bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Educational Background on Preoperative Disease Severity and Postoperative Outcomes Among Patients With Cervical Spondylotic Myelopathy
Authors: Agarwal Nitin , DiGiorgio Anthony , Michalopoulos Giorgos D. , Letchuman Vijay , Chan Andrew K. , Shabani Saman , Lavadi Raj Swaroop , Lu Daniel C. , Wang Michael Y. , Haid Regis W. , Knightly John J. , Sherrod Brandon A. , Gottfried Oren N. , Shaffrey Christopher I. , Goldberg Jacob L. , Virk Michael S. , Hussain Ibrahim , Glassman Steven D. , Shaffrey Mark E. , Park Paul , Foley Kevin T. , Pennicooke Brenton , Coric Domagoj , Upadhyaya Cheerag , Potts Eric A. , Tumialán Luis M. , Fu Kai-Ming G. , Asher Anthony L. , Bisson Erica F. , Chou Dean , Bydon Mohamad , Mummaneni Praveen V. 
Published: December 2023

Study Design:
Retrospective review of a prospectively maintained database.

Objective:
Assess differences in preoperative status and postoperative outcomes among patients of different educational backgrounds undergoing surgical management of cervical spondylotic myelopathy (CSM).

Summary of Background Data:
Patient education level (EL) has been suggested to correlate with health literacy, disease perception, socioeconomic status (SES), and access to health care.

Methods:
The CSM data set of the Quality Outcomes Database (QOD) was queried for patients undergoing surgical management of CSM. EL was grouped as high school or below, graduate-level, and postgraduate level. The association of EL with baseline disease severity (per patient-reported outcome measures), symptoms >3 or ≤3 months, and 24-month patient-reported outcome measures were evaluated.

Results:
Among 1141 patients with CSM, 509 (44.6%) had an EL of high school or below, 471 (41.3%) had a graduate degree, and 161 (14.1%) had obtained postgraduate education. Lower EL was statistically significantly associated with symptom duration of >3 months (odds ratio=1.68), higher arm pain numeric rating scale (NRS) (coefficient=0.5), and higher neck pain NRS (coefficient=0.79). Patients with postgraduate education had statistically significantly lower Neck Disability Index (NDI) scores (coefficient=-7.17), lower arm pain scores (coefficient=−1), and higher quality-adjusted life-years (QALY) scores (coefficient=0.06). Twenty-four months after surgery, patients of lower EL had higher NDI scores, higher pain NRS scores, and lower QALY scores (P<0.05 in all analyses).

Conclusions:
Among patients undergoing surgical management for CSM, those reporting a lower educational level tended to present with longer symptom duration, more disease-inflicted disability and pain, and lower QALY scores. As such, patients of a lower EL are a potentially vulnerable subpopulation, and their health literacy and access to care should be prioritized.
Molecular epidemiology ofCandida africanaisolates collected from vagina swabs in French Guiana
Authors: Bigot J. , Kalboussi Y. , Nkoy Y. Bonkoto , Benmostefa A. , Vellaissamy S. , Benzerara L. , Sainte-Rose V. , Blanchet D. , Demar M. , Guitard J. , Hennequin C. 
Published: December 2023

AbstractCandida africanacorresponds to the clade 13 ofCandia albicans. It has been mostly involved in vulvovaginal candidiasis worldwide but few data exist in South America. The aim of our study was to investigate the prevalence ofC. africanain women living in French Guiana. For this, we first set up a fluorescent-intercalating-dye-real time PCR targeting the hyphal wall protein 1 gene. The test was applied to 212C. albicansisolates collected from May to August 2019 from vaginal swabs, allowing the identification of 6 women harboringC. africana(8 isolates). No demographics or clinical-specific features could be demonstrated. Genetic diversity of those isolates was analyzed through multilocus sequence typing and showed that diploid sequence type 182 was predominant (n=6) and allowed the report of a new diploid sequence type.
Membrane lipid poly-unsaturation selectively affects ligand induced dopamine D2 receptor internalization
Authors: Sposini Silvia , Baccouch Rim , Lescuyer Mathias , De Smedt-Peyrusse Véronique , Heuninck Joyce , Durroux Thierry , Trifilieff Pierre , Perrais David , Alves Isabel 
Published: December 2023

AbstractThe poly-unsaturation of membrane phospholipids is an important feature for the biophysical properties of membranes and membrane proteins. In particular, it regulates the function of some G protein-coupled receptors (GPCR), such as their binding to ligand and G proteins or their membrane diffusion. However, its effects on GPCR internalization and trafficking remain unknown. The brain is highly enriched in poly-unsaturated fatty acids (PUFAs) and their deficiency has been associated with several neuropsychiatric disorders. Importantly, the Dopamine D2 receptor (D2R), a class A GPCR, is consistently impacted in these disorders and represents the main target of most antipsychotics. Here we show that enrichment in two different PUFAs strongly impairs agonist-induced endocytosis of D2R in HEK293 cells, without affecting clathrin-mediated endocytosis. Strikingly, this effect seems to be specific to the D2R as it does not affect various other GPCRs. Using live cell TIRF imaging, we show that D2R clustering is not affected, but that recruitment of β-arrestin2, that occurs prior to receptor internalization, is strongly impaired and endocytic vesicle formation is slowed down. Finally, we show that mutation of key residues in intracellular loop 2 abolishes the sensitivity of D2R endocytosis to PUFA enrichment. We conclude that D2R trafficking is uniquely dependent on membrane PUFAs, which could influence its role in the control of brain activity and behavior.
Efficient Multiplexing of Pollinator Metabarcodes Using Oxford Nanopore MinION Sequencing: Insights for Meadow Management from Floral Environmental DNA
Authors: Harris Stephen E. , Whitehurst Amelia , Buehrer Madeline , Lonker Sydney , Veverka Budd , Nagy Chris 
Published: December 2023

AbstractMany pollinating species are experiencing declines globally, making effective, fast, and portable pollinator monitoring methods more important than ever before. Pollinators can leave DNA on the flowers they visit, and metabarcoding of these environmental DNA (eDNA) traces provides an opportunity to detect the presence of flower visitors. This study introduces an efficient, cost-effective workflow for utilizing DNA barcoding to monitor biodiversity through environmental DNA (eDNA) left on flowers from pollinators, employing the portable MinION and Nanopore sequencing. The developed method employs multiplexing with dual molecular tags on universal cytochrome oxidase 1 (COI) barcode primers. We used this approach to compare the arthropod diversity present in three meadows with different vegetation at three time points during the flowering season. The utility of eDNA metabarcoding in investigating pollinator biodiversity and interactions is highlighted through our results, revealing the presence and interactions of 65 species from 30 families. We multiplexed individual eDNA samples from hundreds of flowers and found plant-pollinator dynamics that showed differences in species richness between sampling times and meadow diversity. Comparative analyses with conventional methods showed eDNA metabarcoding’s ability to identify diverse species and ecological interactions compared to field sampling. While some DNA likely came from eggs or microscopic insects difficult to remove from flowers, traces of eDNA from various arthropods on multiple plant species confirmed the method’s applicability, promising robust ecological monitoring and research potential in the wake of global pollinator declines. This is the first reported use of MinION based nanopore sequencing to detect arthropod species from eDNA samples collected from flowers using the described affordable multiplexing method.
Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 Modulator
Authors: Mandino Francesca , Shen Xilin , Desrosiers-Gregoire Gabriel , O’Connor David , Mukherjee Bandhan , Owens Ashley , Qu An , Onofrey John , Papademetris Xenophon , Chakravarty M. Mallar , Strittmatter Stephen M , Lake Evelyn MR 
Published: December 2023

AbstractAmyloid accumulation in Alzheimer’s disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.
pyQCM-BraTaDio: A tool for visualization, data mining, and modelling of Quartz crystal microbalance with dissipation data
Authors: Pardi Brandon M. , Ahmed Syeda Tajin , Jonguitud Flores Silvia , Flores Warren , Mears Laura L.E. , Yáñez Soto Bernardo , Andresen Eguiluz Roberto C. 
Published: December 2023

AbstractHere, we present a Python based software that allows for the rapid visualization, data mining, and basic model applications of quartz crystal microbalance with dissipation data. Our implementation begins with a Tkinter GUI to prompt the user for all required information, such as file name/location, selection of baseline time, and overtones for visualization (with customization capabilities). These inputs are then fed to a workflow that will use the baseline time to scrub and temporally shift data using the Pandas and Numpy libraries and carry out the plot options for visualization. The last stage consists of an interactive plot, that presents the data and allows the user to select ranges in MatPlotLib-generated panels, followed by application of data models, including Sauerbrey, thin films in liquid, among others, that are carried out with NumPy and SciPy. The implementation of this software allows for simple and expedited data analysis,in lieuof time consuming and labor-intensive spreadsheet analysis.Metadata
A novel integrated extraction protocol for multi-omic studies in heavily degraded samples
Authors: Boggi Byron , Sharpen Jack , Taylor George , Drosou Konstantina 
Published: December 2023

AbstractThe combination of multi-omic techniques, e.g. genomics, transcriptomics, proteomics, metabolomics and epigenomics has revolutionised studies in medical research. These are employed to support biomarker discovery, better understand molecular pathways and identify novel drug targets. Despite concerted efforts in integrating omic datasets, there is an absence for the integration of all four biomolecules in a single extraction protocol. Here, we demonstrate for the first time a novel, minimally destructive integrated protocol for the simultaneous extraction of artificially degraded DNA, proteins, lipids and metabolites from pig brain samples. We used an MTBE-based approach to separate lipids and metabolites, followed by subsequent isolation of DNA and proteins. We have validated this protocol against standalone extraction protocols and show comparable or higher yield of all four biomolecules. This integrated protocol is key towards facilitating preservation of irreplaceable samples while promoting downstream analyses and successful data integration by removing bias from univariate dataset noise and varied distribution characteristics.
Consequences of alternative stable states for short-term model-based control of cyanobacterial blooms
Authors: Jacobs Bas , van Voorn George , van Heijster Peter , Hengeveld Geerten M. 
Published: December 2023

AbstractCyanobacteria can form dense blooms in eutrophic lakes that can be toxic to humans and other animals and harmful to the ecosystem’s functioning. While better nutrient management is generally considered the long-term solution to this problem, short-term mitigation efforts (e.g., flushing, algaecides, flocculants) are becoming increasingly necessary to safeguard water quality and the ecosystem services it provides. Here, we explore potential model-based management strategies for these short-term mitigation efforts. We focus on the case where blooms are linked to the existence of alternative stable states, such that, under the same conditions but depending on the past, a lake may be dominated either by cyanobacteria (causing a harmful algal bloom) or by green algae and macrophytes in a clear water state. Changing conditions may cause the favourable clear water state to disappear through a tipping point, causing the lake to switch rapidly to the turbid cyanobacteria state. At the same time, it may take considerable effort to undo this tipping and return to the favourable state. We identify four different strategies for bloom mitigation in this scenario: Doing nothing, reacting to a bloom, resetting the lake at a later point, and preventing the bloom. We explore the different requirements for these strategies along with their associated cost profiles. We also investigate the effect of transition times from one state to another on the efficacy and costs of different strategies.
Experimental Validation of an Organ-on-Chip for Mechanical Stimulation of Cell Cultures
Authors: Testa Maria , Tornabene Salvatore , Di Leonardo Sofia , Burriesci Gaetano , La Carrubba Vincenzo , Lopresti Francesco 
Published: December 2023

AbstractThis paper focuses on the design, fabrication, and characterization of a platform aiming to dynamically culture cells under mechanical stimulation. The platform, made of polymethylmethacrylate (PMMA), allows real-time mechanical stimuli, providing valuable insights for living tissue models. Through mechanical testing and dynamic microfluidic tests, the chip functionality was assessed. The experimental results validation showcases the potential of the device in mimicking physiological conditions, offering a promising avenue for pharmaceutical testing advancement.
Multiplexed gene editing with a multi-intron containingCas9gene in citrus
Authors: Sarkar Poulami , Vazquez Jorge Santiago , Zhou Mingxi , Levy Amit , Mou Zhonglin , Orbović Vladimir 
Published: December 2023

AbstractThe citrus industry holds significant economic importance in Florida, being one of the leading producers of oranges and grapefruits in the United States. However, several diseases, such as canker and huanglongbing along with natural disasters like hurricanes have rigorously affected citrus production, quality, and yield. Improving citrus through traditional breeding methods requires significant challenges due to time constraints and complexity in genetic enhancements. To overcome these limitations, several expression systems have been developed in clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) framework allowing for gene editing of disease-associated genes across diverse citrus varieties. In this study, we present a new approach employing a multi-intron containingCas9gene plus multiple gRNAs separated with tRNA sequences to target the phytoene desaturase (PDS) gene in both ‘Carrizo’ citrange and ‘Duncan’ grapefruit. Notably, using this unified vector significantly boosted editing efficiency in both citrus varieties, showcasing mutations in all three designated targets. The implementation of this multiplex gene editing system with a multi-intron-containingCas9plus a gRNA-tRNA array demonstrates a promising avenue for efficient citrus genome editing, equipping us with potent tools in the ongoing battle against HLB.Statements and DeclarationsCompeting interestsThe authors declare that they have no competing interests.Supplementary InformationSupplementary File 1
Benchmarking of AlphaFold2 accuracy self-estimates as empirical quality measures and model ranking indicators and their comparison with independent model quality assessment programs
Authors: Edmunds Nicholas S. , Genc Ahmet G. , McGuffin Liam J. 
Published: December 2023

ABSTRACTMotivationDespite an increase in the accuracy of predicted protein structures following the development of AlphaFold2, there remains a gap in the accuracy of predicted model quality assessment scores when compared to those generated with reference to experimental structures. The predictions of model accuracy scores generated by AlphaFold2, plDDT and pTM, have become familiar descriptors of model quality. However, at CASP15 some modelling groups noticed a variation in these scores for models of very similar observed quality, particularly for quaternary structures. There have also been a number of methods describing adaptations of the AlphaFold2 algorithm to purposes such as refinement by custom template recycling and model quality assessment using a similar method of template input. In this study we compare plDDT and pTM to their observed counterparts lDDT (including lDDT-Cα and lDDT-oligo) and TM-score to examine whether they retain their reliability across the whole scoring range for both tertiary and quaternary structures and in situations where the AlphaFold2 algorithm is adapted to customised functionality. In addition, we explore the accuracy with which plDDT and pTM rank AlphaFold2 tertiary and quaternary models and whether these can be improved by the independent model quality assessment programs ModFOLD9 and ModFOLDdock.ResultsFor tertiary structures it was found that plDDT was an accurate descriptor of model quality when compared to observed lDDT-Cα scores (Pearson ρ = 0.97). Additionally, plDDT achieved a tertiary structure ranking agreement with observed scores of 0.34 as measured by true positive rate (TPR) and ModFOLD9 offered similar but not improved performance.However, the accuracy of plDDT (Pearson ρ = 0.67) and pTM (Pearson ρ = 0.70) became more variable for quaternary structures quality assessment where overprediction was seen with both scores for models of lower quality and underprediction was also seen with pTM for models of higher quality. Importantly, ModFOLDdock was able to improve upon AF2-Multimer quaternary structure model ranking as measured by both TM-score (TPR 0.34) and lDDT-oligo (TPR 0.43). Finally, evidence is presented for an increase in variability of both plDDT and pTM when custom template recycling is used, and that this variation is more pronounced for quaternary structures.
MIMt – A curated 16S rRNA reference database with less redundancy and higher accuracy at species-level identification
Authors: Cabezas M. Pilar , Fonseca Nuno A. , Muñoz-Mérida Antonio 
Published: December 2023

AbstractMotivationAccurate determination and quantification of the taxonomic composition of microbial communities, especially at the species level, is one of the major issues in metagenomics. This is primarily due to the limitations of commonly used 16S rRNA reference databases, which either contain a lot of redundancy, or a high percentage of sequences with missing taxonomic information. The use of these incomplete or biased databases may lead to erroneous identifications and, thus, to erroneous conclusions regarding the ecological role and importance of those microorganisms in the ecosystem.ResultsThe current study presents MIMt, a new 16S rRNA database for archaea and bacteria’s identification, encompassing 39 940 sequences, all precisely identified at species level. MIMt aims to be updated at least once a year to include all new sequenced species. We evaluated MIMt against Greengenes, RDP, GTDB and SILVA in terms of sequence distribution and accuracy of taxonomic assignments. Our results showed that MIMt contains less redundancy, and despite being five to 85 times smaller in size than existing databases, outperforms them in completeness and taxonomic accuracy, enabling more precise assignments at lower taxonomic ranks and thus, significantly improving species-level identification.Availability and ImplementationMIMt is freely available for non-commercial purposes athttps://mimt.bu.biopolis.pt
Dia2 formin controls receptor activity by organizing plasma membrane lipid partitioning at the nanoscale
Authors: Li Changting , Hamon Yannick , Mazaud David , Gonzalez Troncoso Pamela , Dessard Marie , He Hai-tao , Lamaze Christophe , Blouin Cedric M. 
Published: December 2023

AbstractActivation of JAK/STAT signaling by IFN-γ requires partitioning of IFN-γR into specific lipid nanodomains at the plasma membrane. Using IFN-γR as a proxy, we investigated the role of actin dynamics in the formation and organization of lipid nanodomains, a process that remains poorly understood. We identified formin Dia2/DIAPH3 as a specific and RhoA -dependent regulator of IFN-γ-induced JAK/STAT signaling. Based on lipidomics and specific probes enabling membrane lipid imaging by super resolution microscopy, we demonstrate that Dia2 is required for proper assembly of sphingomyelin and cholesterol lipid complexes. Finally, we show that the disorganization of lipid nanodomains induced by Dia2 depletion results in drastic changes in nano-partitioning and activity of other membrane proteins, such as Thy1 and PD-L1. Our data establish, therefore, the central role of the RhoA-Dia2 axis in the regulation of IFN-γ induced JAK/STAT signaling, and more broadly, in the nanoscale organization of the plasma membrane.
Locus Coeruleus Norepinephrine Neurons Facilitate Orbitofrontal Cortex Remapping and Behavioral Flexibility
Authors: Ogg M. Cameron , Franks Hunter T. , Lansdell Benjamin J. , Hughes Alex C. , Lee Jimin , Nolen Hunter G. , Shirinifard Abbas , Schwarz Lindsay A. 
Published: December 2023

SUMMARYTo guide behavior, brain regions such as the orbitofrontal cortex (OFC) retain complex information about current tasks and expected outcomes in cellular representations referred to as cognitive maps. When actions produce undesirable results, OFC cognitive maps must update to promote behavioral change. Here, we show that this remapping is driven by the locus coeruleus (LC), a small brainstem nucleus that contains most of the brain’s norepinephrine (NE)-releasing neurons. In a task that tests behavioral flexibility in rodents, LC-NE activity correlated with task acuity and altered depending on trial outcome. Silencing LC neurons caused perseverative behavior and impeded cognitive remapping in OFC, while enhancing LC activity disrupted the ability of new maps to stabilize. These findings reveal a novel role for bidirectional LC-NE signaling in regulation of OFC cognitive map stability and promotion of flexible behavior that differs from the traditional function of this circuit as a global arousal signal.