Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combination of DNA-peptide Probes and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): A Quasi-Targeted Proteomics Approach for Multiplexed MicroRNA Quantification

The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarker. There is much evidence indicating that a panel of miRNAs, termed “miRNA fingerprints”, is more specific and informative than an individual miRNA as biomarker. Thus, multiplex assays for simultaneous quantification of multiple miRNAs could be more potent in clinical practice. However, current available assays normally require pre-enrichment, amplification and labeling steps, and most of them are semi-quantitative or lack of multiplexing capability. In this study, we developed a quasi-targeted proteomics assay for multiplexed miRNA quantification by a combination of DNA-peptide probes and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Specifically, the signal of target miRNAs (i.e., miR-21, miR-let7a, miR-200c, miR-125a and miR-15b) was converted into the mass response of reporter peptides by hybridization of miRNAs with DNA-peptide probes and subsequent tryptic digestion to release the peptides. After a careful optimization of conditions related to binding, conjugation, hybridization and multiple reaction monitoring (MRM) detection, the assay was validated for each miRNA and the limit of quantification (LOQ) for all the miRNAs can achieve 1 pM. Moreover, crosstalk between DNA-peptide probes in multiplex assay was sophisticatedly evaluated. Using this quasi-targeted proteomics assay, the level of target miRNAs was determined in 3 human breast cell lines and 36 matched pairs of breast tissue samples. Finally, simplex assay and qRT-PCR were also performed for a comparison. This approach grafts the strategy of targeted proteomics into miRNA quantification and may offer a new way for multiplexed miRNA profiling.
Genome-Wide Association Study Identifies Nox3 as a Critical Gene for Susceptibility to Noise-Induced Hearing Loss

In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.
Relations between BOLD fMRI-Derived Resting Brain Activity and Cerebral Blood Flow

Consistent resting brain activity patterns have been repeatedly demonstrated using measures derived from resting BOLD fMRI data. While those metrics are presumed to reflect underlying spontaneous brain activity (SBA), it is challenging to prove that association because resting BOLD fMRI metrics are purely model-free and scale-free variables. Cerebral blood flow (CBF) is typically closely coupled to brain metabolism and is used as a surrogate marker for quantifying regional brain function, including resting function. Assessing the correlations between resting BOLD fMRI measures and CBF correlation should provide a means of linking of those measures to the underlying SBA, and a means to quantify those scale-free measures. The purpose of this paper was to examine the CBF correlations of 3 widely used neuroimaging-based SBA measures, including seed-region based functional connectivity (FC), regional homogeneity (ReHo), and amplitude of low frequency fluctuation (ALFF). Test-retest data were acquired to check the stability of potential correlations across time. Reproducible posterior cingulate cortex (PCC) FC vs regional CBF correlations were found in much of the default mode network and visual cortex. Dorsal anterior cingulate cortex (ACC) FC vs CBF correlations were consistently found in bilateral prefrontal cortex. Both ReHo and ALFF were found to be reliably correlated with CBF in most of brain cortex. None of the assessed SBA measures was correlated with whole brain mean CBF. These findings suggest that resting BOLD fMRI-derived measures are coupled with regional CBF and are therefore linked to regional SBA.
Functional asplenia in hemoglobin SC disease.

The incidence of functional asplenia in sickle-hemoglobin C (SC) disease has not been defined, and the use of prophylactic penicillin to prevent life-threatening septicemia in this disorder is controversial. The percentage of red blood cells with pits (pit count) is a reliable assay of splenic function in other disorders but has not been validated in hemoglobin SC disease. To address these issues, we conducted a prospective, multicenter study of splenic function in persons with hemoglobin SC disease. Baseline clinical data were recorded, and red blood cell pit counts were performed on 201 subjects, aged 6 months to 90 years, with hemoglobin SC; 43 subjects underwent radionuclide liver-spleen scanning. Pit counts greater than 20% were associated with functional asplenia as assessed by liver-spleen scan, whereas pit counts less than 20% were found in subjects with preserved splenic function. Pit counts greater than 20% were present in 0 of 59 subjects (0%) less than 4 years of age, in 19 of 86 subjects (22%) 4 to 12 years of age, and in 25 of 56 subjects (45%) greater than 12 years of age. Other subjects with hemoglobin SC, who had previously undergone surgical splenectomy, had higher pit counts (59.7% +/- 9.5%) than splenectomized subjects without hemoglobinopathy (38.5% +/- 8.8%) or with sickle cell anemia (20.5% +/- 1.9%; P < .001). Two subjects with hemoglobin SC disease (not splenectomized), ages 14 and 15 years, with pit counts of 40.3% and 41.7% died from pneumococcal septicemia. These data indicate that functional asplenia occurs in many patients with hemoglobin SC disease, but its development is usually delayed until after 4 years of age. The pit count is a reliable measure of splenic function in hemoglobin SC disease, but values indicative of functional asplenia (> 20% in our laboratory) are higher than in other disorders. The routine administration of prophylactic penicillin to infants and young children with hemoglobin SC disease may not be necessary.
Investigation on a focus of human trichinellosis revealed by an atypical clinical case after wild-boar (Sus scrofa) pork consumption in northern Italy

Trichinellosis is one of the most serious foodborne parasitic zoonoses in Europe. Wild carnivorous and omnivorous hosts are the main reservoirs of Trichinella spp. nematodes in nature. In the winter of 2008-2009, an atypical clinical case of trichinellosis occurred for the consumption of pork from a wild boar (Sus scrofa) hunted in southwestern Alps in Italy. The symptomatic individual showed delayed development of oedemas in the lower limbs and eosinophilia, which appeared three months after infection. Muscle samples harboured 3.8 larvae/g, which were identified as Trichinella britovi. During the epidemiological investigation, anti-Trichinella IgG were detected in five hunters.
Magnesium Deficiency-Dependent Audiogenic Seizures (MDDASs) in Adult Mice: A Nutritional Model for Discriminatory Screening of Anticonvulsant Drugs and Original Assessment of Neuroprotection Properties

A great many animal models for audiogenic seizures have been described. The extent to which these models may provide insight into neuroscience fields such as abnormal locomotor behavior (wild running), seizures and anticonvulsants, and neuroinsults and neuroprotectors is examined here by our study of magnesium deficiency-dependent audiogenic seizures (MDDASs) in adult mice. MDDASs were induced in all of the eight tested adult murine strains and are presented as a sequence of four successive components (latency, wild running, convulsion, and recovery phase periods). Compared with several classic seizure tests, the nutritional MDDAS model responded to low doses of prototype antiepileptic drugs (AEDs), including phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), valproic acid (VPA), ethosuximide (ESM), and diazepam (DZP). Modulation by AEDs of the four components of MDDAS indicated that this seizure test was discriminatory, distinguishing between phenytoinergic (PHT, CBZ), GABAergic (PB, VPA, DZP), and ethosuximide (ESM) compounds. Suitability of the MDDAS test for evaluation of neuroprotective compounds was also examined: it showed partial (melatonin) and complete (WEB2170, an anti-PAF agent) reduction of recovery phase by non-anticonvulsant doses of test compounds. These neuroprotective responses were compared with neuroprotective potentials determined in a model of neonatal cerebral injury induced by focal injection of ibotenate (a glutamate analog). WEB2170 and melatonin reduced the size of lesions in white matter, but only WEB2170 protected cortical plate against ibotenate-induced lesions. In addition to the original neuroprotective behavior of WEB2170, studies on the neuroprotectors also supported GABAergic anticonvulsant activity of melatonin in the MDDAS test.
Frequent daytime naps predict vocabulary growth in early childhood

Background The facilitating role of sleep for language learning is well‐attested in adults and to a lesser extent in infants and toddlers. However, the longitudinal relationship between sleep patterns and early vocabulary development is not well understood. Methods This study investigates how measures of sleep are related to the development of vocabulary size in infants and toddlers. Day and night‐time sleeping patterns of infants and toddlers were compared with their concurrent and subsequent vocabulary development. Sleep assessments were conducted using a sleep diary specifically designed to facilitate accurate parental report. Sleep measures were used as predictors in a multilevel growth curve analysis of vocabulary development. Results The number of daytime naps was positively associated with both predicted expressive (p = .062) and receptive vocabulary growth (p = .006), whereas the length of night‐time sleep was negatively associated with rate of predicted expressive vocabulary growth (p = .045). Sleep efficiency was also positively associated with both predicted receptive (p = .001) and expressive vocabulary growth (p = .068). Conclusions These results point to a longitudinal relationship between sleep and language development, with a particular emphasis on the importance of napping at this age.
Disordered eating behaviors in youth with type 1 diabetes: prospective pilot assessment following initiation of insulin pump therapy.

BACKGROUND There is risk for disordered eating behaviors in type 1 diabetes, especially related to insulin manipulation. Implementation of insulin pump therapy may encourage either normalization of eating behaviors or a greater focus on food intake due to renewed emphasis on carbohydrate counting. There is need for prospective studies to assess disordered eating behaviors upon implementation of pump therapy using diabetes-specific measurement tools. SUBJECTS AND METHODS In a multicenter pilot study, 43 youth with type 1 diabetes, 10-17 years old, were assessed prior to pump initiation and after 1 and 6 months of pump therapy. Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a validated measure of risk for both diabetes-specific and general disordered eating behaviors. RESULTS Youth (45% female), 13.3 years old with diabetes for 2.1 years, had a mean hemoglobin A1c of 8.3±1.3% (68±14.5 mmol/mol) at baseline. DEPS-R scores decreased over time (P=0.01). Overall rate of high risk for eating disorders was low. Overweight/obese youth endorsed more disordered eating behaviors than normal-weight participants. DEPS-R scores were correlated with z-score for body mass index at all three time points and with hemoglobin A1c after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6 months and was higher in overweight/obese compared with normal-weight participants. CONCLUSIONS Initiation of insulin pump therapy was associated with diminished endorsement of disordered eating behaviors in youth with type 1 diabetes. Longer follow-up studies are needed to assess the impact of insulin pump therapy on glycemic control, weight status, and disordered eating behaviors in this vulnerable population.
The brain differentiates human and non-human grammars: Functional localization and structural connectivity

The human language faculty has been claimed to be grounded in the ability to process hierarchically structured sequences. This human ability goes beyond the capacity to process sequences with simple transitional probabilities of adjacent elements observable in non-human primates. Here we show that the processing of these two sequence types is supported by different areas in the human brain. Processing of local transitions is subserved by the left frontal operculum, a region that is phylogenetically older than Broca’s area, which specifically holds responsible the computation of hierarchical dependencies. Tractography data revealing differential structural connectivity signatures for these two brain areas provide additional evidence for a segregation of two areas in the left inferior frontal cortex.
The papilla as screening parameter for early diagnosis of glaucoma.

INTRODUCTION In the industrialized countries 67 million people suffer from glaucoma, which represents the third most common cause of blindness and thus has a high economic impact. Early diagnosis of glaucoma, which does not necessarily involve raised intraocular pressure, is essential because by the time the patient notices functional impairment the damage is irreversible. Early treatment can decrease the rate of blindness 20 years later by about 50%. METHODS Selective literature review and clinical investigation of early glaucoma detection and of screening methods. RESULTS Currently, no evidence-based recommendations for glaucoma screening can be found in the literature. No single method or combination of screening procedures can be recommended unambiguously on economic grounds. DISCUSSION From the clinical perspective sensitive, specific, and cost-effective glaucoma screening seems feasible. The high-risk group would need to be defined on the basis of age and family history. A two-stage screening process would then have to be established with initial computer-supported telemedical sorting followed by telemedical ophthalmological diagnosis of cases selected for clarification.
Intake of foods and nutrients and cancer of the exocrine pancreas: A population‐based case‐control study in the Netherlands

During 1984–88 a population‐based case‐control study was carried out in the Netherlands In collaboration with the International Agency for Research on Cancer in order to investigate the role of diet in exocrine pancreatic carcinoma. A semi‐quantitative food‐frequency questionnaire was used to comprehensively assess usual diet about I year prior to diagnosis of 164 cases or interview of 480 controls. More than half of the cases were directly interviewed. After controlling for age, gender, response status, life‐time cigarette consumption and dietary intake of total energy, monotonic, significantly inverse dose‐response effects with estimates of daily consumption of vegetables were found. The significant inverse effect of total cooked vegetables was primarily concentrated in cruciferous vegetables. Consumption of fresh vegetables was also significantly and inversely related to risk. A monotonic, positive dose‐response gradient was seen for the consumption of eggs, while consumption of fish was significantly related to risk as well. Among direct respondents, significantly inverse relationships were found for the consumption of legumes, tomatoes, cheese and fermented milk products. Inverse associations with consumption of (subgroups of) fruits were observed in women only. The monotonic, significantly inverse relationship for consumption of low‐fibre vegetables and the somewhat weaker, inverse association for high‐fibre vegetables in directly interviewed subjects only, may point to protective agents other than vegetable fibre. Although intake of dietary fibre and beta‐carotene were both inversely related to risk, simultaneous estimation suggested that beta‐carotene or other as yet unknown correlated constituents, rather than dietary fibre, might explain the inverse relationships. A significant protective effect of vitamin C was demonstrated in women but not in men. Our study suggests that, independent of smoking and dietary intake of total energy, low consumption of specific vegetables and possibly fermented milk products and high consumption of eggs and fish may have influenced the development of exocrine pancreatic cancer.
Characterization of the discriminative stimulus effects of lorcaserin in rats

Several decades of preclinical research suggest that drugs with agonist effects at serotonin (5‐HT)2C receptors might be useful for treating substance use disorders. Lorcaserin, a drug currently used to treat obesity and under consideration for treating substance use disorders, has agonist properties at 5‐HT2C receptors; however, recent evidence suggests that it might also have agonist effects at other 5‐HT receptor subtypes. The present experiment used drug discrimination, a procedure that is highly pharmacologically selective, to further investigate the mechanism(s) of action of lorcaserin. Male Sprague‐Dawley rats (n=7) discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed ratio 5 schedule of food presentation. Lorcaserin (0.178–1.0 mg/kg) dose‐dependently increased lorcaserin‐lever responding. Several direct‐acting 5‐HT receptor agonists and antagonists were examined alone and in combination with lorcaserin. The 5‐HT2C receptor agonist mCPP occasioned greater than 90% lorcaserin‐lever responding in 6/7 rats, as did the 5‐HT2A receptor agonist DOM. The 5‐HT1A receptor agonist 8‐OH‐DPAT occasioned greater than 90% lorcaserin‐lever responding in only 4/7 rats. The 5‐HT2C receptor selective antagonist SB 242084 attenuated lorcaserin‐lever responding in all 7 rats. In contrast, the 5‐HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin‐lever responding in 5/7 rats. In addition to producing directly observable behavior consistent with agonist properties at 5‐HT2C receptors (i.e. yawning), at large doses lorcaserin also induces behavioral effects that are consistent with agonist properties at 5‐HT1A receptors (i.e., forepaw treading). Moreover, when examined in combination with a selective 5‐HT2C receptor antagonist lorcaserin also induced behavior consistent with agonist properties at 5‐HT2A receptors (i.e., head twitching). Taken together, these results suggest that in addition to agonist effects at 5‐HT2C receptors, lorcaserin also has agonist effects at 5‐HT2A and 5‐HT1A receptors. Given that 5‐HT2A receptor agonists can be abused (e.g., LSD) it is crucial to fully understand the behavioral effects of lorcaserin if it is to be considered a potential pharmacotherapy for substance use disorders.
Allozymic variability in Spanish populations of Ceratitis capitata

Introduction. The Tephritidae Ceratitis capitata is one of the most important agricultural pests in the world. Eradication programmes need as much genetic information as possible to be efficient. It is vital to know the genetic variation that exists in the areas thought to have been important in the expansion of the species, such as the Iberian Peninsula. The aim of this study was to determine the genetic structure of Spanish C. capitata populations and the relationships between them. Materials and methods. We studied the genetic varia- bility of populations of C. capitata (eight wild samples and one laboratory strain) through the use of the horizontal starch gel electrophoresis technique and the assay of fifteen enzyme- coding loci chosen at random. Results. The quantity of variability detected in this polypha- gous species was not high. Of the 15 loci studied, only four were clearly polymorphic. No significant differences were found in any comparison of populations collected from different hosts. Discussion. The distribution patterns of this variation seem to be the result of gene flow and selection in the form of agricultural practices. Spain / Ceratitis capitata / electrophoresis / genetic variation
Predicting missing links via significant paths

Link prediction plays an important role in understanding the intrinsic evolving mechanisms of networks. With the belief that the likelihood of the existence of a link between two nodes is strongly related to their similarity, many methods have been proposed to calculate node similarity based on node attributes and/or topological structures. Among a large variety of methods that take into account paths connecting the target pair of nodes, most of them neglect the heterogeneity of those paths. Our hypothesis is that a path consisting of small-degree nodes provides a strong evidence of similarity between two ends, accordingly, we propose a so-called significant path index in this letter to leverage intermediate nodes' degrees in similarity calculation. Empirical experiments on twelve disparate real networks demonstrate that the proposed index outperforms the mainstream link prediction baselines.
Active Learning with Feedback on Both Features and Instances

We extend the traditional active learning framework to include feedback on features in addition to labeling instances, and we execute a careful study of the effects of feature selection and human feedback on features in the setting of text categorization. Our experiments on a variety of categorization tasks indicate that there is signiﬁcant potential in improving classiﬁer performance by feature re-weighting, beyond that achieved via membership queries alone (traditional active learning) if we have access to an oracle that can point to the important (most predictive) features. Our experiments on human subjects indicate that human feedback on feature relevance can identify a sufﬁcient proportion of the most relevant features (over 50% in our experiments). We ﬁnd that on average, labeling a feature takes much less time than labeling a document. We devise an al-gorithm that interleaves labeling features and documents which signiﬁcantly accelerates standard active learning in our simulation experiments. Feature feedback can complement traditional active learning in applications such as news ﬁltering, e-mail classiﬁcation, and personalization, where the human teacher can have signiﬁcant knowledge on the relevance of features.