Miracle-dz/UniFAR-FTUs huggingface dataset:
A molecular hybrid comprising AS1411 and PDGF‐BB aptamer, cholesterol, and doxorubicin for inhibiting proliferation of SW480 cells

Cancer treatment commonly relies on chemotherapy. This treatment faces many challenges, including treatment specificity and undesired side effects. To address these, a Dox‐loaded Chol–aptamer molecular hybrid (Dox‐CAH) was developed. This multivalent interaction system combines the key function of each integrated species: doxorubicin, cholesterol, and two aptamers binding to nucleolin and platelet‐derived growth factor BB (PDGF‐BB). The study has four stages: preparation of CAH via oligonucleotide hybridization, intercalation of doxorubicin into CAH, verification of CAH binding on SW480 by fluorescence microscopy and flow cytometry, and investigation of effect of Dox‐CAH on SW480 proliferation. CAH was successfully prepared, as confirmed by electrophoresis. Flow cytometry and fluorescence microscopy demonstrated CAH binding to SW480, due to the presence of the AS1411 aptamer. This molecular hybrid exhibited specific binding because it did not bind to CCD 841 CoN. CAH binding to PDGF‐BB compromises its function, as shown by enzyme‐linked immunosorbent assay (ELISA) and cell assay. The DNA duplex in this molecular hybrid reduces the cytotoxicity of the Dox‐CAH. Binding and the reduction of Dox‐CAH toxicity may improve treatment specificity and minimize side effects. Dox‐CAH is a model for more effective anticancer therapy, allowing incorporation of chemotherapeutic drugs and recognition elements.
Examining Conners Continuous Performance Test-3 (CPT-3) Embedded Performance Validity Indicators in an Adult Clinical Sample Referred for ADHD Evaluation

ABSTRACT This study evaluated multiple previously-identified Continuous Performance Test-Third Edition (CPT-3) scores as embedded validity indicators (EVIs) among 201 adults undergoing neuropsychological evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD) divided into valid (n = 169) and invalid (n = 32) groups based on seven criterion measures. Although 6/10 CPT-3 scores accurately detected invalidity, only two reached minimally acceptable classification accuracy of ≥0.70. The remaining four had unacceptably low accuracy (AUCs = 0.62–0.69) with 0.19–0.41 sensitivity at ≥0.90 specificity. Composite scores did not provide better classification accuracy than individual CPT-3 scores. In sum, CPT-3 individual and composite scores generally are not accurate PVTs among adults undergoing clinical evaluation for ADHD.
Prediction of 28-day mortality in critically ill patients with COVID-19: Development and internal validation of a clinical prediction model

Background COVID-19 pandemic has rapidly required a high demand of hospitalization and an increased number of intensive care units (ICUs) admission. Therefore, it became mandatory to develop prognostic models to evaluate critical COVID-19 patients. Materials and methods We retrospectively evaluate a cohort of consecutive COVID-19 critically ill patients admitted to ICU with a confirmed diagnosis of SARS-CoV-2 pneumonia. A multivariable Cox regression model including demographic, clinical and laboratory findings was developed to assess the predictive value of these variables. Internal validation was performed using the bootstrap resampling technique. The model’s discriminatory ability was assessed with Harrell’s C-statistic and the goodness-of-fit was evaluated with calibration plot. Results 242 patients were included [median age, 64 years (56–71 IQR), 196 (81%) males]. Hypertension was the most common comorbidity (46.7%), followed by diabetes (15.3%) and heart disease (14.5%). Eighty-five patients (35.1%) died within 28 days after ICU admission and the median time from ICU admission to death was 11 days (IQR 6–18). In multivariable model after internal validation, age, obesity, procaltitonin, SOFA score and PaO2/FiO2 resulted as independent predictors of 28-day mortality. The C-statistic of the model showed a very good discriminatory capacity (0.82). Conclusions We present the results of a multivariable prediction model for mortality of critically ill COVID-19 patients admitted to ICU. After adjustment for other factors, age, obesity, procalcitonin, SOFA and PaO2/FiO2 were independently associated with 28-day mortality in critically ill COVID-19 patients. The calibration plot revealed good agreements between the observed and expected probability of death.
Development of a Search Task Using Immersive Virtual Reality: Proof-of-Concept Study

Background Serious games are gaining increasing importance in neurorehabilitation since they increase motivation and adherence to therapy, thereby potentially improving its outcome. The benefits of serious games, such as the possibility to implement adaptive feedback and the calculation of comparable performance measures, can be even further improved by using immersive virtual reality (iVR), allowing a more intuitive interaction with training devices and higher ecological validity. Objective This study aimed to develop a visual search task embedded in a serious game setting for iVR, including self-adapting difficulty scaling, thus being able to adjust to the needs and ability levels of different groups of individuals. Methods In a two-step process, a serious game in iVR (bird search task) was developed and tested in healthy young (n=21) and elderly (n=23) participants and in a group of patients with impaired visual exploration behavior (ie, patients with hemispatial neglect after right-hemispheric stroke; n=11). Usability, side effects, game experience, immersion, and presence of the iVR serious game were assessed by validated questionnaires. Moreover, in the group of stroke patients, the performance in the iVR serious game was also considered with respect to hemispatial neglect severity, as assessed by established objective hemispatial neglect measures. Results In all 3 groups, reported usability of the iVR serious game was above 4.5 (on a Likert scale with scores ranging from 1 to 5) and reported side effects were infrequent and of low intensity (below 1.5 on a Likert scale with scores ranging from 1 to 4). All 3 groups equally judged the iVR serious game as highly motivating and entertaining. Performance in the game (in terms of mean search time) showed a lateralized increase in search time in patients with hemispatial neglect that varied strongly as a function of objective hemispatial neglect severity. Conclusions The developed iVR serious game, “bird search task,” was a motivating, entertaining, and immersive task, which can, due to its adaptive difficulty scaling, adjust and be played by different populations with different levels of skills, including individuals with cognitive impairments. As a complementary finding, it seems that performance in the game is able to capture typical patterns of impaired visual exploration behavior in hemispatial neglect, as there is a high correlation between performance and neglect severity as assessed with a cancellation task.
Systematic mining of fungal chimeric terpene synthases using an efficient precursor-providing yeast chassis

Significance Chimeric terpene synthases, termed PTTSs, are a unique family of enzymes occurring only in fungi. Characterizing PTTSs is challenging due to the complex reactions they catalyze and the structural complexity of their products. Here, by devising an efficient precursor-providing yeast chassis and incorporating a high-throughput automated platform, we identified 34 active PTTSs, which was considerably more than the number of known functional PTTSs. This effective and rapid pipeline can be employed for the characterization of other PTTSs or related terpenoid biosynthetic enzymes. By systematically analyzing the presence/absence of PTTS genes together with phylogenetic analysis, the ancestral PTTS gene was inferred to have undergone duplication and functional divergence, which led to the development of two distinct cyclization mechanisms. Chimeric terpene synthases, which consist of C-terminal prenyltransferase (PT) and N-terminal class I terpene synthase (TS) domains (termed PTTSs here), is unique to fungi and produces structurally diverse di- and sesterterpenes. Prior to this study, 20 PTTSs had been functionally characterized. Our understanding of the origin and functional evolution of PTTS genes is limited. Our systematic search of sequenced fungal genomes among diverse taxa revealed that PTTS genes were restricted to Dikarya. Phylogenetic findings indicated different potential models of the origin and evolution of PTTS genes. One was that PTTS genes originated in the common Dikarya ancestor and then underwent frequent gene loss among various subsequent lineages. To understand their functional evolution, we selected 74 PTTS genes for biochemical characterization in an efficient precursor-providing yeast system employing chassis-based, robot-assisted, high-throughput automatic assembly. We found 34 PTTS genes that encoded active enzymes and collectively produced 24 di- and sesterterpenes. About half of these di- and sesterterpenes were also the products of the 20 known PTTSs, indicating functional conservation, whereas the PTTS products included the previously unknown sesterterpenes, sesterevisene (1), and sesterorbiculene (2), suggesting that a diversity of PTTS products awaits discovery. Separating functional PTTSs into two monophyletic groups implied that an early gene duplication event occurred during the evolution of the PTTS family followed by functional divergence with the characteristics of distinct cyclization mechanisms.
Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C)

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.
Predictors of Neurodevelopmental Impairment After Neonatal Bacterial Meningitis

Background: Neonatal bacterial meningitis has high rates of morbidity and mortality. Early clinical signs and neuroimaging suggest adverse outcomes, but little is known about their combined predictive properties. We evaluated the combination of findings most associated with death and neurodevelopmental impairment. Methods: Single-center retrospective cohort study of term and late preterm neonates with bacterial meningitis. Predictors of death and neurodevelopmental impairment were identified on univariate analysis and incorporated into Lasso models to identify variables best predicting adverse outcomes. Results: Of 103 neonates, 6 died acutely; 30% of survivors had neurodevelopmental impairment. Clinical variables (seizures, pressor support) predicted death and neurodevelopmental impairment better than the neuroimaging or combined findings (area under the curve 0.88 vs 0.79 and 0.83, respectively). Among survivors, neuroimaging findings (cerebrovascular lesions, ventriculomegaly) predicted neurodevelopmental impairment better than clinical or combined findings (area under the curve 0.82 vs 0.80 and 0.77, respectively). Conclusions: Seizures are important predictors of adverse outcomes in neonatal bacterial meningitis. Among survivors, neuroimaging findings help predict neurodevelopmental impairment.
Theoretical investigation of lattice dynamics, infrared reflectivity, polarized Raman spectra and nature of interlayer coupling in two-dimensional layered gallium sulfide

Gallium sulfide (GaS) is a highly promising two-dimensional layered semiconductor owing to its remarkable thickness dependent electronic and physical properties. In this article, we perform a comprehensive ab initio study of lattice dynamics, mode symmetry assignments, polarized Raman and infrared (IR) reflectivity spectra of GaS system. Polarized Raman spectra are obtained for different light polarization set-ups of incoming and scattered light. The frequencies of all allowed vibrational modes at the zone-centre are calculated and symmetry labels are assigned. Furthermore, the variation of frequencies & intensities of Raman/IR active modes of ultrathin GaS films (few layers) as function of film thickness is studied. In addition, we also explore the nature of weak interlayer coupling in GaS. The weak forces between the GaS layers are usually assumed to be due to interlayer van der Waals (vdW) interaction. However, this assumption has not been reasonably explained in reported experimental studies. Our study strongly suggests that weak interlayer interactions in GaS may be primarily electrostatic (Coulomb) in nature and therefore the contribution of vdW interactions to layer–layer coupling and lattice dynamics may be significantly lower than that of electrostatic interaction. The suggested nature of interlayer coupling in GaS and related III–VI semiconductors may have important implications in determination of their various physical properties.
Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study*

Supplemental Digital Content is available in the text. OBJECTIVES: The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. DESIGN: Propensity score–matched retrospective cohort analysis. SETTING: Tertiary North American liver transplant centers. PATIENTS: Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009–2019) and controls from the U.S. Acute Liver Failure Study Group registry. INTERVENTIONS: Molecular adsorbent recirculating system treatment versus standard medical therapy (control). MEASUREMENTS AND MAIN RESULTS: One-hundred four molecular adsorbent recirculating system patients were propensity score–matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King’s College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07–3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone (“model 2”; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05–3.31; p = 0.033), and further adjustment of the “main model” for mechanical ventilation, and grade 3/4 hepatic encephalopathy (“model 3”; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07–3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). CONCLUSIONS: Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.
Unemployment associated with major depression disorder and depressive symptoms: a systematic review and meta-analysis

Objectives. This study investigated the association between unemployment and depressive symptoms and major depression disorder worldwide using a systematic review and meta-analysis. Methods. Search time was limited to all articles published in English until December 2020. In the association between unemployment and depression, first, the results of qualified studies were extracted and, then, the results of each study were pooled with each other using the random effects method. Results. The prevalence of depression in the unemployed is 21%, 95% confidence interval (CI) [18, 24%]. This prevalence for depression symptoms is 24%, 95% CI [20, 28%] and for major depressive disorder is 16%, 95% CI [9–24%]. The association between unemployment and depressive symptoms was odds ratio (OR) 2.06, 95% CI [1.85, 2.30] and the association for major depressive disorder was OR 1.88, 95% CI [1.57, 2.25]. The association between unemployment and depression in men was OR 2.27, 95% CI [1.76, 2.93] and in women was OR 1.62, 95% CI [1.40, 1.87]. Conclusions. What is clear from the present study is that unemployment can lead to a higher prevalence of depressive symptoms and major depressive disorder, thereby undermining the mental health of the unemployed.
Validation of a multi‐species‐specific PCR panel to diagnose patients with suspected postoperative bacterial endophthalmitis

Currently, patients suspected of endophthalmitis are referred to a tertiary centre for a vitreous biopsy and bacterial culture, thereby causing a treatment delay for the intravitreal antibiotics injection. We developed a new diagnostic tool, multi‐mono‐PCR (mm‐PCR), not requiring viable bacteria, allowing antibiotic injection without delay. Performance of mm‐PCR was tested on biopsies from patients with suspected postoperative endophthalmitis with known bacterial culture results.
Evaluating Multiple Biochemical Markers in Xenopus laevis Tadpoles Exposed to the Pesticides Thiacloprid and Trifloxystrobin in Single and Mixed Forms

Pesticide exposure is thought to be one of the common reasons for the decline in amphibian populations, a phenomenon that is a major threat to global biodiversity. Although the single effects of pesticides on amphibians have been well studied, the effects of mixtures are not well known. The present study aimed to evaluate the acute toxicity of the insecticide thiacloprid and the fungicide trifloxystrobin on early developmental stages of Xenopus laevis using various biochemical markers (glutathione S‐transferase, glutathione reductase, acetylcholinesterase, carboxylesterase, glutathione peroxidase, catalase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, Na+K+‐adenosine triphosphatase [ATPase], Ca2+‐ATPase, Mg2+‐ATPase, and total ATPase). The median lethal concentrations (LC50s) of thiacloprid and trifloxystrobin were determined to be 3.41 and 0.09 mg a.i. L–1, respectively. Tadpoles were exposed to the LC50, LC50/2, LC50/10, LC50/20, LC50/50, and LC50/100 of these pesticides. Both pesticides significantly affected (inhibited/activated) the biomarkers even at low concentrations. The pesticides showed a synergistic effect when applied as a mixture and altered the biomarkers more than when applied individually. In conclusion, we can assume that tadpoles are threatened by these pesticides even at environmentally relevant concentrations. Our findings provide important data to guide management of the ecotoxicological effects of these pesticides on nontarget amphibians. Environ Toxicol Chem 2021;40:2846–2860. © 2021 SETAC
Recognizing Vaccine-Induced Immune Thrombotic Thrombocytopenia

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia is an unexpected consequence of the coronavirus disease 2019 pandemic era. We reviewed the pathogenesis, clinical presentation, diagnosis, and treatment of this rare side effect. DATA SOURCES: Online search of published medical literature through PubMed, Scopus, Web of Science, and Google Scholar using the terms “COVID-19,” “vaccine,” “thrombosis” was performed. STUDY SELECTION: Articles were chosen for inclusion based on their relevance to coronavirus disease 2019, vaccine, and thrombosis. DATA SYNTHESIS: Vaccine-induced immune thrombotic thrombocytopenia manifests most often as unusual thromboses (cerebral venous sinus thrombosis, splanchnic vein thrombosis) but sometimes also “usual” thromboses (arterial stroke, pulmonary embolism, deep-vein thrombosis), with oftentimes severe thrombocytopenia, that becomes clinically evident 5–30 days after adenovirus-vectored coronavirus disease 2019 vaccine administration. Most patients have disseminated intravascular coagulation. These features are the result of vaccine-triggered formation of anti-platelet factor 4 immunoglobulin G that activate platelets, clinically mimicking autoimmune heparin-induced thrombocytopenia. Early recognition based on thrombosis (sometimes, hemorrhage), thrombocytopenia, and d-dimer elevation within the day 5–30 postvaccine “window” is important given treatment with high-dose IV immunoglobulin plus nonheparin anticoagulation. CONCLUSIONS: Vaccine-induced immune thrombotic thrombocytopenia is a serious complication of vaccination that is not feasible to anticipate or prevent. When the patient presents with sustained headache, neurologic symptoms/signs, abdominal pain, dyspnea, or limb pain/swelling beginning 5–30 days post vaccination, platelet count and d-dimer must be measured, and imaging for thrombosis performed. Confirmation of vaccine-induced immune thrombotic thrombocytopenia diagnosis should be ordered (platelet factor 4/polyanion enzyme-linked immunosorbent assay; platelet factor 4–enhanced platelet activation testing) as treatment is initiated (nonheparin anticoagulation, IV immunoglobulin).