Miracle-dz/UniFAR-FTUs huggingface dataset:
Biphasic Decline Pattern of Beta-cell Function in Adult-onset Latent Autoimmune Diabetes: an 8-year Prospective Study.

OBJECTIVE To explore the decline pattern and possible determinants of beta-cell function progression in patients with adult-onset latent autoimmune diabetes (LADA). RESEARCH DESIGN AND METHODS One hundred and six LADA individuals were followed up annually in this 8-year prospective study and pattern of beta-cell function progression was assessed. Beta-cell function failure was defined by fasting C-peptide (FCP) <75 pmol/L. Other clinical characteristics including age of onset, body mass index (BMI), GAD autoantibody (GADA) titer were analyzed to find out possible determinants of beta-cell function progression. RESULTS The dropout rate was 4.7%. During the 8 years' follow-up, 29 (28.7%) out of 101 subjects developed beta-cell function failure. The decline pattern of C-peptide in LADA was biphasic, showing an initial rapid linear progression and then followed by a stable mode. The declination speed of FCP was 55.19 pmol/L/year (95%CI -62.54 to -47.84, p <0.001) during the first 5 years and 4.62 pmol/L/year (95%CI -69.83 to 60.60, p=0.790) thereafter. Further analysis showed GADA titer was the most valuable discriminatory parameter related to a higher risk of development of beta-cell function failure (GADA titer of 173.5 WHO units/mL, AUC 0.824). Beta-cell function failure occurred in 71.3% of high GADA titer patients while only 6.2% of low titer ones. CONCLUSIONS The decline pattern of C-peptide was a "fast followed by slow" biphasic mode, with about a quarter of LADA developed beta-cell function failure in the first 8 years' duration. GADA titer less than 173.5 WHO units ⁄mL was propitious for the preservation of beta-cell function.
De-identification of Clinical Text via Bi-LSTM-CRF with Neural Language Models

De-identification of clinical text, the prerequisite of electronic clinical data reuse, is a typical named entity recogni tion (NER) problem. A number of state-of-the-art deep learning methods for NER, such as Bi-LSTM-CRF (bidirec tional long-short-term-memory conditional random fields), have been applied for de-identification. Neural language models used for language representation bring great improvement in lots of NLP tasks when they are integrated with other deep learning methods. In this paper, we introduce Bi-LSTM-CRF with neural language models for de- identification of clinical text, and evaluate it on the de-identification datasets of the i2b2 2014 and the CEGS N- GRID 2016 challenges. Four neural language models of three types individually integrated with Bi-LSTM-CRF are compared in this study. Bi-LSTM-CRF with neural language models achieves the highest "strict" micro-averaged F1-score of 95.50% on the i2b2 2014 dataset and 91.82% on the CEGS N-GRID 2016 dataset, becoming new benchmark results on these two datasets respectively Keywords: De-identification, Named entity recognition, Bidirectional long-short-term-memory, Conditional ran dom fields, Neural language models.
Red Wine Extract Disrupts Th17 Lymphocyte Differentiation in a Colorectal Cancer Context.

SCOPE It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the expression of these mediators and of the pro-inflammatory status that will tip the balance toward tumor progression or anti-tumor immunity. We have demonstrated that a red wine extract (RWE) was able to decrease inflammation through its action on the inflammasome complex. In this study, we sought to determine whether an RWE could impact other key actors of inflammation, in particular T helper 17 (Th17) immune cells. METHODS AND RESULTS Using an RWE containing 4.16 g of polyphenols/liter of wine, we showed that RWE decreased colorectal cancer cells (SW620, HCT116, MC38 and CT26) in vitro and that RWE induced a reduction in colorectal tumor growth associated with a decrease in tumor-infiltrating lymphocytes in vivo. The process of T-lymphocyte differentiation in Th17 cells was altered by RWE, as revealed by the decrease in the expression of key actors controlling this process, such as signal transducer and activator of transcription 3 and retinoid acid-related orphan receptorγt. This disruption was associated with an inhibition of inflammatory interleukin 17 secretion. CONCLUSION The data highlighted the major involvement of Th17 immune cells in the biological effects of an RWE. This article is protected by copyright. All rights reserved.
Salivary profile and dental status of patients with multiple sclerosis.

BACKGROUND Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The MS patients may display biochemical changes in their cerebrospinal fluid, peripheral blood and saliva. Since the salivary profile plays a critical role in maintaining oral health and function, the analysis of saliva in the MS patients would be beneficial to prevent oral diseases, such as dental caries. OBJECTIVES The aim of this study was to evaluate the dental status and salivary profile of the MS patients. MATERIAL AND METHODS The study involved 25 MS patients and 25 healthy controls who were examined with regard to the calcium and phosphorus level, pH and flow rate of saliva as well as the decayed, missing and filled teeth (DMFT) index for permanent first molars. Student's t-test, the χ2 test and the Mann-Whitney test were utilized to compare the study groups. RESULTS Significantly lower salivary flow rates were observed in the MS patients as compared to the controls. The salivary calcium and phosphorus levels were significantly higher in the case group during the first 6 years of the disease and 6-11 years after the onset of the disease, respectively, in comparison with the controls; however, there was no significant difference between the groups in terms of pH. The DMFT index for permanent first molars was higher in the MS patients than in the healthy controls, but not significantly. The number of carious and missing permanent first molars was significantly higher in the MS patients. CONCLUSIONS Multiple sclerosis appears to significantly change the salivary profile and dental status of the patients.
Trust is essential: positive effects of information systems on users’ memory require trust in the system

Abstract Initial results suggest that decision support systems (DSSs) can trigger ‘directed forgetting’ in business settings if users trust in the DSS. In the present study, we further examined this trust effect on DSS-cued forgetting and related positive effects on users’ cognitive resources, performance, and well-being. Moreover, we investigated how trust translates into behavioural intentions to use a DSS, and into actual usage of the DSS. Finally, we examined if risk-related framing of decision outcomes (loss vs. gain framing) moderates trust effects on directed forgetting and behavioural intentions. In line with our expectations, results of an experiment with N = 200 participants confirmed that trust significantly enhances directed forgetting, performance, and well-being. Behavioural intentions fully mediated the trust effect on DSS use. Framing of decision outcomes showed no moderation but a main effect on directed forgetting, with loss framing reducing the directed forgetting effect. Practitioner summary: This experimental study demonstrates the importance of trust in information systems to leverage positive effects of these systems on users’ cognitive resources, performance, and well-being in a simulated complex business setting. Abbreviations: DSS(s): decision support system(s); R–F: remember-forget difference; ANOVA: difference analysis of variance
Platinum nanoparticles induced genotoxicity and apoptotic activity in human normal and cancer hepatic cells via oxidative stress-mediated Bax/Bcl-2 and caspase-3 expression.

Platinum nanoparticles (PtNPs) attract much attention due to their excellent biocompatibility and catalytic properties, but their toxic effects on normal (CHANG) and cancerous (HuH-7) human liver cells are meagre. The cytotoxic and apoptotic effects of PtNPs (average size, 3 nm) were determined in CHANG and HuH-7 cells. After treating these cells were with PtNPs (10, 50, 100, 200, and 300 μg/mL) for 24 and 48 hours, we observed dose- and time-dependent cytotoxicity, as evaluated by using (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, a tetrazole) (MTT) and neutral red uptake (NRU) assays. The production of reactive oxygen species (ROS) was increased in both cells after treatment with the above dose of PtNPs for 24 and 48 hours. Determination of morphological changes of cells, chromosome condensation, mitochondrial membrane potential, and caspase-3 assays showed that PtNPs induce cytotoxicity and apoptosis in CHANG and HuH-7 cells by altering the cell morphology and density, increasing cell population in apoptosis, and causing chromosome condensation. Furthermore, we have studied fragmentation of DNA using alkaline single cell gel electrophoresis and expression of apoptotic genes by real-time PCR (RT-PCR). The percentage of DNA fragmentation was more at 300 μg/mL for 48 hours in both cells, but slightly more fragmentation was found in HuH-7 relative to CHANG cells. Considering all of the above parameters, PtNPs elicited cytotoxicity on CHANG and HuH-7 cells by blocking cell proliferation and inducing apoptosis. Thus this study may be useful in in vitro laboratory studies using cell lines for screening the genotoxic and apoptotic potential of nanoparticles.
Paediatric Medulloblastoma- Comparing Clinical Profile And Outcome With Molecular Subgroups.

Medulloblastoma is the second most common paediatric central nervous system tumour. The treatment is also associated with significant morbidity on a long term basis. We looked at the clinical profile and outcome of children treated for paediatric medulloblastoma under the paediatric haemato-oncology unit and also looked at their molecular subgroups, to see if molecular subgrouping can be used as a better prognostic marker.Quality of life of survivors was analysed using Peds QL. Methods: 109 paediatric medulloblastoma patients were operated on in the neurosurgery department of this hospital between the years 2004-2014. Of these, 73 patients presented to haematooncology for chemotherapy. In addition to this, 3 more patients with biopsy proven medulloblastoma, operated elsewhere, came here for further management. We looked at their clinical profile and outcome in detail. Tumour immunohistochemical markers and histology were used to classify the tumours into WNT, SHH and non WNT/non SHH subgroups. The clinical profile and outcome were compared with the different molecular subgroups. In addition, quality of life of survivors was also analysed using PedsQL, a validated tool for studying quality of life of brain tumour survivors. Results: Of the 76 children, 50 completed treatment. Tumour markers were studied in 43 of the 76 tumours, to classify the tumours into molecular subgroups. 26 out of the 43 tumours in our study belonged to the WNT subgroup. Statistical analysis showed that WNT tumours did better than non WNT tumours in terms of survival. However, there was no difference in their quality of life, probably because of standard treatment received by all patients. Conclusion: On comparison of clinical profile and outcome with molecular subgroups, WNT subgroup has been shown to have a better outcome compared to the other groups. However quality of life analysis does not show any added advantage. Stepping down of therapy for the tumours with better prognosis might be useful in decreasing the long-term morbidity of survivors.
Changes in the mechanical properties of femoral cartilage tissue in advanced osteoarthritis.

PURPOSE The main goal of this article was the analysis of the changes of mechanical properties, thickness and histology of the cartilage in different regions of the femur head in advanced stage of the osteoarthritis. METHODS The study material consisted of cylindrical specimens (9.7 mm) prepared form proximal epiphysis of the human femur bone after hip arthroplasty. The thickness was determined from the reconstruction of the specimen from microtomography (SkyScan 1172, Bruker®) images. Mechanical properties of the cartilage tissue were identified in static indentation test conducted the use of MTS® Synergie 100 testing machine. Histological study enabled us to determine cartilage total thickness as well as location and orientation of the collagen fibers. RESULTS Depending on the region of the head, the cartilage tissue thickness was in the range (0.74-2.23 mm). The lowest thickness values were obtained for the R5 region and the lowest for R4. Samples from R1-R4 regions differ by 24%. Measurements of cartilage tissue indentation, determined with the help of Hayes' formula, showed that the values of mechanical parameters in regions R1, R2, R3 and R5 have similar values (the difference between them is about 5.5%). Region R4, which had the smallest thickness, also had the lowest values of mechanical parameters. CONCLUSIONS Using κ coefficients, proposed by Hayes, enabled us to obtain similar values of mechanical parameters in the regions R1, R2, R3 and R5, despite differences in cartilage tissue thickness. The R4 region, which had the weakest mechanical parameters, was characterized by the strongest reduction of the articular cartilage tissue, which was accompanied by an unformed mass of cartilage residue originating from the abraded surface and bursa fluid.
Building the bond: Predictors of the alliance in neurorehabilitation.

BACKGROUND Neurorehabilitation services are often delivered through group psycho-education programmes. However, little is known about the therapeutic process at work during such sessions. The present study is the first to gain insight into the therapeutic alliance, during a seven-session group programme. In addition, cognitive, emotional, and demographic predictors of the alliance, and participants' feelings towards their group members, were investigated, together with predictors of patient engagement. METHODS Forty-five participants with an acquired brain injury completed a series of questionnaires, and neuropsychological assessment, following group psycho-education. The group facilitator completed a parallel therapeutic alliance questionnaire, and rated participants' engagement. RESULTS Results demonstrated that a strong alliance can be formed in seven group sessions. Notably, no demographic or cognitive factors appear to pose a barrier to developing a therapeutic alliance, nor to group attraction. DISCUSSION High levels of depression, however, may be a challenge, and clinicians may need to tailor their clinical skills to ensure a good therapeutic relationship with such patients. To promote engagement, clinicians may also need to provide additional support to patients with lower levels of education, working memory, and episodic memory impairment.
Muscle BDNF improves synaptic and contractile muscle strength in Kennedy's disease mice in a muscle‐type specific manner

Muscle‐derived neurotrophic factors may offer therapeutic promise for treating neuromuscular diseases. We report that a muscle‐derived neurotrophic factor, BDNF, rescues synaptic and muscle function in a muscle‐type specific manner in mice modelling Kennedy's disease (KD). We also find that BDNF rescues select molecular mechanisms in slow and fast muscle that may underlie the improved cellular function. We also report for the first time that expression of BDNF, but not other members of the neurotrophin family, is perturbed in muscle from patients with KD. Given that muscle BDNF had divergent therapeutic effects that depended on muscle type, a combination of neurotrophic factors may optimally rescue neuromuscular function via effects on both pre‐ and postsynaptic function, in the face of disease.
Profile of RT-PCR for SARS-CoV-2: A Preliminary Study From 56 COVID-19 Patients

Abstract A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered patients with COVID-19. We found viral shedding occurred up to 6 weeks after onset of symptoms. A prolonged observation period is necessary for older patients.
Evaluation of Tumor infiltrating lymphocytes in breast carcinoma and their correlation with molecular subtypes, tumor grade and stage.

BACKGROUND Tumour infiltrating lymphocytes (TILs) exhibit the local immune response directed against tumor growth and metastasis. TILs have emerged as a tool to assess immune-reactivity in various malignancies including colon, ovary, lung, bladder, breast etc as well as independent marker of favourable prognosis in many tumors. TILs in breast cancer (BC) play a role in tumor response to therapy in the adjuvant and neoadjuvant settings, especially in triple-negative cancers. MATERIAL & METHODS This cross sectional study comprised of 101cases of invasive breast carcinoma. For each case, a representative 5 μm H&E stained section was selected and the clinicopathological details were recorded. To establish the molecular subtype of breast cancer, immunohistochemistry for ER, PR and Her2neu was done. Both stromal (sTIL) and intratumoral (iTIL) TILs were assessed based on the recommendations of the International TIL Working Group (ITILWG). RESULTS A statistically significant difference was observed in the mean sTIL as well as iTIL scores and tumor grade, size, molecular type and lymph node metastasis. A signification correlation was observed between stromal TIL and tumor grade, lymph node metastasis, molecular subtype and mitotis. Intratumoral TIL showed a significant correlation with tumor size, mitosis, tumor grade, distant metastasis, stage and lymph node metastasis. Moreover, stromal and intratumoral TIL showed a highly significant correlation with each other. CONCLUSION The IWTILG recommendations are reproducible and reliable for the evaluation of sTILs and iTILs. TILs, as evaluated on Hematoxylin and eosin (H&E) slides, has been shown in numerous studies now to be a reliable, reproducible, inexpensive and readily available marker of pre-existing antitumor immunity in breast cancer. We suggest that TILs should be evaluated for each case of breast carcinoma and should be part of histopathology report.
Improved prediction of MHC II antigen presentation through integration and motif deconvolution of mass spectrometry MHC eluted ligand data

Major Histocompatibility Complex II (MHC II) molecules play a key role in the onset and control of cellular immunity. In a highly selective process, MHC II presents peptides derived from exogenous antigens on the surface of antigen presenting cells for T cell scrutiny. Understanding the rules defining this presentation holds key insights into the regulation and potential manipulation of the cellular immune system. In our work for furthering rational prediction of peptide epitopes, we have integrated data from eluted MHC ligand mass spectrometry assays, that inherently contains signals of the events leading to antigen presentation. The full integration of this data type is a fruit of recent developments of the NNAlign_MA machine learning framework: two output-neuron architecture, encoding of ligand context and logical handling of ligands with multiple potential allele annotation. In large-scale benchmarking, we demonstrate here how these features synergistically improve ligand and CD4 T cell epitope prediction performance beyond that of current state-of-the-art predictors. We observe motifs in ligand termini consistently across MHC alleles and we put forth a strategy of targeting these motifs for MHC II agnostic de-immunization.
A pilot study on the association between the blood oxygen level-dependent signal in the reward system and dopamine transporter availability in adults with attention deficit hyperactivity disorder

Abstract Background It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear. Methods Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test. Result DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls. Conclusions The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal–amygdala neural circuitry during positive‐social emotion regulation

Positive‐social emotions mediate one's cognitive performance, mood, well‐being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top‐down signals that stem from the prefrontal cortices (PFC) which modulate bottom‐up emotional responses in the amygdala. However, it remains unclear if positive‐social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive‐social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive‐social emotion upregulation was associated with an increase in top‐down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.
Stress, Schizophrenia, and Violence: A Machine Learning Approach

This study employs machine learning algorithms to examine the causes for engaging in violent offending in individuals with schizophrenia spectrum disorders. Data were collected from 370 inpatients at the Centre for Inpatient Forensic Therapy, Zurich University Hospital of Psychiatry, Switzerland. Based on findings of the general strain theory and using logistic regression and machine learning algorithms, it was analyzed whether accumulation and type of stressors in the inpatients’ history influenced the severity of an offense. A higher number of stressors led to more violent offenses, and five types of stressors were identified as being highly influential regarding violent offenses. Our findings suggest that an accumulation of stressful experiences in the course of life and certain types of stressors might be particularly important in the development of violent offending in individuals suffering from schizophrenia spectrum disorders. A better understanding of risk factors that lead to violent offenses should be helpful for the development of preventive and therapeutic strategies for patients at risk and could thus potentially reduce the prevalence of violent offenses.