Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of DNA replication initiation by silver nanoclusters

Abstract Silver nanoclusters (AgNCs) have outstanding physicochemical characteristics, including the ability to interact with proteins and DNA. Given the growing number of diagnostic and therapeutic applications of AgNCs, we evaluated the impact of AgNCs on DNA replication and DNA damage response in cell-free extracts prepared from unfertilized Xenopus laevis eggs. We find that, among a number of silver nanomaterials, AgNCs uniquely inhibited genomic DNA replication and abrogated the DNA replication checkpoint in cell-free extracts. AgNCs did not affect nuclear membrane or nucleosome assembly. AgNCs-supplemented extracts showed a strong defect in the loading of the mini chromosome maintenance (MCM) protein complex, the helicase that unwinds DNA ahead of replication forks. FLAG-AgNCs immunoprecipitation and mass spectrometry analysis of AgNCs associated proteins demonstrated direct interaction between MCM and AgNCs. Our studies indicate that AgNCs directly prevent the loading of MCM, blocking pre-replication complex (pre-RC) assembly and subsequent DNA replication initiation. Collectively, our findings broaden the scope of silver nanomaterials experimental applications, establishing AgNCs as a novel tool to study chromosomal DNA replication.
Does gallbladder wall thickness measurement predict esophageal varices in cirrhotic patients with portal hypertension?

Background and study aim Endoscopy is the gold standard investigation for diagnosis of gastroesophageal varices (GOVs), yet it is invasive, associated with complications. Many noninvasive parameters were investigated to predict the presence of GOVs. The current study investigated gallbladder wall thickening (GBWT) measurement as a noninvasive predictor of GOVs in posthepatitic cirrhotic patients with portal hypertension. Patients and methods In this cross-sectional study, 105 cirrhotic patients were divided into, group I and II according to the presence or absence of GOVs, respectively. Group I subdivided into, groups A and B according to the grade of GOVs either nonadvanced (grades I and II) or advanced (grades III and IV), respectively. Complete history taking, full clinical examination, full investigations, upper endoscopy and abdominal ultrasonography were performed to examine all patients. Results Both groups were comparable in their baseline characteristics except for AST to Platelet Ratio Index and Fibrosis-4 scores, which were significantly higher in group I. GBWT, portal vein diameter and spleen length were significantly associated not only with GOVs but also with its advanced grades. GBWT at a cutoff level >3.1 mm can predict the presence of GOVs with 54.29% sensitivity, 97.14% specificity, 97.4% positive predictive value (PPV), 51.5% negative predictive value (NPV) and 68.5% accuracy. GBWT can predict advanced grades of GOVs at a cutoff level >3.5 mm, with 45% sensitivity, 90% specificity, 64.3% PPV, 80.4% NPV and 77.1% accuracy. Conclusion GBWT was associated with the presence of GOVs, and with advanced GOVs in posthepatitis cirrhotic patients with portal hypertension.
Confirmatory factor analysis and psychometric properties of the Emotion Regulation Questionnaire in participants with personality disorders.

Emotional dysregulation is a key symptom in participants with personality disorders. The Emotional Regulation Questionnaire (ERQ) has been studied with non-clinical samples; however, it is necessary to confirm the factorial structure of the ERQ in participants with personality disorders. The aims of the present study were to confirm the factorial structure of the Spanish version of the ERQ and analyze its psychometric properties as well as the association between the ERQ and the Borderline Symptoms List (BSL-23) and the Difficulties in Emotion Regulation Scale (DERS). The overall sample was composed of 250 patients with personality disorders, of whom 195 met the criteria for borderline personality disorder. Confirmatory Factor Analysis was conducted. The two-factor model showed an acceptable fit, similar to the original structure, in the participants with personality disorders and with borderline personality disorder. Cognitive reappraisal was negatively correlated with the DERS and BSL-23, and expressive suppression was positively correlated with the BSL-23. The ERQ is a reliable and valid instrument to evaluate emotional dysregulation in participants with personality disorders and participants with borderline personality disorder.
How clarification systems can affect virgin olive oil composition and quality at industrial scale

The effect of two different clarification systems, vertical centrifugal separator (VCS) with minimal water addition, and conical bottom settling tank (CBST), on virgin olive oil (VOO) composition and quality was studied at industrial scale for three crop years. In general, for the studied clarification systems, higher clarification values were reached for horizontal screw solid bowl (HSSB) oils with higher moisture and solid content. VCS showed higher clarification efficiency for HSSB oils with higher moisture and solid content. No notable differences were observed on the quality indices between evaluated clarification systems. Phenolic compounds showed a significant decrease when the HSSB oils were clarified by CBST. In general, a better sensory score was observed when the oils were clarified by VCS. Practical applications: The VCS with a minimal water addition could result a better option to produce VOO of improved quality, since is an efficient and quick operation that reduces the contact between oil and the remaining water and impurities content during the storage stage. This leads to prolong VOO shelf‐life and conservation of positive sensory notes, due to preservation of the quality indexes and minor components. Besides, this clarification system reduces the water consumption and generated wastewater regarding to conventional vertical centrifugation, and therefore can be considered more environmentally friendly. Effect of two different clarification systems (vertical centrifugal separator with minimal water addition and conical bottom settling tanks) on the virgin olive oil quality parameters, composition, and sensory characteristics.
Microscopic techniques to evaluate the biofilm formation ability of a marine bacterium Pseudomonas aeruginosa PFL‐P1 on different substrata

Biofilm formation in bacteria is strongly affected by the nature of substrata. Different substrata such as glass, polystyrene, steel, ceramic, and rubber were used to assess the biofilm forming ability of a marine bacterium Pseudomonas aeruginosa PFL‐P1 using a scanning electron microscope (SEM), atomic force microscope (AFM), and confocal laser scanning microscope (CLSM). The bacterium formed dense biofilms with varied aggregation on different substrata. SEM study revealed small rod‐shaped cells with diverse arrangements within the biofilms on all the substrata under study. The AFM study revealed the highest roughness of 545 nm on the ceramic substratum. The biofilms formed on ceramic substratum were characterized with maximum roughness (742 nm), maximum peak height (1,480 nm), and maximum arithmetic mean height (611 nm), significantly higher than all the other substrata (p < .05). AFM studies confirmed that P. aeruginosa PFL‐P1 exhibited biofilm heterogeneity on all the substrata. The CLSM study indicated a higher fraction of nucleic acids to α‐polysaccharides ratio in the biofilms. COMSTAT analysis revealed the highest biofilm biomass of ~18 μm3/μm2 on the ceramic substratum. The maximum biofilm thickness of ~50 μm in the native state on the ceramic substratum was significantly higher than glass (p = .0015), polystyrene (p = .0001), steel (p = .0035), and rubber substrata (p = .0001). The higher surface roughness of ceramic substratum is accountable for more area for colonization, as evident from higher biomass and thickness of the biofilm. This study provides insight into the substratum properties, which modulate the biofilm forming ability in bacteria.
18F‐2‐fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography metabolic pattern assessment in the brain of betel quid dependent individuals

The primary objective of this study was to identify the metabolic pattern in the brains of betel quid dependent (BQD) individuals using 18F‐2‐fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography (18F‐FDG‐PET). A total of 42 individuals (16 BQD individuals and 26 healthy controls, HCs) enrolled at the Department of Nuclear Medicine of Xiangya Hospital underwent brain 18F‐FDG‐PET. Group comparisons using statistical parametric mapping (SPM) were performed to identify the 18F‐FDG‐PET patterns. Standardized uptake value ratios of anterior cingulate, frontal, thalamus, parietal, occipital, temporal and cerebellum were calculated by SPM. The characteristics of abnormal metabolism in brain regions were quantified using the xjView toolbox, and a 3‐D brain map was drawn using BrainNet Viewer. We found significant metabolic reduction in the bilateral middle prefrontal cortex (PFC) and the left orbital frontal gyrus (OFC). In contrast, hypermetabolism was observed in the inferior cerebellum, fusiform, superior cerebellum, parahippocampal, vermis, lingual and thalamus. However, we found no significant difference between the BQD and HC group in the anterior cingulate, thalamus, cerebellum and frontal, temporal, parietal and occipital lobes. In summary, we found abnormal 18F‐FDG‐PET metabolic pattern in BQD individuals, and this pattern may help the treatment of BQD.
Blood–brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses

Significance Disruption of the blood–brain barrier (BBB) for drug delivery to the central nervous system (CNS) is achieved clinically through intracarotid artery hyperosmotic mannitol (ICAHM) infusions. However, ICAHM is often viewed as a simple drug delivery mechanism, and biological implications have been largely overlooked. This study demonstrates that BBB disruption by ICAHM generates a transient sterile neuroinflammatory response marked by increased production of cytokines, chemokines, and trophic factors leading activation of astrocytes, microglia, and macrophages. Additionally, unilateral ICAHM generates plasma increases in inflammatory molecules with evidence of sterile inflammation on the untreated contralateral hemisphere. These biological responses to ICAHM suggest its potential for immune modulation in several CNS pathologies. Intracarotid arterial hyperosmolar mannitol (ICAHM) blood–brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown. Temporal proteomic changes in rat brains following ICAHM included increased damage-associated molecular patterns, cytokines, chemokines, trophic factors, and cell adhesion molecules, indicative of a sterile inflammatory response (SIR). Proteomic changes occurred within 5 min of ICAHM infusion and returned to baseline by 96 h. Transcriptomic analyses following ICAHM BBBD further supported an SIR. Immunohistochemistry revealed activated astrocytes, microglia, and macrophages. Moreover, proinflammatory proteins were elevated in serum, and proteomic and histological findings from the contralateral hemisphere demonstrated a less pronounced SIR, suggesting neuroinflammation beyond regions of ICAHM infusion. Collectively, these results demonstrate ICAHM induces a transient SIR that could potentially be harnessed for neuroimmunomodulation.
Mapping autonomic, mood, and cognitive effects of hypothalamic region deep brain stimulation.

Due to its involvement in a wide variety of cardiovascular, metabolic, and behavioral functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequalae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied at multiple international centers 58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation - including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear - were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic gray- and white-matter structures. K-nearest neighbor classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves (AUROC) between 0.67 - 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.
Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes following pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years old with mild TBI (n = 143) versus children with orthopedic injuries (OI; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = .018); the magnitude of group differences declined modestly over time (group X time interaction, p = .055). Effect sizes were d = . 34 at 10 days post-injury, d = . 27 at 3 months, and d = . 10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was due largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.
The effect of brown rice compared to white rice on adiposity indices, lipid profile, and glycemic markers: a systematic review and meta-analysis of randomized controlled trials

Abstract A few randomized controlled trials (RCTs) have assessed the effect of brown rice consumption on metabolic parameters compared to white rice, with inconsistent findings. Therefore, the present systematic review and meta-analysis was designed to evaluate the effect of brown rice on adiposity indices, lipid profile, and glycemic markers in adult subjects compared to white rice. In this study, PubMed/Medline, Scopus, Web of Sciences, and Embase databases were comprehensively searched until March 2021. Thirteen RCTs were selected and then included in the meta-analysis. As reported, brown rice significantly reduced weight by −1.63 kg (95% CI: −2.15 to −1.11, I2 =97%, n = 6), body mass index (BMI) by −0.58 kg/m2 (95% CI: −0.78 to −0.37, I2 =96%, n = 6), and waist circumference by −2.56 cm (95% CI: −4.86 to −0.26, I2 =88%, n = 5) compared with white rice. Moreover, it had no significant effect on lipid profile and glycemic markers. Besides, pre-germinated brown rice significantly declined weight (-1.75 kg, 95% CI: −2.70 to −0.81, I2 =99%, n = 4), total cholesterol (-24.22 mg/dl, 95% CI: −33.03 to −15.41, I2 =78%, n = 5), triglyceride (TG) (-43.28 mg/dl, 95% CI: −74.05 to −12.50, I2 =90%, n = 5), low-density lipoprotein (LDL) (-20.05 mg/dl, 95% CI: −29.57 to −10.52, I2 =71%, n = 5), and fasting blood glucose (FBG) (-15.83 mg/dl, 95% CI: −25.20 to −6.46, I2 =91%, n = 5). In accordance with Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the certainly of the included evidence was low and very low. The results of the present study indicate that, brown rice has anti-obesity effects in comparison with white rice; however, it has no beneficial effects on lipid profile and glycemic markers. Contrary to brown rice, it was shown that, pre-germinated brown rice significantly decreases body weight and improves lipid profile and FBG levels compared to white rice. Accordingly, our results indicate that, pre-germinated brown rice has better functional effects on promoting lipid profile and FBG compared to brown rice.
Physicochemical Variation in Nanogold-Based Ayurved Medicine Suvarna Bhasma Produced by Various Manufacturers Lead to Different In Vivo Bioaccumulation Profiles

Suvarna Bhasma (SB) is a gold particle-based medicine that is used in Ayurved to treat tuberculosis, arthritis and nervous diseases. Traditionally, the Ayurved preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary Ayurved processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (Cmax), half-life (t1/2) and terminal elimination slope (λz) for all the 5 SB preparations. SB-B showed the highest Cmax (8.55 μg/L), whereas SB-D showed the lowest Cmax (4.66 μg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned Ayurved references.
Dexmedetomidine as an adjunctive analgaesic in the perioperative setting: A review of the literature

Though arguably past the initial phase of the opioid epidemic, opioid-sparing or opioid-eliminating pain management regimens remain beneficial for patients and practitioners alike. Providing adequate analgaesia without relying on opioids is especially advantageous in the operative setting, as patients may be able to recover without deep levels of sedation or the need for a high amount of opioid medications. Despite being used primarily as a sedative over the past 20 years, dexmedetomidine, a centrally acting alpha2-agonist, possesses analgaesic properties, though its use has been limited by its well-described cardiovascular suppressive effects. The objective of this review was to determine the efficacy and safety of adjunctive dexmedetomidine for the purposes of analgaesia in the perioperative setting.
Natural Language Processing Performance for the Identification of Venous Thromboembolism in an Integrated Healthcare System

Real-time identification of venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) and pulmonary embolism (PE), can inform a healthcare organization’s understanding of these events and be used to improve care. In a former publication, we reported the performance of an electronic medical record (EMR) interrogation tool that employs natural language processing (NLP) of imaging studies for the diagnosis of venous thromboembolism. Because we transitioned from the legacy electronic medical record to the Cerner product, iCentra, we now report the operating characteristics of the NLP EMR interrogation tool in the new EMR environment. Two hundred randomly selected patient encounters for which the imaging report assessed by NLP that revealed VTE was present were reviewed. These included one hundred imaging studies for which PE was identified. These included computed tomography pulmonary angiography—CTPA, ventilation perfusion—V/Q scan, and CT angiography of the chest/ abdomen/pelvis. One hundred randomly selected comprehensive ultrasound (CUS) that identified DVT were also obtained. For comparison, one hundred patient encounters in which PE was suspected and imaging was negative for PE (CTPA or V/Q) and 100 cases of suspected DVT with negative CUS as reported by NLP were also selected. Manual chart review of the 400 charts was performed and we report the sensitivity, specificity, positive and negative predictive values of NLP compared with manual chart review. NLP and manual review agreed on the presence of PE in 99 of 100 cases, the presence of DVT in 96 of 100 cases, the absence of PE in 99 of 100 cases and the absence of DVT in all 100 cases. When compared with manual chart review, NLP interrogation of CUS, CTPA, CT angiography of the chest, and V/Q scan yielded a sensitivity = 93.3%, specificity = 99.6%, positive predictive value = 97.1%, and negative predictive value = 99%.