Miracle-dz/UniFAR-FTUs huggingface dataset:
Pig‐a gene mutations in bone marrow granulocytes of procarbazine‐treated F344 rats

It was previously demonstrated that procarbazine (PCZ) is positive in the rat erythrocyte Pig‐a gene mutation assay. However, since mammalian erythrocytes lack genomic DNA, it was necessary to analyze nucleated bone‐marrow erythroid precursor cells to confirm that PCZ induces mutations in the Pig‐a gene (Revollo et al., Environ Mol Mutagen, 2020). In this study, the association between Pig‐a mutation and loss of GPI anchors was further strengthened and the genesis of Pig‐a mutation in PCZ‐dosed rats was evaluated by analyzing bone‐marrow granulocytes. Erythrocytes and granulocytes both originate from myeloid progenitor cells, but granulocytes contain DNA throughout their developmental stages. F344 rats were treated with three doses of 150 mg/kg PCZ; 2 weeks later, CD48‐deficient mutant phenotype bone‐marrow granulocytes (BMGs [CD11b+]) were isolated by flow‐cytometric sorting. Sequencing data showed that the CD48‐deficient mutant phenotype BMGs contained mutations in the Pig‐a gene while wild‐type BMGs did not. PCZ‐induced mutations included missense, nonsense and splice site variants; the majority of mutations were A > T, A > C, and A > G, with the mutated A on the nontranscribed DNA strand. The PCZ‐induced mutational analysis in BMGs supports the association between the phenotype measured in the Pig‐a assay and mutation in the Pig‐a gene. Also, PCZ mutation spectra were similar in bone‐marrow erythroids and BMGs, but none of the mutations detected in BMGs were the same as the erythroid precursor cell mutations from the same rats. Thus, mutations induced in the Pig‐a assay appear to be induced after commitment of myeloid progenitor cells to either the granulocyte or erythroid pathway.
Imperative role of glycosylation in human MOG-HLA interaction: molecular insights of MOG-Ab associated demyelination

Abstract Myelin oligodendrocyte glycoprotein is a transmembrane protein found on the outer lamella of the myelin sheath. The autoimmune attack on the MOG leads to demyelination which differs from normal multiple sclerosis. MOG has three epitope regions MOG1–22, MOG35–55, and MOG92–106 in the extracellular region, and the crucial MOG35–55 epitope and Human Leukocyte Antigen (HLA) interaction is the initial step for autoantibody generation. To study the effective role of glycosylation in MOG-HLA interaction, we performed molecular dynamics simulations of the complex where HLA interacts with three MOG epitopes both in the absence and presence of glycan. The results projected that the epitope MOG1–22 is decisive for the HLA interaction in the absence of glycan and HLA interacts with the epitope MOG35–55 irrespective of glycan existence. The residues Arg9, Arg46, and Arg66 were found to interact strongly with HLA even in the presence of glycan. The glycan increased the flexibility of hMOG and enhanced the interaction of MOG with water molecules. Graphical Abstract Communicated by Ramaswamy H. Sarma
Does the Starting of Clozapine Influence Coprescription of Other Medications?

Abstract Purpose/Background Little is understood about the prescription load before and after the starting of clozapine. Accordingly, this study aimed to evaluate the medication load of patients receiving clozapine, just before starting clozapine and after being on clozapine for at least 1 year. Additionally, the impact of clozapine on severity of illness was evaluated. Methods/Procedures Two hundred seventy-seven outpatients receiving clozapine were prospectively evaluated for their prescription after at least 1 year of starting clozapine. Additionally, these patients were assessed on the Clinical Global Impression-Improvement scale to evaluate the overall clinical benefit with clozapine. Findings/Results They had been receiving clozapine for 6.55 (SD, 4.8; range, 1–24; median, 5) years at the time of assessment. At the start of clozapine, more than one third of the patients were receiving 2 antipsychotics. A small proportion was receiving other psychotropics, such as antidepressants, mood stabilizers, and benzodiazepines. After being on clozapine for 1 year, there was a significant reduction in the number of patients receiving two antipsychotic medications (P < 0.001), number of patients receiving antidepressants (if amitriptyline was left out), benzodiazepine (P < 0.001), and anticholinergic medications (P < 0.001). Further, there was a reduction in the mean chlorpromazine equivalent of antipsychotics (P < 0.001) and the total number of medications received by the patients (P < 0.001). However, there was an increase in the prescription rates of antihypertensive drugs (P = 0.03), anti-diabetic medications (P < 0.01), and anti-dyslipidemic medications. At follow-up, there was a significant improvement in symptoms as assessed by Clinical Global Impression-Improvement scale. Implications/Conclusions This study suggests that long-term use of clozapine is associated with substantial improvement in symptoms with a reduction in the medication load.
Do Outcomes between Women and Men Differ after Endovascular Thrombectomy? A Meta-analysis

BACKGROUND: Research on the presence of sex-based differences in the outcomes of patients undergoing endovascular thrombectomy for acute ischemic stroke has reached differing conclusions. PURPOSE: This review aimed to determine whether sex influences the outcome of patients with large-vessel occlusion stroke undergoing endovascular thrombectomy. STUDY SELECTION: We performed a systematic review and meta-analysis of endovascular thrombectomy studies with either stratified cohort outcomes according to sex (females versus males) or effect size reported for the consequence of sex versus outcomes. We included 33 articles with 7335 patients. DATA ANALYSIS: We pooled ORs for the 90-day mRS score, 90-day mortality, symptomatic intracranial hemorrhage, and recanalization. DATA SYNTHESIS: Pooled 90-day good outcomes (mRS ≤ 2) were better for men than women (OR = 1.29; 95% CI, 1.09–1.53; P = <.001, I2 = 56.95%). The odds of the other outcomes, recanalization (OR = 0.94; 95% CI, 0.77–1.15; P = .38, I2 = 0%), 90-day mortality (OR = 1.11; 95% CI, 0.89–1.38; P = .093, I2 = 0%), and symptomatic intracranial hemorrhage (OR = 1.40; 95% CI, 0.99–1.99; P = .069, I2 = 0%) were comparable between men and women. LIMITATIONS: Moderate heterogeneity was found. Most studies included were retrospective in nature. In addition, the randomized trials included were not specifically designed to compare outcomes between sexes. CONCLUSIONS: Women undergoing endovascular thrombectomy for large-vessel occlusion have inferior 90-day clinical outcomes. Sex-specific outcomes should be investigated further in future trials as well as pathophysiologic studies.
EUS-FNA biopsy of parathyroid gland

Ultrasound examination of the neck followed by fine needle aspiration (FNA) biopsy is one of the methods for detecting and diagnosing parathyroid gland lesions. Among parathyroid lesions, there are solitary adenomas, multiple gland hyperplasia decease, double adenomas, carcinomas, etc.[1] However, traditional FNA is not always possible because of difficulties in visualization and access (the location of the lesion behind the thyroid gland, large vessels, cartilage, and bone structures together with such conditions as multinodular goiter, lymph nodes, fibrosis, and other tumors of the neck). [2,3]
Characterization and trypanocidal activity of a β-lapachone-containing drug carrier

The treatment of Chagas disease (CD), a neglected parasitic condition caused by Trypanosoma cruzi, is still based on only two drugs, nifurtimox (Nif) and benznidazole (Bz), both of which have limited efficacy in the late chronic phase and induce severe side effects. This scenario justifies the continuous search for alternative drugs, and in this context, the natural naphthoquinone β-lapachone (β-Lap) and its derivatives have demonstrated important trypanocidal activities. Unfortunately, the decrease in trypanocidal activity in the blood, high toxicity to mammalian cells and low water solubility of β-Lap limit its systemic administration and, consequently, clinical applications. For this reason, carriers as drug delivery systems can strategically maximize the therapeutic effects of this drug, overcoming the above mentioned restrictions. Accordingly, the aim of this study is to investigate the in vitro anti-T. cruzi effects of β-Lap encapsulated in2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) and its potential toxicity to mammalian cells.
Polysubstance use and adherence to antiretroviral treatment in the Miami Adult Studies on HIV (MASH) cohort

ABSTRACT Evidence for a relationship between polysubstance use, depression, and adherence to antiretroviral therapy (ART) is limited. The objectives of this study were to examine the associations of depression, illicit drug, and alcohol use with adherence to ART. People living with HIV (PLHIV) from the Miami Adult Studies on HIV cohort were asked about the number of doses of their ART medication missed to assess ART adherence. Harmful alcohol drinking was evaluated using the Alcohol Use Disorders Identification Test and illicit substance use assessed with self-report and urine screen. The Center for Epidemiologic Studies Depression Scale was used to assess depression symptoms. Of 391 PLHIV, 16.6% missed at least one dose (range:1–4) in the past four days. Cocaine/crack, opiate use, and depression were significantly independently associated with a greater mean number of doses missed. The mean number of doses missed was significantly greater among participants who used alcohol in combination with cocaine/crack, marijuana, and tobacco compared to non-users. In conclusion, polysubstance use increased the risk for poor ART adherence among PLHIV. The use of cocaine/crack or opiates individually and depressive symptoms also promote poor ART adherence. An integrated approach targeting substance disorders and depression may help achieve better ART adherence.
The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients’ response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients’ samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients’ samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients’ samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.
On-block mechanistic determinants of start performance in high performance swimmers.

This study aimed to 1) identify what starting block outcome kinetics have the greatest relationship to 15 m start time; 2) investigate key mechanistic determinants of the block phase and how these forces are sequenced. One hundred and fifty-two high-level competitive swimmers were included in the study. Linear mixed modelling identified four on-block outcome kinetic variables (work, average power, horizontal take-off velocity (HTOV), and average acceleration) as having a very large relationship (R2 = 0.79-0.83) to 15 m start time, with average power having the most substantial impact. On-block force sequencing started with the rear leg, followed by upper limb grab forces and the front leg. Further exploration of underlying determinants was performed for average power and HTOV of the centre of mass. Multiple linear regression identified grab resultant peak force, rear resultant average force, front horizontal peak force, and resultant peak force as significant predictors of average power (R2 = 0.88). HTOV was predicted using the same variables, apart from the inclusion of rear horizontal peak force instead of rear resultant average force (R2 = 0.73). These findings may influence how strength and conditioning and skill acquisition interventions are designed to improve swim start performance.
Dynamic perceptive compensation for the rotating snakes illusion with eye tracking

This study developed a dynamic perceptive compensation system for the rotating snakes illusion (RSI) with eye tracking. Large eye movements, such as saccades and blinks, were detected with an eye tracker, and perceptive compensation was dynamically performed based on the characteristics of RSI perception. The proposed compensation system considered three properties: spatial dependence, temporal dependence, and individual dependence. Several psychophysical experiments were performed to confirm the effectiveness of the proposed system. After the preliminary verification and determination of the temporal-dependent function for RSI perception, the effects of gaze information on RSI control were investigated. Five algorithms were compared using paired comparison. This confirmed that the compensation system that took gaze information into account reduced the RSI effect better than compensation without gaze information at a significance threshold of p < 0.01, calculated with Bonferroni correction. Some algorithms that are dependent on gaze information reduced the RSI effects more stably than still RSI images, whereas spatially and temporally dependent compensation had a lower score than other compensation algorithms based on gaze information. The developed system and algorithm successfully controlled RSI perception in relation to gaze information. This study systematically handled gaze measurement, image manipulation, and compensation of illusory image, and can be utilized as a standard framework for the study of optical illusions in engineering fields.
Comparison of chronic kidney disease trial designs and analysis strategies

Background Despite the large burden of chronic kidney disease (CKD), it is challenging to conduct adequately powered clinical trials in this setting. Sound and efficient trials are needed to advance treatment. Various analysis strategies can be used to compare the efficacy of a parallel trial design with that of three two period trial designs. Methods The type 1 error rates and powers of various trial designs were calculated using simulated data from models fit to two recent CKD trials. In addition, we assessed the influences of a variety of analysis strategies and of the presence of a carryover effect. Results The parallel and crossover designs (with analysis of change from baseline to the off treatment value) maintained the target type 1 error rate in all scenarios. In some scenarios, an open label design yielded inflated type 1 error rates. In many scenarios, the open label and delayed start designs had unacceptably low power and high type 1 error rates. Overall, the crossover design had the highest power by far, and always controlled the type 1 error rate. Conclusion The recommended approach to a CKD trial is a two period design with an endpoint that is the rate of change in estimated glomerular filtration rate from pretreatment to off treatment. As compared to a parallel trial, a crossover study involves a considerably smaller sample size and shorter total follow-up duration. A crossover design may also be preferable for patients, and facilitates recruitment of a sufficient number of subjects.
Design of facile technology for the efficient removal of hydroxypropyl guar gum from fracturing fluid

With the increasing demand for energy, fracturing technology is widely used in oilfield operations over the last decades. Typically, fracturing fluids contain various additives such as cross linkers, thickeners and proppants, and so forth, which makes it possess the properties of considerably complicated components and difficult processing procedure. There are still some difficult points needing to be explored and resolved in the hydroxypropyl guar gum (HPG) removal process, e.g., high viscosity and removal of macromolecular organic compounds. Our works provided a facile and economical HPG removal technology for fracturing fluids by designing a series of processes including gel-breaking, coagulation and precipitation according to the diffusion double layer theory. After this treatment process, the fracturing fluid can meet the requirements of reinjection, and the whole process was environment friendly without secondary pollution characteristics. In this work, the fracturing fluid were characterized by scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), X-ray diffraction (XRD) and Fourier transformed infrared (FTIR) spectroscopy technologies, etc. Further, the micro-stabilization and destabilization mechanisms of HPG in fracturing fluid were carefully investigated. This study maybe opens up new perspective for HPG removal technologies, exhibiting a low cost and strong applicability in both fundamental research and practical applications.
An investigation of the aroma fraction of some Italian wines by solid phase micro extraction gas chromatography mass spectrometry and membrane inlet mass spectrometry

Two analytical approaches have been applied to the characterization of the aroma fraction of five Italian wines, solid-phase micro-extraction coupled with gas chromatography, and membrane inlet mass spectrometry. The first approach resulted in highly specific and reproducible data and permitted the differentiation among wine samples from the same grape but from different production areas. The second technique, notable for its short time of analysis and ease of use, exhibited a lower specificity. © 1998 John Wiley & Sons, Ltd.
SUMOylation promotes extracellular vesicle-mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer.

SUMOylation emerged as the inducer for the sorting of bioactive molecules into extracellular vesicles (EVs) triggering lymphangiogenesis, further driving tumor lymph node (LN) metastasis, but the precise mechanisms remain largely unclear. Herein, we identified that bladder cancer (BCa) cell-secreted EVs mediated the intercellular communication with human lymphatic endothelial cells (HLECs) through the transmission of a long noncoding RNA ELNAT1, and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models. Mechanistically, ELNAT1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1 at lysine-113 residue, which mediated the recognition of ELNAT1 by endosomal sorting complex required for transport (ESCRT) and facilitated their packaging into EVs. EV-mediated ELNAT1 was specifically transmitted into HLECs and epigenetically activated SOX18 transcription to induce lymphangiogenesis. Importantly, blocking the SUMOylation of tumor by downregulating UBC9 expression markedly reduced lymphatic metastasis in EV-mediated ELNAT1-treated BCa in vivo. Clinically, EV-mediated ELNAT1 was correlated with LN metastasis and poor prognosis of patients with BCa. These findings highlight a molecular mechanism that EV-mediated ELNAT1/UBC9/SOX18 regulatory axis promotes the lymphangiogenesis and LN metastasis of BCa in a SUMOylation-dependent manner, and implicate ELNAT1 as an attractive therapeutic target for LN metastatic BCa.
Chronic respiratory failure in bronchopulmonary dysplasia

Although survival has improved dramatically for extremely preterm infants, those with the most severe forms of bronchopulmonary dysplasia (BPD) fail to improve in the neonatal period and go on to develop chronic respiratory failure. When careful weaning of respiratory support is not tolerated, the difficult decision of whether or not to pursue chronic ventilation via tracheostomy must be made. This requires shared decision‐making with an interdisciplinary medical team and the child's family. Although they suffer from increased morbidity and mortality, the majority of these children will survive to tolerate ventilator liberation and tracheostomy decannulation. Care coordination for the technology‐dependent preterm infant is complex, but there is a growing consensus that chronic ventilation can best support neurodevelopmental progress and improve long‐term outcomes.
Identifying neural signatures of tobacco retail outlet exposure: Preliminary validation of a “community neuroscience” paradigm

An extensive epidemiological literature indicates that increased exposure to tobacco retail outlets (TROs) places never smokers at greater risk for smoking uptake and current smokers at greater risk for increased consumption and smoking relapse. Yet research into the mechanisms underlying this effect has been limited. This preliminary study represents the first effort to examine the neurobiological consequences of exposure to personally relevant TROs among both smokers (n = 17) and nonsmokers (n = 17). Individuals carried a global positioning system (GPS) tracker for 2 weeks. Traces were used to identify TROs and control outlets that fell inside and outside their ideographically defined activity space. Participants underwent functional MRI (fMRI) scanning during which they were presented with images of these storefronts, along with similar store images from a different county and rated their familiarity with these stores. The main effect of activity space was additive with a Smoking status × Store type interaction, resulting in smokers exhibiting greater neural activation to TROs falling inside activity space within the parahippocampus, precuneus, medial prefrontal cortex, and dorsal anterior insula. A similar pattern was observed for familiarity ratings. Together, these preliminary findings suggest that the otherwise distinct neural systems involved in self‐orientation/self‐relevance and smoking motivation may act in concert and underlie TRO influence on smoking behavior. This study also offers a novel methodological framework for evaluating the influence of community features on neural activity that can be readily adapted to study other health behaviors.
Chemical Development of CI-1008, an Enantiomerically Pure Anticonvulsant

Development of a manufacturing process for (S)-3-(aminomethyl)-5-methylhexanoic acid, an anticonvulsant, is described. Initial preparation employed an Evans chiral alkylation on (4R,5S)-4-methyl-3-(1-oxo-4-methylpentyl)-5-phenyl-2-oxazolidinone, using benzyl bromoacetate. Use of tert-butyl bromoacetate proved advantageous for large-scale preparation. Route selection for a low-cost manufacturing process was based on “ideal process” cost projections. Four routes were evaluated in the laboratory. Of the four, two were scaled up in the pilot plant, resulting in selection of a route based on synthesis of racemic 3-(aminomethyl)-5-methylhexanoic acid, followed by resolution with (S)-(+)-mandelic acid.