bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of lipidomic profiles sampled with electroporation-based biopsy from healthy skin, squamous cell carcinoma, and basal cell carcinoma
Authors: Louie Leetal , Wise Julia , Berl Ariel , Shir-az Ofir , Kravtsov Vladimir , Yakhini Zohar , Shalom Avshalom , Golberg Alexander , Vitkin Edward 
Published: February 2024

AbstractIncidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are increasing, while the current diagnostic process is time consuming. We introduce a high-throughput sampling approach, termed e-biopsy, utilizing electroporation-based biopsy for efficient collection of tissue lipids. Our study identified 168 lipids using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). The e-biopsy technique demonstrated its ability to profile the human skin lipidome. Comparative analysis revealed 27 differentially expressed lipids (p<0.05). The observed trend of lipidomic profiles was low diglycerides in cSCC and BCC, elevated phospholipids in BCC, and increased lyso-phospholipids in cSCC compared to healthy skin samples. These findings contribute to understanding skin cancers and highlight the potential of e-biopsy for lipidomic analysis in skin tissues.
A Nomogram to Predict Pneumothorax Requiring Chest Tube Placement following Percutaneous CT-guided Lung Biopsy
Authors: Bondarenko Masha , Zhang Jianxiang , Baal Ulysis Hugo , Lam Brian , Chaudhari Gunvant , Lee Yoo Jin , Schroeder Jamie , Vella Maya , Haas Brian , Vu Thienkhai , Kallianos Kimberly , Liu Jonathan , Sridhar Shravan , Elicker Brett , Sohn Jae Ho 
Published: February 2024

ABSTRACTBackgroundPneumothorax requiring chest tube after CT-guided transthoracic lung biopsy is one of the common complications, and the required hospital stay after chest tube placement represents an added clinical risk to patients and cost to the healthcare system. Identifying high-risk patients can prompt alternative biopsy modes and/or better preparation for more focused post-procedural care.PurposeTo develop and externally validate a risk nomogram for pneumothorax requiring chest tube placement following CT-guided lung biopsy, leveraging quantitative emphysema algorithm.Materials & MethodsThis two-center retrospective study included patients who underwent CT-guided lung biopsy from between 1994 and 2023. Data from one hospital was set aside for validation (n=613). Emphysema severity was quantified and categorized to 3-point scale using a previously published algorithm based on 3×3×3 kernels and Hounsfield thresholding, and a risk calculator was developed using forward variable selection and logistic regression. The model was validated using bootstrapping and Harrell’s C-index.Results2,512 patients (mean age, 64.47 years +/-13.38 [standard deviation]; 1250 men) were evaluated, of whom 157 (6.7%) experienced pneumothorax complications requiring chest tube placement. After forward variable selection to reduce the covariates to maximize clinical usability, the risk score was developed using age over 60 (OR 1.80 [1.15-2.93]), non-prone patient position (OR 2.48 [1.63-3.75]), and severe emphysema (OR 1.99 [1.35-2.94]). The nomogram showed mean absolute error of 0.5% in calibration and Harrell’s C-index of 0.664 in discrimination in the internal cohort.ConclusionThe developed nomogram predicts age over 60, non-prone position during biopsy, and severe emphysema to be most predictive of pneumothorax requiring chest tube placement following CT-guided lung biopsy.
Human-like dissociations between confidence and accuracy in convolutional neural networks
Authors: Shekhar Medha , Rahnev Dobromir 
Published: February 2024

AbstractPrior research has shown that manipulating stimulus energy by changing both stimulus contrast and variability results in confidence-accuracy dissociations in humans. Specifically, even when performance is matched, higher stimulus energy leads to higher confidence. The most common explanation for this effect is the positive evidence heuristic where confidence neglects evidence that disconfirms the choice. However, an alternative explanation is the signal-and-variance-increase hypothesis, according to which these dissociations arise from low-level changes in the separation and variance of perceptual representations. Because artificial neural networks lack built-in confidence heuristics, they can serve as a test for the necessity of confidence heuristics in explaining confidence-accuracy dissociations. Therefore, we tested whether confidence-accuracy dissociations induced by stimulus energy manipulations emerge naturally in convolutional neural networks (CNNs). We found that, across three different energy manipulations, CNNs produced confidence-accuracy dissociations similar to those found in humans. This effect was present for a range of CNN architectures from shallow 4-layer networks to very deep ones, such as VGG-19 and ResNet -50 pretrained on ImageNet. Further, we traced back the reason for the confidence-accuracy dissociations in all CNNs to the same signal-and-variance increase that has been proposed for humans: higher stimulus energy increased the separation and variance of the CNNs’ internal representations leading to higher confidence even for matched accuracy. These findings cast doubt on the necessity of the positive evidence heuristic to explain human confidence and establish CNNs as promising models for adjudicating between low-level, stimulus-driven and high-level, cognitive explanations of human behavior.
A Neural Signature of the Bias Towards Self-Focus
Authors: Geisler Danika , Meyer Meghan L. 
Published: February 2024

AbstractPeople are remarkably self-focused, disproportionately choosing to think about themselves relative to other topics. Self-focus can be adaptive, helping individuals fulfill their needs. It can also go haywire, with maladaptive self-focus a risk and maintenance factor for internalizing disorders like depression. Yet, the drive to focus on the self remains to be fully characterized. We discovered a brain state that when spontaneously brought online during a quick mental break predicts the desire to focus on oneself just a few seconds later. In Study 1, we identified a default network neural signature from pre-trial activity that predicts multiple indicators of self-focus within our sample. In Study 2, we applied our neural signature to independent resting-state data from the Human Connectome project. We found that individuals who score high on internalizing, a form of maladaptive self-focus, similarly move in-and-out of this pattern during rest, suggesting a systematic trajectory towards self-focused thought. This is the first work to “decode” the bias to focus on the self and paves the way towards stopping maladaptive self-focus in its course.Significance StatementSelf-help aisles in bookstores, the popularity of self-care culture, curating identities on social media, and the mental health crisis surrounding the rise in depression and anxiety are all symptoms of modern life’s emphasis on the self. Why are people so preoccupied with themselves? Our results suggest self-focus may emerge spontaneously because of the brain state people enter in the default network as soon as they have a mental break. The brain state participants entered in the first few seconds of rest could be used to decode whether they next chose to focus on themselves, as well as subjective and neural markers of self-focus. Moreover, internalizing, a maladaptive form of self-focus, corresponded with systematic timing of the pre-self pattern during a resting state scan, perhaps shaping the timecourse of spontaneous, self-focused thought.
Aging hastens locomotor decline in PINK1 knockout rats in association with decreased nigral, but not striatal, dopamine and tyrosine hydroxylase expression
Authors: Soto Isabel , McManus Robert , Navarrete-Barahona Walter , Kasanga Ella A. , Doshier Kirby , Nejtek Vicki A. , Salvatore Michael F. 
Published: February 2024

AbstractParkinson’s disease (PD) rodent models provide insight into the relationship between nigrostriatal dopamine (DA) signaling and locomotor function. Although toxin-based rat models produce frank nigrostriatal neuron loss and eventual motor decline characteristic of PD, the rapid nature of neuronal loss may not adequately translate premotor traits, such as cognitive decline. Unfortunately, rodent genetic PD models, like the Pink1 knockout (KO) rat, often fail to replicate the differential severity of striatal DA and tyrosine hydroxylase (TH) loss, and a bradykinetic phenotype, reminiscent of human PD. To elucidate this inconsistency, we evaluated aging as a progression factor in the timing of motor and non-motor cognitive impairments. Male PINK1 KO and age-matched wild type (WT) rats were evaluated in a longitudinal study from 3 to 16 months old in one cohort, and in a cross-sectional study of young adult (6-7 months) and aged (18-19 months) in another cohort. Young adult PINK1 KO rats exhibited hyperkinetic behavior associated with elevated DA and TH in the substantia nigra (SN), which decreased therein, but not striatum, in the aged KO rats. Additionally, norepinephrine levels decreased in aged KO rats in the prefrontal cortex (PFC), paired with a higher DA content in young and aged KO. Although a younger age of onset characterizes familial forms of PD, our results underscore the critical need to consider age-related factors. Moreover, the results indicate that compensatory mechanisms may exist to preserve locomotor function, evidenced by increased DA in the SN early in the lifespan, in response to deficient PINK1 function, which declines with aging and the onset of motor impairment.
Altered nuclear envelope homeostasis is a key pathogenic event in C9ORF72-linked ALS/FTD
Authors: Sirtori Riccardo , Gregoire Michelle , Collins Alicia , Santangelo Serena , Chatragadda Bhavya , Cullen Robert , Ratti Antonia , Fallini Claudia 
Published: February 2024

SUMMARYALS and FTD are complex neurodegenerative disorders that primarily affects motor neurons in the brain and spinal cord, and cortical neurons in the frontal lobe. Although the pathogenesis of ALS/FTD is unclear, recent research spotlights nucleocytoplasmic transport impairment, DNA damage, and nuclear abnormalities as drivers of neuronal death. In this study, we show that loss of nuclear envelope (NE) integrity is a key pathology associated with nuclear pore complex (NPC) injury inC9ORF72mutant neurons. Importantly, we show that mechanical stresses generated by cytoskeletal forces on the NE can lead to NPC injury, loss of nuclear integrity, and accumulation of DNA damage. Importantly, we demonstrate that restoring NE tensional homeostasis, by disconnecting the nucleus from the cytoskeleton, can rescue NPC injury and reduce DNA damage inC9ORF72mutant cells. Together, our data suggest that modulation of NE homeostasis and repair may represent a novel and promising therapeutic target for ALS/FTD.
TMEM63B functions as a mammalian thirst receptor
Authors: Zou Wenjie , Chen Xingyu , Ruan Jiamin , Deng Siqi , Wang Huize , Zhan Wuqiang , Wang Jingxin , Liu Zhiyong , Yan Zhiqiang 
Published: February 2024

SummaryThirst drives animals to reinstate water homeostasis by fluid intake. An increase of blood osmolality is thought to induce thirst by activating a thirst receptor expressed in the subfornical organ (SFO), but the molecular identity of this receptor remains elusive. Here, we provide behavioral and functional evidence to show that TMEM63B functions as a mammalian thirst receptor in the SFO and mediates osmotic and dehydrated thirst. First, we showed that TMEM63B is expressed in SFO excitatory neurons and required for the neuronal responses to hypertonic stimulation. Heterologously expressed TMEM63B is activated by hypertonic stimuli and point mutations can alter the reversal potential of the channel. More importantly, purified TMEM63B in liposomes establishes osmolarity-gated currents. Finally, Tmem63b knockout mice have profound deficits in thirst, and deleting TMEM63B within the SFO neurons recapitulated this phenotype. Taken together, these results provide a molecular basis for thirst 82and demonstrate TMEM63B is the long-sought mammalian thirst receptor.
Representational dissimilarity component analysis (ReDisCA)
Authors: Ossadtchi Alexei , Semenkov Ilia , Zhuravleva Anna , Kozunov Vladimir , Serikov Oleg , Voloshina Ekaterina 
Published: February 2024

AbstractThe principle of Representational Similarity Analysis (RSA) posits that neural representations reflect the structure of encoded information, allowing exploration of spatial and temporal organization of brain information processing. Traditional RSA when applied to EEG or MEG data faces challenges in accessing activation time series at the brain source level due to modeling complexities and insufficient geometric/anatomical data.To address this, we introduce Representational Dissimilarity Component Analysis (ReDisCA), a method for estimating spatial-temporal components in EEG or MEG responses aligned with a target representational dissimilarity matrix (RDM). ReDisCA yields informative spatial filters and associated topographies, offering insights into the location of “representationally relevant” sources. Applied to evoked response time series, ReDisCA produces temporal source activation profiles with the desired RDM. Importantly, while ReDisCA does not require inverse modeling its output is consistent with EEG and MEG observation equation and can be used as an input to rigorous source localization procedures.Demonstrating ReDisCA’s efficacy through simulations and comparison with conventional methods, we show superior source localization accuracy and apply the method to real EEG and MEG datasets, revealing physiologically plausible representational structures without inverse modeling. ReDisCA adds to the family of inverse modeling free methods such as independent component analysis [34], Spatial spectral decomposition [41], and Source power comodulation [9] designed for extraction sources with desired properties from EEG or MEG data. Extending its utility beyond EEG and MEG analysis, ReDisCA is likely to find application in fMRI data analysis and exploration of representational structures emerging in multilayered artificial neural networks.
Multiple Loci for Foveolar Vision in Macaque Monkey
Authors: Qian Meizhen , Wang Jianbao , Gao Yang , Chen Ming , Liu Yin , Zhou Dengfeng , Lu Haidong , Zhang Xiaotong , Hu Jiaming , Roe Anna Wang 
Published: February 2024

AbstractA common tenet of neural sensory representation is that species-specific behaviors are reflected in specialized brain organizations1. In humans and nonhuman primates, the central one degree of vision is processed by the foveola2, a retinal structure which comprises a high density of photoreceptors and is crucial for primate-specific high acuity vision, color vision, and gaze-directed visual attention3,4,5. In this study, we have developed high spatial resolution ultrahigh field 7T fMRI methods for functional mapping of foveolar visual cortex in awake monkeys. We provide evidence that, in the ventral pathway (V1-V4 and TEO), viewing of a central small spot elicits a ring of multiple (at least 8) foveolar representations per hemisphere. This ring surrounds a large area called the ‘foveolar core’. This is an area populated by millimeter-scale functional domains sensitive to fine stimuli and high spatial frequencies, consistent with foveolar visual acuity, as well as color and achromatic information, and motion. The unique position of the foveolar core suggests it may be a hub subserving higher order needs of foveolar function, such as integrating different spatial scales of representation, integrating local and global features in object perception, and bringing together the four quadrants of visual space. Thus, this elaborate re-representation of central vision signifies a cortical specialization for various foveation behaviors.
Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants
Authors: Tóth Balázs István , Bazeli Bahar , Janssens Annelies , Lisztes Erika , Racskó Márk , Kelemen Balázs , Herczeg Mihály , Nagy Tamás Milán , Kövér Katalin E. , Mitra Argha , Borics Attila , Bíró Tamás , Voets Thomas 
Published: February 2024

ABSTRACTRapamycin (sirolimus), a macrolide compound isolated from the bacteriumStreptomyces hygroscopicus, is widely used as oral medication for the prevention of transplant rejection and the treatment of lymphangioleiomyomatosis. It is also incorporated in coronary stent coatings to prevent restenosis and in topical preparations for the treatment of skin disorders. Rapamycin’sin vivoactivities are generally ascribed to its binding to the protein FKBP12, leading to potent inhibition of the mechanistic target of rapamycin kinase (mTOR) by the FKBP12-rapamycin complex. The specific rapamycin-induced interaction between domains from mTOR and FKBP12 is also frequently employed in cell biological research, for rapid chemically-induced protein dimerization strategies. Here we show that rapamycin activates TRPM8, a cation channel expressed in sensory nerve endings that serves as the primary cold sensor in mammals. Using a combination of electrophysiology, Saturation Transfer Triple-Difference (STTD) NMR spectroscopy and molecular docking-based targeted mutagenesis, we demonstrate that rapamycin directly binds to TRPM8. We identify a rapamycin-binding site in the groove between voltage sensor-like domain and the pore domain, distinct from the interaction sites of cooling agents and known TRPM8 agonists menthol and icilin. Related macrolide immunosuppressants act as partial TRPM8 agonists, competing with rapamycin for the same binding site. These findings identify a novel molecular target for rapamycin and provide new insights into the mechanisms of TRPM8 activation, which may assist in the development of therapies targeting this ion channel. Moreover, our findings also indicate that caution is needed when using molecular approaches based on rapamycin-induced dimerization to study ion channel regulation.
The timescale and functional form of context-dependence during human value-learning
Authors: Tohidi-Moghaddam Maryam , Tsetsos Konstantinos 
Published: February 2024

AbstractContrary to the predictions of normative theories, choices between two high-value alternatives can be biased by the introduction of a third low-value alternative (dubbed the distractor effect). Normalization-based theories, like divisive and range normalization, explain different forms of the distractor effect by suggesting that the value of each alternative is normalized by a summary statistic of the values encountered in a particular decision context. The decision context can include alternatives encountered over an extended timeframe (temporal context); and alternatives that are available for choice on a given instance (immediate context). To date, the extent to which the immediate and temporal context (co-) shape context-dependent value representations remains unclear. To investigate this, we designed a task in which participants learned the values associated with three different alternatives and provided explicit value estimates before making a series of choices among ternary and binary combinations of those alternatives. We show that context-dependence already emerges in the pre-choice value estimates and is equally present in binary and ternary choice trials. Based on these findings, we conclude that the temporal (and not the immediate) context modulates subjective value representations. Interestingly, the functional form of context-dependence we report runs against both divisive and range normalization theories. Instead, our data are best explained by a stochastic rank-based model, according to which the value of an alternative is distorted by a series of memory-based binary comparisons with previously encountered alternatives.
Energy scarcity and impaired mitochondrial translation induce perinuclear stress granule clustering
Authors: Fernandez-Pelayo Uxoa , Muñoz-Oreja Mikel , Villar-Fernandez Marina , de Arbina Amaia Lopez , Aiestaran-Zelaia Irati , Sánchez-Guisado María Jesús , Pantic Boris , Elicegui Amaia , Zufiria Monica , Iruzubieta Pablo , Sagartzazu-Aizpurua Maialen , Aizpurua Jesús M. , Gegg Matthew , Alonso-Martin Sonia , Ruiz-Cabello Jesus , Gil-Bea Francisco , Spinazzola Antonella , de Munain Adolfo Lopez , Holt Ian James 
Published: February 2024

ABSTRACTMany proteins linked to amyotrophic lateral sclerosis and fronto-temporal dementia (ALS-FTD) change their cellular location and coalesce in cytoplasmic inclusion bodies in the disease state; yet the factors that govern protein relocation and organization remain unclear. Here, we show that inhibition of glycolysis and mitochondrial protein synthesis causes many proteins involved in ALS-FTD to change location, and form a novel structure comprising a ring of stress granules encircling the aggresome, a focal microtubule-based structure beside the nucleus. A perinuclear ring of stress granules also forms in activated microglia of mice exposed to the glycolytic inhibitor, 2-Deoxy-D-glucose. We propose that the new arrangement increases the risk of the stress granules merging and converting from the liquid phase to the insoluble inclusion characteristic of ALS-FTD. Thus, our findings suggest that that compromised nutrient and energy metabolism can precipitate a molecular cascade that ultimately leads to the pathological hallmark of ALS-FTD the perinuclear inclusion body.Graphical abstractInhibition of glycolysis and mitochondrial protein synthesis induces translocation of a swathe of ALS-FTD related proteins in primary human fibroblasts. The relocated proteins form concentric cytoplasmic rings (CCR) comprising stress granules, the Golgi and the aggresome, beside the nucleus. A perinuclear ring of stress granules forms in the mouse brain following intermittent nutrient restriction, with the glucose analog 2DG. The CCR is potentially a key intermediate step in the formation of pathological inclusions and so perturbed nutrient and energy metabolism encompassing impaired mitochondrial translation could precipitate the ALS-FTD disease cascade.