bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary impacts of the COVID-19 pandemic at a tertiary children’s hospital in Canada: a mixed-methods study
Authors: Diskin Catherine , Orkin Julia , Dharmaraj Blossom , Agarwal Tanvi , Parmar Arpita , McNaughton Kelly , Cohen Eyal , Sunderji Alia , Faraoni David , Fecteau Annie , Fischer Jason , Maynes Jason , Mahant Sanjay , Friedman Jeremy 
Published: April 2023

ObjectivesDecisions to pause all non-essential paediatric hospital activities during the initial phase of the COVID-19 pandemic may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived by hospital clinicians to have been negatively impacted because of the changes in healthcare delivery attributing to the restrictions placed resulting from the COVID-19 pandemic.Design and settingThis study used a mixed-methods approach using the following: (1) a quantitative analysis of overall descriptive hospital activity between May and August 2020, and utilisation of data during the study period was performed, and (2) a qualitative multiple-case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a tertiary children’s hospital.ResultsHospital-level utilisation and activity patterns revealed a substantial change to hospital activity including an initial reduction in emergency department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19 to 67% between May and August 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centred care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers.ConclusionBeing aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred paediatric care moving forward.
Stand Down–Think Before You Drink: protocol for an effectiveness-implementation trial of a mobile application for unhealthy alcohol use with and without peer support
Authors: Blonigen Daniel M. , Hawkins Eric J. , Kuhn Eric , Timko Christine , Dulin Patrick L. , Boothroyd Derek , Possemato Kyle 
Published: April 2023

IntroductionMobile apps can increase access to alcohol-related care but only if patients actively engage with them. Peers have shown promise for facilitating patients’ engagement with mobile apps. However, the effectiveness of peer-based mobile health interventions for unhealthy alcohol use has yet to be evaluated in a randomised controlled trial. The goal of this hybrid I effectiveness-implementation study is to test a mobile app (‘Stand Down–Think Before You Drink’), with and without peer support, to improve drinking outcomes among primary care patients.Methods and analysisIn two US Veterans Health Administration (VA) medical centres, 274 primary care patients who screen positive for unhealthy alcohol use and are not currently in alcohol treatment will be randomised to receive usual care (UC), UC plus access to Stand Down (App), or UC plus Peer-Supported Stand Down (PSSD—four peer-led phone sessions over the initial 8 weeks to enhance app engagement). Assessments will occur at baseline and 8-, 20- and 32-weeks postbaseline. The primary outcome is total standard drinks; secondary outcomes include drinks per drinking day, heavy drinking days and negative consequences from drinking. Hypotheses for study outcomes, as well as treatment mediators and moderators, will be tested using mixed effects models. Semi-structured interviews with patients and primary care staff will be analysed using thematic analysis to identify potential barriers and facilitators to implementation of PSSD in primary care.Ethics and disseminationThis protocol is a minimal risk study and has received approval from the VA Central Institutional Review Board. The results have the potential to transform the delivery of alcohol-related services for primary care patients who engage in unhealthy levels of drinking but rarely seek treatment. Study findings will be disseminated through collaborations with healthcare system policymakers as well as publications to scholarly journals and presentations at scientific conferences.Trial registration numberNCT05473598.
HER2-low in gastro-oesophageal adenocarcinoma: a real-world pathological perspective
Authors: Angerilli Valentina , Parente Paola , Campora Michela , Ugolini Clara , Battista Serena , Cassoni Paola , Gambella Alessandro , Cavallin Francesco , De Lisi Giuseppe , Vanoli Alessandro , Grillo Federica , Mastracci Luca , Fassan Matteo 
Published: April 2023

AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005).ConclusionsThis work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued.
Genotype and sleep independently predict mental health in Rett syndrome: an observational study
Authors: Kay Cayla , Leonard Helen , Smith Jeremy , Wong Kingsley , Downs Jenny 
Published: April 2023

BackgroundRett syndrome is a genetically caused neurodevelopmental disorder associated with severe impairments and complex comorbidities. This study examined predictors of anxiety and depression in Rett syndrome, including genotype.MethodsThe International Rett Syndrome Database, InterRett, was the data source for this observational study. Associations between genotype, functional abilities, comorbidities, anxiety and depression were estimated with univariate and multivariate regression models. An additional regression model for anxiety included use of an anxiety medication as a predictor variable.ResultsThe sample included 210 individuals aged 6–51 years of whom 54 (25.7%) were on psychotropic medication for anxiety or depression. Individuals with the p.Arg294* variant had the highest anxiety scores, as did those with insomnia or excessive daytime sleepiness, irrespective of anxiety medication use. Individuals with the p.Arg306Cys variant had the lowest depression scores, as did those with insomnia or excessive daytime sleepiness.ConclusionFindings indicated that genotype and sleep have implications for mental health in Rett syndrome, suggesting that anticipatory guidance and proactive management of poor sleep could improve mental health. More research is needed to understand the effects of psychometric medications, which cannot be inferred from this cross-sectional study.
Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial
Authors: Marnat Gaultier , Kaesmacher Johannes , Buetikofer Lukas , Sibon Igor , Saleme Suzana , Pop Raoul , Henon Hilde , Michel Patrik , Mazighi Mikaël , Kulcsar Zsolt , Janot Kevin , Machi Paolo , Pikula Aleksandra , Gentric Jean-Christophe , Hernández-Pérez María , Krause Lars Udo , Turc Guillaume , Liebeskind David S , Gralla Jan , Fischer Urs 
Published: April 2023

BackgroundIn proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors.MethodsThe SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0–2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay.ResultsWe included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65–81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13–20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses.ConclusionIn this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.
Pericapsular nerve group (PENG) block for early pain management of elderly patients with hip fracture: a single-center double-blind randomized controlled trial
Authors: LIN XUFENG , Liu Christopher Weiyang , Goh Qing Yuan , Sim Eileen Yilin , Chan Steffi Kang Ting , Lim Zhen Wei , Chan Diana Xin Hui 
Published: April 2023

BackgroundThe pericapsular nerve group block (PENG) is a novel technique that blocks the articular branches of the hip joint. This study aimed to compare its effectiveness to a sham block in elderly patients with hip fractures.MethodA randomized double-blind controlled trial was conducted in elderly patients with intertrochanteric and neck of femur fractures. Patients were randomized to receive either PENG block or a sham block. Postblock, systemic analgesia was titrated using a standardized protocol of acetaminophen, oral morphine or patient-controlled analgesia. The primary outcome was the dynamic pain score (Numerical Rating Scale 0–10) at 30 min postblock. Secondary outcomes included pain scores at multiple other time points and 24-hour opioid consumption.Results60 patients were randomized and 57 completed the trial (PENG n=28, control n=29). Patients in PENG group had significantly lower dynamic pain scores at 30 min compared with control group (median (IQR) 3 (0.5–5) vs 5 (3–10), p<0.01). For the secondary outcomes, dynamic pain scores were lower in PENG group at 1 hour (median (IQR) 2 (1–3.25) vs 5 (3–8), p<0.01) and 3 hours postblock (median (IQR) 2 (0–5) vs 5 (2–8), p<0.05). Patients in PENG group had lower 24-hour opioid consumption (median (IQR) oral morphine equivalent dose 10 (0–15) vs 15 (10–30) mg, p<0.05).ConclusionPENG block provided effective analgesia for acute traumatic pain following hip fracture. Further studies are required to validate the superiority of PENG blocks over other regional techniques.Trial registration numberNCT04996979.
Ni(OH)2-MoS2 Nanocomposite Modified Glassy Carbon Electrode for the Detection of Dopamine and α-Lipoic Acid
Authors: Tomy Ann Mary , Sathyan Bhasha , Cyriac Jobin 
Published: April 2023

Here, we report an electrochemical sensor realized using a nanocomposite consisting of nickel hydroxide nanosheets and exfoliated MoS2 nanosheets. The system was able to detect dopamine and α-lipoic acid in phosphate-buffered saline (PBS) solution at a pH of 7.4. The nanocomposites were characterized using microscopic and spectroscopic methods. The electrochemical characterizations were carried out using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). It was observed that Ni(OH)2/MoS2 composite in the weight ratio of 2:1 has better results in terms of electrochemically active surface area, impedance, analytical parameters and stability. The dynamic range for dopamine detection was 0.75 − 95 μM with a LOD value of 56 nM and for α-lipoic acid, the range was 1 − 75 μM and the LOD was 51 nM.
The Role of Inflammation in the Initiation and Progression of Myeloid Neoplasms
Authors: Balandrán Juan Carlos , Lasry Audrey , Aifantis Iannis 
Published: April 2023

Abstract

Myeloid malignancies are devastating hematologic cancers with limited therapeutic options. Inflammation is emerging as a novel driver of myeloid malignancy, with important implications for tumor composition, immune response, therapeutic options, and patient survival. Here, we discuss the role of inflammation in normal and malignant hematopoiesis, from clonal hematopoiesis to full-blown myeloid leukemia. We discuss how inflammation shapes clonal output from hematopoietic stem cells, how inflammation alters the immune microenvironment in the bone marrow, and novel therapies aimed at targeting inflammation in myeloid disease.

Significance:
Inflammation is emerging as an important factor in myeloid malignancies. Understanding the role of inflammation in myeloid transformation, and the interplay between inflammation and other drivers of leukemogenesis, may yield novel avenues for therapy.
A Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue
Authors: Zhao Liming , Lee Andrew S. , Sasagawa Koki , Sokol Jan , Wang Yuting , Ransom Ryan C. , Zhao Xin , Ma Chao , Steininger Holly M. , Koepke Lauren S. , Borrelli Mimi R. , Brewer Rachel E. , Lee Lorene L.Y. , Huang Xianxi , Ambrosi Thomas H. , Sinha Rahul , Hoover Malachia Y. , Seita Jun , Weissman Irving L. , Wu Joseph C. , Wan Derrick C. , Xiao Jun , Longaker Michael T. , Nguyen Patricia K. , Chan Charles K.F. 
Published: April 2023

Background:
Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia.

Methods:

The Actin
CreER
/R26
VT2/GK3
Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions.

Results:

Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105
high
Sca1
low
, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105
low
Sca1
high
and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice.

Conclusions:
These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.
AGK Potentiates Arterial Thrombosis by Affecting Talin-1 and αIIbβ3-Mediated Bidirectional Signaling Pathway
Authors: Zhang Peng , Jiang Haojie , Yang Mina , Bi Changlong , Zhang Kandi , Liu Dongsheng , Wei Meng , Jiang Zheyi , Lv Keyu , Fang Chao , Liu Junling , Zhang Tiantian , Xu Yanyan , Zhang Junfeng 
Published: April 2023

Background:

AGK (acylglycerol kinase) was first identified as a mitochondrial transmembrane protein that exhibits a lipid kinase function. Recent studies have established that AGK promotes cancer growth and metastasis, enhances glycolytic metabolism and function fitness of CD8
+
T cells, or regulates megakaryocyte differentiation. However, the role of AGK in platelet activation and arterial thrombosis remains to be elaborated.

Methods:
We performed hematologic analysis using automated hematology analyzer and investigated platelets morphology by transmission electron microscope. We explored the role of AGK in platelet activation and arterial thrombosis utilizing transgenic mice, platelet functional experiments in vitro, and thrombosis models in vivo. We revealed the regulation effect of AGK on Talin-1 by coimmunoprecipitation, mass spectrometry, immunofluorescence, and Western blot. We tested the role of AGK on lipid synthesis of phosphatidic acid/lysophosphatidic acid and thrombin generation by specific Elisa kits.

Results:
In this study, we found that AGK depletion or AGK mutation had no effect on the platelet average volumes, the platelet microstructures, or the expression levels of the major platelet membrane receptors. However, AGK deficiency or AGK mutation conspicuously decreased multiple aspects of platelet activation, including agonists-induced platelet aggregation, granules secretion, JON/A binding, spreading on Fg (fibrinogen), and clot retraction. AGK deficiency or AGK mutation also obviously delayed arterial thrombus formation but had no effect on tail bleeding time and platelet procoagulant function. Mechanistic investigation revealed that AGK may promote Talin-1Ser425 phosphorylation and affect the αIIbβ3-mediated bidirectional signaling pathway. However, AGK does not affect lipid synthesis of phosphatidic acid/lysophosphatidic acid in platelets.

Conclusions:
AGK, through its kinase activity, potentiates platelet activation and arterial thrombosis by promoting Talin-1 Ser425 phosphorylation and affecting the αIIbβ3-mediated bidirectional signaling pathway.
Bony Stroke: Ischemic Stroke Caused by Mechanical Stress on Brain Supplying Arteries From Anatomical Bone or Cartilage Anomalies
Authors: Haertl Johanna , Renz Martin , Wunderlich Silke , Hemmer Bernhard , Hofauer Benedikt , Gempt Jens , Kallmayer Michael , Boeckh-Behrens Tobias , Kirschke Jan S. , Ikenberg Benno David 
Published: April 2023

Background:
Bone or cartilage anomalies with affection of brain supplying arteries are a potential structural cause for ischemic stroke. In the following, we termed this entity bony stroke. Due to rarity of their description, there is no standardized workup and therapy for bony strokes.

Methods:
Retrospectively, we extracted diagnostic and therapeutic workup of all patients considered to have had a bony stroke between January 2017 to March 2022 at our comprehensive care center.

Results:
In total, 6 patients classified as a bony stroke were identified among 4200 acute patients with ischemic stroke treated during the study period. Each patient had recurrent ischemic strokes in the dependent vascular territory before diagnosis. Diagnosis was achieved by a combination of imaging devices, including sonography, computed tomography, and magnetic resonance imaging. In addition to conventional static imaging, the application of dynamic imaging modalities with the patients’ head in rotation or reclination confirmed a vessel affection following head movements in 3 patients (50%). Treatment options were interdisciplinary assessed and included the following: conservative treatment (n=1), endovascular stenting (n=2) or occlusion (n=2), surgical removal of bone/ cartilage (n=2), and surgical bypass treatment (n=1). In follow-up (mean 11.7 months), no patient experienced further ischemia.

Conclusions:
As a differential diagnosis, bony strokes may be considered in patients with recurrent ischemic stroke of unknown cause in one dependent vascular territory. Interdisciplinary evaluation and treatment may eliminate risk of stroke recurrence.
Spatial Proteomics Analysis of Soft and Stiff Regions in Human Acute Arterial Thrombus
Authors: Mai Hongcheng , Zhang Tianyuan , Zhang Tao , Lu Aijun , Wu Zhengdong , Yang Bing , He Niu , Liu Xiaoyan , Tsang Chi Kwan , Xu Anding , Lu Dan 
Published: April 2023

Background:
The soft regions of a thrombus tend to be more susceptible to r-tPA (recombinant tissue-type plasminogen activator)-mediated thrombolysis and are more easily removed by mechanical thrombectomy than the stiff counterpart. This study aimed to understand the molecular pathological differences between the soft and stiff regions of human arterial thrombus.

Methods:
We developed a spatial proteomic workflow combining proteomics with laser-captured microdissection to analyze human arterial thrombi with Masson trichrome staining to identify stiff and soft regions from 2 independent cohorts of patients with acute myocardial or cerebral infarction. Dysregulated proteins in a C57BL6/J male mouse model of arterial thrombosis were identified by pathway enrichment and pairwise analyses from the common gene ontology enrichment and dysregulated proteins between carotid and coronary arterial thrombi, and validated by immunohistochemistry.

Results:
Spatial proteomics of the coronary arterial thrombi collected from 7 patients with myocardial infarct revealed 7 common dysregulated proteins in 2 cohorts of patients, and upregulation of TGF-β1 (transforming growth factor β1) was the most prominent fibrosis-related protein. Inhibition of TGF-β1 resulted in delayed arterial thrombosis and accelerated blood flow restoration in mouse model. We further expanded the spatial proteomic workflow to the carotid artery thrombi collected from 11 patients with cerebral infarction. Pairwise proteomic analysis of stiff and soft regions between carotid and coronary arterial thrombi further revealed 5 common gene ontology clusters including features of platelet activation, and a common dysregulated protein COL1A1 (collagen type 1 alpha 1) that was reported to be influenced by TGF-β1. We also verified the expression in human and mice carotid arterial thrombi.

Conclusions:
This study demonstrates the spatially distinct composition of proteins in the stiff and soft regions of human arterial thrombi, and suggests that TGF-β1 is a key therapeutic target for promoting arterial thrombolysis.