bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theta Dynamics Contribute to Retrieving Motor Plans after Interruptions in the Primate Premotor Area
Authors: Hosaka Ryosuke , Watanabe Hidenori , Nakajima Toshi , Mushiake Hajime 
Published: October 2021

AbstractTo achieve a behavioral goal, we often need to maintain an internal action plan against external interruption and thereafter retrieve the action plan. We recently found that the maintenance and updating of motor plans are reflected by reciprocal changes in the beta and gamma power of the local field potential (LFP) of the primate medial motor areas. In particular, the maintenance of the immediate motor plan is supported by enhanced beta oscillations. However, it is unclear how the brain manages to maintain and retrieve the internal action plan against interruptions. Here, we show that dynamic theta changes contribute to the maintenance of the action plan. Specifically, the power of the theta frequency band (4–10 Hz) of LFPs increased before and during the interruption in the dorsal premotor areas in two monkeys. Without theta enhancement before the interruption, retrieval of the internal action plan was impaired. Theta and beta oscillations showed distinct changes depending on the behavioral context. Our results demonstrate that immediate and suspended motor plans are supported by the beta and theta oscillatory components of LFPs. Motor cortical theta oscillations may contribute to bridging motor plans across behavioral interruptions in a prospective manner.
Phloem transport limitation in Huanglongbing-affected sweet orange is dependent on phloem-limited bacteria and callose
Authors: Welker Stacy , Pierre Myrtho , Santiago James P , Dutt Manjul , Vincent Christopher , Levy Amit 
Published: October 2021

AbstractHuanglongbing (HLB), caused by Candidatus `Liberibacter asiaticus' (CLas), is a phloem-limited disease that disrupts citrus production in affected areas. In HLB-affected plants, phloem sieve plate pores accumulate callose, and leaf carbohydrate export is reduced. However, whether HLB causes a reduction in carbohydrate phloem translocation speed and the quantitative relationships among callose, CLas population and phloem translocation are still unknown. In this work, a procedure was developed to concurrently measure sugar transport, callose deposition and relative pathogen population at different locations throughout the stem. Increasing quantities of CLas genetic material were positively correlated with quantity and density of callose deposits and negatively correlated with phloem translocation speed. Callose deposit quantity was position and rootstock dependent and was negatively correlated with phloem translocation speed, suggesting a localized relationship. Remarkably, callose accumulation and phloem translocation disruption in the scion were dependent on rootstock genotype. Regression results suggested that the interaction of Ct values and number of phloem callose depositions, but not their size or density, explained the effects on translocation speed. Sucrose, starch and sink 14C label allocation data support the interpretation of a transport pathway limitation by CLas infection. This work shows that the interaction of local accumulation of callose and CLas affects phloem transport. Furthermore, the extent of this accumulation is attenuated by the rootstock and provides important information about the disease mechanism of phloem-inhabiting bacteria. Together, these results constitute the first example of a demonstrated transport limitation of phloem function by a microbial infection.
The Endophytic Fungus Cyanodermella asteris Influences Growth of the Nonnatural Host Plant Arabidopsis thaliana
Authors: Jahn Linda , Storm-Johannsen Lisa , Seidler Diana , Noack Jasmin , Gao Wei , Schafhauser Thomas , Wohlleben Wolfgang , van Berkel Willem J. H. , Jacques Philippe , Kar Tambi , Piechulla Birgit , Ludwig-Müller Jutta 
Published: October 2021

Cyanodermella asteris is a fungal endophyte from Aster tataricus, a perennial plant from the northern part of Asia. Here, we demonstrated an interaction of C. asteris with Arabidopsis thaliana, Chinese cabbage, rapeseed, tomato, maize, or sunflower resulting in different phenotypes such as shorter main roots, massive lateral root growth, higher leaf and root biomass, and increased anthocyanin levels. In a variety of cocultivation assays, it was shown that these altered phenotypes are caused by fungal CO2, volatile organic compounds, and soluble compounds, notably astins. Astins A, C, and G induced plant growth when they were individually included in the medium. In return, A. thaliana stimulates the fungal astin C production during cocultivation. Taken together, our results indicate a bilateral interaction between the fungus and the plant. A stress response in plants is induced by fungal metabolites while plant stress hormones induced astin C production of the fungus. Interestingly, our results not only show unidirectional influence of the fungus on the plant but also vice versa. The plant is able to influence growth and secondary metabolite production in the endophyte, even when both organisms do not live in close contact, suggesting the involvement of volatile compounds. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Association of Lumbosacral Transitional Vertebrae with Low Back Pain and Lumbar Degenerative Findings in MRI
Authors: Hanhivaara Jaakko , Määttä Juhani H. , Karppinen Jaro , Niinimäki Jaakko , Nevalainen Mika T. 
Published: October 2021

Study Design.
A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966).

Objective.
To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using magnetic resonance (MR) imaging.

Summary of Background Data.
LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear.

Methods.
One thousand four hundred sixty eight lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of more than 30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t test and multinomial logistic regression analyses were used.

Results.
LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex, and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (odds ratio [OR] = 8.9, P = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II–IV. DD was more prevalent at L4/L5 in types II–IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at levels from L3/L4 to L4/L5.

Conclusion.
LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.

Level of Evidence: 3
Effects of methylene blue on microcirculatory alterations following cardiac surgery
Authors: Maurin Carole , Portran Philippe , Schweizer Remi , Allaouchiche Bernard , Junot Stéphane , Jacquet-Lagrèze Matthias , Fellahi Jean-Luc 
Published: October 2021

BACKGROUND
Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented.

OBJECTIVE
We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue.

DESIGN
A prospective open-label cohort study.

SETTING
20-Bed ICU of a tertiary care hospital.

PATIENTS
25 Adult patients receiving 1.5 mg kg−1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 μg kg−1 min−1) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min−1 m−2.

MAIN OUTCOME MEASURES
Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time.

RESULTS
Despite normalised CI (2.6 [2.0 to 3.8] l min−1 m−2) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI < 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P = 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm−2 (P = 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm−2 (P = 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s−1 (P = 0.002). Capillary refill time remained unchanged throughout the study.

CONCLUSION
In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence.

TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04250389.
Therapeutic Drug Monitoring of Ganciclovir: Where Are We?
Authors: Märtson Anne-Grete , Edwina Angela E. , Kim Hannah Yejin , Knoester Marjolein , Touw Daan J. , Sturkenboom Marieke G. G. , Alffenaar Jan-Willem C. 
Published: October 2021

Background:
Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of Cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such as myelosuppression, which often leads to therapy cessation. Underdosing, as an attempt to prevent side effects, can lead to drug resistance and therapy failure. Therapeutic drug monitoring (TDM) has been used to overcome these problems. The purpose of this narrative review was to give an overview of ganciclovir TDM, available assays, population pharmacokinetic models, and discuss the current knowledge gaps.

Methods:
For this narrative review, a nonsystematic literature search was performed on the PubMed database in April 2021. The following search terms were used: ganciclovir, valganciclovir, pharmacokinetics, pharmacodynamics, population pharmacokinetics, therapeutic drug monitoring, bioassay, liquid chromatography coupled with tandem mass spectrometry, liquid chromatography, chromatography, spectrophotometry, and toxicity. In addition, the reference lists of the included articles were screened.

Results:
The most common bioanalysis method identified was liquid chromatography coupled with tandem mass spectrometry. There are different models presenting ganciclovir IC50; however, establishing a pharmacokinetic/pharmacodynamic target for ganciclovir based on preclinical data is difficult because there are no studies combining dynamic drug exposure in relation to inhibition of viral replication. The data on ganciclovir TDM show large interindividual variability, indicating that TDM may play a role in modifying the dose to reduce toxicity and prevent treatment failure related to low concentrations. The main hurdle for implementing TDM is the lack of robust data to define a therapeutic window.

Conclusions:
Although the pharmacokinetics (PK) involved is relatively well-described, both the pharmacodynamics (PD) and pharmacokinetic/pharmacodynamic relationship are not. This is because the studies conducted to date have mainly focused on estimating ganciclovir exposure, and owing to the limited therapeutic options for CMV infections, future studies on ganciclovir are warranted.
Successful Novel Treatment of Granuloma Faciale Using CO2 Emulated Er:YAG Laser Ablation
Authors: Bayne Kilee , Fornwalt Brandon E. , Jonda Christopher F. , Cash Adam D. 
Published: October 2021

Summary:
Granuloma faciale is a rare, benign inflammatory skin disease that has multiple medical treatment modalities due to its frequent unresponsiveness to treatment. This skin disease presents as a single, well-demarcated red-brown to violaceous, raised lesion, most commonly on the face, in middle-aged White men. Its etiology is unknown; sun exposure is thought to have some implications in its formation. Treatment modalities for granuloma faciale include topical therapy, intralesional injections, systemic therapies, phototherapy, lasers, cryotherapy, and surgical excision. In this article, we will highlight a rare case of granuloma faciale and its novel and successful treatment with a carbon dioxide emulated Er:YAG laser.
Focusing on the Medically Ready for Discharge Patient Using a Reliable Design Strategy: A Quality Improvement Project to Improve Length of Stay on a Medicine Service
Authors: Meo Nicholas , Cornia Paul B. 
Published: October 2021

Background and Objectives:
Length of stay is a common measure of efficiency of care. We aimed to reduce length of stay on a general medicine service through a structured quality improvement project.

Methods:
A reliable design strategy was implemented in successive stages at a 238-bed academically-affiliated VA hospital. Over a 2-year period, continuous improvement efforts were directed at discrete cohorts of patients deemed medically appropriate for discharge but who remained hospitalized because of discharge barriers. We compared the mean length of stay and medically-ready bed days of care for a hospital in statistical control charts. Pre- and post-intervention comparisons were made using t-tests.

Results:
In total, 5321 discharges were included in this improvement project, accounting for 35 852 bed days of care. Overall, average length of stay was reduced by 15.7%, from 7.62 to 6.40 days (P < .05). There was a significant reduction in the mean number of medically-ready bed days of care from 2.3 to 1.72. Statistical process control charts demonstrated special cause variation across patient cohorts.

Conclusion:
A quality improvement project using reliable design principles was associated with shorter length of stay.
Reperfusion Therapies for Children With Arterial Ischemic Stroke
Authors: Heit Jeremy J. , Muthusami Prakash , Chandra Ronil V. , Hui Ferdinand , Negrotto Matias , Lee Sarah , Wasserman Bruce A. , Abruzzo Todd A. 
Published: October 2021

Abstract
Modern hyperacute reperfusion therapies including intravenous thrombolysis and mechanical thrombectomy have transformed the management of arterial ischemic stroke (AIS) in adults. Multiple randomized clinical trials have demonstrated that these therapies enable remarkable improvements in clinical outcome for properly selected patients with AIS. Because pediatric patients were excluded from predicate clinical trials, there is a conspicuous lack of data to guide selection of therapies and inform age-adjusted and pathology-oriented treatment modifications for children. Specifically, technical guidance concerning treatment eligibility, drug dosing, and device implementation is lacking. This review aims to outline important features that differentiate pediatric AIS from adult AIS and provide practical strategies that will assist the stroke specialist with therapeutic decision making.
A twelve-month projection to September 2022 of the Covid-19 epidemic in the UK using a Dynamic Causal Model
Authors: Bowie Cam , Friston Karl 
Published: October 2021

AbstractObjectivesPredicting the future UK Covid-19 epidemic allows other countries to compare their epidemic with one unfolding without public health measures except a vaccine programme.MethodsA Dynamic Causal Model (DCM) is used to estimate the model parameters of the epidemic such as vaccine effectiveness and increased transmissibility of alpha and delta variants, the vaccine programme roll-out and changes in contact rates. The model predicts the future trends in infections, long-Covid, hospital admissions and deaths.ResultsTwo dose vaccination given to 66% of the UK population prevents transmission following infection by 44%, serious illness by 86% and death by 93%. Despite this, with no other public health measures used, cases will increase from 37 million to 61 million, hospital admission from 536,000 to 684,000 and deaths from 136,000 to 142,000 over twelve months.DiscussionVaccination alone will not control the epidemic. Relaxation of mitigating public health measures carries several risks – overwhelming the health services, the creation of vaccine resistant variants and the economic cost of huge numbers of acute and chronic cases.
Factors affecting the choice of a future medical specialty of the junior doctors in a third world country
Authors: Malik Ifrah J. , Tameez-ud-din Ahsan , Tameez Ud Din Asim , Mohyud Din Farooq 
Published: October 2021

ABSTRACTBackground and ObjectivePakistan is facing a major brain drain and as long as there is not a better understanding of the needs and desires of the junior doctors, this exodus towards the greener pastures shall continue. This study is an effort to recognize the factors which influence the choice of a future specialty of young Pakistani doctors in order to help identify the areas which need improvement.Study designThis descriptive cross-sectional study was conducted from 12th May, 2021 to 2nd August, 2021. Young doctors who had completed their one-year internship in hospitals of Punjab were invited to fill the questionnaire via social media platforms. Data were entered and analyzed using the Statistical Package for Social Sciences (SPSS) version 23.0. Chi-square tests were applied for qualitative variables. A p-value of less than 0.05 was considered significant.ResultsOut of a total 105 participants, 60 (57.1%) were females. More females as compared to males decided the future specialty based on work-life balance (20/27, p= 0.039). Internal medicine and general surgery were the most sought-after fields both before and after the internship. Forty-three (41%) participants wished to change their choice of specialty after their house job experiences. Fifty-eight (55.2%) participants considered the future prospects of the field while deciding their specialty while sixty-three (60%) reported the attitude of the senior doctors as an important deciding factor. The Covid-19 pandemic had an effect on 12 (11.4%) participants’ decision regarding their choice of future specialty.ConclusionMany elements such as internship play a pivotal role in helping the young doctors to narrow their choices. It is important to understand the factors considered by young doctors during their choice of a medical specialty to ensure that a significant proportion of medical work force does not slip through the cracks in our health infrastructure.
SparsePro: an efficient fine-mapping method integrating summary statistics and functional annotations
Authors: Zhang Wenmin , Najafabadi Hamed , Li Yue 
Published: October 2021

AbstractIdentifying causal variants from genome-wide association studies (GWAS) is challenging due to widespread linkage disequilibrium (LD) and the possible existence of multiple causal variants in the same genomic locus. Functional annotations of the genome may help to prioritize variants that are biologically relevant and thus improve fine-mapping of GWAS results. Classical fine-mapping methods conducting an exhaustive search of variant-level causal configurations have a high computational cost, especially when the underlying genetic architecture and LD patterns are complex. SuSiE provided an iterative Bayesian stepwise selection algorithm for efficient fine-mapping. In this work, we build connections between SuSiE and a paired mean field variational inference algorithm through the implementation of a sparse projection, and propose effective strategies for estimating hyperparameters and summarizing posterior probabilities. Moreover, we incorporate functional annotations into fine-mapping by jointly estimating enrichment weights to derive functionally-informed priors. We evaluate the performance of SparsePro through extensive simulations using resources from the UK Biobank. Compared to state-of-the-art methods, SparsePro achieved improved power for fine-mapping with reduced computation time. We demonstrate the utility of SparsePro through fine-mapping of five functional biomarkers of clinically relevant phenotypes. In summary, we have developed an efficient fine-mapping method for integrating summary statistics and functional annotations. Our method can have wide utility in understanding the genetics of complex traits and increasing the yield of functional follow-up studies of GWAS. SparsePro software is available on GitHub athttps://github.com/zhwm/SparsePro.1Author SummaryAccurately identifying causal variants from genome-wide association studies summary statistics is important for understanding genetic architecture of complex traits and identifying therapeutic targets. Functional annotations are commonly used as additional evidence for prioritizing causal variants. In this study, we present SparsePro to integrate summary statistics and functional annotations for accurate identification of causal variants. SparsePro extends the capabilities of a popular fine-mapping method, SuSiE, with important contributions in hyperparameter estimation, posterior summaries and integration of function annotations. Through extensive simulations, we demonstrate that our proposed approach can effectively integrate summary statistics and functional annotation, leading to improved power for identifying causal variants. Furthermore, we evaluate the benefits of incorporating functional annotations through real data analyses of five functional biomarkers. In summary, by improving power and providing valuable insights into complex disease genetics, SparsePro will have wide utility in advancing our knowledge and facilitating follow-up discoveries.