.94 ± 2.74 in outer retina) were significantly greater than those in the late recurrence group (7.54 ± 3.60 in entire retina, p=0.006; 4.08 ± 1.70 in inner retina, p=0.034; 3.46 ± 2.30 in outer retina, p=0.013). Multivariate logistic regression analysis showed that a higher number of HRF increased the risk of early recurrence after intravitreal DEX implantation (odds ratio in entire retina: 1.518, p=0.012; odds ratio in inner retina: 2.058, p=0.027; odds ratio in outer retina: 1.610, p=0.029). Conclusions Higher baseline numbers of HRF on SD-OCT may be a predictive indicator of early recurrence of macular edema after intravitreal DEX implantation for DME.
Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis

Hematopoietic stem cells (HSCs) are characterized by self-renewal and multilineage differentiation potentials. Although they play a central role in hematopoietic homeostasis and bone marrow (BM) transplantation, they are affected by multiple environmental factors in the BM. Here, we review the effects of reactive oxygen species (ROS) and Nrf2 on HSC function and BM transplantation. HSCs reside in the hypoxic microenvironment of BM, and ROS play an important role in HSPC regulation. Recently, an extraphysiologic oxygen shock/stress phenomenon was identified in human cord blood HSCs collected under ambient air conditions. Moreover, Nrf2 has been recently recognized as a master transcriptional factor that regulates multiple antioxidant enzymes. Since several years, the role of Nrf2 in hematopoiesis has been extensively studied, which has functional similarities of cellular oxygen sensor hypoxia-inducible factor-1 as transcriptional factors. Increasing evidence has revealed that abnormally elevated ROS production due to factors such as genetic defects, aging, and ionizing radiation unexceptionally resulted in lethal impairment of HSC function and hematopoiesis. Both experimental and clinical studies have identified elevated ROS levels as a major culprit of ineffective BM transplantation. Lastly, we discuss the possibility of using small molecule antioxidants, such as N-acetyl cysteine, resveratrol, and curcumin, to augment HSC function and improve the therapeutic efficacy of BM transplantation. Further research on the function of ROS levels and improving the efficacy of BM transplantation may have a great potential for broad clinical applications of HSCs.
Estimation of Motor Impairment and Usage of Upper Extremities during Daily Living Activities in Poststroke Hemiparesis Patients by Observation of Time Required to Accomplish Hand Dexterity Tasks

Aim This study evaluated whether specific actual performance could accurately predict body function levels and upper limb use in the real-life functioning of poststroke hemiparesis patients to aid in choosing the most appropriate rehabilitation exercises. Methods We measured the time taken for poststroke patients to move small objects with the paralyzed hand and investigated how the measurement could estimate upper extremity motor impairment and hand usage during activities of daily living (ADL). We examined 86 stroke patients (age 66 ± 16 years) whose upper extremity motor paralysis was measured using the Fugl-Meyer assessment (FMA) and Southampton Hand Assessment Procedure (SHAP), and patient-reported ADL was investigated using the Jikei Assessment Scale for Motor Impairment in Daily Living (JASMID). To identify the time required to perform each SHAP item, we employed a linear regression analysis. The prediction formula was used in the linear regression analysis, and the coefficient of determination (R2) was applied to compare each component item score that was obtained with the predicted values derived from the linear regression analysis. Results The most easily accomplished task was Heavy Power in the SHAP. The R2 between the SHAP Heavy Power item score and the FMA scores was moderate (R2 = 0.344, P < 0.0001), whereas the R2 with the JASMID score was low (R2 = 0.126, P < 0.001). Conclusions By measuring the time it takes for poststroke hemiparesis patients to hold and move an object, we developed a prediction formula for upper extremity motor function and hand dexterity.
Computation of Intersegmental Moments during Standing Posture: Can We Neglect the Horizontal Ground Reaction Force? Results from an Experimental Study

Background The development of postural analysis thanks to force and pressure platforms, in order to determine the center of pressure, can be valuable in the setting of spinal malalignment. The purpose of this study was to compare “pressure” and “force” platforms for the evaluation of the center of pressure. In other words, can we neglect the horizontal ground reaction force in the evaluation of intersegmental moments during standing posture? Methods. Postural data from two healthy adult volunteers were analyzed. Analysis of the posture was done according to a protocol providing sagittal intersegmental moments. A set of 36 markers was used to divide the body in 10 segments. Postacquisition calculations were done in order to obtain the sagittal net intersegmental moments. To evaluate the differences in intersegmental moments between force and pressure platforms, the postacquisition calculations were done with a simulated pressure platform. Mean intersegmental moments between each body segment for each volunteer were compared. Findings There were significant differences between the 2 platforms in intersegmental moments for the lumbo-sacral junction, hips, knees, and ankles (p < 0.005). All differences were inferior to intrasubject variability measured with the force platform (p < 0.001). Results from intra- and interobserver comparisons showed that differences measured with the pressure platform were all inferior to the standard error obtained with the force platform for every intersegmental moment (p < 0.001). Interpretation The use of a simulated pressure platform to determine intersegmental moments has the same clinical efficiency as force platforms. Moreover, the possibility to set the platform into the radiograph room will allow in a second time a correlation between radiographic parameters and biomechanical constraints applied to the spine.
Urinary Matrix Metalloproteinase-7 and Prediction of AKI Progression Post Cardiac Surgery

Aims Early detection of patients at high risk for progressive acute kidney injury (AKI) after cardiac surgery remains a major challenge. We aim to evaluate the utility of urinary matrix metalloproteinase-7 (uMMP-7) and other reported biomarkers for predicting AKI progression during postoperative hospital stay. Methods We conducted a prospective, multicenter cohort study in 121 adult patients with stage 1 or 2 AKI after cardiac surgery. uMMP-7 and other well-reported biomarkers (uIL-18, uNGAL, and UACR) were measured at time of AKI clinical diagnosis. The primary outcome is the progression of AKI after cardiac surgery, defined as worsening of AKI stage (stage 1 to either stage 2 or stage 3 or from stage 2 to stage 3). Results A level of uMMP‐7 > 7.8 μg/g Cr at time of AKI diagnosis conveyed an 8-fold risk of AKI progression as compared to those with uMMP‐7 < 2.7 μg/g after adjusting for clinical risk factors. The performance of uMMP-7 for predicting progressive AKI was good with an AUC of 0.80. The combination of uMMP-7 and IL-18 produces the greatest AUC for predicting progressive AKI. Addition of uMMP-7 to the clinical risk factor model significantly improved risk reclassification for AKI progression. Conclusions uMMP-7, measured at time of AKI clinical diagnosis, is a novel biomarker for predicting the progression of AKI after cardiac surgery. Adding uMMP-7 to the clinical risk factor model may be used as a noninvasive approach to identify a subpopulation that is at high risk for progressive AKI after cardiac surgery.
Effect of Carica papaya Extract toward Incised Wound Healing Process in Mice (Mus musculus) Clinically and Histologically

Wound healing entails a sequence of complex biological processes, which is a protective function of the body that focuses on a quick recovery. Reducing wound healing time is crucial in a wound as it lowers the chance of infection and decreases complications and costs. Papaya extract was obtained by a maceration method. It contains papain enzyme, flavonoid, saponin, and alkaloid, which act as an anti-inflammatory, astringent substance, vasodilator, antioxidant, analgesic, with antifungal, and antibacterial properties, and increase the collagen synthesis. This study aimed to assess the effect of Carica papaya extract application toward incised wound healing process in mice (Mus musculus) clinically and histologically. This experimental laboratory study was performed using 24 mice weighing between 30 and 40 grams and 12 and 14 weeks of age as experimental animals. Each group was incised along 5 mm at the labial gingiva under both of mandible anterior teeth with a depth reaching alveolar bone. Papaya extract was applied topically in the morning and evening for 14 days. The clinical result was obtained by assessing the length of wound closure measured every day for 14 days. Based on the statistic test result, it showed that the papaya extract has a significant effect (p ≤ 0.05) toward the healing process of an incised oral wound in mice. Histologically at day 14, 75% concentration papaya extract showed perfect epithelial layer and fibrillation.
Opportunities and Limitations of Vascular Risk Factor Models in Studying Plasticity-Promoting and Restorative Ischemic Stroke Therapies

Major efforts are currently made promoting neuronal plasticity and brain remodeling in the postacute stroke phase. Experimental studies evaluating new stroke therapies are mostly performed in rodents, which compared to humans exhibit a short lifespan. These studies widely employ young, otherwise healthy, rodents that lack the vascular risk factors and comorbidities of stroke patients. These risk factors compromise postischemic neurological recovery and brain plasticity and in several contexts reduce the brain responsiveness to recovery-inducing plasticity-promoting treatments. By examining risk factor models, which have hitherto been used for studying experimentally induced ischemic stroke, this review outlines the possibilities and limitations of risk factor models in the evaluation of plasticity-promoting and restorative stroke treatments.
Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together

Danio rerio (zebrafish) is an elective model organism for the study of vertebrate development because of its high degree of homology with human genes and organs, including bone. Zebrafish embryos, because of the optical clarity, small size, and fast development, can be easily used in large-scale mutagenesis experiments to isolate mutants with developmental skeletal defects and in high-throughput screenings to find new chemical compounds for the ability to revert the pathological phenotype. On the other hand, the adult zebrafish represents another powerful resource for pathogenic and therapeutic studies about adult human bone diseases. In fish, some characteristics such as bone turnover, reparation, and remodeling of the adult bone tissue cannot be found at the embryonic stage. Several pathological models have been established in adult zebrafish such as bone injury models, osteoporosis, and genetic diseases such as osteogenesis imperfecta. Given the growing interest for metabolic diseases and their complications, adult zebrafish models of type 2 diabetes and obesity have been recently generated and analyzed for bone complications using scales as model system. Interestingly, an osteoporosis-like phenotype has been found to be associated with metabolic alterations suggesting that bone complications share the same mechanisms in humans and fish. Embryo and adult represent powerful resources in rapid development to study bone physiology and pathology from different points of view.