bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome
Authors: Pedapati Ernest V. , Schmitt Lauren M. , Ethridge Lauren E. , Miyakoshi Makoto , Sweeney John A. , Liu Rui , Smith Elizabeth , Shaffer Rebecca C. , Dominick Kelli C. , Gilbert Donald L. , Wu Steve W. , Horn Paul S. , Binder Devin K. , Lamy Martine , Axford Megan , Erickson Craig A. 
Published: May 2022

AbstractFragile X Syndrome (FXS) is a monogenetic form of intellectual disability and autism in which well-established knockout (KO) animal models point to neuronal hyperexcitability and abnormal gamma-frequency physiology as a basis for key disorder features. Translating these findings into patients may identify tractable treatment targets. Using source modeling of resting-state electroencephalography data, we report findings in FXS, including 1) increases in localized gamma activity, 2) pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power, 3) stepwise moderation of low and high-frequency abnormalities based on female sex, and 4) relationship of this physiology to intellectual disability and neuropsychiatric symptoms. Our observations extend findings inFmr1−/−KO mice to patients with FXS and raise a key role for disrupted thalamocortical modulation in local hyperexcitability. This systems-level mechanism has received limited preclinical attention but has implications for understanding fundamental disease mechanisms.
X-box binding protein 1 (XBP1): a potential role in chemotherapy response, clinical pathologic features, non-inflamed tumour microenvironment for breast cancer
Authors: Zhu Zhipeng , Zhan Hongliang , Sun Anran , Huang Heqing , Chen Baisheng , Zhang Fuxing 
Published: May 2022

AbstractX-box binding protein 1 (XBP1) is mainly expressed in breast cancer (BC) in human cancers. Its tumorigenesis and favourable prognosis are contradictory, and its essential role in chemotherapeutic response and immunosuppression is unknown in BC. The study firstly identified XBP1 who received neoadjuvant chemotherapy (NAC) from GSE25055 and GSE24460. Associations between XBP1 expression and clinicopathological characteristics was investigated using Oncomine, TCGA, UALCAN and bc-GenExMiner. The prognostic value of XBP1 was assessed using the Kaplan–Meier Plotter, bc-GenExMiner, GSE25055, and GSE25056. Furthermore, we systematically correlated XBP1 and immunological characteristics in the BC tumour microenvironment (TME) using TISIDB, TIMER, GSE25055, GSE25056 and TCGA dataset. Finally, an essential role of XBP1 in chemotherapy response was evaluated based on GSE25055, GSE25065, GSE24460, GSE5846, ROC Plotter and CELL databases. Furthermore, XBP1 mRNA expression levels were obviously highest in BC among human cancers and were significantly related to a good prognosis. In addition, XBP1 mRNA and protein levels were higher in the luminal subtype than in normal tissues and basal-like subtype, which might be attributed to membrane transport-related processes. Apart from BC, negative immunological correlations of XBP1 were not observed in other malignancies. XBP1 might shape the non-inflamed TME in BC. Finally, XBP1 expression was higher in chemo-resistive than chemo-sensitive cases, it had a predictive value and could independently predict chemotherapy response in BC patients receiving NAC. Our study suggests that the essential role of XBP1 in clinical pathologic features, non-inflamed TME, chemotherapy response in BC.
L’Europe, un acte de fabulation collective pour les tout petits ?
Authors: Fourcaud Christine 
Published: May 2022

L’Europe, un acte de fabulation collective pour les tout petits ?
« Unis dans la diversité ». Cette pierre angulaire de la construction européenne nous exhorte à enrichir le continent de nos nombreuses cultures, traditions et langues européennes. Pour le philosophe Philippe Mengue, l’identité est indissociable d’une narration. Elle s’ancre dans un acte de discours, de récit, de narration par lequel les peuples se racontent. Mais le peuple européen est absent, faute de pouvoir se fabuler. Alors qu’est-ce qui pourrait lier aujourd’hui les Européens pour en faire un peuple politique ? La fixation sur un plurilinguisme qui, en fin de compte, ne promeut que l’anglais, s’avère tout aussi dysfonctionnel pour l’intégration européenne que l’habitus monolingue de nos systèmes éducatifs nationaux. Le réseau des écoles maternelles et Kitas Elysée ratifié en Conseil des Ministres franco-allemand lors du 50ème anniversaire du Traité de l’Elysée (2013), apporte une contribution décisive au développement durable du multilinguisme européen. Cette étude de terrain pose trois questions :
1. Les enfants allophones ne devraient-ils pas d’abord se concentrer sur l’apprentissage de l’allemand avant d’entrer en contact avec le français ?
2. Entre seuils minimaux de compétence et interdépendance développementale, ne sont-ils pas submergés par l’acquisition d’une 3ème, 4ème langue ?
3. Le multilinguisme n’a-t-il pas une influence négative sur le développement linguistique, cognitif et social ?
Self-assembled Pt(II) metallacycles enable precise cancer combination chemotherapy
Authors: Zhang Pengge , Zhou Zhixuan , Long Wen , Yan Yuping , Li Youshan , Fu Ting , Liu Yanlan , Zhao Zilong , Tan Weihong , Stang Peter J. 
Published: May 2022

SignificanceCoadministration of drug molecules in adequate combinations for cancer treatment reduces the doses of each constituent, overcomes resistance mechanisms, and reduces the influence of tumor heterogeneity. Here we utilize coordination-driven self-assembly to prepare platinum(II) metallacycles comprising two drug molecules with distinct anticancer mechanisms in precise ratios. Nanoformulations fabricated by encapsulating the metallacycles into amphiphilic diblock copolymers efficiently enter cancer cells and release the active drug molecules at the exact loading ratio in the reductive cancer microenvironments, leading to a synergistic anticancer effect and therefore a favorable treatment outcome. This study provides a promising supramolecular methodology for the precise organization and delivery of bioactive molecules for inducing synergistic biological effects that maximize therapeutic efficacy.
Screening Criteria of mRNA Indicators for Wound age Estimation
Authors: Du Qiuxiang , Dong Tana , Liu Yuanxin , Zhu Xiyan , Li Na , Dang Lihong , Cao Jie , Jin Qianqian , Sun Junhong 
Published: May 2022

AbstractWound age estimation is a crucial and challenging problem in forensic pathology. Although mRNA is the most commonly used indicator for wound age estimation, screening criteria are lacking. In the present study, the feasibility of screening criteria using mRNA to determine injury time based on the adenylate-uridylate-rich element (ARE) structure and gene ontology (GO) categories were evaluated. A total of 78 Sprague-Dawley male rats were contused and sampled at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h after inflicting injury. The candidate mRNAs were classified based on with or without ARE structure and GO category function. The mRNA expression levels were detected using qRT-PCR. In addition, the standard deviation (STD), mean deviation (MD), relative average deviation (d%), and coefficient of variation (CV) were calculated based on mRNA expression levels. The CV score (CVs) and the CV of CV (CV’CV) were calculated to measure heterogeneity. Finally, based on classic principles, the accuracy of combination of candidate mRNAs was assessed using discriminant analysis to construct a multivariate model for inferring wound age. The results of homogeneity evaluation of each group based on CVs were consistent with the MD, STD, d%, and CV results, indicating the credibility of the evaluation results based on CVs. The candidate mRNAs without ARE structure and classified as cellular component (CC) GO category (ARE–CC) had the highest CVs, showing the mRNAs with these characteristics are the most homogenous mRNAs and best suited for wound age estimation. The highest accuracy was 91.0% when the mRNAs without ARE structure were used to infer the wound age based on the discrimination model. The accuracy of mRNAs classified into CC or multiple function (MF) GO category was higher than mRNAs in the biological process (BP) category. In all subgroups, the accuracy of the composite identification model of mRNA composition without ARE structure and classified as CC was higher than other subgroups. The mRNAs without ARE structure and belonging to the CC GO category were more homogenous, showed higher accuracy for estimating wound age, and were appropriate for rat skeletal muscle wound age estimation.
The impact of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury on mortality and clinical outcomes: a meta-analysis
Authors: Castro Inês , Relvas Miguel , Gameiro Joana , Lopes José António , Monteiro-Soares Matilde , Coentrão Luís 
Published: May 2022

ABSTRACT

Background
Renal replacement therapy (RRT) is essential in the presence of life-threatening complications associated with acute kidney injury (AKI). In the absence of urgent indications, the optimal timing for RRT initiation is still under debate. This meta-analysis aims to compare the benefits between early and late RRT initiation strategies in critically ill patients with AKI.

Methods
Studies were obtained from three databases [Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus], searched from inception to May 2021. The selected primary outcome was 28-day mortality. Secondary outcomes included overall mortality, recovery of renal function (RRF) and RRT-associated adverse events. A random-effects model was used for summary measures. Heterogeneity was assessed through Cochrane I2 test statistics. Potential sources of heterogeneity for the primary outcome were sought using sensitivity analyses. Further subgroup analyses were conducted based on RRT modality and study population.

Results
A total of 13 randomized controlled trials including 5193 participants were analysed. No significant differences were found between early and late RRT initiation regarding 28-day mortality [risk ratio (RR) 1.00; 95% confidence interval (CI) 0.89–1.12, I² = 30%], overall mortality (RR 1.00; 95% CI 0.90–1.12, I² = 42%) and RRF (RR 1.02; 95% CI 0.92–1.13, I² = 53%). However, early RRT initiation was associated with a significantly higher incidence of hypotensive (RR 1.34; 95% CI 1.17–1.53, I² = 6%) and infectious events (RR 1.83; 95% CI 1.11–3.02, I² = 0%).

Conclusions
Early RRT initiation does not improve the 28-day and overall mortality, nor the likelihood of RRF, and increases the risk for RRT-associated adverse events, namely hypotension and infection.
Blood pressure response during treadmill exercise testing and the risk for future development of atrial fibrillation
Authors: Aker A , Saliba W , Hislop E , Zafrir B 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Aims
Hypertension is a well-established risk factor for the onset and progression of atrial fibrillation (AF). Blood pressure (BP) response during routine exercise stress testing (EST) may identify subjects at increased risk for developing AF.

Methods
A retrospective analysis of treadmill EST performed by the Bruce protocol in patients aged ≥40 years without a history of AF (n=17,617; 42% women). BP was measured at rest, peak exercise, and 2-minute recovery, and was analyzed for association with the risk for developing AF.

Results
AF was documented in 4.5% of patients during mean follow-up of 7 years. The incidence rate of AF per 1000 person-years increased with the rise in CHA2DS2VASc score (3.26 in score=0 to 19.78 in scores≥6). Adjusting for CHA2DS2VASc score and exercise capacity, a multivariate analysis of systolic BP at rest (≥130 vs. ≤110 mmHg), peak-exercise (&gt;170 vs. ≤150 mmHg), and recovery (&gt;150 vs. ≤130 mmHg), were associated with increased risk for AF: hazard ratio (HR) 1.68 (95% CI, 1.40-2.01), 1.38 (1.15-1.64), 1.54 (1.27-1.86), respectively. Similarly, diastolic BP analysis at rest (≥90 vs. &lt;80 mmHg), peak-exercise (≥100 vs. &lt;90 mmHg), and recovery (&gt;90 vs. ≤80 mmHg), were associated with increased risk for AF: 1.78 (1.34-2.35), 2.22 (1.37-3.59), 1.73 (0.90-3.25). The association with AF was also observed when BPs were analyzed as continuous variables, including after additional adjustment of exercise and recovery measurements to resting BP.

Conclusions
Systolic and diastolic BP at rest, peak-exercise and recovery phases of EST may provide independent predictive information regarding future risk for developing AF.
Ventricular-arterial coupling derived from proximal aortic stiffness: impact on aerobic capacity across the heart failure spectrum
Authors: Pugliese NR , Balletti A , Armenia S , De Biase N , Faita F , Mengozzi A , Paneni F , Ruschitzka F , Virdis A , Ghiadoni L , Taddei S , Williams B , Antonini-Canterin F , Masi S 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS).

Objectives
To evaluate VAC across the spectrum of heart failure (HF).

Methods
We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress.

Results
aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p&lt;0.01). PWVs were directly related and increased with age (all p&lt;0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.08±0.36) and HFpEF (1.05±0.22), while aa-PWV/GLS was more impaired in HFpEF (0.69±0.11) than HFrEF (0.60±0.15; p&lt;0.01). Stage A-B had values of cf-PWV/GLS and aa-PWV/GLS (0.66±0.25 and 0.47±0.12) higher than controls (0.47±0.10 and 0.40±0.10) but lower than Stage C (all p&lt;0.01). Peak AVO2diff was inversely related with cf-PWV/GLS and aa-PWV/GLS (all p&lt;0.01). cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO2 in the overall population (adjusted R2=0.32 and 0.35; all p&lt;0.0001) but only aa-PWV/GLS was independently associated with flow reserve during exercise (R2=0.51; p&lt;0.0001).

Conclusion
Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.
Invasive exercise hemodynamics predict survival in patients with clinical heart failure irrespective of left ventricular systolic function
Authors: Ahlgrim C , Kocher S , Minners J , Jander N , Neumann FJ , Jadidi A , Arentz T , Mueller-Edenborn B 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
When aiming to stratify heart failure patients for mortality risk, exercise stress testing has proven to be relevant in specific populations of heart failure patients, but is not universally applied. Analysis of left ventricular systolic function (LVEF) remains the cornerstone for stratifying heart failure patients for prognosis and clinical treatment. The aim of the present study is to investigate the prognostic capabilities of invasive exercise testing in a real-world cohort of suspected heart failure patients in whom non-cardiac causes of dyspnea were excluded.

Methods
We retrospectively analyzed survival of patients who underwent right heart catheterization at rest and during exercise between 2007 to 2017 for dyspnea and expected heart failure. Pulmonary capillary wedge pressure (PCWP) at rest and the PCWP response to exercise, expressed as the ratio of PCWP at peak exercise to workload normalized to body weight [PCWL (mmHg/W/kg)], were determined. Mortality data was deducted from the official German death registry.

Results
A total of 682 patients [aged 64.1 ± 12 years, 269 (39.2%) women] were included. Based on LVEF, 515 patients (76.4%) had sustained LVEF ≥50%, 71 patients (10.5%) had heart failure with mildly-impaired LVEF (40-49%) and 88 patients (13.1%) had heart failure with reduced LVEF (≤40%). Absolute LVEF was not associated with all-cause mortality (HR 0.995; 95% CI 0.99-1.00; p=0.231). While increases in PCWP at rest an PCWL during exercise were both associated with death, the discriminative properties of pressure measurements derived during exercise were superior in ROC-analysis (AUC 0.637 for PCWP and AUC 0.728 for PCWL, p&lt;0.001) Exercise hemodynamics and systolic function were next used to re-classify patients in four groups based on normal vs. impaired LVEF (≥/&lt; 50%) and response to exercise (PCWL≥/&lt;25.5 mmHg/W/kg for normal LVEF and PCWL≥/&lt;34.7 mmHg/W/kg for impaired LVEF). In multivariate models adjusted for pertinent baseline parameters, patients with pathological response to exercise carried a 2.0-fold (with sustained LVEF, 95% CI 1.17-3.52, p=0.011) to 3.2-fold (with impaired LVEF, 95% CI 1.83-5.91, p&lt;0.001) increased risk for death. Patients with impaired LVEF but featuring a normal response to exercise did not carry an increased risk for death (HR 1.117, 95% CI 0.453-2.757, p=0.810).
Discussion: In patients with clinical heart failure, invasive exercise testing improves the prediction of mortality. Subjects with a normal response to exercise have a relatively low mortality irrespective of systolic function.
Covid-19 and ischemic heart disease: clinical manifestations, biomarkers, treatment and follow-up
Authors: Tashchuk V , Nesterovska R 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.
The aim of the study: To research the correlation between in-hospital mortality and markers of systemic inflammation in patients with COVID-19 with Ischemic heart disease (IHD) and to evaluate hematological indices under the influence of using quercetin and arginine in basic therapy.

Material and methods
The data from 52 case histories of patients with COVID-19 and IHD, who were hospitalized from February till April 2021, has been analyzed. 40 patients who recovered and were discharged from the hospital were included to group I, 12 patients who died were included to group II. The evaluation of hematological indices under the influence of adding metabolic drugs in the complex therapy was determined in 27 patients from group I, which was also divided into 2 subgroups. Subgroup I A, which consisted of 17 patients, received water-soluble quercetin and subgroup I B (10 patients) - arginine hydrochloride. The severity of systemic inflammation syndrome in the selected groups of patients was evaluate by the number of leukocytes and the cellular composition of peripheral blood on admission of patients to the hospital and on the basis of obtained data the values of hematological integral indices were calculated: blood leukocyte shift index (BLSI) according to N.I. Yabluchansky, neutrophil-lymphocyte ratio (NLR), leukocyte index of intoxication (LII) was determined by J. Kalf-Kalif, nuclear index by G.A. Dashtayantz, neutrophil-to-monocyte ratio (NMR), lymphocyte-to-eosinophil ratio (LER), lymphocyte-to-monocyte ratio (LMR), allergy index (AI).

Results
Patients from group II, who died of cardiovascular complications associated with COVID-19, had a significantly higher level of systemic inflammatory response, which is manifested by a significant increase of the total number of white blood cells (16,85±5,25) × 109/L, in contrast to patients of group I, who were discharged with recovery (5,81±1,75) × 109/L (p&lt;0,05), and had the increasing number of neutrophil percentage (88,09±2,99) % against to (67,71±9,85) % (p&lt;0,05), with a decrease in the percentage of peripheral blood lymphocytes (6,25±1,42) % in patients from group II against (18,13±4,25) % in patients of group I. The patients of clinical group II had the increasing of a number of hematological indices - BLSI: (9,28±2,16) against group I (2,47±0,95) (р&lt;0,05), NLR: (26,99±11,11) against (4,01±2,36) and also the increase of NMR in group II (14,81±3,49) comparing to group I (6,22±2,18) (р&lt;0,05). The obtained results analysis of the distribution of hematological indices in patients of subgroups I A and I B after adding quercetin and arginine to the basic therapy in the inpatient phase of treatment showed that a significant difference between the indicators is not observed.

Conclusions
The results of the study not only suggest new markers of mortality from severe COVID-19, but also identify potential ways of treatments.
Evaluation of treatment adherence and lifestyle modification of moroccan patients with chronic heart failure in cardiac rehabilitation
Authors: Mouine N , Zaimi A , Loudiy N , Bouzelmat H , Lakhal Z , Chaib A , Benyass A 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Cardiac rehabilitation consists of measures that allow patients to recover their functional capacity through physical exercise and therapeutic education. The aim of our study is to evaluate the treatment adherence and lifestyle modification of patients with chronic heart failure in Cardiac Rehabilitation.

Materials and methods
It’s a prospective study included 50 patients with chronic heart failure with reduced ejection fraction (HFrEF), admitted in Cardiac Rehabilitation Unit, Cardiology Centre. All of them had clinical evaluation, echocardiography, cardio respiratory evaluation and Education Program.

Results
The average age of patients was 68, 36±9,3 years with male predominance, they have more than three cardiovascular risk factors dominated by smoking and hypertension, coronary artery disease is the most frequent etiology, they had reduced ejection fraction (EF: 31±6,2%), 53% of patients respect dietary rules and adhere totally to treatment, 34% of patients don't respect diet rules and stopped treatment itself and 13% take irregularly treatment.
After 20 sessions of Exercise training and Education Program; patients have a good quality of life, they become less symptomatic (from dyspnea class III to II of NYHA), they adhere more to diet rules and take regularly their treatment.

Conclusion
This study demonstrated that Cardiac Rehabilitation help patients with Chronic Heart Failure to modify their lifestyle, to respect diet rules and adhere more to treatment.