Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability

Supplemental Digital Content is available in the text. Background: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. Methods: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class<II and absence of significant comorbidities. Cardioneuroablation was performed in both atria by interatrial septum puncture, with irrigated conventional catheter and electroanatomic reconstruction. Ablation targeted the neuromiocardial interface by fragmentation mapping (AF-Nests) using the velocity fractionation software, conventional recording, and anatomic localization of the ganglionated plexi. Heart rate variability (time and frequency domain) and arrhythmias were compared by 24h-Holter, before, and 1 year and 2 years after cardioneuroablation. In a 40 month follow-up, 80% of patients were asymptomatic. Results: Time- and frequency-domain heart rate variability demonstrated significant decrease in all autonomic parameters, showing an important parasympathetic and sympathetic activity reduction at 2-year post-cardioneuroablation (P<0.001). There was no difference in heart rate variability between the 1-year and 2-year post-cardioneuroablation (P>0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). Conclusions: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.
Plastome Characterization and Phylogenomics of East Asian Beeches with a Special Emphasis on Fagus multinervis on Ulleung Island, Korea

Beech trees of the genus Fagus (Fagaceae) are monoecious and distributed in the Northern Hemisphere. They represent an important component of mixed broad-leaved evergreen–deciduous forests and are an economically important source of timber. Despite their ecological and economical importance, however, little is known regarding the overall plastome evolution among Fagus species in East Asia. In particular, the taxonomic position and status of F. multinervis, a beech species endemic to Ulleung Island of Korea, remains unclear even today. Therefore, in this study, we characterized four newly completed plastomes of East Asian Fagus species (one accession each of F. crenata and F. multinervis and two accessions of F. japonica). Moreover, we performed phylogenomic analyses comparing these four plastomes with F. sylvatica (European beech) plastome. The four plastomes were highly conserved, and their size ranged from 158,163 to 158,348 base pair (bp). The overall GC content was 37.1%, and the sequence similarity ranged from 99.8% to 99.99%. Codon usage patterns were similar among species, and 7 of 77 common protein-coding genes were under positive selection. Furthermore, we identified five highly variable hotspot regions of the Fagus plastomes (ccsA/ndhD, ndhD/psaC, ndhF/rpl32, trnS-GCU/trnG-UCC, and ycf1). Phylogenetic analysis revealed the monophyly of Fagus as well as early divergence of the subgenus Fagus and monophyletic Engleriana. Finally, phylogenetic results supported the taxonomic distinction of F. multinervis from its close relatives F. engleriana and F. japonica. However, the sister species and geographic origin of F. multinervis on Ulleung Island could not be determined.
Anaesthesia for ophthalmic procedures in patients with thyroid eye disease

Thyroid eye disease is an autoimmune inflammatory disorder of the orbit in adults. It causes inflammation, expansion and fibrosis of orbital fat, muscles and the lacrimal gland, leading to facial disfigurement, functional disability and, in severe cases, blindness. Overall, approximately 20% of affected patients need some form of surgical intervention requiring anaesthesia. This narrative review explores the background of thyroid eye disease, surgical procedures performed and their implications for anaesthesia. General anaesthesia is used for orbital decompression procedures, strabismus correction surgery and complex oculoplastic procedures. Local anaesthetic infiltration or regional anaesthesia under monitored anaesthesia care are the techniques most commonly employed for eyelid retraction surgery. It is important to limit the volume of local anaesthetic agent used during infiltration and continuously monitor the orbital volume and ocular pressure with a ballottement technique. In addition, the contralateral eye should be checked and, if necessary, protected against corneal exposure. Retrobulbar, peribulbar and sub-Tenon’s blocks are best avoided. Topical anaesthesia has been used for some strabismus correction surgery but its use is limited to motivated and cooperative patients only.
Identification of Functional Single Nucleotide Polymorphisms in Porcine HSD17B14 Gene Associated with Estrus Behavior Difference between Large White and Mi Gilts

Steroid hormone levels are associated with estrous behavior, which affects timely mating and reproductive efficiency in pigs. 17β-hydroxysteroid dehydrogenase type 14 (HSD17B14) modulates steroid synthesis and metabolism. To identify the functional single nucleotide polymorphisms (SNPs) in the porcine HSD17B14 gene, ear tissues from Large White and Mi gilts were collected to extract genomic DNA. Variable lengths of truncated promoter of HSD17B14 gene were used to determine the promoter activity by a dual luciferase reporter system. The vector HSD17B14Phe or HSD17B14Val was transfected into porcine granulosa cells (GCs). The core promoter region was identified between −72 bp and −218 bp. Six of seven SNPs had significant differences of allele frequency between Large White and Mi gilts. The plasmids with the wild genotype AA of rs329427898 maintained a smaller fraction of promoter activity compared with the plasmids with the mutant genotype GG, while the plasmids with wild the genotype TT of rs319864566 had a greater promoter activity than the plasmids with the mutant genotype CC. A missense mutation (Phe73Val) caused changes in the structural dynamics and function of the HSD17B14 protein. The highly expressed HSD17B14Val degraded less estradiol into estrone, while the relatively lowly expressed HSD17B14Phe degraded more estradiol into estrone, suggesting the protein activity of HSD17B14Phe was greater than that of HSD17B14Val. Moreover, the HSD17B14Phe group has a greater apoptosis rate of porcine GCs. The HSD17B14 gene could been used as a candidate molecular marker for estrus behavior in pigs.
Effect of Emotional Response on the Performance of a Simulated Laparoscopic Task.

INTRODUCTION An emotional state impacts task performance and cognition. However, evidence of the effect of an induced emotional state on laparoscopic performance has not yet been documented. We investigated whether surgical residents in whom a positive emotion had been induced would produce a better laparoscopic task performance than residents in whom a negative emotional state had been induced. METHODS This controlled laboratory study recruited a total of 53 junior surgical residents who were divided into 3 groups. Each group was required to watch 1 of 3 ten-minute videos designed to evoke a positive, neutral, or negative emotion before performing a laparoscopic cholecystectomy on a virtual simulation model. Task performances, as evaluated by a global assessment form and psychomotor metrics that included task time, errors, and path lengths, were compared between the 3 groups. RESULTS Video watching induced different emotions, as measured by a Visual Analog Scale on feelings. The task time was significantly shorter in the positive (13.7 ± 2.5 minutes) than in the neutrally (17.7 ± 3.9 minutes) and the negatively (18.5 ± 3.8 minutes) induced-emotion groups (P < 0.001). Participants in the positive emotion group completed a laparoscopic cholecystectomy with a significantly lower error rate (2 vs. 4 vs. 7, P = 0.036) and shorter right-handed path length (1089.6 ± 250.6 cm vs. 1287.2 ± 355.5 cm vs. 1410.3 ± 304.1 cm, P = 0.010) than the participants in the neutral and negative emotion groups. CONCLUSIONS A positive emotion can enhance a simulated laparoscopic task performance as assessed by task time and path length. The results indicate that we might improve surgical task performance by adjusting the surgeon's emotional state. We plan a future study that will continue to investigate whether positive emotions can facilitate skill learning.
Combination therapy of ginsenoside compound K and methotrexate was efficient in elimination of anaemia and reduction of disease activity in adjuvant-induced arthritis rats

Abstract Context Ginsenoside compound K (CK) has anti-inflammatory, immunoregulatory, and myelosuppressive protective effects. Methotrexate (MTX) is widely used in combination therapy for rheumatoid arthritis (RA). Objective To evaluate the effects of combination therapy of CK and MTX on anaemia and anti-arthritis in adjuvant-induced arthritis (AA) rats. Materials and methods AA was induced in rats by Complete Freund’s adjuvant, and divided into five groups (n = 10): normal, AA, CK 80 mg/kg, combination therapy (80 mg/kg CK combined with 0.5 mg/kg MTX), and MTX 0.5 mg/kg. From day 12, CK (once a day for 15 days) or MTX (once every 3 days, five times) were intragastrically administered. Results Combination therapy showed increased haemoglobin to 148.5 ± 10.1 g/L compared with AA (129.8 ± 11.7 g/L) and MTX (128.8 ± 18.4 g/L), and decreased reticulocytes in peripheral blood to 4.9 ± 1.1% compared with MTX (9.3 ± 3.3%). In combination therapy group, paw swelling decreased to 5.6 ± 4.3 mL compared with CK (9.4 ± 3.9 mL) and MTX (13.5 ± 7.4 mL), and swollen joint count decreased to 1.4 ± 0.8 compared with CK (2.1 ± 1.0) and MTX (2.4 ± 1.2) at day 24. Combination therapy showed decreased IL-6 to 25.1 ± 17.2 pg/mL compared with MTX (44.9 ± 4.8 pg/mL), and decreased IL-17 to 5.8 ± 3.9 pg/mL compared with MTX (10.7 ± 4.2 pg/mL). Conclusion The anti-anaemia effect of CK deserves further study, and CK can be a candidate effective drug for combined treatment in RA with anaemia.
Influence of Chitin Source and Polymorphism on Powder Compression and Compaction: Application in Drug Delivery

The objective of the research reported herein is to compare the compaction properties of three different chitin extracts from the organisms most used in the seafood industry; namely crabs, shrimps and squids. The foregoing is examined in relation to their polymorphic forms as well as compression and compaction behavior. Chitin extracted from crabs and shrimps exhibits the α-polymorphic form whilst chitin extracted from squid pins displays a β-polymorphic form. These polymorphs were characterized using FTIR, X-ray powder diffraction and scanning electron microscopy. Pore diameter and volume differ between the two polymorphic powder forms. The β form is smaller in pore diameter and volume. Scanning electron microscopy of the two polymorphic forms shows clear variation in the arrangement of chitin layers such that the α form appears more condensed due to the anti-parallel arrangement of the polymer chains. True, bulk and tapped densities of these polymorphs and their mixtures indicated poor flowability. Nevertheless, compression and compaction properties obtained by applying Heckle and Kawakita analyses indicated that both polymorphs are able to be compacted with differences in the extent of compaction. Chitin compacts, regardless of their origin, showed a very high crushing strength with very fast dissolution which makes them suitable for use as fast mouth dissolving tablets. Moreover, when different chitin powders are granulated with two model drugs, i.e., metronidazole and spiramycin they yielded high crushing strength and their dissolution profiles were in accordance with compendial requirements. It is concluded that the source of chitin extraction is as important as the polymorphic form when compression and compaction of chitin powders is carried out.
BH3 Mimetics for the Treatment of B-Cell Malignancies—Insights and Lessons from the Clinic

Simple Summary B-cell malignancies, including chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and plasma cell dyscrasias, are significant contributors to cancer morbidity and mortality worldwide. The pathogenesis of many B-cell malignancies involves perturbations in the intrinsic pathway of apoptosis that allow cells to evade cell death. BH3 mimetics represent a class of anti-cancer agents that can restore the ability of cancer cells to undergo apoptosis. Venetoclax, a recently approved BH3 mimetic, has transformed the therapeutic landscape for CLL. Other BH3 mimetics are currently under development. This review summarizes the available data on existing BH3 mimetics and highlights both the rapidly expanding role of BH3 mimetics in the treatment of B-cell malignancies and the clinical challenges of their use. Abstract The discovery of the link between defective apoptotic regulation and cancer cell survival engendered the idea of targeting aberrant components of the apoptotic machinery for cancer therapy. The intrinsic pathway of apoptosis is tightly controlled by interactions amongst members of three distinct subgroups of the B-cell lymphoma 2 (BCL2) family of proteins. The pro-survival BCL2 proteins prevent apoptosis by keeping the pro-apoptotic effector proteins BCL2-associated X protein (BAX) and BCL2 homologous antagonist/killer (BAK) in check, while the BH3-only proteins initiate apoptosis by either neutralizing the pro-survival BCL2 proteins or directly activating the pro-apoptotic effector proteins. This tripartite regulatory mechanism is commonly perturbed in B-cell malignancies facilitating cell death evasion. Over the past two decades, structure-based drug discovery has resulted in the development of a series of small molecules that mimic the function of BH3-only proteins called the BH3 mimetics. The most clinically advanced of these is venetoclax, which is a highly selective inhibitor of BCL2 that has transformed the treatment landscape for chronic lymphocytic leukemia (CLL). Other BH3 mimetics, which selectively target myeloid cell leukemia 1 (MCL1) and B-cell lymphoma extra large (BCLxL), are currently under investigation for use in diverse malignancies. Here, we review the current role of BH3 mimetics in the treatment of CLL and other B-cell malignancies and address open questions in this rapidly evolving field.
Impact of transcatheter aortic valve implantation on coexistent mitral regurgitation parameters.

BACKGROUND The data assessing the impact of transcatheter aortic valve implantations (TAVI) on coexisting mitral regurgitation (MR) are still inconsistent. AIMS The study aimed to evaluate the impact of TAVI on coexistent MR depending on its aetiology. METHODS From 311 patients treated with TAVI, we selected 48 patients with coexistent MR: functional (FMR; n=26) or non-functional (nFMR; n = 22). The impact of the procedure on MR was quantitatively assessed during a 1-year follow-up using mitral regurgitation effective regurgitation orifice (MR-ERO) and volume (MR-Vol). RESULTS No change of MR-ERO was observed after a one-year follow-up in all MR patients (0.20 cm2 [IQR 0.17 - 0.23 cm2] vs 0.17 cm2 [0.14 - 0.20 cm2] ; P = 0.054). No change in MR-ERO was observed neither in FMR (0.21 cm2 [0.17 - 0.27 cm2] vs.0.19 cm2 [0.14 - 0.25 cm2] cm2, P = 0.142) nor nFMR (0.17 cm2 [IQR 0.12 - 0.23 cm2] vs 0.17 cm2 [IQR 0.10 - 0.20 cm2], P = 0.238) cohorts. Reduction of MR-Vol was observed in the overall MR population after TAVI (32 ml/b [IQR 28 - 36 ml/b] vs. 26 ml/b [IQR 22 - 28 ml/b], P = 0.002). Similarly, reduction of MR-Vol was noted for both FMR (33 ml/b [IQR 26 - 42 ml/b] vs. 26 ml/b [20 - 40 ml/b], P = 0.042) and nFMR (30 ml/b [IQR 20 - 46 ml/b] vs. 24 ml/b [15 - 33 ml/b], P = 0.015) cohorts. CONCLUSIONS TAVI has no impact on the MR-ERO regardless of the aetiology of regurgitation. The procedure reduces, however, MR-Vol in both FMR and nFMR.
Long-Term Results of One-Stage Laparoscopic-Assisted Endorectal Pull-Through for Rectosigmoid Hirschsprung's Disease in Patients Aged Above 5 Years.

Purpose: Despite the fact that the laparoscopic-assisted endorectal pull-through (LAEPT) for Hirschsprung's disease (HD) was introduced over 20 years ago, published outcomes in older children and adolescent are lacking. To address this, we studied the long-term results of LATEP for rectosigmoid HD in patients above 5 years of age. Materials and Methods: A retrospective review was conducted on all nonsyndromic patients above 5 years of age and who underwent one-stage LAEPT for rectosigmoid HD between January 2002 and December 2017. Late Hirschsprung-associated enterocolitis (HAEC) was defined as HAEC occurring 1 year after the pull-through operation. Postoperative bowel function was assessed using the Krickenbeck classification. Results: Forty-one patients (37 males and 4 females) were included in this study with a median follow-up of 9.0 years. The median age at surgery was 55 days. Two patients had anastomotic leakage. No patient had late HAEC, rectal prolapse, anastomotic stricture, or intestinal obstruction. According to the Krickenbeck classification, all patients had voluntary bowel movements without constipation. Overall, 65.8% of patients had no soiling. However, on subgroup analysis, only 45.4% of patients younger than 11 years of age had no soiling compared with 89.5% in patients at or older than 11 years of age (P = .003). Conclusions: Our results showed that LAEPT for rectosigmoid HD was a safe procedure. Nearly 90% of patients had normal bowel function by puberty. Further studies are needed to address the problem of soiling in patients younger than 11 years of age.
Adherence to Dietary Guidelines in Adults by Diabetes Status: Results From the 2012 Mexican National Health and Nutrition Survey

The aims of the present study were to compare the adherence to dietary guidelines and evaluate potential differences in nutrient profiles among adults by diabetes status. We used the Mexican Alternate Healthy Eating Index (MxAHEI) to evaluate adherence to dietary guidelines. We calculated the MxAHEI scores (total and by dietary component) with scales from 0 (non-adherence) to 100 (perfect adherence) based on a food frequency questionnaire. Mean daily intakes of macronutrients and micronutrients (g, mg, mcg/1000 kcal per day) were also estimated by diabetes status. Sex-specific, multivariable linear regression models were estimated to test whether MxAHEI scores as well as nutrient intakes were different by diabetes status. Mexican adults had low adherence to the dietary guidelines irrespective of their diabetes status (score < 50 points). Among men, the MxAHEI score was 2.6 points higher among those with diabetes than those without diabetes (46.9; 95% confidence intervals (CI): 44.6, 49.2 vs. 44.3; 95% CI: 44.2, 45.6, respectively). Among women, the total MxAHEI score was similar in individuals with diabetes compared to those without diabetes. Lower intakes of carbohydrates and added sugars and higher intakes of protein, calcium, and zinc were observed in individuals with diabetes. Our findings support the development of strategies focused on promoting dietary patterns that can help to prevent and control the disease.
Treatment of keloids through Runx2 siRNA-induced inhibition of the PI3K/AKT signaling pathway

Keloids are a skin fibroproliferative condition characterized by the hyperproliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM) components. Previous studies have determined that Caveolin-1 controlled hyperresponsiveness to mechanical stimuli through Runt-related transcription factor 2 (Runx2) activation in keloids. However, the molecular mechanism of Runx2 regulating the pathological progression of keloids has not been elucidated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that most of the differentially expressed genes (DEGs), including Runx2, were significantly enriched in the biological processes ‘Positive regulation of cell proliferation’, in the cellular components ‘Extracellular matrix’, in the molecular functions ‘Extracellular matrix structural constituents’ and in the KEGG ‘PI3K-Akt signaling pathway’. The aim of the present study was to investigate the expression levels of the Runx2 in human keloid tissues and primary human keloid fibroblasts (HKFs), and to determine the underlying molecular mechanisms involved in the fibrotic roles of Runx2 in keloid formation. Runx2 expression levels were analyzed in patient keloid tissues and HKFs using western blotting, reverse transcription-quantitative PCR (RT-qPCR) and immunofluorescence microscopy. Primary HKFs were transfected with a small interfering RNA (si) specifically targeting Runx2 (si-Runx2). Subsequently, Cell Counting Kit-8, wound healing and Transwell assays, flow cytometry, RT-qPCR and western blotting were applied to evaluate the proliferation, migration, apoptosis, ECM deposition and PI3K/AKT signaling pathway of HKFs, respectively. In addition, western blotting was also used to determine the expression levels of phosphorylated AKT and PI3K in HKFs. The results revealed that Runx2 expression levels were upregulated in keloid tissues and primary HKFs compared with the normal skin tissues and human normal fibroblasts. Following the transfection with si-Runx2, the proliferative and migratory abilities of HKFs were significantly reduced and the apoptotic rate was increased. The expression levels of type I, type III collagen, fibronectin, and α-smooth muscle actin were downregulated in si-Runx2-transfected cells, which was hypothesized to occur through following the downregulation of the phosphorylation levels of PI3K and AKT. In conclusion, the findings of the present study indicated that Runx2 silencing in HKFs might significantly inhibit the cell proliferation, migration and the expression levels of ECM-related proteins, and promote apoptosis via suppressing the PI3K/AKT signaling pathway. Thus, Runx2 siRNA treatment may reverse the pathological phenotype of keloids through the inhibition of PI3K/AKT signaling in patients.