bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimised oxygenation improves functional capacity during daily activities in patients with COPD on long-term oxygen therapy – a randomised crossover trial
Authors: Kofod Linette Marie , Hansen Ejvind Frausing , Brocki Barbara Cristina , Kristensen Morten Tange , Roberts Nassim , Westerdahl Elisabeth 
Published: May 2024

ABSTRACTBackgroundMinimising hypoxemia during submaximal walking tests has a positive effect on exercise capacity and dyspnea in patients with COPD on long-term oxygen therapy (LTOT). However, the impact of optimising oxygenation during everyday tasks remains unexplored. Therefore, we investigated the effects of maintaining a target saturation on activities of daily living (ADL) using automated oxygen titration compared to conventional fixed oxygen flow.MethodsIn a double-blinded, randomised crossover trial, 31 patients with COPD on LTOT performed two GlittreADL tests to assess the functional capacity of everyday activities using a) their fixed oxygen dose and b) an adjusted flow from 0-8 L/min targeting a SpO2of 90-94%. A closed-loop device automatically titrated the oxygen based on information from a Bluetooth wrist pulse oximeter.ResultsThe patients reduced the time to perform the ADL-test by median (IQR) 38 (12–73) seconds, p<0.001, using automated titration compared to the fixed oxygen flow. The oxygen flow in the automated arm more than tripled to 5.4 (4.1–6.8) vs. 1.6 (1.1–2.1) L/min (fixed) during the test, p<0.001, while the time spent within SpO2-target was increased from 19% to 49%, p=0.002. Correspondingly, the patients experienced less dyspnea (BorgCR10); 5 (3–7) vs. 6 (4–8), p<0.001, in favour of the automated oxygen titration.ConclusionsImproving oxygenation and extending the time spent within target saturation reduced dyspnea and improved functional capacity in activities of daily living in patients with COPD on LTOT.Trial registration numberNCT05553847
Home and wild food procurement was associated with greater intake of fruits and vegetables during the COVID-19 pandemic in northern New England
Authors: McCarthy Ashley C. , Angle Ashleigh , Bliss Sam , Bertmann Farryl , Belarmino Emily H. , Rose Kelsey , Niles Meredith T. 
Published: May 2024

AbstractObjectiveThis study examined the effect of home and wild food procurement (HWFP) activities (i.e., gardening, hunting, fishing, foraging, preserving food, raising livestock, and raising poultry for eggs) on food security status, fruit and vegetable intake, and meat consumption.DesignWe used data collected in 2021 and 2022 through two statewide representative surveys (n = 2,001). Dietary intake was assessed using the Dietary Screener Questionnaire. We analyzed the data using linear regression, logistic regression, and ordinal logistic regression models.SettingMaine and Vermont, United StatesParticipants2,001 adults (18 years and older)ResultsSixty-one percent of respondents engaged in HWFP activities; the majority of those gardened. Households engaging in most individual HWFP activities had greater odds of being food insecure. HWFP engagement was positively associated with fruit and vegetable consumption. Specifically, gardening was associated with an additional one cup-equivalent in fruit and vegetable consumption per week compared to respondents that did not garden. Furthermore, when exploring these relationships disaggregated by food security status, we find that this effect is stronger for food insecure households than food secure households. Respondents from households that hunted were more likely to eat wild game meat and also consumed red and white meat more frequently compared to households that did not hunt.ConclusionOverall, our results indicate potential public health and food security benefits from engaging in HWFP activities. Future research should continue to examine a full suite of HWFP activities and their relationship to diet, health, and food security.
Brain lesions causing parkinsonism versus seizures map to opposite brain networks
Authors: Schaper Frederic L.W.V.J. , Morton-Dutton Mae , Drew William , Khosravani Sanaz , Joutsa Juho , Fox Michael D. 
Published: May 2024

AbstractRecent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and utilized human connectome data to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatialr=-0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific for lesions causing parkinsonism versus seizures on a group level (spatialr=- 0.51) and on an individual lesion level (average spatialr=-0.042; p<0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatialr>0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.
Why do different people with Spinal Cord Injury have differing severity of symptoms with Autonomic Dysreflexia? Exploring relationships of vascular alpha-1 adrenoreceptor and baroreflex sensitivity after SCI
Authors: Higano Jennifer Dens , Burns Kathryn , Smith Geoffrey , Solinsky Ryan 
Published: May 2024

ABSTRACTIntroductionIndividuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness.ObjectiveTo evalate relationship between baroreflex and blood vessel sensitivity with autonomic dysreflexia symptoms.DesignCase controlSettingTertiary academic centerPatients14 individuals with SCI, 17 matched uninjured controlsInterventionsAll participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)-AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15-40 mmHg. Continuous heart rate (R-R interval, ECG), beat-to-beat blood pressures (finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated.Main outcome measuresBaroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2-minute area under the curve and change in vascular resistance.ResultsSCI and control cohorts were well-matched with mean age 31.9 and 29.6 years (p=0.41), 21.4% and 17.6% female respectively. Baseline MAP (p=0.83) and R-R interval (p=0.39) were similar. ADFSCI-AD scores were higher following SCI (27.9+/-22.9 vs 4.2+/-2.9 in controls, p=0.002).To quantify SBP response, MAP area under the curve was normalized to dose/bodyweight. Individuals with SCI had significantly larger responses (0.26+/-0.19 mmHg*s/kg*ug) than controls (0.06+/-0.06 mmHg*s/kg*ug, p=0.002). Similarly, leg vascular resistance increased after SCI (24% vs 6% to a normalized dose, p=0.007). Baroreflex sensitivity was significantly lower after SCI (15.0+/-8.3 vs 23.7+/-9.3 ms/mmHg, p=0.01). ADFSCI-AD subscore had no meaningful correlation with vascular responsiveness (R2=0.008) or baroreflex sensitivity (R2=0.092) after SCI.ConclusionsWhile this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms to explain why some individuals with SCI develop symptoms is needed.
Self-determination in minoritized autistic adolescents and adults
Authors: Girolamo Teresa , Birmingham Marissa , Patel Karina , Ghali Samantha , Campos Iván , Greene-Pendelton Kyle , Canale Rebecca , Larson Caroline , Sterling Audra , Shogren Karrie A. 
Published: May 2024

AbstractSelf-determination plays an important role in outcomes in autism and shows intersectional disparities. Yet, little is known about the role of individual differences or social drivers of health in the development of self-determination. Understanding these factors is key for developing effective supports. This mixed-methods convergent study examined self-determination in racially and ethnically minoritized autistic individuals and caregivers. Participants ages 13 to 30 (N= 73) varying widely in language and cognitive ability and caregivers (n=52) completed the Self-Determination Inventory. Autism traits and sense of community predicted caregiver report of self-determination, and autism traits and language predicted self-report of self-determination, consistent with DisCrit and Diversity Science. Self-Determination Inventory interviews of a subset of participants (n= 13) and caregivers (n= 9) were analyzed using inductive thematic analysis. Themes pointed to the role of the intersection of race and disability in shaping self-determination. Altogether, findings point to the importance of these frameworks, environmental influences, and multi-informant perspectives in characterizing self-determination. Future work should focus on the impact of environmental factors in self-determination in minoritized autistic individuals during the transition to adulthood.
Sexually dimorphic phenotypes and the role of androgen receptors in UBE3A-dependent autism spectrum disorder
Authors: Tian Yuan , Qiao Hui , Zhu Ling-Qiang , Man Heng-Ye 
Published: May 2024

AbstractAutism spectrum disorders (ASDs) are characterized by social, communication, and behavioral challenges.UBE3Ais one of the most common ASD genes. ASDs display a remarkable sex difference with a 4:1 male to female prevalence ratio; however, the underlying mechanism remains largely unknown. Using the UBE3A-overexpressing mouse model for ASD, we studied sex differences at behavioral, genetic, and molecular levels. We found that male mice with extra copies ofUbe3Aexhibited greater impairments in social interaction, repetitive self-grooming behavior, memory, and pain sensitivity, whereas female mice with UBE3A overexpression displayed greater olfactory defects. Social communication was impaired in both sexes, with males making more calls and females preferring complex syllables. At the molecular level, androgen receptor (AR) levels were reduced in both sexes due to enhanced degradation mediated by UBE3A. However, AR reduction significantly dysregulated AR target genes only in male, not female, UBE3A-overexpressing mice. Importantly, restoring AR levels in the brain effectively normalized the expression of AR target genes, and rescued the deficits in social preference, grooming behavior, and memory in male UBE3A-overexpressing mice, without affecting females. These findings suggest that AR and its signaling cascade play an essential role in mediating the sexually dimorphic changes in UBE3A-dependent ASD.
Context specific ubiquitin modification of ribosomes regulates translation under oxidative stress
Authors: Dougherty Shannon E. , Barros Géssica C. , Foster Matthew W. , Teo Guoshou , Choi Hyungwon , Silva Gustavo M. 
Published: May 2024

ABSTRACTCellular exposure to stress is known to activate several translational control pathways through ribosome ubiquitination. However, how unique patterns of ribosome ubiquitination act at the site-specific level to drive distinct modes of translation regulation remains unclear. To further understand the complexity of these ubiquitin signals, we developed a new targeted proteomics approach to quantify site-specific ubiquitin modification across the ribosome. This method increased the sensitivity and throughput of current approaches and allowed us to systematically measure the ubiquitin status of 78 ribosome peptides and ubiquitin linkages in response to stress. Using this method, we were able to detect the ubiquitination of several ribosome sites even in steady-state conditions, and to show that their modification increases non-stoichiometrically in a dynamic range of >4 orders of magnitude in response to hydrogen peroxide. Besides demonstrating new patterns of global ribosome ubiquitination, our study also revealed an unexpected increase of ubiquitination of ribosomal protein uS10/Rps20 and uS3/Rps3 independent of the canonical E3 ubiquitin ligase Hel2. Furthermore, we show that unique and mixed patterns of ribosome ubiquitination occur in a stress specific manner, depending on the nature of stressor and the enzymes involved. Finally, we showed that while deletion ofHEL2further induces the integrated stress response in response to the nucleotide alkylating agent 4-NQO, deletion of the E2 conjugaseRAD6leads to sustained translation only in response to H2O2. Our findings contribute to deciphering the complexity of the stress response at the translational level, revealing the induction of dynamic and selective ubiquitin codes, which shed light on the integration of important quality control pathways during cellular response to stress.
Data-driven prediction of spinal cord injury recovery: an exploration of current status and future perspectives
Authors: Håkansson Samuel , Tuci Miklovana , Bolliger Marc , Curt Armin , Jutzeler Catherine R. , Brüningk Sarah 
Published: May 2024

AbstractSpinal Cord Injury (SCI) presents a significant challenge in rehabilitation medicine, with recovery outcomes varying widely among individuals. Machine learning (ML) is a promising approach to enhance the prediction of recovery trajectories, but its integration into clinical practice requires a thorough understanding of its efficacy and applicability. We systematically reviewed the current literature on data-driven models of SCI recovery prediction. The included studies were evaluated based on a range of criteria assessing the approach, implementation, input data preferences, and the clinical outcomes aimed to forecast. We observe a tendency to utilize routinely acquired data, such as International Standards for Neurological Classification of SCI (ISNCSCI), imaging, and demographics, for the prediction of functional outcomes derived from the Spinal Cord Independence Measure (SCIM) III and Functional Independence Measure (FIM) scores with a focus on motor ability. Although there has been an increasing interest in data-driven studies over time, traditional machine learning architectures, such as linear regression and tree-based approaches, remained the overwhelmingly popular choices for implementation. This implies ample opportunities for exploring architectures addressing the challenges of predicting SCI recovery, including techniques for learning from limited longitudinal data, improving generalizability, and enhancing reproducibility. We conclude with a perspective, highlighting possible future directions for data-driven SCI recovery prediction and drawing parallels to other application fields in terms of diverse data types (imaging, tabular, sequential, multimodal), data challenges (limited, missing, longitudinal data), and algorithmic needs (causal inference, robustness).
Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)
Authors: Ghosh Gautam , Neely Benjamin A. , Bland Alison M. , Whitmer Emily R. , Field Cara L. , Duignan Pádraig J. , Janech Michael G. 
Published: May 2024

AbstractSince 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis have consistently increased. Outside of direct measurement of DA in bodily fluids at the time of stranding, currently there are no practical non-lethal clinical tests for the diagnosis of domoic acid toxicosis (DAT) that can be utilized in a large-scale rehabilitation facility. Proteomic analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide (FDR < 0.01). Of these proteins, 83 were significantly different in abundance across the three groups (adj. p < 0.05). Cytoplasmic malate dehydrogenase (MDH1), 5’-3’ exonuclease PLD3, disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), 14-3-3 protein gamma (YWHAG), neurosecretory protein VGF, and calsyntenin-1 (CLSTN1) were able to discriminate California sea lions with or without DAT (ROC > 0.75). Immunoglobulin kappa light chain-like (IGKV2D-28), receptor-type tyrosine-phosphatase F (PTRPF), kininogen-1 (KNG1), prothrombin (F2), and beta-synuclein (SNCB) were able to discriminate acute DAT from chronic DAT (ROC > 0.75). Interestingly, proteins involved in alpha synuclein deposition were over- represented as classifiers of DAT and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions, as well as markers to discriminate between acute or chronic DAT, and should be considered priority for future validation studies as biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD041356 (http://proteomecentral.proteomexchange.org/dataset/PXD041356).
Pools of independently cycling inositol phosphates revealed by pulse labeling with18O-water
Authors: Kim G. , Liu G. , Qiu D. , Gopaldass N. , De Leo G. , Hermes J. , Timmer J. , Saiardi A. , Mayer A. , Jessen H.J. 
Published: May 2024

AbstractInositol phosphates control many central processes in eukaryotic cells, including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate rapid (seconds to minutes), non-radioactive labeling of inositol polyphosphates through18O-water in yeast, amoeba and human cells, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry,18O-water labeling simultaneously dissects thein vivophosphate group dynamics of a broad spectrum of even rare inositol phosphates. The improved temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol poly- and pyrophosphates, whereas others remain remarkably inert. Our observations support a model in which the biosynthetic pathway of inositol poly- and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected.
Combining data independent acquisition with spike-in SILAC (DIA-SiS) improves proteome coverage and quantification
Authors: Welter Anna Sophie , Gerwien Maximilian , Kerridge Robert , Alp Keziban Merve , Mertins Philipp , Selbach Matthias 
Published: May 2024

AbstractData Independent Acquisition (DIA) is increasingly preferred over Data Dependent Acquisition (DDA) due to its higher throughput and fewer missing values. Whereas DDA often utilizes stable isotope labeling to improve quantification, DIA mostly relies on label-free approaches. Efforts to integrate DIA with isotope labeling include chemical methods like mTRAQ and dimethyl labeling, which, while effective, complicate sample preparation. Stable isotope labeling by amino acids in cell culture (SILAC) achieves high labeling efficiency through the metabolic incorporation of heavy labels into proteinsin vivo. However, the need for metabolic incorporation limits the direct use in clinical scenarios. Spike-in SILAC methods utilize an externally generated heavy sample as an internal reference, enabling SILAC-based quantification even for samples that cannot be directly labeled. Here, we combine DIA with spike-in SILAC (DIA-SiS), leveraging the robust quantification of SILAC without the complexities associated with chemical labeling. We developed and rigorously validated DIA-SiS through a mixed-species benchmark to assess its performance in proteome coverage and quantification. We demonstrate that DIA-SiS significantly improves proteome coverage and quantification compared to label-free approaches and reduces the incidence of incorrectly quantified proteins. Additionally, DIA-SiS proves effective in analyzing proteins in low-input formalin-fixed paraffin-embedded (FFPE) tissue sections. DIA-SiS combines the precision of stable isotope-based quantification with the simplicity of label-free sample preparation, facilitating simple, accurate and comprehensive proteome profiling.
Protective role of parenthood on age-related brain function in mid- to late-life
Authors: Orchard Edwina R. , Chopra Sidhant , Ooi Leon Q.R. , Chen Pansheng , An Lijun , Jamadar Sharna D. , Yeo B.T. Thomas , Rutherford Helena J.V. , Holmes Avram J. 
Published: May 2024

AbstractThe experience of parenthood can profoundly alter one’s body, mind, and environment, yet we know little about the long-term associations between parenthood and brain function and aging in adulthood. Here, we investigate the link between number of children parented (parity) and age on brain function in 19,964 females and 17,607 males from the UK Biobank. In both females and males, increased parity was positively associated with functional connectivity, particularly within the somato/motor network. Critically, the spatial topography of parity-linked effects was inversely correlated with the impact of age on functional connectivity across the brain for both females and males, suggesting that a higher number of children is associated with patterns of brain function in the opposite direction to age-related alterations. These results indicate that the changes accompanying parenthood may confer benefits to brain health across the lifespan, highlighting the importance of future work to understand the associated mechanisms.