Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term functional decline of spontaneous intracerebral haemorrhage survivors

Objective To identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline. Methods In a single-centre study, we prospectively included 6-month survivors with a modified Rankin Scale (mRS) score 0–3. We defined functional decline by a transition to mRS 4–5. We evaluated associations of baseline characteristics and new clinical events with functional decline, using univariate and multivariable models. Results Of 560 patients, 174 (31%) had an mRS score 0–3 at 6 months. During a median follow-up of 9 years (IQR 8.1–9.5), 40 (23%) converted to mRS 4–5. Age, diabetes mellitus, ICH volume and higher mRS scores at 6 months were independently associated with functional decline. Among baseline MRI markers, presence of strictly lobar cerebral microbleeds (CMBs), and mixed lobar and deep CMBs were independently associated with functional decline. When new clinical events occurring during follow-up were added in multivariable models, age (cause-specific HR (CSHR): 1.07; 95% CI: 1.03 to 1.11), ICH volume (CSHR: 1.03; 95% CI: 1.01 to 1.06), mRS score at 6 months (CSHR per 1 point increase 1.61, 95% CI 1.07 to 2.43), occurrence of dementia (CSHR: 3.81, 95% CI: 1.78 to 8.16) and occurrence of any stroke (CSHR: 4.29, 95% CI: 1.80 to 10.22) remained independently associated with transition to mRS 4–5. Interpretation Almost one-fourth of patients with spontaneous ICH developed a functional decline over time. Age, ICH volume, higher mRS score at 6 months and new clinical events after ICH are the major determinants.
Total Phenolics and Antioxidant Capacity of Cocoa Pulp: Processing and Storage Study

Cocoa pulp, the white mucilage that surrounds cocoa beans, is the main substrate in cocoa bean fermentation and is rich in macro- and micronutrients. Yet, the presence of phenolics and their antioxidant activity in cocoa pulp has not been explored. The objectives of this study were to quantify the total phenolics of cocoa pulp by using Folin-Ciocalteu assay and antioxidant activity by using Oxygen Radical Absorption Capacity (ORAC) assay as well as Cellular Antioxidant Activity (CAA) assay. The effect of single and double pasteurization was investigated to better understand the potential health value and subsequently promote the utilization of cocoa pulp. Eight weeks storage studies at 4oC, 25oC, and 37oC were also performed to monitor the stability of phenolics, ORAC values, and color of pasteurized cocoa pulp. Single and double pasteurization decreased phenolics content of the cocoa pulp by 25% and 38%, respectively, when compared to unpasteurized pulp (103.76±4.79 mg GAE/100 g pulp). The ORAC values were not significantly different between unpasteurized (1871±58 μmol TE/100 g pulp), single (1835±41 μmol TE/100 g pulp), and double pasteurized (1681±157 μmol TE/100 g pulp) pulp. There was a significant increase in the CAA values (EC50) of double pasteurized pulp (59.76±9.26 μmol QE/100g pulp) as compared to unpasteurized pulp (23.71±3.12 μmol QE/100 g pulp). Thus, there was a weak negative correlation between ORAC and CAA values in quantifying the antioxidant activity of cocoa pulp. Overall color differences (ΔE*) relative to unpasteurized pulp were not significantly different between single (11.50±6.64) and double pasteurized pulp (14.96±8.64). Throughout the eight week storage studies, single and double pasteurized pulp showed very little change in the phenolics content and the ORAC values at 4oC and 25oC. However, at 37°C, up to 50% relative loss in phenolics content and 40% relative loss in the ORAC values were observed in single pasteurized pulp; whereas double pasteurization resulted in lesser relative loss. Both single and double pasteurized pulp showed the lowest lightness (L*) values when stored at 37oC, as well as the lowest hue angle and chroma values when stored at 4oC, suggesting less color changes at lower storage temperature.
Morphosyntactic Evaluation Protocol (MEP): validation of content.

INTRODUCTION the use of language assessment instruments in the area of speech-language-therapy is essential for the diagnosis and, consequently, for therapeutic planning. In Brazil, there is a shortage of instruments constructed and validated in the morphosyntax area. Morphosyntactic Evaluation Protocol (MEP) was constructed based on the main syntactic characteristics of the period of acquisition of children's language, on the Portuguese grammatical structure and the application in a pilot study. OBJECTIVE To verify the validity of MEP content. METHODS for the validation process, the instrument was applied and analyzed through a questionnaire by three judges, a linguist and two speech-language specialists with experience in assisting children with Language Development Disorder. The Index of Judges' Reliability was used to compare the results of the protocol application and the Cronbach's Alpha tests, Spearman-Brown and Content Validity Index (CVI) in the questionnaire responses. RESULTS the statistical tests applied in the validation of content legitimized the reliability of the instrument with indexes considered substantial for both alpha coefficients, higher than 0.80, Spearman and the CVI test had a maximum concept of 1.0. CONCLUSION there were compliance and compatibility in the answers of the experts, which indicates the reliability of the instrument. The results of the statistical tests legitimize the reliability of the instrument with indexes considered substantial for alpha and Spearman coefficient. In the future, the protocol may help characterize the syntactic profile of children with language developmental disorder.
Discovering novel driver mutations from pan-cancer analysis of mutational and gene expression profiles

As the genomic profile across cancers varies from person to person, patient prognosis and treatment may differ based on the mutational signature of each tumour. Thus, it is critical to understand genomic drivers of cancer and identify potential mutational commonalities across tumors originating at diverse anatomical sites. Large-scale cancer genomics initiatives, such as TCGA, ICGC and GENIE have enabled the analysis of thousands of tumour genomes. Our goal was to identify new cancer-causing mutations that may be common across tumour sites using mutational and gene expression profiles. Genomic and transcriptomic data from breast, ovarian, and prostate cancers were aggregated and analysed using differential gene expression methods to identify the effect of specific mutations on the expression of multiple genes. Mutated genes associated with the most differentially expressed genes were considered to be novel candidates for driver mutations, and were validated through literature mining, pathway analysis and clinical data investigation. Our driver selection method successfully identified 116 probable novel cancer-causing genes, with 4 discovered in patients having no alterations in any known driver genes: MXRA5, OBSCN, RYR1, and TG. The candidate genes previously not officially classified as cancer-causing showed enrichment in cancer pathways and in cancer diseases. They also matched expectations pertaining to properties of cancer genes, for instance, showing larger gene and protein lengths, and having mutation patterns suggesting oncogenic or tumor suppressor properties. Our approach allows for the identification of novel putative driver genes that are common across cancer sites using an unbiased approach without any a priori knowledge on pathways or gene interactions and is therefore an agnostic approach to the identification of putative common driver genes acting at multiple cancer sites.
Gottlieb Burckhardt (1836-1907): 19th-Century Pioneer of Psychosurgery

Gottlieb Burckhardt was a 19th-century Swiss psychiatrist who introduced the psychosurgical method known as topectomy as a means to relieve the symptoms of aggression and agitation in individuals diagnosed with mental disease. Specifically, he performed topical excision of part of the cerebral cortex on 6 patients with chronic schizophrenia. Most of these patients became more approachable and easier to manage, but they also showed signs of aphasia or seizures, and 2 died soon after the surgery. Burckhardt’s presentation of the results of his surgical procedures to the Berlin Medical Congress in 1890 caused an enormous controversy within the European medical community and resulted in his ostracism from it. He continued practicing, however and dispensing advice in his role as a mental hospital director, though he soon gave up his surgical endeavours. His innovative theory of higher cerebral functions anticipated the lobotomy procedure that was developed nearly half a century later by the neurologist Egas Moniz (1874-1955).
The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome before and after Curative Surgery.

BACKGROUND We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing's syndrome (CS). METHODS We performed a retrospective cohort study of adult patients with CS seen from 2005 - 2018 (cohort 1, c1, n=68) or 1985 - 1994 (cohort 2, c2, n=55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8AM and ~midnight (PM)), morning triiodothyronine (T3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) (c1) or hourly TSH from 1500-1900h (day) and 2400-04000h (night) (c2), were measured before and after curative surgery. RESULTS While hypercortisolemic, 53% of c1 had central hypothyroidism (low/low normal fT4 + unelevated TSH). Of those followed long-term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6-12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, AM and PM F, ACTH, and UFC were inversely related to TSH, FT4 and/or T3 levels (r -0.24 to -0.52, P <0.0001 to 0.02). In c2, the nocturnal surge of TSH (mIU/L) was subnormal before (day 1.00±0.04 vs night 1.08±0.05, p=0.3) and normal at a mean of 8 months after cure (day 1.30±0.14 vs night 2.17±0.27, p=0.01). UFC >1000 μg /day was an independent adverse prognostic marker of time to thyroid hormone recovery. CONCLUSIONS Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing's syndrome and is reversible after cure.
Supplementation of c-type natriuretic peptide during in vitro growth period benefits the development of murine preantral follicles

Summary The present study investigated the effects of c-type natriuretic peptide (CNP) on the development of murine preantral follicles during in vitro growth (IVG). Preantral follicles isolated from ovaries of Kunming mice were cultured in vitro. In the culture system, CNP was supplemented in the experimental groups and omitted in the control groups. In Experiment 1, CNP was only supplemented at the early stage and follicle development was evaluated. In Experiments 2 and 3, CNP was supplemented during the whole period of in vitro culture. In Experiment 2, follicle development and oocyte maturity were evaluated. In Experiment 3, follicle development and embryo cleavage after in vitro fertilization (IVF) were assessed. The results showed that in the control groups in all three experiments, granulosa cells migrated from within the follicle and the follicles could not reach the antral stage. In the experimental groups in all three experiments, no migration of granulosa cells was observed and follicle development was assessed as attaining the antral stage, which was significantly superior to that of the control group (P < 0.0001). Oocyte meiotic arrest was effectively maintained, hence giving good developmental competence. In conclusion, CNP supplementation in the culture system during IVG benefited the development of murine preantral follicles.
Global Mental Health and Services for Migrants in Primary Care Settings in High-Income Countries: A Scoping Review

Migrants are at a higher risk for common mental health problems than the general population but are less likely to seek care. To improve access, the World Health Organization (WHO) recommends the integration of mental health services into primary care. This scoping review aims to provide an overview of the types and characteristics of mental health services provided to migrants in primary care following resettlement in high-income countries. We systematically searched MEDLINE, EMBASE, PsycInfo, Global Health, and other databases from 1 January 2000 to 15 April 2020. The inclusion criteria consisted of all studies published in English, reporting mental health services and practices for refugee, asylum seeker, or undocumented migrant populations, and were conducted in primary care following resettlement in high-income countries. The search identified 1627 citations and we included 19 studies. The majority of the included studies were conducted in North America. Two randomized controlled trials (RCTs) assessed technology-assisted mental health screening, and one assessed integrating intensive psychotherapy and case management in primary care. There was a paucity of studies considering gender, children, seniors, and in European settings. More equity-focused research is required to improve primary mental health care in the context of global mental health.
Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells

Oncolytic herpes simplex viruses (oHSV) are under development for the treatment of a variety of human cancers, including breast cancer, a leading cause of cancer mortality among women worldwide. Here we report the design of a fully retargeted oHSV for preferential infection of breast cancer cells through virus recognition of GFRα1, the cellular receptor for glial cell-derived neurotrophic factor (GDNF). GFRα1 displays a limited expression profile in normal adult tissue, but is upregulated in a subset of breast cancers. We generated a recombinant HSV expressing a completely retargeted glycoprotein D (gD), the viral attachment/entry protein, that incorporates pre-pro-GDNF in place of the signal peptide and HVEM binding domain of gD and contains a deletion of amino acid 38 to eliminate nectin-1 binding. We show that GFRα1 is necessary and sufficient for infection by the purified recombinant virus. Moreover, this virus enters and spreads in GFRα1-positive breast cancer cells in vitro and caused tumor regression upon intratumoral injection in vivo. Given the heterogeneity observed between and within individual breast cancers at the molecular level, these results expand our ability to deliver oHSV to specific tumors and suggest opportunities to enhance drug or viral treatments aimed at other receptors.
Social Skills and Medical Responsibility Across Development in Youth With Spina Bifida.

OBJECTIVE To examine the predictive role of social skills in youth with spina bifida (SB) on growth in medical responsibility across development. METHODS As part of a larger, longitudinal study, 140 youth with SB were assessed across four time points (ages 8-22 across time points). Mixed-effects models were investigated for change with: (a) no predictors (i.e., change in medical responsibility across age; time was examined using the participant's age, centered at 11.5 years); (b) social variables (i.e., observed social behaviors, parent- and teacher-reported social skills) as predictors; and (c) social variables as predictors with intelligence quotient, lesion level, and sex as covariates. RESULTS Significant growth with age was identified for medical responsibility (p < .0001). Observed, parent-reported, and teacher-reported social skills did not significantly predict this growth; however, all three predicted the intercept for medical responsibility at 11.5 years of age (ps ≤ .047). Parent-reported social skills remained a significant predictor of the intercept at 11.5 years of age when including the covariates (p = .008). CONCLUSIONS Children with SB who exhibited more positive social skills were more likely to a have higher level of medical responsibility in late childhood, but higher levels of social skills were not associated with a more rapid increase in responsibility over time. Identifying existing social strengths and promoting the practice of prosocial skills may have additional benefits to children with SB, including their acquisition of medical responsibility.
Self-assembled nanoparticles of natural phytochemicals (berberine and 3,4,5-methoxycinnamic acid) originated from traditional Chinese medicine for inhibiting multidrug-resistant Staphylococcus aureus.

BACKGROUND In the field of antibacterial, nanomaterials are favored by researchers because of their unique advantages. Medicinal plants, especially traditional Chinese medicine, are considered to be an important source of new chemicals with potential therapeutic effects, as well as an important source for the discovery of new antibiotics. MRSA is endangering people's lives as a kind of multidrug-resistant Staphylococcus aureus which are resistant to tetracycline, amoxicillin, norfloxacin and other first-line antibiotics. It is a hotspot to find good anti-drug-resistant bacteriae, nature-originated nanomaterials with good biocompatibility. OBJECTIVE We reported the formation of phytochemical nanoparticles (NPs) by the self-assembly of berberine (BBR) and 3,4,5-methoxycinnamic acid (3,4,5-TCA) from Chinese herb medicine, which had good antibacterial activity against MRSA. METHOD AND RESULTS We found that NPs had good antibacterial activity against MRSA; especially, its antibacterial activity was better than first-line amoxicillin, norfloxacin and its self-assembling precursors on MRSA. When the concentration reached 0.1 µmol/mL, the inhibition rate of NPs reached 94.62%, which was higher than that of BBR and the other two antibiotics (p < 0.001). It was observed by field-emission scanning electron microscopy (FESEM) that NPs could directly adhere to the bacterial surface, which might be an important aspect of the antibacterial activity of NPs. Meanwhile, we further analyzed that the self-assembly was formed by hydrogen bonds and π-π stacking through ultraviolet-visible (UV-vis), fourier transform infrared spectroscopy (FT-IR), hydrogen nuclear magnetic spectrum (1 H NMR), and powder X-ray diffraction (pXRD). NPs' morphology was observed by FESEM and TEM. The particles size and surface charge were characterized by dynamic light scattering (DLS); and the surface charge was -31.6 mv, which proved that the synthesized NPs were stable. CONCLUSION We successfully constructed a naturally self-assembled nanoparticle, originating from traditional Chinese medicine, which had good antibacterial activity for MRSA. It is a promising way to obtain natural nanoparticles from medicinal plants and apply them to antibacterial therapy.
YAP and Wnt3a independently promote AECIIs proliferation and differentiation by increasing nuclear β-catenin expression in experimental bronchopulmonary dysplasia

Arrested alveolar development is the main pathological characteristic of neonatal bronchopulmonary dysplasia (BPD); however, a number of studies aiming to improve alveolarization have focused on alveolar epithelial cell damage and impairment. Previously, the authors reported that the Wnt signaling plays a key role in alveolar injury and repair by regulating alveolar epithelial type II cell (AECII) proliferation and differentiation. In the present study, the authors wished to investigate whether Yes-associated protein (YAP), a transcriptional coactivator in the Hippo signaling pathway, affects AECII proliferation and differentiation via the Wnt/β-catenin pathway in BPD. It was found that YAP regulated AECII proliferation and differentiation. A decreased expression of YAP, Wnt3a and nuclear β-catenin was observed in lung tissues affected by BPD. In vitro, YAP and Wnt3a overexpression in BPD promoted AECII proliferation and differentiation into AECIs by increasing the nuclear transfer of β-catenin and vice versa. The effects of a decreased Wnt3a expression in primary AECIIs in BPD were compensated by YAP overexpression, as were the effects of Wnt3a knockdown in primary AECIIs. On the whole, the findings of the present study demonstrate that YAP and Wnt3a independently promote AECII proliferation and differentiation in experimental BPD by increasing the nuclear β-catenin levels. Therefore, Wnt3a or YAP may be candidate regulatory targets for improving the outcomes of BPD.
Upregulation of KIF20A promotes tumor proliferation and invasion in renal clear cell carcinoma and is associated with adverse clinical outcome

Extensive research has revealed the pivotal role of kinesin family member 20A (KIF20A) in cancer. However, its latent involvement in renal clear cell carcinoma (ccRCC) still remains unclear. Thus, here we explored the role of KIF20A in ccRCC. For this, a series of software including R (v. 3.6.1), SPSS (v. 23), ImageJ and FlowJo were used for the analyses. Open-access data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-expression Network Analysis (WGCNA) was used for module gene identification. In vitro results indicated that KIF20A expression is up-regulated in ccRCC tissue. KIF20A knockdown was able to inhibite cell proliferation and invasion of kidney A498 and Caki-1 cells. Meanwhile, KIF20A showed a strong association with immune infiltration. Particularly, KIF20A had a strong positive correlation with Th2 cells, Treg cells and Macrophages, but a negative correlation with Th17 cells, Mast cells and NK cells. These correlations may suggest the use of KIF20A as an underlying immunotherapy target in ccRCC. Our data indicated that KIF20A may promote cell invasion and proliferation in ccRCC, thus serving as an independent tumor marker and a putative therapeutic target.
Class Incremental Learning With Few-Shots Based on Linear Programming for Hyperspectral Image Classification

Hyperspectral imaging (HSI) classification has drawn tremendous attention in the field of Earth observation. In the big data era, explosive growth has occurred in the amount of data obtained by advanced remote sensors. Inevitably, new data classes and refined categories appear continuously, and such data are limited in terms of the timeliness of application. These characteristics motivate us to build an HSI classification model that learns new classifying capability rapidly within a few shots while maintaining good performance on the original classes. To achieve this goal, we propose a linear programming incremental learning classifier (LPILC) that can enable existing deep learning classification models to adapt to new datasets. Specifically, the LPILC learns the new ability by taking advantage of the well-trained classification model within one shot of the new class without any original class data. The entire process requires minimal new class data, computational resources, and time, thereby making LPILC a suitable tool for some time-sensitive applications. Moreover, we utilize the proposed LPILC to implement fine-grained classification via the well-trained original coarse-grained classification model. We demonstrate the success of LPILC with extensive experiments based on three widely used hyperspectral datasets, namely, PaviaU, Indian Pines, and Salinas. The experimental results reveal that the proposed LPILC outperforms state-of-the-art methods under the same data access and computational resource. The LPILC can be integrated into any sophisticated classification model, thereby bringing new insights into incremental learning applied in HSI classification.