Miracle-dz/UniFAR-FTUs huggingface dataset:
MYB transcription factors in alfalfa (Medicago sativa): genome-wide identification and expression analysis under abiotic stresses

Background Alfalfa is the most widely cultivated forage legume and one of the most economically valuable crops in the world. Its survival and production are often hampered by environmental changes. However, there are few studies on stress-resistance genes in alfalfa because of its incomplete genomic information and rare expression profile data. The MYB proteins are characterized by a highly conserved DNA-binding domain, which is large, functionally diverse, and represented in all eukaryotes. The role of MYB proteins in plant development is essential; they function in diverse biological processes, including stress and defense responses, and seed and floral development. Studies on the MYB gene family have been reported in several species, but they have not been comprehensively analyzed in alfalfa. Methods To identify more comprehensive MYB transcription factor family genes, the sequences of 168 Arabidopsis thaliana, 430 Glycine max, 185 Medicago truncatula, and 130 Oryza sativa MYB proteins were downloaded from the Plant Transcription Factor Database. These sequences were used as queries in a BLAST search against the M. sativa proteome sequences provided by the Noble Research Institute. Results In the present study, a total of 265 MsMYB proteins were obtained, including 50 R1-MYB, 186 R2R3-MYB, 26 R1R2R3-MYB, and three atypical-MYB proteins. These predicted MsMYB proteins were divided into 12 subgroups by phylogenetic analysis, and gene ontology (GO) analysis indicated that most of the MsMYB genes are involved in various biological processes. The expression profiles and quantitative real-time PCR analysis indicated that some MsMYB genes might play a crucial role in the response to abiotic stresses. Additionally, a total of 170 and 914 predicted protein–protein and protein-DNA interactions were obtained, respectively. The interactions between MsMYB043 and MSAD320162, MsMYB253 and MSAD320162, and MsMYB253 and MSAD308489 were confirmed by a yeast two-hybrid system. This work provides information on the MYB family in alfalfa that was previously lacking and might promote the cultivation of stress-resistant alfalfa.
Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes

Abstract Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.
Biomarkers In Chronic Spontaneous Urticaria: Current Targets And Clinical Implications

Abstract Chronic urticaria (CU) is a mast cell-driven disease characterized by the development of wheals, angioedema, or both for more than 6 weeks. The two major sub-types are chronic spontaneous urticaria (CSU) and inducible urticaria. In the last decade different pathophysiological mechanisms, potentially responsible for the development of the disease, have been described. It is likely that the activation of mast cells and basophils in CSU can be the results of immune system dysregulation, activation of the inflammatory cascade, and of the extrinsic coagulation pathway. Some of the mediators involved in the pathophysiological mechanisms of CSU have recently been identified as potential biomarkers useful for the diagnosis, follow-up, and management of the disease, even if they are not yet available in clinical practice. Thus, in this review we discuss new insights in the mediators involved in the pathogenesis of CSU, highlighting their potential role as biomarkers in the activity and progression of the disease and response to therapies.
Long noncoding RNA PVT1 promotes hepatoblastoma cell proliferation through activating STAT3

Background Hepatoblastoma is the most common liver malignancy in children. The long noncoding RNA (IncRNA) PVT1 plays oncogenic roles in human cancers; however, its regulation and function in hepatoblastoma remain poorly understood. Purpose This study was designed to investigate the regulation and function of PVT1 in hepatoblastoma. Methods PVT1 expression was compared between human hepatoblastoma tissues and adjacent non-tumor tissues, and then analyzed using Kaplan-Meier method. The proliferation of hepatoblastoma cells was determined by BrdU incorporation assay. The tumor xenograft model was used to assess tumor proliferation in vivo. The gene expression level was measured by qRT-pCR, Western blot and immunohistochemistry analyses. Results Compared with normal counterparts, PVT1 is upregulated in human hepatoblastoma tissues as well as in hepatoblastoma cell lines. Additionally, PVT1 promotes the proliferation of hepatoblastoma cells in vitro and accelerates tumor growth in xenograft model in vivo. Mechanistically, PVT1 promotes the activation of the signal transducer and activator of transcription 3 (STAT3), which leads to the transcriptional activation of downstream targets involved in cell cycle progression, and moreover,STAT3 inhibition with the selective inhibitor stattic abolishes PVT1 pro-proliferative role in hepatoblastoma cells. Conclusion PVT1 promotes hepatoblastoma cell proliferation through activating STAT3-induced cell cycle progression, which may implicate PVT1 as a potential therapeutic target for hepatoblastoma treatment.
Prediction model for patients with acute respiratory distress syndrome: use of a genetic algorithm to develop a neural network model

Background Acute respiratory distress syndrome (ARDS) is associated with significantly increased risk of death, and early risk stratification may help to choose the appropriate treatment. The study aimed to develop a neural network model by using a genetic algorithm (GA) for the prediction of mortality in patients with ARDS. Methods This was a secondary analysis of two multicenter randomized controlled trials conducted in forty-four hospitals that are members of the National Heart, Lung, and Blood Institute, founded to create an acute respiratory distress syndrome Clinical Trials Network. Model training and validation were performed using the SAILS and OMEGA studies, respectively. A GA was employed to screen variables in order to predict 90-day mortality, and a neural network model was trained for the prediction. This machine learning model was compared to the logistic regression model and APACHE III score in the validation cohort. Results A total number of 1,071 ARDS patients were included for analysis. The GA search identified seven important variables, which were age, AIDS, leukemia, metastatic tumor, hepatic failure, lowest albumin, and FiO2. A representative neural network model was constructed using the forward selection procedure. The area under the curve (AUC) of the neural network model evaluated with the validation cohort was 0.821 (95% CI [0.753–0.888]), which was greater than the APACHE III score (0.665; 95% CI [0.590–0.739]; p = 0.002 by Delong’s test) and logistic regression model, albeit not statistically significant (0.743; 95% CI [0.669–0.817], p = 0.130 by Delong’s test). Conclusions The study developed a neural network model using a GA, which outperformed conventional scoring systems for the prediction of mortality in ARDS patients.
Intratumoral IL-12 Gene Therapy Inhibits Tumor Growth In A HCC-Hu-PBL-NOD/SCID Murine Model

Purpose This study aimed to evaluate the efficacy and safety of intratumoral IL-12 gene therapy in an HCC-hu-PBL-NOD/SCID mouse model. Materials and methods The HCC murine model was generated in NOD/SCID mice, and mice with grafted tumors were injected intraperitoneally with 2 × 107 human peripheral blood lymphocytes 14 days after modeling. After 4 days, mice were randomly divided into the 9597/IL-12 group, the 9597/plasmid group and the PBS group. The changes of tumor volume were measured and mouse peripheral blood was sampled post-treatment for ELISA and CBA analyses, and the grafted tumors were collected 28 days post-treatment for immunohistochemistry, ELISA, CBA and detection of cell cycle and apoptosis. Results The tumor volume was smaller in the 9597/IL-12 group than in the 9597/plasmid and PBS groups on days 7, 14, 21, and 28 post-treatment (P < 0.05). Higher IL-12 levels were detected in the peripheral blood and the supernatants of grafted tumor homogenates in the 9597/IL-12 group than in the 9597/plasmid and PBS groups 7, 14, 21 and 28 days post-treatment (P < 0.05). IHC revealed higher counts of CD3+T cells, CD4+T helper cells, IFN-γ Th1 cells+ and S-100 protein positive dentric cells and lower MVD in the 9597/IL-12 group than in the 9597/plasmid and PBS groups (P < 0.05). Flow cytometry showed a significantly higher proportion of HCC cells at the G0/G1 phase and a significantly lower proportion of HCC cells at the S phase in the 9597/IL-12 group than in the PBS group (P < 0.05) and a greater apoptotic rate of HCC cells in the 9597/IL-12 group than in the 9597/plasmid and PBS groups (P < 0.05). Conclusion Intratumoral IL-12 gene therapy may inhibit tumorigenesis with mild adverse effects in a HCC-hu-PBL-NOD/SCID murine model through inhibiting angiogenesis, arresting cells in G0/G1 phase and inducing apoptosis.
The Risk Of Seizure-Related Hospitalization Among Older Adults On Levetiracetam Monotherapy: A Retrospective Comparative Cohort Study

Background Antiepileptic drug monotherapy is the mainstay of treatment for epilepsy; however, the efficacy of different antiepileptic drugs in reducing the incidence of seizure-related hospitalization among older adults, who are at higher risk of developing epilepsy compared to their younger counterparts, has not been examined. Purpose The objective of the present study was to compare the rate of seizure-related hospitalization among older adults on levetiracetam compared to different antiepileptic drugs (AEDs). Patients and methods This was a retrospective cohort study of older adults (≥60 years) in two tertiary care hospitals. Patients who are 60 years of age and older, have a confirmed diagnosis of epilepsy, and are taking a single and the same antiepileptic drug for at least 36 months were included. The patients were followed up for 24 months after 12 months of treatment with no incidence of seizure-related hospitalization via their health records. Multiple Poisson regression with robust error variance was used to estimate the relative risk of hospitalization for patients on levetiracetam compared to different antiepileptic drugs controlling for age, gender, number of prescription medications, dosage strengths, and Charlson Comorbidity Index (CCI) score. Results One hundred and thirty-six patients met the inclusion criteria and were included in the study. The recruited patients were on one of the following four antiepileptic drugs: carbamazepine (n=44), levetiracetam (n=39), phenytoin (n=31), and valproic acid (n=22). Patients on levetiracetam were more than twice as likely to be hospitalized due to seizures within the 24 months of follow-up compared to their counterparts on other AEDs (RR=2.76, 95% CI=1.16–6.53, P=0.021). Conclusion This study suggests that older adults on old generation AEDs such as phenytoin, carbamazepine, and valproic acid appear to have a lower risk of seizure-related hospitalization compared to their counterparts on levetiracetam.
Dual targeting of RANKL and PD‐1 with a bispecific antibody improves anti‐tumor immunity

The addition of RANKL/RANK blockade to immune checkpoint inhibitors (ICIs) such as anti‐PD‐1/PD‐L1 and anti‐CTLA4 antibodies is associated with increased anti‐tumor immunity in mice. Recent retrospective clinical studies in patients with advanced melanoma and lung cancer suggest the addition of anti‐RANKL antibody to ICI increases the overall response rate relative to ICI treatment alone. Based on this rationale, we developed a novel bispecific antibody (BsAb) co‐targeting RANKL and PD‐1.
Diurnal Stability Of Peripapillary Vessel Density And Nerve Fiber Layer Thickness On Optical Coherence Tomography Angiography In Healthy, Ocular Hypertension And Glaucoma Eyes

Purpose By using optical coherence tomography angiography (OCTA), to evaluate diurnal changes of the following parameters: vessel density in the peripapillary area (PP-VD) and in the optic nerve head (ONH-VD); thickness of retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC). Methods All prospectively enrolled participants were imaged on the same day at 8 am and 7 pm by means of the XR Avanti device with AngioVue and AngioAnalytics software (Optovue Inc., Fremont, CA, USA). Only eyes with correct automatic segmentation and good-quality images (scan quality > 7/10) were included. Results Forty-six eyes from 28 patients with glaucoma, 53 from 31 patients with ocular hypertension, and 62 from 38 controls were assessed. The mean measurements of all parameters investigated were significantly different in the morning and in the evening values in all three groups, with lower values in glaucomatous eyes (p<0.014). In control eyes, as well as in eyes of patients with ocular hypertension and glaucoma the daily changes were minimal and not statistically significant with means of +0.17%, −0.31% and −0.54% for ONH-VD (p=0.83) and means of +0.2%, +0.1% and +0.29% for PP-VD (p=0.83), respectively. Likewise, daily fluctuations in GCC and RNFL thickness were not significant in any of the three groups, with means of +0.16 µm, +0.66 µm and −0.15 µm for GCC (p=0.58) and means of +0.24 µm, +0.58 µm and −0.24 µm for ONH-RNFL (p=0.90), respectively. Systemic hypertension, age, axial length, daily changes in intraocular pressure or scan quality did not correlate with daily fluctuations of any of the parameters investigated (p>0.1). Conclusion Vessel density, GCC and RNFL were stable during daytime thus corroborating the clinical relevance of OCTA regardless the time of acquisition.
Application of single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients after bilioenteric Roux-en-Y anastomosis: Experience of multi-disciplinary collaboration

BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.
Preliminary psychometric properties of the Arabic version of Sheu and colleagues Perceived Stress Scale among nursing students at Jordanian universities

Purpose Nursing is known to be a stressful profession, as it necessitates constant interaction with different individuals in an environment that is described as highly stressed. The stress phenomenon mainly affects the students of nursing more than other health-related students. The Perceived Stress Scale (PSS), which is developed by Sheu and colleagues represents the most implemented instrument to examine stress among nursing students that belong to different cultures in different countries. Previous studies have not fully examined the psychometric properties of the PSS, especially in the Arab World. Therefore, this study aims to assess the psychometric properties of the Arabic version of Sheu and colleagues Perceived Stress Scale (PSS), which is used to measure the clinical stress among nursing students. Patients and methods This methodological study utilized a cross-sectional design to test the PSS preliminary psychometric properties among 320 nursing students at 5 Jordanian universities. Results The Arabic version of the PSS showed high internal consistency reliability (Cronbach’s α was 0.90 in addition to an excellent content validity (CVI was 0.94). The exploratory factor analysis indicated that 54.54% of the total variance was accounted for by the five factors model, which confirmed the construct validity of the Arabic version of PSS. The findings of this study revealed that the Arabic version of PSS can be appropriately implemented among nursing students. Conclusion This study supports and recommends the use of the Arabic version of PSS to measure clinical stress among nursing students at Jordanian Universities.
Collisional mechanics of the diagonal gaits of horses over a range of speeds

One of the goals of the neuromotor control system is to minimize the cost of locomotion by reducing mechanical energy losses. Collisional mechanics, which studies the redirection of the downwards motion of the center of mass (COM) by ground reaction forces (GRF) generated by the limbs, represents an important source of energy loss. The primary objective of this study was to compare collisional mechanics and the associated mechanical energy losses in horses performing diagonally-synchronized gaits over a range of speeds. It is to be expected that collisional energy losses will be high when the COM velocity vector is closely aligned with the GRF vector. This condition is achieved in piaffe, an artificial gait performed in dressage competitions that has a diagonal limb coordination pattern similar to trot but performed with little or no forward velocity. Therefore, we hypothesized that collisional energy losses would be higher in piaffe than in trot. Synchronized kinematic and GRF data were collected from three highly-trained horses performing piaffe, passage and trot at a range of speeds. Derived variables were vertical excursion and velocity of the trunk COM, fore and hind limb compression expressed as percentage reduction of standing limb lengths, range of limb pro-retraction, GRF vector magnitude and vector angle, collision angle (Φ), and mechanical cost of motion (CoMotmech). Linear regression was used to investigate the relationship between CoMotmech and speed for each gait. Partial correlation was used to seek relationships between COM excursion and limb mechanics for each gait. Piaffe, passage and trot were clearly separated on the basis of speed. In all gaits the trunk was high at contact and lift off and descended to its lowest point in midstance following the pattern typical of spring mass mechanics. Mechanical cost was significantly (p < .05) and inversely related to speed in trot and piaffe with the value increasing steeply as speed approached zero due to a near vertical orientation of both the COM velocity vector and the GRF vector. Limb compression during stance was significantly (p < .05) linked to trunk COM vertical excursion in all gaits, with a stronger relationship in the forelimb. Hindlimb compression was, however, large in piaffe where the force magnitudes are notably smaller. The study illustrates the potential value of studying artificial gaits to provide data encompassing the entire range of locomotor capabilities. The results supported the experimental hypothesis by showing a threefold increase in collisional energy losses in piaffe compared with trot. In all gaits, dissociation between diagonal limb contacts and lift offs was thought to be an important strategy in reducing in collisional losses. Piaffe, the most costly gait, has similar characteristics to hopping on the spot. It appears that greater hindlimb compliance and a lower step frequency are important energy conservation strategies for piaffe.