Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimuli-responsive star polyethylene glycol conjugates for improved intracellular delivery of N-acetyl cysteine in neuroinflammation

N-Acetyl cysteine (NAC) is an important drug currently under clinical trials for the treatment of neuroinflammation in maternal-fetal applications. The free sulfhydryl groups in NAC lead to high plasma protein binding, resulting in low bioavailability. Preparation and activity of conjugates of NAC with thiol terminated multi-arm (6 and 8) poly(ethylene-glycol) (PEG) with disulfide linkages involving sulfhydryls of NAC are reported. Multiple copies (5 and 7) of NAC were conjugated on 6 and 8-arm PEG respectively. Both the conjugates released 74% of NAC within 2h by thiol exchange reactions in the redox environment provided by glutathione (GSH) intracellularly (2–10 mM). At physiological extracellular glutathione concentration (2µM) both the conjugates were stable and did not release NAC. MTT assay showed comparable cell viability for unmodified PEGs and both the PEG-S-S-NAC conjugates. The conjugates were readily endocytosed by cells, as confirmed by flow cytometry and confocal microscopy. Efficacy of 6 and 8-arm PEG-S-S-NAC conjugates was evaluated on activated microglial cells (the target cells, in vivo ) by monitoring cytokine release in lipopolyssacharide (LPS) induced inflammatory response in microglial cells using the reactive oxygen species (ROS), free radical nitrile (NO), anti-inflammatory activity and GSH depletion. The conjugates showed significant increase in antioxidant activity (more than a factor of 2) compared to free drug as seen from the inhibition of LPS induced ROS, NO, GSH and tumor necrosis factor-alpha (TNF- α ) release in microglial cells.
Impact of a Hemoglobin Trigger Communication Tool on Perioperative Transfusion in Cardiac Surgery

Blood transfusion strategies in cardiac surgeries have been subject to multiple studies to avoid the hazards associated with blood product transfusion while maintaining safe outcomes. This article investigates the effect of implementing a verbal hemoglobin trigger in the surgical timeout on perioperative transfusion in cardiac surgery. Abstract Objectives Blood transfusion represents an important and potentially modifiable risk in the daily practice of cardiac surgery. The risk profile and increasing cost of transfusion led us to study the effect of different maneuvers, interventions, or surgical techniques to minimize transfusion while maintaining patient safety. This study compares postoperative outcomes before and after incorporating a verbal hemoglobin (Hb) trigger during the surgical timeout in which the surgeon and anesthesiologist preemptively agree on a threshold for packed red blood cell (PRBC) administration in the perioperative period. Methods The authors performed a chart review of patients who underwent cardiac surgery from July 2013 through June 2014 at our institution. Patients who underwent surgery from July 2013 through December 2013 served as the pre-Hb trigger group, and patients who underwent surgery from January 2014 through June 2014 served as the post-Hb trigger group. Information collected included patient demographics, type of cardiac surgery, preoperative Hb, Hb trigger, and intraoperative and postoperative variables. The primary outcome was the incidence of PRBC transfusions. Secondary outcomes included the incidence of frozen plasma (FP) transfusion, mechanical ventilation beyond postoperative day 1, and 30-day mortality. Results The study included 191 patients, with 84 in the pre-Hb trigger group and 107 in the post-Hb trigger group. Intraoperative PRBC transfusions did not decrease in the posttrigger group compared with the pretrigger group (pretrigger 51.4% vs posttrigger 52.4%, P = 1.0); however, intraoperative FP administration was lower in the posttrigger group (65.4% vs 50.0%, P = 0.038). Postoperative mechanical ventilation beyond postoperative day 1 also was significantly lower in the posttrigger group compared with the pretrigger group (27.1% vs 14.3%, P = 0.035). Conclusions Implementation of a verbal Hb trigger during the surgical timeout was associated with a reduction in FP administration and duration of mechanical ventilation, but not a decrease in PRBC transfusion and mortality.
Does Finding Cecal Adenoma Increase the Risk of Discovering More and Advanced Adenomas in the Remainder of the Colon?

This is the first retrospective study highlighting the association of colonic adenoma location with finding multiple and advanced adenomas in remainder of the colon. Clinically finding a cecal adenoma should prompt endoscopists to be more thorough and vigilant when evaluating the entire colon, specifically on the right side. Abstract Objectives Adenomatous polyps are common, occurring in up to 25% of the population older than 50 years of age in the United States. Conflicting data are present in the literature about the impact of specific adenoma locations and the prediction on the number and advanced histology of adenomas elsewhere. With this study we aimed to review the association between cecal adenoma and the risk of discovering more and advanced adenomas in the remainder of the colon. Methods We performed a retrospective study of 1880 patients who received outpatient colonoscopies between June 2012 and December 2014 at the Veterans Affairs Medical Center in Oklahoma City. The data collected included patient demographics, indications for colonoscopy, smoking history, alcohol use, family history of colon cancer, quality of bowel preparation, number of adenomas, location, size of adenomas, and the histology of adenomas and colon cancer. Results The mean age of the study population was 61.6 ± 9.4 year, with 95% of the population being men. Cecal adenomas were found in 243 (12.9%) of patients. Patients with cecal adenoma tended to be older (65 ± 7 vs 61 ± 10, P < 0.0001), more likely to be men (97% vs 94%, P = 0.06) and less likely to have a colonoscopy done for screening indication (11% vs. 13%., P = 0.03). After adjusting for age, sex, indication, and quality of bowel preparation, patients with cecal adenoma were found to have a sixfold increase in finding ≥10 other adenomas elsewhere (4.5% vs 0.8% P = 0.0009) and a threefold increase in finding advanced adenomas (17.7% vs 9.9% P = 0.002) in the remainder of the colon. Stratifying by location, the increased risk was more pronounced in the right side (24.7% vs 8.9% P ≤ 0.0001) compared with the left side. Conclusions Cecal adenoma is associated with an increased risk of finding more and advanced adenomas in the remainder of the colon, especially on the right side; therefore, the discovery of a cecal adenoma should prompt a more thorough evaluation of the entire colon, particularly the right colon.
Muscarinic type-1 receptors regulate I K,ACh in human atrial cardiomyocytes and are upregulated in patients with chronic atrial fibrillation

Background— Basal and acetylcholine-gated inward-rectifier K + -currents (I K1 and I K,ACh , respectively) are altered in atrial fibrillation (AF). G i -protein-coupled muscarinic (M) receptors type-2 are considered the predominant receptors activating I K,ACh . Although a role for G q -coupled non-M 2 -receptor subtypes has been suggested, the precise regulation of I K,ACh by multiple M-receptor subtypes in the human atrium is unknown. Here, we investigated M 1 -receptor-mediated I K,ACh regulation and its remodeling in chronic AF (cAF). Methods and Results— M 1 -receptor mRNA and protein abundance were increased in atrial cardiomyocyte fractions and atrial homogenates from cAF patients, whereas M 2 -receptor levels were unchanged. The regulation of I K,ACh by M 1 - receptors was investigated in right-atrial cardiomyocytes using two applications of the M-receptor agonist carbachol (CCh, 2 μM), with pharmacological interventions during the second application. CCh application produced a rapid current increase (Peak-I K,ACh ), which declined to a quasi-steady-state level (Qss-I K,ACh ). In sinus rhythm (Ctl) the selective M 1 -receptor antagonists pirenzepine (10 nM) and muscarinic toxin-7 (MT-7, 10 nM) significantly inhibited CCh-activated Peak-I K,ACh , whereas in cAF they significantly reduced both Peak- and Qss-I K,ACh , with no effects on basal inward-rectifier currents in either group. Conversely, the selective M 1 -receptor agonist McN-A-343 (100 μM) induced a current similar to the CCh-activated current in Ctl atrial cardiomyocytes pretreated with pertussis toxin to inhibit M 2 -receptor-mediated G i -protein signaling, which was abolished by MT-7. Computational modeling indicated that M 1 - and M 2 -receptors redundantly activate I K,ACh to abbreviate APD, albeit with predominant effects of M 2 -receptors. Conclusion— Our data suggest that G q -coupled M 1 -receptors also regulate human atrial I K,ACh and that their relative contribution to I K,ACh activation is increased in cAF patients. We provide novel insights about the role of non-M 2 -receptors in human atrial cardiomyocytes, which may have important implications for understanding AF pathophysiology. The present study was designed to identify functional non-M 2 receptors in human atrial cardiomyocytes, to study whether and how they affect M-receptor-gated I K,ACh and atrial repolarization, and to explore the consequences of AF-related remodeling for non-M 2 receptor function. Our results identify a novel role for M 1 -receptor-mediated regulation of I K,ACh in human atrial cardiomyocytes, with upregulation of M 1 -receptors in cAF, which may have important consequences for the function of the diseased atrium, particularly in AF.
Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H411E hepatoma cells

Hepatic metabolism and gene expression are among the factors controlled by the cellular hydration state, which changes within minutes in response to aniso-osmotic environments, cumulative substrate uptake, oxidative stress and under the influence of hormones such as insulin. The signalling events coupling cell-volume changes to altered cell function were studied in H4IIE rat hepatoma cells. Hypo-osmotic cell swelling resulted within 1 min in a tyrosine kinase-mediated activation of the extracellular signal-regulated protein kinases Erk-I and Erk-2, which was independent of protein kinase C and cytosolic calcium. Activation
BIANCHI TYPE-III COSMOLOGICAL MODELS WITH BULK VISCOSITY IN f(R) THEORY

The paper is devoted to study the Bianchi type VI0 space-time filled with Bulk viscous in the framework of f(R) gravity. The model initially accelerates for a certain period of time and decelerates thereafter . The physical and kinematical features of the models are studied and discussed. The function f(R) of the Ricci scalar is also evaluated for the model. PACS codes: 04.20. -q; 04.20. Jb; 04.20. Dv; 04.20. Ex
N-cadherin Overexpression Enhances the Reparative Potency of Human iPSC-Derived Cardiac Myocytes in Infarcted Mouse Hearts.

AIMS In regenerative medicine, cellular cardiomyoplasty is one of the promising options for treating myocardial infarction (MI); however, the efficacy of such treatment has shown to be limited due to poor survival and/or functional integration of implanted cells. Within the heart, the adhesion between cardiac myocytes (CMs) is mediated by N-cadherin (CDH2), and is critical for the heart to function as an electromechanical syncytium. In this study, we have investigated whether the reparative potency of human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) can be enhanced through CDH2 overexpression. METHODS AND RESULTS CDH2-hiPSC-CMs and control WT-hiPSC-CMs were cultured in myogenic differentiation medium for 28 days. Using a mouse MI model, the cell survival/engraftment rate, infarct size, and cardiac functions were evaluated post MI, at day 7 or day 28. In vitro, conduction velocities were significantly greater in CDH2-hiPSC-CMs than in WT-hiPSC-CMs. While, in vivo, measurements of cardiac functions: left-ventricular (LV) ejection fraction, reduction in infarct size, and the cell engraftment rate were significantly higher in CDH2-hiPSC-CMs treated MI group than in WT-hiPSC-CMs treated MI group. Mechanistically, paracrine activation of ERK signal transduction pathway by CDH2-hiPSC-CMs, significantly induced neo-vasculogenesis, resulting in a higher survival of implanted cells. CONCLUSIONS Collectively, these data suggest that CDH2 overexpression enhances not only the survival/engraftment of cultured CDH2-hiPSC-CMs, but also the functional integration of these cells, consequently, the augmentation of the reparative properties of implanted CDH2-hiPSC-CMs in the failing hearts. TRANSLATIONAL PERSPECTIVE Our study proposes to combine cellular cardiomyoplasty with gene therapy to improve LV function and remodeling after MI. The reparative potency of hiPSC-CMs could be enhanced through CDH2 overexpression. This unique approach displays several features required for clinical application, which would open new perspectives in clinical setting for the effective management of MI, and thus, can lead to functional enhancement of a failing heart.
Factors Associated with Caregiver Attendance in the Community Implementation of Multiple Evidence-Based Practices in Youth Mental Health Services

Objective: The implementation of evidence-based practices (EBPs) in community mental health settings for youth has consistently yielded weakened effects compared to controlled trials. There is a need to feasibly measure the quality of large-scale implementation efforts to inform improvement targets. This study used therapist-reported caregiver attendance (CA) in sessions as a quality indicator in the community-implementation of EBPs. Methods: Data were collected from therapists practicing in agencies contracted to provide publicly-funded children’s mental health services following a system-driven implementation of multiple EBPs. Community therapists (N=101) provided information about youth clients (N=267) and psychotherapy sessions (N=685). Youth presented with a range of mental health problems and 254 (95%) were of racial/ethnic groups. Multivariable binomial logistic regressions were conducted to examine CA and its associations with therapist factors (e.g., licensure status, education), youth factors (e.g., gender, age), and the type of EBP delivered. Results: CA occurred in 288 (42%) sessions. The following factors were associated with increased odds of caregiver session attendance: younger client age, male youth client, externalizing presenting problem, and delivery of an EBP that prescribes CA in all sessions. Conclusions: Overall, the patterns of CA, within the context of the community implementation of EBPs, appear consistent with the empirically-informed practice parameters for caregiver treatment involvement. Yet, the rates of CA in externalizing-focused sessions were suboptimal and a gender-difference disfavoring girls suggests targeted areas for quality improvement. Potential reasons for these quality gaps are discussed.
Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity

Rationale: Maternal obesity is associated with asthma in the offspring. Whether cord blood leptin is associated with risk of asthma in offspring is unclear. Objectives: To assess whether cord blood leptin from women with pregestational obesity predict preschool asthma. Methods: In this birth cohort study, we divided pregnant women into three weight categories during the ﬁ rst obstetric visit: normal (NL), overweight (OW), and obese (OB). Results: We followed the offspring recording atopy, wheezing, and other respiratory illnesses through 30 months of age. Cord blood and peripheral blood at 30 months of age were taken to measure cytokines, adipokines, metabolic biomarkers, and speci ﬁ c immunoglobulin E. Adjusted regression models were used to evaluate the association between maternal obesity and offspring asthma risk, de ﬁ ned by a positive Asthma Predictive Index. Three hundred thirty-nine mothers were recruited; 140 offspring were born from NL, 80 from OW, and 119 from OB mothers. OB women were older and less educated and had higher parity and higher C-section frequency. Offspring from OB women had higher birthweight, head circumference, and placental weight compared with other groups. The proportion of Asthma Predictive Index positive at 30 months of age was 12.2% in the NL, 14.7% in the OW, and 16.8% in the OB group ( P = 0.18). Offspring from OB women had higher leptin, leptin/adiponectin ratio, interleukin-10, and insulin than the OW group and higher leptin than the NL group. In the adjusted analysis, offspring from OB mothers with high cord blood leptin had increased risk of asthma (adjusted odds ratio, 1.30; 95% con ﬁ dence interval, 1.1 – 1.55; P = 0.003). Conclusions: Offspring from obese mothers with high cord blood leptin have 30% higher asthma risk at age 3. Clinical trial registered with ClinicalTrials.gov (NCT02903134).
Tracheal Anatomy and Factors Contributing to Tissue Engineering

: The trachea is a respiratory organ, which connects the larynx to the main flageolet and the lungs, made up of cartilaginous rings and a mucosal layer-lined tube characterized by smooth muscle and connective tissue. Tissue engineering is one of the most promising and potent therapeutic approaches for curing long-segment tracheal stenosis. This study reviewed articles indexed in scientific databases including ISI, SID, PubMed, and PubMed Central between 1993 and 2022. Although three-dimensional scaffolds are a new therapeutic approach, they have opened up new avenues for renovating pathologically problematic tissues. This review article discusses the anatomy of the trachea and therapeutic approaches such as tissue engineering to construct tracheal cartilage to replace the damaged trachea. Next, we concisely review the recent advances in stem cell biology in scaffolds and their interplay with growth factors to optimize an engineered tracheal epithelium.
Retrieval of Thermal and Microphysical Variables in Observed Convective Storms. Part II: Sensitivity of Cloud Processes to Variation of the Microphysical Parameterization

Abstract The hydrometeor content and thermal fields in a thunderstorm are estimated from a three-dimensional kinematic cloud model employing Doppler wind fields and parameterized microphysical processes. The sensitivity of the cloud model calculations to variation of the microphysical parameterization is determined by comparing results of model runs with modified parameterizations to the results of a standard or control model run with complete warm/cold cloud microphysics. Changes of certain calculated or specified model parameters and alternate exclusion or inclusion of the ice phase modulate extreme values of precipitation content. Differences between the model solutions, which result from altering the balance between predominant precipitation processes, are traced through analysis of model output to some major change of the precipitation accretion mechanism. The largest differences in maximum retrieved graupel/hail content and radar reflectivity associate with the parameterizations which fix the graupe.
Analysis of DAT Combined with the VSD Technique in Wound Repair of Rats and Its Effect on Inflammatory Factors

The clinical efficacy of decellularized adipose tissue (DAT) combined with vacuum sealing drainage (VSD) in the treatment of wound healing in rats is investigated, and the changes of inflammatory factors are analyzed. The tissue defect model of SD (Sprague-Dawley) rats is established and divided into the combined group (n = 12) and the control group (n = 12) according to different treatment methods. The control group is treated with a single VSD technique, and the combined group is treated with DAT on the basis of the control group. The wound healing time of the two groups is observed. Wound tissue is collected 1 day, 10 days, 20 days, and 30 days after treatment, and neutrophil infiltration is observed by HE (hematoxylin-eosin) staining. The expression changes of IL-6 and IL-13 at each time point before and after treatment are compared. Histological observation shows that the cell infiltration is reduced in both groups, and the wound repair in the combined group is better than that in the control group. The experimental results show that the DAT combined with the VSD technique can further speed up wound healing and reduce inflammation in rats.
Comparison of snowpack structure in gaps and under the canopy in a humid boreal forest

The boreal forest covers a significant portion of the Northern Hemisphere and is snow‐covered for over half of the year. Understanding the interactions between the forest canopy and snow is essential in hydrological, meteorological, and climate modelling. However, this is challenging because the density of a forest can range from closed canopies to open gaps. In winter 2018–2019, we assessed differences in snowpack microstructure in small forest gaps and under the canopy of a humid boreal site in eastern Canada. Our experimental approach consisted of quasi‐continuous weekly observations of stratigraphy and measurements of density profiles and temperature in a series of snow pits in both environments. High‐resolution specific surface area (SSA) profiles were measured twice, allowing for an estimation of snow permeability and hydraulic conductivity. The shallower snowpack under the canopy displayed a stronger vertical temperature gradient and less compaction than in forest gaps. This resulted in the dominance of faceted snow crystals with a small SSA. In contrast, we observed that small, rounded grains with a larger SSA than that of faceted crystals prevailed in the gaps. Due to denser snow and higher SSA, snow permeability inside gaps was found to be lower than under the canopy. Implicitly, the estimated hydraulic conductivity was also lower in gaps. Following rain‐on‐snow events, snow under the canopy displayed layers of melt‐freeze polycrystals, while in the gaps, well‐defined ice layers were formed. The combination of low snow permeability and ice layers is likely to affect liquid water transport in the gap snowpack as compared to the canopy. Although observed at relatively small scales in our study, if these differences are confirmed at a catchment scale, they are likely to impact the hydrology of forested areas during snowmelt.