bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal DNA sequences of the Pacific saury genome: versatile resources for fishery science and comparative biology
Authors: Sato Mana , Fukuda Kazuya , Kadota Mitsutaka , Makino-Itou Hatsune , Tatsumi Kaori , Yamauchi Shinya , Kuraku Shigehiro 
Published: October 2023

AbstractPacific saury (Cololabis saira) is a commercially important small pelagic fish species in Asian. In this study, we conducted the first-ever whole genome sequencing of this species, with single molecule, real-time (SMRT) sequencing technology. The obtained high-fidelity (HiFi) long-read sequence data, which amount to approximately 30 folds of its haploid genome size that was measured with quantitative PCR (1.17 Gb), were assembled into contigs. Scaffolding with Hi-C reads yielded a whole genome assembly containing 24 chromosome-scale sequences, with a scaffold N50 length of 47.7 Mb. Screening of repetitive elements including telomeric repeats was performed to characterize possible factors that need to be resolved towards ‘telomere-to-telomere’ sequencing. The larger genome size than in medaka, a close relative in Beloniformes, is at least partly explained by larger repetitive element quantity, which is reflected in more abundant tRNAs, in the Pacific saury genome. Protein-coding regions was predicted using transcriptome data, which resulted in 22,274 components. Retrieval of Pacific saury homologs of aquaporin (AQP) genes known from other teleost fishes validated high completeness and continuity of the genome assembly. These resources are available athttps://treethinkers.nig.ac.jp/saira/and will assist various molecular-level studies in fishery science and comparative biology.
Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma
Authors: Galvan C , Flores A , Cerrillos V , Avila I , Murphy C , Zheng W , To TT , Christofk HR , Lowry WE 
Published: October 2023

AbstractAmong the numerous changes associated with the transformation to cancer, cellular metabolism is one of the first discovered and most prominent[1, 2]. However, despite the knowledge that nearly every cancer is associated with the strong upregulation of various metabolic pathways, there has yet to be much clinical progress on the treatment of cancer by targeting a single metabolic enzyme directly[3–6]. We previously showed that inhibition of glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells of origin had no effect on the initiation or progression of cutaneous squamous cell carcinoma[7], suggesting that these cancers are metabolically flexible enough to produce the necessary metabolites required for sustained growth in the absence of glycolysis. Here we focused on glutaminolysis, another metabolic pathway frequently implicated as important for tumorigenesis in correlative studies. We genetically blocked glutaminolysis through glutaminase (GLS) deletion in cancer cells of origin, and found that this had little effect on tumorigenesis, similar to what we previously showed for blocking glycolysis. Tumors with genetic deletion of glutaminolysis instead upregulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We also found that the metabolic flexibility observed upon inhibition of glycolysis or glutaminolysis is due to post-transcriptional changes in the levels of plasma membrane lactate and glutamine transporters. To define the limits of metabolic flexibility in cancer initiating hair follicle stem cells, we genetically blocked both glycolysis and glutaminolysis simultaneously and found that frank carcinoma was not compatible with abrogation of both of these carbon utilization pathways. These data point towards metabolic flexibility mediated by regulation of nutrient consumption, and suggest that treatment of cancer through metabolic manipulation will require multiple interventions on distinct pathways.
Multicolor fluorescence microscopy for surgical guidance using a chip-scale imager with a low-NA fiber optic plate and a multi-bandpass interference filter
Authors: Roschelle Micah , Rabbani Rozhan , Papageorgiou Efthymios , Zhang Hui , Cooperberg Matthew , Stohr Bradley A. , Niknejad Ali , Anwar Mekhail 
Published: October 2023

AbstractIn curative-intent cancer surgery, intraoperative fluorescence imaging of both diseased and healthy tissue can help to ensure successful removal of all gross and microscopic disease with minimal damage to neighboring critical structures, such as nerves. Current fluorescence-guided surgery (FGS) systems, however, rely on bulky and rigid optics that incur performance-limiting trade-offs between sensitivity and maneuverability. Moreover, many FGS systems are incapable of multiplexed imaging. As a result, clinical FGS is currently limited to millimeter-scale detection of a single fluorescent target. Here we present a scalable, lens-less fluorescence imaging chip, VISION, capable of sensitive and multiplexed detection within a compact form factor. Central to VISION is a novel optical frontend design combining a low-numerical-aperture fiber optic plate (LNA-FOP) and a multi-bandpass interference filter, which is affixed to a custom CMOS image sensor. The LNA-FOP acts as a planar collimator to improve resolution and compensate for the angle-sensitivity of the interference filter, enabling high-resolution and multiplexed fluorescence imaging without lenses. We show VISION is capable of detecting tumor foci of less than 100 cells at near video framerates and, as proof of principle, can simultaneously visualize both tumor and nerves inex vivoprostate tissue.
Angiopoietin-like protein 2 mediates vasculopathy driven fibrogenesis in a mouse model of systemic sclerosis
Authors: Saha Dyuti , Thannimangalath Sujaya , Pincha Neha , Kiran Ravi , Hegde Akshay , Kataria Sunny , Dam Binita , Hiwale Ankita , Ravula Venkatesh , Rahulan Lekshmi Minikumari , Nigam Neha , Singh Neha , Agarwal Vikas , Vemula Praveen K. , Jamora Colin 
Published: October 2023

ABSTRACTVasculopathy is a common hallmark of various fibrotic disorders including systemic sclerosis (SSc), yet its underlying etiology and contribution to fibrogenesis remain ill-defined. In SSc the vasculopathy typically precedes the onset of fibrosis and we observed that this phenomenon is recapitulated in the Snail transgenic mouse model of SSc. The vascular anomalies manifest as deformed vessels, endothelial cell dysfunction and vascular leakage. Our investigation into the underlying mechanism of this phenotype revealed that Angiopoietin-like protein 2 (Angptl2), secreted by the Snail transgenic keratinocytes, is a principal driver of fibrotic vasculopathy. In endothelial cells, Angptl2 upregulates pro-fibrotic genes, downregulates the tight junction protein Claudin 5, and prompts the acquisition of mesenchymal characteristics. Inhibiting endothelial cell junctional instability and consequently vascular leakage with a synthetic analog of the microbial metabolite Urolithin A (UAS03) effectively mitigated the vasculopathy and inhibited fibrogenesis. Thus, Angptl2 emerges as a promising early biomarker of the disease and inhibiting the vasculopathy inducing effects of this protein with agents such as UAS03 presents an appealing therapeutic avenue to reduce disease severity. These insights hold the potential to revolutionize the approach to the treatment of fibrotic diseases by targeting the vascular defects.
Instability in computational models of vascular smooth muscle cell contraction
Authors: Giudici Alessandro , Szafron Jason M , Ramachandra Abhay B , Spronck Bart 
Published: October 2023

AbstractPurposeThrough their contractile and synthetic capacity, vascular smooth muscle cells play a key role in regulating the stiffness and resistance of the circulation. To model the contraction of blood vessels, an active stress component can be added to the (passive) Cauchy stress tensor. Different constitutive formulations have been proposed to describe this active stress component. Notably, however, theex vivomeasurement of the biomechanical behaviour of contacted blood vessels presents several experimental challenges, which complicate the acquisition of comprehensive data sets to inform complex active stress models. In this work, we examine formulations for use with limited experimental contraction data as well as those developed to capture more comprehensive data sets.MethodsWe prove analytically that a subset of these formulations exhibits unstable behaviours (i.e., a non-unique diameter solution for a given pressure) in certain parameter ranges, particularly when contractile deformations are large. Furthermore, using experimental literature data, we present two case studies where these active stress models are used to capture the contractile response of vascular smooth muscle cells in the presence of 1) limited and 2) extensive contraction data.ResultsOur work shows how limited contraction data complicates the selection of an appropriate active stress model for vascular applications, potentially resulting in unrealistic modelled behaviours.ConclusionAs such, the data presented herein provide a useful reference for the selection of an active stress model which balances the trade-off between accuracy and the available biomechanical information.
Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells
Authors: Schutt Katherine , Queen Katelyn A. , Fisher Kira , Budington Olivia , Mao Weifeng , Liu Wei , Xiao Yisong , Aswad Fred , Joseph James , Stumpff Jason 
Published: October 2023

ABSTRACTThe mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors. In this study, we investigated the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue. Mutations in S284 cause relocalization of KIF18A from the plus-ends of spindle microtubules to the spindle poles. Furthermore, KIF18A S284 mutants display loss of KIF18A function and fail to support proliferation in CIN tumor cells. Interestingly, similar effects on KIF18A localization and function were seen after treatment of CIN cells with KIF18A inhibitory compounds that are predicted to interact with residues within the alpha-4 helix. These data implicate the KIF18A alpha-4 helix as an effective target for inhibition and demonstrate that small molecules targeting KIF18A selectively limit CIN tumor cell proliferation and result in phenotypically similar effects on mitosis at the single cell level compared to genetic perturbations.
The fitness consequences of genetic divergence between polymorphic gene arrangements
Authors: Charlesworth Brian 
Published: October 2023

AbstractInversions restrict recombination when heterozygous with standard arrangements, but often have few noticeable phenotypic effects. Nevertheless, there are several examples of inversions that can be maintained polymorphic by strong selection under laboratory conditions. A long-standing model for the source of such selection is divergence between arrangements with respect to recessive or partially recessive deleterious mutations, resulting in a selective advantage to heterokaryotypic individuals over homokaryotypes. This paper uses a combination of analytical and numerical methods to investigate this model, for the simple case of an autosomal inversion with multiple independent nucleotide sites subject to deleterious mutations. A complete lack of recombination in heterokaryotypes is assumed, as well as constancy of the frequency of the inversion over space and time. It is shown that a significantly higher mutational load will develop for the less frequent arrangement. A selective advantage to heterokaryotypes is only expected when the two alternative arrangements are nearly equal in frequency, so that their mutational loads are very similar in size. The effects of someDrosophila pseudoobscurapolymorphic inversions on fitness traits seem to be too large to be explained by this process, although it may contribute to some of the observed effects. Several population genomic statistics can provide evidence for signatures of a reduced efficacy of selection associated with the rarer of two arrangements, but there is currently little published data that are relevant to the theoretical predictions.
Continuously fluctuating selection reveals extreme granularity and parallelism of adaptive tracking
Authors: Bitter M.C. , Berardi S. , Oken H. , Huynh A. , Schmidt P. , Petrov D.A. 
Published: October 2023

SummaryTemporally fluctuating environmental conditions are a ubiquitous feature of natural habitats. Yet, how finely natural populations adaptively track fluctuating selection pressures via shifts in standing genetic variation is unknown. We generated high-frequency, genome-wide allele frequency data from a genetically diverse population ofDrosophila melanogasterin extensively replicated field mesocosms from late June to mid-December, a period of ∼12 generations. Adaptation throughout the fundamental ecological phases of population expansion, peak density, and collapse was underpinned by extremely rapid, parallel changes in genomic variation across replicates. Yet, the dominant direction of selection fluctuated repeatedly, even within each of these ecological phases. Comparing patterns of allele frequency change to an independent dataset procured from the same experimental system demonstrated that the targets of selection are predictable across years. In concert, our results reveal fitness-relevance of standing variation that is likely to be masked by inference approaches based on static population sampling, or insufficiently resolved time-series data. We propose such fine-scaled temporally fluctuating selection may be an important force maintaining functional genetic variation in natural populations and an important stochastic force affecting levels of standing genetic variation genome-wide.
Tripod transcranial alternating current stimulation at 5-Hz to alleviate anxiety symptoms: a preliminary report
Authors: Lee Tien-Wen , Li Chiang-Shan R. , Tramontano Gerald 
Published: October 2023

ABSTRACTIntroductionOne of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS).MethodsA total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 minutes. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments.ResultsOf the 27 patients, 19 (70.4%) experienced a reduction in symptom severity greater than 50%, with an average reduction of BAI 58.5%. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments.ConclusionThe results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy.
GRAMD2+alveolar type I cell plasticity facilitates cell state transitions in organoid culture
Authors: Shen Hua , Chen Weimou , Liu Yixin , Castaldi Alessandra , Castillo Jonathan , Horie Masafumi , Flodby Per , Sundar Shivah , Li Changgong , Ji Yanbin , Minoo Parviz , Marconett Crystal N , Zhou Beiyun , Borok Zea 
Published: October 2023

SUMMARYAlveolar epithelial regeneration is critical for normal lung function and becomes dysregulated in disease. While alveolar type 2 (AT2) and club cells are known distal lung epithelial progenitors, determining if alveolar epithelial type 1 (AT1) cells also contribute to alveolar regeneration has been hampered by lack of highly specific mouse models labeling AT1 cells. To address this, theGramd2CreERT2transgenic strain was generated and crossed toRosamTmGmice. Extensive cellular characterization, including distal lung immunofluorescence and cytospin staining, confirmed that GRAMD2+AT1 cells are highly enriched for green fluorescent protein (GFP). Interestingly,Gramd2CreERT2GFP+cells were able to form organoids in organoid co-culture with Mlg fibroblasts. Temporal scRNAseq revealed thatGramd2+AT1 cells transition through numerous intermediate lung epithelial cell states including basal, secretory and AT2 cell in organoids while acquiring proliferative capacity. Our results indicate thatGramd2+AT1 cells are highly plastic suggesting they may contribute to alveolar regeneration.
Encoding of melody in the human auditory cortex
Authors: Sankaran Narayan , Leonard Matthew K. , Theunissen Frederic , Chang Edward F. 
Published: October 2023

AbstractMelody is a core component of music in which discrete pitches are serially arranged to convey emotion and meaning. Perception of melody varies along several pitch-based dimensions: (1) the absolute pitch of notes, (2) the difference in pitch between successive notes, and (3) the higher-order statistical expectation of each note conditioned on its prior context. While humans readily perceive melody, how these dimensions are collectively represented in the brain and whether their encoding is specialized for music remains unknown. Here, we recorded high-density neurophysiological activity directly from the surface of human auditory cortex while Western participants listened to Western musical phrases. Pitch, pitch-change, and expectation were selectively encoded at different cortical sites, indicating a spatial code for representing distinct dimensions of melody. The same participants listened to spoken English, and we compared evoked responses to music and speech. Cortical sites selective for music were systematically driven by the encoding of expectation. In contrast, sites that encoded pitch and pitch-change used the same neural code to represent equivalent properties of speech. These findings reveal the multidimensional nature of melody encoding, consisting of both music-specific and domain-general sound representations in auditory cortex.TeaserThe human brain contains both general-purpose and music-specific neural populations for processing distinct attributes of melody.
Diabetes Diagnosis through Machine Learning: Investigating Algorithms and Data Augmentation for Class Imbalanced BRFSS Dataset
Authors: Chowdhury Mohammad Mihrab , Ayon Ragib Shahariar , Hossain Md Sakhawat 
Published: October 2023

AbstractDiabetes is a prevalent chronic condition that poses significant challenges to early diagnosis and identifying at-risk individuals. Machine learning plays a crucial role in diabetes detection by leveraging its ability to process large volumes of data and identify complex patterns. However, imbalanced data, where the number of diabetic cases is substantially smaller than non-diabetic cases, complicates the identification of individuals with diabetes using machine learning algorithms. Our study focuses on predicting whether a person is at risk of diabetes, considering the individual’s health and socio-economic conditions while mitigating the challenges posed by imbalanced data. To minimize the impact of imbalance data, we employed several data augmentation techniques such as oversampling (SMOTE-N), undersampling (ENN), and hybrid sampling techniques (SMOTE-Tomek and SMOTE-ENN) on training data before applying machine learning algorithms. Our study sheds light on the significance of carefully utilizing data augmentation techniques, without any data leakage, in enhancing the effectiveness of machine learning algorithms. Moreover, it offers a complete machine learning structure for healthcare practitioners, from data obtaining to ML prediction, enabling them to make data-informed strategies.
Dynamic evaluation of spine kinematics in individuals with Parkinson’s disease and freezing of gait
Authors: Palmisano C. , Farinelli V. , Camuncoli F. , Favata A. , Pezzoli G. , Frigo C.A. , Isaias I.U. 
Published: October 2023

AbstractBackgroundFreezing of gait (FoG) is an episodic failure of gait exposing people with Parkinson’s disease (PD) to a high risk of falling. Despite growing evidence of the interconnection between impaired trunk control and FoG, a detailed description of spinal kinematics during walking is still lacking in this population.Research questionDo spinal alterations impact gait performance in individuals with PD and FoG?MethodsWe analyzed kinematic data of 47 PD participants suffering (PD-FOG, N=24) or not suffering from FoG (PD-NFOG, N=23) and 15 healthy controls (HCO) during quiet standing and unperturbed walking. We estimated the main spinal variables (i.e., spinal length, lordosis and kyphosis angles, trunk inclination), the pelvis angles, and the shoulder-pelvis angles during gait and standing. We studied differences across conditions and groups and the relationships between postural and gait parameters using linear regression methods.ResultsDuring standing and walking, both PD groups showed increased trunk inclination and decreased lordosis angle with respect to HCO, as well as a decreased range in variation of kyphosis angle, pelvic obliquity, and shoulder-pelvis angles. Only PD-FOG participants showed reduced range of lordosis angle and spinal length compared to HCO. PD-FOG individuals were also not able to straighten their spine during walking compared to standing. Stride length and velocity were decreased in both patient groups compared to HCO, while swing duration was reduced only in the PD-FOG group. In individuals with PD-FOG, trunk inclination and lordosis angle showed moderate but significant positive correlations with all gait alterations.SignificanceSpine alterations impacted gait performance in individuals with PD suffering from FoG. Excessive trunk inclination and poor mastering of the lordosis spinal region may create an unfavourable postural precondition for forward walking. Physical therapy should target combined spinal and stepping alterations in these individuals.