bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial strain performance in patients with paroxysmal atrial fibrillation undergoing successful radio-frequency catheter ablation
Authors: Katbeh A , De Potter T , Geelen P , Nagumo S , Balogh Z , Albano M , Van Camp G , Penicka M
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): International PhD Program in Cardiovascular Pathophysiology and Therapeutics CardioPaTh

Background

Radio-frequency catheter ablation (CA) is associated with changes of left atrial (LA) structure and function. However, there is limited knowledge regarding the long-term impact of successful CA on atrial morphology and mechanics.

Purpose

To compare the time course of LA and right atrial (RA) performance in patients with paroxysmal atrial fibrillation (AF) undergoing the first CA.

Methods

This prospective study included 89 consecutive patients (age:62 ± 21 years; 66% male) with a history of symptomatic AF who underwent successful CA. All patients maintained SR during follow-up. A comprehensive echocardiographic examination was performed 1- day before and 1-day, 3-month and 12-month after CA. The reservoir and contractile strain for both LA and RA (LAS, RAS), and left intra-atrial mechanical dispersion (LAMD) were assessed using 2D speckle tracking echocardiography in all three apical views (only 4CH view for RAS and LAMD).

Results

At baseline, all patients with paroxysmal AF showed a significant reduction of reservoir and contractile LAS and RAS compared with controls (all p < 0.01). CA was associated with a significant decrease in reservoir and contractile LAS while no significant difference was observed for RAS. At 3-month follow-up, the LAS showed full recovery, whereas the RAS did not show any significant change from 1-day post CA values. At 12-month follow-up, both reservoir and contractile LAS showed further improvement compared to baseline and 3-month values. LAMD derived from the LA strain curve followed a similar trend. Although the RA motion was not affected in the early phase, both reservoir and contractile RAS showed a significant increase between 3-month and 12-month follow-up.

Conclusion

Although the radio-frequency CA affected negatively LA performance in the acute phase, it has a long-term positive impact on both left and right atrial function.

Figure

Time course of reservoir and contractile LAS and RAS at Baseline, 1-day, 3-month and 12-month follow-up.

Abstract Figure.
Functional adaptation of the right ventricle to different degrees of the left ventricular systolic dysfunction in patients with left-sided heart disease: a three-dimensional echocardiography study
Authors: Surkova E , Kovacs A , Tokodi M , Lakatos BK , Muraru D , Badano LP
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Right ventricular (RV) systolic dysfunction in patients with left-sided heart disease is known adverse factor. However, the RV adaptation at the different degrees of left ventricular (LV) dysfunction remains to be clarified.

Purpose

 to assess the change in RV contraction pattern in relation to LV ejection fraction (EF) in patients with left-sided heart disease.

Methods. LV and RV volumes and EF were measured by 3D-echocardiography in 295 patients with left-sided heart disease (59 ± 17years, 69% male). The 3D meshmodel of the RV was postprocessed by the ReVISION software and its contraction pattern was decomposed along the longitudinal, radial and anteroposterior directions (Fig. A) providing longitudinal, radial and anteroposterior EF (LEF, REF, AEF). Relative contribution of each component to the RV systolic function was measured as the ratio between LEF, REF and AEF and global RVEF (LEFi, REFi, AEFi).

Results. Patients with LV systolic dysfunction also had reduced RVEF. Relative contribution of the longitudinal and anteroposterior components decreased, while radial component increased in patients with reduced LVEF (Table).

RV LEF and AEF significantly correlated with the LVEF (Rho 0.50 and 0.51, p < 0.0001), while the correlation between REF and LVEF was weak (Rho 0.22, p = 0.0002).

There was a significant drop in LEF and AEF (Fig. B) and their relative contribution to the total RVEF (Fig. C) starting from the earlier stages of LV dysfunction. However, it was effectively compensated by significant increase in the radial RV component resulting in preservation of total RVEF in those with normal, mildly and moderately reduced LVEF (50 [46;54] vs 47 [44;52] vs 46 [42;49]%), whereas total RVEF dropped significantly only in severe LV dysfunction (30 [25;39]%; p < 0.0001) (Fig. D).

Conclusions. The longitudinal and anteroposterior RV contraction was related to the LVEF and decreased from early stages of the LV systolic dysfunction. Increase in the radial component compensated for the loss of longitudinal and anteroposterior RV components in mild and moderate LV dysfunction to maintain total RVEF. Drop in all three components resulted in significant reduction of total RVEF in severe LV dysfunction.

Characteristics of study population Overall (N = 295) LVEF≥50% (N = 166) LVEF < 50% (N = 129) LV EF, % 49.6 ± 14.3 59.9 ± 5.6 36.4 ± 10.9* RV EF, % 46.5 ± 9.2 49.8 ± 6.9 42.3 ± 10.0* RV LEFi 0.42 ± 0.09 0.45 ± 0.09 0.38 ± 0.09* RV REFi 0.47 ± 0.1 0.45 ± 0.1 0.50 ± 0.09* RV AEFi 0.39 ± 0.08 0.41 ± 0.08 0.37 ± 0.07* *p < 0.0001 Abstract Figure.
Retrogated compressed sensing cine in one minute
Authors: Longere B , Grenier L , Pagniez J , Silvestri V , Simeone A , Hennicaux J , Toupin S , Pontana F
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

PURPOSE

Real-time compressed sensing cine (CSrt) provides reliable quantifications for both ventricles but impairs image quality . This aim of this study was to assess the accuracy of left (LV) and right ventricular (RV) volumes, ejection fraction and mass quantifications based on a retrogated segmented compressed sensing-fashioned accelerated 2D cine sequence (CSrg). Image quality was also evaluated.

METHOD AND MATERIALS

Thirty patients were enrolled. Each patient underwent the reference retrogated segmented steady-state free precession cine sequence (SSFPref), the first generation real-time CSrt cine and the segmented retrogated prototype CSrg sequence providing the same numbers and positions of slices. Functional parameters quantification was performed on SSFPref and CSrg images sets. Image quality was assessed for the three sequences by using edge sharpness which is an estimate of the edge spread function.

RESULTS

Mean scan times were

SSFPref = 512 ± 15 s, CSrt = 24 ± 5 s and CSrg = 58 ± 15 s. CSrg provided LV and RV functional parameters (end-systolic, end-diastolic, ejection fraction and LV mass) which were not significantly different from the one assessed with SSFPref (p > 0.05). Edge sharpness was significantly better with CSrg (0.083 ± 0.013 pixel-1) than with CSrt (0.070 ± 0.011 pixel-1; p = 0.0004) and not different from the reference techniques (0.075 ± 0.016 pixel-1; p = 0.0516). Inter and intrarater variabilities demonstrated intraclass correlation coefficients over 0.96.

CONCLUSION

CSrg cine provides in one minute an accurate quantification of LV and RV functional parameters without compromising the sharpness of myocardial boarders which was impaired by the first-generation real-time compressed sensing sequence.

Abstract Figure. Image quality and volumes assessment
Can deep learning identify normal coronary flow reserve from rubidium myocardial PET perfusion?
Authors: Hoath J , Menezes LJ , Hamilton O , Endozo R , Wan S , Katramados I , Kayani I , Groves AM
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Impaired vasodilator function is an early manifestation of coronary artery disease (CAD) and may precede angiographic stenosis.  Rest and stress myocardial blood flow (MBF) are calculated from dynamic imaging during rest/stress Rubidium (Rb) myocardial PET perfusion.  Coronary flow reserve (CFR) equals stress divided by rest MBF.  CFR is an independent predictor of cardiac mortality in patients with known or suspected CAD.  We evaluated the prediction of CFR from analysis of stress/rest PET images by deep learning (DL) as compared with standard calculation of CFR using supervised learning applied methodology using within a commercial DL training platform.

Methods

1036 patients (625 male, 411 female, mean age: 64.3 years old) were studied. Patients underwent Stress/rest Rb PET perfusion, and CFR calculated using MBF software by an expert user. Abnormal CFR was defined as <2.0. The left ventricle myocardium was segmented using standard software.

DL was trained using polar distribution of normalized PET uptake at stress and rest, processed stress and rest images were cropped, the stress images were then subtracted from the rest images. DL was trained using 935 subtracted images and tested using the remaining 101 images. DL was trained with supervision to classify images. The image shows examples of subtracted  abnormal cases (1a & 1b).

Results

Using our supervised training methodology, the commercial MBF software platform reported 465 cases as abnormal, with 48 of these were included in the DL test set. The DL platform produced abnormal output classifiers for all the whole test set. DL accurately detected over 70% of abnormal cases.

The commercial MBF software reported 571 cases as normal; with 50 of these contributing to the DL test set. DL was accurate in 48.0% of normal cases. Statistical results are shown in the table.

Conclusion

We have shown the proof of concept that DL algorithms trained with supervision can detect abnormal CFR. Our work shows that further work is needed to develop supervised learning methodology in order to improve accuracy for clinical use.

Statistical Results Statistic Value Sensitivity 63.16% Specificity 56.67% + Predictive Value 48.00% - Predictive Value 70.83% Accuracy 59.18% Abstract Figure.
The association between coronary graft patency and clinical status in patients with coronary artery disease
Authors: Gaudino Mario , Di Franco Antonino , Bhatt Deepak L , Alexander John H , Abbate Antonio , Azzalini Lorenzo , Sandner Sigrid , Sharma Garima , Rao Sunil V , Crea Filippo , Fremes Stephen E , Bangalore Sripal
Published: February 2021

The concept of a direct association between coronary graft patency and clinical status is generally accepted. However, the relationship is more complex and variable than usually thought. Key issues are the lack of a common definition of graft occlusion and of a standardized imaging protocol for patients undergoing coronary bypass surgery. Factors like the type of graft, the timing of the occlusion, and the amount of myocardium at risk, as well as baseline patients’ characteristics, modulate the patency-to-clinical status association. Available evidence suggests that graft occlusion is more often associated with non-fatal events rather than death. Also, graft failure due to competitive flow is generally a benign event, while graft occlusion in a graft-dependent circulation is associated with clinical symptoms. In this systematic review, we summarize the evidence on the association between graft status and clinical outcomes.
Divergence in Coding Sequence and Expression of Different Functional Categories of Immune Genes between Two Wild Rodent Species
Authors: Zhong Xiuqin , Lundberg Max , Råberg Lars
Published: February 2021

Differences in immune function between species could be a result of interspecific divergence in coding sequence and/or expression of immune genes. Here, we investigate how the degree of divergence in coding sequence and expression differs between functional categories of immune genes, and if differences between categories occur independently of other factors (expression level, pleiotropy). To this end, we compared spleen transcriptomes of wild-caught yellow-necked mice and bank voles. Immune genes expressed in the spleen were divided into four categories depending on the function of the encoded protein: pattern recognition receptors (PRR); signal transduction proteins; transcription factors; and cyto- and chemokines and their receptors. Genes encoding PRR and cyto-/chemokines had higher sequence divergence than genes encoding signal transduction proteins and transcription factors, even when controlling for potentially confounding factors. Genes encoding PRR also had higher expression divergence than genes encoding signal transduction proteins and transcription factors. There was a positive correlation between expression divergence and coding sequence divergence, in particular for PRR genes. We propose that this is a result of that divergence in PRR coding sequence leads to divergence in PRR expression through positive feedback of PRR ligand binding on PRR expression. When controlling for sequence divergence, expression divergence of PRR genes did not differ from other categories. Taken together, the results indicate that coding sequence divergence of PRR genes is a major cause of differences in immune function between species.
Intellectual property and essential medicines in the COVID-19 pandemic
Authors: De Campos-Rudinsky Thana C
Published: February 2021

Global justice theorists have widely discussed how the international intellectual property rights regime (i.e., the TRIPs regime of the World Trade Organization) makes it more difficult to achieve the goal of universal access to generic (and more affordable) vital COVID-19 treatments (including potential COVID-19 vaccines). This article argues that while patents can impose certain barriers to universal access to generic COVID-19 treatments, the TRIPs regime itself is an integral part of an equitable global solution to the pandemic. More specifically, it argues that article 31bis of the TRIPs, in allowing for a cooperation strategy predicated on complementary importing and exporting of vital COVID-19 generic treatments, is key for successful pandemic suppression. By providing a normative interpretative analysis of article 31bis in light of the ethical requirements of global justice, and by responding to possible objections to its core argument, this article substantiates the ideal of multilateral solidarity among nations. In times of crisis—not only a crisis of global public health, but also a crisis of multilateralism—this complementary cooperation strategy that article 31bis allows for shows a way forward in upholding the global common good that the international legal order seeks to safeguard.
On the Definition of Irreducible Holomorphic Symplectic Manifolds and Their Singular Analogs
Authors: Schwald Martin
Published: February 2021

In the definition of irreducible holomorphic symplectic manifolds the condition of being simply connected can be replaced by vanishing irregularity. We discuss holomorphic symplectic, finite quotients of complex tori with ${\operatorname{h}}^0(X,\,\Omega ^{[2]}_X)=1$ and their Lagrangian fibrations. Neither $X$ nor the base can be smooth unless $X$ is a $2$-torus.
Optimal feed level during the transition period to achieve faster farrowing and high colostrum yield in sows
Authors: Feyera Takele , Skovmose Sigrid J W , Nielsen Signe E , Vodolazska Darya , Bruun Thomas S , Theil Peter K
Published: February 2021

This study aimed to determine the optimal supply of lactation feed during the transition period to minimize farrowing duration (FD) and maximize colostrum yield (CY) and quality with the overall aim of reducing piglet mortality. A total of 48 sows were stratified for body weight and assigned to six levels of feed supply (1.8, 2.4, 3.1, 3.7, 4.3, and 5.0 kg/d) from day 108 of gestation until 24 h after the onset of farrowing. The number of total born, live-born, and stillborn piglets; birth time and birth weight of each piglet; and frequency of farrowing assistance (FA) was recorded, and blood samples were obtained from newborn piglets at birth. Live-born piglets were further weighed at 12 and 24 h after birth to record weight gain, which in turn was used to estimate intake and yield of colostrum. Colostrum samples were collected at 0, 12, 24, and 36 h after the onset of farrowing. FD was shortest (4.2 h) at intermediate (3.7 kg/d), longest (7.1 to 7.6 h) at low (1.8 and 2.4 kg/d), and intermediate (5.6 to 5.7 h) at high (4.3 and 5.0 kg/d) feed intake (P = 0.004; mean comparison). FA was lowest (0.7% to 0.8%) at intermediate feed intake (3.7 and 4.3 kg/d) and substantially elevated (4.3% to 4.7%) at both lower and higher feed intake (P = 0.01; mean comparison). The cubic contrast revealed 4.1 kg/d as the optimal feed intake to achieve the shortest FD and to minimize FA. Newborn piglets from second-parity sows were less vital than piglets from gilts as evaluated by blood biochemical variables immediately after birth. CY was greatest at 3.1 kg/d (P = 0.04), whereas the cubic contrast revealed 3.0 kg/d as the optimal feed intake to maximize CY. Concentrations of colostral components were affected by the diet, parity, and their interaction except for lactose concentrations. In conclusion, the study demonstrated the importance of proper feed level during the transition period on sow productivity. Moreover, this study estimated 4.1 and 3.0 kg/d as the optimal feed intake during the transition period to improve farrowing characteristic and CY, respectively, and these two feed intake levels supplied daily 38.8 MJ metabolizable energy (ME) and 23.9 g standardized ileal digestible (SID) lysine (3.0 kg/d) or 53.0 MJ ME and 32.7 g SID lysine (4.1 kg/d). The discrepancy of optimal feed intake for optimal farrowing and colostrum performance suggests that it may be advantageous to lower dietary lysine concentration in the diet fed prepartum.
Brexit and Trade Defence: Effects of a Changed Territory
Authors: Bickel Fabian
Published: February 2021

After the UK’s withdrawal from the European Union (EU), the EU’s trade defence measures no longer applied to the territory of the UK. This means that the UK now applies its own trade defence measures and has transitioned some of the EU’s trade defence measures. The EU applies its trade defence measures to the reduced territory of the EU27, while third parties that had imposed trade defence measures against the EU now apply them against the EU27 and the UK. This article analyses the compatibility of these changed measures with WTO law. It argues first that in principle WTO law allows changes in the territorial scope of trade defence measures if the investigation and imposition of the measures remain attributable to the imposing WTO Member. This defends the EU’s and the UK’s approaches. Second, changed circumstances’ reviews or adaptations of the measures by the EU or the UK may be necessary. However, this happens rarely and only if specific evidence is provided. Third, subject to review or adaptations where warranted, third countries can apply their measures targeting the EU against the EU27 and the UK.
Comparison of performances of different fungal laccases in delignification and detoxification of alkali-pretreated corncob for bioethanol production
Authors: Liu Shenglong , Liu Huan , Shen Chen , Fang Wei , Xiao Yazhong , Fang Zemin
Published: February 2021

The performance of the alkaline fungal laccase PIE5 (pH 8.5) in the delignification and detoxification of alkali-pretreated corncob to produce bioethanol was evaluated and compared with that of the neutral counterpart (rLcc9, 6.5), with the acidic laccase rLacA (4.0) was used as an independent control. Treatment with the three laccases facilitated bioethanol production compared with their respective controls. The lignin contents of alkali-pretreated corncob reduced from 4.06%, 5.06%, and 7.80% to 3.44%, 3.95%, and 5.03%, after PIE5, rLcc9, and rLacA treatment, respectively. However, the performances of the laccases were in the order rLacA > rLcc9 > PIE5 in terms of decreasing total phenol concentration (0.18, 0.36, and 0.67 g/l), boosting ethanol concentration (8.02, 7.51, and 7.31 g/l), and volumetric ethanol productivity (1.34, 0.94, and 0.91 g/l hr), and shortening overall fermentation time. Our results would inform future attempts to improve laccases for ethanol production. Furthermore, based on our data and the fact that additional procedures, such as pH adjustment, are needed during neutral/alkaline fungal laccase treatment, we suggest acidic fungal laccases may be a better choice than neutral/alkaline fungal laccases in bioethanol production.
Standard contractual clauses for cross-border transfers of health data after Schrems II
Authors: Bradford Laura , Aboy Mateo , Liddell Kathleen
Published: February 2021

Standard contractual clauses (SCCs) have long been considered the most accessible method to transfer personal data legally across borders. In July 2020, the Court of Justice of the European Union (CJEU) in Data Protection Commissioner v Facebook Ireland Limited, Maximillian Schrems (Schrems II) placed heavy conditions on their use. The Schrems II Court found that SCCs were valid as ‘appropriate safeguards’ for data transfers from EU entities to others outside the EU/EEA as long as unspecified ‘supplementary measures’ were in place to compensate for the lack of data protection in the third country. Data protection officers are under intense pressure to explain these measures and allow routine transfers to continue. Some authorities interpret the decision as preventing the use of SCCs to transfer personal data outside of the EU because private contracts cannot comprehensively redress gaps in national law. This article argues that these authorities are mistaken and that notwithstanding Schrems II SCCs can still be useful instruments for cross-border transfers. This is especially true in highly regulated contexts such as medical research. This paper traces the history of SCCs under the General Data Protection Regulation (GDPR) and shows how the CJEU in Schrems II misunderstood the purpose of SCCs and other Article 46 GDPR ‘appropriate safeguards’. The CJEU mistakenly approached Article 46 safeguards such as SCCs as being similar to country-specific adequacy rulings under Article 45 GDPR. But unlike Article 45 adequacy rulings, SCCs were not intended to provide a stand-alone mechanism for transfer reliant on the law of the importing country. Rather SCCs provide an alternative, multi-layered standard for data protection that encompasses law, technology and organizational commitments. Their purpose is to be used in situations where legislation alone is insufficient to protect data subject rights. The European Commission’s new draft SCCs support this analysis.
PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS: the conductors of dual reproduction in plants with vegetative storage organs
Authors: Khosa Jiffinvir , Bellinazzo Francesca , Kamenetsky Goldstein Rina , Macknight Richard , Immink Richard G H
Published: February 2021

Geophytes, the plants that form vegetative storage organs, are characterized by a dual reproduction system, in which vegetative and sexual propagation are tightly regulated to ensure fitness in harsh climatic conditions. Recent findings highlight the role of the PEBP (PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN) gene family in geophytes as major players in the molecular cascades underlying both types of reproduction. In this review, we briefly explain the life cycle and reproduction strategies of different geophytes and what is known about the physiological aspects related to these processes. Subsequently, an in-depth overview is provided of the molecular and genetic pathways driving these processes. In the evolution of plants, the PEBP gene family has expanded, followed by neo- and subfunctionalization. Careful characterization revealed that differential expression and differential protein complex formation provide the members of this gene family with unique functions, enabling them to mediate the crosstalk between the two reproductive events in geophytes in response to environmental and endogenous cues. Taking all these studies into account, we propose to regard the PEBPs as conductors of geophyte reproductive development.
The integrity of the U12 snRNA 3′ stem–loop is necessary for its overall stability
Authors: Norppa Antto J , Frilander Mikko J
Published: February 2021

Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C>U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C>T mutation in the U12 snRNA gene (RNU12). We show that the 84C>U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3′-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C>U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3′-to-5′ exonuclease. Finally, we show that several other single-nucleotide variants in the 3′ stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3′ stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.
Neurosurgery Resident Interviews: The Prevalence and Impact of Inappropriate and Potentially Illegal Questions
Authors: Limoges Natalie , Zuckerman Scott L , Chambless Lola B , Benzil Deborah L , Cruz Aurora , Borden Jonathan H , Durham Susan
Published: February 2021

BACKGROUND

The impact of workplace discrimination has gained recognition. Nearly two-thirds of all medical residency applicants reported being asked inappropriate or potentially illegal interview questions. The use of such questions during neurosurgery residency interviews has not yet been studied.

OBJECTIVE

To evaluate the prevalence of inappropriate or potentially illegal questions in residency interviews and the impact on applicants’ rank lists.

METHODS

All 2018 to 2019 United States neurosurgery resident applicants were anonymously surveyed. The survey included 46 questions focused on demographics; if they were asked questions regarding rank list, age, gender, marital status, family planning, religion, sexual orientation, or disability and whether such questions affected their rank list formation.

RESULTS

Of 265 surveyed United States applicants, 133 (50%) responded. Most respondents were male (78%), 24% were married, and 10% had children. During the formal interview, 94% were asked at least 1 inappropriate or potentially illegal question. About 78% reported being asked about marital status, 29% were asked about intent to have children. About 46% reported being counseled on their personal life, 30% were asked about their ethnic background, and 15% were asked about their religion. A total of 2 candidates reported questions about mental illness/disability, and 2 candidates reported being asked about sexual orientation. About 45% of applicants that were asked at least 1 of these questions ranked those programs lower.

CONCLUSION

Nearly all (94%) neurosurgical residency applicants reported being asked at least 1 inappropriate or potentially illegal question during interviews. Our results indicate that inappropriate questions negatively affected program rankings.
Re-evaluating Biopsy for Recurrent Glioblastoma: A Position Statement by the Christopher Davidson Forum Investigators
Authors: Nduom Edjah K , Gephart Melanie Hayden , Chheda Milan G , Suva Mario L , Amankulor Nduka , Battiste James D , Campian Jian L , Dacey Ralph G , Das Sunit , Fecci Peter E , Hadjipanayis Constantinos G , Hoang Kimberly B , Jalali Ali , Orringer Daniel , Patel Akash J , Placantonakis Dimitris , Rodriguez Analiz , Yang Isaac , Yu Jennifer S , Zipfel Greg J , Dunn Gavin P , Leuthardt Eric C , Kim Albert H ,   on behalf of the Christopher Davidson Forum Investigators
Published: February 2021

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.
Analysis of the Driving Factors of Active and Rapid Growth Clusters Among CRF07_BC-Infected Patients in a Developed Area in Eastern China
Authors: Fan Qin , Zhang Jiafeng , Luo Mingyu , Yao Jiaming , Ge Rui , Yan Yong , Ding Xiaobei , Chen Wanjun , Pan Xiaohong
Published: February 2021

Background

The purpose of this study was to research the molecular transmission and genetic evolutionary characteristics among CRF07_BC-infected patients in a developed area in Eastern China.

Methods

Plasma samples from newly diagnosed HIV-1-positive patients from 2015–2018 and basic demographic and epidemiological information were obtained. Pol sequences from CRF07_BC-infected patients were selected for phylogenetic, molecular transmission network, and Bayesian evolutionary analyses.

Results

Pol sequences were successfully obtained from 258 samples of CRF07_BC. Phylogenetic analysis revealed 2 distinct lineages: lineage 1 (66.3%, 171/258), primarily from men who have sex with men (MSM) and some heterosexual individuals, and lineage 2 (33.7%, 87/258), primarily from heterosexual individuals. Under an optimal genetic distance of 0.01 substitutions/site, 163 individuals (63.2%, 163/258) formed 23 groups comprising 6 clusters and 17 dyads in the networks. A distinctly large and rapidly growing cluster (C1) containing 105 individuals was identified, in which MSM with ≥4 links had quite a high transmission risk (low educational background, active sexual behavior, low sexual protection awareness, etc.). According to Bayesian analyses, most C1 clades formed from 2005 to 2009, most of which were closely geographically related to CRF07_BC epidemic strains from Anhui province.

Conclusions

Here, we elucidated the local transmission characteristics and epidemic pattern of HIV-1 CRF07_BC, revealing that MSM (especially with ≥4 links) may be a significant driver in the formation of active and rapid growth networks in regional CRF07_BC epidemics. Thus, unique region– and risk group–specific transmission network analysis based on a molecular approach can provide critical and insightful information for more effective intervention strategies to limit future HIV-1 transmission.
Spatially resolved X-ray spectroscopy of the archetype type 2 active galactic nucleus NGC 1068 with Chandra
Authors: Nakata Ryo , Hayashida Kiyoshi , Noda Hirofumi , Yoneyama Tomokage , Matsumoto Hironori , Imanishi Masatoshi
Published: February 2021

We investigate spatial distributions of iron Kα (Fe-Kα) lines in the cental 100 pc of the Seyfert 2 galaxy NGC 1068 observed with Chandra. The spatial distributions of Fe-Kα lines, neutral and highly ionized, around the center of the galactic nucleus are not isotropic, as consistently confirmed in both image and spectral analyses. The hydrogen number density of the gas clouds responsible for the neutral Fe-Kα line emission is estimated to be 102–103 cm−3 for the sampled regions near the galactic core. The photo-ionization model, where iron is assumed to be ionized by X-rays from the galactic nucleus, yields ionization parameters lower than 19 for these clouds. The range of this ionization parameter is two or three orders of magnitude lower than the theoretically expected value to produce the observed helium-like Fe-Kα line intensities. Therefore, the photo-ionization model is excluded from the explanation of the amount of highly ionized iron that is responsible for the observed Fe-Kα lines. Also, we find anti-correlation in the spatial distributions between the molecular cloud in the area observed with ALMA and that of the Fe-Kα lines, including that from neutral iron. We suggest that X-ray iron-line and radio molecular cloud observations are complementary to probe the distribution of matters in the central regions around the cores of active galactic nuclei.
Nutrition in Physical Therapist Practice: Tools and Strategies to Act Now
Authors: Berner Patrick , Bezner Janet R , Morris David , Lein Donald H
Published: February 2021

It has been established that physical therapist practice includes screening for and providing information on diet and nutrition to patients, clients, and the community. Yet, an overwhelming amount of often contradictory diet and nutrition information poses a challenge for physical therapists to identify and maintain knowledge that they can rely on to screen for and discuss these topics with their patients, clients, and community members. The purposes of this perspective paper are to summarize the best known screening tools for general health, diet, and nutrition; provide intervention strategies that can be used to support behavior change related to diet and nutrition; and identify the most relevant resources and approaches from which physical therapist clinicians can build skill in addressing the nutritional needs of patients, clients, and the community.
Reinterpreting pagtitimpi as a Filipino value in mitigating the COVID-19 transmission
Authors: Galang Joseph Renus F
Published: February 2021

Aside from the Christmas season, another cultural period that stimulates abundant tourism and travel in the Philippines is the Lenten season. Hence, this season is a major setback in the containment of the coronavirus disease 2019. Fasting and abstinence, acts which mark the Lenten season, are closely tied up with the Filipino cultural value of pagtitimpi in that both promote restraint and self-denial. Ultimately, this article suggests that reinterpreting pagtitimpi can be crucial in controlling the virus.
Cross-Border Bank Flows and Monetary Policy
Authors: Correa Ricardo , Paligorova Teodora , Sapriza Horacio , Zlate Andrei
Published: February 2021

We analyze the impact of monetary policy on cross-border bank flows for a large sample of countries over two decades. We find evidence in favor of a cross-border risk-taking channel, as the monetary policy stance of source countries is an important determinant of cross-border bank flows. A relatively tighter monetary policy in source countries prompts banks to reallocate their lending toward safer foreign counterparties. The cross-border reallocation of credit is more pronounced for source countries with lower-capitalized banks. Also, the reallocation is directed toward foreign borrowers in relatively safer destinations, such as advanced economies or economies with investment-grade sovereign ratings.
Diagnostic criteria for early hip osteoarthritis: first steps, based on the CHECK study
Authors: Runhaar Jos , Özbulut Ömer , Kloppenburg Margreet , Boers Maarten , Bijlsma Johannes W J , Bierma-Zeinstra Sita M A ,   the CREDO expert group
Published: February 2021

Objectives

Although there is a general focus on early diagnosis and treatment of hip OA, there are no validated diagnostic criteria for early-stage hip OA. The current study aimed to take the first steps in developing diagnostic criteria for early-stage hip OA, using factors obtained through history taking, physical examination, radiography and blood testing at the first consultation in individuals presenting with hip pain, suspicious for hip OA, in primary care.

Methods

Data of the 543 individuals with 735 symptomatic hips at baseline who had any follow-up data available from the prospective CHECK cohort study were used. A group of 26 clinical experts [general practitioners (GPs), rheumatologists and orthopaedic surgeons] evaluated standardized clinical assessment forms of all subjects on the presence of clinically relevant hip OA 5–10 years after baseline. Using the expert-based diagnoses as reference standard, a backward selection method was used to create predictive models based on pre-defined baseline factors from history taking, physical examination, radiography and blood testing.

Results

Prevalence of clinically relevant hip OA during follow-up was 22%. Created models contained four to eight baseline factors (mainly WOMAC pain items, painful/restricted movements and radiographic features) and obtained area under the curve between 0.62 (0.002) and 0.71 (0.002).

Conclusion

Based on clinical and radiographic features of hip OA obtained at first consultation at a GP for pain/stiffness of the hip, the prediction of clinically relevant hip OA within 5–10 years was ‘poor’ to ‘fair’.
A dysregulated interleukin-18–interferon-γ–CXCL9 axis impacts treatment response to canakinumab in systemic juvenile idiopathic arthritis
Authors: Hinze Tanja , Kessel Christoph , Hinze Claas H , Seibert Julia , Gram Hermann , Foell Dirk
Published: February 2021

Objectives

The monoclonal IL-1β antibody canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (SJIA). Its efficacy has been proven in several trials, but not all patients show a complete and sustained response to therapy. We aimed to analyse the association of baseline serum biomarkers with treatment outcome in patients with SJIA treated with canakinumab.

Methods

Serum samples from 54 patients with active SJIA without recent macrophage activation syndrome (MAS) treated with canakinumab in an open-label response characterization study were subjected to a multiplexed bead array assay. Interesting targets from these analyses were validated by ELISA. Clinical treatment outcomes included modified paediatric ACR (pACR) 30 and 90 responses, clinically inactive disease (CID) within 15 days of treatment and sustained complete response, defined as pACR100 or CID within 15 days of treatment plus no future flare or MAS.

Results

In canakinumab-naïve patients most biomarkers were elevated when compared with healthy controls at baseline and some rapidly decreased by day 15 [IL-1 receptor antagonist (IL-1RA), IL-6, IL-18 and S100A12]. Responders had higher IL-18 and IFN-γ levels and lower chemokine (C-X-C motif) ligand 9 (CXCL9) levels at baseline, emphasized by the IL-18: CXCL9 and IFN-γ: CXCL9 ratios. These ratios had significant accuracy in predicting treatment responses.

Conclusion

Differential regulation of the IL-18–IFN-γ–CXCL9 axis is observed in patients with SJIA. Higher IL-18: CXCL9 and IFN-γ: CXCL9 ratios at baseline are associated with a better clinical response to canakinumab treatment in SJIA. Future studies are needed to validate these findings and determine their generalizability to patients with recent MAS.
Characteristics associated between the incidence of hip osteoarthritis and early hip complaints (CHECK study) within 10 years
Authors: van Berkel Annemaria C , Schiphof Dieuwke , Waarsing Jan H , Runhaar Jos , van Ochten John M , Bindels Patrick J E , Bierma-Zeinstra Sita M A
Published: February 2021

Objective

To determine which baseline characteristics, especially clinically variables like pain, stiffness, physical functioning and disease variables, are associated with incident hip OA within 10 years in first presenters with hip complaints.

Rheumatology key messages History taking and not physical exam variables are associated with incident hip osteoarthritis. Specific questions about daily life activities are associated with incident hip OA. These questions are about pain while walking/shopping, difficulties putting socks on/off and rising from bed.

Methods

Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study (n = 1002). Incident hip OA was defined as fulfilling the clinical ACR criteria for hip OA, a Kellgren and Lawrence score ≥2 with hip pain, or received a hip replacement during follow-up. Baseline measurements were used of participants with hip complaints and without hip OA. Principal component analysis (PCA) was used to reduce the number of correlated variables. Associations between baseline characteristics (including PCA components) and incident hip OA were investigated using logistic regression analysis, adjusted for age, sex and BMI.

Results

In total, 312 participants (85% female and 98% Caucasian) were included, 181 developed hip OA. PCA resulted in four components. Incident hip OA was associated with (i) component 1 (general presence of pain and symptoms) [odds ratio (OR) = 1.46 (95%CI: 1.08, 1.98)], (ii) component 3 (relatively high levels of pain during shopping/walking combined with less difficulty with putting socks on/off and rising from bed) [OR = 1.58 (95%CI: 1.18, 2.12)] and (iii) knee pain [OR = 0.34 (95% CI: 0.17, 0.66)].

Conclusion

In first presenters with hip complaints, use of a few history-taking variables might allow better recognition of those at higher odds for incident hip OA within 10 years.
Test-and-treat coverage and HIV virulence evolution among men who have sex with men
Authors: Stansfield Sarah E , Herbeck Joshua T , Gottlieb Geoffrey S , Abernethy Neil F , Murphy James T , Mittler John E , Goodreau Steven M
Published: February 2021

HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage. We extended a stochastic, dynamic network model (EvoNetHIV). We varied relationship patterns (MSM vs. heterosexual), HIV transmission models (increasing vs. plateauing probability of transmission at very high viral loads), and treatment roll-out (with explicit testing or fixed intervals between infection and treatment). In scenarios most similar to previous models (longer relational durations and the plateauing transmission function), we replicated trends previously found: increasing treatment coverage led to increased virulence (0.12 log10 increase in mean population SPVL between 20% and 100% treatment coverage). In scenarios reflecting MSM behavioral data using the increasing transmission function, increasing treatment coverage selected for viruses with lower virulence (0.16 log10 decrease in mean population SPVL between 20% and 100% treatment coverage). These findings emphasize the impact of sexual network conditions and transmission function details on predicted epidemiological and evolutionary outcomes. Varying these features creates very different evolutionary environments, which in turn lead to opposite effects in mean population SPVL evolution. Our results suggest that, under some realistic conditions, effective test-and-treat strategies may not face the previously reported tradeoff in which increasing coverage leads to evolution of greater virulence. This suggests instead that a virtuous cycle of increasing treatment coverage and diminishing virulence is possible.
Plant–Microbe Interactions: From Genes to Ecosystems Using Populus as a Model System
Authors: Cregger Melissa A. , Carper Dana L. , Christel Stephan , Doktycz Mitchel J. , Labbé Jessy , Michener Joshua K. , Dove Nicholas C. , Johnston Eric R. , Moore Jessica A. M. , Vélez Jessica M. , Morrell-Falvey Jennifer , Muchero Wellington , Pelletier Dale A. , Retterer Scott , Tschaplinski Timothy J. , Tuskan Gerald A. , Weston David J. , Schadt Christopher W.
Published: February 2021

Plant–microbe symbioses span a continuum from pathogenic to mutualistic, with functional consequences for both organisms in the symbiosis. In order to increase sustainable food and fuel production in the future, it is imperative that we harness these symbioses. The tree genus Populus is an excellent model system for studies examining plant–microbe interactions due to the wealth of genomic information available and the molecular tools that have been developed to manipulate Populus–microbe symbioses. In this review, we highlight how Populus can serve as a model system to explore plant–microbe interactions. Specifically, we highlight research linking Populus–microbe interactions from the gene to the ecosystem level. We explore why Populus is an excellent model for perennial plant systems, the molecular underpinnings of Populus–microbe interactions, how host genetics influence microbial community composition, and how microbial communities vary at fine spatial scales and between Populus spp. Furthermore, we explore how changes in the microbiome may affect ecosystem-level functions in managed and natural ecosystems. Understanding and manipulating these interactions in Populus has the potential to improve plant health and affect ecosystem sustainability and processes because Populus trees function as foundational species in many natural ecosystems and are also deployed in managed ecosystems for various agroforestry applications.

[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 .
Detection and Characterization of Fusarium Wilt (Fusarium oxysporumf. sp.vasinfectum) Race 4 Causing Fusarium Wilt of Cotton Seedlings in New Mexico
Authors: Zhu Yi , Abdelraheem Abdelraheem , Lujan Phillip , Idowu John , Sullivan Patrick , Nichols Robert , Wedegaertner Tom , Zhang Jinfa
Published: February 2021

Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. vasinfectum (Atk.) W.C. Snyder & H.N. Hans (FOV), is one of the most destructive diseases of cotton (Gossypium spp.) worldwide. FOV race 4 (FOV4) is a highly virulent nominal race of this pathogen and a significant threat to cotton production in the western and southwestern USA and, potentially, the entire Cotton Belt. A field survey to identify FOV4 was performed in three southern counties of New Mexico in 619 cotton fields from 2018 to 2020. From 132 samples of cotton plants that exhibited wilt symptoms, Fusarium spp. were the most frequently isolated group of fungal species, with an isolation frequency of 57.4%. Eighty-four Fusarium spp. isolates were subsequently characterized by a DNA sequence analysis of three genes, EF-1α, PHO, and BT, encoding for translation elongation factor, phosphate permease, and β-tubulin, respectively. Forty-two isolates from 10 cotton fields were identified as FOV4 and confirmed with a positive 500-bp fragment diagnostic for FOV4. Twenty-six (62%) of the 42 FOV4 isolates were T type and the remainder (38%) were null type with and without a Tfo1 insertion in PHO, respectively. Each FOV4-infested field contained the same FOV4 genotype. Ten representative FOV4 isolates (one each from the 10 FOV4-infested fields) were evaluated for their pathogenicity on resistant Pima PHY 841 RF and susceptible Upland PHY 725 RF at 7, 14, 21, and 28 days after inoculation under temperature-controlled conditions at 21 to 22°C. Based on the disease severity rating, mortality rate, and area under the disease progress curve value, all 10 isolates were pathogenic to both cotton cultivars and differed in virulence; four isolates of the T genotype as a whole were more virulent than the six isolates of the N genotype. PHY 841 RF had significantly higher levels of resistance than PHY 725 RF to all FOV4 isolates. The results provide the first comprehensive account of the occurrence, distribution, and virulence of FOV4 in cotton production in New Mexico and will be useful for developing an effective strategy to manage FW in the state of New Mexico and the entire western and southwestern Cotton Belt.