Miracle-dz/UniFAR-FTUs huggingface dataset:
Research Review: The strength of the genetic overlap between ADHD and other psychiatric symptoms - a systematic review and meta-analysis.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with other psychiatric disorders. Twin studies have established that these co-occurrences are in part due to shared genetic risks. However, the strength of these genetic overlaps and the potential heterogeneity accounted for by type of psychiatric symptoms, age, and methods of assessment remain unclear. We conducted a systematic review to fill this gap. METHODS We searched PubMed, PsycINFO, Embase, and Web of Science until March 07, 2019. Genetic correlations (rg ) were used as effect size measures. RESULTS A total of 31 independent studies fulfilled the inclusion criteria. The pooled estimates showed that the associations between ADHD and other psychiatric symptoms were partly explained by shared genetic factors, with a pooled genetic correlation of 0.50, 95% confidence interval: 0.46-0.60. The genetic correlations (rg ) between ADHD and externalizing (rg = .49 [0.37-0.61]), internalizing (rg = .50 [0.39-0.69]), and neurodevelopmental (rg = .56 [0.47-0.66]) symptoms were similar in magnitude. The genetic correlations in childhood and adulthood were rg = . 53 (0.43-0.63) and rg = . 51 (0.44-0.56), respectively. For methods of assessment, the genetic correlations were also similar in strength, self-reports rg = . 52 (0.47-0.58), other informants rg = . 55 (0.41-0.69), and combined raters rg = . 50 (0.33-0.65). CONCLUSIONS These findings indicate that the co-occurrence of externalizing, internalizing, and neurodevelopmental disorder symptoms in individuals with ADHD symptoms in part is due to a shared genetic risk.
Adult and Cord Blood-Derived High-Affinity gB-CAR-T Cells Effectively React Against Human Cytomegalovirus Infections

Human cytomegalovirus (HCMV) reactivations are associated with lower overall survival after transplantations. Adoptive transfer of HCMV-reactive expanded or selected T cells can be applied as a compassionate use, but requires that the human leukocyte antigen-matched donor provides memory cells against HCMV. To overcome this, we developed engineered T cells expressing chimeric antigen receptors (CARs) targeted against the HCMV glycoprotein B (gB) expressed upon viral reactivation. Single-chain variable fragments (scFvs) derived from a human high-affinity gB-specific neutralizing monoclonal antibody (SM5-1) were fused to CARs with 4-1BB (BBL) or CD28 (28S) costimulatory domains and subcloned into retroviral vectors. CD4+ and CD8+ T cells obtained from HCMV-seronegative adult blood or cord blood (CB) transduced with the vectors efficiently expressed the gB-CARs. The specificity and potency of gB-CAR-T cells were demonstrated and compared in vitro using the following: 293T cells expressing gB, and with mesenchymal stem cells infected with a HCMV TB40 strain expressing Gaussia luciferase (HCMV/GLuc). BBL-gB-CAR-T cells generated with adult or CB demonstrated significantly higher in vitro activation and cytotoxicity performance than 28-gB-CAR-T cells. Nod.Rag. Gamma (NRG) mice transplanted with human CB CD34+ cells with long-term human immune reconstitution were used to model HCMV/GLuc infection in vivo by optical imaging analyses. One week after administration, response to BBL-gB-CAR-T cell therapy was observed for 5/8 mice, defined by significant reduction of the bioluminescent signal in relation to untreated controls. Response to therapy was sporadically associated with CAR detection in spleen. Thus, exploring scFv derived from the high-affinity gB-antibody SM5-1 and the 4-1BB signaling domain for CAR design enabled an in vitro high on-target effect and cytotoxicity and encouraging results in vivo. Therefore, gB-CAR-T cells can be a future clinical option for treatment of HCMV reactivations, particularly when memory T cells from the donors are not available.
Nano/Microscale Thermal Field Distribution: Conducting Thermal Decomposition of Pyrolytic-Type Polymer by Heated AFM Probes

In relevant investigations and applications of the heated atomic force microscope (AFM) probes, the determination of the actual thermal distribution between the probe and the materials under processing or testing is a core issue. Herein, the polyphthalaldehyde (PPA) film material and AFM imaging of the decomposition structures (pyrolytic region of PPA) were utilized to study the temperature distribution in the nano/microscale air gap between heated tips and materials. Different sizes of pyramid decomposition structures were formed on the surface of PPA film by the heated tip, which was hovering at the initial tip–sample contact with the preset temperature from 190 to 220 °C for a heating duration ranging from 0.3 to 120 s. According to the positions of the 188 °C isothermal surface in the steady-state probe temperature fields, precise 3D boundary conditions were obtained. We also established a simplified calculation model of the 3D steady-state thermal field based on the experimental results, and calculated the temperature distribution of the air gap under any preset tip temperature, which revealed the principle of horizontal (<700 nm) and vertical (<250 nm) heat transport. Based on our calculation, we fabricated the programmable nano-microscale pyramid structures on the PPA film, which may be a potential application in scanning thermal microscopy.
Development and application of TK6-derived cells expressing human cytochrome P450s for genotoxicity testing.

Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress one of eight cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using two prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared to EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared to EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.
Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China

Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20–24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p < 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p < 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.
Selective screw fixation is associated with early failure of primary acetabular components for aseptic loosening

Selective supplementation of acetabular component fixation with a screw during primary total hip arthroplasty (THA) assumes that the surgeon can detect when an acetabular component needs additional stability. In contrast, nonselective screw users do not alter their practice based on their interpretation of stability and either use screws all or none of the time. We aimed to determine the effect of selective screw use on aseptic acetabular component loosening. We retrospectively reviewed aseptic failures of acetabular components after primaty THA. We compared the survivorship of selective and nonselective supplementation of acetabular fixation with respect to time to revision, obesity, and screw use. Selective screw use (n = 16) was associated with earlier acetabular component aseptic loosening (median: 1.9 years; interquartile range [IQR]: 1.1‐5.0) compared to nonselective screw use (n = 22; median: 5.6 years; IQR: 2.0‐15.3; P = .010). Selective screw use was independently associated with earlier revision after adjusting for patient obesity. Obesity was associated with selective screw use in 50% of the cases vs 14% of nonselective cases (odds ratio: 6.3; confidence interval: 1.2‐25.2; P = .028), possibly reflecting the increased difficulty in achieving acetabular component stability in this and other settings with compromised bone. Surgeons should carefully assess component stability at time of primary THA. If the acetabulum is not stable, the addition of screws alone may not be sufficient for acetabular component stability.
Cardiac iron concentration in relation to systemic iron status and disease severity in non‐ischaemic heart failure with reduced ejection fraction

Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non‐advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non‐advanced HFrEF and explored CI association with systemic iron status and disease severity.
Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3

ABSTRACT Objective To evaluate the density of anti-galectin-3-immunostained cells, collagen percentage, mast cell density and presence of pathological processes in intestinal muscle biopsies of patients. Methods Thirty-five patients who underwent intestinal biopsy were selected from 1997 to 2015. Patients were divided into three groups: chagasic patients with mucosal lesion (n=13), chagasic patients with intact mucosa (n=12) and non-chagasic patients with no mucosal lesion (n=10). Histological processing of the biopsied fragments and immunohistochemistry for galectin-3 were performed. Additional sections were stained with hematoxylin and eosin to evaluate the general pathological processes, picrosirius for evaluation of collagen and toluidine blue to evaluate the mast cell density. Results Patients of mucosal lesion group had a significantly higher frequency of ganglionitis and myositis when compared to the chagasic patients with intact mucosa and non-chagasic group. The density of anti-galectin-3-immunostained cells was significantly higher in the chagasic patients with intact mucosa group when compared to the non-chagasic group. The group of chagasic patients with intact mucosa presented a higher percentage of collagen in relation to the patients with mucosal lesion and to the non-chagasic group, with a significant difference. There was no significant difference in mast cell density among the three groups. Conclusion The higher density of anti-galectin-3-immunostained cells in patients in the chagasic patients with intact mucosa group suggested the need for greater attention in clinical evaluation of these patients, since this protein is associated with neoplastic transformation and progression.
Antioxidant Content of Frozen, Convective Air-Dried, Freeze-Dried, and Swell-Dried Chokecherries (Prunus virginiana L.)

Chokecherry (Prunus virginiana L.) is rich in bioactive molecules as phenolics, which can act as antioxidants, anti-inflammatory, anticancer, among others; however, due to its high perishability, most of this fruit is wasted. Freezing and sun drying have been the most adopted techniques to avoid its postharvest deterioration. Nevertheless, both processes have presented some drawbacks as high storage costs and losses of bioactive molecules. Therefore, to preserve these molecules, this study compared the impact of convective airflow drying (CAD), freezing (FR), freeze drying (FD), and swell drying (SD). Total phenolics content (TPC), total flavonoids content (TFC), kuromanin concentration (KC), and antioxidant activity (antiradical activity (ARA) and Trolox equivalent antioxidant capacity assay (TEAC)) of chokecherries were measured. “Swell drying” is a drying process coupling convective airflow drying to the Instant Controlled Pressure Drop (DIC) expansion. A central composite rotatable design was applied to optimize the DIC variables and responses. Results showed that both freezing and swell drying effectively preserve the TPC, TFC, KC, and ARA. Moreover, SD samples also presented the highest TEAC. Contrary, in the case of CAD, it caused the highest losses of both antioxidant content and activity. Swell drying remedies the shrinkage and collapsing of dried food structure, which results in a better antioxidants extraction.
Eye Irritation Potential of Microglycine and Microglycine-Containing Ointments: An in vitro Study on Reconstructed Human Corneal Epithelium

Objective To assess the eye tolerability of a buffered ophthalmic solution containing microglycine (sodium hydroxymethylglycinate, mwaterTM) in an in vitro model. Materials and Methods A multiple endpoint analysis (MEA) approach was applied to the reconstructed human corneal epithelium (HCE) model. Sodium hydroxymethylglycinate solution (0.04%) and two ophthalmic ointments containing microglycine (Protectorial, containing 0.02% of sodium hydroxymethylglycinate, and Edenight, containing 0.04% of sodium hydroxymethylglycinate) were investigated. The buffered solution and the ointments were tested on HCE after acute (one application in 24 hrs, followed or not by 16 hrs of recovery) or repeated (one application per day for three consecutive days) exposures; benzalkonium chloride (BAK) 0.01% and saline isotonic solution were used as positive and negative controls, respectively. Cellular viability, trans-epithelial electrical resistance (TEER), lactate dehydrogenase (LDH) release and histo-morphology were evaluated. Results BAK 0.01% toxicity in HCE was confirmed for the 24+16 hrs acute and repeated exposure protocols, while, after 24–hours acute treatment, only modifications of the superficial cell layer were visible compared with the negative control. Sodium hydroxymethylglycinate had a very good tolerability profile and a neutral impact on the corneal surface after acute or repeated exposure. The Protectorial and Edenight ointments preserved cell viability in the different exposure protocols, suggesting a good local tolerability profile. Modifications of the superficial layers were observed on histo-morphological analysis and confirmed by increased release of LDH after 24+16 hrs acute exposure (+65% and +76% for Protectorial and Edenight, respectively) and TEER values after 24+16 hrs and 72 hrs exposure protocols. These results were dependent on the ointments’ accumulation on the corneal epithelium due to their physical form (semi-solid) and lipophilic properties. Conclusion Sodium hydroxymethylglycinate, alone or as part of eye ointments, was found to be non-toxic after acute or repeated exposure in the reconstructed HCE model.
A Protein in the Yeast Saccharomyces cerevisiae Presents DNA Binding Homology to the p53 Checkpoint Protein and Tumor Suppressor

Saccharomyces cerevisiae does not contain a p53 homolog. Utilizing this yeast as an in vivo test tube model, our aim was to investigate if a yeast protein would show p53 DNA binding homology. Electrophoretic mobility shift analyses revealed the formation of specific DNA-protein complexes consisting of S. cerevisiae nuclear protein(s) and oligonucleotides containing p53 DNA binding sites. A S. cerevisiae p53 binding site factor (Scp53BSF) bound to a p53 synthetic DNA-consensus sequence (SCS) and a p53 binding-site sequence from the MDM2 oncogene. The complexes were of comparable size. Like mammalian p53, the affinity of Scp53BSF for the SCS oligonucleotide was higher than for the MDM2 oligonucleotide. Binding of Scp53BSF to the SCS and MDM2 oligonucleotides was strongly competed by unlabeled oligonucleotides containing mammalian p53 sites, but very little by a mutated site oligonucleotide. Importantly, Scp53BSF-DNA binding activity was significantly induced in extracts from cells with DNA damage. This resulted in dose-dependent coordinated activation of transcription when using p53-binding site reporter constructs. An ancient p53-like DNA binding protein may have been found, and activation of DNA-associated factors to p53 response elements may have functions not yet determined.
Epidemiology and outcomes of non-HACEK infective endocarditis in the southeast United States

Objectives Infective endocarditis (IE) with non-HACEK Gram-negative (GN) organisms is rare, but associated with poor outcomes. The purpose of this study was to quantify the microbiology, treatment strategies, and frequency of poor outcomes in patients with non-HACEK GN IE. Materials Retrospective cohort of adults with definite non-HACEK GN IE from 1/11-1/19. The primary endpoint was poor patient outcome, defined as a composite of all-cause death or infection-related readmission within 90-days of index infection. Results 43 patients were included: 51% patients were men, and the median (IQR) age was 40 (31–50) years. Forty patients reported injection drug use. The most common organisms were Pseudomonas aeruginosa (68%) and Serratia marcescens (9%). Seventy-six percent of patients received definitive combination therapy; the most common antibiotics used in combination with a β-lactam were aminoglycosides (50%) and fluoroquinolones (34%). Three patients discontinued combination therapy due to toxicity. Twelve-month, all-cause mortality and readmission was 30% and 54%, respectively. In multivariable logistic regression, variables independently associated with composite poor outcome were receipt of fluoroquinolone-based IE combination therapy and septic shock. Conclusions Long-term mortality and readmission rates were high. Patients who received fluoroquinolone-based IE combination therapy more frequently developed poor outcomes than those who did not.
The Role of Combined Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced MRI for Differentiating Malignant From Benign Breast Lesions Presenting Washout Curve

Purpose: The aim of this study is to evaluate the diagnostic performance of combined breast magnetic resonance imaging (MRI) protocol including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with enhancing lesions that demonstrated washout curve and to determine whether applying apparent diffusion coefficient (ADC) cutoff value could improve the diagnostic value of breast MRI. Methods: The retrospective study included 116 patients with 116 suspicious breast lesions, which showed washout curve on DCE-MRI, who underwent subsequent biopsy. Morphologic characteristics on DCE-MRI and ADC values on DWI were evaluated. Apparent diffusion coefficient values and morphologic features of benign and malignant lesions were compared. Diagnostic values of DCE-MRI and combined MRI, including DCE-MRI and DWI (applying an ADC cutoff value) for distinguishing malignancy from benign lesions, were calculated. Results: Of the 116 breast lesions, 79 were malignant and 37 were benign. The ADC value of malignant tumors (median ADC, 0.72 × 10−3 mm2/s) was significantly lower than that of benign lesions (median ADC, 1.03 × 10−3 mm2/s; P < .000). The sensitivity and specificity of an ADC cutoff value of 0.89 × 10−3 mm2/s were 92% and 95%, respectively. Dynamic contrast-enhanced MRI alone presented 100% sensitivity and 59.4% specificity. Adding an ADC cutoff value of 0.89 × 10−3 mm2/s provided 100% sensitivity and 81% specificity, which would have prevented biopsy for 21.6% of benign lesions without missing any malignancies. Conclusion: Applying an ADC cutoff value to DCE-MRI provides an improvement in the diagnostic value of breast MRI for differentiating among lesions presenting washout curve.
A study of alternative approaches to non-normal latent trait distributions in item response theory models used for health outcome measurement

It is often unrealistic to assume normally distributed latent traits in the measurement of health outcomes. If normality is violated, the item response theory (IRT) models that are used to calibrate questionnaires may yield parameter estimates that are biased. Recently, IRT models were developed for dealing with specific deviations from normality, such as zero-inflation (“excess zeros”) and skewness. However, these models have not yet been evaluated under conditions representative of item bank development for health outcomes, characterized by a large number of polytomous items. A simulation study was performed to compare the bias in parameter estimates of the graded response model (GRM), polytomous extensions of the zero-inflated mixture IRT (ZIM-GRM), and Davidian Curve IRT (DC-GRM). In the case of zero-inflation, the GRM showed high bias overestimating discrimination parameters and yielding estimates of threshold parameters that were too high and too close to one another, while ZIM-GRM showed no bias. In the case of skewness, the GRM and DC-GRM showed little bias with the GRM showing slightly better results. Consequences for the development of health outcome measures are discussed.