Miracle-dz/UniFAR-FTUs huggingface dataset:
Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma: Carcinogenesis of Perihilar Type and Aggressive Behavior of Peripheral Type

S100P is expressed in several kinds of malignant tumors. Intracellular S100P interacts with ezrin, and extracellular S100P activates the receptor for advanced glycation endproducts. However, little is known about the biological significance of S100P and related proteins in cholangiocarcinoma. Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar or perihilar cholangiocarcinoma. We examined S100P, ezrin, and the receptor for advanced glycation end product expression in 39 BilIN and 110 intrahepatic cholangiocarcinoma (ICC) cases, and analyzed its relationship with clinicopathologic factors and outcomes. S100P expression increased from reactive epithelium to low-grade BilIN to high-grade BilIN. S100P and ezrin expression rates in perihilar-type ICC were higher than those in peripheral-type ICC (P<0.0001, P=0.0008, respectively). S100P nuclear expression in peripheral-type ICC significantly correlated with vascular invasion (P=0.0209), lymphatic invasion (P=0.0003), and lymph node metastasis (P=0.003). S100P and ezrin expression was significantly correlated. S100P-positive and ezrin-positive cases indicate shorter survival in survival analysis of the peripheral type (P=0.001, P=0.0728, respectively). Our results suggest that S100P-ezrin signaling has different roles of carcinogenesis of perihilar ICC and an aggressive course of peripheral ICC.
Restoration of Medial Hinge in Acute Complex Proximal Humeral Fractures using Intra-Medullary Strut Allograft

Background Proximal humerus fractures with medial column comminution/collapse often pose management dilemmas to the treating surgeon. Medial column mechanical support of these fractures plays a significant role in the ultimate stability of fixation until healing. Methods Twelve patients (four men and eight women) with unstable proximal humerus fractures were taken up for study. The fractures were stabilized with intramedullary strut allograft and locking plate (PHILOS) by a deltoid splitting approach. The outcome was assessed clinically by Oxford Shoulder Score and radiologically by measuring the head shaft angle at follow-up. Results The mean age of the patients was 65 years (range 54 years to 72 years) with the dominant arm affected in nine. All fractures progressed to union at an average of 4 months and 15 days (3 months to 11 months). At final follow-up (average 29.7 months), all patients had good functional outcome, with an average Oxford Shoulder Score of 19.2 (12 to 32). The average loss of head shaft angle was 6° (0° to 8°). Conclusion The technique has potential technical advantages in the management of proximal humeral fractures with medial column comminution/collapse. The rate of union has been encouraging and we recommend it as a method of treatment.
Orexins/hypocretins and orexin receptors in apoptosis: a mini‐review

An unexpected and fascinating aspect of the neuropeptides orexins has recently emerged when it was shown that orexins acting at orexin receptors OX1R or OX2R induce dramatic apoptosis resulting in massive reduction in cell growth in various cancer cell lines. This mini‐review will provide the reader with recent findings related to the proapoptotic actions of orexins and the entirely novel mechanism whereby the seven membrane‐spanning G‐protein‐coupled receptor (GPCR) OX1R triggers apoptosis. Recent data show that orexins induce tyrosine phosphorylation of the tyrosine‐based motifs – immunoreceptor tyrosine‐based inhibitory motif and immunoreceptor tyrosine‐based switch motif – in OX1R. These phosphorylations result in the recruitment and activation of the phosphotyrosine phosphatase SHP‐2 and subsequent cytochrome c‐mediated mitochondrial apoptosis. Finally, this mini‐review will also speculate on: (1) the potential importance of tyrosine‐based motifs in the large family of GPCRs; (2) the interest of orexin receptors as therapeutic targets in cancer therapy; (3) the possible role of orexin receptor‐mediated apoptosis in physiology and pathophysiology in the brain (neurodevelopment, neurodegenerative diseases) and in the periphery.
More single‐nucleotide mutations surround small insertions than small deletions in primates

Early studies have shown that single‐nucleotide mutation rates increase close to insertions and deletions, but it is not fully understood how natural selection shapes genome‐wide patterns of indels and their nearby single‐nucleotide mutations. In this study, we find that, in primates, more single‐nucleotide mutations surround small insertions than small deletions. This pattern affects <150 base pair (bp) sequences close to indels and persists under different genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated sequences, replication timing, recombination rates, indel density, and guanine–cytosine (GC) content. We propose two different, but not mutually exclusive, hypothetical mechanisms to explain the pattern. One mechanism is that the sequence context preferring insertion formation may also favor nucleotide substitutions. Another mechanism is related to a hypothesis in which indel heterozygosity tends to increase nearby nucleotide substitution rates. It means that if insertions spend more time in heterozygotes, insertions may accumulate more surrounding single‐nucleotide changes. In conclusion, we characterize a special genome‐wide evolutionary pattern for indels and nearby single‐nucleotide changes. This pattern may be driven by natural selection and bias primates' genome evolution and phenotypic variations. Hum Mutat 33:1099–1106, 2012. © 2012 Wiley Periodicals, Inc.
Clinical Relevance of Detection of Lymphovascular Invasion in Primary Melanoma Using Endothelial Markers D2-40 and CD34

Immunohistochemistry (IHC) using endothelial markers may facilitate the detection of lymphovascular invasion (LVI) in primary melanoma; however, the clinical implications of enhanced detection are unknown. We evaluated whether the use of lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI positivity relative to routine histology alone and then evaluated the prognostic relevance of LVI detected using these markers in terms of disease-free (DFS) and overall survival (OS). A total of 246 primary melanomas were assessed for LVI using D2-40, CD34, and routine histology. Associations between LVI positivity and clinicopathologic variables, DFS, and OS were compared using univariate and multivariate analyses. The use of endothelial markers increased the rate of LVI positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P<0.0001). On univariate analysis, IHC-detected LVI was significantly associated with more adverse clinicopathologic variables (thickness, ulceration, mitoses, and nodular subtype) compared with LVI detected by routine histology (thickness and ulceration only). In a multivariate model controlling for stage, LVI detected using IHC markers remained a significant marker of both reduced DFS [hazard ratio (HR), 2.01; 95% confidence interval (CI): 1.27-3.18; P=0.003] and OS (HR, 2.08; 95% CI: 1.25-3.46; P=0.005). Results show that D2-40 and CD34 increase the detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance.
Integration of perceptual information in word access

According to experiential theories of language comprehension, perceptual information plays an essential role when word meanings are accessed. We conducted four experiments to investigate how different types of perceptual information such as colour and shape are combined during word access. One possibility is that the colour and shape of a word's referent are activated independently from one another and are combined in an additive manner. Alternatively, words might activate perceptual representations via a multiplicative integration of colour and shape. Experiment 1 established that participants follow a multiplicative similarity rule when they judge the similarity of schematic pictures to actual fruits and vegetables. In Experiments 2 to 4, participants performed a classification task, a lexical decision task, or a word-naming task on names of fruits and vegetables that were superimposed on a background picture. Responses were facilitated only when both colour and shape of the picture matched the word's referents. Response times were associated negatively with mean similarity ratings and the consistency of these ratings obtained in the first experiment. These results suggest a multiplicative integration of different types of perceptual information during word access.
Validation of a quantitative PCR–high‐resolution melting protocol for simultaneous screening of COL1A1 and COL1A2 point mutations and large rearrangements: Application for diagnosis of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a connective tissue disorder mostly characterized by autosomal dominant inheritance. Over 1,100 causal mutations have been identified scattered along all exons of genes encoding type I collagen precursors, COL1A1 and COL1A2. Because of the absence of mutational hotspots, Sanger sequencing is considered the gold standard for molecular analysis even if the workload is very laborious and expensive. To overcome this issue, different prescreening methods have been proposed, including DHPLC and biochemical studies on cultured dermal fibroblasts; however, both approaches present different drawbacks. Moreover, in case of patients who screen negative for point mutations, an additional screening step for complex rearrangements is required; the added causative variants expected from this approach are about 1–2%. The aim of this study was to optimize and validate a new protocol that combines quantitative PCR (qPCR) and high‐resolution melting (HRM) curve analysis to reduce time and costs for molecular diagnosis. Results of qPCR–HRM screening on 57 OI patients, validated by DHPLC–direct sequencing and multiplex ligation‐dependent probe amplification (MLPA), indicate that all alterations identified with the mentioned methodologies are successfully detected by qPCR–HRM. Moreover, HRM was able to discriminate complex genotypes and homozygous variants. Finally, qPCR–HRM outperformed direct sequencing and DHPLC–MLPA in terms of rapidity and costs. Hum Mutat 33:1697–1707, 2012. © 2012 Wiley Periodicals, Inc.
Dietary habits for non-smoking females living with smokers or non-smokers

Background: To investigate whether dietary habits among non-smoking females were different between those living with smokers and non-smokers in two countries. Methods: A questionnaire was sent to 5,000 females in Sweden and Switzerland. After selection regarding smoking habits, a questionnaire on life style factors and diet was distributed. Results: Females living with smokers showed strong tendencies to be overrepresented among those with less frequent consumption of vegetables, fruit and fibre-rich food and in Switzerland among those with a more less frequent consumption of alcohol. Conclusions: The results suggest that non-smoking females living with smokers or non-smokers differ in their dietary habits. Some smokers' habits represent risk factors for disease and should be controlled for in studies on environmental tobacco smoke.
ALSoD: A user‐friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics

Amyotrophic lateral sclerosis (ALS) is the commonest adult onset motor neuron disease, with a peak age of onset in the seventh decade. With advances in genetic technology, there is an enormous increase in the volume of genetic data produced, and a corresponding need for storage, analysis, and interpretation, particularly as our understanding of the relationships between genotype and phenotype mature. Here, we present a system to enable this in the form of the ALS Online Database (ALSoD at http://alsod.iop.kcl.ac.uk), a freely available database that has been transformed from a single gene storage facility recording mutations in the SOD1 gene to a multigene ALS bioinformatics repository and analytical instrument combining genotype, phenotype, and geographical information with associated analysis tools. These include a comparison tool to evaluate genes side by side or jointly with user configurable features, a pathogenicity prediction tool using a combination of computational approaches to distinguish variants with nonfunctional characteristics from disease‐associated mutations with more dangerous consequences, and a credibility tool to enable ALS researchers to objectively assess the evidence for gene causation in ALS. Furthermore, integration of external tools, systems for feedback, annotation by users, and two‐way links to collaborators hosting complementary databases further enhance the functionality of ALSoD. Hum Mutat 33:1345–1351, 2012. © 2012 Wiley Periodicals, Inc.
Trial after trial: General processing consequences as a function of repetition and change in multidimensional sound

While there are pointers relating to the consequences of repetition, a general framework regarding the cognitive implications of processing multidimensional stimuli as a function of previous stimulus history is currently lacking. Three experiments using sounds varying in location and pitch were carried out, in which the immediate consequences of repeating or changing task-relevant and task-irrelevant attributes were orthogonally examined. A consistent pattern of data was shown, in that the magnitude of selective attention failure was larger when the task-relevant value repeated across trials, while differences between dimensions were larger when the task-relevant value changed across trials. These effects of irrelevance and dimension as a function of intertrial contingency are summarized in a model depicting the dynamic allocation of processing resource.
The Origin of Switch Costs: Task Preparation or Task Application?

Recent studies have shown that switch costs (i.e., slower responding on task-alternation trials than on task-repetition trials) are not observed when on the preceding trial a no-go signal instructed the participant to withhold the response to the target stimulus. This finding suggests that neither task set is inhibited on no-go trials, and that the origin of switch costs is located in the application of the task set to the target stimulus. However, these studies also showed that responding after a no-go trial is substantially slower than after a go trial. This suggests that both task sets are inhibited on no-go trials and that switch costs originate from the preparation of a task set. In two experiments we created conditions that revealed an absence of switch costs in conjunction with relatively fast responding after no-go trials. Together these findings confirm that switch costs originate from the application of the task set.
Internal Facial Features are Signals of Personality and Health

We investigated forms of socially relevant information signalled from static images of the face. We created composite images from women scoring high and low values on personality and health dimensions and measured the accuracy of raters in discriminating high from low trait values. We also looked specifically at the information content within the internal facial features, by presenting the composite images with an occluding mask. Four of the Big Five traits were accurately discriminated on the basis of the internal facial features alone (conscientiousness was the exception), as was physical health. The addition of external features in the full-face images led to improved detection for extraversion and physical health and poorer performance on intellect/imagination (or openness). Visual appearance based on internal facial features alone can therefore accurately predict behavioural biases in the form of personality, as well as levels of physical health.
Improving college students’ evaluation of text learning using idea-unit standards

When recalling key definitions from class materials, college students are often overconfident in the quality of their responses. Even with commission errors, they often judge that their response is entirely or partially correct. To further understand this overconfidence, we investigated whether idea-unit judgements would reduce overconfidence (Experiments 1 and 2) and whether students inflated their scores because they believed that they knew answers but just responded incorrectly (Experiment 2). College students studied key-term definitions and later attempted to recall each definition when given the key term (e.g., What is the availability heuristic? ). All students judged the quality of their recall, but some were given a full-definition standard to use, whereas other students first judged whether their response included each of the individual ideas within the corresponding correct answer. In Experiment 1, making these idea-unit judgements reduced overconfidence for commission errors. In Experiment 2, some students were given the correct definitions and graded other students’ responses, and some students generated idea units themselves before judging their responses. Students were overconfident even when they graded other students’ responses, and, as important, self-generated idea units for each definition also reduced overconfidence in commission errors. Thus, overconfidence appears to result from difficulties in evaluating the quality of recall responses, and such overconfidence can be reduced by using idea-unit judgements.
Observation and physical practice: Coding of simple motor sequences

An experiment was conducted to determine the coordinate system used in the development of movement codes during observation and utilized on later physical practice performance of a simple spatial–temporal movement sequence. The task was to reproduce a 1.3-s spatial–temporal pattern of elbow flexions and extensions. An intermanual transfer paradigm with a retention test and two transfer tests was used: a mirror transfer test where the same pattern of muscle activation and limb joint angles was required and a nonmirror transfer test where the visual–spatial pattern of the sequence was reinstated on the transfer test. The results indicated a strong advantage for participants in the physical practice condition when transferred to the mirror condition in which the motor coordinates (e.g., pattern of muscle activation and joint angles) were reinstated relative to transfer performance when the visual–spatial coordinates were reinstated (visual and spatial location of the target waveform). The observation group, however, demonstrated an advantage when the visual–spatial coordinates were reinstated. These results demonstrate that codes based in motor coordinates can be developed relatively quickly for simple rapid movement sequences when participants are provided physical practice, but observational practice limits the system to the development of codes based in visual–spatial coordinates. Performances of control participants, who were not permitted to practise or observe the task, were quite poor on all tests.
Sprint exercise enhances skeletal muscle p70S6k phosphorylation and more so in women than in men

Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in the regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross‐sectional area in women than men. Therefore, we tested the hypothesis that the activation of mTOR signalling is more pronounced in women than in men. Healthy men (n = 9) and women (n = 8) performed three bouts of 30‐s sprint exercise with 20‐min rest in between.
Consensus Collaboration Enhances Group and Individual Recall Accuracy

We often remember in groups, yet research on collaborative recall finds “collaborative inhibition”: Recalling with others has costs compared to recalling alone. In related paradigms, remembering with others introduces errors into recall. We compared costs and benefits of two collaboration procedures—turn taking and consensus. First, 135 individuals learned a word list and recalled it alone (Recall 1). Then, 45 participants in three-member groups took turns to recall, 45 participants in three-member groups reached a consensus, and 45 participants recalled alone but were analysed as three-member nominal groups (Recall 2). Finally, all participants recalled alone (Recall 3). Both turn-taking and consensus groups demonstrated the usual pattern of costs during collaboration and benefits after collaboration in terms of recall completeness. However, consensus groups, and not turn-taking groups, demonstrated clear benefits in terms of recall accuracy, both during and after collaboration. Consensus groups engaged in beneficial group source-monitoring processes. Our findings challenge assumptions about the negative consequences of social remembering.
GALNT12 is Not a Major Contributor of Familial Colorectal Cancer Type X

Previous evidence indicates that mutations in the GALNT12 gene might cause a fraction of the unexplained familial colorectal cancer (CRC) cases: GALNT12 is located in 9q22‐33, in close proximity to a CRC linkage peak; and germline missense variants that reduce the enzymatic activity of the protein have been identified in CRC patients, some of them with familial CRC history. We hypothesized that mutations in GALNT12 might explain part of the high‐risk families grouped as familial CRC type X (fCRC‐X), that is, Amsterdam‐positive families with mismatch repair proficient tumors. We sequenced the coding regions of the gene in 103 probands of fCRC‐X families, finding no functionally relevant mutations. Our results rule out GALNT12 as a major high CRC susceptibility gene. Additional studies are required to provide further evidence about its role as a moderate/low susceptibility gene in familial aggregation of cancer.
Producing and recognizing words with two pronunciation variants: Evidence from novel schwa words

This study examined the lexical representations and psycholinguistic mechanisms underlying the production and recognition of novel words with two pronunciation variants in French. Participants first learned novel schwa words (e.g., /ʃənyk/), which varied in their alternating status (i.e., whether these words were learned with one or two variants) and, for alternating words, in the frequency of their variants. They were then tested in picture-naming (free or induced) and recognition memory tasks (i.e., deciding whether spoken items were learned during the experiment or not). Results for free naming show an influence of variant frequency on responses, more frequent variants being produced more often. Moreover, our data show an effect of the alternating status of the novel words on naming latencies, with longer latencies for alternating than for nonalternating novel words. These induced naming results suggest that both variants are stored as lexical entries and compete during the lexeme selection process. Results for recognition show an effect of variant frequency on reaction times and no effect of variant type (i.e., schwa versus reduced variant). Taken together, our findings suggest that participants both comprehend and produce novel French schwa words using two lexical representations, one for each variant.