bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functioning in the fibromyalgia syndrome: validity and reliability of the WHODAS 2.0
Authors: Barreto Marina Carvalho Arruda , Moraleida Fabianna Resende Jesus , Graminha Cristiane Vitaliano , Leite Camila Ferreira , Castro Shamyr Sulyvan , Nunes Ana Carla Lima 
Published: September 2021

Abstract
Background
Fibromyalgia syndrome (FMS) is both a challenging and disabling condition. The International Association for the Study of Pain (IASP) classifies FMS as chronic primary pain, and it can negatively impact individuals’ functioning including social, psychological, physical and work-related factors. Notably, while guidelines recommend a biopsychosocial approach for managing chronic pain conditions, FMS assessment remains clinical. The WHODAS 2.0 is a unified scale to measure disability in the light of the International Classification of Functioning, Disability and Health. Thus, this study aimed to evaluate the reliability and validity of the Brazilian version of WHODAS 2.0 for use in individuals with FMS.

Methods
Methodological study of the validity and reliability of the Brazilian version of the 36-item WHODAS 2.0 with 110 individuals with FMS. The instrument gives a score from 0 to 100, the higher the value, the worse the level of functioning. We assessed participants with Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (0–100), Fibromyalgia Impact Questionnaire (FIQ) (0–10) and Beck Depression Inventory instrument (BDI) (0–63). The construct validity, internal consistency, and test–retest stability. We used SF-36, FIQ and BDI to study construct validity analysis. For statistical analysis, we performed the intraclass correlation (ICC), Spearman correlation, and Cronbach's alpha, with a statistical level of 5%.

Results
Most participants were female (92.27%), aged 45 (± 15) years. The test–retest reliability analysis (n = 50) showed stability of the instrument (ICC = 0.54; ρ = 0.84, p < 0.05). The test–retest correlation between the domains was moderate to strong (ρ > 0.58 and < 0.90). Internal consistency was satisfactory for total WHODAS 2.0 (0.91) and also for domains, ranging from 0.44 to 0.81. The construct validity showed satisfactory values with all moderately correlated with WHODAS 2.0 instruments (> 0.46 and < 0.64; p < 0.05). WHODAS 2.0 evaluates the functioning encompassing components of health-related quality of life, functional impact, and depressive symptoms in those with FMS.

Conclusions
WHODAS 2.0 is a reliable and valid instrument to evaluate functioning of Brazilians with FMS. It provides reliable information on individuals' health through of a multidimensional perspective, that allows for individual-centered care.
Zebrafish toxicological screening could aid Leishmaniosis drug discovery
Authors: Fukushima Hirla Costa Silva , Bailone Ricardo Lacava , Corrêa Tatiana , Janke Helena , De Aguiar Luís Kluwe , Setti Princia Grejo , Borra Ricardo Carneiro 
Published: September 2021

Abstract
Background
Recently a screen from a library of 1.8 million compounds identified in vitro a potent activity of the 2-aminobenzimidazoles series against Leishmania infantum, the etiological agent responsible by over 20.000 deaths each year. Several analogs were synthesized and in vitro tested through an optimization program, leading to a promising 2-aminobenzimidazoles derived compound (2amnbzl-d) that was progressed to in vivo mice studies. However, the not expected toxic effects prevented its progression to more advanced preclinical and clinical phases of drug development. Due to limitations of cell models in detecting whole organism complex interactions, 90% of the compounds submitted to pre-clinical tests are reproved. The use of Zebrafish embryo models could improve this rate, saving mammals, time and costs in the development of new drugs. To test this hypothesis, we compared 2amnbzl-d with two compounds with already established safety profile: carbamazepine and benznidazole, using an embryo Zebrafish platform based on acute toxicity, hepatotoxicity, neurotoxicity and cardiotoxicity assays (Pltf-AcHpNrCd).

Results
Tests were performed blindly, and the results demonstrated the presence of lethal and teratogenic effects (CL50%: 14.8 µM; EC50%: 8.6 µM), hepatotoxic in concentrations above 7.5 µM and neurotoxic in embryos exposed to 15 µM of 2amnbzl-d. Nevertheless, benznidazole exposition showed no toxicity and only the 100 µM of carbamazepine induced a bradycardia.

Conclusions
Results using Pltf-AcHpNrCd with zebrafish reproduced that found in the toxicological tests with mammals to a portion of the costs and time of experimentation.
Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study
Authors: Moon Sang Won , Park Sinhyung , Oh Minkyung , Wang Joon Ho 
Published: September 2021

Abstract
Background
The study investigated whether allogeneic human umbilical cord blood-derived MSCs (hUCB-MSCs) could be safely used without treatment-related adverse events, reducing tunnel enlargement, and improve clinical results in human anterior cruciate ligament (ACL) reconstruction.

Methods
Thirty patients were enrolled consecutively. They were divided into three groups by randomization. In the negative control group, ACL reconstruction surgery without additional treatment was performed. In the experimental group, a hUCB-MSC and hyaluronic acid mixture was applied to the tendon-bone interface of the femoral tunnels during ACL reconstruction surgery. In the positive control group, only hyaluronic acid was applied. Finally, 27 patients were analyzed after the exclusion of three patients. The incidence of treatment-related adverse events, clinical outcomes, including second-look arthroscopic findings, and the amount of tunnel enlargement, were evaluated.

Results
There were no treatment-related adverse events in the treatment groups. Tunnel enlargement in the experimental group (579.74 ± 389.85 mm3) was not significantly different from those in the negative (641.97 ± 455.84 mm3) and positive control (421.96 ± 274.83 mm3) groups (p = 0.6468). There were no significant differences between the groups in clinical outcomes such as KT-2000 measurement (p = 0.793), pivot shift test (p = 0.9245), International Knee Documentation Committee subjective score (p = 0.9195), Tegner activity level (p = 0.9927), and second-look arthroscopic findings (synovial coverage of the graft, p = 0.7984; condition of the graft, p = 0.8402).

Conclusions
Allogeneic hUCB-MSCs were used safely for ACL reconstruction without treatment-related adverse event in a 2-year follow-up. However, our study did not suggest any evidence to show clinical advantage such as the prevention of tunnel enlargement postoperatively and a decrease in knee laxity or improvement of clinical outcomes.

Trial registration
CRIS, Registration Number: KCT0000917. Registered on 12 November 2013; https://cris.nih.go.kr/cris/index.jsp
Giant descending aortic pseudo-aneurysm in an adult man with uncorrected aortic coarctation
Authors: Jabbary Zahra , Toufan Mehrnoush 
Published: September 2021

Abstract
Background
Aortic coarctation (CoAo) accounts for 6 to 8% of all congenital heart diseases and occurs two to five times more often in males. The uncorrected aortic coarctation is complicated by hypertension, ascending and descending aortic aneurysms, endarteritis, and heart failure. The aortic pseudo-aneurysm (APD) usually occurs in patients with endarteritis. We report an adult man with bicuspid aortic valve, perimembranous ventricular septal defect, and uncorrected aortic coarctation complicated by descending aortic pseudo-aneurysm without aortic endarteritis.

Case presentation
A 40-year-old man was referred to our division for hemoptysis and severe aortic coarctation. Echocardiography confirmed the aortic coarctation diagnosis and showed a large aortic pseudo-aneurysm at the coarctation site with intra-cavity mural thrombus. Subsequently, the patient underwent contrast-enhanced computed tomography angiography, and diagnosis of coarctation and APD was confirmed. Due to various malformations and considering that the patient had become unstable due to hemoptysis, it was discussed in the heart team, and it was decided that the patient would undergo staged surgery.

Conclusions
The aortic pseudo-aneurysm is a rare complication in patients with untreated coarctation that requires prompt surgery, and this complication should be considered in patients with untreated aortic coarctation who present with hemoptysis.
Association of COVID-19 infection with large thrombi in left and right atrial appendages
Authors: Ghodsi Saeed , Taghi Sara , Alizadeh-Sani Zahra , Jenab Yaser , Hosseini Zahra , Vaskelyte Laura 
Published: September 2021

AbstractBackgroundMultiple intra-atrial thrombi are found rarely except in the presence of prosthetic valves, intra-cardiac devices, structural connections like foramen ovale and thrombophilia.Case presentationWe reported acute thrombosis formation in right and left atrial appendages of a 66-year old man admitted due to progressive dyspnea since 7 days earlier. He had a history of prior laryngeal Squamous Cell Carcinoma, apical hypertrophic cardiomyopathy (HCM), and atrial fibrillation (AF). Infection with COVID-19 was confirmed thereafter. Cardiac Magnetic Resonance Imaging (CMR) suggested the diagnosis of atrial clot superior to neoplasm. After surgical removal of the thrombi, symptoms as well as imaging features of pneumonia were resolved.ConclusionsWe should focus on different presentations and complications of systemic inflammation especially in the setting of COVID-19 infection. Although risk factors of thrombosis are present in some of these patients, rapid progression as well as unusual types of involvement may indicate to a new trigger.
Inhaled prostacyclin analogues in COVID-19 associated acute respiratory distress syndrome: scientific rationale
Authors: Mulia Eka Prasetya Budi , Luke Kevin 
Published: September 2021

Abstract
Background
COVID-19 associated acute respiratory distress syndrome (CARDS) is a severe form of SARS CoV-2 infection and affects about 15–30% of hospitalized patients with a high mortality rate. Growing research and data suggest several available drugs with appropriate pharmacological effects to treat COVID-19.

Main body
Prostacyclin analogues are regiments for pulmonary artery hypertension. Prostacyclin analogues are expected to be beneficial in treating CARDS based on at least four rationales: (1) inhaled prostacyclin analogues improve oxygenation, V/Q mismatch, and act as an ARDS therapy alternative; (2) it alleviates direct SARS-CoV-2-related coagulopathy; (3) increases nitric oxide production; and (4) possible anti-inflammatory effect. Prostacyclin analogues are available in oral, intravenous, and inhaled forms. The inhaled form has the advantage over other forms, such as parenteral administration risks. Previously, a meta-analysis demonstrated the beneficial effects of inhaled prostaglandins for ARDS treatment, such as improved PaO2/FiO2 and PaO2 along with reduced pulmonary artery pressure. Currently, two ongoing randomized controlled trials are evaluating inhaled epoprostenol (VPCOVID [NCT04452669]) and iloprost (ILOCOVID [NCT04445246]) for severe COVID-19 patients.

Conclusions
Inhaled prostacyclin could be considered in patients with refractory, life-threatening hypoxia despite standard management.
Implementation of a central-line bundle: a qualitative study of three clinical units
Authors: Goldman Joanne , Rotteau Leahora , Shojania Kaveh G. , Baker G. Ross , Rowland Paula , Christianson Marlys K. , Vogus Timothy J. , Cameron Connie , Coffey Maitreya 
Published: September 2021

Abstract
Background
Evidence for the central line-associated bloodstream infection (CLABSI) bundle effectiveness remains mixed, possibly reflecting implementation challenges and persistent ambiguities in how CLABSIs are counted and bundle adherence measured. In the context of a tertiary pediatric hospital that had reduced CLABSI by 30% as part of an international safety program, we aimed to examine unit-based socio-cultural factors influencing bundle practices and measurement, and how they come to be recognized and attended to by safety leaders over time in an organization-wide bundle implementation effort.

Methods
We used an interpretivist qualitative research approach, based on 74 interviews, approximately 50 h of observations, and documents. Data collection focused on hospital executives and safety leadership, and three clinical units: a medical specialty unit, an intensive care unit, and a surgical unit. We used thematic analysis and constant comparison methods for data analysis.

Results
Participants had variable beliefs about the central-line bundle as a quality improvement priority based on their professional roles and experiences and unit setting, which influenced their responses. Nursing leaders were particularly concerned about CLABSI being one of an overwhelming number of QI targets for which they were responsible. Bundle implementation strategies were initially reliant on unit-based nurse education. Over time there was recognition of the need for centralized education and reinforcement tactics. However, these interventions achieved limited impact given the influence of competing unit workflow demands and professional roles, interactions, and routines, which were variably targeted in the safety program. The auditing process, initially a responsibility of units, was performed in different ways based on individuals’ approaches to the process. Given concerns about auditing reliability, a centralized approach was implemented, which continued to have its own variability.

Conclusions
Our findings report on a contextualized, dynamic implementation approach that required movement between centralized and unit-based approaches and from a focus on standardization to some recognition of a role for customization. However, some factors related to bundle compliance and measurement remain unaddressed, including harder to change socio-cultural factors likely important to sustainability of the CLABSI reductions and fostering further improvements across a broader safety agenda.
Analytical method development and validation for simultaneous estimation of Fimasartan Potassium Trihydrate and Cilnidipine in synthetic mixture by HPLC for the treatment of hypertension stage-II
Authors: Sojitra Radhika G. , Chotaliya Urvi J. 
Published: September 2021

Abstract
Background
A specific, accurate, precise, robust, and cost-effective HPLC method was developed and validated for quantitative analysis of Fimasartan Potassium Trihydrate and Cilnidipine in fixed-dose combination. The isocratic elution was accomplished by Symmetry C18 column (150 mm × 4.6 mm, 5 µm) at 25 °C. Mobile phase composition is Methanol: Acetonitrile: Potassium Dihydrogen Phosphate buffer (pH 3) (60:05:35%v/v/v) at a flow rate of 1.0 mL/min, injection volume 20 µL with DAD detection at 240 nm.

Result
Fimasartan Potassium Trihydrate and Cilnidipine were eluted with retention time 2.65 min and 5.51 min respectively. This method was validated as per ICH guideline (Q2 R1). The calibration plots were over the concentration range of 15–90 μg/mL and 2.5–15 μg/mL for Fimasartan Potassium Trihydrate and Cilnidipine with correlation coefficient 0.9992 and 0.9989 respectively. Accuracy was obtained between 99.51–101.65% and 100.06–101.20% for Fimasartan Potassium Trihydrate and Cilnidipine respectively. LOD were found to be 0.97 μg/mL and 0.57 μg/mL and LOQ were found to be 2.95 μg/mL and 1.75 μg/mL for Fimasartan Potassium Trihydrate and Cilnidipine respectively.

Conclusion
The results showed that the developed method is reliable for the routine analysis for simultaneous determination of Fimasartan Potassium Trihydrate and Cilnidipine.
Identifying Barriers and Facilitators to Scalp Cooling Therapy Through a National Survey of the Awareness, Practice Patterns, and Attitudes of Oncologists
Authors: Novice Madison , Novice Taylor , Henry N. Lynn , Johnson Kyle , Jeruss Jacqueline S. , Kidwell Kelley M. , Burness Monika L. 
Published: September 2021

PURPOSE: Scalp cooling therapy (SCT) is the most effective method to reduce chemotherapy-induced alopecia (CIA), a highly distressing side effect of cancer treatment. Despite data supporting SCT efficacy and safety, SCT use in the United States is not widespread. Oncologists' interactions with scalp cooling were examined to identify facilitators and barriers to SCT implementation. METHODS: A 33-question survey was distributed through the ASCO Research Survey Pool to a nationally representative, random sample of 600 oncology providers. Outcome measures included knowledge of SCT, frequency of initiating conversations about SCT with patients, degree of support, and barriers for SCT. Significance was defined as P < .001. RESULTS: Of 155 (25.8%) responding providers, 62% of providers were in favor of SCT always or most of the time, but only 26% reported initiating discussions about SCT always or most of the time. Providers who treat breast cancer ( P ≤ .0001), those who report being very familiar with SCT ( P ≤ .0001), those who report having read SCT literature in the past 2 years ( P ≤ .0001), and those who work at a facility with machine SCT ( P ≤ .0001) were significantly more likely to initiate conversations with patients about SCT. Financial concerns (58%) were the primary reason for not recommending SCT use; efficacy (31%), staff or facility (24%), and safety (15%) concerns were also noted. Although safety concerns have decreased markedly over time, 14% of providers report patients who continue to express these concerns and 17% of providers see safety issues as barriers to supporting SCT. CONCLUSION: Our findings suggest that oncology provider familiarity and experience with SCT lead to increased support for scalp cooling, which may ultimately result in greater availability and utilization of SCT when indicated.
Advances in live imaging early mouse development: exploring the researcher's interdisciplinary toolkit
Authors: Stower Matthew J. , Srinivas Shankar 
Published: September 2021

ABSTRACT
Live imaging is an important part of the developmental biologist's armoury of methods. In the case of the mouse embryo, recent advances in several disciplines including embryo culture, microscopy hardware and computational analysis have all contributed to our ability to probe dynamic events during early development. Together, these advances have provided us with a versatile and powerful ‘toolkit’, enabling us not only to image events during mouse embryogenesis, but also to intervene with them. In this short Spotlight article, we summarise advances and challenges in using live imaging specifically for understanding early mouse embryogenesis.
Development of follicular dendritic cells in lymph nodes depends on retinoic acid-mediated signaling
Authors: Koning Jasper J. , Rajaraman Anusha , Reijmers Rogier M. , Konijn Tanja , Pan Junliang , Ware Carl F. , Butcher Eugene C. , Mebius Reina E. 
Published: September 2021

ABSTRACTSpecialized stromal cells occupy and help define B- and T-cell domains, which are crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF receptors is crucial for the development of different stromal subsets, which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known. Using in vitro cultures of embryonic mouse stromal cells, we show that retinoic acid-mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, and also blocks lymphotoxin-mediated Ccl19pos fibroblastic reticular cell lineage differentiation. Accordingly, at the day of birth we observe the presence of Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, and complete blockade of retinoic acid signaling prevents the formation of FDC networks in lymph nodes.
Mycobacteriophage–antibiotic therapy promotes enhanced clearance of drug-resistant Mycobacterium abscessus
Authors: Johansen Matt D. , Alcaraz Matthéo , Dedrick Rebekah M. , Roquet-Banères Françoise , Hamela Claire , Hatfull Graham F. , Kremer Laurent 
Published: September 2021

ABSTRACT
Infection by multidrug-resistant Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF) patients, leaving clinicians with few therapeutic options. A compassionate study showed the clinical improvement of a CF patient with a disseminated M. abscessus (GD01) infection, following injection of a phage cocktail, including phage Muddy. Broadening the use of phage therapy in patients as a potential antibacterial alternative necessitates the development of biological models to improve the reliability and successful prediction of phage therapy in the clinic. Herein, we demonstrate that Muddy very efficiently lyses GD01 in vitro, an effect substantially increased with standard drugs. Remarkably, this cooperative activity was retained in an M. abscessus model of infection in CFTR-depleted zebrafish, associated with a striking increase in larval survival and reduction in pathological signs. The activity of Muddy was lost in macrophage-ablated larvae, suggesting that successful phage therapy relies on functional innate immunity. CFTR-depleted zebrafish represent a practical model to rapidly assess phage treatment efficacy against M. abscessus isolates, allowing the identification of drug combinations accompanying phage therapy and treatment prediction in patients.
This article has an associated First Person interview with the first author of the paper.
Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis
Authors: Alves Liliana S. , Marques André R. A. , Padrão Nuno , Carvalho Filomena A. , Ramalho José , Lopes Catarina S. , Soares Maria I. L. , Futter Clare E. , Pinho e Melo Teresa M. V. D. , Santos Nuno C. , Vieira Otília V. 
Published: September 2021

ABSTRACT
In atherosclerotic lesions, vascular smooth muscle cells (VSMCs) represent half of the foam cell population, which is characterized by an aberrant accumulation of undigested lipids within lysosomes. Loss of lysosome function impacts VSMC homeostasis and disease progression. Understanding the molecular mechanisms underlying lysosome dysfunction in these cells is, therefore, crucial. We identify cholesteryl hemiazelate (ChA), a stable oxidation end-product of cholesteryl-polyunsaturated fatty acid esters, as an inducer of lysosome malfunction in VSMCs. ChA-treated VSMCs acquire a foam-cell-like phenotype, characterized by enlarged lysosomes full of ChA and neutral lipids. The lysosomes are perinuclear and exhibit degradative capacity and cargo exit defects. Lysosome luminal pH is also altered. Even though the transcriptional response machinery and autophagy are not activated by ChA, the addition of recombinant lysosomal acid lipase (LAL) is able to rescue lysosome dysfunction. ChA significantly affects VSMC proliferation and migration, impacting atherosclerosis. In summary, this work shows that ChA is sufficient to induce lysosomal dysfunction in VSMCs, that, in ChA-treated VSMCs, neither lysosome biogenesis nor autophagy are triggered, and, finally, that recombinant LAL can be a therapeutic approach for lysosomal dysfunction.