Miracle-dz/UniFAR-FTUs huggingface dataset:
Apolipoprotein B/AI ratio as an independent risk factor for intracranial atherosclerotic stenosis

To investigate the relation of higher apolipoprotein B/apolipoprotein AI (apoB/AI) ratio with the risk of suffering intracranial atherosclerotic stenosis (ICAS) in both stroke and non-stroke population, we enrolled 1138 patients with acute ischemic stroke (359 with ICAS, 779 without ICAS) and 1072 non-stroke controls (239 with ICAS, 833 without ICAS) into the study. ICAS was defined as atherosclerotic stenosis >50% or the occlusion of the several main intracranial arteries. ApoB/AI ratio of patients with ICAS was significantly higher than those of individuals without ICAS in both stroke group and non-stroke groups. Increased ratio of apoB/AI was an independent risk factor for ICAS in both stroke group (OR 2.80, 95% CI 1.45-5.42, p=0.002) and non-stroke groups (OR 3.38, 95% CI 1.61-7.12, p<0.001). Compared with the lowest quartile, the third (Stroke OR=1.71, 95%CI, 1.11-2.63, p=0.014; Non-stroke OR=1.71, 95%CI, 1.04-2.82, p=0.033) and forth quartiles (Stroke OR=2.06, 95%CI, 1.27-3.35, p=0.003; Non-stroke OR=2.00, 95%CI, 1.16-3.49, p=0.012) were independent risk factors for ICAS in both stroke (p value for trend=0.001)) and non-stroke (p value for trend=0.006) groups. In summary, increased apoB/AI ratio was a valuable independent risk factor for ICAS in stroke patients as well as in non-stroke controls.
Impact of a New Consumer Form on the Quantity and Quality of Adverse Event Reports Submitted to the United States Food and Drug Administration

Consumers and healthcare professionals can voluntarily report adverse experiences associated with drug products to the United States Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Consumers and healthcare professionals used the same general voluntary reporting form (GVR) until mid‐2013, when a consumer voluntary reporting form (ConVR), written in plain language, was implemented. The objective of this study was to examine the effect of the ConVR on the quality and quantity of consumer reports submitted directly to FAERS.
Effect of Aggression on Peer Acceptance Among Adolescents During School Transition and Non-Transition: Focusing on the Moderating Effects of Gender and Physical Education Activities

The present study examined the effect of aggression on peer acceptance among adolescents. We focused on the moderating effects of gender and participation in physical education activities and examined whether these effects varied during school transition. We used longitudinal data of adolescents aged 10 to 17 years that were obtained from a survey that was conducted by the National Youth Policy Institute. In only early adolescence, the interaction effect of gender and physical education activity influenced the relationship between aggression and peer acceptance. Specifically, the negative relationship between aggression and peer acceptance was strengthened among female students who participated in physical education activities as compared to female students who did not. This effect was not observed in male students. However, during transition from primary to secondary school, the negative effect of physical education activities did not exist. For middle-adolescents, for whom physical education activities increased more than previous years, the negative relationship between aggression and peer acceptance worsened. These influences were the same, regardless of gender. Thus, this study suggests that physical education activities improve the negative relationship between aggression and peer acceptance during school transition.
Evidence of orofacial myofunctional therapy patients with asthma and rhinitis: a systematic review.

PURPOSE to evaluate the efficacy of orofacial myofunctional therapy in improving orofacial function and nasal breathing in patients with asthma and rhinitis and, consequently, achieve clinical control of these conditions. RESEARCH STRATEGIES We used the elements of the PICOT method (study population, intervention, comparison, outcomes and type of studies) to define the eligibility criteria: (1) Population: patients with asthma and rhinitis; (2) Intervention: orofacial myofunctional therapy to improve chewing, swallowing, and breathing; (3) Comparison: control group without orofacial myofunctional therapy; (4) Predefined outcomes: clinical control of asthma and improvement of orofacial functions and nasal breathing; (5) Study type: clinical trials. The data were collected from PubMed, SCOPUS, Web of Science, Science Direct, LILACS, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), OATD, and Open Thesis, in November 2018. SELECTION CRITERIA Randomized controlled trials published in full-text versions without language restriction, no filter was used. DATA ANALYSIS Demographic characteristics of study participants, specific diagnosis of asthma and control medication, type, duration, intensity and follow-up of orofacial myofunctional therapy, and outcome data. The risk of bias was assessed according to the Cochrane guidelines for clinical trials. RESULTS One study met the eligibility criteria: although the study has shown an improvement of functional control and clinical scores of asthma, the evidence is very low. CONCLUSION There is no scientific evidence on the efficacy of orofacial myofunctional therapy in improving clinical control, orofacial function, and nasal breathing in patients with asthma and rhinitis.
Glucose Concentration Measurement in Human Blood Plasma Solutions with Microwave Sensors

Three microwave sensors are used to track the glucose level of different human blood plasma solutions. In this paper, the sensors are evaluated as glucose trackers in a context close to real human blood. Different plasma solutions sets were prepared from a human blood sample at several added glucose concentrations up to 10 wt%, adding also ascorbic acid and lactic acid at different concentrations. The experimental results for the different sensors/solutions combinations are presented in this work. The sensors show good performance and linearity as glucose level retrievers, although the sensitivities change as the rest of components vary. Different sensor behaviors depending upon the concentrations of glucose and other components are identified and characterized. The results obtained in terms of sensitivity are coherent with previous works, highlighting the contribution of glucose to the dielectric losses of the solution. The results are also consistent with the frequency evolution of the electromagnetic signature of glucose found in the literature, and are helpful for selecting frequency bands for sensing purposes and envisioning future approaches to the challenging measurement in real biological contexts. Discussion of the implications of the results and guidelines for further research and development of more accurate sensors is offered.
Antimicrobial Activity of Protamine-Loaded Calcium Phosphates against Oral Bacteria

Protamine is an antimicrobial peptide extracted from fish. In this study, we loaded protamine onto dicalcium phosphate anhydride (DCPA), a dental material. Protamine was loaded by stirring DCPA into a protamine solution. To explore the antimicrobial activity of the materials, we cultivated Streptococcus mutans on fabricated discs for 24 h. When S. mutans was cultivated on the discs under no sucrose conditions, the loaded protamine was not released, and the ratio of dead bacteria increased on the surface of P (125) DCPA (half of the saturated level of protamine (125 ppm protamine) was loaded). Aside from P (500) DCPA (saturated level of protamine was loaded), some protamine was released, and the number of planktonic bacteria in the supernatant decreased. Using medium containing 1% sucrose, the release of protamine was promoted from P (125) DCPA due to lowered pH. However, lowering of the pH decreased the antimicrobial activity of protamine. On the other hand, P (500) DCPA released protamine before the pH was lowered, and biofilm formation was inhibited. The loaded protamine expressed antimicrobial activity, both on the surface of the materials and in the surrounding environment. The interaction of loaded protamine with calcium phosphates could promote the application of protamine in the dental field.
Association between intrahepatic cholestasis in pregnancy and gestational diabetes mellitus. A retrospective analysis.

OBJECTIVES Intrahepatic cholestasis of pregnancy (ICP) is a liver specific disorder affecting 0.08%-27.6% pregnant women.It is characterized by reduced expression of the primary bile acid farnesoid receptor (FXR). In recent studies, it has beenshowed that FXR has an impact on normal glucose homeostasis. Based on that it was suggested that the level of bile acidscorrelates with glucose level. The aim of the study was to evaluate the association between ICP and gestational diabetesmellitus (GDM). MATERIAL AND METHODS 102 singleton patients complicated by ICP were included to the study and divided into twogroups: non-GDM group (74 patients) and GDM group (28 patients). ICP was diagnosed based on the serum bile acidslevel > 10 μmol/L and GDM with the 75 g oral glucose tolerance test and FIGO guidelines. Demographic and clinical outcomedata (including maternal age, BMI and infant weight) and ICP and GDM biochemical markers were collected. RESULTS The incidence of GDM in ICP patients was 27.45%. 73% of women included to the study developed mild cholestasis.Lower levels of serum bile acids were correlated with GDM group. When compared mean total bilirubin level wassignificantly higher in non-GDM group. Transaminases (ALT, AST) and neonate condition including mean birth weightrevealed no significant difference between the groups. On the other hand, prevalence of large for gestational age wassignificantly higher in non-GDM group (p < 0.00001). CONCLUSIONS The incidence of ICP is higher in women with GDM.
Improving the Dynamic Mechanical Properties of XNBR Using ILs/KH550-Functionalized Multilayer Graphene

Graphene has been considered an ideal nanoscale reinforced phase for preparing high-performance composites, but the poor compatibility and weak interfacial interaction with the matrix have limited its application. Here a highly effective and environmentally friendly method for the functionalization of graphene is proposed through an interaction between as-exfoliated graphene and (3-aminopropyl) triethoxysilane (KH550), in which 1-butylsulfonate-3-methylimidazolium bisulfate (BSO3HMIm)(HSO4) ionic-liquids-modified graphene was prepared via an electrochemical exfoliation of graphite in (BSO3HMIm)(HSO4) solution, then (BSO3HMIm)(HSO4)-modified graphene as a precursor was reacted with amine groups of KH550 for obtaining (BSO3HMIm)(HSO4)/KH550-functionalized graphene. The final products as filler into carboxylated acrylonitrile‒butadiene rubber (XNBR) improve the dynamic mechanical properties. The improvement in the dynamic mechanical properties of the nanocomposite mainly depends on high interfacial interaction and graphene’s performance characteristics, as well as a good dispersion between functionalized graphene and the XNBR matrix.
Comparison of MRI IVIM and MR perfusion imaging in acute ischemic stroke due to large vessel occlusion

Purpose Intravoxel incoherent motion is a diffusion-weighted imaging magnetic resonance imaging technique that measures microvascular perfusion from a multi-b value sequence. Intravoxel incoherent motion microvascular perfusion has not been directly compared to conventional dynamic susceptibility contrast perfusion-weighted imaging in the context of acute ischemic stroke. We determined the degree of correlation between perfusion-weighted imaging and intravoxel incoherent motion parameter maps in patients with acute ischemic stroke. Methods We performed a retrospective cohort study of acute ischemic stroke patients undergoing thrombectomy treatment triage by magnetic resonance imaging. Intravoxel incoherent motion perfusion fraction maps were derived using two-step voxel-by-voxel post-processing. Ischemic core, penumbra, non-ischemia, and contralateral hemisphere were delineated based upon diffusion-weighted imaging and perfusion-weighted imaging using a Tmax >6 s threshold. Signal intensity within different brain compartments were measured on intravoxel incoherent motion (IVIM f, IVIM D*, IVIM fD*) parametric maps and compared the differences using one-way ANOVA. Ischemic volumes were measured on perfusion-weighted imaging and intravoxel incoherent motion parametric maps. Bland–Altman analysis and voxel-based volumetric comparison were used to determine the agreements among ischemic volumes of perfusion-weighted imaging and intravoxel incoherent motion perfusion parameters. Inter-rater reliability on intravoxel incoherent motion maps was also assessed. Significance level was set at α < 0.05. Results Twenty patients (11 males, 55%; mean age 67.1 ± 13.8 years) were included. Vessel occlusions involved the internal carotid artery (6 patients, 30%) and M1 segment of the middle cerebral artery (14, 70%). Mean pre-treatment core infarct volume was 19.07 ± 23.56 ml. Mean pre-treatment ischemic volumes on perfusion-weighted imaging were 10.90 ± 13.33 ml (CBV), 24.83 ± 23.08 ml (CBF), 58.87 ± 37.85 ml (MTT), and 47.53 ± 26.78 ml (Tmax). Mean pre-treatment ischemic volumes on corresponding IVIM parameters were 23.20 ± 25.63 ml (IVIM f), 14.01 ± 16.81 ml (IVIM D*), and 27.41 ± 40.01 ml (IVIM fD*). IVIM f, D, and fD* demonstrated significant differences (P < 0.001). The best agreement in term of ischemic volumes and voxel-based overlap was between IVIM fD* and CBF with mean volume difference of 0.5 ml and mean dice similarity coefficient (DSC) of 0.630 ± 0.136. Conclusion There are moderate differences in brain perfusion assessment between intravoxel incoherent motion and perfusion-weighted imaging parametric maps, and IVIM fD* and perfusion-weighted imaging CBF show excellent agreement. Intravoxel incoherent motion is promising for cerebral perfusion assessment in acute ischemic stroke patients.
Severity of Dyskinesia and D3R Signaling Changes Induced by L-DOPA Treatment of Hemiparkinsonian Rats Are Features Inherent to the Treated Subjects

Extensive damage to nigrostriatal dopaminergic neurons leads to Parkinson’s disease (PD). To date, the most effective treatment has been administration of levodopa (L-DOPA) to increase dopaminergic tone. This treatment leads to responses that vary widely among patients, from predominantly beneficial effects to the induction of disabling, abnormal movements (L-DOPA induced dyskinesia (LID)). Similarly, experimental studies have shown animals with widely different degrees of LID severity. In this study, unilateral injections of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB) produced more than 90% depletion of dopamine in both the striatum and the substantia nigra reticulata (SNr) of rats. Population analysis showed that dopamine depletion levels were clustered in a single population. In contrast, analysis of abnormal involuntary movements (AIMs) induced by L-DOPA treatment of 6-OHDA-lesioned animals yielded two populations: one with mild LID, and the other with severe LID, which are also related to different therapeutic responses. We examined whether the severity of LID correlated with changes in dopamine 3 receptor (D3R) signaling because of the following: (a) D3R expression and the induction of LID are strongly correlated; and (b) dopaminergic denervation induces a qualitative change in D3R signaling in the SNr. We found that the effects of D3R activation on cAMP accumulation and depolarization-induced [3H]-gamma-aminobutyric acid ([3H]-GABA) release were switched. L-DOPA treatment normalized the denervation-induced changes in animals with mild LID. The D3R activation caused depression of both dopamine 1 receptor (D1R)-induced increases in cAMP production and depolarization-induced [3H]-GABA release, which were reversed to their pre-denervation state. In animals with severe LID, none of the denervation-induced changes were reversed. The finding that in the absence of identifiable differences in 6-OHDA and L-DOPA treatment, two populations of animals with different D3R signaling and LIDs severity implies that mechanisms intrinsic to the treated subject determine the segregation.
Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study

Abstract Objective To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures. Design Retrospective cohort study. Setting The Health Improvement Network (THIN), a database of electronic patient records from UK primary care. Participants Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017. Exposure TSH concentration in patients with hypothyroidism. Main outcome measures Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome. Results 162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)). Conclusions In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.
Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice

Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of-function mechanism caused by nucleus-retained mutant DMPK (DM1 protein kinase) transcripts containing CUG expansions (CUGexps). However, systemic use of ASOs for this muscular disease remains challenging due to poor drug distribution to skeletal muscle. To overcome this limitation, we test an arginine-rich Pip6a cell-penetrating peptide and show that Pip6a-conjugated morpholino phosphorodiamidate oligomer (PMO) dramatically enhanced ASO delivery into striated muscles of DM1 mice following systemic administration in comparison with unconjugated PMO and other ASO strategies. Thus, low-dose treatment with Pip6a-PMO-CAG targeting pathologic expansions is sufficient to reverse both splicing defects and myotonia in DM1 mice and normalizes the overall disease transcriptome. Moreover, treated DM1 patient–derived muscle cells showed that Pip6a-PMO-CAG specifically targets mutant CUGexp-DMPK transcripts to abrogate the detrimental sequestration of MBNL1 splicing factor by nuclear RNA foci and consequently MBNL1 functional loss, responsible for splicing defects and muscle dysfunction. Our results demonstrate that Pip6a-PMO-CAG induces long-lasting correction with high efficacy of DM1-associated phenotypes at both molecular and functional levels, and strongly support the use of advanced peptide conjugates for systemic corrective therapy in DM1.
Lesion-based Evaluation Predicts Treatment Response to Lenvatinib For Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Korean Multicenter Retrospective Study.

BACKGROUND Lenvatinib, a tyrosine kinase inhibitor (TKI) recently approved for treating radioactive iodine-refractory differentiated thyroid cancer, has been shown to delay disease progression and provide meaningful benefit for overall survival. However, there is no predictive marker for response to lenvatinib before initiating treatment. We comprehensively analyzed clinical and radiological parameters to predict response to lenvatinib using lesion-based assessments. METHODS Medical records were collected from 67 patients treated with lenvatinib in 11 referral hospitals across Korea from June 2015 to December 2017. Up to 96 measurable lesions, defined per RECIST version 1.1, were evaluated serially until progressive disease occurred, and tumor doubling time (TDT) was calculated based on changes between historical computed tomography (CT) scans and baseline CT scans performed at treatment initiation. RESULTS Excluding patients with anaplastic thyroid cancer, no thyroidectomy, non-target lesions only, or treatment periods of less than one month, 57 patients were analyzed, of whom seven (12.2%) were TKI-naïve. The median progression-free survival (PFS) was 5.1 months (95% confidence interval [CI], 4.4-9.5), the median overall survival (OS) was 19.3 months (95% CI 12.4-not reached), the mean duration of response was 6.0 ± 4.4 months, and the objective response rate was 38%. In lesion-based assessments, 31 lesions (32.2%) with significant tumor shrinkage (complete remission or partial response) were significantly associated with shorter TDT (<12 months) (p = 0.02). Patients with rapidly progressive disease with a shorter initial TDT (<6 months) were more likely to respond to lenvatinib (p = 0.03). Patients exposed to lenvatinib at an average of ≥16 mg per day, or who were TKI-naïve prior to treatment with lenvatinib, had a lower risk of progression; however, the risk reduction did not reach statistical significance (daily dosage p = 0.07, TKI exposure p = 0.09). CONCLUSIONS Tumor doubling time calculations at the beginning of treatment and lesion-based tumor assessment may help identify potential responders to lenvatinib therapy and predict therapeutic responses.
Mucosal IgG in inflammatory bowel disease – a question of (sub)class?

ABSTRACT Immunoglobulins (Igs) form a cornerstone of mucosal immunity. In the gastrointestinal tract, secretory IgA and IgM bind to commensal microorganisms within the intestinal lumen to prevent them from breaching the intestinal epithelium – a process known as immune exclusion. In recent years, there has been renewed interest in the role of IgG in intestinal immunity, driven in part by a genetic association of an affinity-lowering variant of an IgG receptor, FcγRIIA, with protection from ulcerative colitis (UC), a subclass of inflammatory bowel disease (IBD). We recently demonstrated a role for IgG and Fcγ receptor signalling in driving pathogenic IL-1β production by colonic mononuclear phagocytes and the subsequent induction of a local type 17 response in UC. Here, we discuss the potential relevance of our observations to the other major subclass of IBD – Crohn’s disease (CD) – where the genetic association with FCGR variants is less robust and consider how this may impact therapeutic interventions in these disease subsets.