Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease

A sensitive blood diagnostic assay can identify patients with variant Creutzfeldt-Jakob disease before symptoms appear and during the clinical phase. A new blood test for prion diseases Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease that can be transmitted from person to person through medical procedures. The development of a diagnostic blood test is an urgent priority. Bougard et al. describe a sensitive and specific blood test based on a prion capture step and an amplification method. This test for vCJD was very accurate and worked not only for blood samples from patients suffering from vCJD but also for samples taken from two individuals 1.3 and 2.6 years before they developed clinical symptoms. This blood test has important implications for transfusion medicine and public health. Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity [95% confidence interval (CI), 81.5 to 100%], 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.
Shear-Friction Behavior of Recycled and Natural Aggregate Concrete—An Experimental Investigation

The results of an experimental investigation of the shear-friction behavior of recycled and natural coarse aggregate concrete are reported. Eighteen non-precracked pushoff specimens were tested. The percentages of replacement of coarse aggregates with recycled aggregates in the concrete mixtures were 0%, 50%, or 100%. The specimens made of the same concrete had different amounts of clamping reinforcement across the shear-transfer plane. It is shown that all specimens with clamping reinforcement resisted significant post-ultimate strengths, in addition to relatively large slips along the shear-transfer planes. It is also shown that the full replacement of conventional aggregate with recycled aggregate had a limited effect on the ultimate and post-ultimate reserve shearing strength, while partial replacement (50%) caused a more significant reduction in the ultimate shearing strength. The results also showed that the ultimate strength was reached as soon as the clamping steel yielded. The nominal strength calculated using the shear friction model of the ACI Code, using a coefficient of friction suitable for monolithic construction, was significantly lower than the observed ultimate strength. The calculated strength was closer to the post-ultimate strength.
Potential of pine needles for PLA‐based composites

The article describes the mechanical properties of biodegradable composites. The composites were made using biodegradable plastics like polylactic acid reinforced with Pinus roxburghii needles. The composites were characterized by their tensile strength, flexural strength, Rockwell hardness, thermal stability, and FTIR analysis as well as morphological and water absorption behavior. The composites possessed high tensile and flexural strength on addition of 8.77% fibers. The tensile and flexural strength increased 1.7 and 3.5 times, respectively, in comparison to virgin PLA. Biodegradation studies revealed that the composites have the capability to degrade in the natural environment. These results reveal that pine needles can be prospective candidates for use in natural fiber-reinforced polymer composites. POLYM. COMPOS. , 2016. © 2016 Society of Plastics Engineers
Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques

Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104–106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1–>8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology after vaginal ZIKV transmission compared to a mosquito transmitted ZIKV.
N-glycome of the Lysosomal Glycocalyx is Altered in Niemann-Pick Type C Disease (NPC) Model Cells*

Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including the rare inherited lysosomal storage disorders (LSDs) and the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's disease (AD and PD). Although the triggers of the lysosomal impairment may involve the accumulated macromolecules or dysfunction of the lysosomal enzymes, the role of the lysosomal glycocalyx in the lysosomal (dys)function has not been studied. The goal of this work was to analyze whether there are changes in the lysosomal glycocalyx in a cellular model of a LSD Niemann-Pick type C disease (NPC). Using the ferrofluid nanoparticles we isolated lysosomal organelles from NPC1-null and CHOwt cells. The magnetically isolated lysosomal fractions were enriched with the lysosomal marker protein LAMP1 and showed the key features of NPC disease: 3-fold higher cholesterol content and 4–5 fold enlarged size of the particles compared with the lysosomal fractions of wt cells. These lysosomal fractions were further processed to isolate lysosomal membrane proteins using Triton X-114 and their N-glycome was analyzed by HILIC-UPLC. N-glycans presented in each chromatographic peak were elucidated using MALDI-TOF/TOF-MS. We detected changes in the N-glycosylation pattern of the lysosomal glycocalyx of NPC1-null versus wt cells which involved high-mannose and sialylated N-glycans. To the best of our knowledge this study is the first to report N-glycome profiling of the lysosomal glycocalyx in NPC disease cellular model and the first to report the specific changes in the lysosomal glycocalyx in NPC1-null cells. We speculate that changes in the lysosomal glycocalyx may contribute to lysosomal (dys)function. Further glycome profiling of the lysosomal glycocalyx in other LSDs as well as the most common neurodegenerative diseases, such as AD and PD, is necessary to better understand the role of the lysosomal glycocalyx and to reveal its potential contribution in lysosomal dysfunction leading to neurodegeneration.
Family matters: How MYC family oncogenes impact small cell lung cancer

ABSTRACT Small cell lung cancer (SCLC) is one of the most deadly cancers and currently lacks effective targeted treatment options. Recent advances in the molecular characterization of SCLC has provided novel insight into the biology of this disease and raises hope for a paradigm shift in the treatment of SCLC. We and others have identified activation of MYC as a driver of susceptibility to Aurora kinase inhibition in SCLC cells and tumors that translates into a therapeutic option for the targeted treatment of MYC-driven SCLC. While MYC shares major features with its paralogs MYCN and MYCL, the sensitivity to Aurora kinase inhibitors is unique for MYC-driven SCLC. In this review, we will compare the distinct molecular features of the 3 MYC family members and address the potential implications for targeted therapy of SCLC.
Single-site ventricular pacing via the coronary sinus in patients with tricuspid valve disease

Aims To evaluate coronary sinus single-site (CSSS) left ventricular pacing in adult patients with normal left ventricular ejection fraction (LVEF) when traditional right ventricular lead implantation is not feasible or is contraindicated. Methods and results We performed a retrospective analysis of 23 patients with tricuspid valve surgery/disease who received a CSSS ventricular pacing lead to avoid crossing the tricuspid valve. Two matched control populations were obtained from patients receiving (i) conventional right ventricular single-site (RVSS) leads and (ii) coronary sinus leads for cardiac resynchronization therapy (CSCRT). Main outcomes of interest were lead stability, electrical lead parameters and change in LVEF during long-term follow-up. Successful CSSS pacing was accomplished in all 23 patients without any procedural complications. During the 5.3 ± 2.8-year follow-up 22/23 (95.7%) leads were functional with stable pacing and sensing parameters, and 1/23 (4.3%) was extracted for unrelated reasons. Compared to CSSS leads, the lead revision/abandonment was similar with RVSS leads (Hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.03, 22.0), but was higher with CSCRT leads (HR 7.41, 95% CI 1.30, 139.0). There was no difference in change in LVEF between CSSS and RVSS groups (-2.4 ± 11.0 vs. 1.5 ± 12.8, P = 0.76), but LVEF improved in CSCRT group (11.2 ± 16.5%, P = 0.002). Fluoroscopy times were longer during implantation of CSSS compared to RVSS leads (25.6 ± 24.6 min vs. 12.3 ± 18.6 min, P = 0.049). Conclusion In patients with normal LVEF, single-site ventricular pacing via the coronary sinus is a feasible, safe and reliable alternative to right ventricular pacing.
Receptor-interacting protein kinase 3 promotes platelet activation and thrombosis

Significance Receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes such as necroptosis, apoptosis, and inflammation. Here, using RIP3-knockout mice, we show that RIP3 is essential for in vivo thrombosis and hemostasis. Mice lacking RIP3 exhibited prolonged tail-bleeding times and reduced arterial thrombus formation. We demonstrate that RIP3, expressed in platelets and interacting with Gα13, promotes platelet aggregation, secretion, spreading on fibrinogen, and clot retraction. RIP3 inhibitor dose-dependently inhibits platelet aggregation and prevents arterial thrombus formation. Our findings indicate a role for RIP3 in promoting in vivo thrombosis and hemostasis by amplifying platelet activation. RIP3 may represent a novel therapeutic target for thrombotic diseases. Previous studies have shown that receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes, including necroptosis, apoptosis, and inflammation. Here we show that RIP3 plays a critical role in regulating platelet functions and in vivo thrombosis and hemostasis. Tail bleeding times were significantly longer in RIP3-knockout (RIP3−/−) mice compared with their wild-type (WT) littermates. In an in vivo model of arteriole thrombosis, mice lacking RIP3 exhibited prolonged occlusion times. WT mice repopulated with RIP3−/− bone marrow-derived cells had longer occlusion times than RIP3−/− mice repopulated with WT bone marrow-derived cells, suggesting a role for RIP3-deficient platelets in arterial thrombosis. Consistent with these findings, we observed that RIP3 was expressed in both human and mice platelets. Deletion of RIP3 in mouse platelets caused a marked defect in aggregation and attenuated dense granule secretion in response to low doses of thrombin or a thromboxane A2 analog, U46619. Phosphorylation of Akt induced by U46619 or thrombin was diminished in RIP3−/− platelets. Moreover, RIP3 interacted with Gα13. Platelet spreading on fibrinogen and clot retraction were impaired in the absence of RIP3. RIP3 inhibitor dose-dependently inhibited platelet aggregation in vitro and prevented arterial thrombus formation in vivo. These data demonstrate a role for RIP3 in promoting in vivo thrombosis and hemostasis by amplifying platelet activation. RIP3 may represent a novel promising therapeutic target for thrombotic diseases.
Decision-making for tracheostomy in amyotrophic lateral sclerosis (ALS): a retrospective study

Abstract Background: ALS patients should discuss the issue of tracheostomy before the onset of terminal respiratory failure. While the process of shared decision-making is desirable, there are few data on the practical application of this real-life situation. Aim of the study: To determine how a decision-making process is actually carried out, we analysed the episodes of acute respiratory failure preceding tracheostomy. Methods: We studied the charts of a group of ALS patients after tracheostomy. An interview focusing on the existence of anticipated directives was carried out. Tracheostomies were classified as planned or unplanned according to the presence of a decision plan. Results: A total of 209 ALS patients were cared for during a three-year period. Of these patients, 34 (16%) were tracheotomised. In 38% of cases, tracheostomy was planned, 41% were unplanned, and 21% remained undiagnosed. Conclusions: A minority of ALS patients make a voluntary decision for tracheostomy before the procedure is conducted. The advising process of care still presents limits that have been thus far poorly addressed. In the future, we will need to develop guidelines for the timing and content of the shared-decision making process.
Cross-type Biomedical Named Entity Recognition with Deep Multi-Task Learning

Motivation State-of-the-art biomedical named entity recognition (BioNER) systems often require handcrafted features specific to each entity type, such as genes, chemicals and diseases. Although recent studies explored using neural network models for BioNER to free experts from manual feature engineering, the performance remains limited by the available training data for each entity type. Results We propose a multi-task learning framework for BioNER to collectively use the training data of different types of entities and improve the performance on each of them. In experiments on 15 benchmark BioNER datasets, our multi-task model achieves substantially better performance compared with state-of-the-art BioNER systems and baseline neural sequence labeling models. Further analysis shows that the large performance gains come from sharing character- and word-level information among relevant biomedical entities across differently labeled corpora. Availability Our source code is available at https://github.com/yuzhimanhua/lm-lstm-crf. Contact xwang174@illinois.edu, xiangren@usc.edu.
Pulmonary Function Tests Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?

Objective: The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity. Methods: It is an observational case-control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was further subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid-forced expiratory flow of 25% to 75% (FEF 25%–75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group. Results: There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state as regards FEV1, FVC, FEF 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEF 25% to 75%, and DLCO. Conclusions: Subclinical PFTs abnormalities are common in pediatric IBD even during remission period. So, periodic PFTs evaluation should be considered in the routine follow-up of IBD children.
General practitioners and preconception weight management in New Zealand

Childhood obesity is a growing concern internationally and a top priority for the World Health Organization. Preconception overweight, obesity and excess gestational weight gain significantly increase childhood obesity risk. Optimising preconception weight is a key preventative measure toward reducing childhood obesity. In 2014, the New Zealand (NZ) Ministry of Health released guidance for health practitioners on healthy weight gain in pregnancy in an effort to reduce the burden of childhood obesity.
Differential contribution of orexin receptors within the ventral tegmental area to modulation of persistent inflammatory pain

Orexinergic neurons in the lateral hypothalamus (LH) play an important role in pain modulation. In addition, ventral tegmental area (VTA) is known as a part of descending pain modulatory circuitry. Little is known about the interaction between the LH and neural substrates involving in modulation of formalin‐induced nociception. Accordingly, we aimed to examine the pain modulatory role of VTA orexin receptors in the formalin test.
Idiom Variation: Experimental Data and a Blueprint of a Computational Model

Corpus surveys have shown that the exact forms with which idioms are realized are subject to variation. We report a rating experiment showing that such alternative realizations have varying degrees of acceptability. Idiom variation challenges processing theories associating idioms with fixed multi-word form units (Bobrow & Bell, 1973), fixed configurations of words (Cacciari & Tabossi, 1988), or fixed superlemmas (Sprenger, Levelt, & Kempen, 2006), as they do not explain how it can be that speakers produce variant forms that listeners can still make sense of. A computational model simulating comprehension with naive discriminative learning is introduced that provides an explanation for the different degrees of acceptability of several idiom variant types. Implications for multi-word units in general are discussed.
Efficacy of Cognitive Rehabilitation Therapy on Poststroke Depression among Survivors of First Stroke Attack in Ibadan, Nigeria

Background and Purpose Poststroke depression (PSD) is a common complication after stroke. There is no adequate treatment for PSD. This study examined efficacy of cognitive rehabilitation therapy (CRT) in the treatment of PSD among stroke survivors. Methods An experimental design, 30 participants with poststroke depression were randomly assigned into 3 groups of cognitive rehabilitation therapy (CRT), psychoeducation (PE), and the control group (CG). CRT consisted of nine sessions with three-phased sessions focusing on activity stimulation, negative thoughts, and people contacts, PE consisted of nine sessions focusing on knowledge on stroke and poststroke depression, and the CG group was on the waiting list. The BDI scale was used for assessing PSD at posttest. Results There was a significant difference in the efficacy of CRT, PE, and the CG on PSD, with CRT–CG mean difference of −9.4 ± 3.11 and PE–CG 1.0 ± 3.83. Furthermore, stress was not a confounding variable on the efficacy of CRT. The type of therapy significantly influenced PSD at posttest, with the CRT having greater mean reduction to CG (−11.1 ± 3.1) than PE to the CG (3.0 ± 3.8). Conclusions Cognitive rehabilitation therapy significantly reduced poststroke depression. Hence, it should be integrated as an adjunct treatment of poststroke depression.
A Replication Study for Association of LBX1 Locus With Adolescent Idiopathic Scoliosis in French–Canadian Population

Study Design. A case-control association study. Objectives. To investigate the relationship between LBX1 (lady bird homeobox1) polymorphisms and adolescent idiopathic scoliosis (AIS) in French–Canadian population. Summary of Background Data. It is widely accepted that genetic factors contribute to AIS. Although the LBX1 locus is so far the most successfully replicated locus in different AIS cohorts, these associations were replicated mainly in Asian populations, with few studies in Caucasian populations of European descent. Methods. We recruited 1568 participants (667 AIS patients and 901 healthy controls) in the French–Canadian population. Genomic data were generated using the Illumina Human Omni 2.5M BeadChip. An additional 121 AIS cases and 51 controls were genotyped for specific single-nucleotide polymorphisms (SNPs) by multiplex polymerase chain reaction using standard procedures. BEAGLE 3 was used to impute the following markers: rs7893223, rs11190878, and rs678741 against the 1000-genomes European cohort phased genotypes given that they were absent in our genome wide association studies (GWAS) panel. Resulting genotypes were combined then used for single marker and haplotyped-based association. Results. Four markers showed association with AIS in our cohort at this locus; rs11190870 the most studied marker, rs7893223, rs594791, and rs11190878. When we restricted the analysis to severe cases only, four additional SNPs showed associations: rs11598177, rs1322331, rs670206, and rs678741. In addition, we analyzed the associations of the observed haplotypes and dihaplotypes formed by these SNPs. The haplotype TTAAGAAA and its homozygous dihaplotype showed the highest association with our severe group and was the highest risk haplotype. The haplotype CCGCAGGG was significantly more associated with the control group, and its homozygous or heterozygous dihaplotype was less frequent in the severe group compared with the control group, suggesting that CCGCAGGG may represent a protective haplotype. Conclusion. We have replicated the association of the LBX1 locus with AIS in French–Canadian population, a novel European descent cohort, which is known for its unique genetic architecture. Level of Evidence: 3