bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher Advanced Glycation End-products (AGEs) content and reduced bone strength
Authors: Leanza Giulia , Cannata Francesca , Faraj Malak , Pedone Claudio , Viola Viola , Tramontana Flavia , Pellegrini Niccolò , Vadalà Gianluca , Piccoli Alessandra , Strollo Rocky , Zalfa Francesca , Beeve Alec , Scheller Erica L , Tang Simon , Civitelli Roberto , Maccarrone Mauro , Papalia Rocco , Napoli Nicola 
Published: October 2023

AbstractType 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOSTandRUNX2) and Advanced Glycation End-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D [(T2D 0.249% (0.156-0.366) vs non-diabetic subjects 0.352% (0.269-0.454); p=0.053)], as well as reduced bone strength [T2D 21.60 MPa (13.46-30.10) vs non-diabetic subjects 76.24 MPa (26.81-132.9); p=0.002]. We also showed that gene expression of Wnt agonistsLEF-1(p=0.0136) andWNT10B(p=0.0302) were lower in T2D. Conversely, gene expression ofWNT5A(p=0.0232),SOST(p<0.0001) andGSK3B(p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated withSOSTandWNT5A(r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated withLEF-1andCOL1A1(r= -0,7500, p=0.0255; r= -0,9762, p=0.0004).SOSTwas associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereasWNT5AandGSK3Bwere only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young’s Modulus was negatively correlated withSOST(r=-0.5675, p=0.0011),AXIN2(r=-0.5523, p=0.0042) andSFRP5(r=-0.4442, p=0.0437), while positively correlated withLEF -1(r=0.4116, p=0.0295) andWNT10B(r=0.6697, p=0.0001). These findings suggest that Wnt signaling, and AGEs could be the main determinants of bone fragility in T2D.Graphical abstract
Rethinking Blood Eosinophils for Assessing ICS Response in COPD: A Post-Hoc Analysis from FLAME
Authors: Mathioudakis Alexander G. , Bate Sebastian , Sivapalan Pradeesh , Jensen Jens-Ulrik , Singh Dave , Vestbo Jørgen 
Published: October 2023

AbstractBackgroundThe varied treatment response to inhaled corticosteroids (ICS) in COPD, and the increased risk of pneumonia necessitate a personalised ICS approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. This post-hoc analysis evaluates the ability of different BEC measurements to predict ICS treatment response. BEC measured either on or off ICS treatment, and BEC change during ICS treatment were investigated.MethodsFLAME, a 52-week, double-blind RCT compared LABA/LAMA versus LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre and post run-in period BEC to represent BEC on and off ICS, respectively. In this post-hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS containing regimen.ResultsOur study confirms that LABA/LAMA combination is superior, or at least non-inferior, to LABA/ICS in curbing exacerbations for most FLAME participants. Lower BEC off and BEC on ICS and lack of significant BEC suppression during ICS treatment corresponded to superior response to LABA/LAMA in terms of exacerbation rate, time-to-first exacerbation, and time-to-first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment, and higher BEC on ICS did not predict ICS treatment response. For these patients BEC off ICS and BEC change proved more predictive.ConclusionThis exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response.What is already known on this topicBlood eosinophil count (BEC) is used to guide the administration of inhaled corticosteroids (ICS) for COPD, but they may be suppressed in response to systemic or inhaled corticosteroids.What this study addsThis post-hoc analysis suggests that BEC change during treatment with ICS and this change is associated with treatment response to ICS containing regimens. More specifically, BEC suppression is associated with favourable response to ICS, while unchanged or increased BEC is associated with inferior ICS treatment effect and increased risk of pneumonia. In 9% of participants, BEC changes significantly (≥200 cells/μL) during ICS treatment, and in these patients, BEC on ICS is not reliable in predicting treatment response to ICS, as it appears that some ICS responders may actually have low BEC on ICS and vice versa.How this study might affect research, practice or policyThese findings highlight the potential utility of BEC change during ICS treatment as a predictive biomarker of treatment response to ICS and question the use of BEC on ICS to guide withdrawal of ICS, but need prospective validation.
Optimal targeting of interventions uses estimated risk of infectiousness to control a pandemic with minimal collateral damage
Authors: Petrie James , Masel Joanna 
Published: October 2023

1AbstractIn this paper, we present a simple model that shows how to optimally target interventions based on the estimated risk of infectiousness of individuals. Our model can help policymakers decide when to use different types of interventions during a pandemic, depending on their precision, which is the fraction of positive predictions that are true positives. We show that targeted interventions, even with very low precision, can impose a much smaller overall burden on the population than non-targeted alternatives, such as lockdowns or mass testing. To illustrate this, we use data from the NHS contact tracing system in the UK to construct a risk function based on second degree contact tracing, which is similar to the strategy used by Vietnam in 2020. We find that with moderate precision (greater than 1/1000) and sufficient sensitivity (greater than 1 − 1/R0), countries can cope with a large number of imported cases without resorting to social distancing measures, while keeping the per-person probabilities of both infection and quarantine very low. We also show that targeted strategies are often orders of magnitude better than default strategies, making them robustly beneficial even under significant uncertainty about most parameters.
Facilitators and barriers to community pharmacy PrEP delivery: A scoping review
Authors: Harrison China , Family Hannah , Kesten Joanna , Denford Sarah , Scott Anne , Dawson Sarah , Scott Jenny , Sabin Caroline , Copping Joanna , Harryman Lindsey , Cochrane Sarah , Horwood Jeremy 
Published: October 2023

AbstractIntroductionPre-exposure prophylaxis (PrEP) is an effective medication to reduce the risk of acquiring HIV. PrEP is available free of charge in the United Kingdom from sexual health clinics. Expanding PrEP delivery to community pharmacies holds promise and aligns with UK government goals to eliminate new cases of HIV by 2030. The aim of this scoping review was to describe the existing evidence about the barriers to and facilitators of community pharmacy PrEP delivery, for pharmacists and pharmacy clients, as aligned with the Capacity Opportunity, Motivation Behaviour (COM-B) Model.MethodsFive bibliographic and five review databases were searched from inception to August 2023. Literature of any study design was included if it discussed barriers and facilitators of community pharmacy PrEP delivery. Trial registrations, protocols and news articles were excluded.ResultsA total of 649 records were identified, 73 full texts were reviewed, and 56 met the inclusion criteria. Most of the included literature was original research (55%), from the United States of America (77%) conducted during or after the year 2020 (63%). Barriers to PrEP delivery for pharmacists included lack of knowledge, training and skills (capability), not having the necessary facilities (opportunity), concern about the costs of PrEP and believing that PrEP use could lead to risk behaviour’s and STIs (motivation). Facilitators included staff training (capability), time, the right facilities (opportunity), believing PrEP could be a source of profit and could reduce new HIV infections (motivation). For clients, barriers included lack of PrEP awareness (capability), pharmacy facilities (opportunity) and not considering pharmacists as healthcare providers (motivation). Facilitators included awareness of PrEP and pharmacist’s training to deliver it (capability), the accessibility of pharmacies (opportunity) and having an interest in PrEP (motivation).ConclusionTo effectively enhance PrEP delivery in UK community pharmacies, the identified barriers and facilitators should be explored for relevance in the UK and subsequently addressed and leveraged at the pharmacy team, client and care pathway level. By comprehensively considering all aspects of the COM-B framework, community pharmacies could become crucial providers in expanding PrEP accessibility, contributing significantly to HIV prevention efforts.
Virtual Primary Care for People with Opioid Use Disorder: A Scoping Review of Current Strategies, Benefits, and Challenges
Authors: Narayan Shawna , Gooderham Ellie , Spencer Sarah , McCracken Rita , Hedden Lindsay 
Published: October 2023

ABSTRACTBackgroundThere is a pressing need to understand the implications of the rapid adoption of virtual primary care for people with opioid use disorder. Potential impacts, including disruptions to opiate agonist therapies, and the prospect of improved service accessibility remain underexplored. This scoping review synthesizes current literature on virtual primary care for people with opioid use disorder, with a specific focus on benefits, challenges, and strategies.MethodsWe followed the Joanna Briggs Institute methodological approach for scoping reviews and reported our findings consistent with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We conducted searches on MEDLINE, Web of Science, CINAHL Complete, and Embase using our developed search strategy with no date restrictions. We incorporated all study types that included the three concepts (i.e., virtual care; primary care; people with opioid use disorder). We excluded research on minors, asynchronous virtual modalities, and care not provided in a primary care setting. We used Covidence to screen and extract data, pulling information on study characteristics, health system features, patient outcomes, and challenges and benefits of virtual primary care. We conducted inductive content analysis and calculated descriptive statistics. We appraised the quality of studies using the Quality Assessment with Diverse Studies tool and categorized findings using the Consolidated Framework for Implementation Science.ResultsOur search identified 1474 studies. We removed 536 duplicates, leaving 936 studies for title and abstract screening. After a double review process, we retained 28 studies for extraction. Most studies described virtual primary care delivered via phone (n=18, 64.3%) rather than video. While increased healthcare accessibility was a significant benefit (n=13, 46.4%) to the adoption of virtual visits, issues around access to technology and digital literacy stood out as the main challenge (n=12, 42.9%).ConclusionsThe available studies highlight the potential for enhancing accessibility and continuous access care for people with opioid use disorder using virtual modalities. Future research and policies must focus on bridging gaps to ensure virtual primary care does not exacerbate or entrench health inequities.
Stroke Incidence According to Cardiorespiratory Fitness: A Cohort Study of 483,379 Hypertensive Patients
Authors: Kokkinos Peter , Faselis Charles , Pittaras Andreas , Samuel Immanuel Babu Henry , Lavie Carl J. , Ross Robert , Lamonte Michael , Franklin Barry A. , Sui Xuemei , Myers Jonathan 
Published: October 2023

AbstractObjectivesWe assessed stroke incidence in hypertensive patients according to cardiorespiratory fitness (CRF) and changes in CRF.MethodsA prospective cohort study of 483,379 US Veterans. Participants completed a maximal standardized Exercise Treadmill test (ETT) performed within the Veterans Affairs medical centers across the United States between 1999 and 2020. None exhibited evidence of unstable cardiovascular disease during the ETT. Participants were stratified into 5 age-and-gender specific CRF categories based on the peak metabolic equivalents (METs) achieved. A subgroup of participants with two ETT evaluations (n=110, 576) were also assigned to 4 categories based on MET changes from the initial ETT to the final ETT. Multivariable Cox models, adjusted for age, and co-morbidities were used to estimate HRs and 95% CIs for stroke risk.ResultsThe mean age ± standard deviation (SD) was 59.4±9.0 years. During the median follow-up time of 10.6 years (5,182,179 person-years), there were 15,925 stroke events with an average annual rate of 3.1 events per 1,000 person-years. In a final adjusted model, relatively poor CRF was the strongest predictor of stroke risk than any other comorbidity (HR: 2.24; 95% CI: 2.10-2.40; P< 0.001). For each 1-MET higher exercise capacity, the risk was 10% lower (0.90, 95% CI 0.90-0.91, p<0.001). Compared to the Least-fit, stroke risk was 23% lower for Low-fit individuals (HR 0.77; 95% CI, 0.73-0.80; p<0.001); and declined progressively to 55% for those in the highest CRF category (HR 0.45; 95% CI 0.42-0.48; p<0.001). We also assessed stroke incidence according to change in CRF. Compared to fit individuals during both evaluations, the risk was 27% higher for those who became unfit (HR 1.27, 95% CI 1.15-1.41, p<0.001), and not significantly different for unfit who became fit (HR 1.10, 95% CI 0.97-1.25, p=0.13).ConclusionsPoor CRF was the strongest predictor of stroke incidence in hypertensive patients, regardless of age race, or gender. The association was independent, inverse, and graded for all stroke types. Changes in CRF over time reflected inverse changes in stroke risk, suggesting that risk of stroke can be modulated by improved CRF.
A Flat Protein Complex Shapes Rough ER Membrane Sheets
Authors: Sawyer Eric M. , Jensen Liv E. , Meehl Janet B. , Larsen Kevin P. , Petito Daniel A. , Hurley James H. , Voeltz Gia K. 
Published: October 2023

SUMMARYRough ER sheets are a fundamental domain of the ER and the gateway into the secretory pathway. While reticulon proteins stabilize high-curvature ER tubules, it is unclear if other proteins scaffold the flat membranes of rough ER sheets. Through a proteomics screen using ER sheet localized RNA-binding proteins as bait, we identify the Sigma-1 receptor (SigmaR1) as an ER sheet shaping factor. High-resolution live cell imaging and electron tomography assign SigmaR1 as an ER sheet-localized factor whose levels determine the amount of rough ER sheets in cells. Structure-guided mutagenesis and in vitro reconstitution on giant unilamellar vesicles further support a mechanism whereby SigmaR1 oligomers use their extended arrays of amphipathic helices to bind and flatten the lumenal leaflet of ER membranes. Our results demonstrate an unexpected way for proteins to sense and propagate flat membrane sheets.
Intrinsic disorder specifies discreet functions of nucleoplasmin-like histone chaperones
Authors: Gauthier Courtney M. , LeGallais Josey , Savic Neda , Moradi-Fard Sarah , Grew Arden , Loe Martin , Kirlikaya Baran , Cobb Jennifer , Nelson Christopher J. 
Published: October 2023

ABSTRACTNucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear if all NPM functions require these unstructured features. We assessed the importance of IDRs in yeast NPM-like proteins and found that regulation of rDNA copy number, and genetic interactions with the nucleolar RNA surveillance machinery require the highly conserved FKBP prolyl isomerase domain, but not the NPM domain or IDRs. By contrast, transcriptional silencing in the nucleus requires IDRs. We demonstrate that multiple lysines in poly-acidic serine/lysine motifs of IDRs are required for both lysine polyphosphorylation and NPM-mediated transcriptional silencing. These results demonstrate that NPM-like proteins do not rely on IDRs for all chromatin-related functions.
Traumatic brain injury disrupts state-dependent functional cortical connectivity in a mouse model
Authors: Bottom-Tanzer Samantha , Corella Sofia , Meyer Jochen , Sommer Mary , Bolaños Luis , Murphy Timothy , Quiñones Sadi , Heiney Shane , Shtrahman Matthew , Whalen Michael , Oren Rachel , Higley Michael J. , Cardin Jessica A. , Noubary Farzad , Armbruster Moritz , Dulla Chris 
Published: October 2023

ABSTRACTTraumatic brain injury (TBI) is the leading cause of death in young people and can cause cognitive and motor dysfunction and disruptions in functional connectivity between brain regions. In human TBI patients and rodent models of TBI, functional connectivity is decreased after injury. Recovery of connectivity after TBI is associated with improved cognition and memory, suggesting an important link between connectivity and functional outcome. We examined widespread alterations in functional connectivity following TBI using simultaneous widefield mesoscale GCaMP7c calcium imaging and electrocorticography (ECoG) in mice injured using the controlled cortical impact (CCI) model of TBI. Combining CCI with widefield cortical imaging provides us with unprecedented access to characterize network connectivity changes throughout the entire injured cortex over time. Our data demonstrate that CCI profoundly disrupts functional connectivity immediately after injury, followed by partial recovery over 3 weeks. Examining discrete periods of locomotion and stillness reveals that CCI alters functional connectivity and reduces theta power only during periods of behavioral stillness. Together, these findings demonstrate that TBI causes dynamic, behavioral state-dependent changes in functional connectivity and ECoG activity across the cortex.
AleRax: A tool for gene and species tree co-estimation and reconciliation under a probabilistic model of gene duplication, transfer, and loss
Authors: Morel Benoit , Williams Tom A. , Stamatakis Alexandros , Szöllősi Gergely J. 
Published: October 2023

ABSTRACTMotivationGenomes are a rich source of information on the pattern and process of evolution across biological scales. How best to make use of that information is an active area of research in phylogenetics. Ideally, phylogenetic methods should not only model substitutions along gene trees, which explain differences between homologous gene sequences, but also the processes that generate the gene trees themselves along a shared species tree. To conduct accurate inferences, one needs to account for uncertainty at both levels, that is, in gene trees estimated from inherently short sequences and in their diverse evolutionary histories along a shared species tree.ResultsWe present AleRax, a software that can infer reconciled gene trees together with a shared species tree using a simple, yet powerful, probabilistic model of gene duplication, transfer, and loss. A key feature of AleRax is its ability to account for uncertainty in the gene tree and its reconciliation by using an efficient approximation to calculate the joint phylogenetic-reconciliation likelihood and sample reconciled gene trees accordingly. Simulations and analyses of empirical data show that AleRax is one order of magnitude faster than competing gene tree inference tools while attaining the same accuracy. It is consistently more robust than species tree inference methods such as SpeciesRax and ASTRAL-Pro 2 under gene tree uncertainty. Finally, AleRax can process multiple gene families in parallel thereby allowing users to compare competing phylogenetic hypotheses and estimate model parameters, such as DTL probabilities for genome-scale datasets with hundreds of taxaAvailability and ImplementationGNU GPL athttps://github.com/BenoitMorel/AleRaxand data are made available athttps://cme.h-its.org/exelixis/material/alerax_data.tar.gz.ContactBenoit.Morel@h-its.orgSupplementary informationSupplementary material is available.
Cue-specific neuronal ensembles span intermittent rate coding of working memory
Authors: Panichello Matthew F , Jonikaitis Donatas , Oh Jin , Zhu Shude , Trepka Ethan B , Moore Tirin 
Published: October 2023

AbstractPersistent, memorandum-specific neuronal spiking activity has long been hypothesized to underlie working memory. However, emerging evidence suggests a possible role for ‘activity-silent’ synaptic mechanisms. This issue remains controversial because evidence for either view has largely depended on datasets that fail to capture single-trial population dynamics or on indirect measures of neuronal spiking. We addressed this by examining the dynamics of mnemonic information on single trials obtained from large, local populations of prefrontal neurons recorded simultaneously in monkeys performing a working memory task. We show that mnemonic information does not persist in the spiking activity of prefrontal neurons, but instead alternates between ‘On’ and ‘Off’ periods during memory delays. At the level of single neurons, Off periods are driven by a coordinated loss of selectivity for memoranda and a return of firing rates to baseline levels. Further exploiting the large-scale recordings, we asked whether the functional connectivity among large neuronal ensembles depended on information held in working memory. We show that mnemonic information is available in the pattern of ensemble connectivity during the memory delay in both On and Off periods of neuronal activity. Intermittent epochs of memoranda-specific spiking therefore coexist with activity-silent mechanisms to span memory delays.