Miracle-dz/UniFAR-FTUs huggingface dataset:
Sulfonylurea antidiabetics are associated with lower risk of out‐of‐hospital cardiac arrest: Real‐world data from a population‐based study

Out‐of‐hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP‐regulated K+ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes.
Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report

Background Pembrolizumab is a humanized monoclonal antibody that is used to treat a variety of cancers. It exerts its mechanism of action by blocking the programmed death receptor-1 (PD-1). Toxicity concerns include immune-related toxicities, including colitis, hepatitis, pneumonitis, nephritis, endocrine toxicities and more rarely, myocarditis and other organ system toxicities. Objective To review a real-world case involving immunotherapy induced myocarditis after a patient received pembrolizumab and discuss how the current pandemic created complexity in toxicity management. Discussion An 83 year old male with metastatic lung cancer developed fatal myocarditis after receiving 2 doses of pembrolizumab. Applying the Naranjo score, the likelihood of pembrolizumab causing the myocarditis is probable, with a score of 6. Severe cardiac toxicities are rare with pembrolizumab, but can still occur. It is vital to be aware of these toxicities, and educate patients on signs and symptoms. Complicating the situation even further was the global pandemic, which created fear and hesitation in the patient and the patient’s family to seek medical treatment out of fear of exposure. This pandemic adds another layer to the complexity of care for patients with cancer and management of toxicities. Pharmacists play a significant role in ensuring the safety and efficacy of medications, especially oncology agents. Conclusion Proper education of patients regarding symptoms and when to report are paramount to assisting in early detection and intervention for immunotherapy-related adverse events. New management and treatment strategies will need to be discussed and implemented considering the changing landscape around the SARS-CoV-2 pandemic.
Cytocompatible scaffolds of poly(L-lactide)/reduced graphene oxide for tissue engineering

Abstract Poly(L-lactide)/reduced graphene oxide (PLLA/rGO) scaffolds were studied in the present work. The scaffolds were fabricated by TIPS (thermally induced phase separation). Nonisothermal crystallization study for PLLA/rGO was investigated and revealed the nucleating effect of rGO. rGO effect on cytotoxicity, thermal properties, and hydrolysis resistance of PLLA and PLLA/rGO scaffolds were analysed. In vitro degradation in phosphate-buffered solution at 37 °C is analyzed over twelve weeks. A high crystalline behaviour reduces the speed of hydrolysis and therefore implies less variation in pH, mass loss and water up take. The rGO does not seem to accelerate the degradation process. Finally, rGO contents in PLLA up to 1 wt% dos not lead to cytotoxic effect, the scaffolds supporting cell adhesion and proliferation.
Effects of delta‐tocotrienol supplementation on Glycemic Control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: A randomized control trial

The study aimed to ascertain the effects of delta‐tocotrienol (δT3) supplementation on glycemic control, oxidative stress, inflammation and related micro‐ribonucleic acid (miRNA) expression in patients with type 2 diabetes mellitus (T2DM). Total 110 patients of T2DM on oral hypoglycemic agents, were randomly divided into tocotrienol and placebo groups and given 250 mg δT3 or cellulose soft gel capsule once daily respectively for 24 weeks. Glycemic control, oxidative stress, inflammatory biomarkers, and miRNAs expression were measured in serum at baseline and end of the intervention by using standard laboratory methods. Compared to the placebo, δT3 supplementation resulted in a significant (p ≤ .05) reduction [mean difference (95% confidence interval)] in plasma glucose [−0.48 (−0.65, −0.30)], insulin [−1.19 (−1.51, −0.87)], homeostatic model assessment of insulin resistance [−0.67 (−0.86, −0.49)], glycosylated hemoglobin [−0.53 (−0.79, −0.28)], malondialdehyde [−0.34 (−0.45, −0.22)], high sensitive‐C‐reactive protein[−0.35 (−0.54, −0.16)], tumor necrosis factor‐alpha [−1.22 (−1.62, −0.83)], and interleukin‐6[−2.30 (−2.91, −1.68)]. More than twofold downregulation in miRNA‐375, miRNA‐34a, miRNA‐21, and upregulation in miRNA‐126, miRNA‐132 expression was observed in the δT3 group compared to the placebo. The study demonstrated that δT3 supplementation in addition to oral hypoglycemic agents, improved glycemic control, inflammation, oxidative stress, and miRNA expression in T2DM without any adverse effect. Thus, δT3 might be considered as an effective dietary supplement to prevent long‐term diabetic complications.
Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort

Abstract Introduction The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder. Material and Methods We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. Results When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis. Conclusion The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.
Genomic and epigenomic active vitamin Dresponses in human colonic organoids.

BACKGROUND & AIMS Active vitamin D, 1α,25(OH)2D3, is a nuclear hormone with roles in colonic homeostasis and carcinogenesis; yet, mechanisms underlying these effects are incompletely understood. Organoids are an ideal system to study genomic and epigenomic host-environment interactions. We utilize colonic organoids to measure 1α,25(OH)2D3 responses on genome-wide gene expression and chromatin accessibility over time. METHODS Human colonic organoids were treated in triplicate with 100nM 1α,25(OH)2D3 or vehicle control for 4 and 18 hours (h) for chromatin accessibility, and 6 and 24h for gene expression. ATAC- and RNA-sequencing were performed. Differentially accessible peaks were analyzed using DiffBind and EdgeR; differentially expressed genes were analyzed using DESeq2. Motif enrichment was determined using HOMER. RESULTS At 6h and 24h, 2870 and 2721 differentially expressed genes, respectively (false discovery rate, FDR<5%) were identified with overall stronger responses with 1α,25(OH)2D3. Vitamin Dtreatment led to stronger chromatin accessibility especially at 4h. The vitamin D receptor (VDR) motif was strongly enriched among accessible chromatin peaks with 1α,25(OH)2D3 treatment accounting for 30.5% and 11% of target sequences at 4h and 18h, respectively (FDR<1%). Genes such as CYP24A1, FGF19, MYC, FOS and TGFBR2 showed significant transcriptional and chromatin accessibility responses to 1α,25(OH)2D3 treatment with accessible chromatin located distant from promoters for some gene regions. CONCLUSIONS Assessment of chromatin accessibility and transcriptional responses to 1α,25(OH)2D3 yielded new observations about vitamin D genome-wide effects in the colon facilitated by application of human colonic organoids. This framework can be applied to study host-environment interactions between individuals and populations in future.
The Management of Indirect Inguinal Hernia Sac in Laparoscopic Inguinal Hernia Repair: A Systemic Review of Literature

Background: The aim of this study is to investigate the current management strategy of indirect hernia sac during laparoscopic inguinal hernia repair. Objectives: The aim was to evaluate the various indirect hernia sac management strategies when performing laparoscopic inguinal hernia repair. Data Sources: Major databases (PubMed, Embase, Springer, and Cochrane Library). Review Methods: MeSH and free-text searching include “laparoscopic inguinal hernia” “TAPP,” “TEP,” “inguinal hernia,” “indirect inguinal hernia sac,” “distal sac,” “sac transection,” “sac ligation,” and “sac reduction. ” Results: The present study enrolled 7 trials, 4 studies compared the results of indirect hernia sac transection and complete sac reduction. The pooled results indicated that indirect hernia sac transection was associated increased seroma formation (odds ratio=2.74, 95% confidence interval: 1.41-4.31), and there was no statistical difference in the incidence of postoperative pain, operative time, hernia recurrence, and time to return to normal activity between the sac transection and sac reduction groups. Two studies reported the application of adjuncts in the management of distal sac during laparoscopic large inguinoscrotal hernia repair. The seroma formation could be reduced by adjuncts of fixing the distal hernia sac to posterior abdominal wall with either suture or tacks. Conclusion: Indirect sac transection during laparoscopic indirect inguinal hernia repair is associated with a higher incidence of postoperative seroma. Additional adjuncts to the divided distal hernia sac, including distal sac fixation with either suture or tacks, are effective methods to prevent postoperative seroma.
Toluene Dose-Response and Preliminary Study of Proteomics for Neuronal Cell Lines

Abstract : Toluene, a jet fuel component, is a potential contaminant in aircraft. Effects of toluene exposure include headache or fatigue. The objective of this study was to perform a preliminary investigation of the cellular and molecular effects of toluene on murine cell lines including Cath.a, C8-B4, CLU199, and HT22. The study tests two methods: direct dosing of toluene in the media and vapor exposure in glass chambers. To better define the complex signaling response to toluene, the two exposure models are characterized by cell viability assays and Tandem Mass Tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS) quantitative proteomics proteome pathway analysis. Cell viability in response to direct dosing in a vehicle demonstrated a dose-dependent decrease in cell viability for all cell lines. Cytoscape 3.1. 0 Reactome FI pathway analysis of Cath.a cells following direct dosing with 0.2 and 2 mM toluene revealed a dose-dependent toxicity increase of modulated protein nodes related to oxidative stress such as energy reserve metabolism, cell-death signaling, cytoskeletal rearrangement, DNA damage response, targeted protein degradation and apoptosis. While cell viability testing of all four cell lines exposed to 200 ppm toluene vapor for 1hour did not result in any detectable decrease of cell viability, proteomic analysis displayed minor signs of cellular stress with a majority of modulated proteins. These findings contribute to understanding the complex protein modifications within normally conserved proteins and toluene induced activation of cellular signaling pathways, which will aid in determining initiating mechanisms of brain toxicity from low level doses.
Effects of Altering Heparan Sulfate Proteoglycan Binding and Capsid Hydrophilicity on Retinal Transduction by Adeno-associated Virus

Rationally guided engineering of AAV capsids aims to create new generations of vectors with enhanced potential for human gene therapy. By applying rational design principles to AAV2-based capsids, we evaluated the influence of hydrophilic and hydrophobic amino acid mutations on retinal transduction as it relates to vector administration route. ABSTRACT Adeno-associated viruses (AAVs) have recently emerged as the leading vector for retinal gene therapy. However, AAV vectors that are capable of achieving clinically relevant levels of transgene expression and widespread retinal transduction are still an unmet need. Using rationally designed AAV2-based capsid variants, we investigate the role of capsid hydrophilicity and hydrophobicity as it relates to retinal transduction. We show that hydrophilic, single-amino-acid mutations (V387R, W502H, E530K, L583R) in AAV2 negatively impact retinal transduction when heparan sulfate proteoglycan (HSPG) binding remains intact. Conversely, addition of hydrophobic point mutations to an HSPG binding-deficient capsid (AAV2ΔHS) leads to increased retinal transduction in both mouse and macaque. Our top performing vector, AAV2(4pMut)ΔHS, achieved robust rod and cone photoreceptor (PR) transduction in macaque, especially in the fovea, and demonstrates the ability to spread laterally beyond the borders of the subretinal injection (SRI) bleb. This study both evaluates biophysical properties of AAV capsids that influence retinal transduction and assesses the transduction and tropism of a novel capsid variant in a clinically relevant animal model. IMPORTANCE Rationally guided engineering of AAV capsids aims to create new generations of vectors with enhanced potential for human gene therapy. By applying rational design principles to AAV2-based capsids, we evaluated the influence of hydrophilic and hydrophobic amino acid mutations on retinal transduction as it relates to vector administration route. Through this approach, we identified a largely deleterious relationship between hydrophilic amino acid mutations and canonical HSPG binding by AAV2-based capsids. Conversely, the inclusion of hydrophobic amino acid substitutions on an HSPG binding-deficient capsid (AAV2ΔHS) generated a vector capable of robust rod and cone photoreceptor (PR) transduction. This vector AAV2(4pMut)ΔHS also demonstrates a remarkable ability to spread laterally beyond the initial subretinal injection (SRI) bleb, making it an ideal candidate for the treatment of retinal diseases that require a large area of transduction.
Investigating hypothyroidism

• Suspect hypothyroidism in patients with convincing symptoms and/or signs, especially if they have risk factors for hypothyroidism, and refer them for thyroid stimulating hormone (TSH) measurement • An elevated serum TSH and a low serum free thyroxine are diagnostic for primary hypothyroidism, and levothyroxine, adjusted every 4-6 weeks until TSH normalises, is the treatment of choice • Universal screening for hypothyroidism is not recommended, as it may result in overdiagnosis, unnecessary treatment, and increased healthcare costs
Practices of Professional Learning Communities

Building professional learning communities (PLC) has become a widely recognized strategy for school development and for student achievement. Four Finnish comprehensive schools were identified as being ready to be PLCs in a previous quantitative study, and the purpose of this study was to investigate practices of PLCs in these schools. In this paper, we used data from qualitative multiple-case study, which investigated practices of leadership, culture, teacher collaboration, professional learning, and development. The results showed that the principals had played the main role in the progression of schools as PLCs. Principals were described as visionary leaders who had started positive progression, shared the leadership, and created commitment to common goals. The results indicated also that a change of leaders can have a positive effect. Decision-making processes were participative, inclusive, democratic, and collaborative, aiming for a satisfactory level of consensus. Relationships among staff were reported as being based on mutual trust and openness, and members were encouraged to express their opinions. Common responsibility of students, peer support, encouragement, and co-teaching were practiced. Co-teaching practices were identified as an effective form of collaborative work-embedded professional learning which is related to the core principles of professional learning communities. Structural conditions were reported as barriers to schools’ development as PLCs.
Adaptive Quantization in Multispectral Image Compression for Equalizing Visual Error Distribution

This article proposes an adaptive nonlinear quantization method for multispectral image compression. When linear scalar quantization is applied for multispectral image compression, extremely large error is perceived in low-luminance colors due to the nonlinear phenomenon of human vision. In the proposed method, quantization tables are switched pixel by pixel depending on the corresponding luminance. The switching rule is determined according to the relationship between the luminance and the error in the uniform color space. As a result, distribution of the error in the uniform color space can be equalized and the error in the low-luminance pixels is suppressed. Experimental results using a 16-band multispectral image of an oil painting shows the effectiveness of the proposed method.
Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson’s disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12–35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.
Changes in Vitamin A Levels and the Effect of Early Vitamin A Supplementation on Vitamin A Levels in Infants Throughout the First 6 Months of Life: A Prospective Cohort Study in Chongqing, China

Objectives: This study aimed to explore the changes in infant vitamin A (VA) status and the effect of early VA supplementation on VA level throughout the first 6 months of life. Methods: A prospective cohort study was conducted in Chongqing, China. A total of 1,016 healthy infants were enrolled at birth. Then, 930, 882, 854 and 822 healthy infants were followed up at postnatal day 7 and postnatal months 1, 3, and 6, respectively. Blood samples and dietary survey and physical development data were collected. Serum VA was measured by chromatography tandem-mass spectrometry and was classified according to the VA deficiency (VAD) criteria for older children aged 6–70 months (<0.70, 0.70–1.05, ≥1.05 μmol/L). Normally distributed continuous variables are presented as the mean ± standard deviation. The categorical variables are described by the frequency and percentage (%). The reference interval for the VA level was the 2.5th−97.5th percentile. Changes in VA status with age and the relationship of VA supplementation with VA level were investigated by generalized estimating equations followed by Bonferroni post hoc test, controlling for the effects of feeding pattern and sex. Results: Infant VA levels increased significantly from 0.499 ± 0.146 to 1.061 ± 0.414 μmol/L with age at 6 months, even without VA supplementation (P < 0.05). From birth to 6 months, the percentage of infants with a VA level <0.70 μmol/L decreased from 88.6 to 19.5%. During follow-up, no infant demonstrated clinical VAD conditions, such as night blindness, conjunctival xerosis or Bitot's spots. Less than 7.0% of infants were underdeveloped in terms of weight, length and head circumference. The VA status of infants with VA≥0.588 μmol/L at birth gradually increased to adequate VA (VA ≥ 1.05 μmol/L) at 6 months. For these infants, there was no significant difference in VA level between the VA supplementation and non-supplementation groups (P > 0.05). Infants with VA <0.430 μmol/L at birth still had VA <0.70 μmol/L at 6 months; in this group, VA levels increased by 0.08 μmol/L more among supplemented infants than among non-supplemented infants (P < 0.05). Conclusions: A low VA level among neonates at birth may be a normal physiological state and may increase with age; thus, not all neonates may need early VA supplementation. More multicenter studies are needed to determine a new cutoff point for the diagnosis of neonatal VAD and the administration of nutritional intervention.