bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent changes in sleep and cognitive function during retirement transition: the Finnish Retirement and Aging Study
Authors: Teräs Tea , Myllyntausta Saana , Pentti Jaana , Pasanen Jesse , Rovio Suvi , Stenholm Sari 
Published: May 2024

ABSTRACTBackgroundThe transition to retirement has been shown to be accompanied by increased sleep duration and improved sleep quality. In addition, some studies suggest accelerated decline in cognitive function in post-retirement years. However, less is known about their interconnectedness. The aim of this study was to examine the concurrent changes in sleep and cognitive function during retirement transition.MethodsThe study population consisted of 250 public sector workers (mean age before retirement 63.1 years, standard deviation 1.4) from the Finnish Retirement and Aging study. The participants used a wrist-worn ActiGraph accelerometer, responded to the Jenkins Sleep Problem Scale and underwent cognitive testing annually before and after retirement. Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB®) was used to evaluate learning and memory, working memory, sustained attention and information processing, executive function and cognitive flexibility and reaction time.ResultsCognitive function improved in all cognitive domains, except for reaction time, during 1- year retirement transition period. The improvement was temporary in learning and memory, working memory and executive function and cognitive flexibility, which plateaued in post- retirement years. The participants were categorized into constantly short (49%), increasing (20%), decreasing (6%), and constantly mid-range (25%) sleep duration; and constantly without (36%), increasing (10%), decreasing (16%), and constantly with (38%) sleep difficulties. There were no associations between changes in sleep duration or sleep difficulties and cognitive function during retirement transition.ConclusionsCognitive function improves temporarily during transition to retirement, but the improvement is independent of changes in sleep characteristics.
Neurobiology-based Cognitive Biotypes Using Multi-scale Intrinsic Connectivity Networks in Psychotic Disorders
Authors: Andrés-Camazón Pablo , Martínez Diaz-Caneja Covadonga , Ballem Ram , Chen Jiayu , Calhoun Vince D. , Iraji Armin 
Published: May 2024

ABSTRACTObjectiveUnderstanding the neurobiology of cognitive dysfunction in psychotic disorders remains elusive, as does developing effective interventions. Limited knowledge about the biological heterogeneity of cognitive dysfunction hinders progress. This study aimed to identify subgroups of patients with psychosis with distinct patterns of functional brain alterations related to cognition (cognitive biotypes).MethodsB-SNIP consortium data (2,270 participants including participants with psychotic disorders, relatives, and controls) was analyzed. Researchers used reference-informed independent component analysis and the NeuroMark 100k multi-scale intrinsic connectivity networks (ICN) template to obtain subject-specific ICNs and whole-brain functional network connectivity (FNC). FNC features associated with cognitive performance were identified through multivariate joint analysis. K-means clustering identified subgroups of patients based on these features in a discovery set. Subgroups were further evaluated in a replication set and in relatives.ResultsTwo biotypes with different functional brain alteration patterns were identified. Biotype 1 exhibited brain-wide alterations, involving hypoconnectivity in cerebellar-subcortical and somatomotor-visual networks and worse cognitive performance. Biotype 2 exhibited hyperconnectivity in somatomotor-subcortical networks and hypoconnectivity in somatomotor-high cognitive processing networks, and better preserved cognitive performance. Demographic, clinical, cognitive, and FNC characteristics of biotypes were consistent in discovery and replication sets, and in relatives. 70.12% of relatives belonged to the same biotype as their affected family members.ConclusionsThese findings suggest two distinctive psychosis-related cognitive biotypes with differing functional brain patterns shared with their relatives. Patient stratification based on these biotypes instead of traditional diagnosis may help to optimize future research and clinical trials addressing cognitive dysfunction in psychotic disorders.
SAFETY AND IMMUNOGENICITY OF A PHH-1V BOOSTER DOSE AFTER DIFFERENT PRIME VACCINATION SCHEMES AGAINST COVID-19: PHASE III CLINICAL TRIAL FINAL RESULTS UP TO ONE YEAR
Authors: Natalini Martínez Silvina , Ramos Rafael , Navarro-Perez Jorge , Lopez Maria Jesus , Vazquez Maria del Mar , Molto Jose , Munoz Patricia , Echave Jose M , Arribas Jose R , Alvarez Melchor , Arana-Arri Eunate , Calls Jordi , Otero-Romero Susana , Scaglione Francesco , Bernad Laia , Pérez-Caballero Raúl , Prado Julia G , Esteban Ignasi , Aurrecoechea Elena , Pomarol Roc , Plana Montserrat , Soriano Alex 
Published: May 2024

AbstractIn this phase III, open label, single arm, multicenter clinical study, we report safety, tolerability and immunogenicity of PHH-1V as a booster dose in subjects primary vaccinated against COVID-19 with the BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S vaccines, with or without previous COVID-19 infection. A total of 2661 subjects were included in this study and vaccinated with the PHH-1V vaccine. Most treatment-emergent adverse events (TEAE) were solicited local and systemic reactions with grade 1 (58.70%) or grade 2 (27.58%) intensity, being the most frequently reported injection site pain (82.83%), fatigue (31.72%) and headache (31.23%). Additionally, immunogenicity was assessed at Baseline and Days 14, 91, 182 and 365 in a subset of 235 subjects primary vaccinated. On Day 14, geometric mean triter (GMT) in neutralizing antibody against SARS-CoV-2 Wuhan and Beta, Delta and Omicron BA.1 variants increased in all primary vaccination with a geometric mean fold raise (GMFR) of 6.90 (95% CI 4.96-9.58), 12.27 (95% CI 8.52-17.67), 7.24 (95% CI 5.06-10.37) and 17.51 (95% CI 12.28-24.97), respectively. Despite GMT decay after day 14, it remains in all cases significatively higher from baseline up to 1 year after PHH-1V booster administration and GMFR against Beta and Omicron BA.1 variants over 3 at 1 year after booster compared to baseline. PHH-1V booster vaccination elicited also a significant RBD/Spike-specific IFN-γ+T-cell responses on Day 14. Overall, PHH-1V vaccine was immunogenic and well-tolerated regardless of the previous primary vaccination scheme received with no reported cases of severe COVID-19 infection throughout the entire study.
Evaluating the Effectiveness of the Mozambique-Canada Maternal Health (MCMH) Project Abstraction Tool in the Identification of Maternal Near-Miss (MNM) Events
Authors: Muosieyiri Maud Z , Andre Fernanda , Forsyth Jessie , Adoni Ana Paula Ferrão da Silva , Muhajarine Nazeem 
Published: May 2024

AbstractMaternal Near-Miss (MNM) is described as a woman who survives a severe obstetric event. The World Health Organization (WHO) developed an abstraction tool in 2009 for identifying MNMs, but it has come under criticism for not being suitable for use in low-resource settings. The maternal near-miss tool developed by the Mozambique-Canada Maternal Health Project, including additional clinical criteria, is an adaptation of the WHO version to suit the resource availability in Mozambique. This study examined whether these additional criteria enhanced maternal near-miss identification; if so, whether this was observed in particular groups of women.A cross-sectional study was conducted in two hospitals, the Provincial Hospital of Inhambane province, a tertiary referral care center, and a rural hospital, Vilankulo Rural Hospital, with a large rural catchment area (approximately 46,543 inhabitants), in the Inhambane province in Mozambique. Consecutive admissions in the maternity wards in these two hospitals between August 2021 and February 2022 were eligible and data from 2057 women were included. Chi-square test of independence, kappa statistics, and multiple logistic regression analyses were performed to address the study aims.The newer tool with additional clinical criteria identified more maternal near-misses (Expanded Disease criterion = 28.2%; Comorbidities criterion = 21.1%) than the original WHO tool (16.20%). Hypertension and Anemia, two criteria in the newer tool, showed strong associations with the original WHO disease criterion (p < 0.001). Hypertension demonstrated a moderate agreement with the WHO disease criterion (κ = 0.58, 95% CI: 0.53-0.63) while anemia showed a fair agreement (κ = 0.21, 95% CI: 0.16-0.26). However, HIV/AIDS, the most prevalent comorbidity, was not significantly associated with the original WHO disease criterion. Furthermore, socio-demographic indicators like distance from home to hospital, age of woman, and type of health facility (provincial or rural district) were significant predictors of identifying maternal near-misses.In conclusion, incorporating additional criteria enhances – it casts a larger net – the original WHO disease criterion’s capacity to identify maternal near-misses. Distance from home to the hospital and age emerge as strong predictors for recognizing MNMs in Inhambane province.
Birds affected by a 2021 avian mortality event are strongly associated with supplemental feeding and ground foraging behaviors
Authors: Ayala Andrea J. , Baillargeon Tessa , Gordon Lawrence M. , Greening Sabrina S. , Mwakibete Lusajo , Sevigny Joseph L. , Burrell Caitlin E. , Casey Christine , Driscoll Cindy P. , Klein Patrice , Lewis Nicole L. , Murphy Lisa A. , Poppenga Robert , Thomas W. Kelly , Yabsley Michael J. , Gagne Roderick B. , Nemeth Nicole M. , Tato Cristina M. , Needle David B. , Ogbunugafor C. Brandon 
Published: May 2024

AbstractIn 2021, news outlets and state natural resources agencies reported a large number of avian deaths across several states in the eastern and midwestern USA. This event fomented a rapid and robust response from animal health experts from across the country. Given the clustered pattern of disease and death, an infectious etiology was rigorously investigated. No single causative pathogen was identified, leaving the cause and thus epidemiology of the mortality event unex-plained. In this study, we attempted to hone in on potential causes or contributors to this event by constructing a dataset on affected birds’ life history, phylogeny, and ecology. After a preliminary analysis of these features, we developed a statistical pipeline to test two hypotheses regarding features of birds associated with the mortality event: (1) that a significant proportion of affected birds in the total sample are members of the Cornell Feederwatch list (i.e., birds that consume supplemental feed, and their predators), and that (2) ground-feeding species would be significantly represented in the sample. While logistic regression models support the plausibility of the two hypotheses, they are statistically indistinguishable. We discuss the implications of these findings, propose future work, and highlight the importance of ecological and behavioral expertise in understanding epidemiological phenomena.
Plasma-derived Extracellular Vesicles (EVs) as Biomarkers of Sepsis in Burn Patients via Label-free Raman Spectroscopy
Authors: O’Toole Hannah J. , Lowe Neona , Arun Vishalakshi , Kolesov Anna V. , Palmieri Tina L. , Tran Nam K. , Carney Randy P. 
Published: May 2024

AbstractSepsis following burn trauma is a global complication with high mortality, with ∼60% of burn patient deaths resulting from infectious complications. Sepsis diagnosis is complicated by confounding clinical manifestations of the burn injury, and current biomarkers markers lack the sensitivity and specificity required for prompt treatment. Circulating extracellular vesicles (EVs) from patient liquid biopsy as biomarkers of sepsis due to their release by pathogens from bacterial biofilms and roles in subsequent immune response. This study applies Raman spectroscopy to patient plasma derived EVs for rapid, sensitive, and specific detection of sepsis in burn patients, achieving 97.5% sensitivity and 90.0% specificity. Furthermore, spectral differences between septic and non-septic burn patient EVs could be traced to specific glycoconjugates of bacterial strains associated with sepsis morbidity. This work illustrates the potential application of EVs as biomarkers in clinical burn trauma care, and establishes Raman analysis as a fast, label-free method to specifically identify features of bacterial EVs relevant to infection amongst the host background.
Dishevelled localization and function are differentially regulated by structurally distinct sterols
Authors: Sengupta Sonali , Yaeger Jazmine D.W. , Schultz Maycie M. , Francis Kevin R. 
Published: May 2024

SUMMARYThe Dishevelled (DVL) family of proteins form supramolecular protein and lipid complexes at the cytoplasmic interface of the plasma membrane to regulate tissue patterning, proliferation, cell polarity, and oncogenic processes through DVL-dependent signaling, such as Wnt/β-catenin. While DVL binding to cholesterol is required for its membrane association, the specific structural requirements and cellular impacts of DVL-sterol association are unclear. We report that intracellular sterols which accumulate within normal and pathological conditions cause aberrant DVL activity.In silicoand molecular analyses suggested orientation of the β- and α-sterol face within the DVL-PDZ domain regulates DVL-sterol binding. Intracellular accumulation of naturally occurring sterols impaired DVL2 plasma membrane association, inducing DVL2 nuclear localization via Foxk2. Changes to intracellular sterols also selectively impaired DVL2 protein-protein interactions This work identifies sterol specificity as a regulator of DVL signaling, suggests intracellular sterols cause distinct impacts on DVL activity, and supports a role for intracellular sterol homeostasis in cell signaling.
Clonal determinants of organotropism and survival in metastatic uveal melanoma
Authors: Jones Bailey S.C.L. , Demkowicz Patrick C. , Matesva Mitchelle , Lim Renelle Pointdujour , Sinard John H. , Bacchiocchi Antonietta , Halaban Ruth , Bosenberg Marcus , Sznol Mario , Kluger Harriet M. , Bakhoum Mathieu F. 
Published: May 2024

AbstractUveal melanoma (UM), the most common intraocular primary cancer in adults, demonstrates a unique proclivity for liver metastasis. To understand the molecular underpinnings of this organotropism, we analyzed the genomic features of liver and extrahepatic UM metastases, identifying distinct molecular signatures that mirror the clonal diversity in primary UM tumors. Liver metastases were enriched inBAP1mutations and exhibited a higher prevalence of monosomy 3 compared to extrahepatic metastases. Analysis of the tumor-liver microenvironment crosstalk at the single-cell level underscored a significant role for hepatic stellate cells in facilitating UM growth and establishment in the liver. Notably, within the primary tumor, clones that demonstrated a high affinity for the liver, compared to those with low liver affinity, exhibited a distinct transcriptional profile characterized by the upregulation of pathways that activate hepatic stellate cells, specifically involving TGF-β signaling, cytokine signaling, extracellular matrix remodeling, and angiogenesis. Liver-tropic clones displayed not only an increased affinity for liver colonization but were also associated with worse survival outcomes, underscoring the adverse prognostic significance of hepatic metastases in UM. Our findings demonstrate that trajectories of metastatic dissemination and patient survival in UM are established early in the primary tumor’s evolution, opening pathways for the development of targeted therapeutic interventions to improve patient outcomes.
Exogenous lipid vesicles induce endocytosis-mediated cellular aggregation in a close unicellular relative of animals
Authors: Kidner Ria Q. , Goldstone Eleanor B. , Rodefeld Henry J. , Brokaw Lorin P. , Gonzalez Aria M. , Ros-Rocher Núria , Gerdt Joseph P. 
Published: May 2024

ABSTRACTCapsaspora owczarzakiis a protozoan that may both reveal aspects of animal evolution and also curtail the spread of schistosomiasis, a neglected tropical disease.Capsasporaexhibits a chemically regulated aggregative behavior that resembles cellular aggregation in some animals. This behavior may have played a key role in the evolution of animal multicellularity. Additionally, this aggregative behavior may be important forCapsaspora’s ability to colonize the intermediate host of parasitic schistosomes and potentially prevent the spread of schistosomiasis. Both applications demand elucidation of the molecular mechanism ofCapsasporaaggregation. Toward this goal, we first determined the necessary chemical properties of lipid cues that activate aggregation. We found that a wide range of abundant zwitterionic lipids induced aggregation, revealing that the aggregative behavior could be activated by diverse lipid-rich conditions. Furthermore, we demonstrated that aggregation inCapsasporarequires clathrin-mediated endocytosis, highlighting the potential significance of endocytosis-linked cellular signaling in recent animal ancestors. Finally, we found that aggregation was initiated by post-translational activation of cell-cell adhesion—not transcriptional regulation of cellular adhesion machinery. Our findings illuminate the chemical, molecular and cellular mechanisms that regulateCapsasporaaggregative behavior—with implications for the evolution of animal multicellularity and the transmission of parasites.
Early and widespread engagement of the cerebellum during hippocampal epileptiform activity Format: Brief Communication
Authors: Streng M.L. , Kottke B.W. , Wasserman E.M. , Zecker L. , Luong L. , Ebner T.J. , Krook-Magnuson E. 
Published: May 2024

AbstractDespite research illustrating the cerebellum may be a critical circuit element in the epilepsies, remarkably little is known about cerebellar engagement during seizures. We therefore implemented a novel method for repeated imaging of the cerebellum in awake, chronically epileptic animals. We found widespread changes in cerebellar calcium signals during behavioral seizuresandduring hippocampal seizures that remained electrographic only, arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Changes were noted in the anterior and posterior cerebellum, along the midline, and both ipsilaterally and contralaterally to the seizure focus. Remarkably, changes in the cerebellum also occurredpriorto any noticeable change in the hippocampal electrographic recordings, suggesting a special relationship between the cerebellum and hippocampal epileptiform activity. Together these results underscore the importance of the cerebellum in epilepsy, warranting a more consistent consideration of the cerebellum when evaluating epilepsy patients.
Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in theOa1-/-mouse model of Ocular albinism
Authors: Guha Sonia , Nguyen Andrew M. , Young Alejandra , Mondell Ethan , Farber Debora B. 
Published: May 2024

SummaryMutations in the human Ocular albinism type-1 geneOA1are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from misrouting of ipsilateral retinal ganglion cell (iRGC) axons to the brain. We studied the latter using wild-type (WT) andOa1-/-mouse eyes. At embryonic stages, the WT RPE-specific Oa1 protein signals through cAMP/Epac1-Erk2-CREB. Following CREB phosphorylation, a pCREB gradient extends from the RPE to the differentiating retinal amacrine and RGCs. In contrast to WT, theOa1-/-RPE and ventral ciliary-margin-zone, a niche for iRGCs, express less pCREB while their retinas have a disrupted pCREB gradient, indicating Oa1’s involvement in pCREB maintenance.Oa1-/-retinas also show hyperproliferation, enlarged nuclei, reduced differentiation, and fewer newborn amacrine and RGCs than WT retinas. Our results demonstrate that Oa1’s absence leads to reduced binocular vision through a hyperproliferation-associated block in differentiation that impairs neurogenesis. This may affect iRGC axon’s routing to the brain.
Structure-activity relationship of pyrrolidine pentamine derivatives as inhibitors of the aminoglycoside 6′-N-acetyltransferase type Ib
Authors: Sklenicka Jan , Tran Tung , Ramirez Maria S. , Donow Haley M. , Magaña Angel J. , LaVoi Travis , Mamun Yasir , Chapagain Prem , Santos Radleigh , Pinilla Clemencia , Giulianotti Marc A. , Tolmasky Marcelo E. 
Published: May 2024

AbstractResistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive compounds to be developed as drugs. Mixture-based combinatorial libraries and positional scanning strategy led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1 - R5), inhibits AAC(6′)-Ib-mediated inactivation of amikacin. Structure-activity relationship (SAR) studies showed that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds,2700.001and2700.003, reduced inhibition levels, demonstrating the essential nature not only of the presence of anS-phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions have varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity.HighlightsAmikacin resistance in Gram-negatives is mostly caused by the AAC(6′)-Ib enzymeAAC(6′)-Ib has been identified in most Gram-negative pathogensInhibitors of AAC(6′)-Ib could be used to treat resistant infectionsCombinatorial libraries and positional scanning identified an inhibitorThe lead compound can be optimized by structure activity relationship studies