bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal origin of mouse claustrum and development of its cortical projections
Authors: Hoerder-Suabedissen Anna , Ocana-Santero Gabriel , Draper Thomas H , Scott Sophie A , Kimani Jesse G , Shelton Andrew M , Butt Simon J B , Molnár Zoltán , Packer Adam M 
Published: September 2022

AbstractThe claustrum is known for its extensive connectivity with many other forebrain regions, but its elongated shape and deep location have made further study difficult. We have sought to understand when mouse claustrum neurons are born, where they are located in developing brains, and when they develop their widespread connections to the cortex. We established that a well-characterized parvalbumin plexus, which identifies the claustrum in adults, is only present from postnatal day (P) 21. A myeloarchitectonic outline of the claustrum can be derived from a triangular fiber arrangement from P15. A dense patch of Nurr1+ cells is present at its core and is already evident at birth. Bromodeoxyuridine birth dating of forebrain progenitors reveals that the majority of claustrum neurons are born during a narrow time window centered on embryonic day 12.5, which is later than the adjacent subplate and endopiriform nucleus. Retrograde tracing revealed that claustrum projections to anterior cingulate (ACA) and retrosplenial cortex (RSP) follow distinct developmental trajectories. Claustrum–ACA connectivity matures rapidly and reaches adult-like innervation density by P10, whereas claustrum–RSP innervation emerges later over a protracted time window. This work establishes the timeline of claustrum development and provides a framework for understanding how the claustrum is built and develops its unique connectivity.
Dynamic Energy Budget models: fertile ground for understanding resource allocation in plants in a changing world
Authors: Russo Sabrina E , Ledder Glenn , Muller Erik B , Nisbet Roger M 
Published: September 2022

Abstract
Climate change is having dramatic effects on the diversity and distribution of species. Many of these effects are mediated by how an organism’s physiological patterns of resource allocation translate into fitness through effects on growth, survival and reproduction. Empirically, resource allocation is challenging to measure directly and so has often been approached using mathematical models, such as Dynamic Energy Budget (DEB) models. The fact that all plants require a very similar set of exogenous resources, namely light, water and nutrients, integrates well with the DEB framework in which a small number of variables and processes linked through pathways represent an organism’s state as it changes through time. Most DEB theory has been developed in reference to animals and microorganisms. However, terrestrial vascular plants differ from these organisms in fundamental ways that make resource allocation, and the trade-offs and feedbacks arising from it, particularly fundamental to their life histories, but also challenging to represent using existing DEB theory. Here, we describe key features of the anatomy, morphology, physiology, biochemistry, and ecology of terrestrial vascular plants that should be considered in the development of a generic DEB model for plants. We then describe possible approaches to doing so using existing DEB theory and point out features that may require significant development for DEB theory to accommodate them. We end by presenting a generic DEB model for plants that accounts for many of these key features and describing gaps that would need to be addressed for DEB theory to predict the responses of plants to climate change. DEB models offer a powerful and generalizable framework for modelling resource allocation in terrestrial vascular plants, and our review contributes a framework for expansion and development of DEB theory to address how plants respond to anthropogenic change.
Impact of anti-arrhythmic drugs and catheter ablation on the survival of patients with atrial fibrillation: a population study based on 199 433 new-onset atrial fibrillation patients in the UK
Authors: Chung Sheng-Chia , Lai Alvina , Lip Gregory Y H , Lambiase Pier D , Providencia Rui 
Published: September 2022

AbstractAimsUtilizing real-world UK data, we aimed to understand: (i) whether anti-arrhythmic drugs and catheter ablation are effective in improving the survival of atrial fibrillation (AF) patients and (ii) which rhythm control option produces better results for the whole AF population and for specific groups of patients, stratified by age, sex, and history of heart failure.Methods and resultsWe identified 199 433 individuals (mean age at diagnosis 75.7 ± 12.7 years; 50.2% women) with new-onset AF diagnosis in nationwide electronic health records linking primary care consultation with hospital data and death registry data from 1998 to 2016. We investigated the survival and causes of death of new-onset AF patients receiving vs. not-receiving rhythm control therapies. During a median follow-up of 2.7 (0.7–6.0) years, we observed a significantly lower mortality in patients receiving rhythm control [multivariate-adjusted hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.84–0.88]. Pulmonary vein isolation was associated with a two-third significant mortality reduction compared with no rhythm control (HR = 0.36, 95% CI 0.28–0.48), flecainide with 50% reduction (HR = 0.52, 95% CI 0.48–0.57), and propafenone and sotalol with reduction by a third (HR = 0.63, 95% CI 0.50–0.81, 0.71, 95% CI 0.68–0.74, respectively). Amiodarone showed no survival benefit in individuals &lt;70 years (HR = 0.99, 95% CI 0.97–1.02). Otherwise, the effect of rhythm control on survival did not differ by age, sex, nor history of heart failure.ConclusionAmong individuals with new-onset AF, favourable survival was observed for patients receiving rhythm control treatment. Among different rhythm control strategies, pulmonary vein isolation showed the most pronounced survival benefit.
Assessment of electrical dyssynchrony in cardiac resynchronization therapy: 12-lead electrocardiogram vs. 96-lead body surface map
Authors: Sedova Ksenia A , van Dam Peter M , Sbrollini Agnese , Burattini Laura , Necasova Lucie , Blahova Marie , Bocek Jan , Sramko Marek , Kautzner Josef 
Published: September 2022

AbstractAimsThe standard deviation of activation time (SDAT) derived from body surface maps (BSMs) has been proposed as an optimal measure of electrical dyssynchrony in patients with cardiac resynchronization therapy (CRT). The goal of this study was two-fold: (i) to compare the values of SDAT in individual CRT patients with reconstructed myocardial metrics of depolarization heterogeneity using an inverse solution algorithm and (ii) to compare SDAT calculated from 96-lead BSM with a clinically easily applicable 12-lead electrocardiogram (ECG).Methods and resultsCardiac resynchronization therapy patients with sinus rhythm and left bundle branch block at baseline (n = 19, 58% males, age 60 ± 11 years, New York Heart Association Classes II and III, QRS 167 ± 16) were studied using a 96-lead BSM. The activation time (AT) was automatically detected for each ECG lead, and SDAT was calculated using either 96 leads or standard 12 leads. Standard deviation of activation time was assessed in sinus rhythm and during six different pacing modes, including atrial pacing, sequential left or right ventricular, and biventricular pacing. Changes in SDAT calculated both from BSM and from 12-lead ECG corresponded to changes in reconstructed myocardial ATs. A high degree of reliability was found between SDAT values obtained from 12-lead ECG and BSM for different pacing modes, and the intraclass correlation coefficient varied between 0.78 and 0.96 (P &lt; 0.001).ConclusionStandard deviation of activation time measurement from BSM correlated with reconstructed myocardial ATs, supporting its utility in the assessment of electrical dyssynchrony in CRT. Importantly, 12-lead ECG provided similar information as BSM. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG in larger patient cohorts, including those with ischaemic cardiomyopathy.
Rapid detection of isthmus block and rhythm change using local electrogram changes during complex atrial flutter ablation
Authors: Padanilam Benzy J , Whittam Sarah W , Clark Brad A , Olson Jeffrey A , Nair Girish V , Joshi Sandeep A , Prystowsky Eric N , Patel Parin J , Gilge Jasen L 
Published: September 2022

AbstractAimsMultiple re-entry circuits may operate simultaneously in the atria in the form of dual loop re-entry using a common isthmus, or multiple re-entrant loops without a common isthmus. When two or more re-entrant circuits coexist, ablation of an individual isthmus may lead to a seamless transition (without significant changes in surface electrocardiogram, coronary sinus activation or tachycardia cycle length) to a second rhythm, and the isthmus block can go unnoticed.Methods and resultsWe hypothesize and subsequently illustrate in three patient cases, methods to rapidly identify a transition in the rhythm and isthmus block using local electrogram changes at the ablation site.ConclusionLocal activation sequence changes, electrogram timing, and the behaviour of pre-existing double potentials can reveal isthmus block promptly when rhythm transitions occur during ablation of multiloop re-entry tachycardias.
Assessing the use of a clinical decision support tool for pain management in primary care
Authors: Apathy Nate C , Sanner Lindsey , Adams Meredith C B , Mamlin Burke W , Grout Randall W , Fortin Saura , Hillstrom Jennifer , Saha Amit , Teal Evgenia , Vest Joshua R , Menachemi Nir , Hurley Robert W , Harle Christopher A , Mazurenko Olena 
Published: September 2022

Abstract

Objective
Given time constraints, poorly organized information, and complex patients, primary care providers (PCPs) can benefit from clinical decision support (CDS) tools that aggregate and synthesize problem-specific patient information. First, this article describes the design and functionality of a CDS tool for chronic noncancer pain in primary care. Second, we report on the retrospective analysis of real-world usage of the tool in the context of a pragmatic trial.

Materials and methods
The tool known as OneSheet was developed using user-centered principles and built in the Epic electronic health record (EHR) of 2 health systems. For each relevant patient, OneSheet presents pertinent information in a single EHR view to assist PCPs in completing guideline-recommended opioid risk mitigation tasks, review previous and current patient treatments, view patient-reported pain, physical function, and pain-related goals.

Results
Overall, 69 PCPs accessed OneSheet 2411 times (since November 2020). PCP use of OneSheet varied significantly by provider and was highly skewed (site 1: median accesses per provider: 17 [interquartile range (IQR) 9–32]; site 2: median: 8 [IQR 5–16]). Seven “power users” accounted for 70% of the overall access instances across both sites. OneSheet has been accessed an average of 20 times weekly between the 2 sites.

Discussion
Modest OneSheet use was observed relative to the number of eligible patients seen with chronic pain.

Conclusions
Organizations implementing CDS tools are likely to see considerable provider-level variation in usage, suggesting that CDS tools may vary in their utility across PCPs, even for the same condition, because of differences in provider and care team workflows.
Natural borneol enhances the anti-cerebral ischaemia efficacy of formononetin in MCAO/R rats by promoting its delivery in the brain
Authors: Li Jia-Yu , Wang Jin-Xin , Li Qiu-Hao , Li Xiao-Feng , Xiao Jun-Ping , Li Shan-Shan , Shen Xiu-Ping , Zhang Wei-Dong , Shen Yun-Heng 
Published: September 2022

Abstract
Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery.
Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol’s promoting formononetin delivery in the brain.
Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol.
Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.
An exploration of the properties of cluster profiles for the thermal and kinetic Sunyaev–Zel’dovich effects
Authors: Lee Billy K K , Coulton William R , Thiele Leander , Ho Shirley 
Published: September 2022

ABSTRACT
With the advent of high-resolution, low-noise CMB measurements, the ability to extract cosmological information from thermal Sunyaev–Zel’dovich effect and kinetic Sunyaev–Zel’dovich effect will be limited not by statistical uncertainties but rather by systematic and theoretical uncertainties. The theoretical uncertainty is driven by the lack of knowledge about the electron pressure and density. Thus, we explore the electron pressure and density distributions in the IllustrisTNG hydrodynamical simulations, and we demonstrate that the cluster properties exhibit a strong dependence on the halo concentration – providing some of the first evidence of cluster assembly bias in the electron pressure and density. Further, our work shows evidence for a broken power-law mass dependence, with lower pressure in lower mass haloes than previous work and a strong evolution with mass of the radial correlations in the electron density and pressure. Both of these effects highlight the differing impact of active galactic nuclei and supernova feedback on the gas in galaxy groups compared to massive clusters. We verified that we see qualitatively similar features in the SIMBA hydrodynamical simulations, suggesting these effects could be generic features. Finally, we provide a parametric formula for the electron pressure and density profile as a function of dark matter halo mass, halo concentration, and redshift. Despite our extensions, the best-fitting formulae are not able to fully capture the features seen in certain mass, radius, and redshift regimes, thereby highlighting the challenges of precision modelling gas profiles.
Double-strand break toxicity is chromatin context independent
Authors: Friskes Anoek , Koob Lisa , Krenning Lenno , Severson Tesa M , Koeleman Emma S , Vergara Xabier , Schubert Michael , van den Berg Jeroen , Evers Bastiaan , Manjón Anna G , Joosten Stacey , Kim Yongsoo , Zwart Wilbert , Medema René H 
Published: September 2022

AbstractCells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single double-strand break generated via CRISPR/Cas9 is sufficient to delay cell cycle progression and compromise cell viability. However, we also found that the cellular response to DSBs can vary, independent of the number of lesions. This implies that not all DSBs are equally toxic, and raises the question if the location of a single double-strand break could influence its toxicity. To systematically investigate if DSB-location is a determinant of toxicity we performed a CRISPR/Cas9 screen targeting 6237 single sites in the human genome. Next, we developed a data-driven framework to design CRISPR/Cas9 sgRNA (crRNA) pools targeting specific chromatin features. The chromatin context was defined using ChromHMM states, Lamin-B1 DAM-iD, DNAseI hypersensitivity, and RNA-sequencing data. We computationally designed 6 distinct crRNA pools, each containing 10 crRNAs targeting the same chromatin state. We show that the toxicity of a DSB is highly similar across the different ChromHMM states. Rather, we find that the major determinants of toxicity of a sgRNA are cutting efficiency and off-target effects. Thus, chromatin features have little to no effect on the toxicity of a single CRISPR/Cas9-induced DSB.
Correlation of SARS-CoV-2 Nasopharyngeal CT Values With Viremia and Mortality in Adults Hospitalized With COVID-19
Authors: Hagman Karl , Hedenstierna Magnus , Widaeus Jacob , Arvidsson Emelie , Hammas Berit , Grillner Lena , Jakobsson Jan , Gille-Johnson Patrik , Ursing Johan 
Published: September 2022

AbstractBackgroundBoth severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viremia and nasopharyngeal viral load have been suggested to be predictors of unfavorable outcome in coronavirus disease 2019 (COVID-19). This study aimed to investigate whether nasopharyngeal viral load is correlated with viremia and unfavorable outcome.MethodsThe presence of SARS-CoV-2 RNA was determined in paired nasopharyngeal and serum samples collected at admission from patients hospitalized for COVID-19. Standardized cycle threshold values (CT values) were used as an indicator of viral load. An adjusted logistic regression was used to estimate the risk of viremia at different nasopharyngeal CT values. A Cox regression was used to estimate the risk of 60-day mortality.ResultsA total of 688 patients were included. Viremia at admission was detected in 63% (146/230), 46% (105/226), and 31% (73/232) of patients with low, intermediate, and high nasopharyngeal CT values. The adjusted odds ratios of being viremic were 4.4 (95% CI, 2.9–6.8) and 2.0 (95% CI, 1.4–3.0) for patients with low and intermediate CT values, compared with high CT values. The 60-day mortality rate was 37% (84/230), 15% (36/226), and 10% (23/232) for patients with low, intermediate, and high nasopharyngeal CT values at admission, respectively. Adjusted hazard ratios were 2.6 (95% CI, 1.6–4.2) and 1.4 (95% CI, 0.8–2.4) for patients with low and intermediate CT values compared with high CT values.ConclusionsThere was a dose-dependent correlation between nasopharyngeal CT values and viremia at admission for COVID-19. Moreover, there was an increased risk of 60-day mortality for patients with low, compared with high, nasopharyngeal CT values.
Insights into the molecular mechanisms of CRISPR/Cas9-mediated gene targeting at multiple loci in Arabidopsis
Authors: Zhang Zhengjing , Zeng Wenjie , Zhang Wenxin , Li Jing , Kong Dali , Zhang Lei , Wang Rui , Peng Fangnan , Kong Zhe , Ke Yongping , Zhang Heng , Kim Chanhong , Zhang Huiming , Botella Jose Ramón , Zhu Jian-Kang , Miki Daisuke 
Published: September 2022

Abstract
Homologous recombination-mediated gene targeting (GT) enables precise sequence knockin or sequence replacement, and thus is a powerful tool for heritable precision genome engineering. We recently established a clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9)-mediated approach for heritable GT in Arabidopsis (Arabidopsis thaliana), but its broad utility was not tested, and the underlying molecular mechanism was unclear. Here, we achieved precise GT at 14 out of 27 tested endogenous target loci using the sequential transformation approach and obtained vector-free GT plants by backcrossing. Thus, the sequential transformation GT method provides a broadly applicable technology for precise genome manipulation. We show that our approach generates heritable GT in the egg cell or early embryo of T1 Arabidopsis plants. Analysis of imprecise GT events suggested that single-stranded transfer DNA (T-DNA)/VirD2 complexes produced during the Agrobacterium (Agrobacterium tumefaciens) transformation process may serve as the donor templates for homologous recombination-mediated repair in the GT process. This study provides new insights into the molecular mechanisms of CRISPR/Cas9-mediated GT in Arabidopsis.
Evaluating the Effectiveness of Joint Specialist Case Conferences in Improving Diabetes Control in Patients With Schizophrenia on Clozapine
Authors: Zheng Yu , Meyerowitz-Katz Gideon , Bramwell Sian , Jayaballa Rajini , Assur Yolinda , Vasani Deepali , Ganapathy Ramanathan , Maberly Glen , Brakoulias Vlasios 
Published: September 2022

Abstract
Clozapine treatment for schizophrenia is typically long-term and is associated with a high rate of diabetes. Mental health and diabetes specialist teams at a local hospital in Australia have undertaken a series of joint specialist case conferences (JSCCs) where the diabetes team works with the psychiatry team to improve diabetes management. In this retrospective cohort study conducted between 2013 and 2018, we found that glycemic control in clozapine clinics linked with JSCCs was improved significantly compared with that in the non-JSCC clinics. In the non-JSCC clozapine clinics (control), the poor glycemic control rates stayed at a similar level: 23% in 2013 and 24% in 2018. In contrast, whereas the control patients' poor glycemic rate in JSCC clozapine clinics in 2013 was 24%, it decreased markedly in 2018 to 13%. This study indicates that JSCCs can improve diabetes outcomes in a group of patients with severe mental illness.
Effect of Plasma Resuscitation with Adjunctive Peritoneal Resuscitation on Hepatic Blood Flow and End-Organ Damage after Hemorrhagic Shock
Authors: Smith Jason W , Schucht Jessica E , Harbrecht Brian G , Bond Logan M , Matheson Paul J 
Published: September 2022

BACKGROUND:
Intestinal injury from resuscitated hemorrhagic shock (HS) disrupts intestinal microvascular flow and causes enterocyte apoptosis, intestinal barrier breakdown, and injury to multiple organs. Fresh frozen plasma (FFP) resuscitation or directed peritoneal (DPR) resuscitation protect endothelial glycocalyx, improve intestinal blood flow, and alleviate intestinal injury. We postulated that FFP plus DPR might improve effective hepatic blood flow (EHBF) and prevent associated organ injury (liver, heart).

STUDY DESIGN:
Anesthetized Sprague-Dawley rats underwent HS (40% mean arterial pressure, 60 minutes) and were randomly assigned to groups (n = 8 per group): Sham; crystalloid resuscitation (CR; shed blood + 2 volumes CR); DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood + 1 vol IV FFP); FFP + DPR. EHBF was measured at postresuscitation timepoints. Organ injury was evaluated by serum ELISA (fatty acid-binding protein [FABP]-1 [liver], FABP-3 [heart], Troponin-I [heart], and Troponin-C [heart]) and hematoxylin and eosin. Differences were evaluated by 1-way ANOVA and 2-way repeated-measures ANOVA.

RESULTS:
CR resuscitation alone did not sustain EHBF. FFP resuscitation restored EHBF after resuscitation (2 hours, 3 hours, and 4 hours). DPR resuscitation restored EHBF throughout the postresuscitation period but failed to restore serum FABP-1 VS other groups. Combination FFP + DPR rapidly and sustainably restored EHBF and decreased organ injury. CR and DPR alone had elevated organ injury (FABP-1 [hepatocyte], FABP-3 [cardiac], and Troponin-I/C), whereas FFP or FFP + DPR demonstrated reduced injury at 4 hours after resuscitation.

CONCLUSION:
HS decreased EHBF, hepatocyte injury, and cardiac injury as evidenced by serology. FFP resuscitation improved EHBF and decreased organ damage. Although DPR resuscitation resulted in sustained EHBF, this alone failed to decrease hepatocyte or cardiac injury. Combination therapy with DPR and FFP may be a novel method to improve intestinal and hepatic blood flow and decrease organ injury after HS/resuscitation.