bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural correlates of drinking reduction during cognitive behavioral therapy for alcohol use disorder
Authors: Naqvi Nasir H. , Srivastava A. Benjamin , Sanchez-Peña Juan , Lee Jessica , Mariani John J. , Patel Gaurav H. , Levin Frances R. 
Published: February 2023

AbstractCognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a brain region implicated in cognitive control and goal-directed behavior, plays a role behavior change during CBT by facilitating regulation of craving. To examine this, treatment-seeking participants with AUD (N=22) underwent functional MRI scanning both before and after a 12-week single-arm trial of CBT, using a regulation of craving (ROC) fMRI task designed to measure an individual’s ability to control alcohol craving and previously shown to engage the DLPFC. We found that both the number of heavy drinking days (NHDD, the primary clinical outcome) and the self-reported alcohol craving measured during the ROC paradigm were significantly reduced from pre- to post-CBT [NHDD: t=15.69, p<0.0001; alcohol craving: (F(1,21)=16.16; p=0.0006)]. Contrary to our hypothesis, there was no change in regulation effects on self-reported craving over time (F(1,21)=0.072; p=0.79), nor was there was a significant change in regulation effects over time on activity in any parcel. Searching the whole brain for neural correlates of reductions in drinking and craving after CBT, we found a significant 3-way interaction between the effects of cue-induced alcohol craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on NHDD in a parcel corresponding to area 46 of the right DLPFC (ß=-0.37, p=0.046, FDR corrected). Follow-up analyses showed that reductions in cue-induced alcohol craving from pre- to post-CBT were linearly related to reductions in alcohol cue-induced activity in area 46 only among participants who ceased heavy drinking during CBT (r=0.81, p=0.005) but not among those who continued to drink heavily (r=0.28, p=0.38). These results are consistent with a model in which CBT impacts heavy drinking by increasing the engagement of the DLPFC during cue-induced craving.
Broadband aperiodic components of local field potentials reflect inherent differences between cortical and subcortical activity
Authors: Bush Alan , Zou Jasmine , Lipski Witold J. , Kokkinos Vasileios , Richardson R. Mark 
Published: February 2023

AbstractInformation flow in brain networks is reflected in intracerebral local field potential (LFP) measurements that have both periodic and aperiodic components. The 1/fχbroadband aperiodic component of the power spectra has been shown to track arousal level and to correlate with other physiological and pathophysiological states, with consistent patterns across cortical regions. Previous studies have focused almost exclusively on cortical neurophysiology. Here we explored the aperiodic activity of subcortical nuclei from the human thalamus and basal ganglia, in relation to simultaneously recorded cortical activity. We elaborated on the FOOOF (fitting of one over f) method by creating a new parameterization of the aperiodic component with independent and more easily interpretable parameters, which allows seamlessly fitting spectra with and without anaperiodic knee, a component of the signal that reflects the dominant timescale of aperiodic fluctuations. First, we found that the aperiodic exponent from sensorimotor cortex in Parkinson’s disease (PD) patients correlated with disease severity. Second, although the aperiodic knee frequency changed across cortical regions as previously reported, no aperiodic knee was detected from subcortical regions across movement disorders patients, including the ventral thalamus (VIM), globus pallidus internus (GPi) and subthalamic nucleus (STN). All subcortical region studied exhibited a relatively low aperiodic exponent (χSTN=1.3±0.2, χVIM=1.4±0.1, χGPi=1.4±0.1) that differed markedly from cortical values (χCortex=3.2±0.4, fkCortex=17±5 Hz). These differences were replicated in a second dataset from epilepsy patients undergoing intracranial monitoring that included thalamic recordings. The consistently lower aperiodic exponent and lack of an aperiodic knee from all subcortical recordings may reflect cytoarchitectonic and/or functional differences between subcortical nuclei and the cortex.Significance StatementThe broadband aperiodic component of local field potentials is a useful and reproducible index of neural activity. Here we refined a widely used phenomenological model for extracting aperiodic parameters, with which we fit cortical, basal ganglia and thalamic intracranial local field potentials, recorded from unique cohorts of movement disorders and epilepsy patients. We found that the aperiodic exponent in motor cortex is higher in Parkinson’s disease patients with more severe motor symptoms, suggesting that aperiodic features may have potential as electrophysiological biomarkers for movement disorders symptoms. Remarkably, we found conspicuous differences in the broadband aperiodic components of basal ganglia and thalamic signals compared to those from neocortex, suggesting that the aperiodic neural timescale of subcortical LFPs is slower than that in cortex.
Differences in spore size and atmospheric survival shape stark contrasts in the dispersal dynamics of two closely related fungal pathogens
Authors: Golan Jacob , Oneto Daniele Lagomarsino , Ding Shunping , Kessenich Reinhard , Sandler Melvin , Rush Tomás A. , Levitis Daniel , Gevens Amanda , Seminara Agnese , Pringle Anne 
Published: February 2023

AbstractA frequently ignored but critical aspect of microbial dispersal is survival in the atmosphere. We exposed spores of two closely related, morphologically dissimilar, and economically important fungal pathogens to typical atmospheric environments and modeled their movement in the troposphere. We first measured the mortality ofAlternaria solaniandA. alternataconidia exposed to ranges of solar radiation, relative humidity, and temperature. We then measured survival in an advantageous environment over 12 days.A. solaniconidia are nearly 10 times larger thanA. alternataconidia and most die after 24 hours. By contrast, over half ofA. alternataconidia remained viable at 12 days. The greater viability of the smaller spores is counterintuitive as larger spores are assumed to be more durable. To elucidate the consequences of survival rates for dispersal, we deployed models of atmospheric spore movement across North American. We predict 99% of the largerA. solaniconidia settle within 24 hours, with a maximum dispersal distance of 100 km. By contrast, mostA. alternataconidia remain airborne for more than 12 days and long-distance dispersal is possible, e.g., from Wisconsin to the Atlantic Ocean. We observe that the larger conidia ofA. solanisurvive poorly but also land sooner and move over shorter distances as compared to the smaller conidia ofA. alternata. Our data relating larger spore size to poorer survival in the atmosphere and shorter distances travelled likely translate to other fungal species and highlight the potential for starkly different dispersal dynamics among even closely related fungi.
Disentangling the effects of metabolic cost and accuracy on movement vigor
Authors: Bruening Garrick W. , Sukumar Shruthi , Courter Robert J. , O’Brien Megan K. , Ahmed Alaa A. 
Published: February 2023

AbstractOn any given day, we make countless reaching movements to objects around us. While such ubiquity may suggest uniformity, each movement is unique in the speed with which it is made. Some movements are slow, while others are fast. These variations in reach speed have long been known to be influenced by accuracy constraints; we slow down when accuracy demands are high. However, in other forms of movement like walking, metabolic cost is the primary determinant of movement speed. Here we ask, how do metabolic cost and accuracy interact to determine speed of reaching movements? First we systematically measure the effect of increasing mass on the metabolic cost of reaching across a range of movement speeds. Next, in a sequence of three experiments, we examine how added mass affects preferred movement speeds in a simple reaching task with increasing accuracy requirements. We find that mass consistently increased metabolic cost and led to slower movements. Yet, intriguingly, preferred reach speeds were slower than metabolically optimal. We then demonstrate how a single model that, critically, considers both accuracy and metabolic cost can explain preferred movement speeds across the range of accuracy and effort requirements tested. Together, these findings provide a unifying framework to explain the combined effects of metabolic cost and accuracy on movement speed, and also highlight the integral role metabolic cost plays in determining reach speed.
Social Conformity Updates the Neural Representation of Facial Attractiveness
Authors: Chen Danni , Yao Ziqing , Liu Jing , Wu Haiyan , Hu Xiaoqing 
Published: February 2023

AbstractPeople readily change their behavior to comply with others. However, to which extent they will internalize the social influence remains elusive. In this preregistered electroencephalogram (EEG) study, we investigated how learning from one’s in-group or out-group members about facial attractiveness would change explicit attractiveness ratings and spontaneous neural representations of facial attractiveness. Specifically, we quantified the neural representational similarities of learned faces with prototypical attractive faces during a face perception task without overt social influence and intentional evaluation. We found that participants changed their explicit attractiveness ratings to both in-group and out-group influences. Moreover, social conformity updated spontaneous neural representation of facial attractiveness, an effect particularly evident when participants learned from their in-group members and among those who perceived tighter social norms. These findings offer insights into how group affiliations and individual differences in perceived social norms modulate the internalization of social influence.
Cost Effectiveness of Newborn Screening for Spinal Muscular Atrophy in England
Authors: Weidlich Diana , Servais Laurent , Kausar Imran , Howells Ruth , Bischof Matthias 
Published: February 2023

ABSTRACTIntroductionWe sought to evaluate the cost effectiveness of newborn screening (NBS) versus no NBS for 5q spinal muscular atrophy (SMA) in England.MethodsA cost-utility analysis using a combination of decision tree and Markov model structures was developed to estimate the lifetime health effects and costs of NBS for SMA, compared with no NBS, from the perspective of the National Health Service (NHS) in England. A decision tree was designed to capture NBS outcomes, and Markov modelling was used to project long-term health outcomes and costs for each patient group following diagnosis. Model inputs were based on existing literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess the robustness of the model and the validity of the results.ResultsThe introduction of NBS for SMA in England is estimated to identify approximately 56 (96% of cases) infants with SMA per year. Base-case results indicate that NBS is dominant (less costly and more effective) than a scenario without NBS, with a yearly cohort of newborns accruing incremental savings of £62,191,531 and an estimated gain in quality-adjusted life-years of 529 years over their lifetime. Deterministic and probabilistic sensitivity analyses demonstrated the robustness of the base-case results.ConclusionsNBS improves health outcomes for patients with SMA and is less costly compared with no screening; therefore, it is a cost-effective use of resources from the perspective of the NHS in England.
Divergence of wastewater SARS-CoV-2 and reported laboratory-confirmed COVID-19 incident case data coincident with wide-spread availability of at-home COVID-19 antigen tests
Authors: Boehm Alexandria B. , Wolfe Marlene K. , White Bradley J. , Hughes Bridgette , Duong Dorothea 
Published: February 2023

AbstractConcentrations of SARS-CoV-2 RNA in wastewater settled solids from publicly owned treatment works (POTWs) historically correlated strongly with laboratory confirmed incident COVID-19 case data. With the increased availability of at-home antigen tests since late 2021 and early 2022, laboratory test availability and test seeking behavior has decreased. In the United States, the results from at-home antigen tests are not typically reportable to public health agencies and thus are not counted in case reports. As a result, the number of reported laboratory-confirmed incident COVID-19 cases has decreased dramatically, even during times of increased test positivity rates and wastewater concentrations of SARS-CoV-2 RNA. Herein, we tested whether the correlative relationship between wastewater concentrations of SARS-CoV-2 RNA and reported laboratory-confirmed COVID-19 incidence rate has changed since 1 May 2022, a point in time immediately before the onset of the BA.2/BA.5 surge, the first surge to begin after at-home antigen test availability was high in the region. We used daily data from three POTWs in the Greater San Francisco Bay Area of California, USA for the analysis. We found that although there is a significant positive association between wastewater measurements and incident rate data collected after 1 May 2022, the parameters describing the relationship are different than those describing the relationship between the data collected prior to 1 May 2022. If laboratory test seeking or availability continues to change, the relationship between wastewater and reported case data will continue to change. Results suggests that, assuming SARS-CoV-2 RNA shedding remains relatively stable among those infected with the virus as different variants emerge, that wastewater concentrations of SARS-CoV-2 RNA can be used to estimate COVID-19 cases as they would have been during the time when laboratory testing availability and test seeking behavior were at a high (here, before 1 May 2022) using the historical relationship between SARS-CoV-2 RNA and COVID-19 case data.
Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis
Authors: Niranjan Rituraj , Sankari T , Manoj H , Jayashree A. K. , Sanya Rameela , Varghese Basil , kumar N. Pradeep , Muthukumaravel S , Kumar Ashwani 
Published: February 2023

AbstractThe mutations are the key mechanisms responsible for virus survival and its fitness in the host. This process of mutation is implicated in the development of pathogenesis of the dengue viral disease. We report that, all the four serotypes were found to be circulating in Kerala sate of India. Serotypes 1 and 3 were the predominant type (33.3 %) compared to others. The prevalence of co-infection of serotype 1 and 4 was the highest percentage (11.1 %) compared to serotype 2 and serotype 3 (5.5 %). We further highlighted the immunopathological mechanisms of antibody neutralization, CD4+T cell response and antibody dependent enhancements (ADE) for the possible cause of disease severity in coinfections. Serotype-1 does not show much variations from the previously reported strains from various regions of India. However, serotype-2 showed variations in the sequences from the other strains of serotype-2 previously reported from various regions of India and formed a distinct clade in the genotype-4. Serotype-3 and serotype-4 showed similarity with previously reported strains from India. Moreover, serotype-1 was grouping in genotype-5. Importantly, the serotype-2 grouped with genoptype-4 but exist separately. Serotype-3 was found to be grouped with the genotype-3. The serotype-4 show the very much similarities from the genotype-1 and shows little difference from the previously reported strains from India. Further, mutation in DENV-3 sequences, at position 235 (C to T) and 322 (G to T) shows an important phenomenon which might be adopted by the virus to survive. As severe dengue is linked with the serotype-2, the genetic variations in this serotype points towards the much specific strategy to be adopted in near future to manage the severe dengue disease. In conclusion, we can say that, genetic diversity in the CprM region is present in the different serotypes circulating in the patients from Kerala India and this information may help in the management of dengue viral disease.
The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
Authors: Montibus Bertille , Ragheb Ramy , Diamanti Evangelia , Dunn Sara-Jane , Reynolds Nicola , Hendrich Brian 
Published: February 2023

AbstractAs cells exit the pluripotent state and begin to commit to a specific lineage they must activate genes appropriate for that lineage while silencing genes associated with pluripotency and preventing activation of lineage-inappropriate genes. The Nucleosome Remodelling and Deacetylation (NuRD) complex is essential for pluripotent cells to successfully undergo lineage commitment. NuRD controls nucleosome density at regulatory sequences to facilitate transcriptional responses, and also has been shown to prevent unscheduled transcription (transcriptional noise) in undifferentiated pluripotent cells. How these activities combine to ensure cells engage a gene expression program suitable for successful lineage commitment has not been determined. Here we show that while NuRD is not required to silence all genes, its activity is important to restrict expression of genes primed for activation upon exit from the pluripotent state, and that NuRD activity facilitates their subsequent transcriptional activation. We further show that NuRD coordinates gene expression changes, which acts to maintain a barrier between different stable states. Thus NuRD-mediated chromatin remodelling serves multiple functions, including reducing transcriptional noise, priming genes for activation and coordinating the transcriptional response to facilitate lineage commitment.
Genotypic-phenotypic landscape computation based on first principle and deep learning
Authors: Liu Yuexing , Luo Yao , Lu Xin , Gao Hao , He Ruikun , Zhang Xin , Zhang Xuguang , Li Yixue 
Published: February 2023

AbstractThe relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the Phenotypic-Embedding theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness (CoT2G-F) model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning (SFT) that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (R0) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness, and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.
Diffsig: Associating Risk Factors With Mutational Signatures
Authors: Park Ji-Eun , Smith Markia A. , Van Alsten Sarah C. , Walens Andrea , Wu Di , Hoadley Katherine A. , Troester Melissa A. , Love Michael I. 
Published: February 2023

AbstractSomatic mutational signatures elucidate molecular vulnerabilities to therapy and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors. Here we presentDiffsig, a model and R package for estimating the association of risk factors with mutational signatures, suggesting etiologies for the pre-defined mutational signatures.Diffsigis a Bayesian Dirichlet-multinomial hierarchical model that allows testing of any type of risk factor while taking into account the uncertainty associated with samples with a low number of observations. In simulation, we found that our method can accurately estimate risk factor-mutational signal associations. We appliedDiffsigto breast cancer data to assess relationships between five established breast-relevant mutational signatures and etiologic variables, confirming known mechanisms of cancer development.Diffsigis implemented as an R package available at:https://github.com/jennprk/diffsig.
Stochastic Modeling of Tinnitus Loudness
Authors: Kwak Sangyeop , Lee Daehee , Jang Sungshin , Kim Songhwa , Kim Sunghwan , Doo Woojin , Kwak Eunyee 
Published: February 2023

AbstractThere has been no study on the relationship between chronic tinnitus and harmonic templates. Harmonic templates are harmonically structured receptive fields in the auditory system in which all frequency components are integer multiples of a common fundamental frequency (F0). In this study, data from 19 harmonic templates from each of 196 chronic tinnitus patients were analyzed and mathematical modeling was performed to quantify the loudness of chronic tinnitus. High-resolution hearing threshold data were obtained by algorithmic pure tone audiometry (PTA) conducting automated PTA at 134 frequency bands with 1/24 octave resolution from 250 Hz to 12,000 Hz. The result showed that there is an intriguing relationship between the auditory instability of harmonic templates and simplified tinnitus severity score (STSS). This study provides several mathematical models to estimate tinnitus severity and the precise quantification of the loudness of chronic tinnitus. Our computational models and analysis of the behavioral hearing threshold fine structure suggest that the cause of severe chronic tinnitus could be a severe disparity between different temporal capacities of each neural oscillator in a certain harmonic template.