bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning methods to predict amyotrophic lateral sclerosis disease progression
Authors: Pancotti Corrado , Birolo Giovanni , Rollo Cesare , Sanavia Tiziana , Di Camillo Barbara , Manera Umberto , Chiò Adriano , Fariselli Piero 
Published: August 2022

AbstractAmyotrophic lateral sclerosis (ALS) is a highly complex and heterogeneous neurodegenerative disease that affects motor neurons. Since life expectancy is relatively low, it is essential to promptly understand the course of the disease to better target the patient’s treatment. Predictive models for disease progression are thus of great interest. One of the most extensive and well-studied open-access data resources for ALS is the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) repository. In 2015, the DREAM-Phil Bowen ALS Prediction Prize4Life Challenge was held on PRO-ACT data, where competitors were asked to develop machine learning algorithms to predict disease progression measured through the slope of the ALSFRS score between 3 and 12 months. However, although it has already been successfully applied in several studies on ALS patients, to the best of our knowledge deep learning approaches still remain unexplored on the ALSFRS slope prediction in PRO-ACT cohort. Here, we investigate how deep learning models perform in predicting ALS progression using the PRO-ACT data. We developed three models based on different architectures that showed comparable or better performance with respect to the state-of-the-art models, thus representing a valid alternative to predict ALS disease progression.
Rational peptide design for regulating liquid–liquid phase separation on the basis of residue–residue contact energy
Authors: Kamagata Kiyoto , Ariefai Maulana , Takahashi Hiroto , Hando Atsumi , Subekti Dwiky Rendra Graha , Ikeda Keisuke , Hirano Atsushi , Kameda Tomoshi 
Published: August 2022

AbstractSince liquid–liquid phase separation (LLPS) of proteins is governed by their intrinsically disordered regions (IDRs), it can be controlled by LLPS-regulators that bind to the IDRs. The artificial design of LLPS-regulators based on this mechanism can be leveraged in biological and therapeutic applications. However, the fabrication of artificial LLPS-regulators remains challenging. Peptides are promising candidates for artificial LLPS-regulators because of their ability to potentially bind to IDRs complementarily. In this study, we provide a rational peptide design methodology for targeting IDRs based on residue–residue contact energy obtained using molecular dynamics (MD) simulations. This methodology provides rational peptide sequences that function as LLPS regulators. The peptides designed with the MD-based contact energy showed dissociation constants of 35–280 nM for the N-terminal IDR of the tumor suppressor p53, which are significantly lower than the dissociation constants of peptides designed with the conventional 3D structure-based energy, demonstrating the validity of the present peptide design methodology. Importantly, all of the designed peptides enhanced p53 droplet formation. The droplet-forming peptides were converted to droplet-deforming peptides by fusing maltose-binding protein (a soluble tag) to the designed peptides. Thus, the present peptide design methodology for targeting IDRs is useful for regulating droplet formation.
Sequence analyses of Malaysian Indigenous communities reveal historical admixture between Hoabinhian hunter-gatherers and Neolithic farmers
Authors: Aghakhanian Farhang , Hoh Boon-Peng , Yew Chee-Wei , Kumar Subbiah Vijay , Xue Yali , Tyler-Smith Chris , Ayub Qasim , Phipps Maude E. 
Published: August 2022

AbstractSoutheast Asia comprises 11 countries that span mainland Asia across to numerous islands that stretch from the Andaman Sea to the South China Sea and Indian Ocean. This region harbors an impressive diversity of history, culture, religion and biology. Indigenous people of Malaysia display substantial phenotypic, linguistic, and anthropological diversity. Despite this remarkable diversity which has been documented for centuries, the genetic history and structure of indigenous Malaysians remain under-studied. To have a better understanding about the genetic history of these people, especially Malaysian Negritos, we sequenced whole genomes of 15 individuals belonging to five indigenous groups from Peninsular Malaysia and one from North Borneo to high coverage (30X). Our results demonstrate that indigenous populations of Malaysia are genetically close to East Asian populations. We show that present-day Malaysian Negritos can be modeled as an admixture of ancient Hoabinhian hunter-gatherers and Neolithic farmers. We observe gene flow from South Asian populations into the Malaysian indigenous groups, but not into Dusun of North Borneo. Our study proposes that Malaysian indigenous people originated from at least three distinct ancestral populations related to the Hoabinhian hunter-gatherers, Neolithic farmers and Austronesian speakers.
Self-induced consensus of Reddit users to characterise the GameStop short squeeze
Authors: Mancini Anna , Desiderio Antonio , Di Clemente Riccardo , Cimini Giulio 
Published: August 2022

AbstractThe short squeeze of GameStop (GME) shares in mid-January 2021 has been primarily orchestrated by retail investors of the Reddit r/wallstreetbets community. As such, it represents a paramount example of collective coordination action on social media, resulting in large-scale consensus formation and significant market impact. In this work we characterise the structure and time evolution of Reddit conversation data, showing that the occurrence and sentiment of GME-related comments (representing how much users are engaged with GME) increased significantly much before the short squeeze actually took place. Taking inspiration from these early warnings as well as evidence from previous literature, we introduce a model of opinion dynamics where user engagement can trigger a self-reinforcing mechanism leading to the emergence of consensus, which in this particular case is associated to the success of the short squeeze operation. Analytical solutions and model simulations on interaction networks of Reddit users feature a phase transition from heterogeneous to homogeneous opinions as engagement grows, which we qualitatively compare to the sudden hike of GME stock price. Although the model cannot be validated with available data, it offers a possible and minimal interpretation for the increasingly important phenomenon of self-organized collective actions taking place on social networks.
80 Hz but not 40 Hz, transcranial alternating current stimulation of 80 Hz over right intraparietal sulcus increases visuospatial working memory capacity
Authors: Park Jimin , Lee Chany , Lee Sangjun , Im Chang-Hwan 
Published: August 2022

AbstractWorking memory (WM) is a complex cognitive function involved in the temporary storage and manipulation of information, which has been one of the target cognitive functions to be restored in neurorehabilitation. WM capacity is known to be proportional to the number of gamma cycles nested in a single theta cycle. Therefore, gamma-band transcranial alternating current stimulation (tACS) should be dependent of the stimulation frequency; however, the results of previous studies that employed 40 Hz tACS have not been consistent. The optimal locations and injection currents of multiple scalp electrodes were determined based on numerical simulations of electric field. Experiments were conducted with 20 healthy participants. The order of three stimulation conditions (40 Hz tACS, 80 Hz tACS, and sham stimulation) were randomized but counterbalanced. Visual hemifield-specific visual WM capacity was assessed using a delayed visual match to the sample task. High gamma tACS significantly increased WM capacity, while low gamma tACS had no significant effect. Notably, 80 Hz tACS increased WM capacity on both the left and right visual hemifields, while previous tACS studies only reported the effects of tACS on contralateral hemifields. This is the first study to investigate the frequency-dependent effect of gamma-band tACS on WM capacity. Our findings also suggest that high gamma tACS might influence not only WM capacity but also communication between interhemispheric cortical regions. It is expected that high gamma tACS could be a promising neurorehabilitation method to enhance higher-order cognitive functions with similar mechanisms.
Risk score-based substratification improves surveillance costs after transurethral resection of bladder tumor in patients with primary high-risk non-muscle-invasive bladder cancer
Authors: Fujita Naoki , Hatakeyama Shingo , Momota Masaki , Tobisawa Yuki , Yoneyama Tohru , Yamamoto Hayato , Ito Hiroyuki , Yoneyama Takahiro , Hashimoto Yasuhiro , Yoshikawa Kazuaki , Ohyama Chikara 
Published: August 2022

AbstractHigh-risk non-muscle-invasive bladder cancer (NMIBC) has a heterogeneity and intensive surveillances after transurethral resection of bladder tumor (TURBT) are major factors of increased costs. Therefore, we aimed to develop optimized surveillance protocols based on the risk score-based substratifications to improve surveillance costs. We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT. Patients were substratified into intra-lower, intra-intermediate, and intra-higher groups or UUT-lower, UUT-intermediate, and UUT-higher groups by summing each of the independent risk factors of intravesical and UUT recurrences, respectively. The optimized surveillance protocols that enhance cost-effectiveness were then developed using real incidences of recurrence after TURBT. The 10-year total surveillance costs were compared between the European Association of Urology (EAU) guidelines-based and optimized surveillance protocols. The Kaplan–Meier curves of intravesical and UUT recurrence-free survivals were clearly separated among the substratified groups. The optimized surveillance protocols promoted a 43% reduction ($487,599) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. These results suggest that the optimized surveillance protocols based on risk score-based substratifications could potentially reduce over investigation and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.
Inhibition of current perception thresholds in A-delta and C fibers through somatosensory stimulation of the body surface
Authors: Shimo Kazuhiro , Ogawa Sho , Niwa Yuto , Tokiwa Yuji , Dokita Ayaka , Kato Sho , Hattori Takafumi , Matsubara Takako 
Published: August 2022

AbstractSomatosensory stimulation of the body surface, such as through tactile and noxious stimulation, is widely known to inhibit pain. However, no studies have measured the threshold changes due to somatosensory stimulation of each nerve fiber (Aβ, Aδ, and C) separately. We examined the changes in the current perception thresholds of Aδ, C, and Aβ fibers induced by non-noxious and noxious somatosensory stimulation of the body surface. The current stimuli were sinusoidal waves at frequencies of 2000 Hz, 250 Hz, and 5 Hz, which selectively stimulated the Aβ, Aδ, and C fibers, respectively. In the case of non-noxious stimulation, lightly rubbing the dorsal side of the forearm with a brush showed no significant physiological or clinical changes in the current perception thresholds of the Aδ, and C fibers; a significant increase was observed only in the Aβ fibers. However, applying noxious stimulation to the body surface through hand immersion in cold water increased pain thresholds in both the Aδ and C fibers, and sensory threshold of the Aβ fibers; changes in tactile thresholds were not significant. Inhibition of sensory information by nociceptive inputs may selectively suppress nociceptive stimuli.
Genomic and transcriptomic profiling of phoenix colonies
Authors: Sindeldecker Devin , Dunn Matthew , Zimmer Aubree , Anderson Matthew , Alfonzo Juan , Stoodley Paul 
Published: August 2022

AbstractPseudomonas aeruginosa is a Gram-negative bacterium responsible for numerous human infections. Previously, novel antibiotic tolerant variants known as phoenix colonies as well as variants similar to viable but non-culturable (VBNC) colonies were identified in response to high concentrations of aminoglycosides. In this study, the mechanisms behind phoenix colony and VBNC-like colony emergence were further explored using both whole genome sequencing and RNA sequencing. Phoenix colonies were found to have a single nucleotide polymorphism (SNP) in the PA4673 gene, which is predicted to encode a GTP-binding protein. No SNPs were identified within VBNC-like colonies compared to the founder population. RNA sequencing did not detect change in expression of PA4673 but revealed multiple differentially expressed genes that may play a role in phoenix colony emergence. One of these differentially expressed genes, PA3626, encodes for a tRNA pseudouridine synthase which when knocked out led to a complete lack of phoenix colonies. Although not immediately clear whether the identified genes in this study may have interactions which have not yet been recognized, they may contribute to the understanding of how phoenix colonies are able to emerge and survive in the presence of antibiotic exposure.
In situ melt pool measurements for laser powder bed fusion using multi sensing and correlation analysis
Authors: Wang Rongxuan , Garcia David , Kamath Rakesh R. , Dou Chaoran , Ma Xiaohan , Shen Bo , Choo Hahn , Fezzaa Kamel , Yu Hang Z. , Kong Zhenyu 
Published: August 2022

AbstractLaser powder bed fusion is a promising technology for local deposition and microstructure control, but it suffers from defects such as delamination and porosity due to the lack of understanding of melt pool dynamics. To study the fundamental behavior of the melt pool, both geometric and thermal sensing with high spatial and temporal resolutions are necessary. This work applies and integrates three advanced sensing technologies: synchrotron X-ray imaging, high-speed IR camera, and high-spatial-resolution IR camera to characterize the evolution of the melt pool shape, keyhole, vapor plume, and thermal evolution in Ti–6Al–4V and 410 stainless steel spot melt cases. Aside from presenting the sensing capability, this paper develops an effective algorithm for high-speed X-ray imaging data to identify melt pool geometries accurately. Preprocessing methods are also implemented for the IR data to estimate the emissivity value and extrapolate the saturated pixels. Quantifications on boundary velocities, melt pool dimensions, thermal gradients, and cooling rates are performed, enabling future comprehensive melt pool dynamics and microstructure analysis. The study discovers a strong correlation between the thermal and X-ray data, demonstrating the feasibility of using relatively cheap IR cameras to predict features that currently can only be captured using costly synchrotron X-ray imaging. Such correlation can be used for future thermal-based melt pool control and model validation.
Use of centrifugal systems for investigating water flow processes in unsaturated soils
Authors: Qin Huanhuan 
Published: August 2022

AbstractCentrifugal modelling, both physical and numerical, has been used for studying groundwater flow and transport processes in the past. However, there was disagreement in previous studies whether numerical models can be used in simulating centrifugal systems under unsaturated flow condition. In the present study, a numerical model based on Richards’ equation was developed to predict one-dimensional unsaturated flow in centrifugal systems. The validity of the model was tested using data from physical models in four published benchmark problems. The ability of the numerical model to close mass balance was also tested. It was shown that the newly developed numerical model was able to recreate the four benchmark problems quite successfully, indicating that using such a model under unsaturated flow condition is feasible. The mass conservation result shows that the model is more sensitive to spatial grid resolution than to specified temporal step. Therefore, fine spatial discretization is suggested to ensure the simulation quality. Additionally, adaptive temporal time stepping method can be used to improve the computational efficiency. It was found that the dimensionless factors used for scaling physical dimensions by 1/N, seepage velocity by N, and temporal dimension by 1/N2 were useful parameters for scaling centrifugal systems.
Spatial autocorrelation signatures of ecological determinants on plant community characteristics in high Andean wetlands
Authors: Lozada Adriana , Bertin Angéline 
Published: August 2022

AbstractUnderstanding how biological communities are shaped is a central tenet of community ecology. Recent evidence highlights the potential of decoupling diversity spatial autocorrelation into its positive and negative components to reveal community assembly processes that would otherwise remain undetected, as well as to improve understanding of their impacts on different facets of diversity. Yet, such approaches have only been implemented to investigate the effects of a few assembly drivers on a small number of diversity components. Here, we used high Andean wetland plant communities over a strong latitudinal gradient to investigate the effects of various ecological factors on spatial autocorrelation patterns of nine community metrics with different informative values, including measures of richness, dominance, evenness and beta-diversity. By combining Moran’s Eigenvector Maps, partial least squares structural equation modeling, and regression analyses, we revealed two groups of community parameters presenting contrasting spatial patterns due to specific sensitivities to ecological factors. While environmental variation and wetland connectivity increased positive spatial autocorrelation in richness and dominance-related parameters, species co-occurrence promoted negative spatial autocorrelation in evenness-related parameters. These results offer new insights regarding both how ecological processes affect species assembly, as well as the information captured by classical taxonomic parameters.
A life history model of the ecological and evolutionary dynamics of polyaneuploid cancer cells
Authors: Bukkuri Anuraag , Pienta Kenneth J. , Austin Robert H. , Hammarlund Emma U. , Amend Sarah R. , Brown Joel S. 
Published: August 2022

AbstractTherapeutic resistance is one of the main reasons for treatment failure in cancer patients. The polyaneuploid cancer cell (PACC) state has been shown to promote resistance by providing a refuge for cancer cells from the effects of therapy and by helping them adapt to a variety of environmental stressors. This state is the result of aneuploid cancer cells undergoing whole genome doubling and skipping mitosis, cytokinesis, or both. In this paper, we create a novel mathematical framework for modeling the eco-evolutionary dynamics of state-structured populations and use this framework to construct a model of cancer populations with an aneuploid and a PACC state. Using in silico simulations, we explore how the PACC state allows cancer cells to (1) survive extreme environmental conditions by exiting the cell cycle after S phase and protecting genomic material and (2) aid in adaptation to environmental stressors by increasing the cancer cell’s ability to generate heritable variation (evolvability) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to allow cancer cells to persist under therapy and evolve therapeutic resistance. By eliminating cells in the PACC state through appropriately-timed PACC-targeted therapies, we show how we can prevent the emergence of resistance and promote cancer eradication.
The exquisitely preserved integument of Psittacosaurus and the scaly skin of ceratopsian dinosaurs
Authors: Bell Phil R. , Hendrickx Christophe , Pittman Michael , Kaye Thomas G. , Mayr Gerald 
Published: August 2022

AbstractThe Frankfurt specimen of the early-branching ceratopsian dinosaurPsittacosaurusis remarkable for the exquisite preservation of squamous (scaly) skin and other soft tissues that cover almost its entire body. New observations under Laser-Stimulated Fluorescence (LSF) reveal the complexity of the squamous skin ofPsittacosaurus, including several unique features and details of newly detected and previously-described integumentary structures. Variations in the scaly skin are found to be strongly regionalized inPsittacosaurus. For example, feature scales consist of truncated cone-shaped scales on the shoulder, but form a longitudinal row of quadrangular scales on the tail. Re-examined through LSF, the cloaca ofPsittacosaurushas a longitudinal opening, or vent; a condition that it shares only with crocodylians. This implies that the cloaca may have had crocodylian-like internal anatomy, including a single, ventrally-positioned copulatory organ. Combined with these new integumentary data, a comprehensive review of integument in ceratopsian dinosaurs reveals that scalation was generally conservative in ceratopsians and typically consisted of large subcircular-to-polygonal feature scales surrounded by a network of smaller non-overlapping polygonal basement scales. This study highlights the importance of combining exceptional specimens with modern imaging techniques, which are helping to redefine the perceived complexity of squamation in ceratopsians and other dinosaurs.
A co-crystal berberine-ibuprofen improves obesity by inhibiting the protein kinases TBK1 and IKKɛ
Authors: Wang Man , Xu Rong , Liu Xiaoli , Zhang Ling , Qiu Siyan , Lu Yuting , Zhang Peng , Yan Ming , Zhu Jing 
Published: August 2022

AbstractBerberine (BBR) exerts specific therapeutic effects on various diseases such as diabetes, obesity, and other inflammation-associated diseases. However, the low oral bioavailability (below 1%) of berberine due to its poor solubility and membrane permeability limits its clinical use. In this paper, we have prepared a 1:1 co-crystal berberine-ibuprofen (BJ) using drug salt metathesis and co-crystal technology. Pharmacokinetic studies demonstrate a 3-fold increase in vivo bioavailability of BJ compared to that of BBR, and BJ is more effective in treating obesity and its related metabolism in vitro and in vivo. We also find that BJ promotes mitochondrial biogenesis by inhibiting TBK1 and inducing AMP‐activated protein kinase (AMPK) phosphorylation, and BJ increases adipocyte sensitivity to catecholamine by inhibiting IKKε. Together, our findings support that co-crystal BJ is likely to be an effective agent for treating obesity and its related metabolic diseases targeting TBK1 and IKKε.
Ultimate speed limits to the growth of operator complexity
Authors: Hörnedal Niklas , Carabba Nicoletta , Matsoukas-Roubeas Apollonas S. , del Campo Adolfo 
Published: August 2022

AbstractIn an isolated system, the time evolution of a given observable in the Heisenberg picture can be efficiently represented in Krylov space. In this representation, an initial operator becomes increasingly complex as time goes by, a feature that can be quantified by the Krylov complexity. We introduce a fundamental and universal limit to the growth of the Krylov complexity by formulating a Robertson uncertainty relation, involving the Krylov complexity operator and the Liouvillian, as generator of time evolution. We further show the conditions for this bound to be saturated and illustrate its validity in paradigmatic models of quantum chaos.