bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome
Authors: Tiberi Alexia , Borgonovo Giulia , Testa Giovanna , Pacifico Paola , Jacob Ajesh , Di Caprio Mariachiara , Totaro Valentino , Calvello Mariantonietta , Cattaneo Antonino , Capsoni Simona 
Published: August 2023

Abstract
Rett syndrome is a rare genetic neurodevelopmental disease, affecting 1 in over 10 000 females born worldwide, caused by de novo mutations in the X-chromosome-located methyl-CpG-binding protein 2 (MeCP2) gene. Despite the great effort put forth by the scientific community, a therapy for this devastating disease is still needed. Here, we tested the therapeutic effects of a painless mutein of the nerve growth factor (NGF), called human NGF painless (hNGFp), via a non-invasive intranasal delivery in female MeCP2+/− mice. Of note, previous work had demonstrated a broad biodistribution of hNGFp in the mouse brain by the nasal delivery route.
We report that (i) the long-term lifelong treatment of MeCP2+/− mice with hNGFp, starting at 2 months of age, increased the chance of survival while also greatly improving behavioural parameters. Furthermore, when we assessed the phenotypic changes brought forth by (ii) a short-term 1-month-long hNGFp-treatment, starting at 3 months of age (right after the initial presentation of symptoms), we observed the rescue of a well known neuronal target population of NGF, cholinergic neurons in the medial septum. Moreover, we reveal a deficit in microglial morphology in MeCP2+/− mice, completely reversed in treated animals. This effect on microglia is in line with reports showing microglia to be a TrkA-dependent non-neuronal target cell population of NGF in the brain.
To understand the immunomodulatory activity of hNGFp, we analysed the cytokine profile after hNGFp treatment in MeCP2+/− mice, to discover that the treatment recovered the altered expression of key neuroimmune-communication molecules, such as fractalkine.
The overall conclusion is that hNGFp delivered intranasally can ameliorate symptoms in the MeCP2+/− model of Rett syndrome, by exerting strong neuroprotection with a dual mechanism of action: directly on target neurons and indirectly via microglia.
ALCAM on human oligodendrocytes mediates CD4 T cell adhesion
Authors: Jamann Hélène , Desu Haritha L , Cui Qiao-Ling , Halaweh Alexandre , Tastet Olivier , Klement Wendy , Zandee Stephanie , Pernin Florian , Mamane Victoria H , Ouédraogo Oumarou , Daigneault Audrey , Sidibé Hadjara , Millette Florence , Peelen Evelyn , Dhaeze Tessa , Hoornaert Chloé , Rébillard Rose-Marie , Thai Karine , Grasmuck Camille , Vande Velde Christine , Prat Alexandre , Arbour Nathalie , Stratton Jo Anne , Antel Jack , Larochelle Catherine 
Published: August 2023

Abstract
Multiple sclerosis is a chronic neuroinflammatory disorder characterized by demyelination, oligodendrocyte damage/loss and neuroaxonal injury in the context of immune cell infiltration in the CNS. No neuroprotective therapy is available to promote the survival of oligodendrocytes and protect their myelin processes in immune-mediated demyelinating diseases. Pro-inflammatory CD4 Th17 cells can interact with oligodendrocytes in multiple sclerosis and its animal model, causing injury to myelinating processes and cell death through direct contact. However, the molecular mechanisms underlying the close contact and subsequent detrimental interaction of Th17 cells with oligodendrocytes remain unclear.
In this study we used single cell RNA sequencing, flow cytometry and immunofluorescence studies on CNS tissue from multiple sclerosis subjects, its animal model and controls to characterize the expression of cell adhesion molecules by mature oligodendrocytes. We found that a significant proportion of human and murine mature oligodendrocytes express melanoma cell adhesion molecule (MCAM) and activated leukocyte cell adhesion molecule (ALCAM) in multiple sclerosis, in experimental autoimmune encephalomyelitis and in controls, although their regulation differs between human and mouse. We observed that exposure to pro-inflammatory cytokines or to human activated T cells are associated with a marked downregulation of the expression of MCAM but not of ALCAM at the surface of human primary oligodendrocytes. Furthermore, we used in vitro live imaging, immunofluorescence and flow cytometry to determine the contribution of these molecules to Th17-polarized cell adhesion and cytotoxicity towards human oligodendrocytes. Silencing and blocking ALCAM but not MCAM limited prolonged interactions between human primary oligodendrocytes and Th17-polarized cells, resulting in decreased adhesion of Th17-polarized cells to oligodendrocytes and conferring significant protection of oligodendrocytic processes.
In conclusion, we showed that human oligodendrocytes express MCAM and ALCAM, which are differently modulated by inflammation and T cell contact. We found that ALCAM is a ligand for Th17-polarized cells, contributing to their capacity to adhere and induce damage to human oligodendrocytes, and therefore could represent a relevant target for neuroprotection in multiple sclerosis.
Rapid Identification of Alkaloids and Flavonoids in Fissistigma oldhamii var. longistipitatum by Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Tandem Mass Spectrometry
Authors: Liu Huizhen , Chen Jiaqian , Yuan Cheng Jun , He Junwei , Chen Heying , Jin Chen , Guo Qiang , Huang Huilian 
Published: August 2023

Abstract
The herb Fissistigma oldhamii var. longistipitatum has been used for a long time in Asian folk medicine in the treatment of several diseases, including rheumatoid arthritis and other inflammatory conditions. Researchers in China and elsewhere have analyzed and characterized its chemical content. In this study, a UHPLC-Q-TOF-MS/MS method, run in both positive and negative modes, was used to identify the main chemical compounds in dichloromethane extracts of this F. oldhamii variant. A total of 64 compounds, including 44 alkaloids and 20 flavonoids, were rapidly identified or tentatively characterized by comparing the molecular ion peaks and MS2 mass spectrometry fragment ions, combined with the mass spectrometry information of reference substances, appropriate fragmentation ions and related literatures. For the first time, the developed UHPLC-Q-TOF-MS/MS analysis method allows for the determination of 64 compounds from extracts of the F. oldhamii variant. The method presented here produced results that will be useful in further studies of this herb.
Clinical Epidemiology and Risk Factors for Critical Outcomes Among Vaccinated and Unvaccinated Adults Hospitalized With COVID-19—VISION Network, 10 States, June 2021–March 2023
Authors: Griggs Eric P , Mitchell Patrick K , Lazariu Victoria , Gaglani Manjusha , McEvoy Charlene , Klein Nicola P , Valvi Nimish R , Irving Stephanie A , Kojima Noah , Stenehjem Edward , Crane Bradley , Rao Suchitra , Grannis Shaun J , Embi Peter J , Kharbanda Anupam B , Ong Toan C , Natarajan Karthik , Dascomb Kristin , Naleway Allison L , Bassett Elizabeth , DeSilva Malini B , Dickerson Monica , Konatham Deepika , Fireman Bruce , Allen Katie S , Barron Michelle A , Beaton Maura , Arndorfer Julie , Vazquez-Benitez Gabriela , Garg Shikha , Murthy Kempapura , Goddard Kristin , Dixon Brian E , Han Jungmi , Grisel Nancy , Raiyani Chandni , Lewis Ned , Fadel William F , Stockwell Melissa S , Mamawala Mufaddal , Hansen John , Zerbo Ousseny , Patel Palak , Link-Gelles Ruth , Adams Katherine , Tenforde Mark W 
Published: August 2023

Abstract

Background
The epidemiology of coronavirus disease 2019 (COVID-19) continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of COVID-19 hospitalizations and risk factors for critical outcomes over time.

Methods
We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021–March 2023. We evaluated changes in demographics, clinical characteristics, and critical outcomes (intensive care unit admission and/or death) and evaluated critical outcomes risk factors (risk ratios [RRs]), stratified by COVID-19 vaccination status.

Results
A total of 60 488 COVID-19–associated hospitalizations were included in the analysis. Among those hospitalized, median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, and critical outcomes declined from 24.8% to 19.4% (all P &lt; .001) between the Delta (June–December, 2021) and post-BA.4/BA.5 (September 2022–March 2023) periods. Hospitalization events with critical outcomes had a higher proportion of ≥4 categories of medical condition categories assessed (32.8%) compared to all hospitalizations (23.0%). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated: adjusted RR, 2.27 [95% confidence interval {CI}, 2.14–2.41]; vaccinated: adjusted RR, 1.73 [95% CI, 1.56–1.92]) across periods.

Conclusions
The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time, and median patient age increased with time. Multimorbidity was most strongly associated with critical outcomes.
Chronic Hepatitis B Finite Treatment: Similar and Different Concerns With New Drug Classes
Authors: Peters Marion G , Yuen Man-Fung , Terrault Norah , Fry John , Lampertico Pietro , Gane Ed , Hwang Carey , Stamm Luisa M , Leus Mitchell , Maini Mala K , Mendez Patricia , Lonjon-Domanec Isabelle , Berg Thomas , Wang Su , Mishra Poonam , Donaldson Eric , Buchholz Stephanie , Miller Veronica , Lenz Oliver 
Published: August 2023

Abstract
Chronic hepatitis B, a major cause of liver disease and cancer, affects &gt;250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative hepatitis B virus (HBV) therapies are underway, consisting of combinations of multiple novel agents with or without nucleos(t)ide reverse-transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, along with subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives, and regulatory agencies. This Viewpoints article outlines areas of consensus within our multistakeholder group for stopping finite therapies in chronic hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, predefined stopping criteria, predefined retreatment criteria, duration of investigational therapies, and follow-up after stopping therapy. Future research of unmet needs are discussed.
Trunk muscle quality and quantity are associated with renal volume in nondiabetic people
Authors: Tanaka Muhei , Okada Hiroshi , Hashimoto Yoshitaka , Kumagai Muneaki , Yamaoka Miyoko , Nishimura Hiromi , Fukui Michiaki 
Published: August 2023

ABSTRACT

Background
Renal disease is a major problem in terms of community health and the economy. Skeletal muscle is involved in crosstalk with the kidney. We therefore investigated the relationship between muscle quality and quantity, and renal parenchymal volume (RPV).

Methods
The association between the parameters of skeletal muscle and RPV/body surface area (BSA) was analyzed by computed tomography in 728 middle-aged participants without kidney disease or diabetes mellitus in a cross-sectional study. A retrospective cohort study of 68 participants was undertaken to analyze the association between changes in RPV/BSA and muscle parameters. Parameter change was calculated as follows: parameter at the follow-up examination/parameter at the baseline examination. The normal attenuation muscle (NAM) and low attenuation muscle (LAM) were identified by Hounsfield Unit thresholds of +30 to +150, and –29 to +29, respectively.

Results
Positive correlations were found between estimated glomerular filtration rate and RPV/BSA (r = 0.451, P &lt; .0001). Multiple regression analyses revealed that the NAM index was positively related to RPV/BSA (β = 0.458, P &lt; .0001), whereas the LAM index was negatively related to RPV/BSA (β = –0.237, P &lt; .0001). In this cohort study, a change in the LAM index was independently associated with a change in RPV/BSA (β = –0.349, P = .0032).

Conclusion
Both trunk muscle quantity and quality were associated with renal volume related to renal function in nondiabetic people. An increase in low quality muscle volume might be related to a decrease in renal volume.
Incidence and prognosis of acute kidney injury versus acute kidney disease among 71 041 inpatients
Authors: Xu Lingyu , Li Chenyu , Li Na , Zhao Long , Zhu Zhihui , Zhang Xiaosu , Wang Jing , Zhao Jun , Huang Junyan , Zheng Zhihua , Anders Hans-Joachim , Xu Yan 
Published: August 2023

ABSTRACT

Background
Acute kidney disease (AKD) defines patients with acute kidney injury (AKI) or subacute loss of kidney function lasting for &gt;7 days. Little is known about the prognosis of AKD in hospitalized patients. The aim of this study was to investigate the risk factors and prognosis of AKD and to compare different types of acute/subacute renal impairment among Chinese inpatients.

Methods
Complete data were available for 71 041 patients for a range of 5–63 months. AKI and AKD were diagnosed based on the Acute Disease Quality Initiative criteria of 2017.

Results
Of 71 041 inpatients, 16 098 (22.7%) patients developed AKI or AKD; 5895 (8.3%) AKI patients recovered within 7 days, 5623 (7.9%) AKI patients developed AKD and 4580 (6.4%) patients developed AKD without AKI. Mortality was proportional to stages of AKI and AKD (P &lt; .05), while AKI followed by AKD was associated with a higher risk of long-term mortality [hazard ratio (HR) 4.51] as compared with AKD without AKI (HR 2.25) and recovery from AKI (HR 1.18). The AKD criteria were robustly associated with overall survival [area under the receiver operating characteristic curve (AUROC) 0.71] and de novo CKD (AUROC 0.71), while the AKI criteria showed a relatively lower ability to fit the risk of overall survival (AUROC 0.65) and CKD (AUROC 0.63).

Conclusions
AKD and AKD stages are useful clinical definitions for clinical practice, as they predict unfortunate clinical outcomes such as overall long-term mortality and CKD. Research activities should focus on AKD.
Stroke risk management in carotid atherosclerotic disease: a clinical consensus statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases
Authors: Musialek Piotr , Bonati Leo H , Bulbulia Richard , Halliday Alison , Bock Birgit , Capoccia Laura , Eckstein Hans-Henning , Grunwald Iris Q , Lip Peck Lin , Monteiro Andre , Paraskevas Kosmas I , Podlasek Anna , Rantner Barbara , Rosenfield Kenneth , Siddiqui Adnan H , Sillesen Henrik , Van Herzeele Isabelle , Guzik Tomasz J , Mazzolai Lucia , Aboyans Victor , Lip Gregory Y H 
Published: August 2023

Abstract
Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded the knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (i) establishing a unified knowledge foundation and (ii) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailors personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology, and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promoting patient’s active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management including statins, novel lipid-lowering and antithrombotic strategies, and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multi-morbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for inter-disciplinary collaboration and prioritized patient-centric decision-making.
Males at the Tails: How Socioeconomic Status Shapes the Gender Gap
Authors: Autor David , Figlio David , Karbownik Krzysztof , Roth Jeffrey , Wasserman Melanie 
Published: August 2023

Abstract
We document that the female advantage in childhood behavioural and academic outcomes is driven by gender gaps at the extremes of the outcome distribution. Using unconditional quantile regression, we show that family socioeconomic status particularly influences boys’ relative to girls’ outcomes at the lower tails of the outcome distribution, precisely where gender gaps are most pronounced. These relationships are not explained by school or neighbourhood factors, or parents’ differential treatment of boys. The disproportionate effect of socioeconomic status on boys at the tails substantially contributes to the gender gap in high school dropout.
2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG
Authors: Byrne Robert A , Fremes Stephen , Capodanno Davide , Czerny Martin , Doenst Torsten , Emberson Jonathan R , Falk Volkmar , Gaudino Mario , McMurray John J V , Mehran Roxana , Milojevic Milan , Uva Miguel Sousa 
Published: August 2023

Abstract
Task Force structure and summary of clinical evidence of 2022 ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; LM, left main; SYNTAX, Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. a‘Event’ refers to the composite of death, myocardial infarction (according to Universal Definition of Myocardial Infarction if available, otherwise protocol defined) or stroke.
In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force (TF) to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with left main (LM) disease with low-to-intermediate SYNTAX score (0-32). This followed the withdrawal of support by the EACTS in 2019 for the recommendations about the management of LM disease of the previous guideline. The TF was asked to review all new relevant data since the 2018 guidelines including updated aggregated data from the four randomized trials comparing percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary artery bypass grafting (CABG) in patients with LM disease. This document represents a summary of the work of the TF; suggested updated recommendations for the choice of revascularization modality in patients undergoing myocardial revascularization for LM disease are included. In stable patients with an indication for revascularization for LM disease, with coronary anatomy suitable for both procedures and a low predicted surgical mortality, the TF concludes that both treatment options are clinically reasonable based on patient preference, available expertise, and local operator volumes. The suggested recommendations for revascularization with CABG are Class I, Level of Evidence A. The recommendations for PCI are Class IIa, Level of Evidence A. The TF recognized several important gaps in knowledge related to revascularization in patients with LM disease and recognizes that aggregated data from the four randomized trials were still only large enough to exclude large differences in mortality.
Economic burden of cardiovascular diseases in the European Union: a population-based cost study
Authors: Luengo-Fernandez Ramon , Walli-Attaei Marjan , Gray Alastair , Torbica Aleksandra , Maggioni Aldo P , Huculeci Radu , Bairami Firoozeh , Aboyans Victor , Timmis Adam D , Vardas Panos , Leal Jose 
Published: August 2023

Abstract

Background and Aims
Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021.

Methods
Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials.

Results
CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs.

Conclusions
This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability.