Inv(3) Acute Myeloid Leukemia in a Young Adult and Review of the Literature.

Acute myeloid leukemia (AML) with the high-risk variant inv(3)/t(3;3) or t(3;3)(q21;26.2) is rarely seen in the pediatric and young adult population. It is associated with poor outcomes with ineffective therapeutic options.

Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss.

The melanocortin-4 receptor (MC4R) is a centrally expressed, class A GPCR that plays a key role in the regulation of appetite and food intake. Deficiencies in MC4R signaling result in hyperphagia and increased body mass in humans. Antagonism of MC4R signaling has the potential to mitigate decreased appetite and body weight loss in the setting of anorexia or cachexia due to underlying disease.

Intersecting distributed networks support convergent linguistic functioning across different languages in bilinguals.

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, whether and how this hypothesis applies at the finer-grained levels of both brain anatomical organization and linguistic functions remains unknown.

Dipole moment background measurement and suppression for levitated charge sensors.

Optically levitated macroscopic objects are a powerful tool in the field of force sensing, owing to high sensitivity, absolute force calibration, environmental isolation, and the advanced degree of control over their dynamics that have been achieved. However, limitations arise from the spurious forces caused by electrical polarization effects that, even for nominally neutral objects, affect the force sensing because of the interaction of dipole moments with gradients of external electric fields. Here, we introduce a technique to measure, model, and eliminate dipole moment interactions, limiting the performance of sensors using levitated objects.

The impact of contact tracing and testing on controlling COVID-19 outbreak without lockdown in Hong Kong: An observational study.

Background: Maintaining effective contact tracing to control COVID-19 is challenging. Rapid growth in the number of infected cases can overload tracing and testing capacity, resulting in failure to trace contacts and delays in confirming an infection until after symptom onset (confirmation delay), hence increasing transmissibility. A substantial outbreak in Hong Kong, which was suppressed with non-pharmaceutical interventions (NPIs), provided an opportunity to assess the impact of overloading contact tracing and of efforts to improve its efficiency.

New treatment for amblyopia based on rules of synaptic plasticity: a randomized clinical trial.

Amblyopia resulting from early deprivation of vision or defocus in one eye reflects an imbalance of input from the eyes to the visual cortex. We tested the hypothesis that asynchronous stimulation of the two eyes might induce synaptic plasticity and rebalance input. Experiments on normal adults showed that repetitive brief exposure of grating stimuli, with the onset of each stimulus delayed by 8.

The impact of multiple non-pharmaceutical interventions on controlling COVID-19 outbreak without lockdown in Hong Kong: A modelling study.

Background: The 'third wave' of COVID-19 in Hong Kong, China was suppressed by non-pharmaceutical interventions (NPIs). Although social distancing regulations were quickly strengthened, the outbreak continued to grow, causing increasing delays in tracing and testing. Further regulations were introduced, plus 'targeted testing' services for at-risk groups.

Synthesis of α-Heteroaryl Propionic Esters by Palladium-Catalyzed α-Heteroarylation of Silyl Ketene Acetals.

A practical and efficient synthesis of α-heteroaryl propionic esters is developed by employing palladium-catalyzed α-heteroarylation of silyl ketene acetals, forming a wide variety of α-heteroaryl propionic esters with various substituents and functionalities in high yields. The success of this transformation is credited to the development of the bulky P,P═O ligand. The method has provided an efficient synthesis of α-heteroaryl propionic acids.

High sensitivity, levitated microsphere apparatus for short-distance force measurements.

A high sensitivity force sensor based on dielectric microspheres in vacuum, optically trapped by a single, upward-propagating laser beam, is described. Off-axis parabolic mirrors are used both to focus the 1064 nm trapping beam and to recollimate it to provide information on the horizontal position of the microsphere. The vertical degree of freedom is readout by forming an interferometer between the light retroreflected by the microsphere and a reference beam, hence eliminating the need for auxiliary beams.

I haven't a clue! Expectations based on repetitions and hints facilitate perceptual experience of ambiguous images.

In recent years, the role of top-down expectations on perception has been extensively researched within the framework of predictive coding. However, less attention has been given to the different sources of expectations, how they differ, and how they interact. In this article, we examined the effects of informative hints on perceptual experience and how these interact with repetition-based expectations to create a long-lasting effect.

Seeing a Work of Art Indirectly: When a Reproduction Is Better Than an Indirect View, and a Mirror Better Than a Live Monitor.

Visiting a museum and seeing an original artwork can be a special experience. We use a survey and a set of hypothetical questions to explore how such experience would be affected by changes in how the artwork is seen. In a first study, participants imagined that they had traveled to see a painting that they particularly like.

Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead 2 derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor 3.

Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate.

The neural tube defects anencephaly and spina bifida are two of the most common serious congenital malformations. Most cases can be prevented by consuming sufficient folic acid immediately before pregnancy and in early pregnancy. Fortification of flour with folic acid to prevent these defects has been implemented in 81 countries without public objection or indication of harm.

Building Bridges through Science.

Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.

Search for Screened Interactions Associated with Dark Energy below the 100 μm Length Scale.

We present the results of a search for unknown interactions that couple to mass between an optically levitated microsphere and a gold-coated silicon cantilever. The scale and geometry of the apparatus enable a search for new forces that appear at distances below 100  μm and which would have evaded previous searches due to screening mechanisms. The data are consistent with electrostatic backgrounds and place upper limits on the strength of new interactions at <0.

Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer.

Background: Recently introduced multigene panel testing including BRCA1 and BRCA2 genes for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study was to evaluate rates of pathogenic BRCA1/2 mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multigene testing.

Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution.

'Super-Enrichment' Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease.

Background: Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment.

Implementing the 3Rs in neuroscience research: a reasoned approach.

The 3Rs--replacement, reduction, and refinement--are aimed at minimizing the welfare costs to animals used in research. Some neuroscientists fear that implementing the 3Rs will prohibit essential studies. Others view them as fundamental ethical principles that improve the quality of research.

Synaesthetic perception of colour and visual space in a blind subject: an fMRI case study.

In spatial sequence synaesthesia (SSS) ordinal stimuli are perceived as arranged in peripersonal space. Using fMRI, we examined the neural bases of SSS and colour synaesthesia for spoken words in a late-blind synaesthete, JF. He reported days of the week and months of the year as both coloured and spatially ordered in peripersonal space; parts of the days and festivities of the year were spatially ordered but uncoloured.

Sequence-specific single-molecule analysis of 8-oxo-7,8-dihydroguanine lesions in DNA based on unzipping kinetics of complementary probes in ion channel recordings.

Translocation measurements of intact DNA strands with the ion channel α-hemolysin (α-HL) are limited to single-stranded DNA (ssDNA) experiments as the dimensions of the channel prevent double-stranded DNA (dsDNA) translocation; however, if a short oligodeoxynucleotide is used to interrogate a longer ssDNA strand, it is possible to unzip the duplex region when it is captured in the α-HL vestibule, allowing the longer strand to translocate through the α-HL channel. This unzipping process has a characteristic duration based on the stability of the duplex. Here, ion channel recordings are used to detect the presence and relative location of the oxidized damage site 8-oxo-7,8-dihydroguanine (OG) in a sequence-specific manner.

Functional characterisation of sensory ERPs using probabilistic ICA: effect of stimulus modality and stimulus location.

Objective: To decompose sensory event-related brain potentials (ERPs) into a set of independent components according to the modality and the spatial location of the eliciting sensory stimulus, and thus provide a quantitative analysis of their underlying components.

Methods: Auditory, somatosensory and visual ERPs were recorded from 124 electrodes in thirteen healthy participants. Probabilistic Independent Component Analysis (P-ICA) was used to decompose these sensory ERPs into a set of independent components according to the modality (auditory, somatosensory, visual or multimodal) and the spatial location (left or right side) of the eliciting stimulus.

Cardiac stress tests - which one should I choose?

Chest pain is a common cause of presentation to the Acute Medical Unit and the use of cardiac stress imaging in these patients is becoming more widespread. This article aims to provide Acute Physicians with a basic understanding of the different modalities and how to select a particular test for a given patient.