bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comprehensive Guide to MEGA-PRESS for GABA Measurement
Authors: Peek AL , Rebbeck TJ , Leaver AM , Puts NA , Foster SL , Refshauge KM , Oeltzschner G ,   MRS Expert Panel
Published: November 2021

ABSTRACTBackgroundThe aim of this guideline is to provide a series of evidence-based recommendations that allow those new to the field of MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats.MethodsThe guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesised and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds.ResultsThe final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel.ConclusionThese 23 expert-reviewed recommendations and accompanying extended documentation form a readily usable guideline to allow those new to the field of MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.
Life course traumas, phenotypic aging, and cardiovascular disease: retrospective analysis of 104,939 UKB participants
Authors: Cao Xingqi , Zhang Jingyun , Ma Chao , Li Xueqin , Kuo Chia-Ling , Levine Morgan E. , Hu Guoqing , Allore Heather , Chen Xi , Wu Xifeng , Liu Zuyun 
Published: November 2021

AbstractBackgroundWhile childhood and adulthood traumatic experiences have been linked to subsequent cardiovascular disease (CVD), the relationship between life course traumas and CVD and the underpinning pathways are poorly understood. This study aimed to: (1) examine the associations of childhood, adulthood, and lifetime traumas with CVD; (2) examine the associations between diverse life course traumatic profiles and CVD; and (3) examine the extent to which Phenotypic Age (PhenoAge), a well-developed phenotypic aging measure, mediates these associations.MethodsWe included 104,939 participants from the UK Biobank who completed the 2016 online mental health questionnaire. CVD outcomes including ischemic heart disease, myocardial infarction, and stroke were ascertained. Childhood, adulthood, and lifetime traumas were categorized into three subgroups (mild, moderate, and severe), respectively. Four life course traumatic profiles were defined as non-severe traumas across life course, non-severe childhood and severe adulthood traumas, severe childhood and non-severe adulthood traumas, and severe traumas across life course based on both childhood and adulthood traumas. PhenoAge was measured using an equation previously developed. Multivariable logistic models and formal mediation analyses were performed.ResultsOf 104,939 participants, 7,398 (7.0%) were diagnosed with CVD. Subgroups of childhood, adulthood, and lifetime traumas were associated with CVD, respectively. Furthermore, life course traumatic profiles were significantly associated with CVD. For instance, compared with subgroups experiencing non-severe traumas across life course, those who experienced non-severe childhood and severe adulthood traumas, severe childhood and non-severe adulthood traumas, and severe traumas across life course had higher odd of CVD, with odds ratios of 1.07 (95% confidence interval [CI]: 1.00, 1.15), 1.17 (95% CI: 1.09, 1.25), and 1.33 (95% CI: 1.24, 1.43), respectively. Formal mediation analyses suggested that PhenoAge partially mediated the above associations. For instance, PhenoAge mediated 5.8% of increased CVD events in subgroups who experienced severe childhood traumas, relative to those experiencing mild childhood traumas.ConclusionsChildhood, adulthood, and lifetime traumas, as well as diverse life course traumatic profiles, were associated with CVD. Furthermore, phenotypic aging partially mediated these associations. These findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumatic events over the life course in ameliorating inequalities in cardiovascular health.
Transcriptomic-based clustering of advanced atherosclerotic plaques identifies subgroups of plaques with differential underlying biology that associate with clinical presentation
Authors: Mokry Michal , Boltjes Arjan , Cui Kai , Slenders Lotte , Mekke Joost M. , Depuydt Marie A.C. , Timmerman Nathalie , Waissi Farahnaz , Verwer Maarten C , Turner Adam W. , Khan Mohammad Daud , Hodonsky Chani J. , Benavente Ernest Diez , Hartman Robin J.G. , van den Dungen Noortje A M , Lansu Nico , Nagyova Emilia , Prange Koen H.M. , Pavlos Eleftherios , Andreakos Evangelos , Schunkert Heribert , Owens Gary K. , Monaco Claudia , Finn Aloke V , Virmani Renu , Leeper Nicholas J. , de Winther Menno P.J. , Kuiper Johan , de Borst Gert J. , Stroes Erik S.G. , Civelek Mete , de Kleijn Dominique P.V. , den Ruijter Hester M. , Asselbergs Folkert W. , van der Laan Sander W. , Miller Clint L. , Pasterkamp Gerard 
Published: November 2021

AbstractHistopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub- phenotyping. We hypothesized that unbiased clustering of plaques based on gene expression results in an alternative categorization of late-stage atherosclerotic lesions.We analyzed the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These novel plaque phenotypes associated with clinical presentation (p<0.001) and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. This highlighted plaque phenotype showed high expression of genes involved in active inflammatory processes, neutrophil degranulation, matrix turnover, and metabolism. For clinical translation, we did a first promising attempt to identify circulating biomarkers that mark these newly identified plaque phenotypes.In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in- depth transcriptomic based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to differential underlying biology of symptomatic lesions.
The COVID-19 pandemic and temporal change in metabolic risk factors for cardiovascular disease: a natural experiment within the HELIUS study
Authors: Hummel Bryn , Yerkes Mara A , Harskamp Ralf E , Galenkamp Henrike , Kunst Anton E , Lok Anja , van Valkengoed Irene GM 
Published: November 2021

AbstractObjectiveWe studied the association between the coronavirus disease 2019 (COVID-19) pandemic, including the restrictive measures, and metabolic risk factors for cardiovascular disease (CVD) in women and men. Next, we analysed whether changes in these metabolic risk factors were mediated by psychological and behavioural mechanisms.DesignIn this natural experiment, we assessed changes from baseline in metabolic CVD risk factors in the exposed group (whose follow-up measurements were taken during the pandemic), and compared these to the changes in the control group (whose follow-up measurements were taken before the pandemic).ParticipantsThis study used data from 6962 participants from six different ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan) of the HELIUS study, based in Amsterdam, the Netherlands. We included women and men without prior CVD, who participated in both the baseline (2011-2015) and follow-up measurements (2019-2021).Outcome measuresChanges between baseline and follow-up measurements in six metabolic CVD risk factors were calculated for systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR).ResultsThe exposed group experienced somewhat less favourable changes over time in SBP, DBP and FPG (the latter only in women) than the control group, while temporal changes in HbA1c and eGFR were more favourable among the control group. For instance, SBP was 1.119 mmHg [0.046, 2.193] higher in exposed than non-exposed women, and 1.380 [0.288, 2.471] in men. Changes in SBP and DBP were partially mediated by changes in behavioural factors, most notably BMI and alcohol consumption.ConclusionsThe COVID-19 pandemic, including the restrictive lockdown measures, is associated with a deterioration of several CVD risk factors in women and men. These findings may aid in decision making concerning the management of and the recovery following the pandemic.Article SummaryStrengths and limitations of this studyThe COVID19 pandemic lockdown measures led to a pause in the data collection for the prospective, population-based HELIUS study, which shaped a natural experiment.Natural experiments, as quasi-experimental designs, are generally considered stronger than cross-sectional studies.Through inverse-probability weighting, this study aimed to account for baseline differences between the control and exposed group.We could not adjust for differences in follow-up time that occurred as a result of the restrictive measures, which may have affected estimates of variables that change with age.The effects of certain mediators may be underestimated, as the data available for defining these variables were largely based on self-reports.
Prophylactic Magnesium Supplementation and New-Onset Atrial Fibrillation in a General Critical Care Population: A Prescribing Preference Instrumental Variable Analysis
Authors: Wilson Matthew G. , Rashan Aasiyah , Klapaukh Roman , Asselbergs Folkert W. , Harris Stephen K. 
Published: November 2021

AbstractAimsAtrial fibrillation is frequently encountered in critical illness and causes adverse effects including haemodynamic decompensation, stroke and longer hospital stay. It is common to supplement serum magnesium for the purpose of preventing new-onset atrial fibrillation. However, no randomised studies support this practice in the non-cardiac surgery critical care population, and its effectiveness is unclear. We sought to investigate the effectiveness of magnesium supplementation in preventing new-onset atrial fibrillation in a mixed critical care population.MethodsWe conducted a single centre retrospective observational study of adult critical care patients. We employed a natural experiment design, using the supplementation preference of the bedside critical care nurse as an instrumental variable.Using the electronic patient record, magnesium supplementation opportunities were defined and linked to the bedside nurse. Nurse preference for administering magnesium was obtained using multilevel modelling. The results were used to define ‘pro’ and ‘anti’ supplementation groups, which were inputted into an instrumental variable regression to obtain an estimate of the effect of magnesium supplementation.Results9,114 magnesium supplementation opportunities were analysed, representing 2,137 critical care admissions for 1,914 patients. There was significant variation in magnesium supplementation practices attributable to the individual nurse, after accounting for covariates. The instrumental variable analysis showed magnesium supplementation was associated with a 3% decreased chance of experiencing new-onset atrial fibrillation (95% CI −0.06 to −0.04, p = 0.03).ConclusionsThis study supports the strategy of routine magnesium supplementation, but further work is required to identify optimal serum magnesium targets for prophylaxis of atrial fibrillation.What’s New?Routine administration of supplemental magnesium sulphate is associated with a reduced chance of developing new-onset Atrial Fibrillation, in a general critical care cohort.This finding agrees with previous Randomised Controlled Trial results which are limited to the cardiac critical care population.This finding disagrees with previously published observational studies, which is likely due to better control of unmeasured confounding.There is significant variation in serum magnesium supplementation attributable to the individual bedside critical care nurse.Electronic health records offer the ability to evaluate the effectiveness of routinely administered treatments which lack evidence in an affordable way.Natural experiments and instrumental variable analysis offer the opportunity to derive causally robust estimations of treatment effectiveness by better accounting for unobserved confounding.
Predicting Post-operative Pain in Lung Cancer Patients using Pre-operative Peak Alpha Frequency
Authors: Millard Samantha K. , Furman Andrew J. , Kerr Amy , Seminowicz David A. , Gao-Smith Fang , Naidu Babu V. , Mazaheri Ali 
Published: November 2021

Aims and ObjectivesExperimental models of neuropathic pain suggest that individual peak alpha frequency (PAF), measured using electroencephalography (EEG), can predict future pain sensitivity in experimental settings. Here, we tested whether PAF could predict future pain severity in a clinical setting in patients undergoing thoracotomy.MethodsRecorded using wearable around the ear electrodes (cEEGrids), the feasibility and efficacy of pre-operative PAF as a neuro-marker for post-operative pain was assessed in 16 patients undergoing thoracic surgery for lung cancer (age = 67.53 ± 4.38 [SD]). Patients also provided numerical ratings (0-10) of current, average, and worst pain pre-operatively as well as within three days post-operativelyResults and SignificancePre-operative PAF of less than 9 Hz was highly sensitive (1.0) and specific (0.86) in identifying patients who would go on to experience severe (>7/10) worst pain. Moreover, PAF was negatively correlated with patients’ current, average, and worst post-operative pain. PAF was significantly higher for those reporting lower pain severity compared to those reporting higher pain severity in the immediate post-operative period. This suggests that PAF is a promising neuro-marker to pre-operatively assess individual susceptibility to severe pain in the immediate post-operative period, possibly enabling more informed assessment of an individual’s suitability for surgery.
Future prevalence of type 2 diabetes – a comparative analysis of chronic disease projection methods
Authors: Voeltz Dina , Tönnies Thaddäus , Brinks Ralph , Hoyer Annika 
Published: November 2021

AbstractBackgroundAccurate projections of the future number of people with chronic diseases are necessary for effective resource allocation and health care planning in response to changes in disease burden.AimTo introduce and compare different projection methods to estimate the number of people with diagnosed type 2 diabetes (T2D) in Germany in 2040.MethodsWe compare three methods to project the number of males with T2D in Germany in 2040. Method 1) simply combines the sex- and age-specific prevalence of T2D in 2010 with future population distributions projected by the German Federal Statistical Office (FSO). Methods 2) and 3) additionally account for the incidence of T2D and mortality rates using partial differential equations (PDEs). Method 2) models the prevalence of T2D employing a scalar PDE which incorporates incidence and mortality rates. Subsequently, the estimated prevalence is applied to the population projection of the FSO. Method 3) uses a two-dimensional system of PDEs and estimates future case numbers directly while future mortality of people with and without T2D is modelled independently from the projection of the FSO.ResultsMethod 1) projects 3.6 million male people with diagnosed T2D in Germany in 2040. Compared to 2.8 million males in 2010, this equals an increase by 29%. Methods 2) and 3) project 5.9 million (+104% compared to 2010) and 6.0 million (+116%) male T2D patients, respectively.ConclusionsThe results of the three methods differ substantially. It appears that ignoring temporal trends in incidence and mortality may result in misleading projections of the future number of people with chronic diseases. Hence, it is essential to include these rates as is done by method 2) and 3).
Distinct and interchangeable growing patterns in colorectal cancer stem-like cells are regulated by Musashi-1
Authors: Coppo Roberto , Kondo Jumpei , Iida Keita , Okada Mariko , Onuma Kunishige , Tanaka Yoshihisa , Kamada Mayumi , Ohue Masayuki , Kawada Kenji , Obama Kazutaka , Inoue Masahiro 
Published: November 2021

AbstractThe dynamic and heterogeneous features of cancer stem-like cells (CSCs) have been widely recognized, but their nongenetic cellular plasticity mechanisms remain elusive. By using colorectal cancer organoids, we phenotypically tracked their spheroid formation and growth capacity to a single-cell resolution, and we discovered that the spheroid-forming cells exhibit a heterogeneous growth pattern, consisting of slow- and fast-growing spheroids. The isolated fast-growing spheroids seem to preserve a dual-growing pattern through multiple passages, whereas the isolated slow-growing spheroids are restricted to a slow-growing pattern. Notably, the spheroids of both patterns were tumorigenic. Moreover, the expression of CSC markers varied among the subpopulations with different growth patterns. The isolated slow-growing spheroids adopted the dual-growing pattern by various extrinsic triggers, in which Musashi-1 plays a key role. The slow-growing fraction was resistant to chemotherapy, and its successful isolation can provide an in vitro platform allowing us to elucidate their role in drug resistance.
Experimental Investigation of Pulse Sterilization of Pathogens
Authors: Chumakov Volodymyr , Ostryzhnyi Mykhailo , Kharchenko Oksana , Rybalchenko Nataliya , Muraveinyk Vasiliy , Tarasevich Aleksandr 
Published: November 2021

AbstractThe results of experimental investigations of the effect of high-intensity pulsed UV radiation on reference strains of opportunistic pathogens S, aureus and E. coli are presented. The modified pulse UV sterilizer MПК-300-3 based on an end-face plasma accelerator was used as a radiation source, which provides a power pulsed discharge in an open atmosphere. The high efficiency of inactivation of the pathogens was provided within a short period of time. The possibility of providing urgent 100% sterilization of a pathogens has been shown. The prospects for the application of pulse sterilization technology to combat pathogens are considered.
Adaptor linked K63 di-Ubiquitin activates Nedd4/Rsp5 E3 ligase
Authors: Zhu Lu , Zhang Qing , Cordeiro Ciro , Banjade Sudeep , Sardana Richa , Mao Yuxin , Emr Scott D. 
Published: November 2021

AbstractNedd4/Rsp5 family E3 ligases mediate numerous cellular processes, many of which require the E3 ligase to interact with PY-motif containing adaptor proteins. Several Arrestin-Related Trafficking adaptors(ARTs) of Rsp5 were self-ubiquitinated for activation, but the regulation mechanism remains elusive. Remarkably, we demonstrate that Art1, Art4, and Art5 undergo K63-linked di-ubiquitination by Rsp5. This modification enhances the PM recruitment of Rsp5 by Art1 or Art5 upon substrate induction, required for cargo protein ubiquitination. In agreement with these observations, we find that di-ubiquitin strengthens the interaction between the Pombe orthologs of Rsp5 and Art1, Pub1 and Any1. Further, we discover that the HECT domain exosite protects the K63-linked di-ubiquitin on the adaptors from cleavage by the deubiquitination enzyme Ubp2. Strikingly, loss of this protection results in the loss of K63-linked di-ubiquitin from the adaptors and diverts the adaptors for K48-linked poly-ubiquitination and proteasome-mediated degradation. Together, our study uncovers a novel ubiquitination modification implemented by Rsp5 adaptor proteins, underscoring the regulatory mechanism of how adaptor proteins control the recruitment and activity of Rsp5 for the turnover of membrane proteins.
Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system
Authors: Lee Soo Min , Fan Yu , Lee Bonghyo , Kim Sang Chan , Bills Kyle B. , Steffensen Scott C. , Kim Hee Young 
Published: November 2021

AbstractNociceptive signals interact with various regions of the brain, including those involved in physical sensation, reward, cognition, and emotion. Emerging evidence points to a role of nociception in the modulation of the mesolimbic reward system. The mechanism by which nociception affects dopamine (DA) signaling and reward is unclear. The lateral hypothalamus (LH) and the lateral habenula (LHb) receive somatosensory inputs and are structurally connected with the mesolimbic DA system. Here we show that the LH-LHb pathway is necessary for nociceptive modulation of this system. Our extracellular single-unit recordings and head-mounted microendoscopic calcium imaging revealed that nociceptive stimulation by tail-pinch excited LHb and LH neurons, which was inhibited by chemical lesion of the LH. Tail-pinch decreased extracellular DA release in the nucleus accumbens ventrolateral shell, which was blocked by disruption of the LH. Furthermore, tail-pinch attenuated cocaine-induced locomotor activity, 50-kHz ultrasonic vocalizations and reinstatement of cocaine-seeking behavior, which was inhibited by chemogenetic silencing of the LH-LHb pathway. Our findings suggest that nociceptive stimulation recruits the LH-LHb pathway to inhibit mesolimbic DA system and drug reinstatement.