bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics profiling reveals a distinct high-risk molecular subtype of hypertrophic cardiomyopathy
Authors: Liang Lusha W , Raita Yoshihiko , Hasegawa Kohei , Fifer Michael A , Maurer Mathew S , Reilly Muredach P , Shimada Yuichi J 
Published: March 2022

ObjectiveHypertrophic cardiomyopathy (HCM) is a heterogeneous disease, likely encompassing several subtypes of disease with distinct biological mechanisms (ie, molecular subtypes). Current models based solely on clinical data have yielded limited accuracy in predicting the risk of major adverse cardiovascular events (MACE). Our aim in this study was to derive molecular subtypes in our multicentre prospective cohort of patients with HCM using proteomics profiling and to examine their longitudinal associations with MACE.MethodsWe applied unsupervised machine learning methods to plasma proteomics profiling data of 1681 proteins from 258 patients with HCM who were prospectively followed for a median of 2.8 years. The primary outcome was MACE, defined as a composite of arrhythmia, heart failure, stroke and sudden cardiac death.ResultsWe identified four molecular subtypes of HCM. Time-to-event analysis revealed significant differences in MACE-free survival among the four molecular subtypes (plogrank=0.007). Compared with the reference group with the lowest risk of MACE (molecular subtype A), patients in molecular subtype D had a higher risk of subsequently developing MACE, with an HR of 3.41 (95% CI 1.54 to 7.55, p=0.003). Pathway analysis of proteins differentially regulated in molecular subtype D demonstrated an upregulation of the Ras/mitogen-activated protein kinase and associated pathways, as well as pathways related to inflammation and fibrosis (eg, transforming growth factor-β pathway).ConclusionsOur prospective plasma proteomics study not only exhibited the presence of HCM molecular subtypes but also identified pathobiological mechanisms associated with a distinct high-risk subtype of HCM.
Patient Reported Outcome Measures for Rheumatoid Arthritis Disease Activity: a systematic review following COSMIN guidelines
Authors: Pickles Tim , Macefield Rhiannon , Aiyegbusi Olalekan Lee , Beecher Claire , Horton Mike , Christensen Karl Bang , Phillips Rhiannon , Gillespie David , Choy Ernest 
Published: March 2022

BackgroundThe current standard of care in rheumatoid arthritis (RA) requires regular assessment of disease activity (DA). All standard RA DA measurement instruments require joint counts to be undertaken by a healthcare professional with/without a blood test. Few healthcare providers have the capacity to assess patients as frequently as stipulated by guidelines. Patient Reported Outcome Measures (PROMs) could be an efficient and informative way to assess RA DA, which is highlighted by the SARS-COV-2 pandemic, as most consultations are remote rather than face-to-face. We aimed to assess all PROMs for RA DA against the internationally recognised COSMIN guidelines to provide evidence‐based recommendations to select the most suitable PROMs.MethodsReview registered on PROSPERO as CRD42020176176. The search strategy was based on a previous similar systematic review and expanded to include all articles up to January 2019. All identified articles were rated by two independent assessors following the COSMIN guidelines.Results668 abstracts were identified, with 10 articles included. A further 21 were identified from a previous review. Ten PROMs were identified. There was insufficient evidence to place any of the identified PROMs into recommendation for use category A due to lack of evidence for content validity, as stipulated by the COSMIN guidelines.ConclusionLack of evidence of content validity limits suitable PROM selection, therefore none can be recommended for use. It is acknowledged that all included PROMs were developed before the COSMIN guidelines were published. Future research on PROMs for RA DA must provide evidence of content validity.
Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): a cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis
Authors: Guldberg-Møller Jørgen , Mogensen Mette , Ellegaard Karen , Zavareh Ali , Wakefield Richard J , Tan Ai Lyn , Boesen Mikael , Dehmeshki Jamshid , Kubassova Olga , Dreyer Lene , Henriksen Marius , Kristensen Lars Erik 
Published: March 2022

ObjectiveCan ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)?MethodsIn this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses.ResultsNew bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting.ConclusionHigh grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance.
On the velocity of a quantum particle in the de Broglie–Bohm quantum mechanics: the case of the bouncing ball
Authors: Feoli A. , Benedetto E. , Iannella A. L. 
Published: March 2022

AbstractStarting from the dynamics of a bouncing ball in classical and quantum regime, we suggest a modification of the probability current in quantum mechanics. We consider the consequences of this generalization on the resulting velocity of a quantum particle in the de Broglie–Bohm interpretation of quantum mechanics.
Art Communities at Risk: On Ukraine
Authors: Biedarieva Svitlana 
Published: March 2022

Abstract
This text analyses the impact of Russia's war against Ukraine on Ukrainian art and features interviews with five Ukrainian artists: Alevtina Kakhidze, Maria Kulikovska, Lia Dostlieva, Andrii Dostliev, and Piotr Armianovski. The artists speak about their experiences of displacement and migration following the annexation of Crimea and the occupation of parts of Donbas in 2014 as well as their premonitions of the full-scale Russian invasion that was to come.
Distinction Between Hepatocellular Carcinoma and Hypervascular Liver Metastases in Non-cirrhotic Patients Using Gadoxetate Disodium-Enhanced Magnetic Resonance Imaging
Authors: Ichikawa Shintaro , Morisaka Hiroyuki , Omiya Yoshie , Onishi Hiroshi 
Published: March 2022

Purpose: This study aims to identify the hallmarks of gadoxetate disodium-enhanced magnetic resonance imaging distinguishing hepatocellular carcinoma (HCC) from hypervascular liver metastases (HLMs). Methods: Between January 2008 and October 2020, among patients who underwent gadoxetate disodium-enhanced MRI, those who met the following criteria were retrospectively included: without chronic hepatitis or liver stiffness ≤ 2.5 kPa on magnetic resonance elastography or F0/F1 on pathological assessment. Two blinded radiologists reviewed the imaging findings to judge the presence or absence of the enhancing capsule, nonperipheral washout, corona enhancement, hypointensity in the transitional/hepatobiliary phase (HBP), hyperintensity on T2-weighted/diffusion-weighted imaging (DWI), mosaic architecture, and blood products/fat in mass. The lesion-to-liver signal intensity ratios in HBP and DWI were also calculated. Univariate and multivariate analyses were performed to identify the imaging hallmarks distinguishing HCC from HLM. Interobserver agreement was calculated using kappa values and intraclass correlation coefficients (ICCs). Results: The final study cohort comprised 72 lesions in 44 patients (mean age, 65.0±11.9 years). Univariate analysis revealed higher frequencies of the following features in HCC than in HLM (P < .10): nonperipheral washout, corona enhancement, transitional phase hypointensity, mosaic architecture, and fat in mass (P = .002-.073). Multivariate analysis revealed that nonperipheral washout and mosaic architecture favored the diagnosis of HCC over that of HLM with odds ratios of 7.66 and 14.6, respectively (P = .038 and .029, respectively). The interobserver agreement for each item was moderate or substantial (kappa or ICC = .447-.792). Conclusion: Peripheral washout and mosaic architecture may be reliable imaging hallmarks for distinguishing HCC from HLM.
Polyaspartic acid, 2-acrylamido-2-Methyl propane sulfonic acid and sodium alginate based biocompatible stimuli responsive polymer gel for controlled release of GHK-Cu peptide for wound healing
Authors: Sharma Shilpa , Anwar Mohammad Faiyaz , Dinda Amit kumar , Singhal Maneesh , Dua Amita , Malik Amita 
Published: March 2022

Stimuli responsive polymer based on Polyaspartic acid, 2-Acrylamido-2-methylpropane sulfonic acid and sodium alginate (NaAlg) were synthesized using two cross-linkers Ethylene glycol dimethacrylate (EGDMA) and TMPTA (Trimethylolpropane triacrylate). The polymers were standardized and optimized to obtain a polymer with maximum swelling in distilled water, saline, glucose and solutions of varying pH. The synthesized polymer swelled well in distilled water, glucose solution and acidic- alkaline medium. The biocompatibility of the polymer was evaluated for blood compatibility and protein adsorption. The polymer with maximum swelling property was used for peptide release studies. The polymer was further used to study the peptide encapsulation and release efficiency of the polymeric material which was confirmed by FTIR, Scanning Emission Microscope and EDX. The encapsulation efficiency of the polymer for encapsulating (glycyl-l-histidyl-l-lysine-copper) GHK-Cu was observed to be 55.26% and peptide release of 51.84% was observed for Ethylene glycol dimethacrylate based polymer after 24 h whereas for Trimethylolpropane triacrylate based polymer the encapsulation efficiency was observed to be 49.6% and release was 39.01%. The EGDMA based polymer was further examined under in vivo studies in order to evaluate the efficiency of the synthesized polymer. The in vivo studies include wound closure, histopathological analysis, biochemical and toxicity assay. The material has shown promising results for both in vivo and in vitro studies.
Injectable in situ intelligent thermo-responsive hydrogel with glycyrrhetinic acid-conjugated nano graphene oxide for chemo-photothermal therapy of malignant hepatocellular tumor
Authors: Wang Huahua , Wang Baiyan , Wang Shasha , Chen Jiaqi , Zhi Weiwei , Guan Yanbin , Cai Bangrong , Zhu Yanhui , Jia Yongyan , Huang Shengnan , Zhu Xiali 
Published: March 2022

Malignant tumor is one of the major diseases with high morbidity and mortality. The purpose of this study is to prepare berberine hydrochloride (BH) in situ thermo-sensitive hydrogel based on glycyrrhetinic acid (GA) modified nano graphene oxide (NGO) (GA-BH-NGO-gel). NGO was taken as the photosensitizer, GA was taken as the target molecule, and BH was taken as the model drug. The physicochemical properties and anti-tumor activity in vivo and in vitro were also studied. This subject could provide a certain theoretical basis for the chemo-photothermal therapy combined treatment of malignant tumor. The release behavior of GA-BH-NGO-gel in vitro presented sustained and temperature-dependent drug release effect. The anti-tumor activity studies in vivo and in vitro had shown that GA-BH-NGO-gel had stronger anti-tumor activity, which could be targeting distributed to the tumor tissues. Moreover, the inhibitory effect of GA-BH-NGO-gel was enhanced when combined with 808 nm of laser irradiation. In this research, the chemo-photothermal combination therapy was applied into the tumor treatment, which may provide certain research ideas for the clinical treatment of malignant tumor.
Injectable metronidazole-eluting gelatin-alginate hydrogels for local treatment of periodontitis
Authors: Zussman Merav , Zilberman Meital 
Published: March 2022

Infection of the periodontal pocket presents two major challenges for drug delivery: administration into the periodontal pocket and a high fluid clearance rate in the pocket. The current study aimed to develop and study a novel hydrogel system for delivery of the antibiotic drug metronidazole directly into the periodontal pocket via injection followed by in situ gelation. The natural polymers gelatin and alginate served as basic materials, and their crosslinking using a carbodiimide resulted in a dual hydrogel network. The study focused on the effects of the hydrogel’s formulation parameters on the drug release profile and the hydrogel’s physical and mechanical properties. A cell viability test was conducted on human fibroblasts. The metronidazole-loaded hydrogels demonstrated a decreasing release rate with time, where most of the drug eluted within 24 h. These hydrogels exhibited fibroblast viability of at least 75% after 24 and 48 h, indicating that they are highly biocompatible. Although the alginate concentration used in this study was relatively low, it had a strong effect on the physical as well as the mechanical properties of the hydrogel. An increase in the alginate concentration increased the crosslinking rate and enabled enhanced entanglement of the 3D structure, resulting in a decrease in the gelation time (less than 10 s) and swelling degree, which are both desired for the studied periodontal application. Increasing the gelatin concentration without changing the crosslinker concentration resulted in significant changes in the physical properties and slight changes in the mechanical properties. Metronidazole incorporation slightly decreased the hydrophilicity of the hydrogel and therefore also its viscosity, and affected the sealing ability and the tensile and compression moduli. The developed hydrogels exhibited controllable mechanical and physical properties, can target a wide range of conditions, and are therefore of high significance in the field of periodontal treatment.
A Randomized Controlled Study Addressing Dexamethasone Tolerability in the Treatment of Acute Asthma in Children: Mary Poppins on Trial!
Authors: Sonnenberg Lyn Kathryn , Sinclair Douglas 
Published: March 2022

Aim Emesis of oral medications continues to be a problem in the management of acute pediatric asthma exacerbations; therefore, we set out to assess whether smaller volumes of oral dexamethasone resulted in better tolerability. Methods: Children aged 2–14 years, presenting to the emergency department with acute asthma exacerbation, were enrolled in this open, prospective randomized controlled trial. Participants received 0.3 mg/kg of dexamethasone in either its concentrated volume (10 mg/mL) or mixed with Ora Sweet (1 mg/mL). Tolerability was measured by vomiting within 45 minutes of receiving dexamethasone, with stratification, a priori, for prior vomiting. Results: 430 participants were enrolled. 23/213 (11%) in the 10 mg/mL group vomited dexamethasone compared to 16/217 (7%) in the 1 mg/mL group (P = .29). 11/179 (6%) in the 10 mg/mL group vomited compared to 8/183 (3%) in the 1 mg/mL group (.61). For those 68 stratified with prior vomiting, 12/34 (35%) in the 10 mg/mL group vomited compared to 8/34 (24%) in the 1 mg/mL group (P = .43). None of these results were statistically different. Prior vomiting increased the risk of vomiting, regardless of the formulation given (P < .001). Conclusions: Volume does not play a significant role in the tolerability of dexamethasone. Therefore, palatability should not be sacrificed for a smaller volume of dexamethasone to improve tolerability.
Lower socioeconomic status worsens outcome of patients with systemic lupus erythematosus independently of access to healthcare
Authors: Sagy Iftach , Cohen Yarden , Nahum Yehudit , Pokroy-Shapira Elisheva , Abu-Shakra Mahmoud , Molad Yair 
Published: March 2022

Objectives Socioeconomic status (SES) has been found to be associated with worse outcomes of systemic lupus erythematosus (SLE). The impact of national health insurance on SLE outcomes has not been explored. Methods A retrospective inception cohort of patients older than 18 years with SLE diagnosed and followed in lupus clinics of two large tertiary medical centers were included. Patients were stratified into three groups by SES: lower 25th quantile, middle 25th‐75th quantile, and upper 75th quantile. Primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and score ≤ 4 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) at the last visit. Results We identified 617 patients (548 females, 88.8%) with a median follow-up of 15 years (range, 8.0–23.0). Compared to the middle and upper SES groups, the lower SES group was characterized by younger age at disease onset (31.5 years vs. 34.3 and 37.4 years, respectively, p = 0.011) and higher rate of lupus nephritis (42.7% vs. 35.7% and 23.8%, respectively, p = 0.002). In multivariate models, patients in the middle and upper SES groups had a significantly lower risk of mortality (HR = 0.45; 95% CI, 0.24–0.82, p = 0.010) and ESKD (HR = 0.24; 95% CI, 0.08–0.73, p = 0.012), with no effect on the rate of SLEDAI 2K ≤ 4 (OR = 1.49; 95% CI, 0.92–2.40, p = 0.09). Conclusion Even within a health system that provides high and equal accessibility to medical care, low SES is associated with worse outcomes of SLE. Policymakers should focus on managing possible barriers that prevent patients of lower SES from obtaining optimal care.
Treatment of diabetic macular edema with intravitreal DEX Implant in Germany: Efficacy and safety in naïve and pre-treated patients in clinical practice
Authors: Augustin Albert Joseph 
Published: March 2022

Purpose To investigate the efficacy and safety of dexamethasone (DEX) implant in eyes with diabetic macular edema (DME) over 12-months. Methods In this retrospective study charts from a single center were analysed, including naïve and pre-treated patients. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated at baseline, months 1–2, 3–4, 5–6 and 7–12. Results Data of 77 eyes were analysed (58.4% were pre-treated with anti-VEGF inhibitors). Mean baseline BCVA values for the whole sample, pre-treated and naïve patients, were 60.94 (SD 13.74), 60.85 (SD 13.80) and 61.01 (SD 13.86) letters, respectively. In the whole sample BCVA changes against baseline were significant (p < 0.05) at months 1–2, 3–4 and 7–12. In the pre-treated group changes were statistically significant at months 1–2 and 7–12. No statistically significant differences were found in the naïve group and between subgroups. In the whole group and the pre-treated group, CRT changes against baseline were significant (p < 0.05) at all time points, while in the naïve group changes were only significant at time point months 3–4. No statistically significant differences were found between subgroups. IOP increases were moderate and successfully managed with topical medication. Conclusion After treatment with DEX implant, BCVA increased and CRT decreased significantly in the whole population at all time points. No significant differences were found between naïve and pre-treated patients. Changes in BCVA and CRT in the naïve group were not statistically significant. This was most likely attributable to the small sample size. The data underlines the importance of DEX implant as an efficacious and safe alternative to VEGF- inhibitors in real world practice.
An Investigation of the Mechanisms of Radiation-Induced Muscle Injury in a Tree Shrew (Tupaia belangeri) Model
Authors: Zhao Pengcheng , Xia Wei , Wei Jianglian , Feng Yiwei , Xie Mao , Niu Zhijie , Liu Heng , Ke Shenghui , Liu Huayu , Tang Anzhou , He Guangyao 
Published: March 2022

Background Animal models suitable for investigating mechanisms behind radiation-induced muscle injury are lacking. We developed a tree shrew model of such injury and investigated pathological changes and mechanisms. Methods Animals were divided into control (n = 5), radiation-induced acute injury (n = 5), and radiation-induced chronic injury (n = 5) groups. Tensor veli palatini (TVP) muscles of acute injury and chronic injury groups were dissected under a microscope at 1 and 24 weeks after radiation therapy, respectively. TVP muscles were stained with HE and Masson to visualize pathological changes. ELISA was performed to measure oxidative injury. RT-qPCR and immunohistochemical staining was performed to measure expression levels of miR-206 and histone deacetylase 4 (HDAC4). Results Compared to the control group, acute injury group showed a significant decrease in miR-206 expression (.061 ± .38, P < .05) and a significant increase in HDAC4 expression (37.05 ± 20.68, P < .05). Chronic injury group showed a significant decrease in miR-206 expression (.23 ± .19, P < .05) and a significant increase in HDAC4 expression (9.66 ± 6.12, P < .05). Discussion A tree shrew model of radiation-induced muscle injury was established by exposing TVP muscle region to radiation of 20-Gy. Experimental results indicated that injury caused by radiation persisted despite gradual healing of the TVP muscle and miR-206 regulatory pathway plays a key role in regulating radiation-induced muscle injury.
Physiotherapy management of atraumatic anterior sternoclavicular joint instability: A prospective case series
Authors: Tunnicliffe Helen , Athanatos Lambros , Singh Harvinder , Armstrong Alison 
Published: March 2022

Background Atraumatic sternoclavicular joint (SCJ) instability is rare. Long-term outcomes are presented for patients managed with physiotherapy. A standardised method of assessment and treatment with a structured physiotherapy programme is also presented. Methods Long-term outcome was analysed in this prospectively collected series (2011-2019) of patients who were assigned to a structured physiotherapy programme for atraumatic SCJ instability. Outcome-measures (subjective SCJ grading of joint stability (SSGS score), Oxford shoulder instability score (OSIS adapted for SCJ) and visual analogue scale (VAS) for pain) were collected at discharge and long-term follow up. Results 26 patients (29 SCJ's) responded (return rate 81%). Mean follow-up was 5.1 years (range 0.9-8.3 years). 17/26 patients were hyperlax. 93% (27/29) of SCJs achieved a stable joint on SSGS score. Mean OSIS score at long-term follow up was 33.4 (range 3-48) and VAS 2.7 (range 0-9). 95% who were compliant with physiotherapy had a stable SCJ (mean OSIS 37.8 (SD 7.3) and VAS 1.6 (SD 2.1)). Those non-compliant, 90% were stable but had lower function (mean OSIS 25 (SD 14, p = 0.02) and more pain, VAS 4.9 (SD 2.9, p = 0.006). Conclusion The structured physiotherapy programme is highly effective in treating patients with atraumatic SCJ instability. Compliance was essential in ensuring better outcomes.