bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Carfilzomib Therapy on Left Ventricular Function in Multiple Myeloma Patients
Authors: Mingrone Giulia , Astarita Anna , Airale Lorenzo , Maffei Ilaria , Cesareo Marco , Crea Teresa , Bruno Giulia , Leone Dario , Avenatti Eleonora , Catarinella Cinzia , Salvini Marco , Cetani Giusy , Gay Francesca , Bringhen Sara , Veglio Franco , Vallelonga Fabrizio , Milan Alberto 
Published: April 2021

Background: Carfilzomib improves the prognosis of multiple myeloma (MM) patients but significantly increases cardiovascular toxicity. The timing and effect of Carfilzomib therapy on the left ventricular function is still under investigation. We sought to assess the echocardiographic systo-diastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy.Methods: Eighty-eight patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after 6 months. All patients were clinically followed up to early identify the occurrence of CVAEs during the whole therapy duration.Results: After Carfilzomib treatment, mean GLS slightly decreased (−22.2% ± 2.6 vs. −21.3% ± 2.5; p &lt; 0.001). Fifty-eight percent of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, and 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS ≥ −21% and/or left ventricular ejection fraction (LVEF) ≤ 60% had a greater risk of major CVAEs (OR = 6.2, p = 0.004; OR = 3.7, p = 0.04, respectively). Carfilzomib led to a higher risk of diastolic dysfunction (5.6 vs. 13.4%, p = 0.04) and to a rise in E/e′ ratio (8.9 ± 2.7 vs. 9.7 ± 3.7; p = 0.006).Conclusion: Carfilzomib leads to early LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic parameters, especially GLS and LVEF, might improve cardiovascular risk stratification before treatment.
Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery
Authors: Zimmerli Aurelia , Monti Matteo , Fenwick Craig , Eckerle Isabella , Beigelman-Aubry Catherine , Pellaton Céline , Jaton Katia , Dumas Dominique , Stamm Gian-Marco , Infanti Laura , Andreu-Ullrich Heidrun , Germann Daphné , Mean Marie , Vollenweider Peter , Stadelmann Raphael , Prella Maura , Comte Denis , Guery Benoit , Gachoud David , Rufer Nathalie 
Published: April 2021

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients.
Reference Values for Five-Repetition Chair Stand Test Among Middle-Aged and Elderly Community-Dwelling Chinese Adults
Authors: Gao Shan-Yan , Xia Yang , Wu Qi-Jun , Chang Qing , Zhao Yu-Hong 
Published: April 2021

Background: Previous studies on the five-repetition chair stand test (CS-5) are limited by the representativeness of the sample or the lack of reference equations for CS-5. Defined reference values for CS-5 in a large population are not available for middle-aged and elderly Chinese adults.Objective: We established age- and sex-stratified reference values for CS-5 times in a large population in China, and to investigate the associations between demographic and anthropometric factors and CS-5 times.Methods: Analysis of data from the national baseline survey of the China Health and Retirement Longitudinal Study, a nationally representative longitudinal survey that includes 450 urban communities and rural villages within 28 provinces, municipalities, and autonomous regions of China.Results: Twelve thousand six hundred five of seventeen thousand seven hundred eight participants were included for the reference value analyses. Twelve thousand three hundred out of seventeen thousand seven hundred eight participants were included for the risk factor analyses. Of 12,605 participants, the mean CS-5 time was 10.13 s (SD, 3.32) in men and 11.03 s (SD, 3.54) in women aged 40+ year. The CS-5 times were shorter in men than women of all age categories (P &lt; 0.001). The cut-off points ranged from 5.36 to 9.98 s and from 6.48 to 10.29 s in men and women, respectively. Mean velocity was higher in men than in women (P &lt; 0.001). Age, waist circumference, living in a rural village, and having chronic diseases were positively associated with CS-5 time, whereas male, handgrip strength, currently married, income, and current or ex-drinker were negatively associated with CS-5 time in this population (all P &lt; 0.001).Conclusions: The comprehensive normative values for CS-5 are essential for enabling clinicians to better evaluate functional performance, determine the appropriate interventional strategy, and promote healthy aging of older adults.
Exploring Variances of White Matter Integrity and the Glymphatic System in Simple Febrile Seizures and Epilepsy
Authors: Salimeen Mustafa Salimeen Abdelkareem , Liu Congcong , Li Xianjun , Wang Miaomiao , Singh Martha , Si Shuqing , Li Mengxuan , Cheng Yannan , Wang Xiaoyu , Zhao Huifang , Wu Fan , Zhang Yuli , Tafawa Habib , Pradhan Anuja , Yang Guanyu , Yang Jian 
Published: April 2021

Background: Simple febrile seizures (SFS) and epilepsy are common seizures in childhood. However, the mechanism underlying SFS is uncertain, and the presence of obvious variances in white matter (WM) integrity and glymphatic function between SFS and epilepsy remain unclear. Therefore, this study aimed to investigate the differences in WM integrity and glymphatic function between SFS and epilepsy.Material and Methods: We retrospectively included 26 children with SFS, 33 children with epilepsy, and 28 controls aged 6–60 months who underwent magnetic resonance imaging (MRI). Tract-based spatial statistics (TBSS) were used to compare the diffusion tensor imaging (DTI) metrics of WM among the above-mentioned groups. T2-weighted imaging (T2WI) was used to segment the visible Virchow-Robin space (VRS) through a custom-designed automated method. VRS counts and volume were quantified and compared among the SFS, epilepsy, and control groups. Correlations of the VRS metrics and seizure duration and VRS metrics and the time interval between seizure onset and MRI scan were also investigated.Results: In comparison with controls, children with SFS showed no significant changes in fractional anisotropy (FA), axial diffusivity (AD), or radial diffusivity (RD) in the WM (P &gt; 0.05). Decreased FA, unchanged AD, and increased RD were observed in the epilepsy group in comparison with the SFS and control groups (P &lt; 0.05). Meanwhile, VRS counts were higher in the SFS and epilepsy groups than in the control group (VRS_SFS, 442.42 ± 74.58, VRS_epilepsy, 629.94 ± 106.55, VRS_control, 354.14 ± 106.58; P &lt; 0.001), and similar results were found for VRS volume (VRS_SFS, 6,228.18 ± 570.74 mm3, VRS_epilepsy, 9,684.84 ± 7,292.66mm3, VRS_control, 4,007.22 ± 118.86 mm3; P &lt; 0.001). However, VRS metrics were lower in the SFS group than in the epilepsy group (P &lt; 0.001). In both SFS and epilepsy, VRS metrics positively correlated with seizure duration and negatively correlated with the course after seizure onset.Conclusion: SFS may not be associated with WM microstructural disruption; however, epilepsy is related to WM alterations. Seizures are associated with glymphatic dysfunction in either SFS or epilepsy.
Involvement of Nrf2-HO-1/JNK-Erk Signaling Pathways in Aconitine-Induced Developmental Toxicity, Oxidative Stress, and ROS-Mitochondrial Apoptosis in Zebrafish Embryos
Authors: Xia Qing , Gao Shuo , Rapael Gnanamuthu Samuel Rajendran , Zhuang Kaiyan , Song Zhenzhen , Zhang Yun , Wang Xue , Tu Pengfei , Li Jianheng , Liu Kechun 
Published: April 2021

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from Aconitum plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 μM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 μM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (Nrf2, HO-1, Cat, and Sod-1) Erk1/2 and Bcl-2 were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (Bad, Bax, Cyto C, Casp-9, and Casp-3) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.
Therapeutic Potential of Bioactive Compounds in Honey for Treating Osteoarthritis
Authors: Martinez-Armenta Carlos , Camacho-Rea María Carmen , Martínez-Nava Gabriela Angélica , Espinosa-Velázquez Rocio , Pineda Carlos , Gomez-Quiroz Luis Enrique , López-Reyes Alberto 
Published: April 2021

Dysregulation of joint tissue homeostasis induces articular degenerative changes and musculoskeletal diseases such as osteoarthritis. This pathology represents the first cause of motor disability in individuals over 60 years of age, impacting their quality of life and the costs of health systems. Nowadays, pharmacological treatments for cartilage disease have failed to achieve full tissue regeneration, resulting in a functional loss of the joint; therefore, joint arthroplasty is the gold standard procedure to cure this pathology in severe cases of Osteoarthritis. A different treatment is the use of anti-inflammatory drugs which mitigate pain and inflammation in some degree, but without significant inhibition of disease progression. In this sense, new therapeutic alternatives based on natural compounds have been proposed to delay osteoarthritis progression, particularly those agents that regulate articular homeostasis. Preclinical studies have shown a therapeutic application of honey and its bioactive compounds, ranging from treating wounds, coughs, skin infections, and are also used as a biological stimulant by exerting antioxidant and anti-inflammatory properties. In this article, we reviewed the current medicinal applications of honey with particular emphasis on its use regulating articular homeostasis by inhibiting inflammation and oxidative stress.
Novel 3D Pixel Sensors for the Upgrade of the ATLAS Inner Tracker
Authors: Terzo Stefano , Boscardin Maurizio , Carlotto Juan , Dalla Betta Gian-Franco , Darbo Giovanni , Dorholt Ole , Ficorella Francesco , Gariano Giuseppe , Gemme Claudia , Giannini Giulia , Grinstein Sebastian , Heggelund Andreas , Huiberts Simon , Kok Angela , Koybasi Ozhan , Lapertosa Alessandro , Lauritzen Magne Elk , Manna Maria , Mendicino Roberto , Oide Hideyuki , Pellegrini Giulio , Povoli Marco , Quirion David , Rohne Ole Myren , Ronchin Sabina , Sandaker Heidi , Abdulla Samy Md. Arif , Stugu Bjarne , Vannoli Leonardo 
Published: April 2021

The ATLAS experiment will undergo a full replacement of its inner detector to face the challenges posed by the High Luminosity upgrade of the Large Hadron Collider (HL-LHC). The new Inner Tracker (ITk) will have to deal with extreme particle fluences. Due to its superior radiation hardness the 3D silicon sensor technology has been chosen to instrument the innermost pixel layer of ITk, which is the most exposed to radiation damage. Three foundries (CNM, FBK, and SINTEF), have developed and fabricated novel 3D pixel sensors to meet the specifications of the new ITk pixel detector. These are produced in a single-side technology on either Silicon On Insulator (SOI) or Silicon on Silicon (Si-on-Si) bonded wafers by etching both n- and p-type columns from the same side. With respect to previous generations of 3D sensors they feature thinner active substrates and smaller pixel cells of 50 × 50 and 25 × 100 µm2. This paper reviews the main design and technological issues of these novel 3D sensors, and presents their characterization before and after exposure to large radiation doses close to the one expected for the innermost layer of ITk. The performance of pixel modules, where the sensors are interconnected to the recently developed RD53A chip prototype for HL-LHC, has been investigated in the laboratory and at beam tests. The results of these measurements demonstrate the excellent radiation hardness of this new generation of 3D pixel sensors that enabled the project to proceed with the pre-production for the ITk tracker.
Multimorbidity and Its Outcomes Among Patients Attending Psychiatric Care Settings: An Observational Study From Odisha, India
Authors: Pati Sanghamitra , Mahapatra Pranab , Dwivedi Rinshu , Athe Ramesh , Sahoo Krushna Chandra , Samal Mousumi , Das Ram Chandra , Hussain Mohammad Akhtar 
Published: April 2021

Background: Multimorbidity, the presence of two or more chronic health conditions is linked to premature mortality among psychiatric patients since the presence of one can further complicate the management of either. Little research has focused on the magnitude and effect of multimorbidity among psychiatric patients in low-and middle-income settings. Our study, provides the first ever data on multimorbidity and its outcomes among patients attending psychiatric clinics in Odisha, India. It further explored whether multimorbidity was associated with higher medical expenditure and the interaction effect of psychiatric illness on this association.Methods: This cross-sectional study included 500 adult patients presenting to the psychiatric clinic of a medical college hospital in Odisha over a period of 6 months (February 2019–July 2019). A validated structured questionnaire, “multimorbidity assessment questionnaire for psychiatric care” (MAQ-PsyC) was used for data collection. We used multinomial logistic model for the effect estimation. Odds ratios (OR) and 95% confidence intervals (CI) for high healthcare utilization and expenditure were calculated by number and pattern of multimorbidity. Data was analyzed by STATA 14.Results: Half (50%) of the psychiatric outpatients had multimorbidity. The relative probabilities of having one additional condition were 5.3 times (RRR = 5.3; 95% CI: 2.3, 11.9) and multiple morbidities were 6.6 times (RRR = 6.6; 95%CI: 3.3, 13.1) higher for patients in 60+ age group. Healthcare utilization i.e., medication use and physician consultation was significantly higher for psychiatric conditions such as mood disorders, schizophrenia, schizotypal and delusional disorders, and for hypertension, cancer, diabetes, among somatic conditions. Out of pocket expenditure (OOPE) was found to be highest for laboratory investigations, followed by medicines and transport expenditure. Within psychiatric conditions, mood disorders incurred highest OOPE ($93.43) while hypertension was the most leading for OOPE in physical morbidities ($93.43). Psychiatric illnesses had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001).Conclusion: Multimorbidity is highly prevalent in psychiatric patients associated with significantly high healthcare utilization and medical expenditure. Such disproportionate effect of psychiatric multimorbidity on healthcare cost and use insinuates the need for stronger financial protection and tailor-made clinical decision making for these vulnerable patient subgroups.
A Nanoscale Photonic Crystal Cavity Optomechanical System for Ultrasensitive Motion Sensing
Authors: Xia Ji , Wang Fuyin , Cao Chunyan , Hu Zhengliang , Yang Heng , Xiong Shuidong 
Published: April 2021

Optomechanical nanocavities open a new hybrid platform such that the interaction between an optical cavity and mechanical oscillator can be achieved on a nanophotonic scale. Owing to attractive advantages such as ultrasmall mass, high optical quality, small mode volume and flexible mechanics, a pair of coupled photonic crystal nanobeam (PCN) cavities are utilized in this paper to establish an optomechanical nanosystem, thus enabling strong optomechanical coupling effects. In coupled PCN cavities, one nanobeam with a mass meff~3 pg works as an in-plane movable mechanical oscillator at a fundamental frequency of πΩm/2π=4.148 MHz. The other nanobeam couples light to excite optical fundamental supermodes at 1542.858 and 1554.464 nm with a Qo larger than 4 × 104. Because of the optomechanical backaction arising from an optical force, abundant optomechanical phenomena in the unresolved sideband are observed in the movable nanobeam. Moreover, benefiting from the in-plane movement of the flexible nanobeam, we achieved a maximum displacement of the movable nanobeam as 1468 fm/Hz1/2. These characteristics indicate that this optomechanical nanocavity is capable of ultrasensitive motion measurements.
Al-Islam dan Kemuhammadiyahan (Aik) dalam Pandangan Mahasiswa Universitas Muhammadiyah Malang (Umm)
Authors: Faridi Faridi 
Published: April 2021

There are three reasons for al-Islam and Kemuhammadiyahan (AIK) to be used as courses at Muhammadiyah Higher Education, including: so that students are able to become Indonesians who are Muslim and have a modern mindset; students can be touched by their souls and able to practice their values; and fostering student ethics in the midst of the Muhammadiyah Higher Education environment. However, when AIK came into contact with students who had various religious ideological backgrounds, it gave birth to various perceptions. Based on this reality, the focus of this research is formulated in the form of a question: how are students' responses and perceptions to the AIK course system? This research is descriptive analytical with data collection techniques in the form of interviews and open-ended questionnaires. This research concluded that all respondents agreed that AIK was used as a subject for reasons, among others: it was able to understand Muhammadiyah's struggle; and he is able to have a strong Islamic provision, knowledge and understanding of pure Islam, and can practice Islamic values ​​in real life. However, AIK learning is considered too monotonous which emphasizes cognitive aspects, so that AIK does not encourage the awakening of daily values; learning methods, facilities and infrastructure also need improvement so that students avoid burnout.
Keywords: religion, Islam, students
Ada tiga alasan al-Islam dan Kemuhammadiyahan (AIK) dijadikan mata kuliah di Perguruan Tinggi Muhammadiyah, antara lain: agar mahasiswa mampu menjadi bangsa Indonesia yang beragama Islam dan mempunyai alam pikiran modern; mahasiswa dapat tersentuh jiwanya serta mampu mengamalkan nilai-nilainya; dan menumbuhkan etika kemahasiswaan di tengah-tengah lingkungan Perguruan Tinggi Muhammadiyah. Namun, ketika AIK bersentuhan dengan mahasiswa yang mempunyai latar ideologi keagamaan yang beragam melahirkan berbagai persepsi. Berdasarkan realitas tersebut, fokus riset ini dirumuskan dalam bentuk pertanyaan: bagaimana respon dan persepsi mahasiswa terhadap sistem mata kuliah AIK?. Riset ini bersifat deskriptif analitis dengan teknik pengumpulan data berupa wawancara dan angket yang sifatnya terbuka. Riset ini menyimpulkan, semua responden menyetujui AIK dijadikan mata kuliah dengan alasan, antara lain: bisa untuk memahami perjuangan Muhammadiyah; dan ia mampu memiliki bekal keislaman yang kuat, pengetahuan dan pemahaman tentang Islam yang murni, serta dapat mengamalkan nilai-nilai Islam dalam kehidupan yang sebenarnya. Namun pembelajaran AIK dinilai terlalu monoton yang menekankan pada aspek kognitif, sehingga AIK kurang mendorong terbangunnya penjiwaan nilai nilai keseharian; metode pembelajaran, sarana maupun prasarana juga perlu pembenahan agar mahasiswa terhindar dari kejenuhan.
Kata Kunci: agama, Islam, mahasiswa
Les balises 3-6-9-12, un guide des écrans en famille, pour apprendre à s’en servir et à s’en passer
Authors: Tisseron Serge 
Published: April 2021

Face aux problèmes que peuvent constituer les écrans pour les enfants, les parents ont besoin de conseils adaptés et opérants, étayés sur des constats scientifiques rigoureux. Depuis 2008, les « balises 3-6-9-12 », calées sur les âges 3 ans, 6 ans, 9 ans et 12 ans, donnent des repères à partir desquels les différents types d’écrans et leurs usages possibles peuvent être proposés aux enfants sans risques. Elles soulignent aussi les aspects positifs des écrans dans un usage accompagné et encadré, « pour apprendre à s’en servir et apprendre à s’en passer ». Car limiter les temps d’écran ne suffit pas. Exactement comme la prise de nourriture fait l’objet de rituels sociaux, il nous faut apprendre aujourd’hui à sortir du numérique dérégulé en créant autour des écrans des rituels familiaux qui apprennent à l’enfant à attendre, à ne pas s’énerver et à partager.