Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroanatomy of expressive suppression: The role of the insula.

Expressive suppression is a response-focused regulatory strategy aimed at concealing the outward expression of emotion that is already underway. Expressive suppression requires the integration of interoception, proprioception, and social awareness to guide behavior in alignment with personal and interpersonal goals-all processes known to involve the insular cortex. Frontotemporal dementia (FTD) provides a useful patient model for studying the insula's role in socioemotional regulation. The insula is a key target of early atrophy in FTD, causing patients to lose the ability to represent the salience of internal and external conditions and to use these representations to guide behavior. We examined a sample of 59 patients with FTD, 52 patients with Alzheimer's disease (AD), and 38 neurologically healthy controls. Subjects viewed 2 disgust-eliciting films in the laboratory. During the first film, subjects were instructed to simply watch (emotional reactivity trial); during the second, they were instructed to hide their emotions (expressive suppression trial). Structural images from a subsample of participants (n = 42; 11 FTD patients, 11 AD patients, and 20 controls) were examined in conjunction with behavior. FreeSurfer was used to quantify regional gray matter volume in 41 empirically derived neural regions in both hemispheres. Of the 3 groups studied, FTD patients showed the least expressive suppression and had the smallest insula volumes, even after controlling for age, gender, and emotional reactivity. Among the brain regions examined, the insula was the only significant predictor of expressive suppression ability, with lower insula gray matter volume in both hemispheres predicting less expressive suppression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Surveillance of swine influenza viruses in sentinel familial farms in Hung Yen province in Northern Vietnam in 2013–2014

From May 2013 to April 2014, 15 swine family‐run farms (17 pig litters) in two districts in Hung Yen province, near Hanoi, were virologically and epizootiologically monitored for swine influenza viruses (SIV) monthly. No SIV was isolated from nasal swabs. Maternal antibodies were detected in 10 litters, and seroconversion against SIV was detected in six litters. There was a marked difference in patterns of SIV transmission in the two districts. Van Lam district which has low density of swine with mainly smallholder farms had low intensity of SIV, with much of the infection caused by H1N1 2009 pandemic‐like viruses A(H1N1)pdm09, likely originated from humans. In contrast, Van Giang district, which has high swine density and larger farms, had high levels of typical SIV (triple reassortants H3N2 and H3N2 Binh Duong lineage viruses) circulating within swine. With one exception, the SIV lineages detected were those we concurrently isolated from studies in a large central abattoir in Hanoi. Influenza‐like illness symptoms reported by farmers were poorly correlated with serological evidence of SIV infection.
DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes

A Zika virus vaccine administered to macaques before conception reduces maternal viremia and improves fetal outcomes. Curbing congenital Zika virus infection The impact on a developing fetus is one of the most pressing concerns for developing vaccines or treatments for Zika virus. To assess fetal protection, Van Rompay et al. immunized nonhuman primates with a DNA vaccine before conception and then performed multiple Zika virus challenges in the first few months of pregnancy. Compared to unvaccinated controls, vaccinated animals had reduced viremia in terms of both magnitude and duration. Early fetal loss and fetal pathology was accordingly reduced. These results show that Zika virus vaccines given to women of childbearing age may help prevent damaging sequelae in offspring. Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.
Retrospective Analysis of Patients With Acute Invasive Fungal Rhinosinusitis in a Single Tertiary Academic Medical Center: A 10-Year Experience

Background Acute invasive fungal rhinosinusitis (AIFRS) is an aggressive, potentially fatal disease that can spread rapidly to the orbit and intracranial structures causing significant mortality and morbidity. Objective In this study, we present a 10-year experience from a tertiary academic medical center of patients presenting with AIFRS. Data on presentation, mortality rate, comorbidities, surgical, and medical management were analyzed. Methods A retrospective chart review was performed in a tertiary academic medical center of patients with AIFRS from January 2009 through February 2019. Data collected included demographics, presenting symptoms, comorbidities, immunosuppression status, endoscopic and imaging findings, orbital and intracranial complications, surgical and medical management, as well as outcomes and mortality. Results A total of 34 patients were identified. In our series, mortality was noted to be 61.8%, excluding patients who were lost to follow-up. The most common presenting symptoms included facial pain, ophthalmologic complaints, headaches, and proptosis. Only 4 of the 34 patients did not undergo surgical intervention, as they were not deemed surgical candidates; they all succumbed to their disease. Twenty-six of the 30 surgical patients (86.7%) underwent endoscopic sinus surgery, 8 underwent an open approach (26.7%), while 7 patients underwent orbital exenteration (23.3%). All patients had surgical pathology consistent with AIFRS. Fungal species isolated from culture included Aspergillus, Mucor/Rhizopus, Candida, Cunninghamella Scedosporium boydii, Paecilomyces, and Scopulariopsis. Medical therapies included intravenous amphotericin B, caspofungin, posaconazole, voriconazole, isavuconazole, and micafungin. Conclusion AIFRS was associated with 61.8% mortality in our series of 34 patients over the past 10 years. Early diagnosis, as well as rapid and aggressive surgical and medical management, is necessary for optimal outcomes in this devastating disease.
Association between serum iron levels and the risk of cervical cancer in Chinese: a meta-analysis

Objectives To evaluate the association between serum iron levels and cervical cancer risk in Chinese populations. Methods A literature search was conducted using the PubMed, WanFang, and SinoMed databases up to April 30, 2019. Pooled standard mean differences (SMD) and 95% confidence intervals (CI) were analyzed using R software with a random-effects model. Results Data from nine studies comprising 454 cervical cancer patients and 880 controls were used in the analysis. Our results demonstrated that serum iron levels in cervical cancer patients were significantly lower than those in controls in Chinese populations (summary SMD = −1.24, 95%CI = −1.37 to −1.10; I2 = 93.4%). No publications bias was detected. Sensitivity analysis indicated that no single study had a significant effect on the overall SMD. Conclusions Our findings show that serum iron levels are lower in patients with cervical cancer than in control individuals. However, further high-quality studies are necessary to clarify the role of serum iron levels in cervical cancer risk.
High intracranial pressure may be the initial inducer of elevated plasma D-dimer level after aneurysmal subarachnoid haemorrhage

Abstract Objective: The plasma D-dimer has been regarded as a poor prognosis factor in aneurysmal subarachnoid haemorrhage (aSAH) patients, but the reason of elevated D-dimer level has not been revealed. In this study, we retrospectively explored the potential clinical parameters which might be related to D-dimer level and further attempted to explain the pathological process of D-dimer level elevation in aSAH patients. Patients and methods: The qualified patients with aSAH were recruited and treated in Sichuan Provincial People's Hospital from 1 October 2015 to 28 February 2018. All clinical data were collected, the blood samples were gathered on admission and the levels of D-dimer were detected by the clinical laboratory. The χ2-test, univariate and multiple linear regression analysis were used to seek the relationship between clinical variables and D-dimer level. Results: Total 98 aSAH patients were enrolled. The χ2-test showed a significant difference in clinical characteristics of gender, hyperlipidaemia and ICP between the patients with normal D-dimer level and the others with a high D-dimer level (p < .05). The univariate linear regression analysis and the multiple linear regression analysis showed the combined CCT and ICP were still significantly related to D-dimer level (p < .05). Conclusion: Besides the other related factors, the increased ICP was obviously associated with the elevated plasma D-dimer level. It may indicate that the high ICP acted as the initial role, then led to poor perfusion, even induced the microthrombosis and activated the fibrinolytic system, which eventually contributed to D-dimer level increasing in aSAH patients.
Power to the People: Power, Negative Results and Sample Size.

The practical application of statistical power is becoming an increasingly important part of experimental design, data analysis, and reporting. Power is essential to estimating sample size as part of planning studies and obtaining ethical approval for them. Furthermore, power is essential for publishing and interpreting negative results. In this manuscript, we review what power is, how it can be calculated, and reporting recommendations if a null result is found. Power can be thought of as reflecting the signal to noise ratio of an experiment. The conventional wisdom that statistical power is driven by sample size (which increases the signal in the data), while true, is a misleading oversimplification. Relatively little discussion covers the use of experimental designs which control and reduce noise. Even small improvements in experimentaldesign can achieve high power at much lower sample sizes than (for instance) a simple t test. Failure to report experimentaldesign or the proposed statistical test on animal care and use protocols creates a dilemma for IACUCs, because it is unknownwhether sample size has been correctly calculated. Traditional power calculations, which are primarily provided for animal number justifications, are only available for simple, yet low powered, experimental designs, such as paired t tests. Thus, in most controlled experimental studies, the only analyses for which power can be calculated are those that inheriently have low statistical power; these analyses should not be used because they require more animals than necessary. We provide suggestions for more powerful experimental designs (such as randomized block and factorial designs) that increase power, and we describe methods to easily calculate sample size for these designs that are suitable for IACUC number justifications. Finally we also provide recommendations for reporting negative results, so that readers and reviewers can determine whetheran experiment had sufficient power. The use of more sophisticated designs in animal experiments will inevitably improve power, reproducibility, and reduce animal use.
Combined albumin-bilirubin grade and Mac-2 binding protein glycosylation isomer as a useful predictor in compensated liver cirrhosis

Abstract We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.
Wobble-Board Balance Intervention to Decrease Symptoms and Prevent Reinjury in Athletes with Chronic Ankle Instability: An Exploration Case Series.

Controlled research has shown that a single-exercise wobble-board intervention is effective at reducing symptoms and increasing function in patients with chronic ankle instability. However, the effectiveness of this protocol has not been documented in a realistic intercollegiate athletics environment. Eight intercollegiate athletes with chronic ankle instability participated in an 8-week (3 sessions/wk) wobble-board intervention. In a realistic environment, this simple intervention was feasible to implement and resulted in meaningful improvements in patient-reported stability for more than half of the patients (5 of 8) but only improved the global rating of function and pain for a minority of the patients (2 of 8 and 3 of 8, respectively). Not all patients experienced equal symptom reduction; however, no new ankle sprains occurred during the intervention.
NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non‐inflammatory breast cancers

Inflammatory breast cancer (IBC) is the most pro‐metastatic form of breast cancer. Better understanding of its pathophysiology and identification of actionable genetic alterations (AGAs) are crucial to improve systemic treatment. We aimed to define the DNA profiles of IBC vs noninflammatory breast cancer (non‐IBC) clinical samples in terms of copy number alterations (CNAs), mutations, and AGAs. We applied targeted next‐generation sequencing (tNGS) and array‐comparative genomic hybridization (aCGH) to 57 IBC and 50 non‐IBC samples and pooled these data with four public datasets profiled using NGS and aCGH, leading to a total of 101 IBC and 2351 non‐IBC untreated primary tumors. The respective percentages of each molecular subtype [hormone receptor‐positive (HR+)/HER2−, HER2+, and triple‐negative] were 68%, 15%, and 17% in non‐IBC vs 25%, 35%, and 40% in IBC. The comparisons were adjusted for both the molecular subtypes and the American Joint Committee on Cancer (AJCC) stage. The 10 most frequently altered genes in IBCs were TP53 (63%), HER2/ERBB2 (30%), MYC (27%), PIK3CA (21%), BRCA2 (14%), CCND1 (13%), GATA3 (13%), NOTCH1 (12%), FGFR1 (11%), and ARID1A (10%). The tumor mutational burden was higher in IBC than in non‐IBC. We identified 96 genes with an alteration frequency (p < 5% and q < 20%) different between IBC and non‐IBC, independently from the molecular subtypes and AJCC stage; 95 were more frequently altered in IBC, including TP53, genes involved in the DNA repair (BRCA2) and NOTCH pathways, and one (PIK3CA) was more frequently altered in non‐IBC. Ninety‐seven percent of IBCs displayed at least one AGA. This percentage was higher than in non‐IBC (87%), notably for drugs targeting DNA repair, NOTCH signaling, and CDK4/6, whose pathways were more frequently altered (DNA repair) or activated (NOTCH and CDK4/6) in IBC than in non‐IBC. The genomic landscape of IBC is different from that of non‐IBC. Enriched AGAs in IBC may explain its aggressiveness and provide clinically relevant targets.
Comparative study on the replication of HCV1b genome between wild‐type and cell culture‐adaptive mutant in regard to sensitivities against anti‐HCV drugs

The replicon system, which mimics viral genome replication in culture cells, has been widely used to analyze the genome replication of the hepatitis C virus (HCV). However, most HCV genomes used in the system include adaptive mutations (AMs) that are vital for replication in culture cells despite the nonexistence of such mutations in the genome of wild‐type (WT) HCV in patients. In order to study the genome replications of WT HCV, new HCV subgenomic replicon (SGR) systems were established using Huh‐7.5‐derived cells producing Sec14‐like protein 2 constitutively and SGR of KT9 (one of the HCV genotype 1b clones) with WT genome (SGR KT9WT) in this study. The replication efficiency and sensitivities of SGR KT9WT to anti‐HCV drugs in the cloned cells permanently bearing replicon RNA, HS55‐4 cells, were similar to those of reports using SGR, including AM. The SGR transient transfection system using SGR KT9WT and SGR KT9AM encoding secreted Nano‐luciferase and HS55‐4C cells established by the elimination of SGR KT9 RNA from HS55‐4 cells, however, showed that the replication efficiency of SGR KT9WT was much lower than that of SGR KT9AM under a same condition. Furthermore, the sensitivities of SGR KT9WT to almost all tested anti‐HCV reagents, except the inhibitor of miR‐122, a cellular factor important for HCV replication, were quite low compared with SGR KT9AM. These results suggested that the new replicon systems might not only provide information about precise responses against new anti‐HCV drugs but also reveal novel molecular mechanisms supporting negligent proliferation of HCV.
Longitudinal RNA-Seq Analysis of the Repeatability of Gene Expression and Splicing in Human Platelets Identifies a Platelet SELP Splice QTL

Supplemental Digital Content is available in the text. Rationale: Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gene variant and expression studies. However, longitudinal analyses of gene expression in healthy individuals—especially with regards to alternative splicing—are lacking for most primary cell types, including platelets. Objective: To assess repeatability of gene expression and splicing in platelets and use repeatability to identify novel platelet expression quantitative trait loci (QTLs) and splice QTLs. Methods and Results: We sequenced the transcriptome of platelets isolated repeatedly up to 4 years from healthy individuals. We examined within and between individual variation and repeatability of platelet RNA expression and exon skipping, a readily measured alternative splicing event. We find that platelet gene expression is generally stable between and within-individuals over time—with the exception of a subset of genes enriched for the inflammation gene ontology. We show an enrichment among repeatable genes for associations with heritable traits, including known and novel platelet expression QTLs. Several exon skipping events were also highly repeatable, suggesting heritable patterns of splicing in platelets. One of the most repeatable was exon 14 skipping of SELP. Accordingly, we identify rs6128 as a platelet splice QTL and define an rs6128-dependent association between SELP exon 14 skipping and race. In vitro experiments demonstrate that this single nucleotide variant directly affects exon 14 skipping and changes the ratio of transmembrane versus soluble P-selectin protein production. Conclusions: We conclude that the platelet transcriptome is generally stable over 4 years. We demonstrate the use of repeatability of gene expression and splicing to identify novel platelet expression QTLs and splice QTLs. rs6128 is a platelet splice QTL that alters SELP exon 14 skipping and soluble versus transmembrane P-selectin protein production.
Clinical experience combined with therapeutic drug monitoring of lacosamide

Lacosamide (LCM) is an antiepileptic drug (AED) with insufficient clinical experience in patients with intellectual disability (ID). They often have more severe epilepsy with comorbidities. The objective was to evaluate the efficacy and tolerability of lacosamide (LCM) in patients with refractory epilepsy with and without ID in a real‐life setting, taking drug monitoring (TDM) data into account therapeutic.
Use of in-gel peroxidase assay for cytochrome c to visualize mitochondrial complexes III and IV

ABSTRACT The in-gel activity assay (IGA) is a powerful technique that uses enzymatic activity and compares intensities of detected bands in mitochondrial respiratory chain supercomplexes, and it is applicable to eukaryotic organisms. However, no IGA has been established for complex III because of the difficulty of access by ubiquinol, a substrate for complex III. Herein, we demonstrate that cytochrome c (Cyt c) showed peroxidase activity on IGA as a component of complexes III and IV. We used pre-incubation with sodium dodecyl sulfate (SDS) before IGA to loosen complexes in the gel after high-resolution clear native polyacrylamide gel electrophoresis (hrCN-PAGE), a refinement of blue native PAGE. The signals of IGA based on peroxidase activity were obtained using enhanced chemiluminescence solution. Then, the gel was directly used in western blotting or hrCN/SDS two-dimensional PAGE. Our findings indicate that IGA for Cyt c reflected the indirect activity of complexes III and IV. Summary: An improved in-gel activity assay visualized respiratory chain complexes III, IV and supercomplexes through cytochrome c. Pre-incubation of detergents enhanced the in-gel activity assay.