bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning for Automatic Detection of Velopharyngeal Dysfunction: A Preliminary Report
Authors: Lucas Claiborne , Torres-Guzman Ricardo , James Andrew J. , Corlew Scott , Stone Amy , Powell Maria E. , Golinko Michael , Pontell Matthew E. 
Published: May 2024

Background:
Even after palatoplasty, the incidence of velopharyngeal dysfunction (VPD) can reach 30%; however, these estimates arise from high-income countries (HICs) where speech-language pathologists (SLP) are part of standardized cleft teams. The VPD burden in low- and middle-income countries (LMICs) is unknown. This study aims to develop a machine-learning model that can detect the presence of VPD using audio samples alone.

Methods:
Case and control audio samples were obtained from institutional and publicly available sources. A machine-learning model was built using Python software.

Results:
The initial 110 audio samples used to test and train the model were retested after format conversion and file deidentification. Each sample was tested 5 times yielding a precision of 100%. Sensitivity was 92.73% (95% CI: 82.41%–97.98%) and specificity was 98.18% (95% CI: 90.28%–99.95%). One hundred thirteen prospective samples, which had not yet interacted with the model, were then tested. Precision was again 100% with a sensitivity of 88.89% (95% CI: 78.44%–95.41%) and a specificity of 66% (95% CI: 51.23%–78.79%).

Discussion:
VPD affects nearly 100% of patients with unrepaired overt soft palatal clefts and up to 30% of patients who have undergone palatoplasty. VPD can render patients unintelligible, thereby accruing significant psychosocial morbidity. The true burden of VPD in LMICs is unknown, and likely exceeds estimates from HICs. The ability to access a phone-based screening machine-learning model could expand access to diagnostic, and potentially therapeutic modalities for an innumerable amount of patients worldwide who suffer from VPD.
Exploring media representation of the exotic pet trade: taxonomic, framing, and language biases in peer-reviewed publications and newspaper articles
Authors: Bielby Jon , Austen Gail E. , McMillan Kirsten M. , Wafflart Shannen M. 
Published: May 2024

AbstractThe exotic pet trade is a global industry with considerable implications for a range of taxa and stakeholders. The scale of the trade means it receives coverage in both popular and scientific media, and some narratives may receive more attention than others. As these media play an important role in shaping public opinion, policy, and legislation, we should consider and acknowledge biases and language use when reporting on the exotic pet trade.We use 320 peer-reviewed journal articles, and 191 newspaper articles on the exotic pet trade between 2001 and 2020 to investigate the frequency of use, citation rate, and language-use across framing categories and taxonomic foci within and between media-types.Our results suggest consistent biases in reporting of the trade within and between media-types, highlighting limitations in both. Aspects of welfare were underrepresented in peer-reviewed articles relative to other framings, but it was the most common focus of newspaper articles.If the exotic pet trade is to develop into a more ethical, sustainable, economically beneficial sector, then reassessing our narratives, improving knowledge flow, and encouraging interdisciplinary and comprehensive debates within the field will be essential parts of the process.
Consistent movement of viewers’ facial keypoints while watching emotionally evocative videos
Authors: Tripathi Shivansh Chandra , Garg Rahul 
Published: May 2024

AbstractNeuropsychological research aims to unravel how diverse individuals’ brains exhibit similar functionality when exposed to the same stimuli. The evocation of consistent responses when different subjects watch the same emotionally evocative stimulus has been observed through modalities like fMRI, EEG, physiological signals and facial expressions. We refer to the quantification of these shared consistent signals across subjects at each time instant across the temporal dimension as Consistent Response Measurement (CRM). CRM is widely explored through fMRI, occasionally with EEG, physiological signals and facial expressions using metrics like Inter-Subject Correlation (ISC). However, fMRI tools are expensive and constrained, while EEG and physiological signals are prone to facial artifacts and environmental conditions (such as temperature, humidity, and health condition of subjects). In this research, facial expression videos are used as a cost-effective and flexible alternative for CRM, minimally affected by external conditions. By employing computer vision-based automated facial keypoint tracking, a new metric similar to ISC, called theAverage t-statistic, is introduced. Unlike existing facial expression-based methodologies that measure CRM of secondary indicators like inferred emotions, keypoint, and ICA-based features, theAverage t-statisticis closely associated with the direct measurement of consistent facial muscle movement using the Facial Action Coding System (FACS). This is evidenced in DISFA dataset where the time-series ofAverage t-statistichas a high correlation (R2= 0.78) with a metric calledAU consistency, which directly measures facial muscle movement through FACS coding of video frames. The simplicity of recording facial expressions with the automatedAverage t-statisticexpands the applications of CRM such as measuring engagement in online learning, customer interactions, etc., and diagnosing outliers in healthcare conditions like stroke, autism, depression, etc. To promote further research, we have made the code repository publicly available.
Larval motility assay using WMicrotracker™: a high throughput test to discriminate between resistance and susceptibility to anthelmintic drugs in nematodes
Authors: Alberich Mélanie , Garcia Marie , Petermann Julie , Blancfuney Clara , Jouffroy Sophie , Jacquiet Philippe , Lespine Anne 
Published: May 2024

AbstractGrazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. Treatment predominantly relies on macrocyclic lactone (ML) anthelmintics, but their widespread application has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need for robust resistance detection methods in field parasites. We investigated the potential of the WMicrotrackerTM(WMi) motility assay, previously unexplored in ML resistance assessment. The assay first compared ivermectin (IVM) susceptibility among wild-type Bristol N2 (N2B), IVM-selected (IVR10), andnhr-8loss-of-function (AE501;nhr8(ok186))Caenorhabditis elegansstrains. Dose-response curves indicated differences in IVM susceptibility among strains, with IVR10 exhibiting a 2.12-fold decrease in sensitivity compared to N2B. Cross-resistance between IVM, moxidectin (MOX), and eprinomectin (EPR) was explored, demonstrating reduced susceptibility in IVR10 across all drugs compared to N2B. Further investigation was conducted usingHaemonchus contortus(H. contortus) to assess the assay’s applicability in discriminating susceptible from resistant isolates. Results revealed significant differences in drug potency between susceptible and resistant isolates, with MOX demonstrating the highest efficacy. Resistance factors (RF) highlighted the substantial resistance of the resistant isolate to EPR. The motility assay effectively discriminated susceptible from resistant isolates in bothC. elegansandH. contortus. Our findings demonstrate, for the first time, the relevance of the motility assay by WMi as a functional indicator of resistance in nematodes, offering a promising avenue for detecting resistance to MLs. This research sheds light on a novel approach for monitoring drug resistance, vital for effective parasite management strategies.
Differential control of intestine function by genetically defined enteric neurons
Authors: Shi David , Reddy Pranav , Walker Christopher , Marrin McKayla , Siu Catherine , Sharma Nikhil 
Published: May 2024

AbstractThe function of the intestine is regulated by direct innervation from a combination of enteric, sensory, and autonomic neurons. A central question in neurobiology is how these distinct peripheral neuron populations collectively control intestinal function. However, disambiguating the functions of intestine-innervating neuronal populations has been a challenge. Using intersectional genetic approaches in mice, we enable precise manipulations of defined neuronal populations within the intestinal tract. We examined enteric neurons, which represent the majority of intestine-innervating neurons, by genetically isolating neuronal subclasses, identifying their morphological specializations, and defining subclass-specific influences on intestinal functions. We further found that food consumption can be modulated by select enteric neuron populations via the spinal sensory afferent pathway. Taken together, the presented molecular genetic characterization of intestine-innervating neurons establishes a foundation for detailed studies of the enteric nervous system and its interactions with the broader neural networks of the body.
Light environment and seasonal variation in the visual system of the red shiner (Cyprinella lutrensis)
Authors: Foster Tarah N. , Williamson Alyssa G. , Foster Bradley R. , Toomey Matthew B. 
Published: May 2024

AbstractThe light environment underwater can vary dramatically over space and time, challenging the visual systems of aquatic organisms. To meet these challenges, many species shift their spectral sensitivities through changes in visual pigment chromophore and opsin expression. The red shiner (Cyprinella lutrensis) is a cyprinid minnow species that has rapidly expanded its range throughout North America and inhabits a wide range of aquatic habitats. We hypothesized that visual system plasticity has contributed to the red shiner’s success. We investigated plasticity in chromophore usage and opsin expression by collecting red shiners from three Oklahoma creeks that vary in turbidity throughout the year. We characterized the light environment by spectroradiometry, measured chromophore composition of the eyes with high performance liquid chromatography, characterized CYP27C1 enzyme function through heterologous expression, and examined ocular gene expression by RNA sequencing andde novotranscriptome assembly. We observed significantly higher proportions of the long- wavelength shifted A2chromophore in the eyes of fish from the turbid site and in samples collected in winter, suggesting that there may be a temperature-dependent trade-off between chromophore-based spectral tuning and chromophore-related noise. Opsin expression varied between turbid and clear creeks, but did not align with light environment as expected, and the magnitude of these differences was limited compared to the differences in chromophore composition. We confirmed that red shinerCYP27C1catalyzes the conversion of A1to A2, but the ocular expression ofCYP27C1was not well correlated with A2levels in the eye, suggesting conversion may be occurring outside of the eye.
Tumor microenvironment noise-induced polarization: the main challenge in macrophages’ immunotherapy for cancer
Authors: Sierra Jesus , Avila-Ponce de León Ugo , Padilla-Longoria Pablo 
Published: May 2024

AbstractDisturbance of epigenetic processes can lead to altered gene function and malignant cellular transformation. In particular, changes in the epigenetic landscape are a central topic in cancer biology. The initiation and progression of cancer are now recognized to involve both epigenetic and genetic alterations. In this paper, we study the epigenetic mechanism (related to the tumor microenvironment) responsible for increasing tumor-associated macrophages that promote the occurrence and metastasis of tumor cells, support tumor angiogenesis, inhibit T cell-mediated anti-tumor immune response, and lead to tumor progression. We show that the tumor benefits from the macrophages’ high degree of plasticity and larger epigenetic basins corresponding to phenotypes that favor cancer development through a process that we call noise-induced polarization. Moreover, we propose a mechanism to promote the appropriate epigenetic stability for immunotherapies involving macrophages, which includes p53 and APR-246 (eprenetapopt). Our results show that a combination therapy may be necessary to ensure the proper epigenetic stability of macrophages, which otherwise will contribute to cancer progression. On the other hand, we conclude that macrophages may remain in the anti-tumoral state in types of cancer that exhibit less TP53 mutation, like colorectal cancer; in these cases, macrophages’ immunotherapy may be more suitable. We finally mention the relevance of the epigenetic potential (Waddington’s landscape) as the backbone for our study, which encapsulates the biological information of the system.
Cortical circuit principles predict patterns of trauma induced tauopathy in humans
Authors: Barbas Helen , Garcia-Cabezas Miguel Angel , John Yohan , Bautista Julied , McKee Ann , Zikopoulos Basilis 
Published: May 2024

AbstractConnections in the cortex of diverse mammalian species are predicted reliably by the Structural Model for direction of pathways and signal processing (reviewed in1,2). The model is rooted in the universal principle of cortical systematic variation in laminar structure and has been supported widely for connection patterns in animals but has not yet been tested for humans. Here, inpostmortembrains of individuals neuropathologically diagnosed with chronic traumatic encephalopathy (CTE) we studied whether the hyperphosphorylated tau (p-tau) pathology parallels connection sequence in time by circuit mechanisms. CTE is a progressive p-tau pathology that begins focally in perivascular sites in sulcal depths of the neocortex (stages I-II) and later involves the medial temporal lobe (MTL) in stages III-IV. We provide novel quantitative evidence that the p-tau pathology in MTL A28 and nearby sites in CTE stage III closely follows the graded laminar patterns seen in homologous cortico-cortical connections in non-human primates. The Structural Model successfully predicted the laminar distribution of the p-tau neurofibrillary tangles and neurites and their density, based on the relative laminar (dis)similarity between the cortical origin (seed) and each connection site. The findings were validated for generalizability by a computational progression model. By contrast, the early focal perivascular pathology in the sulcal depths followed local columnar connectivity rules. These findings support the general applicability of a theoretical model to unravel the direction and progression of p-tau pathology in human neurodegeneration via a cortico-cortical mechanism. Cortical pathways converging on medial MTL help explain the progressive spread of p-tau pathology from focal cortical sites in early CTE to widespread lateral MTL areas and beyond in later disease stages.
Repurposing mitochondrial-targeting anthelmintic agents with GLUT1 inhibitor BAY-876 for cancer therapy
Authors: Schumacher Tanner J. , Iyer Ananth V. , Rumbley Jon , Ronayne Conor T. , Mereddy Venkatram R. 
Published: May 2024

ABSTRACTCancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of efficacyin vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors. To test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Here, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested. In this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies warrant further investigation into targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.
Adaptive optical third-harmonic generation microscopy for in vivo imaging of tissues
Authors: Rodríguez Cristina , Pan Daisong , Natan Ryan G. , Mohr Manuel A. , Miao Max , Chen Xiaoke , Northen Trent R. , Vogel John P. , Ji Na 
Published: May 2024

AbstractThird-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated a recently developed compact adaptive optics module into a third-harmonic generation microscope, to measure and correct for optical aberrations in complex tissues. Taking advantage of the high sensitivity of the third-harmonic generation process to material interfaces and thin membranes, along with the 1,300-nm excitation wavelength used here, our adaptive optical third-harmonic generation microscope enabled high-resolution in vivo imaging within highly scattering biological model systems. Examples include imaging of myelinated axons and vascular structures within the mouse spinal cord and deep cortical layers of the mouse brain, along with imaging of key anatomical features in the roots of the model plantBrachypodium distachyon. In all instances, aberration correction led to significant enhancements in image quality.
Untargeted Plasma Metabolomics Unveils Distinct Metabolite Profiles in Parkinson’s Disease Subtypes: A Focus on idiopathic REM Sleep Behavior Disorders
Authors: Lee Sunjae , Kim Jihyun , Baek Jaewoo , Jung Ki-Young , Lee Yunjong , Koh Ara , Kim Han-Joon 
Published: May 2024

AbstractBackgroundParkinson’s disease (PD) is characterized by diverse clinical presentations and etiological complexities, with rapid eye movement (REM) sleep behavior disorder (RBD) serving as a prodromal marker. While extensive unbiased metabolic profiling of plasma samples from PD subjects has been conducted to identify novel PD metabolic biomarkers, comprehensive metabolic profiling of PD subtypes based on RBD status remains limited.MethodsWe conducted a comprehensive metabolic profiling of PD subtypes at disease onset, considering the presence or absence of RBD, utilizing an untargeted metabolomics approach. Plasma samples were collected from subjects with PD with and without RBD at the initial stages of disease, idiopathic RBD, and healthy controls to elucidate similarities and differences among PD subtypes. Based on ordination analysis and metabolome-wide association study (Wilcoxon rank-sum tests and generalized fold changes), we identified specific groups of metabolites enriched in the PD_Only group and RBD groups (iRBD & PD_RBD+), with few metabolites shared between groups. Furthermore, pathway enrichment analysis (hypergeometric tests) identified specific groups enriched with metabolites from specific origins and associated biospecimens, as well as disease-associated metabolites. Finally, we evaluated the biomarker potential of the identified disease metabolites by ROC curves and proposed logistic regression models of key biomarkers and clinical parameters for predicting disease status.ResultsMetabolomic analysis revealed distinct metabolic profiles between PD subtypes with and without RBD. Our analysis confirmed previously reported PD metabolic markers, such as a reduction in caffeine and urate, as well as an increase in cortisol, secondary bile acids, and p-cresol sulfate. However, our stratified analyses based on the presence of RBD discriminated RBD-associated metabolites from those associated with PD_Only (without RBD). PD patients with RBD exhibited enrichment of gut microbial-origin metabolites, including secondary bile acids and p-cresol sulfate, compared to PD patients without RBD. Conversely, metabolites associated with neuro-psychiatric diseases were enriched in PD patients without RBD.ConclusionsOur study elucidates the heterogeneous nature of PD subtypes, particularly differentiated with the presence of RBD. The metabolic features of PD with RBD subtype supports the “body-first” concept of PD pathogenesis originating from the gut.
Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults, a randomized, parallel arm, double-blind, placebo-controlled, pilot study
Authors: Stubbs Brianna J. , Stephens Elizabeth B. , Senadheera Chatura , Peralta Sawyer , Roa-Diaz Stephanie , Alexander Laura , Silverman-Martin Wendie , Garcia Thelma Y. , Yukawa Michi , Morris Jenifer , Blonquist Traci M. , Johnson James B. , Newman John C. 
Published: May 2024

AbstractObjectivesKetone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to determine tolerability and safety of KE ingestion in older adults.DesignRandomized, placebo-controlled, double-blinded, parallel-arm trial, with a 12-week intervention period (NCT05585762).SettingGeneral community, Northern California, USA.ParticipantsCommunity-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n=30) were randomized and n=23 (M= 14, F=9) completed the protocol.InterventionParticipants were randomly allocated to consume either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil.MeasurementsTolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events.ResultsThere was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n =2 (14.3% [90% CI = 2.6 – 38.5]); PLA n=1 (7.1% [90% CI = 0.4 – 29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 – 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group.ConclusionsThis KE was safe and well-tolerated in healthy older adults. These results provide a foundation for use of KEs in aging research.HighlightsKetones esters induce ketosis without dietary changes and may target aging biologyStudies of ketone esters were limited in duration and focused on younger adultsWe found ketone esters were safe and tolerable for 12 weeks in healthy older adults