bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous estimation of genotype error and uncalled deletion rates in whole genome sequence data
Authors: Masaki Nobuaki , Browning Sharon R. , Browning Brian L. 
Published: February 2024

AbstractGenotype data include errors that may influence conclusions reached by downstream statistical analyses. Previous studies have estimated genotype error rates from discrepancies in human pedigree data, such as Mendelian inconsistent genotypes or apparent phase violations. However, uncalled deletions, which generally have not been accounted for in these studies, can lead to biased error rate estimates. In this study, we propose a genotype error model that considers both genotype errors and uncalled deletions when calculating the likelihood of the observed genotypes in parent-offspring trios. Using simulations, we show that when there are uncalled deletions, our model produces genotype error rate estimates that are less biased than estimates from a model that does not account for these deletions. We applied our model to SNVs in 77 sequenced White British parent-offspring trios in the UK Biobank. We use the Akaike information criterion to show that our model fits the data better than a model that does not account for uncalled deletions. We estimate the genotype error rate at SNVs with minor allele frequency > 0.001 in these data to be 3.2 × 10−4(90% CI: [2.8 × 10−4, 6.2 × 10−4]). We estimate that 77% of the genotype errors at these markers are attributable to uncalled deletions (90% CI: [73%, 88%]).Author summaryA genotype error occurs when the genotype identified through molecular analysis does not match the actual genotype of the individual being analyzed. Because genotype errors can influence downstream statistical results, previous studies have attempted to estimate the rate of genotype errors in a study sample. However, uncalled deletions, which generally have not been accounted for in these studies, can lead to biased error rate estimates. In this study, we formulate a model adjusting for uncalled deletions when estimating genotype error rates. We show that when uncalled deletions are present, this model results in less biased estimates of genotype error rates compared to a model that does not adjust for uncalled deletions. We apply this model to SNVs in 77 sequenced White British parent-offspring trios in the UK Biobank and estimate the genotype error rate and the proportion of genotype errors that are attributable to uncalled deletions at SNVs with minor allele frequency > 0.001.
The neurohormone tyramine stimulates the secretion of an Insulin-Like Peptide from the intestine to modulate the systemic stress response in C. elegans
Authors: Veuthey Tania , Giunti Sebastián , De Rosa María José , Alkema Mark , Rayes Diego 
Published: February 2024

ABSTRACTThe DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, lifespan, and stress resistance. InC. elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood. Here, we show that the ILP, INS-3, plays a crucial role in modulating the response to different types of stressors inC. elegans.ins-3mutants display increased resistance to both heat and oxidative stress; however, under favorable conditions, this advantage is countered by slower reproductive development.ins-3expression in both neurons and the intestine is downregulated in response to environmental stressors. Conversely, the neurohormone tyramine, which is released during the acute flight response, triggers an upregulation inins-3expression. Moreover, we found that tyramine negatively impacts environmental stress resistance by stimulating the release of INS-3 from the intestine. The subsequent release of INS-3 systemically activates the DAF-2 pathway, resulting in the inhibition of cytoprotective mechanisms mediated by DAF-16/FOXO and HSF-1. These studies offer mechanistic insights into the brain-gut communication pathway that weighs adaptive strategies to respond to acute and long-term stress scenarios.
Comparison of Prompt Engineering and Fine-Tuning Strategies in Large Language Models in the Classification of Clinical Notes
Authors: Zhang Xiaodan , Talukdar Nabasmita , Vemulapalli Sandeep , Ahn Sumyeong , Wang Jiankun , Meng Han , Bin Murtaza Sardar Mehtab , Leshchiner Dmitry , Dave Aakash Ajay , Joseph Dimitri F. , Witteveen-Lane Martin , Chesla Dave , Zhou Jiayu , Chen Bin 
Published: February 2024

AbstractThe emerging large language models (LLMs) are actively evaluated in various fields including healthcare. Most studies have focused on established benchmarks and standard parameters; however, the variation and impact of prompt engineering and fine-tuning strategies have not been fully explored. This study benchmarks GPT-3.5 Turbo, GPT-4, and Llama-7B against BERT models and medical fellows’ annotations in identifying patients with metastatic cancer from discharge summaries. Results revealed that clear, concise prompts incorporating reasoning steps significantly enhanced performance. GPT-4 exhibited superior performance among all models. Notably, one-shot learning and fine-tuning provided no incremental benefit. The model’s accuracy sustained even when keywords for metastatic cancer were removed or when half of the input tokens were randomly discarded. These findings underscore GPT-4’s potential to substitute specialized models, such as PubMedBERT, through strategic prompt engineering, and suggest opportunities to improve open-source models, which are better suited to use in clinical settings.
Reversal of neuronal tau pathology, metabolic dysfunction, and electrophysiological defects via adiponectin pathway-dependent AMPK activation
Authors: McGregor Eric R. , Lasky Danny J. , Rippentrop Olivia J. , Clark Josef P. , Wright Samantha L. G. , Jones Mathew V. , Anderson Rozalyn M. 
Published: February 2024

AbstractChanges in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b. The transcriptional response to AR included broad metabolic and functional pathways. Induction of lysosomal pathways involved activation of LC3 and p62, and restoration of neuronal outgrowth required the stress-responsive kinase JNK. Negative consequences of NFTs on mitochondrial activity, ATP production, and lipid stores were corrected. Defects in electrophysiological measures (e.g., resting potential, resistance, spiking profiles) were also corrected. These findings reveal a network linking mitochondrial function, cellular maintenance processes, and electrical aspects of neuronal function that can be targeted via adiponectin receptor activation.
Single-cell trait diversity explains niche and fitness differences in aquatic microbial communities
Authors: Fontana Simone , Schmitz Désirée A. , Daniels Michael , Danza Francesco , Röösli Thomas , Bruderer Hannah , Walser Jean-Claude , Dekaezemacker Julien , Escrig Stephane , Meibom Anders , Pomati Francesco , Schreiber Frank 
Published: February 2024

AbstractTwo fundamental questions in ecology are how biodiversity is maintained and how it affects ecosystem functioning. Until now, it has been difficult to study the above mechanisms in natural microbial communities, yet they are important drivers of biogeochemical ecosystem functions. Here, we use a new approach to define and measure biodiversity in complex lake microbial communities (Lake Cadagno, Switzerland) based on the cell-to-cell variation in multiple functionally relevant phenotypic traits. We use stable isotope probing coupled to correlative imaging using confocal laser scanning microscopy (CLSM) and nanometer-scale secondary ion mass spectrometry (NanoSIMS) to obtain morphological (size), physiological (pigments) and metabolic (carbon and nitrogen isotope uptake and sulfur content) traits for a large number of individual cells along the environmental gradient found across lake depth. We show that cell-to-cell trait variation is significantly correlated with cell densities as a proxy for ecosystem functioning, whereas genetic diversity measured at the level of 16S and 18S is not. Our single-cell analysis provides evidence for a simultaneous increase in niche partitioning (measured as increased evenness in pigment composition) and decrease in fitness differences (measured as decreased variability in sulfur content) due to light limitation and competition for nutrients in deep layers of the lake. This leads to a negative relationship between niche and fitness differences. Our results suggest that niche and fitness differences in natural microbial communities can be understood at the level of single-cell traits, providing a mechanistic understanding of the relationship between microbial diversity and ecosystem functioning.
Multi-site Ultrashort Echo Time 3D Phosphorous MRSI repeatability using novel Rosette Trajectory (PETALUTE)
Authors: Alcicek Seyma , Craig-Craven Alexander Richard , Shen Xin , Chiew Mark , Ozen Ali , Sawiak Stephen , Pilatus Ulrich , Emir Uzay E 
Published: February 2024

AbstractPurposeThis study aims 1) to implement an operator-independent acquisition, reconstruction, and processing pipeline using a novel rosette k-space pattern for UTE31P 3D MRSI and 2) to evaluate the clinical applicability and replicability at different experimental setups.MethodsA multicenter repeatability study was conducted for the novel UTE31P 3D Rosette MRSI at three institutions with different experimental setups. Non-localized31P MRSI data of 5 healthy subjects at each site were acquired with an acquisition delay of 65 μs and a final resolution of 10 × 10 × 10 mm3in 9 min. Spectra were quantified using the LCModel package. The potential acceleration was achieved using compressed sensing on retrospectively undersampled data. Reproducibility at each site was evaluated using the inter-subject coefficient of variance.ResultsThis novel acquisition and advanced processing techniques yielded high-quality spectra and enabled the detection of the critical brain metabolites at three different sites with different hardware specifications. In vivo, feasibility with an acceleration factor of 4 in 6.75 min resulted in a mean Cramér-Rao lower bounds below 20% for PCr, ATPs, PME, and the mean CoV of ATP/PCr resulted in below %20.ConclusionWe demonstrated that UTE31P 3D Rosette MRSI acquisition, combined with compressed sensing and LCModel analysis, allows patient-friendly, operator-independent, high-resolution31PMRSI to be acquired at clinical setups.
Long-term disruption of glucose homeostasis in a rodent model of preterm birth
Authors: Diao Sihao , Guenoun David , Chen Shiou-Ping , Cruciani-Guglielmacci Céline , Pansiot Julien , Laforge Mireille , Raho Ilyes , Faivre Valérie , Degos Vincent , Gressens Pierre , Nadjar Agnès , Steenwinckel Juliette Van , Adle-Biassette Homa , Magnan Christophe , Jacquens Alice , Bokobza Cindy 
Published: February 2024

AbstractAround 1 of every 10 babies is born preterm, and the incidence of preterm birth has been rising. The long-term consequences of preterm survivors are not fully understood. Preterm birth is proven to be associated with metabolic diseases and related disorders later in life. Preterm newborns are susceptible to perinatal inflammatory events such as chorioamnionitis, hypoxia-ischemia, and sepsis. We hypothesized that perinatal inflammation has a role in the developmental programming of metabolic diseases and related disorders. In the present study, perinatal inflammation was modeled by systemic administration of IL-1β in mice. We observed a pronounced sexual dimorphism where only the males presented significant insulin resistance and glucose intolerance accompanied by leptin resistance in the long term following perinatal inflammation exposure. Adiposity and energy homeostasis were intact. It showed that perinatal inflammation selectively contributes to the long-term dysregulation of glucose metabolism in a sex-dependent manner. The underlying mechanism might be linked with hypothalamic inflammation and upregulated circulating CCL5. Metformin treatment might be optional to treat insulin resistance resulting from perinatal inflammation.HighlightsPerinatal inflammation is common in preterm infants, often leading to perinatal brain injuries. However, the long-term metabolic outcomes of these infants are not fully revealed.We explored the long-term metabolic outcomes in mice with perinatal IL-1β exposure and sought its association with inflammation.Perinatal inflammation has a profound and deleterious role in glucose metabolism in a sex-dependent and time-dependent manner.Perinatal inflammation might be a risk factor for metabolic disorders in preterm survivors.
Insulin resistance alters the coupling between cerebral blood flow and glucose metabolism in younger and older adults: Implications for neurovascular coupling
Authors: Deery H.A. , Liang E. , Di Paolo R. , Voigt K. , Murray G. , Siddiqui M.N. , Egan G.F. , Moran C. , Jamadar S.D. 
Published: February 2024

ABSTRACTRising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of insulin resistance and age to the coupling of cerebral blood flow and glucose metabolism; a critical process in the supply of energy for the brain. Thirty-four younger (20-42 years) and 41 older (66-86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive coupling. In insulin resistant younger adults, coupling showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates and coupling of cerebral blood flow and metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.
Spike Neural Network of Motor Cortex Model for Arm Reaching Control
Authors: Jiang Hongru , Bu Xiangdong , Sui Xiaohong , Tang Huajin , Pan Xiaochuan , Chen Yao 
Published: February 2024

AbstractMotor cortex modeling is crucial for understanding movement planning and execution. While interconnected recurrent neural networks have successfully described the dynamics of neural population activity, most existing methods utilize continuous signal-based neural networks, which do not reflect the biological spike neural signal. To address this limitation, we propose a recurrent spike neural network to simulate motor cortical activity during an arm-reaching task. Specifically, our model is built upon integrate-and-fire spiking neurons with conductance-based synapses. We carefully designed the interconnections of neurons with two different firing time scales - “fast” and “slow” neurons. Experimental results demonstrate the effectiveness of our method, with the model’s neuronal activity in good agreement with monkey’s motor cortex data at both single-cell and population levels. Quantitative analysis reveals a correlation coefficient 0.89 between the model’s and real data. These results suggest the possibility of multiple timescales in motor cortical control.
Dijet and electroweak limits on a
Z′
boson coupled to quarks
Authors: Dobrescu Bogdan A. , Yu Felix 
Published: February 2024

An insightful way of presenting the LHC limits on dijet resonances is the coupling-mass plot for a Z′ boson that has flavor-independent quark interactions. This also illustrates the comparison of low-mass LHC sensitivity with constraints on the flavor-independent Z′ boson from electroweak and quarkonium measurements. To derive these constraints, we compute the Z′ mixing with the Z, the photon, and the ϒ meson, emphasizing the logarithmic dependence on the masses of the new electroweak-charged fermions (“anomalons”) required to cancel the gauge anomalies. We update the coupling-mass plot, extending it for Z′ masses from 5 GeV to 5 TeV.

Published by the American Physical Society
2024
95.4 GeV diphoton excess at ATLAS and CMS
Authors: Biekötter Thomas , Heinemeyer Sven , Weiglein Georg 
Published: February 2024

The ATLAS Collaboration has recently reported the results of a low-mass Higgs-boson search in the diphoton final state based on the full Run 2 dataset. The results are based on an improved analysis with respect to the previous analysis, which included a part of the Run 2 data, with a substantially better sensitivity. The “model-dependent” search carried out by ATLAS shows an excess of events at a mass of about 95.4 GeV with a local significance of 1.7σ. The results are compatible with a previously reported excess at the same mass, but with somewhat higher significance of 2.9σ, from the CMS collaboration, also based on the full Run 2 dataset. Combining the two results (neglecting possible correlations), we find a signal strength of μγγATLAS+CMS=0.24−0.08+0.09, corresponding to an excess of 3.1σ. In this work, we investigate the implications of this result, updating a previous analysis based solely on the CMS Run 2 data. We demonstrate that the ATLAS/CMS combined diphoton excess can be interpreted as the lightest Higgs boson in a Two-Higgs doublet model that is extended by a complex singlet (S2HDM) of Yukawa types II and IV, while being in agreement with all other experimental and theoretical constraints.

Published by the American Physical Society
2024
Nuclear deexcitation simulator for neutrino interactions and nucleon decays of
C12
and
O16
based on TALYS
Authors: Abe Seisho 
Published: February 2024

Nuclear deexcitation associated with neutrino interactions and nucleon decays has a significant impact on a recent key observable for neutrino detectors: neutron multiplicity. Although several deexcitation simulation studies have been conducted, most are closed-source or have limitations in application. Therefore, we need an open-source deexcitation simulator to be used as a standard deexcitation module in existing neutrino Monte Carlo event generators. To predict the neutron multiplicity comprehensively, the author developed a dedicated nuclear deexcitation simulator based on named ucex. ucex can be used for neutrino interactions and nucleon decays for C12 and O16. The author provides the ucex codes and sample codes for applying the ucex to widely used neutrino Monte Carlo event generators, NEUT, NuWro, and GENIE.

Published by the American Physical Society
2024
Unveiling dark matter free streaming at the smallest scales with the high redshift Lyman-alpha forest
Authors: Iršič Vid , Viel Matteo , Haehnelt Martin G. , Bolton James S. , Molaro Margherita , Puchwein Ewald , Boera Elisa , Becker George D. , Gaikwad Prakash , Keating Laura C. , Kulkarni Girish 
Published: February 2024

This study introduces novel constraints on the free streaming of thermal relic warm dark matter (WDM) from Lyman-α forest flux power spectra. Our analysis utilizes a high resolution, high redshift sample of quasar spectra observed using the HIRES and UVES spectrographs (z=4.2–5.0). We employ a Bayesian inference framework and a simulation-based likelihood that encompasses various parameters including the free streaming of dark matter, cosmological parameters, the thermal history of the intergalactic medium, and inhomogeneous reionization to establish lower limits on the mass of a thermal relic WDM particle of 5.7 keV (at 95% CL). This result surpasses previous limits from the Lyman-α forest through reduction of the measured uncertainties due to a larger statistical sample and by measuring clustering to smaller scales (kmax=0.2  km−1 s). The approximately two-fold improvement due to the expanded statistical sample suggests that the effectiveness of Lyman-α forest constraints on WDM models at high redshifts are limited by the availability of high quality quasar spectra. Restricting the analysis to comparable scales and thermal history priors as in prior studies (kmax<0.1  km−1 s) lowers the bound on the WDM mass to 4.1 keV. As the precision of the measurements increases, it becomes crucial to examine the instrumental and modeling systematics. On the modeling front, we argue that the impact of the thermal history uncertainty on the WDM particle mass constraint has diminished due to improved independent observations. At the smallest scales, the primary source of modeling systematic arises from the structure in the peculiar velocity of the intergalactic medium and inhomogeneous reionization.

Published by the American Physical Society
2024
Fluxbranes, generalized symmetries, and Verlinde’s metastable monopole
Authors: Cvetič Mirjam , Heckman Jonathan J. , Hübner Max , Torres Ethan 
Published: February 2024

The stringy realization of generalized symmetry operators involves wrapping “branes at infinity”. We argue that in the case of continuous (as opposed to discrete) symmetries, the appropriate objects are fluxbranes. We use this perspective to revisit the phase structure of Verlinde’s monopole, a proposed particle satisfies the Bogomol’nyi-Prasad-Sommerfield (BPS) condition when gravity is decoupled, but is non-BPS and metastable when gravity is switched on. Geometrically, this monopole is obtained from branes wrapped on locally stable but globally trivial cycles of a compactification geometry. The fluxbrane picture allows us to characterize electric (respectively magnetic) confinement (respectively screening) in the 4D theory as a result of monopole decay. In the presence of the fluxbrane, this decay also creates lower-dimensional fluxbranes, which in the field theory is interpreted as the creation of an additional topological field theory sector.

Published by the American Physical Society
2024
Grain-Boundary Structural Relaxation in
Sb2Se3
Thin-Film Photovoltaics
Authors: Lomas-Zapata R.A. , McKenna K.P. , Ramasse Q.M. , Williams R.E. , Phillips L.J. , Durose K. , Major J.D. , Mendis B.G. 
Published: February 2024

Grain boundaries play an important role in the efficiency of thin-film photovoltaics, where the absorber layer is invariably polycrystalline. Density-functional-theory simulations have previously identified a “self-healing” mechanism in Sb2Se3 that passivates the grain boundaries. During “self-healing,” extensive structural relaxation at the grain boundary removes the band-gap electronic defect states that give rise to high carrier recombination rates. In this work, lattice imaging in a transmission electron microscope is used to uncover evidence for the theoretically proposed structural relaxation in Sb2Se3. The strain measured along the [010] crystal direction is found to be dependent on the nature of the grain-boundary plane. For a (010) grain boundary, the strain and structural relaxation is minimal, since no covalent bonds are broken by termination of the grain. On the other hand, strains of up to approximately 4% extending approximately 2 nm into the grain interior are observed for a (041) grain boundary, where grain termination results in significant structural relaxation due to the ideal atomic coordination being disrupted. These results are consistent with theory and suggest that Sb2Se3 may have a high level of grain-boundary-defect tolerance.

Published by the American Physical Society
2024