Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood Clot Identification Procedures in Clinical Laboratory Sampling.

BACKGROUND Monitoring of anticoagulation therapy is based on screening tests: prothrombin time (PT) and activated partial thromboplastin time (APTT). The accidental presence of a clot in the coagulation samples determines a false prolongation of PT by fibrinogen (FI) consumption and the false or delayed prolongation of APTT, depending on FI consumption or activation. The purpose of this study is to document from the present data re-garding procedures used to exclude the accidental presence of clot in the sample. METHODS For a more efficient approach, we conducted a study based on research from the main databases that included original and peer-reviewed studies. RESULTS We have reported studies in which pre-analytical procedures have been recommended and studies that have also presented post-analytical protocols. A correlation between the efficiency of the procedures in terms of additional laboratory costs has been performed, as well. CONCLUSIONS Focusing on patient safety, it remains a continuous challenge for each laboratory to be able to establish its own pre-analytical and post-analytical procedure for highlighting accidental clot presence, thus ensuring provision of results with maximum confidence to the clinicians.
Effects of low and moderate treadmill exercise on liver of d‐galactose‐exposed aging rat model

Aging increases liver susceptibility to diseases and it causes inflammation in liver tissue which can lead to fibrosis. Studies suggest that aging is caused by the accumulation of free radicals. Lack of physical activity can lower hormone levels and increase free radicals that can accelerate the aging process. Hence, physical activity is very important to maintain functions of organs. This research was aimed to study the effects of low and moderate treadmill exercise on d‐Galactose‐exposed aging rat model by evaluating the degree of hepatic fibrosis, number of M1 and M2, and M1/M2 ratio. Twenty‐four 3‐month‐old male Wistar aging model rats were randomly divided into four groups, that is, three treatment groups with daily 300 mg kgBW−1 d‐Galactose injection administrated intraperitoneally for 4 weeks and 1 control group with normal saline injection. Two of the d‐Galactose treated groups were given low and moderate treadmill exercise for 4 weeks. It was concluded that low intensity treadmill exercise significantly lowered the degree of d‐Galactose‐exposed hepatic fibrosis, and moderate treadmill exercise was able to restore the injured liver tissue back to the non‐aging state. Administration of d‐Galactose causes inflammation marked by the elevated number of M1 and M2 macrophages. Moderate treadmill exercise drove M1/M2 ratio back to the control condition.
Impact of a charged neighboring particle on Förster resonance energy transfer (FRET)

Förster resonance energy transfer (FRET) is an important physical phenomenon which demands precise control over the FRET rate for its wide range of applications. Hence, enhancing the FRET rate using different techniques has been extensively studied in the literature. Research indicates that introducing additional particles to a system consisting of a donor-acceptor pair can change the behaviour of FRET in the system. One such technique is to utilize the collective oscillations of the surface electrons of a neighboring electrically-neutral metal nanoparticle (MNP). However, the perceived changes on the FRET rate between the donor and the acceptor, when the MNP carries excess electrical charges are yet unknown. In this paper, we study these changes by introducing a charged MNP, in the proximity of an excited donor and a ground state acceptor. We deploy the classical Green’s tensor to express the FRET rate in the system. We consider an effective dielectric response for the MNP, which accounts for the extraneous surface charge effects. We analyze the electrical potential at the acceptor position due to the changed dipole moment of the donor molecule as a result of the electric field induced at the donor position, and obtain the FRET rate of the system. This model considers arbitrary locations and orientations of the two molecular dipole moments with regard to the position of the spherical MNP. We present the enhancement of the FRET rate, predominantly caused by both the surface plasmon excitations and the extraneous surface electrical charges carried by the neighboring MNP. We obtain the results by varying the separation distance between the molecules and the MNP, the transition frequency of the donor-acceptor pair and the size of the metallic sphere. Specifically, we demonstrate that a donor-acceptor pair placed in the vicinity of an electrically-charged Silver MNP exhibits a remarkable improvement in the FRET rate. Furthermore, the aggregate FRET enhancement is determined by other characteristics such as the location of the donor, transition frequency, separation distances and the radius of the MNP. In essence, these findings reveal an approach to realize the enhanced FRET rate in a larger span in a more controlled manner that is desirable in many FRET-based applications including spectroscopic measurements.
Spirulina maxima L Asparaginase: Immobilization, Antiviral and antiproliferation activities.

BACKGROUND L-asparaginase (L-AsnA) enzyme has gained significant attention in the food, biocatalysts and pharmaceutics industry. It (L-AsnA) has been widely used in food processing industries as a promising acrylamide mitigating agent and as a therapeutic agent in the treatment of certain human cancers. OBJECTIVE Based on US Patent (4,433,054; 1984), the L-asparaginase (L-AsnA) enzyme is immobilized by admixing the active enzyme on the polysaccharide to be in a gel form [1]. The storage stability of immobilized L-AsnA enzyme and its anti-proliferation and antiviral activity were determined. METHODS In the present study, S. maxima was cultured at large scales (300 liter) for the production of enough extracellular L-asparaginase (L-AsnA) using modified (high N concentration) Zarrouk [2] medium as we reported in a previous study [3]. The L-AsnA was immobilized on natural polymers, as agar cake beads, agarose pieces and gelatin blocks, in order to evaluate the efficiency physical entrapment techniques. Anti-proliferation properties of L-AsnA against lung carcinoma A549, hepatocellular carcinoma Hep-G2 and prostate carcinoma PC3 human cancer cell lines was assessed by the MTT cell viability method. In addition, the antiviral activity against Coxsackie B3 (CSB3) Virus was assessed. RESULTS The highest L-AsnA immobilized activity and immobilization yield were achieved with agar cakes bead. The purified S. maxima L-AsnA showed a good antiviral activity against Coxsackie B3 (CSB3) Virus in a dose dependent manner with an IC50 value 17.03 µg/ml. The antiviral mode of action is presumably due to their capability of inhibiting attachment, blocking the adsorption and penetration event of the viral replication cycle with 89.24%, 72.78% and 72.78%, respectively. Also, S. maxima L-AsnA showed anti-proliferation effect against lung carcinoma A549, hepatocellular carcinoma Hep-G2 and prostate carcinoma PC3 human cancer cell lines, with an IC50 of 22.54, 24.65 and 56.61 µg/ml, respectively. CONCLUSION It is interesting to favor the L-asparaginase of S. maxima showed antiviral activity and anti-proliferation effect against different types of human cell lines. Thus, S. maxima microalgae might be a good source for L-AsnA enzymes and can be immobilized on natural polymers.
Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.
Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter?#

Abstract Purpose Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology. Materials and methods A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher’s exact test was used for categorical variables and the Kruskal–Wallis test was used for continuous variables. The level of significance was p<. 05. Results Of 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (p = .12). There were no differences in any of the maternal or obstetric outcomes including gestational age at delivery and mode of delivery between the groups. The primary outcome of neonatal respiratory distress was not statistically different between groups (p = .66). Median neonatal length of stay following delivery ranged from 3 to 4 days, and time to postnatal resection was similar as well, with a median of 126 days for CPAM type 1, 122 days for CPAM type 2, and 132 days for bronchopulmonary sequestration (p = .76). Conclusions In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.
A Novel Human Congenital Cataract Mutation in EPHA2 Kinase Domain (p.G668D) Alters Receptor Stability and Function.

Purpose To identify the genetic defect in a four-generation Chinese family that causes autosomal dominant congenital posterior subcapsular cataracts, and to understand how this EPHA2 kinase domain mutation affects EPHA2 activity. Methods Variants in 54 cataract-associated genes were screened by targeted next generation sequencing (NGS) and then validated by Sanger sequencing. EPHA2 wild-type cDNA was synthesized in vitro, and EPHA2 p.G668D mutant was constructed by PCR site-directed mutagenesis. Western blotting and fluorescence microscopy were used to analyze the expression level of protein and its subcellular localization, respectively. A wound-healing assay was performed to analyze changes to cell migration. Results A novel heterozygous missense mutation was identified in the kinase domain of the EPHA2 gene (c.2003G>A, p.G668D). This is the third congenital cataract mutation being reported in this domain. Functional study revealed that the kinase domain mutation (p.G668D) decreased EphA2 protein level (P = 0.036) via a proteasome-dependent pathway, altered its subcellular localization of the EphA2 from cell-cell contacts to a diffuse perimembranous distribution, and changed the distribution of β-catenin as well. The expression of mutant EphA2 significantly promoted the migration of human lens epithelial cells (P = 0.002). Conclusions Our study presented the evidence for a novel EPHA2 kinase domain mutation that causes congenital posterior subcapsular cataracts. The first functional study on an EPHA2 kinase domain mutation that causes a congenital cataract revealed that the G668D mutation destabilized the receptor, changed its subcellular localization, and altered the activation of EphA2 with its ligand ephrin. The mutant EphA2 resulted in a reduced inhibition of cell migration. As a consequence, the c.G668D mutation promoted cell migration and caused the formation of cataracts.
Training Characteristics of Male and Female Professional Road Cyclists: A 4-Year Retrospective Analysis.

PURPOSE To describe the training intensity and load characteristics of professional cyclists using a 4-year retrospective analysis. Particularly, this study aimed to describe the differences in training characteristics between men and women professional cyclists. METHOD For 4 consecutive years, training data were collected from 20 male and 10 female professional cyclists. From those training sessions, heart rate, rating of perceived exertion, and power output (PO) were analyzed. Training intensity distribution as time spent in different heart rate and PO zones was quantified. Training load was calculated using different metrics such as Training Stress Score, training impulse, and session rating of perceived exertion. Standardized effect size is reported as Cohen's d. RESULTS Small to large higher values were observed for distance, duration, kilojoules spent, and (relative) mean PO in men's training (d = 0.44-1.98). Furthermore, men spent more time in low-intensity zones (ie, zones 1 and 2) compared with women. Trivial differences in training load (ie, Training Stress Score and training impulse) were observed between men's and women's training (d = 0.07-0.12). However, load values expressed per kilometer were moderately (d = 0.67-0.76) higher in women compared with men's training. CONCLUSIONS Substantial differences in training characteristics exist between male and female professional cyclists. Particularly, it seems that female professional cyclists compensate their lower training volume, with a higher training intensity, in comparison with male professional cyclists.
A distinct class of eukaryotic MT-A70 methyltransferases maintain symmetric DNA N6-adenine methylation at the ApT dinucleotides as an epigenetic mark associated with transcription

Abstract Rediscovered as a potential eukaryotic epigenetic mark, DNA N6-adenine methylation (6mA) varies across species in abundance and its relationships with transcription. Here we characterize AMT1—representing a distinct MT-A70 family methyltransferase—in the ciliate Tetrahymena thermophila. AMT1 loss-of-function leads to severe defects in growth and development. Single Molecule, Real-Time (SMRT) sequencing reveals that AMT1 is required for the bulk of 6mA and all symmetric methylation at the ApT dinucleotides. The detection of hemi-methylated ApT sites suggests a semi-conservative mechanism for maintaining symmetric methylation. AMT1 affects expression of many genes; in particular, RAB46, encoding a Rab family GTPase involved in contractile vacuole function, is likely a direct target. The distribution of 6mA resembles H3K4 methylation and H2A.Z, two conserved epigenetic marks associated with RNA polymerase II transcription. Furthermore, strong 6mA and nucleosome positioning in wild-type cells is attenuated in ΔAMT1 cells. Our results support that AMT1-catalyzed 6mA is an integral part of the transcription-associated epigenetic landscape. AMT1 homologues are generally found in protists and basal fungi featuring ApT hyper-methylation associated with transcription, which are missing in animals, plants, and true fungi. This dichotomy of 6mA functions and the underlying molecular mechanisms may have implications in eukaryotic diversification.
Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL.

Pan and colleagues report one of the first prospective evaluations of planned sequential chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and then CD22 in a phase 1 trial, indicating acceptable toxicity and encouraging durable efficacy in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL).
Spirituality in heart failure: a review of the literature from 2014 to 2019 to identify spiritual care needs and spiritual interventions.

PURPOSE OF REVIEW The burden of heart failure is significant and its management is complex. Current evidence confirms a high level of spiritual distress and a strong desire for spiritual support, which is endorsed by healthcare policy, yet spiritual support is rarely provided for this patient group. There is a need to identify how spiritual support might be meaningfully included within holistic heart failure multidisciplinary care and how its effectiveness might be demonstrated. RECENT FINDINGS A literature review was undertaken to identify recent evidence (2014-2019) of the spiritual care needs of heart failure patients/carers and the nature and effectiveness of spiritual interventions in heart failure care. SUMMARY Taken as a whole, studies exploring heart failure patients'/carers' needs reflected the broad spectrum of spirituality as defined by international consensus, however, some studies focused on only some aspects of spirituality and on advanced disease. All studies were limited. No single spiritual intervention was identified as effective in enhancing quality of life in patients with heart failure. Life review and relaxation/meditation appeared ineffective. Interventions, which included elements of 'talking' about spiritual matters, 'spiritual coping' and those involving a holistic person-centred team approach to care of which spiritual care was an aspect, are worth investigating further in well designed randomized controlled trials.
PROSPECTIVE MONITORING OF DRUG USE: DRUG-INDUCED LIVER INJURY IN A PRIMARY HEALTHCARE CENTER.

BACKGROUND Drug-induced liver injury is still misunderstood in Brazil due to diagnostic difficulties or lack of reporting incidents. OBJECTIVE To assess the frequency of adverse events related to the use of medicines in a primary healthcare unit, in a city locate southwestern of the state of Bahia, Brazil. METHODS Prospective study conducted at the Primary Center for Specialized Health (CEMEA), February at August of 2013 in Vitoria da Conquista, Bahia, Brazil. Interviews were conducted with patients over 18 years old, and their clinical and laboratorial data were collected. The CIOMS scale was used to validate the cases. RESULTS A total of 149 patients, mainly Afro-Brazilian women, received follow-up. Among these patients, three cases of hepatotoxicity were identified, and the medicines associated to drug-induced liver injuries were: nimesulide, budesonide and valacyclovir. CONCLUSION Drug-induced liver injury is rare in primary healthcare units. It also allowed estimating the incidence of hepatotoxicity induced by allopathic medicines which are standardized by public healthcare authorities.
Characterisation of the developing heart in a pressure overloaded model utilising RNA sequencing to direct functional analysis

Cardiogenesis is influenced by both environmental and genetic factors, with blood flow playing a critical role in cardiac remodelling. Perturbation of any of these factors could lead to abnormal heart development and hence the formation of congenital heart defects. Although abnormal blood flow has been associated with a number of heart defects, the effects of abnormal pressure load on the developing heart gene expression profile have to date not clearly been defined. To determine the heart transcriptional response to haemodynamic alteration during development, outflow tract (OFT) banding was employed in the chick embryo at Hamburger and Hamilton stage (HH) 21. Stereological and expression studies, including the use of global expression analysis by RNA sequencing with an optimised procedure for effective globin depletion, were subsequently performed on HH29 OFT‐banded hearts and compared with sham control hearts, with further targeted expression investigations at HH35. The OFT‐banded hearts were found to have an abnormal morphology with a rounded appearance and left‐sided dilation in comparison with controls. Internal analysis showed they typically had a ventricular septal defect and reductions in the myocardial wall and trabeculae, with an increase in the lumen on the left side of the heart. There was also a significant reduction in apoptosis. The differentially expressed genes were found to be predominately involved in contraction, metabolism, apoptosis and neural development, suggesting a cardioprotective mechanism had been induced. Therefore, altered haemodynamics during development leads to left‐sided dilation and differential expression of genes that may be associated with stress and maintaining cardiac output.
Semisupervised Bayesian Gaussian Mixture Models for Non-Gaussian Soft Sensor

Soft sensors have been widely accepted for online estimating key quality-related variables in industrial processes. The Gaussian mixture models (GMM) is one of the most popular soft sensing methods for the non-Gaussian industrial processes. However, in industrial applications, the quantity of samples with known labels is usually quite limited because of the technical limitations or economical reasons. Traditional GMM-based soft sensor models solely depending on labeled samples may easily suffer from singular covariances, overfitting, and difficulties in model selection, which results in the performance deterioration. To tackle these issues, we propose a semisupervised Bayesian GMM (S2BGMM). In the S2BGMM, we first propose a semisupervised fully Bayesian model, which enables learning from both the labeled and unlabeled datasets for remedying the deficiency of infrequent labeled samples. Subsequently, a general framework of weighted variational inference is developed to train the S2BGMM, such that the rate of learning from unlabeled samples can be controlled by penalizing the unlabeled dataset. Case studies are carried out to evaluate the performance of the S2BGMM through a numerical example and two real-world industrial processes, which demonstrate the effectiveness and reliability of the proposed approach.
Sox9 overexpression exerts multiple stage‐dependent effects on mouse spinal cord development

The high‐mobility‐group (HMG)‐domain protein Sox9 is one of few transcription factors implicated in gliogenesis in the vertebrate central nervous system. To further study the role of Sox9 in early spinal cord development, we generated a mouse that allows expression of Sox9 in a temporally and spatially controlled manner. Using this mouse, we show that premature Sox9 expression in neural precursor cells disrupted the neuroepithelium of the ventricular zone. Sox9 also compromised development and survival of neuronal precursors and neurons. Additionally, we observed in these mice substantial increases in oligodendroglial and astroglial cells. Reversing the normal order of appearance of essential transcriptional regulators during oligodendrogenesis, Sox10 preceded Olig2. Our study reinforces the notion that Sox9 has a strong gliogenic activity. It also argues that Sox9 expression has to be tightly controlled to prevent negative effects on early spinal cord structure and neuronal development.