Ectopic production of beta-hCG in anal cancer: A case report.

Key Clinical Message: Beta-hCG-producing anal cancer, though rare, poses significant diagnostic challenges and may resist standard therapies. Recognizing the potential for hormone production in anal cancer is important, as it underscores the need for more specialized diagnostic techniques and tailored treatments. Abstract: This case report describes the second reported case of ectopic production of beta-hCG in anal cancer. A 53-year-old female presented with a new anal lesion. Biopsy showed a poorly differentiated squamous cell cancer (SCC) with undifferentiated sarcomatoid features, stage IIIA (cT2cN1cM0). Before starting concurrent chemotherapy and radiation, the patient had a positive urine pregnancy test. The beta-human chorionic gonadotropin (beta-hCG) production was attributed to the tumor, and upon completion of treatment, beta-hCG normalized. Six weeks from treatment completion, recurrence was noted along with a positive beta-hCG urine test. This case aims to highlight beta-hCG as an ectopic hormone that can indicate the presence of squamous cell anal cancer and discuss the potential implications it may have on management.

Global and regional temperature change over the past 4.5 million years.

Much of our understanding of Cenozoic climate is based on the record of δ18O measured in benthic foraminifera. However, this measurement reflects a combined signal of global temperature and sea level, thus preventing a clear understanding of the interactions and feedbacks of the climate system in causing global temperature change. Our new reconstruction of temperature change over the past 4.5 million years includes two phases of long-term cooling, with the second phase of accelerated cooling during the Middle Pleistocene Transition (1.5 to 0.9 million years ago) being accompanied by a transition from dominant 41,000-year low-amplitude periodicity to dominant 100,000-year high-amplitude periodicity. Changes in the rates of long-term cooling and variability are consistent with changes in the carbon cycle driven initially by geologic processes, followed by additional changes in the Southern Ocean carbon cycle.

Deglacial release of petrogenic and permafrost carbon from the Canadian Arctic impacting the carbon cycle.

The changes in atmospheric pCO2 provide evidence for the release of large amounts of ancient carbon during the last deglaciation. However, the sources and mechanisms that contributed to this process remain unresolved. Here, we present evidence for substantial ancient terrestrial carbon remobilization in the Canadian Arctic following the Laurentide Ice Sheet retreat. Glacial-retreat-induced physical erosion of bedrock has mobilized petrogenic carbon, as revealed by sedimentary records of radiocarbon dates and thermal maturity of organic carbon from the Canadian Beaufort Sea. Additionally, coastal erosion during the meltwater pulses 1a and 1b has remobilized pre-aged carbon from permafrost. Assuming extensive petrogenic organic carbon oxidation during the glacial retreat, a model-based assessment suggests that the combined processes have contributed 12 ppm to the deglacial CO2 rise. Our findings suggest potentially positive climate feedback of ice-sheet retreat by accelerating terrestrial organic carbon remobilization and subsequent oxidation during the glacial-interglacial transition.

Symmetry Processing in the Macaque Visual Cortex.

Symmetry is a highly salient feature of the natural world that is perceived by many species. In humans, the cerebral areas processing symmetry are now well identified from neuroimaging measurements. Macaque could constitute a good animal model to explore the underlying neural mechanisms, but a previous comparative study concluded that functional magnetic resonance imaging responses to mirror symmetry in this species were weaker than those observed in humans. Here, we re-examined symmetry processing in macaques from a broader perspective, using both rotation and reflection symmetry embedded in regular textures. Highly consistent responses to symmetry were found in a large network of areas (notably in areas V3 and V4), in line with what was reported in humans under identical experimental conditions. Our results suggest that the cortical networks that process symmetry in humans and macaques are potentially more similar than previously reported and point toward macaque as a relevant model for understanding symmetry processing.

Perceived group size is determined by the centroids of the component elements.

To accomplish the deceptively simple task of perceiving the size of objects in the visual scene, the visual system combines information about the retinal size of the object with several other cues, including perceived distance, relative size, and prior knowledge. When local component elements are perceptually grouped to form objects, the task is further complicated because a grouped object does not have a continuous contour from which retinal size can be estimated. Here, we investigate how the visual system solves this problem and makes it possible for observers to judge the size of perceptually grouped objects. We systematically vary the shape and orientation of the component elements in a two-alternative forced-choice task and find that the perceived size of the array of component objects can be almost perfectly predicted from the distance between the centroids of the component elements and the center of the array. This is true whether the global contour forms a circle or a square. When elements were positioned such that the centroids along the global contour were at different distances from the center, perceived size was based on the average distance. These results indicate that perceived size does not depend on the size of individual elements, and that smooth contours formed by the outer edges of the component elements are not used to estimate size. The current study adds to a growing literature highlighting the importance of centroids in visual perception and may have implications for how size is estimated for ensembles of different objects.

Visual and auditory brain areas share a representational structure that supports emotion perception.

Emotionally expressive music and dance occur together across the world. This may be because features shared across the senses are represented the same way even in different sensory brain areas, putting music and movement in directly comparable terms. These shared representations may arise from a general need to identify environmentally relevant combinations of sensory features, particularly those that communicate emotion. To test the hypothesis that visual and auditory brain areas share a representational structure, we created music and animation stimuli with crossmodally matched features expressing a range of emotions. Participants confirmed that each emotion corresponded to a set of features shared across music and movement. A subset of participants viewed both music and animation during brain scanning, revealing that representations in auditory and visual brain areas were similar to one another. This shared representation captured not only simple stimulus features but also combinations of features associated with emotion judgments. The posterior superior temporal cortex represented both music and movement using this same structure, suggesting supramodal abstraction of sensory content. Further exploratory analysis revealed that early visual cortex used this shared representational structure even when stimuli were presented auditorily. We propose that crossmodally shared representations support mutually reinforcing dynamics across auditory and visual brain areas, facilitating crossmodal comparison. These shared representations may help explain why emotions are so readily perceived and why some dynamic emotional expressions can generalize across cultural contexts.

The human visual system preserves the hierarchy of two-dimensional pattern regularity.

Symmetries are present at many scales in natural scenes. Humans and other animals are highly sensitive to visual symmetry, and symmetry contributes to numerous domains of visual perception. The four fundamental symmetries-reflection, rotation, translation and glide reflection-can be combined into exactly 17 distinct regular textures. These wallpaper groups represent the complete set of symmetries in two-dimensional images. The current study seeks to provide a more comprehensive description of responses to symmetry in the human visual system, by collecting both brain imaging (steady-state visual evoked potentials measured using high-density EEG) and behavioural (symmetry detection thresholds) data using the entire set of wallpaper groups. This allows us to probe the hierarchy of complexity among wallpaper groups, in which simpler groups are subgroups of more complex ones. We find that both behaviour and brain activity preserve the hierarchy almost perfectly: subgroups consistently produce lower-amplitude symmetry-specific responses in visual cortex and require longer presentation durations to be reliably detected. These findings expand our understanding of symmetry perception by showing that the human brain encodes symmetries with a high level of precision and detail. This opens new avenues for research on how fine-grained representations of regular textures contribute to natural vision.

A case-control study of visual, auditory and audio-visual sensory interactions in children with autism spectrum disorder.

To assess the relative integrity of early visual and auditory processes in autism spectrum disorder (ASD), we used frequency-tagged visual and auditory stimulation and high-density electroencephalogram recordings of unimodal and dual-modality responses in a case-control design. To test for the specificity of effects on ASD, we recorded from a smaller group of children with attention-deficit hyperactivity disorder (ADHD). Horizontal 3 cycle per degree (cpd) gratings were presented at 5 Hz, and a random stream of /ba/, /da/, /ga/ syllables was presented at 6 Hz. Grating contrast response functions were measured unimodally and in the presence of a 64-dB auditory input. Auditory response functions were measured unimodally and in the presence of a 40% contrast grating. Children with ASD (n = 34) and ADHD (n = 13) showed a common lack of audio-visual interaction compared to typically developing children (n = 40) when measured at the first harmonic of the visual stimulus frequency. Both patient groups also showed depressed first harmonic responses at low contrast, but the ADHD group had consistently higher first-harmonic responses at high contrast. Children with ASD had a preferential loss of second-harmonic (transient) responses. The alteredtransient responses in ASD are likely to arise very early in the visual pathway and could thus have downstream consequences for many other visual mechanisms and processes. The alteration in audio-visual interaction could be a signature of a comorbid phenotype shared by ASD and ADHD, possibly due to alterations in attentional selection systems.

Immunological and functional features of decellularized xenogeneic heart valves after transplantation into GGTA1-KO pigs.

Decellularization of xenogeneic heart valves might lead to excellent regenerative implants, from which many patients could benefit. However, this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological risk. Here, we investigated the regenerative and immunogenic potential of xenogeneic decellularized heart valve implants using pigs deficient for the galactosyltransferase gene (GGTA1-KO) as novel large animal model. Decellularized aortic and pulmonary heart valves obtained from sheep, wild-type pigs or GGTA1-KO pigs were implanted into GGTA1-KO pigs for 3, or 6 months, respectively. Explants were analyzed histologically, immunhistologically (CD3, CD21 and CD172a) and anti-αGal antibody serum titers were determined by ELISA. Xenogeneic sheep derived implants exhibited a strong immune reaction upon implantation into GGTA1-KO pigs, characterized by massive inflammatory cells infiltrates, presence of foreign body giant cells, a dramatic increase of anti-αGal antibody titers and ultimately destruction of the graft, whereas wild-type porcine grafts induced only a mild reaction in GGTA1-KO pigs. Allogeneic implants, wild-type/wild-type and GGTA1-KO/GGTA1-KO valves did not induce a measurable immune reaction. Thus, GGTA1-KO pigs developed a 'human-like' immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization, which detracts from their regenerative potential.

Interglacials of the Quaternary defined by northern hemispheric land ice distribution outside of Greenland.

Glacial/interglacial dynamics during the Quaternary were suggested to be mainly driven by obliquity (41-kyr periodicity), including irregularities during the last 1 Myr that resulted in on average 100-kyr cycles. Here, we investigate this so-called Mid-Pleistocene Transition via model-based deconvolution of benthic δ18O, redefining interglacials by lack of substantial northern hemispheric land ice outside of Greenland. We find that in 67%, 88% and 52% of the obliquity cycles during the early, middle and late Quaternary, respectively, a glacial termination is realized leading to irregular appearances of new interglacials during various parts of the last 2.6 Myr. This finding suggests that the proposed idea of terminations leading to new interglacials in the Quaternary as obliquity driven with growing influence of land ice volume on the timing of deglaciations during the last 1 Myr might be too simple. Alternatively, the land ice-based definition of interglacials needs revision if applied to the entire Quaternary.

The neural signature of numerosity by separating numerical and continuous magnitude extraction in visual cortex with frequency-tagged EEG.

The ability to handle approximate quantities, or number sense, has been recurrently linked to mathematical skills, although the nature of the mechanism allowing to extract numerical information (i.e., numerosity) from environmental stimuli is still debated. A set of objects is indeed not only characterized by its numerosity but also by other features, such as the summed area occupied by the elements, which often covary with numerosity. These intrinsic relations between numerosity and nonnumerical magnitudes led some authors to argue that numerosity is not independently processed but extracted through a weighting of continuous magnitudes. This view cannot be properly tested through classic behavioral and neuroimaging approaches due to these intrinsic correlations. The current study used a frequency-tagging EEG approach to separately measure responses to numerosity as well as to continuous magnitudes. We recorded occipital responses to numerosity, total area, and convex hull changes but not to density and dot size. We additionally applied a model predicting primary visual cortex responses to the set of stimuli. The model output was closely aligned with our electrophysiological data, since it predicted discrimination only for numerosity, total area, and convex hull. Our findings thus demonstrate that numerosity can be independently processed at an early stage in the visual cortex, even when completely isolated from other magnitude changes. The similar implicit discrimination for numerosity as for some continuous magnitudes, which correspond to basic visual percepts, shows that both can be extracted independently, hence substantiating the nature of numerosity as a primary feature of the visual scene.

Elevated Atmospheric CO2 Concentration Has Limited Effect on Wheat Grain Quality Regardless of Nitrogen Supply.

Elevated atmospheric CO2 concentrations (e[CO2]) can decrease the grain quality of wheat. However, little information exists concerning interactions between e[CO2] and nitrogen fertilization on important grain quality traits. To investigate this, a 2-year free air CO2 enrichment (FACE) experiment was conducted with two CO2 (393 and 600 ppm) and three (deficiency, adequate, and excess) nitrogen levels. Concentrations of flour proteins (albumins/globulins, gliadins, and glutenins) and key minerals (iron, zinc, and sulfur) and baking quality (loaf volume) were markedly increased by increasing nitrogen levels and varied between years. e[CO2] resulted in slightly decreased albumin/globulin and total gluten concentration under all nitrogen conditions, whereas loaf volume and mineral concentrations remained unaffected. Two-dimensional gel electrophoresis revealed strong effects of nitrogen supply and year on the grain proteome. Under adequate nitrogen, the grain proteome was affected by e[CO2] with 19 downregulated and 17 upregulated protein spots. The downregulated proteins comprised globulins but no gluten proteins. e[CO2] resulted in decreased crude protein concentration at maximum loaf volume. The present study contrasts with other FACE studies showing markedly stronger negative impacts of e[CO2] on chemical grain quality, and the reasons for that might be differences between genotypes, soil conditions, or the extent of growth stimulation by e[CO2].

EEGSourceSim: A framework for realistic simulation of EEG scalp data using MRI-based forward models and biologically plausible signals and noise.

BACKGROUND: Electroencephalography (EEG) is widely used to investigate human brain function. Simulation studies are essential for assessing the validity of EEG analysis methods and the interpretability of results. NEW METHOD: Here we present a simulation environment for generating EEG data by embedding biologically plausible signal and noise into MRI-based forward models that incorporate individual-subject variability in structure and function. RESULTS: The package includes pipelines for the evaluation and validation of EEG analysis tools for source estimation, functional connectivity, and spatial filtering. EEG dynamics can be simulated using realistic noise and signal models with user specifiable signal-to-noise ratio (SNR). We also provide a set of quantitative metrics tailored to source estimation, connectivity and spatial filtering applications. COMPARISON WITH EXISTING METHOD(S): We provide a larger set of forward solutions for individual MRI-based head models than has been available previously. These head models are surface-based and include two sets of regions-of-interest (ROIs) that have been brought into registration with the brain of each individual using surface-based alignment - one from a whole brain and the other from a visual cortex atlas. We derive a realistic model of noise by fitting different model components to measured resting state EEG. We also provide a set of quantitative metrics for evaluating source-localization, functional connectivity and spatial filtering methods. CONCLUSIONS: The inclusion of a larger number of individual head-models, combined with surface-atlas based labeling of ROIs and plausible models of signal and noise, allows for simulation of EEG data with greater realism than previous packages.

Image Segmentation Based on Relative Motion and Relative Disparity Cues in Topographically Organized Areas of Human Visual Cortex.

The borders between objects and their backgrounds create discontinuities in image feature maps that can be used to recover object shape. Here we used functional magnetic resonance imaging to identify cortical areas that encode two of the most important image segmentation cues: relative motion and relative disparity. Relative motion and disparity cues were isolated by defining a central 2-degree disk using random-dot kinematograms and stereograms, respectively. For motion, the disk elicited retinotopically organized activations starting in V1 and extending through V2 and V3. In the surrounding region, we observed phase-inverted activations indicative of suppression, extending out to at least 6 degrees of retinal eccentricity. For disparity, disk activations were only found in V3, while suppression was observed in all early visual areas. Outside of early visual cortex, several areas were sensitive to both types of cues, most notably LO1, LO2 and V3B, making them additional candidate areas for motion- and disparity-cue combination. Adding an orthogonal task at fixation did not diminish these effects, and in fact led to small but measurable disk activations in V1 and V2 for disparity. The overall pattern of extra-striate activations is consistent with recent three-stream models of cortical organization.

Neural dynamics underlying coherent motion perception in children and adults.

Motion sensitivity increases during childhood, but little is known about the neural correlates. Most studies investigating children's evoked responses have not dissociated direction-specific and non-direction-specific responses. To isolate direction-specific responses, we presented coherently moving dot stimuli preceded by incoherent motion, to 6- to 7-year-olds (n = 34), 8- to 10-year-olds (n = 34), 10- to 12-year-olds (n = 34) and adults (n = 20). Participants reported the coherent motion direction while high-density EEG was recorded. Using a data-driven approach, we identified two stimulus-locked EEG components with distinct topographies: an early component with an occipital topography likely reflecting sensory encoding and a later, sustained positive component over centro-parietal electrodes that we attribute to decision-related processes. The component waveforms showed clear age-related differences. In the early, occipital component, all groups showed a negativity peaking at ˜300 ms, like the previously reported coherent-motion N2. However, the children, unlike adults, showed an additional positive peak at ˜200 ms, suggesting differential stimulus encoding. The later positivity in the centro-parietal component rose more steeply for adults than for the youngest children, likely reflecting age-related speeding of decision-making. We conclude that children's protracted development of coherent motion sensitivity is associated with maturation of both early sensory and later decision-related processes.

Comparative Effectiveness and Maintenance of Diabetes Self-Management Education Interventions for Marshallese Patients With Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: Marshallese adults experience high rates of type 2 diabetes. Previous diabetes self-management education (DSME) interventions among Marshallese were unsuccessful. This study compared the extent to which two DSME interventions improved glycemic control, measured on the basis of change in glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS: A two-arm randomized controlled trial compared a standard-model DSME (standard DSME) with a culturally adapted family-model DSME (adapted DSME). Marshallese adults with type 2 diabetes (n = 221) received either standard DSME in a community setting (n = 111) or adapted DSME in a home setting (n = 110). Outcome measures were assessed at baseline, immediately after the intervention, and at 6 and 12 months after the intervention and were examined with adjusted linear mixed-effects regression models. RESULTS: Participants in the adapted DSME arm showed significantly greater declines in mean HbA1c immediately (-0.61% [95% CI -1.19, -0.03]; P = 0.038) and 12 months (-0.77% [95% CI -1.38, -0.17]; P = 0.013) after the intervention than those in the standard DSME arm. Within the adapted DSME arm, participants had significant reductions in mean HbA1c from baseline to immediately after the intervention (-1.18% [95% CI -1.55, -0.81]), to 6 months (-0.67% [95% CI -1.06, -0.28]), and to 12 months (-0.87% [95% CI -1.28, -0.46]) (P < 0.001 for all). Participants in the standard DSME arm had significant reductions in mean HbA1c from baseline to immediately after the intervention (-0.55% [95% CI -0.93, -0.17]; P = 0.005). CONCLUSIONS: Participants receiving the adapted DSME showed significantly greater reductions in mean HbA1c immediately after and 12 months after the intervention than the reductions among those receiving standard DSME. This study adds to the body of research that shows the potential effectiveness of culturally adapted DSME that includes participants' family members.

Deglacial mobilization of pre-aged terrestrial carbon from degrading permafrost.

The mobilization of glacial permafrost carbon during the last glacial-interglacial transition has been suggested by indirect evidence to be an additional and significant source of greenhouse gases to the atmosphere, especially at times of rapid sea-level rise. Here we present the first direct evidence for the release of ancient carbon from degrading permafrost in East Asia during the last 17 kyrs, using biomarkers and radiocarbon dating of terrigenous material found in two sediment cores from the Okhotsk Sea. Upscaling our results to the whole Arctic shelf area, we show by carbon cycle simulations that deglacial permafrost-carbon release through sea-level rise likely contributed significantly to the changes in atmospheric CO2 around 14.6 and 11.5 kyrs BP.

Revisiting the functional significance of binocular cues for perceiving motion-in-depth.

Binocular differencing of spatial cues required for perceiving depth relationships is associated with decreased sensitivity to the corresponding retinal image displacements. However, binocular summation of contrast signals increases sensitivity. Here, we investigated this divergence in sensitivity by making direct neural measurements of responses to suprathreshold motion in human adults and 5-month-old infants using steady-state visually evoked potentials. Interocular differences in retinal image motion generated suppressed response functions and correspondingly elevated perceptual thresholds compared to motion matched between the two eyes. This suppression was of equal strength for horizontal and vertical motion and therefore not specific to the perception of motion-in-depth. Suppression is strongly dependent on the presence of spatial references in the image and highly immature in infants. Suppression appears to be the manifestation of a succession of spatial and interocular opponency operations that occur at an intermediate processing stage either before or in parallel with the extraction of motion-in-depth.

Measuring Integration Processes in Visual Symmetry with Frequency-Tagged EEG.

Symmetry is a highly salient feature of the natural world which requires integration of visual features over space. The aim of the current work is to isolate dynamic neural correlates of symmetry-specific integration processes. We measured steady-state visual evoked potentials (SSVEP) as participants viewed symmetric patterns comprised of distinct spatial regions presented at two different frequencies (f1 and f2). We measured intermodulation components, shown to reflect non-linear processing at the neural level, indicating integration of spatially separated parts of the pattern. We generated a wallpaper pattern containing two reflection symmetry axes by tiling the plane with a two-fold reflection symmetric unit-pattern and split each unit-pattern diagonally into separate parts which could be presented at different frequencies. We compared SSVEPs measured for wallpapers and control patterns for which both images were equal in terms of translation and rotation symmetry but reflection symmetry could only emerge for the wallpaper pattern through integration of the image-pairs. We found that low-frequency intermodulation components differed between the wallpaper and control stimuli, indicating the presence of integration mechanisms specific to reflection symmetry. These results showed that spatial integration specific to symmetry perception can be isolated through a combination of stimulus design and the frequency tagging approach.