Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction Biases: An Integrative Review

Research in psychology and related fields has documented a myriad of prediction biases, such as the underprediction of hedonic adaptation and the overprediction of other people’s concern for fairness. These prediction biases are ostensibly independent, each with its own cause. We argue, however, that many of these seemingly disparate biases are specific instances of a general bias—situation insensitivity: People are insensitive to variations in the situational variable that underlies the target variable (the variable to be predicted). Consequently, when encountering a condition in which the situational variable is at one of its ends such that the value of the target variable is low, people overpredict the value; conversely, when encountering a condition in which the situational variable is at its other end such that the value of the target variable is high, people underpredict it. Most prior research documenting prediction biases has focused on only one end of the situational variable and therefore has shown either only an overprediction bias or only an underprediction bias. We argue that at the other end of the situational variable, the originally documented bias can disappear or even reverse. Our framework not only explains known biases but also predicts new biases.
Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes become staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents. Impact Statement Electrophysiological recordings from mouse spinal motoneurons reveal key roles for ion channels in establishing the differential activation of motoneuron subtypes during postnatal development.
The Cost of Untracked Diversity in Brain-Imaging Prediction

Brain-imaging research enjoys increasing adoption of supervised machine learning for singlesubject disease classification. Yet, the success of these algorithms likely depends on population diversity, including demographic differences and other factors that may be outside of primary scientific interest. Here, we capitalize on propensity scores as a composite confound index to quantify diversity due to major sources of population stratification. We delineate the impact of population heterogeneity on the predictive accuracy and pattern stability in two separate clinical cohorts: the Autism Brain Imaging Data Exchange (ABIDE, n=297) and the Healthy Brain Network (HBN, n=551). Across various analysis scenarios, our results uncover the extent to which cross-validated prediction performances are interlocked with diversity. The instability of extracted brain patterns attributable to diversity is located preferentially to the default mode network. Our collective findings highlight the limitations of prevailing deconfounding practices in mitigating the full consequences of population diversity.
Accurate Protein Function Prediction via Graph Attention Networks with Predicted Structure Information

Experimental protein function annotation does not scale with the fast-growing sequence databases. Only a tiny fraction (<0.1%) of protein sequences in UniProtKB has experimentally determined functional annotations. Computational methods may predict protein function in a high-throughput way, but its accuracy is not very satisfactory. Based upon recent breakthroughs in protein structure prediction and protein language models, we develop GAT-GO, a graph attention network (GAT) method that may substantially improve protein function prediction by leveraging predicted inter-residue contact graphs and protein sequence embedding. Our experimental results show that GAT-GO greatly outperforms the latest sequence- and structure-based deep learning methods. On the PDB-mmseqs testset where the train and test proteins share <15% sequence identity, GAT-GO yields Fmax(maximum F-score) 0.508, 0.416, 0.501, and AUPRC(area under the precision-recall curve) 0.427, 0.253, 0.411 for the MFO, BPO, CCO ontology domains, respectively, much better than homology-based method BLAST (Fmax 0.117,0.121,0.207 and AUPRC 0.120, 0.120, 0.163). On the PDB-cdhit testset where the training and test proteins share higher sequence identity, GAT-GO obtains Fmax 0.637, 0.501, 0.542 for the MFO, BPO, CCO ontology domains, respectively, and AUPRC 0.662, 0.384, 0.481, significantly exceeding the just-published graph convolution method DeepFRI, which has Fmax 0.542, 0.425, 0.424 and AUPRC 0.313, 0.159, 0.193.
High Heritabilities for Antibiotic Usage Show Potential to Breed for Disease Resistance in Finishing Pigs

The use of antimicrobials in animal production is under public debate, mainly due to the risk of transfer of resistance to pathogenic bacteria in humans. Therefore, measures have been taken during the last decades to reduce antibiotic usage in animals, for instance by national monitoring programmes and by improving animal health management. Although some initiatives exist in molecular genetic selection, quantitative genetic selection of animals towards decreased antibiotic usage is an underexplored area to reduce antibiotic usage. However, this strategy could yield cumulative effects. In this study we derived new phenotypes from on-farm parenteral antibiotic records from commercially grown crossbred finishing pigs used in the progeny test of Piétrain terminal sires to investigate the heritability of antibiotics usage. Parenteral antibiotic records, production parameters and pedigree records of 2238 fullsib pens from two experimental farms in Belgium between 2014 and 2020 were analysed. Heritability estimates were moderate (18-44%) for phenotypes derived from all antibiotic treatments, and low (1-15%) for phenotypes derived from treatments against respiratory diseases only. Moreover, genetic correlations between these new phenotypes and mortality were low to moderate (0.08-0.60) and no strong adverse genetic correlations with production traits were found. The high heritabilities and favourable genetic correlations suggest these new phenotypes derived from on-farm antibiotics records to be promising for inclusion in future pig breeding programs to breed for a decrease in antibiotics usage.
Evaluation of spontaneous seizure activity, sex-dependent differences, behavioral comorbidities, and alterations in CA1 neuron firing properties in a mouse model of Dravet Syndrome

Dravet syndrome (DS) is a rare childhood epilepsy disorder resulting in spontaneous, recurrent seizures (SRS) and behavioral co-morbidities. To facilitate the discovery and development of anti-seizure drugs for DS, the contract site of the NINDS Epilepsy Therapy Screening Program (ETSP) has continued to evaluate a mouse model of DS. Scn1aA1783V/WT mice exhibited increased hyperactivity, thigmotaxis, and deficits in nest-building behavior. Ex-vivo brain slice electrophysiology experiments revealed increased excitability of hippocampal CA1 neurons specifically due to increased action potential firing frequency in response to brief depolarizations and decreased frequency of spontaneous GABAergic synaptic events. A video-EEG study revealed mice had on average, 1 seizure per day, with males seizing significantly more frequently than females. Increased proportion of seizure activity occurred during the dark phase of the light/dark cycle in both sexes. While clobazam, a drug commonly prescribed to patients with DS, had no effect on SRS activity at the tested doses, the seizure history and frequency observed in this study aids in determining the sample sizes and experimental timeline needed for adequately powered preclinical drug studies. Overall, this study provides a broad description of the Scn1aA1783V/WT mouse and highlights the utility of this model in therapy discovery.
Running head: EXTINCTION VIA IMAGERY Psychophysiological Evidence for Fear Extinction Learning via Mental Imagery

Imagery-based extinction procedures have long been used in the treatments of fearrelated conditions. The assumption is that imagery can substitute for the perceptual stimuli in the extinction process. Yet, experimental validations of this assumption have been limited in number and some have relied exclusively on measures of autonomic reactivity without consideration of conscious feelings of fear. The current investigation sought to assess whether imagery-based exposure could lead to extinction of conditioned fear to the corresponding perceptual stimulus. Conditioned fear responses were measured by both a physiological (i.e., skin conductance response/SCR) and a subjective (i.e., self-reported fear) measure. Participants (N = 56) first underwent perceptual differential fear conditioning, then imagery extinction, then perceptual extinction. SCR evidence was found for successful fear conditioning, generalization of fear from viewing to imagery, and most importantly, the absence of differential fear after imagery extinction upon re-exposure to the conditioned perceptual stimulus. Self-reported fear confirmed the acquisition and generalization of fear and provided evidence of a significant reduction in differential fear conditioning across extinction. Consistent with clinical evidence of the efficacy of imagery extinction and the existing limited experimental literature, the current study offers support for fear extinction to perceptual stimuli via imagery exposure.
Acentrosomal spindle assembly and stability in C. elegans oocytes requires a kinesin-12 non-motor microtubule interaction domain

During the meiotic divisions in oocytes, microtubules are sorted and organized by motor proteins to generate a bipolar spindle in the absence of centrosomes [1]. In most organisms, kinesin-5 family members crosslink and slide microtubules to generate outward force that promotes acentrosomal spindle bipolarity [2–7]. However, the mechanistic basis for how other kinesin families act on acentrosomal spindles has not been explored. We investigated this question in C. elegans oocytes, where kinesin-5 is not required to generate outward force [8]. Instead, the kinesin-12 family motor KLP-18 performs this function [9–12]. KLP-18 acts with adaptor protein MESP-1 (meiotic spindle 1) to sort microtubule minus ends to the periphery of a microtubule array, where they coalesce into spindle poles [12]. If either of these proteins is depleted, outward sorting of microtubules is lost and minus ends converge to form a monoaster. Here we use a combination of in vitro biochemical assays and in vivo mutant analysis to provide insight into the mechanism by which these proteins collaborate to promote acentrosomal spindle assembly. We identify a microtubule binding site on the C-terminal stalk of KLP-18 and demonstrate that a direct interaction between the KLP-18 stalk and MESP-1 activates non-motor microtubule binding. We also provide evidence that this C-terminal domain is required for KLP-18 activity during spindle assembly and show that KLP-18 is continuously required to maintain spindle bipolarity. This study thus provides new insight into the construction and maintenance of the oocyte acentrosomal spindle as well as into kinesin-12 mechanism and regulation.
Pairwise tests for conditional selection use evolutionary logic to predict intrinsic drug resistance in ALK alterations

Background Genomic data can facilitate personalized treatment decisions by enabling therapeutic hypotheses in individual patients. Conditional selection (encompassing both mutual exclusivity and co-occurrence) is commonly used to consider rare genomic variants relative to established cancer drivers. However, the direct comparison of p-values across multiple pairs of genes is confounded by the often-dramatic differences in sample size between established driver mutations and novel findings. Methods We develop a resampling based method for the direct pairwise comparisons of conditional selection between sets of gene pairs. This effectively creates quantitative positive control guideposts of conditional selection that normalize differences in population size. We applied this method to a transcript variant of ALK in melanoma, termed ALKATI, which has been the subject of a recent controversy in the literature. We reproduced some of the original cell transformation experiments, performed rescue experiments, and analyzed drug response data to revisit the original ALKATI findings. Finding We found that we are powered to quantitatively compare the degree of relative mutual exclusivity (down to an abundance of 10 patients in a cohort of 500) between novel gene variants and positive controls. We also found that ALKATI is not as mutually exclusive as BRAF and NRAS are with each other. Our in vitro transformation assays and rescue assays suggested that alternative transcript initiation in ALK is not likely to be necessary or sufficient for cellular transformation or growth. Interpretation Pairwise comparisons of conditional selection represent a sensitive method of utilizing existing genomic data to directly and quantitatively compare relative levels of conditional selection. The results of using our method in ALKATI and our experiments strongly disfavor the role of ALKATI as a targetable oncogenic driver. The progress of other experimental agents in late stage melanoma and our experimental and computational re-analysis led us to conclude that further single agent testing of ALK inhibitors in patients with ALKATI should be limited to cases where no other treatment hypotheses can be identified.
National Trends and Disparities in Hospitalization for Hypertensive Emergencies Among Medicare Beneficiaries, 1999-2019

Background: In the last two decades, hypertension control in the U.S. population has not improved, and there are widening disparities. Less is known, however, about progress in reducing hospitalizations related to hypertensive emergencies. Methods: We conducted serial cross-sectional analysis of Medicare fee-for-service beneficiaries aged 65 years or older between 1999 and 2019 using Medicare denominator and inpatient files. We evaluated trends in national hospitalization rates for hypertensive emergencies and longer-term outcomes, including 30-day readmission and 30-day mortality. Because substantial demographic and regional variation may exist in hypertension prevalence and outcomes, we also evaluated rates of hospitalization and associated outcomes by demographic subgroups and county. We identified all beneficiaries admitted with a primary discharge diagnosis of hypertensive emergency, hypertension urgency, or hypertension crisis (ICD-9 code of 401.0, 402.0x, 403.0x, 404.0x, and 405.0x from January 1, 1999, to September 31, 2015, ICD-10 code of I100, I119, I110, I120, I132, I150, and I158 from October 1, 2015, to September 31, 2016, ICD-10 code of I16.0, I16.1, I16.9 from October 1, 2016, to December 31, 2019). Results: The sample consisted of 397,238 individual Medicare fee-for-service beneficiaries. From 1999 through 2019, the annual hospitalization rates for hypertensive emergencies increased significantly from 51.5 to 125.9 per 100,000 beneficiary-years; this increase was most pronounced among the following subgroups: adults [≥]85 years (66.8 to 274.1), females (64.9 to 160.1), Blacks (144.4 to 369.5), and Medicare-Medicaid insured (dual eligible, 93.1 to 270.0). Across all subgroups, Black adults had the highest hospitalization rate in 2019, and there was a significant increase in the differences in hospitalizations between Blacks and Whites from 1999 to 2019. Marked geographic variation was also present, with the highest hospitalization rates in the South (so-called "Stroke Belt"). Among 3,143 counties and county-equivalents included in the study, less than 1% of counties either had no change (n=7) or decreased (n=20) hospitalization rates since 1999. Among patients hospitalized for a hypertensive emergency, the observed 30-day all-cause mortality rate decreased from 2.6% to 1.7% and 30-day all-cause readmission rate decreased from 15.7% to 11.8%. Conclusion: Among Medicare fee-for-service beneficiaries aged 65 years or older, hospitalization rates for hypertensive emergencies increased substantially and significantly from 1999 to 2019. Black adults had the largest increase in hospitalization rates across age, sex, race, and dual-eligible strata. There was significant national variation, with the highest rates generally in the South.
WHotLAMP: A simple, inexpensive, and sensitive molecular test for the detection of SARS-CoV-2 in saliva

Despite the development of effective vaccines against SARS-CoV-2, epidemiological control of the virus is still challenging due to slow vaccine rollouts, incomplete vaccine protection to current and emerging variants, and unwillingness to get vaccinated. Therefore, frequent testing of individuals to identify early SARS-CoV-2 infections, contact-tracing and isolation strategies remain crucial to mitigate viral spread. Here, we describe WHotLAMP, a rapid molecular test to detect SARS-CoV-2 in saliva. WHotLAMP is simple to use, highly sensitive (3.6 viral RNA copies per microliter of saliva) and specific, as well as inexpensive, making it ideal for frequent screening. Moreover, WHotLAMP does not require harsh chemicals or specialized equipment and thus can be performed in point-of-care settings, and may also be adapted for resource-limited environments or home use. While applied here to SARS-CoV-2, WHotLAMP can be easily modified to detect other pathogens, making it adaptable for other diagnostic assays, including for use in future outbreaks.
Products of 1,8-Cineole Oxidation by a Pseudomonad

A bacterium having close affinity with Pseudomonas flava was isolated from eucalypt leaves for its ability to utilize 1,8-cineole (1) as a carbon source. The bacterium is also capable of utilizing α-terpineol, camphor, isoborneol and geraniol but failed to grow on borneol, limonene and piperitone. Growth of the organism in mineral salts medium containing 1,8-cineole resulted in the formation of four oxidation products. Keto lactone (2), alcohols (3) and (4) and ketone (5) arereported as natural products arising from the oxidation of 1,8-cineole by the bacterium.
Running head: SELECTIVE ATTENTION AND REWARD

21 Reward enhances stimulus processing in the visual cortex, but the mechanisms through which this 22 effect occurs remain unclear. Reward prospect can both increase the deployment of voluntary 23 attention and increase the salience of previously neutral stimuli. In this study we orthogonally 24 manipulated reward and voluntary attention while human participants performed a global motion 25 detection task. We recorded steady-state visual evoked potentials (SSVEPs) to simultaneously 26 measure the processing of attended and unattended stimuli linked to different reward probabilities, 27 as they compete for attentional resources. The processing of the high rewarded feature was 28 enhanced independently of voluntary attention, but this gain diminished once rewards were no 29 longer available. Neither the voluntary attention nor the salience account alone can fully explain 30 these results. Instead, we propose how these two accounts can be integrated to allow for the flexible 31 balance between reward-driven increase in salience and voluntary attention. 32 33
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1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Endoscopy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China
Temporal Variation in the Genetic Composition of an Endangered Marsupial Reflects Reintroduction History

The loss of genetic variation and genetic divergence from source populations are common problems for reintroductions that use captive animals or a small number of founders to establish a new population. This study evaluated the genetic changes occurring in a captive and a reintroduced population of the dibbler (Parantechinus apicalis) that were established from multiple source populations over a twelve-year period, using 21 microsatellite loci. While the levels of genetic variation within the captive and reintroduced populations were relatively stable, and did not differ significantly from the source populations, their effective population size reduced 10–16-fold over the duration of this study. Evidence of some loss of genetic variation in the reintroduced population coincided with genetic bottlenecks that occurred after the population had become established. Detectable changes in the genetic composition of both captive and reintroduced populations were associated with the origins of the individuals introduced to the population. We show that interbreeding between individuals from different source populations lowered the genetic relatedness among the offspring, but this was short-lived. Our study highlights the importance of sourcing founders from multiple locations in conservation breeding programs to avoid inbreeding and maximize allelic diversity. The manipulation of genetic composition in a captive or reintroduced population is possible with careful management of the origins and timings of founder releases.