bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informant-rated change in personality traits, psychological distress, well-being, and social connection with dementia
Authors: Sutin Angelina R. , Luchetti Martina , Stephan Yannick , Terracciano Antonio 
Published: August 2023

AbstractObjectives:Studies of retrospective personality change with dementia consistently find caregivers report large changes in personality (e.g., increases in neuroticism) of their care recipients compared to before dementia. This work seeks to replicate the established pattern of personality change, extend it to change in psychological distress, well-being, and social connection, and evaluate whether changes vary by stage of dementia.Methods:Caregivers of people with dementia (N=194) reported on the psychological and social health of their care recipient currently and how they were before they developed dementia. Personality was measured as five factor model traits. Psychological distress was measured as symptoms of depression and anxiety, perceived stress, and pessimism. Psychological well-being was measured as purpose in life, life satisfaction, happiness, self-efficacy, and optimism. Social connection was measured as loneliness, belonging, social support, and social strain.Results:There were substantial increases in neuroticism (d=1.10) and decreases in the other four personality traits (drange=-.82 to −1.31). There were significant increases in psychological distress (e.g.,d=1.05 for depression) and substantial decreases in well-being (e.g.,d=-1.07 for purpose in life) and social connection (e.g.,d=-1.09 for belonging). Change was apparent across dementia stage and generally larger in more severe dementia.Discussion:In addition to personality, there are large retrospective changes in psychological distress, well-being, and social connection with dementia. These quantitative findings complement clinical observations of the natural history of psychosocial changes in people with dementia, and can inform families, clinicians, and researchers on commonly observed changes and improve interventions to mitigate dementia burden.
Increasing emergency department referral of chest pain patients for non-invasive cardiac testing does not improve two-year clinical outcomes
Authors: Mark Dustin G. , Huang Jie , Ballard Dustin W. , Vinson David R. , Rana Jamal S. , Sax Dana R. , Rauchwerger Adina S. , Reed Mary E. ,   the Kaiser Permanente CREST Network Investigators
Published: August 2023

AbstractBackgroundNon-invasive cardiac testing (NICT) has been associated with decreased long-term risks of major adverse cardiac events (MACE) among emergency department (ED) patients at high coronary risk. It is unclear whether this association extends to patients without evidence of myocardial injury on initial electrocardiogram and cardiac troponin testing.MethodsRetrospective cohort study of patients presenting with chest pain between 2013-2019 to 21 EDs within an integrated health care system, excluding patients with ST-elevation myocardial infarction or myocardial injury by serum troponin testing. To account for confounding by indication, we grouped patient encounters by the NICT referral rate of the initially assigned emergency physician, relative to local peers within discrete time periods. The primary outcome was MACE within two years. Secondary outcomes were coronary revascularization and MACE inclusive of all-cause mortality (MACE-ALL). Associations between NICT referral group (low, intermediate, or high) and outcomes were assessed using risk-adjusted proportional hazards methods with censoring for competing events.ResultsAmong 144,577 eligible patient encounters, 30-day NICT referral was 13.0%, 19.9% and 27.8% in low, intermediate, and high NICT referral groups, respectively, with good balance of baseline covariates between groups. Compared with the low group, there was no significant decrease in the adjusted hazard ratio (aHR) of MACE within the intermediate (aHR 1.08, 95% CI 1.02-1.14, adjusted p = 0.024) or high (aHR 1.05, 95% CI 0.99-1.11, adjusted p = 0.13) NICT referral groups. Results were similar for MACE-ALL and coronary revascularization, as well as subgroup analyses stratified by estimated risk (HEART score; 48.2% low-risk, 49.2% moderate-risk, 2.7% high-risk).ConclusionIncreased NICT referral was not associated with a decreased hazard of MACE within two years following ED visits for chest pain without evidence of acute myocardial injury. These findings further highlight the need for evidence-based guidance regarding appropriate use of NICT in this population.What is KnownIn emergency department patients with chest pain but no evidence of acute myocardial injury, referral for non-invasive cardiac testing is not associated with improved outcomes within 6 to 12 months.There is some evidence that non-invasive cardiac testing may improve longer-term outcomes, especially among patients at moderate to high risk of coronary disease.What the Study AddsHigher non-invasive cardiac testing was not associated with improved outcomes within two years following emergency department visits for chest pain, absent evidence of acute myocardial injury.This finding was most evident among patients at low to moderate predicted coronary risk.
Linking cognitive integrity to working memory dynamics in the aging human brain
Authors: Monov G , Stein H , Klock L , Gallinat J , Kühn S , Lincoln T , Krkovic K , Murphy PR , Donner TH 
Published: August 2023

AbstractAging is accompanied by a decline of multiple cognitive capacities, including working memory: the ability to maintain information online for the flexible control of behavior. Working memory involves stimulus-selective neural activity, persisting after stimulus presentation in widely distributed cortical areas. Here, we unraveled the mechanisms of working memory in healthy older adults and patients with mild cognitive impairment (MCI), a condition associated with increased risk of developing dementia. We studied a sample of 19 older adults diagnosed with MCI and 20 older healthy controls using a combination of model-based behavioral psychophysics, neuropsychological assessment, and magnetoencephalographic (MEG) recordings of brain activity. Twenty-one younger healthy adults were studied with model-based behavioral psychophysics only. All subjects performed a visuo-spatial delayed-match-to-sample working memory task under systematic manipulation of the temporal delay and the spatial distance between successively presented sample and test stimuli. We developed a computational model of the latent dynamics underlying task behavior and fit this to individual behavior. In the model, working memory representations diffused over time, a threshold was applied to produce a match/non-match decision about sample and test locations, and occasional lapses produced random decisions. For the older participants, we related the individual model parameters to a summary measure of individual cognitive integrity obtained from a large neuropsychological test battery, as well as to cortical MEG activity during the delay interval of the working memory task. For all groups, task accuracy decreased with delay duration and sample-test distance. When sample/test distances were small, older adults exhibited larger false alarm rates than younger adults. The behavioral effects were well captured by the model, which explained the age-related differences in terms of a deterioration of the quality of working memory representations, rather than differences in task strategy (i.e., threshold parameter). Task accuracy as well as the parameters governing behavioral stochasticity (diffusion noise and lapse rate combined) were correlated with overall cognitive integrity in the MCI group, but not in the older healthy controls. Individual task accuracy and stochasticity parameters (diffusion noise and lapse rate) were also correlated with stimulus-selective cortical activity during the delay interval, as assessed by decoding of the MEG signals, corroborating their validity as markers of cortical working memory mechanisms. Our findings provide insight into the mechanistic basis of aging-related changes in working memory maintenance and reveal a link between individual working memory dynamics and cognitive integrity in MCI.
Parallel trophic diversifications in polyploid cyprinid fish from East Africa: from preadaptive polymorphism to trophic specialization
Authors: Levin Boris A. , Komarova Aleksandra S. , Tiunov Alexei V. , Golubtsov Alexander S. 
Published: August 2023

AbstractTrophic diversification is one of the main mechanisms driving the adaptive radiation. The polyploid lineage of the cyprinid genusLabeobarbusrepresent an excellent model for studying the trophically-based adaptive radiation in either lacustrine or riverine environments. Recently discovered four diversifications in rivers of the Ethiopian Highlands (East Africa) demonstrate independently evolved repeated mouth polymorphisms each represented by four core mouth phenotypes: (i) generalized, (ii) thick-lipped, (iii) scraping, and iv) large-mouthed. Mouth phenotypes in some radiations can be further divided to subtypes representing from four to eight sympatric ecomorphs. Using the stable isotope and gut content analyses we tested hypothesis on trophic resource partitioning within each radiation, revealed disparity in degree of diversification between radiations and tried to reconstruct the process of trophic diversification. Three of four radiations demonstrated partitioning of trophic resources within five trophic niches: i) detritophagy, ii) macrophytophagy, iii) invertivorous benthophagy, iv) periphyton feeding, and v) piscivory. The studied riverine radiations were likely at the different stages of the diversification. One radiation having a similar set of mouth phenotypes was not trophically divergent displaying a remarkable decouple of form and function. A unique case of ecologically non-functional mouth polymorphism at an incipient stage of trophic diversification supports a concept of the plasticity-first evolution. This phenomenon stems from the pre-existing genomic templates of mouth polymorphism ancestrally inherited upon the allopolyploid origin of theLabeobarbuslineage. The predetermined and preadaptive mouth polymorphism can be considered a key innovation of theLabeobarbusthat promoted to resource-based diversification via adaptive radiation.
An extracellular vesicle delivery platform based on the PTTG1IP protein
Authors: Perez Carla Martin , Liang Xiuming , Gupta Dhanu , Conceição Mariana , Mäger Imre , Andaloussi Samir EL , Wood Matthew J.A. , Roberts Thomas C. 
Published: August 2023

AbstractExtracellular vesicles (EVs) hold great promise as therapeutic delivery vehicles, although their potential is limited by a lack of efficient EV engineering strategies to enhance loading and functional delivery of therapeutic cargo. Here, we identified N-glycosylation as a putative EV- sorting feature using a novel bioinformatics analysis strategy. We exploited this finding to develop a platform for EV-mediated delivery of macromolecular cargoes based on PTTG1IP, a small N- glycosylated, single spanning transmembrane protein. We demonstrate that PTTG1IP EV enrichment is dependent on its N-glycosylation at two sites, and that PTTG1IP is a suitable scaffold for EV loading of therapeutic cargoes. To achieve functional delivery, cargoes were fused to PTTG1IP, separated by various self-cleaving sequences intended to promote cargo release from the scaffold after EV loading. In addition, the fusogenic VSVG protein was co-expressed to enhance endosomal escape. This PTTG1IP-based strategy enabled highly efficient functional delivery of Cre protein to recipient cells and mouse xenograft tumors, as well as Cas9 and Cas9/sgRNA complex delivery to reporter cells. Importantly, PTTG1IP exhibited improved protein delivery potential relative to a scaffold based on CD63 (a common EV marker). Moreover, we developed various PTTG1IP variants with improved properties, demonstrating the versatility of PTTG1IP as an EV scaffold. The EV-loading platform described in this study offers significant advantages over other strategies, such as favourable membrane topology, the potential for further engineering, and functional delivery capability, which will enable the development of improved EV-based therapeutics.
Consensus prediction of cell type labels with popV
Authors: Ergen Can , Xing Galen , Xu Chenling , Jayasuriya Michael , McGeever Erin , Pisco Angela Oliveira , Streets Aaron , Yosef Nir 
Published: August 2023

AbstractCell-type classification is a crucial step in single-cell analysis. To facilitate this, several methods have been proposed for the task of transferring a cell-type label from an annotated reference atlas to unannotated query data sets. Existing methods for transferring cell-type labels lack proper uncertainty estimation for the resulting annotations, limiting interpretability and usefulness. To address this, we propose popular Vote (popV,https://github.com/YosefLab/popV), an ensemble of prediction models with an ontology-based voting scheme. PopV achieves accurate cell-type labeling and provides effective uncertainty scores. In multiple case studies, popV confidently annotates the majority of cells while highlighting cell populations that are challenging to annotate. This additional step helps to reduce the load of manual inspection, which is often a necessary component of the annotation process, and enables one to focus on the most problematic parts of the annotation, streamlining the overall annotation process.
Longevity Bottlenecks
Authors: Florea Michael , Hamalainen Mark , Seebold Patrick , Cheng Nathan , Murray Paul , Colville Alex James , Zheng Sally , Ingham Dylan , Kantelal Ridhi , De Sicilia Rose ,   (Longevity Biotech Fellowship consortium)
Published: August 2023

AbstractThe longevity field has received an influx of capital and talent over the past 5 years, but it is unclear where directing these resources would result in the biggest positive impact. We aimed to establish a systematic, rigorous and unbiased way to identify the areas where increased investment would accelerate progress across the whole longevity field the most. To do so, we surveyed ∼400 participants across various sectors of longevity, asking them to 1) identify the major bottlenecks they are experiencing, 2) list their most needed solution, and 3) rate the potential efficacy and barriers to development of various aging intervention strategies. We built a classification system of Bottlenecks and Solutions based on grouping related answers and found the most frequently listed bottlenecks to be 1) lack of validated aging biomarkers; 2) an overall lack of funding; and 3) lack of good models for aging studies. Surprisingly, the most wanted solution was greater availability of large public datasets. Indeed, a common theme across all answers was the need for a new data-centric structure of scientific research, where large datasets are routinely gathered and made available, access walls are removed, protocols are standardized, negative and unpublished data are shared, and AI systems are released on the data for automated discovery. Finally, a lack of regulatory clarity was listed as the biggest barrier to development across all interventions, whereas cellular reprogramming, organ replacement, and genetic medicine (gene therapies and gene editing) were perceived as the intervention strategies with the highest potential for increasing healthy lifespan. We provide these data as a resource for funding agencies, philanthropists, entrepreneurs and newcomers to the field as a means to identify high impact areas to fund and work on.Key takeaways395 Participants were surveyed for their biggest bottlenecks and most needed solutionsTop Bottlenecks: lack of Validated Biomarkers; Overall lack of Funding and Slow & Expensive Models.Top proposed Solutions: more Public Datasets; improved Regulatory Path; and Overall More Funding.Bottlenecks and Solutions vary substantially across industry areas.Rapamycin and calorie restriction are perceived as the most efficacious interventions in the near term.Somatic reprogramming, organ replacement, and genetic medicine are perceived as the most efficacious interventions in the long term (25 years).Sirtuin and NAD targeting therapies are seen as the least efficacious interventions in all time-frames.Across all interventions, Regulatory Issues are perceived as the most severely inhibiting factor in the development of the intervention.
Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis - Insights from structural connectome graph theoretical network analysis
Authors: Hechler André , Kuchling Joseph , Müller-Jensen Leonie , Klag Johanna , Paul Friedemann , Prüss Harald , Finke Carsten 
Published: August 2023

AbstractIntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis.ObjectiveTo investigate changes in structural connectivity and network efficiency in NMDAR encephalitis by use of probabilistic whole-brain tractography and graph theoretical analysis of structural brain networks.MethodsStructural networks from sixty-one NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and sixty-one age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically-constrained tractography and spherical deconvolution-informed filtering of tractograms. We calculated global, modular, and nodal graph measures indicative of structural connectivity and network reorganization with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were included in multiple regression analyses to investigate their potential association with clinical course, disease severity, and cognitive outcome.ResultsPatients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left:p=0.049; right:p=0.013) and increased node strength of right precuneus (p=0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p=0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p=0.021)ConclusionFocal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.
Partial Anchored Capture and Long-Read Sequencing (PACLseq) Enable a Stand-alone Diagnostic Method for Ph-like Acute Lymphoblastic Leukemia
Authors: Zhang Hang , Yu Huan , Chen Yanmei , Jiang Kai , Huo Beibei , Li Jialin , Liu Ting , Xie Dan 
Published: August 2023

AbstractFusion genes play a crucial role in the development of Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL). Timely and accurate determination of malgenic fusion transcripts that cause Ph-like ALL is essential for guiding treatment decisions. However, due to the complexity of possible gene fusion combination of Ph-like ALL, prevailing molecular diagnostic methods for Ph-like ALL are inefficient and lack of standardization, resulting in a slow diagnostic process. We introduce Partial Anchored Capture and Long-Read Sequencing (PACLseq), a nanopore-sequencing-technology-based approach, which enables fast stand-alone identification of fusion genes with a mere 10ng of input RNA. With extensive testing using BCR-ABL1 standards and 47 clinical samples to validate the efficacy of PACLseq, we demonstrated that PACLseq performs excellently in target region coverage and fusion gene detection accuracy, achieving a sensitivity of 93.33% and specificity of 100%. These findings highlight the reliability and versatility of PACLseq as a streamlined method for the clinical diagnosis of Ph-like ALL. By offering rapid and accurate fusion gene detection, PACLseq has the potential to significantly improve diagnostic efficiency, facilitate timely treatment decisions, and enhance patient outcomes in the management of Ph-like ALL.
Nigral volume loss in prodromal, early, and moderate Parkinson’s disease
Authors: Langley Jason , Hwang Kristy S. , Huddleston Daniel E. , Hu Xiaoping P. 
Published: August 2023

AbstractThe loss of melanized neurons in the substantia nigra pars compacta (SNc) is a hallmark pathology in Parkinson’s disease (PD). Melanized neurons in SNc can be visualizedin vivousing magnetization transfer (MT) effects. Nigral volume was extracted in data acquired with a MT-prepared gradient echo sequence in 33 controls, 83 non-manifest carriers (42 LRRK2 and 41 GBA nonmanifest carriers), 65 prodromal hyposmic participants, 105de novoPD patients and 26 48-month PD patients from the Parkinson’s Progressive Markers Initiative. No difference in nigral volume was seen between controls and LRRK2 and GBA non-manifest carriers (F=0.076;P=0.927). A significant main effect in group was observed between controls, prodromal hyposmic participants, and overt PD patients (F=5.192;P=0.002). Longer disease duration significantly correlated with lower nigral volume (r=-0.252;P=0.010). This study shows that nigral depigmentation can be robustly detected in prodromal hyposmic participants and overt PD patients.