Miracle-dz/UniFAR-FTUs huggingface dataset:
Corneal Dystrophy‐Causing SLC4A11 Mutants: Suitability for Folding‐Correction Therapy

SLC4A11 mutations cause some cases of the corneal endothelial dystrophies, congenital hereditary endothelial corneal dystrophy type 2 (CHED2), Harboyan syndrome (HS), and Fuchs endothelial corneal dystrophy (FECD). SLC4A11 protein was recently identified as facilitating water flux across membranes. SLC4A11 point mutations usually cause SLC4A11 misfolding and retention in the endoplasmic reticulum (ER). We set about to test the feasibility of rescuing misfolded SLC4A11 protein to the plasma membrane as a therapeutic approach. Using a transfected HEK293 cell model, we measured functional activity present in cells expressing SLC4A11 variants in combinations representing the state found in CHED2 carriers, affected CHED2, FECD individuals, and unaffected individuals. These cells manifest respectively about 60%, 5%, and 25% of the water flux activity, relative to the unaffected (WT alone). ER‐retained CHED2 mutant SLC4A11 protein could be rescued to the plasma membrane, where it conferred 25%–30% of WT water flux level. Further, some ER‐retained CHED2 mutants expressed at 30°C supported increased water flux compared with 37°C cultures. Caspase activation and cell vitality assays revealed that expression of SLC4A11 mutants in HEK293 cells does not induce cell death. We conclude that therapeutics able to increase cell surface localization of ER‐retained SLC4A11 mutants hold promise to treat CHED2 and FECD patients.
Enrichment of LOVD‐USHbases with 152 USH2A Genotypes Defines an Extensive Mutational Spectrum and Highlights Missense Hotspots

Alterations of USH2A, encoding usherin, are responsible for more than 70% of cases of Usher syndrome type II (USH2), a recessive disorder that combines moderate to severe hearing loss and retinal degeneration. The longest USH2A transcript encodes usherin isoform b, a 5,202‐amino‐acid transmembrane protein with an exceptionally large extracellular domain consisting notably of a Laminin N‐terminal domain and numerous Laminin EGF‐like (LE) and Fibronectin type III (FN3) repeats. Mutations of USH2A are scattered throughout the gene and mostly private. Annotating these variants is therefore of major importance to correctly assign pathogenicity. We have extensively genotyped a novel cohort of 152 Usher patients and identified 158 different mutations, of which 93 are newly described. Pooling this new data with the existing pathogenic variants already incorporated in USHbases reveals several previously unappreciated features of the mutational spectrum. We show that parts of the protein are more likely to tolerate single amino acid variations, whereas others constitute pathogenic missense hotspots. We have found, in repeated LE and FN3 domains, a nonequal distribution of the missense mutations that highlights some crucial positions in usherin with possible consequences for the assessment of the pathogenicity of the numerous missense variants identified in USH2A.
Does Visual Working Memory Work as a Few Fixed Slots?

The present study investigated whether visual working memory (VWM) functions as a few (about 3 ∼ 4) fixed slots by examining how the distribution of VWM is adjusted. Adopting a change-detection paradigm, we required subjects to memorize four items, one of which was prioritized. If VWM functions as 3 ∼ 4 slots, allocating multiple slots to the prioritized item would leave no slot for some other items; consequently no information would be stored for them, leading to a substantial decrease in change-detection performance no matter whether small or large changes occurred. The result showed that small changes on the unfavoured items were detected less accurately, indicating that more VWM was allocated to the favoured item. Yet meanwhile large changes that occurred on those unfavoured items could still be detected as well as those on the favoured one, indicating that each of them was still stored to some extent rather than completely discarded. The results suggested that VWM may not work as 3 ∼ 4 fixed slots. Possible mechanisms were discussed based on the present results, including a modified slot model with more available slots, a continuous resource model, and a hierarchical model that assumes storage of ensemble information in addition to the information of individual items.
Flexible, Scalable, and Efficient Targeted Resequencing on a Benchtop Sequencer for Variant Detection in Clinical Practice

The release of benchtop next‐generation sequencing (NGS) instruments has paved the way to implement the technology in clinical setting. The need for flexible, qualitative, and cost‐efficient workflows is high. We used singleplex‐PCR for highly efficient target enrichment, allowing us to reach the quality standards set in Sanger sequencing‐based diagnostics. For the library preparation, a modified NexteraXT protocol was used, followed by sequencing on a MiSeq instrument. With an innovative pooling strategy, high flexibility, scalability, and cost‐efficiency were obtained, independent of the availability of commercial kits. The approach was validated for ∼250 genes associated with monogenic disorders. An overall sensitivity (>99%) similar to Sanger sequencing was observed in combination with a positive predictive value of >98%. The distribution of coverage was highly uniform, guaranteeing a minimal number of gaps to be filled with alternative methods. ISO15189‐accreditation was obtained for the workflow. A major asset of the singleplex PCR‐based enrichment is that new targets can be easily implemented. Diagnostic laboratories have validated assays available ensuring that the proposed workflow can easily be adopted. Although our platform was optimized for constitutional variant detection of monogenic disease genes, it is now also used as a model for somatic mutation detection in acquired diseases.
Stability of Two Extemporaneously Prepared Oral Metoprolol and Carvedilol Liquids

The stability of metoprolol and carvedilol in extemporaneously prepared oral liquids was studied. An aqueous liquid formulation of each drug was prepared by reconstituting the powder from triturated tablets with a mixture of deionized water and 70% sorbitol solution. The expected metoprolol concentration was 1.25 mg/mL and for carvedilol was 0.625 mg/mL. Polyethylene terephthalate (PET) plastic bottles containing metoprolol and carvedilol liquids were stored at ambient room temperature (22° to 26°C, and in the refrigerator (4° to 8C). After storage periods of 1, 2, 4, and 8 weeks, these samples were analyzed in triplicate for the respective drug concentrations by high-performance liquid chromatography (HPLC). The concentration of each drug was found to be within the acceptable limit (± 10% of the initial concentration) in all test samples, which indicated that metoprolol and carvedilol liquids were stable at room temperature and refrigerated for up to 8 weeks. However, there were signs of possible decomposition in metoprolol oral liquid after 8 weeks of storage at room temperature. Additionally, our study findings revealed that there was no microbial growth in either drug liquid after a refrigerated storage period of 2 weeks. Hosp Pharm — 2006;41:254-259
Attentional Bias Induced by Solving Simple and Complex Addition and Subtraction Problems

The processing of numbers has been shown to induce shifts of spatial attention in simple probe detection tasks, with small numbers orienting attention to the left and large numbers to the right side of space. Recently, the investigation of this spatial–numerical association has been extended to mental arithmetic with the hypothesis that solving addition or subtraction problems may induce attentional displacements (to the right and to the left, respectively) along a mental number line onto which the magnitude of the numbers would range from left to right, from small to large numbers. Here we investigated such attentional shifts using a target detection task primed by arithmetic problems in healthy participants. The constituents of the addition and subtraction problems (first operand; operator; second operand) were flashed sequentially in the centre of a screen, then followed by a target on the left or the right side of the screen, which the participants had to detect. This paradigm was employed with arithmetic facts (Experiment 1) and with more complex arithmetic problems (Experiment 2) in order to assess the effects of the operation, the magnitude of the operands, the magnitude of the results, and the presence or absence of a requirement for the participants to carry or borrow numbers. The results showed that arithmetic operations induce some spatial shifts of attention, possibly through a semantic link between the operation and space.
Occupational Chemical Exposures among Cosmetologists

More research is needed to understand possible occupational reproductive risks for cosmetologists, specifically hairdressers and nail technicians, two occupations that often share workspace and exposure to hair dyes and nail polish. Cosmetologists are predominantly females of reproductive age; thus, they may be at higher risk for the effects of exposure to reproductive toxins. The purpose of this article is to inform nurses and public health professionals about occupational exposures for cosmetologists and discuss interventions to reduce the risks of reproductive disorders among susceptible worker populations.
Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs.

OBJECTIVES The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age. METHODS A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were interviewed by a veterinary behaviourist. Structured phone interviews were used to gather information about four behavioural categories related to cognitive impairment: sleep/wake cycles, social interaction, learning and house training and signs of disorientation. RESULTS Signs of cognitive impairment showed a prevalence of 22.5 per cent in geriatric dogs. Sex and age emerged as significant predictor variables. Females and neutered dogs were significantly more affected than males and entire dogs, respectively. Prevalence and severity increased with age. Although weight was not a statistically significant predictor variable, smaller animals had greater odds of showing age-related cognitive impairment. The most impaired behavioural categories were social interaction and house training. CLINICAL SIGNIFICANCE Age-related behavioural changes should be considered by practicing veterinarians because of their relative high prevalence among geriatric dogs, especially in females.
Caracterización de los efectos tisulares en los segmentos adyacentes a los stents liberadores de paclitaxel según el análisis de datos de radiofrecuencia procedentes de ecocardiografía intravascular seriada: estudio BETAX (BEside TAXus)

Introduccion y objetivos En la actualidad se desconoce el efecto de paclitaxel en la composicion tisular en los segmentos adyacentes (bordes) del stent Taxus®. El objetivo de este estudio fue investigar in vivo los cambios temporales que se producen en los bordes del stent liberador de paclitaxel segun un analisis de los datos de radiofrecuencia procedentes de ecografia intravascular (EIV). Metodos En total participaron 24 pacientes (26 segmentos con stents liberadores de paclitaxel). Se obtuvieron imagenes con EIV de los 5 mm proximales y los 5 mm distales de los bordes del stent transcurridos 6 meses del implante. Para realizar un analisis posterior, los segmentos proximales y distales se fraccionaron en cinco subsegmentos de 1 mm cada uno. Resultados En los primeros dos subsegmentos adyacentes al stent del borde proximal, la pared del vaso crece para compensar el crecimiento de la placa sin que ello afecte a la luz, mientras en los siguientes 3 subsegmentos se observo una sobrecompensacion (la pared del vaso aumento mas que el tamano de la placa). Por lo tanto, aumento el tamano luminal. En el borde distal, se observo sobrecompensacion en todos los subsegmentos, seguida de un aumento del tamano luminal. En general, el crecimiento proximal y distal se baso en un aumento de la placa fibrolipidica (p Conclusiones Se observo un remodelado vascular expansivo y seriado en los bordes proximal y distal del stent, para acomodar un crecimiento tisular principalmente debido al aumento del tejido fibrolipidico.
A SAMHD1 mutation associated with Aicardi–Goutières syndrome uncouples the ability of SAMHD1 to restrict HIV‐1 from its ability to downmodulate type I interferon in humans

Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi–Goutières syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has led to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV‐1 infection of macrophages, dendritic cells, and resting CD4+ T cells. To gain insights on the SAMHD1 molecular determinants that are responsible for the deregulated production of type I IFN, we explored the biochemical, cellular, and antiviral properties of human SAMHD1 mutants known to correlate with the development of AGS. Most of the studied SAMHD1 AGS mutants exhibit defects in the ability to oligomerize, decrease the levels of cellular deoxynucleotide triphosphates in human cells, localize exclusively to the nucleus, and restrict HIV‐1 infection. At least half of the tested variants preserved the ability to be degraded by the lentiviral protein Vpx, and all of them interacted with RNA. Our investigations revealed that the SAMHD1 AGS variant p.G209S preserve all tested biochemical, cellular, and antiviral properties, suggesting that this residue is a determinant for the ability of SAMHD1 to negatively regulate the type I IFN response in human patients with AGS. Overall, our work genetically separated the ability of SAMHD1 to negatively regulate the type I IFN response from its ability to restrict HIV‐1.
Fit to last: Exploring the longevity of the survival processing effect

Mounting evidence indicates that processing items for their survival value produces superior recall compared to a number of other well-known memory-enhancing techniques, and that this mnemonic advantage remains up to 48 hours after encoding (Raymaekers et al., 2014). However, little attention has been dedicated to the survival processing effect in location memory, which may represent a better test of adaptive memory than retrieval of verbal information. The current study aims to fill this gap by exploring the longevity of the survival processing effect with both word list (Experiment 1) and location-based (Experiment 2) stimuli. Participants rated target items using a single incidental encoding scenario, either Survival versus Pleasantness (word stimuli) or Survival versus Scavenger Hunt (location stimuli). They were then asked to complete a surprise recall task immediately after the ratings and a second recall task 96 hours later. The results demonstrated that, despite a general reduction in memory performance across time, the survival processing advantage was detected at both test times for both stimuli types. These findings provide further support for the survival processing effect and extend the observed effect duration for both word lists and location to 96 hours.
Influence of warmth and competence on the promotion of safe in-group selection: Stereotype content model and social categorization of faces

Categorizing an individual as a friend or foe plays a pivotal role in navigating the social world. According to the stereotype content model (SCM), social perception relies on two fundamental dimensions, warmth and competence, which allow us to process the intentions of others and their ability to enact those intentions, respectively. Social cognition research indicates that, in categorization tasks, people tend to classify other individuals as more likely to belong to the out-group than the in-group (in-group overexclusion effect, IOE) when lacking diagnostic information, probably with the aim of protecting in-group integrity. Here, we explored the role of warmth and competence in group-membership decisions by testing 62 participants in a social-categorization task consisting of 150 neutral faces. We assessed whether (a) warmth and competence ratings could predict the in-group/out-group categorization, and (b) the reliance on these two dimensions differed in low-IOE versus high-IOE participants. Data showed that high ratings of warmth and competence were necessary to categorize a face as in-group. Moreover, while low-IOE participants relied on warmth, high-IOE participants relied on competence. This finding suggests that the proneness to include/exclude unknown identities in/from one's own in-group is related to individual differences in the reliance on SCM social dimensions. Furthermore, the primacy of the warmth effect seems not to represent a universal phenomenon adopted in the context of social evaluation.
DeepBipolar: Identifying genomic mutations for bipolar disorder via deep learning

Bipolar disorder, also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression, and overexcitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from bipolar disorder. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to the conventional lengthy and costly postsymptom clinical diagnosis. Motivated by this study, leveraging several emerging deep learning algorithms, we design an end‐to‐end deep learning architecture (called DeepBipolar) to predict bipolar disorder based on limited genomic data. DeepBipolar adopts the Deep Convolutional Neural Network (DCNN) architecture that automatically extracts features from genotype information to predict the bipolar phenotype. We participated in the Critical Assessment of Genome Interpretation (CAGI) bipolar disorder challenge and DeepBipolar was considered the most successful by the independent assessor. In this work, we thoroughly evaluate the performance of DeepBipolar and analyze the type of signals we believe could have affected the classifier in distinguishing the case samples from the control set.
Editorial QJEP Classics Revisited

ISSN: 1747-0218 (Print) 1747-0226 (Online) Journal homepage: http://www.tandfonline. com/loi/pqje20 Editorial QJEP Classics Revisited Marc Brysbaert To cite this article: Marc Brysbaert (2016) Editorial QJEP Classics Revisited, The Quarterly Journal of Experimental Psychology, 69:10, 1861-1863, DOI: 10.1080/17470218.2016. 1195415 To link to this article: http://dx.doi. org/10.1080/17470218.2016. 1195415
In Defence of High-Speed Memory Scanning

This paper reviews some of the evidence that bears on the existence of a mental high-speed serial exhaustive scanning process (SES) used by humans to interrogate the active memory of a set of items to determine whether it contains a test item. First proposed in the 1960s, based on patterns of reaction times (RTs), numerous later studies supported, elaborated, extended, and limited the generality of SES, while critics claimed that SES never occurred, that predictions from SES were violated, and that other mechanisms produced the RT patterns that led to the idea. I show that some of these claims result from ignoring variations in experimental procedure that produce superficially similar but quantitatively different RT patterns and that, for the original procedures, the most frequently repeated claims that predictions are violated are false. I also discuss evidence against the generality of competing theories of active-memory interrogation, especially those that depend on discrimination of directly accessible “memory-strength”. Some of this evidence has been available since the 1960s but has been ignored by some proponents of alternative theories. Other evidence presented herein is derived from results of one relevant experiment described for the first time, results of another described in more detail than heretofore, and new analyses of old data. Knowledge of brain function acquired during the past half century has increased the plausibility of SES. The conclusion: SES is alive and well, but many associated puzzles merit further investigation, suggestions for which are offered.
The Effects of Increasing Semantic-Associate List Length on the Deese–Roediger–McDermott False Recognition Memory: Dual False-Memory Process in Retrieval from Sub- and Supraspan Lists

In this study, the number of semantic associates in Deese–Roediger–McDermott (DRM) lists was varied from 4 to 14 in a modified Sternberg paradigm. The false alarm (FA) and correct rejection (CR) reaction time (RT)/memory-set size (MSS) functions of critical lures showed a cross-over interaction at approximately MSS 7, suggesting a reversal of the relative dominance between these two responses to the critical lure at this point and also indicating the location of the boundary between the sub- and supraspan MSS. For the subspan lists, FA to critical lures was slower than CR, suggesting a slow, strategic mechanism driving the false memory. Conversely, for the supraspan lists, critical lure FA was faster than its CR, suggesting a spontaneous mechanism driving the false memory. Results of two experiments showed that an automatic, fast, and a slow, controlled process could be error-prone or error-corrective, depending on the length of the DRM memory list. Thus there is a dual retrieval process in false memory as in true memory. The findings can be explained by both the activation/monitoring and the fuzzy-trace theories.
How Young Adults with Autism Spectrum Disorder Watch and Interpret Pragmatically Complex Scenes

The aim of the current study was to investigate subtle characteristics of social perception and interpretation in high-functioning individuals with autism spectrum disorders (ASDs), and to study the relation between watching and interpreting. As a novelty, we used an approach that combined moment-by-moment eye tracking and verbal assessment. Sixteen young adults with ASD and 16 neurotypical control participants watched a video depicting a complex communication situation while their eye movements were tracked. The participants also completed a verbal task with questions related to the pragmatic content of the video. We compared verbal task scores and eye movements between groups, and assessed correlations between task performance and eye movements. Individuals with ASD had more difficulty than the controls in interpreting the video, and during two short moments there were significant group differences in eye movements. Additionally, we found significant correlations between verbal task scores and moment-level eye movement in the ASD group, but not among the controls. We concluded that participants with ASD had slight difficulties in understanding the pragmatic content of the video stimulus and attending to social cues, and that the connection between pragmatic understanding and eye movements was more pronounced for participants with ASD than for neurotypical participants.