Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

PURPOSE: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. METHODS: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. RESULTS: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. CONCLUSION: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

Time and memory distrust shape the dynamics of recollection and belief-in-occurrence.

The current study examined how people's metamemory judgments of recollection and belief-in-occurrence change over time. Furthermore, we examined to what extent these judgments are affected by memory distrust - the subjective appraisal of one's memory functioning - as measured by the Memory Distrust Scale (MDS) and the Squire Subjective Memory Scale (SSMQ). Participants (N = 234) studied pictorial stimuli and were tested on some of these stimuli later in the same session, but were tested on other stimuli 1, 2, 4, 8, and 17 days later. Recollection and belief ratings were correlated highly and followed similar declining patterns over time. However, belief decreased relatively more slowly than recollection, such that the discrepancy between recollection and belief increased over time. Memory distrust moderated the association between recollection and belief, with this association being weaker among people who reported greater (versus lower) memory distrust. Memory distrust also interacted with retention period to predict memory judgments. Two measures of memory distrust diverged in their predictive power. In particular, only the MDS predicted the spontaneous reporting of nonbelieved memories. Our results provide support to the theoretical perspective that belief-in-occurrence is a summative judgment informed not only by recollective phenomenology but also by metamemorial beliefs.

The spectrum of cochlear malformations in CHARGE syndrome and insights into the role of the CHD7 gene during embryogenesis of the inner ear.

PURPOSE: We reviewed the genotypes and the imaging appearances of cochleae in CHARGE patients from two large tertiary centres and analysed the observed cochlear anomalies, providing detailed anatomical description and a grading system. The goal was to gain insight into the spectrum of cochlear anomalies in CHARGE syndrome, and thus, in the role of the CHD7 gene in otic vesicle development. METHODS: We retrospectively reviewed CT and/or MR imaging of CHARGE patients referred to our institutions between 2005 and 2022. Cochlear morphology was analysed and, when abnormal, divided into 3 groups in order of progressive severity. Other radiological findings in the temporal bone were also recorded. Comparison with the existing classification system of cochlear malformation was also attempted. RESULTS: Cochlear morphology in our CHARGE cohort ranged from normal to extreme hypoplasia. The most common phenotype was cochlear hypoplasia in which the basal turn was relatively preserved, and the upper turns were underdeveloped. All patients in the cohort had absent or markedly hypoplastic semicircular canals and small, misshapen vestibules. Aside from a stenotic cochlear aperture (fossette) being associated with a hypoplastic or absent cochlear nerve, there was no consistent relationship between cochlear nerve status (normal, hypoplasia, or aplasia) and cochlear morphology. CONCLUSION: Cochlear morphology in CHARGE syndrome is variable. Whenever the cochlea was abnormal, it was almost invariably hypoplastic. This may shed light on the role of CHD7 in cochlear development. Accurate morphological description of the cochlea contributes to proper clinical diagnosis and is important for planning surgical treatment options.

Preference for cheap-and-easy memory verification strategies is strongest among people with high memory distrust.

When choosing strategies for verifying one's memory, people are more influenced by the perceived cost of using a strategy than by its likelihood of yielding reliable information (i.e., cheap-strategy bias). The current preregistered study investigated whether people with high memory distrust are less likely to exhibit this bias than their low memory distrust counterparts. Participants (N = 535) imagined a scenario in which they witnessed an accident and were then led by friends to question their memories about the accident. Participants had to propose five strategies for verifying that particular memory. Following this, they rated each strategy's cost, reliability, and their likelihood of using it, as well as completing two validated measures of trait memory distrust. Contrary to our prediction, compared with participants with low memory distrust, participants with higher memory distrust exhibited a larger cheap-strategy bias. Follow-up analyses suggested that compared with memory-trusters, memory distrusters' strategy choices were more influenced by a strategy's perceived cost, and less influenced by its perceived reliability. Our results suggest that people who are more skeptical about their memories may be more cynical about the worthwhileness of verifying their memory, which could make them especially susceptible to misinformation acceptance and false memory creation.

Effects of cueing multiple memories of eating on people's judgments about their diet.

Past research shows that recalling a single positive health-related experience, such as exercising, can encourage people's subsequent healthy behaviours. In contrast, we reasoned that attempting to recall many healthy experiences might elicit a metacognitive experience of difficulty that would lead people to perceive themselves as less healthy, and perhaps to make other health-related judgments based on this perception. In two pre-registered experiments (combined N = 729), participants recalled either "few" or "many" instances of eating either healthily or unhealthily, before rating the healthiness of their diets and completing measures of their eating preferences and choices. Contrary to our predictions, our pre-registered analyses provided minimal evidence that the number of memories people retrieved affected their judgments. However, exploratory mediation analyses suggested that two counteracting effects may have occurred, whereby retrieving more (un)healthy memories led people to identify as more (un)healthy, yet also created a sense of subjective difficulty that partially or wholly negated these effects. These findings suggest that whereas probing people's dietary memories might sometimes lead to healthier self-perceptions and dietary choices, we should also consider the possibility of backfire effects.

Radiologic diagnosis of non-traumatic paediatric head and neck emergencies.

Imaging plays a crucial role in evaluating paediatric patients with non-traumatic head and neck lesions in an emergency setting because clinical manifestations of these entities can overlap. For this reason, radiologists must be familiar with the clinical and imaging findings of prevalent paediatric head and neck emergencies. In this review, we present techniques and imaging clues for common complications of pathological processes in the paediatric head and neck, with a focus on the clinical scenario as a starting point for the radiologic approach.

Introduction of C-alkyl branches to L-iminosugars changes their active site binding orientation.

L-ido-Deoxynojirimycin (L-ido-DNJ) itself showed no affinity for human lysosomal acid α-glucosidase (GAA), whereas 5-C-methyl-L-ido-DNJ showed a strong affinity for GAA, comparable to the glucose analog DNJ, with a Ki value of 0.060 µM. This excellent affinity for GAA and enzyme stabilization was observed only when methyl and ethyl groups were introduced. Docking simulation analysis revealed that the alkyl chains of 5-C-alkyl-L-ido-DNJs were stored in three different pockets, depending on their length, thereby the molecular orientation was changed. Comparison of the binding poses of DNJ and 5-C-methyl-L-ido-DNJ showed that they formed a common ionic interaction with Asp404, Asp518, and Asp616, but both the binding orientation and the distance between the ligand and each amino acid residue were different. 5-C-Methyl-L-ido-DNJ dose-dependently increased intracellular GAA activity in Pompe patient fibroblasts with the M519V mutation and also promoted enzyme transport to lysosomes. This study provides the first example of a strategy to design high-affinity ligands by introducing alkyl branches into rare sugars and L-sugar-type iminosugars to change the orientation of binding.

Transcriptome visualization and data availability at the Saccharomyces Genome Database.

The Saccharomyces Genome Database (SGD; www.yeastgenome.org) maintains the official annotation of all genes in the Saccharomyces cerevisiae reference genome and aims to elucidate the function of these genes and their products by integrating manually curated experimental data. Technological advances have allowed researchers to profile RNA expression and identify transcripts at high resolution. These data can be configured in web-based genome browser applications for display to the general public. Accordingly, SGD has incorporated published transcript isoform data in our instance of JBrowse, a genome visualization platform. This resource will help clarify S. cerevisiae biological processes by furthering studies of transcriptional regulation, untranslated regions, genome engineering, and expression quantification in S. cerevisiae.

Memories people no longer believe in can still affect them in helpful and harmful ways.

People can come to "remember" experiences they never had, and these false memories-much like memories for real experiences-can serve a variety of helpful and harmful functions. Sometimes, though, people realize one of their memories is false, and retract their belief in it. These "retracted memories" continue to have many of the same phenomenological characteristics as their believed memories. But can they also continue to serve functions? Across four experiments, we asked subjects to rate the extent to which their retracted memories serve helpful and harmful functions and compared these functions with those served by "genuine" autobiographical memories. People rated their retracted memories as serving both helpful and harmful functions, much like their genuine memories. In addition, we found only weak relationships between people's belief in their memories and the extent to which those memories served perceived functions. These results suggest memories can serve functions even in the absence of belief and highlight the potential for false memories to affect people's thinking and behavior even after people have retracted them.

Front-of-pack health imagery on both 'healthy' and 'unhealthy' foods leads people to misremember seeing health claims: Two memory experiments.

Front-of-pack health imagery can shape people's inferences about food products' health benefits, even leading people to falsely remember reading health claims they never saw. However, research has typically examined these effects in situations where participants have little contextual information to guide their inferences about a product. The present research aimed to replicate the finding that front-of-pack health imagery leads participants to falsely remember reading health claims. It also extends that finding, by exploring whether this effect is moderated by the presence of contextual information signaling the product's actual 'healthiness'. In two pre-registered experiments, participants saw images of fictitious food products accompanied by written nutrition claims. Some of the products contained a health-related image whereas others did not. The supposed 'healthiness' of each product was manipulated by altering the color of the products' multiple traffic light (MTL) label (Experiment 1), or with an explicit healthiness statement (Experiment 2). Participants then attempted to remember the written claims that had appeared on each product's packaging. Health-related images increased participants' tendency to falsely remember reading health claims. But this was true regardless of whether or not participants saw contextual cues about the products' healthiness, either indirectly (Experiment 1) or directly (Experiment 2). These findings suggest that the presence of health imagery on a food product's package can lead consumers to infer health benefits, even when other, more direct cues indicate that the product is unhealthy. This research informs debates on safeguarding consumers from potentially misleading health claims, through the regulation of imagery in food marketing.

False remembering in real life: James Ost's contributions to memory psychology.

This special issue honours James Ost's (1973-2019) contributions to our understanding of false and distorted remembering. In our editorial, we introduce some of James' distinctive research themes including the experiences of people who retract "recovered" memories, social (e.g., co-witness and interviewer influence) and personality influences on false remembering, the nature of false remembering itself (e.g., different types of false memories; false memories vs. false beliefs), public understanding of (false) memory, and a historical link to the work of Frederic Bartlett. We illustrate these themes through a number of key publications. The unifying thread behind James' work is his core interest in false/distorted remembering in real-life (typically high-stake) situations, in line with his engagement with the British False Memory Society and his role as an expert witness in court trials. The articles included in this special issue elaborate on the research themes to which James devoted his career and his curiosity.

Iminosugar Amino Acid idoBR1 Reduces Inflammatory Responses in Microglia.

(1) Background. Inflammation is reported to be a key factor in neurodegeneration. The microglia are immune cells present in the central nervous system; their activation results in the release of inflammatory cytokines and is thought to be related to aging and neurodegenerative disorders, such as Alzheimer's disease. (2) Methods. A mouse BV-2 microglia cell line was activated using LPS and the anti-inflammatory cucumber-derived iminosugar amino acid idoBR1, (2R,3R,4R,5S)-3,4,5-trihydroxypiperidine-2-carboxylic acid, was used alongside dexamethasone as the control to determine whether it could reduce the inflammatory responses. (3) Results. A dose-dependent reduction in the LPS-induced production of the proinflammatory factors TNFα, IL-6, and nitric oxide and the transcription factor NF-κB was found. (4) Conclusions. Further investigations of the anti-inflammatory effects of idoBR1 in other models of neurodegenerative diseases are warranted.

Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy.

Tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesised via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT), a promising radiation type for cancer, as this therapy does little damage to biological tissue. An unexpected decarbonylation/decarboxylation to five 2,3,4,5-tetrachlorobenzamides was observed and confirmed by X-ray crystallography studies, thus, giving access to a family of borylated 2,3,4,5-tetrachlorobenzamides. Biological evaluation showed the benzamide drugs to possess good to weak potencies (74.7-870 µM) in the inhibition of glycosidases, and to have good to moderate selectivity in the inhibition of a panel of 18 glycosidases. Furthermore, in the inhibition of selected glycosidases, there is a core subset of three animal glycosidases, which is always inhibited (rat intestinal maltase α-glucosidase, bovine liver ß-glucosidase and ß-galactosidase). This could indicate the involvement of the boron atom in the binding. These glycosidases are targeted for the management of diabetes, viral infections (via a broad-spectrum approach) and lysosomal storage disorders. Assays against cancer cell lines revealed potency in growth inhibition for three molecules, and selectivity for one of these molecules, with the growth of the normal cell line MCF10A not being affected by this compound. One of these molecules showed both potency and selectivity; thus, it is a candidate for further study in this area. This paper provides numerous novel aspects, including expedited access to borylated 2,3,4,5-tetrachlorophthalimides and to 2,3,4,5-tetrachlorobenzamides. The latter constitutes a novel family of glycosidase modulating drugs. Furthermore, a greener synthetic access to such structures is described.

Synthesis of (+)-(R)-Tiruchanduramine.

The absolute stereochemistry of the marine alkaloid (+)-(R)-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH.

Misremembering Brexit: partisan bias and individual predictors of false memories for fake news stories among Brexit voters.

Exposure to fake news stories can result in false memories for the events portrayed, and this effect can be enhanced if the stories conform to the reader's ideological position. We exposed 1299 UK residents to fabricated news stories about Brexit. 44% of participants reported a false memory for at least one fabricated story, with a higher rate of false memories for stories that reflected poorly on the opposing side. This effect of ideological congruency was somewhat greater among participants who were exposed to a threat to their social identity as a Leave or Remain supporter; however, this moderating effect was only statistically significant in exploratory analyses using a more conservative definition of false memory. Participants with higher cognitive ability and analytical reasoning scores were less susceptible to false memories. Individuals with better knowledge about Brexit showed better discrimination between true and false stories, while self-reported engagement with the Brexit debate was associated with an increased tendency to "remember" any story, regardless of its truth. These results implicate a combination of social and individual factors in the development of false memories from fake news, and suggest that exposure to social identity threats may enhance the polarising effects of fake news.

Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation.

Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike protein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS-CoV-2 spike protein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 µg/ml) and garcinoic acid (1.25, 2.5, and 5 µM) significantly reduced SARS-CoV-2 spike protein S1-induced secretion of TNFα, IL-6, IL-1ß, and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and garcinoic acid reduced expressions of both phospho-p65 and phospho-IκBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike protein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike protein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm in severe SARS-CoV-2 and other coronavirus infections.

Saccharomyces genome database informs human biology.

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is an expertly curated database of literature-derived functional information for the model organism budding yeast, Saccharomyces cerevisiae. SGD constantly strives to synergize new types of experimental data and bioinformatics predictions with existing data, and to organize them into a comprehensive and up-to-date information resource. The primary mission of SGD is to facilitate research into the biology of yeast and to provide this wealth of information to advance, in many ways, research on other organisms, even those as evolutionarily distant as humans. To build such a bridge between biological kingdoms, SGD is curating data regarding yeast-human complementation, in which a human gene can successfully replace the function of a yeast gene, and/or vice versa. These data are manually curated from published literature, made available for download, and incorporated into a variety of analysis tools provided by SGD.

Front-of-pack images can boost the perceived health benefits of dietary products.

Images on dietary supplement packaging can help identify the products' supposed function. However, research shows that these images can also lead people to infer additional health benefits of consuming the products. The present research investigated the extent to which front-of-pack imagery affects people's perceptions of the health risks and benefits of fictional products. In three randomized experiments, participants saw fictitious dietary supplement packages. Some of the packages included a health-related image (e.g. a heart), whereas others did not. Participants were asked to infer the products' intended purpose and then to rate the perceived risks and benefits of consuming the product. In Experiment 1 (N = 546), the inclusion of a health-related image increased the perceived benefits of consuming the product, with minimal effect on the perceived risks. This finding was replicated in Experiment 2 (N = 164), but was contingent on whether each product's assumed health function was confirmed or disconfirmed. In Experiment 3 (N = 306), which used a pre-registered design and analysis plan, the inclusion of a health-related image increased the perceived benefits and decreased the perceived risks of consuming the product. Again, these effects were contingent on whether the assumed health functions were confirmed or disconfirmed. These findings indicate that health-related imagery could lead consumers to infer additional health properties from non-diagnostic information featured on a product's packaging, perhaps as a consequence of increased processing fluency. This research underscores the importance of regulating the use of imagery in health marketing, to protect consumers from the effects of potentially misleading claims.

Weak memory for future-oriented feedback: investigating the roles of attention and improvement focus.

Recent research showed that people recall past-oriented, evaluative feedback more fully and accurately than future-oriented, directive feedback. Here we investigated whether these memory biases arise from preferential attention toward evaluative feedback during encoding. We also attempted to counter the biases via manipulations intended to focus participants on improvement. Participants received bogus evaluative and directive feedback on their writing. Before reading the feedback, some participants set goals for improvement (experiments 1 and 2), or they wrote about their past or future use of the writing skills, and/or were incentivised to improve (experiment 3); we objectively measured participants' attention during feedback reading using eyetracking. Finally, all participants completed a recall test. We successfully replicated the preferential remembering of evaluative feedback, but found little support for an attentional explanation. Goal-setting reduced participants' tendency to reproduce feedback in an evaluative style, but not their preferential remembering of evaluative feedback. Neither orienting participants toward their past or future use of the writing skills, nor incentivising them to improve, influenced their attention toward or memory for the feedback. These findings advance the search for a mechanism to explain people's weaker memory for future-oriented feedback, demonstrating that attentional and improvement-oriented accounts cannot adequately explain the effect.

Strategy for Designing Selective Lysosomal Acid α-Glucosidase Inhibitors: Binding Orientation and Influence on Selectivity.

Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site. Our design of α-1-C-heptyl-1,4-dideoxy-1,4-imino-l-arabinitol (LAB) produced a potent inhibitor of the GAA, with an IC50 value of 0.44 µM. It displayed a remarkable selectivity toward GAA (selectivity index value of 168.2). A molecular dynamic simulation study revealed that the ligand-binding conformation stability gradually improved with increasing length of the α-1-C-alkyl chain. It is noteworthy that α-1-C-heptyl-LAB formed clearly different interactions from DNJ and had favored hydrophobic interactions with Trp481, Phe525, and Met519 at the alkyl chain storage pocket of GAA. Moreover, a molecular docking study revealed that endoplasmic reticulum (ER) α-glucosidase II does not have enough space to accommodate these alkyl chains. Therefore, the design strategy focusing on the shape and acceptability of long alkyl chain at each α-glucosidase may lead to the creation of more selective and practically useful inhibitors.