bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison common equations for LDL-C calculation with direct assay and developing a novel formula in Iranian children and adolescents: the CASPIAN V study
Authors: Molavi Fatemeh , Namazi Nazli , Asadi Mojgan , Sanjari Mahnaz , Motlagh Mohammad Esmaeil , Shafiee Gita , Qorbani Mostafa , Heshmat Ramin , Kelishadi Roya 
Published: June 2020

Abstract
Background
Hypercholesterolemia is a common dyslipidemia that leads to atherosclerosis. It is proved that early stages of atherosclerosis begins in early stages of life. In several studies, widespread prevalence of dyslipidemia in children is reported. So, assessment of lipid profile in children and adolescence is necessary for early diagnosis of dyslipidemia. Laboratory methods for measuring LDL are not available and economical. So, in some laboratories Friedwald method is used to determine LDL level. But, the preciseness of this method is not acceptable. Further, the preciseness of this method was not assayed in children and adolescence. So, it seems that assaying the preciseness of different methods is necessary.

Methods
The methodology of this work is on the basis of findings of the Caspian V study. This study was conducted in 30 provinces of Iran during 2015. The population of this work was rural and urban students aged 7–18 years old. The level of total cholesterol (TC), HDL, LDL, and TG were measured using laboratory methods. The average and variances values were determined for each group of data using SPSS. Further, LDL values were calculated with a new formula introduced in this work. A comparison was made between the new formula and the other methods.

Results
In the present study, we found that compare to four common formulas, Friedwald was the best equation to estimate LDL-C concentrations in Iranian children and adolescents and the new formula was the next accurate equation. The strongest correlation between Friedwald and the new equation was found for those with 15–18 years old.

Conclusion
Considering the cut-off points of TG (100 mg/dL), we observed the strongest correlation between Friedwald equation and direct assay and the weakest one was for Ahmadi formula in subjects with either greater or lower TG concentrations. Furthermore, we found that Anandraja equation had the most sensitivity (89.5%), while the most specificity was dedicated to the new formula (98.9%).
FTY720 ameliorates GvHD by blocking T lymphocyte migration to target organs and by skin fibrosis inhibition
Authors: Ryu Jaeyoon , Jhun Jooyeon , Park Min-Jung , Baek Jin-ah , Kim Se-Young , Cho Keun-Hyung , Choi Jeong-Won , Park Sung-Hwan , Choi Jong Young , Cho Mi-La 
Published: June 2020

AbstractBackgroundFibrosis is the formation of excess connective tissue in an organ or tissue during a reparative or reactive process. Graft-versus-host disease (GvHD) is a medical complication of allogeneic tissue transplantation with transplanted donor T cell-mediated inflammatory response; it is characterized by a severe immune response with fibrosis in the final stage of the inflammatory process. T helper 17 cells play a critical role in the pathogenesis of GvHD. Fingolimod (FTY720), an analogue of sphingosine-1-phosphate (S1P), is an effective immunosuppressive agent in experimental transplantation models.MethodsIn this study, we evaluated the effects of FTY720 as a treatment for an animal GvHD model with inflammation and fibrosis. The splenocytes, lymph nodes, blood, tissues from Syngeneic mice and GvHD-induced mice treated vehicle or FTY720 were compared using flow cytometry, hematological analyses, histologic analyses.ResultsFTY720 reduced clinical scores based on the following five clinical parameters: weight loss, posture, activity, fur texture, and skin integrity. FACS data showed that T lymphocyte numbers increased in mesenteric lymph nodes and decreased in splenocytes of FTY720-treated mice. Tissue analysis showed that FTY720 reduced skin, intestinal inflammation, and fibrotic markers. FTY720 dramatically decreased α-smooth muscle actin, connective tissue growth factor, and fibronectin protein levels in keloid skin fibroblasts.ConclusionsThus, FTY720 suppressed migration of pathogenic T cells to target organs, reducing inflammation. FTY720 also inhibited fibrogenesis marker expression in vitro and in vivo. Together, these results suggest that FTY720 prevents GvHD progression via immunosuppression of TH17 and simultaneously acts an anti-fibrotic agent.
Kynurenine pathway modulation reverses the experimental autoimmune encephalomyelitis mouse disease progression
Authors: Sundaram Gayathri , Lim Chai K. , Brew Bruce J. , Guillemin Gilles J. 
Published: June 2020

AbstractBackgroundMultiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterized by demyelination, neuroinflammation, and neurodegeneration. Activation of the kynurenine pathway (KP) results from acute and chronic neuroinflammation leading to both immune suppression and neurotoxicity. However, the exact effects of KP metabolites and changes in neurodegenerative diseases over time are not fully understood. Studies, including those in MS models, have reported that short-term KP activation is beneficial through immune tolerance. However, the effects of long-term KP activation are poorly understood. We hypothesized that such chronic activation is responsible for the neurodegeneration in MS, and further, modulating the KP in EAE-induced mice could significantly decrease the EAE disease severity.MethodsWe biochemically altered the KP at different stages of the disease in experimental allergic encephalomyelitis (EAE) mouse model of MS and at two different enzymatic levels of the KP (IDO-1 (indoleamine 2,3 dioxygenase)) and KMO (kynurenine monooxygenase). CNS tissue and blood samples were analyzed longitudinally using GCMS, HPLC, IHC, and RT-PCR.ResultsWe showed that the KP was steadily upregulated correlating with disease severity and associated with a shift towards increasing concentrations of the KP metabolite quinolinic acid, a neuro- and gliotoxin. KP modulation by inhibition of IDO-1 with 1-methyl tryptophan (1-MT) was dependent on the timing of treatment at various stages of EAE. IDO-1 inhibition at EAE score 2 led to significantly higher numbers of FoxP3 cells (p< 0.001) in the spleen than earlier IDO-1 inhibition (prophylactic 1-MT treatment group (p< 0.001)), 1-MT treatment after EAE induction (EAE score 0;p< 0.001), and 1-MT treatment at EAE score of 1 (p< 0.05). Significant improvement of disease severity was observed in EAE mice treated with 1-MT at EAE score 2 compared to the untreated group (p< 0.05). KP modulation by KMO inhibition with Ro 61-8048 led to significantly greater numbers of Foxp3 cells (p< 0.05) in Ro 61-8048 treated mice and even more significant amelioration of EAE disease compared to the 1-MT treatment groups.ConclusionsThese results provide a new mechanistic link between neuroinflammation and neurodegeneration and point to KP modulation at the KMO level to preserve immune tolerance and limit neurodegeneration in EAE. They provide the foundation for new clinical trials for MS.
Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal
Authors: Lee Tsong-Hai , Chen Jiun-Liang , Liu Pei-Shan , Tsai Ming-Ming , Wang Su-Jane , Hsieh Hsi-Lung 
Published: June 2020

Abstract
Background
Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegeneration. In addition, protein kinase Cs (PKCs) has been shown to be involved in regulation of various inflammatory factors like MMP-9 by several stimuli in many cell types. Several phytochemicals are believed to reduce the risk of several inflammatory disorders including the CNS diseases. The rottlerin, a principal phenolic compound of the Kamala plant Mallotus philippinensis, has been shown to possess an array of medicinal properties, including anti-PKC-δ, antitumor, anti-oxidative, and anti-inflammatory activities.

Methods
Herein, we used rat brain astrocytes (RBA) to demonstrate the signaling mechanisms of phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression by zymographic, RT-PCR, subcellular isolation, Western blot, ROS detection, and promoter reporter analyses. Then, we evaluate the effects of rottlerin on PMA-induced MMP-9 expression in RBA and its influencing mechanism.

Results
We first demonstrated that PMA stimulated activation of various types of PKC, including PKC-δ in RBA. Subsequently, PMA induced MMP-9 expression via PKCδ-mediated reactive oxygen species (ROS) generation, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, and then induced c-Fos/AP-1 signaling pathway. Finally, upregulation of MMP-9 by PMA via the pathway may promote astrocytic migration, and the event could be attenuated by rottlerin.

Conclusions
These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of PKC-δ-dependent ROS-mediated MMP-9 expression in brain astrocytes.
Exercise training alone or in combination with high-protein diet in patients with late onset Pompe disease: results of a cross over study
Authors: Sechi Annalisa , Zuccarelli Lucrezia , Grassi Bruno , Frangiamore Rita , De Amicis Ramona , Marzorati Mauro , Porcelli Simone , Tullio Annarita , Bacco Anna , Bertoli Simona , Dardis Andrea , Biasutti Lea , Pasanisi Maria Barbara , Devigili Grazia , Bembi Bruno 
Published: June 2020

Abstract
Background
Late onset Pompe disease (LOPD) is a lysosomal neuromuscular disorder which can progressively impair the patients’ exercise tolerance, motor and respiratory functions, and quality of life. The available enzyme replacement therapy (ERT) does not completely counteract disease progression. We investigated the effect of exercise training alone, or associated with a high-protein diet, on the exercise tolerance, muscle and pulmonary functions, and quality of life of LOPD patients on long term ERT.

Methods
The patients were asked to participate to a crossover randomized study comprehending a control period (free diet, no exercise) followed by 2 intervention periods: exercise or exercise + diet, each lasting 26 weeks and separated by 13 weeks washout periods. Exercise training included moderate-intensity aerobic exercise on a cycle ergometer, stretching and balance exercises, strength training. The diet was composed by 25–30% protein, 30–35% carbohydrate and 35–40% fat. Before and after each period patients were assessed for: exercise tolerance test on a cycle-ergometer, serum muscle enzymes, pulmonary function tests and SF36 questionnaire for quality of life. Compliance was evaluated by training and dietary diaries. Patients were contacted weekly by researchers to optimize adherence to treatments.

Results
Thirteen LOPD patients, median age 49 ± 11 years, under chronic ERT (median 6.0 ± 4.0 years) were recruited. Peak aerobic power (peak pulmonary O2 uptake) decreased after control, whereas it increased after exercise, and more markedlyafter exercise + diet. Serum levels of lactate dehydrogenase (LDH) significantly decreased after exercise + diet; both creatine kinase (CK) and LDH levels were significantly reduced after exercise + diet compared to exercise. Pulmonary function showed no changes after control and exercise, whereas a significant improvement of forced expiratory volume in 1 sec (FEV1) was observed after exercise + diet. SF36 showed a slight improvement in the “mental component” scale after exercise, and a significant improvement in “general health” and “vitality” after exercise + diet. The compliance to prescriptions was higher than 70% for both diet and exercise.

Conclusions
Exercise tolerance (as evaluated by peak aerobic power) showed a tendency to decrease in LOPD patients on long term ERT. Exercise training, particularly if combined with high-protein diet, could reverse this decrease and result in an improvement, which was accompanied by improved quality of life. The association of the two lifestyle interventions resulted also in a reduction of muscle enzyme levels and improved pulmonary function.
Thyroid cancer among patients with thyroid nodules in Yemen: a three-year retrospective study in a tertiary center and a specialty clinic
Authors: Al-Sharafi Butheinah A. , AlSanabani Jamila A. , Alboany Ibraheem M. , Shamsher Amani M. 
Published: June 2020

Abstract
Background
The prevalence of thyroid cancer is increasing worldwide. No previous data are available on the prevalence of thyroid cancer in Yemen. We performed this study to determine the prevalence of thyroid cancer among patients with thyroid nodules in Yemen.

Methods
A retrospective chart review was performed for 550 patients with thyroid nodules who underwent fine needle aspiration and/or thyroid surgery at a private endocrine clinic and at an endocrine clinic in a tertiary hospital in Yemen over a 3 -year period from October 2016–2019. The prevalence of thyroid cancer; the sonographic findings, Bethesda classification, age, sex, thyroid stimulating hormone (TSH) levels of the patients; and the nodule size and number were reviewed.

Results
A total of 550 charts were reviewed [501 females (91.1%) and 49 males (8.9%)]. The thyroid cancer prevalence among the patients was 13.8% (CI = 10.9–16.7), and the mean age of the patients was 38.5 years (SD = 12.2). The TSH level and the rate of cancer were significantly related (P = 0.01), but no significant difference in the prevalence of thyroid cancer was found between females (13.4%) and males (18.4%) (P = 0.334). When correlating the rate of cancer with the ultrasound guided fine needle aspiration (UG-FNA) result, those with Bethesda system category III and IV, V and VI had malignancy rates of 20.8, 27.2, 52.4 and 69.2%, respectively. Thyroid nodules highly suspicious for malignancy on ultrasound had a 70% cancer diagnosis rate. The most common thyroid cancer was papillary cancer (71%), followed by follicular cancer (23.7%). Among those undergoing surgery, 44.2% had thyroid cancer, and 5.2% had a premalignant diagnosis.

Conclusion
Thyroid cancer has a higher prevalence in Yemen than in other middle eastern countries. Our study also reports a higher rate of follicular thyroid cancer than that in other published data, which has to be confirmed by further studies. The malignancy and premalignant diagnosis rate was ~ 50% in our patients who underwent surgery. Many centers in Yemen still do not perform FNA before thyroid surgery. It is important that other centers in the country start emphasizing the need for FNA before surgery. This will decrease the number of unnecessary surgeries and associated complications.
A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA
Authors: Sehn Laurie H. , Martelli Maurizio , Trněný Marek , Liu Wenxin , Bolen Christopher R. , Knapp Andrea , Sahin Deniz , Sellam Gila , Vitolo Umberto 
Published: June 2020

Abstract
Background
Rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the current standard therapy for diffuse large B cell lymphoma (DLBCL). Obinutuzumab (G), a glycoengineered, type II anti-CD20 monoclonal antibody, has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in patients with advanced DLBCL. We present the final analysis results of the Phase III GOYA study (NCT01287741), which compared the efficacy and safety of G-CHOP versus R-CHOP in patients with previously untreated DLBCL.

Methods
Patients aged ≥ 18 years with previously untreated advanced DLBCL were randomly assigned to receive eight 21-day cycles of R or G, plus six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival, other time-to-event endpoints, and safety; investigator-assessed PFS by cell of origin subgroup was an exploratory endpoint.

Results
A total of 1418 patients were randomized, with 1414 included in this final analysis (G-CHOP, N = 704; R-CHOP, N = 710). Five-year PFS rates were 63.8% and 62.6% for G-CHOP and R-CHOP, respectively (stratified hazard ratio 0.94, 95% CI 0.78–1.12; p = 0.48). The results of the secondary efficacy endpoints did not show a benefit of G-CHOP over R-CHOP. In the exploratory analysis, a trend towards benefit with G-CHOP over R-CHOP was apparent in the patients with germinal center B cell DLBCL. The safety profile of G-CHOP was as expected, and no new safety signals were observed. More grade 3–5 (75.1% vs 65.8%), serious (44.4% vs 38.4%), and fatal (6.1% vs 4.4%) adverse events (AEs) were observed in the G-CHOP arm compared with the R-CHOP arm, respectively, with the most common fatal AEs being infections. A higher incidence of late-onset neutropenia occurred in the G-CHOP arm (8.7%) versus the R-CHOP arm (4.9%).

Conclusions
The final analysis, similar to the primary analysis, did not show a PFS benefit of G-CHOP over R-CHOP in previously untreated patients with DLBCL. The results of the secondary endpoints were consistent with the primary endpoint. Further exploratory analyses and investigation of biomarkers are ongoing.
Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among high risk breast Cancer patients: a retrospective chart review study
Authors: Bobbili Priyanka , Olufade Temitope , DerSarkissian Maral , Shenolikar Rahul , Yu Hong , Duh Mei Sheng , Tung Nadine 
Published: June 2020

Abstract
Background
Testing for BRCA variants can impact treatment decisions for breast cancer patients and affect surveillance and prevention strategies for both patients and their relatives. National Comprehensive Cancer Network (NCCN) guidelines recommend testing for patients at heightened risk of BRCA pathogenic variant. We examined the BRCA testing rate among high risk breast cancer patients treated in community oncology practices.

Methods
We conducted a retrospective medical chart review among community-based US oncologists using a physician panel approach. High risk breast cancer patients with a known family history of cancer and diagnosis with breast cancer at age ≥ 18 years between January 2013–October 2017 were included. We assessed the proportions of patients tested for BRCA variants in accordance with NCCN guidelines.

Results
Charts from 63 physicians, averaging 16 years of practice, were included; 97% were medical oncologists and 66.7% had a genetic counselor in their practice. We analyzed data for 410 randomly-selected patients with mean age of 52 years; 95% were female, 74% were White, and 19% had Ashkenazi Jewish ancestry. Among all patients, 94% were tested for BRCA variants. The testing rate ranged from 78 to 100% in various high risk groups; lower rates were observed among Black patients (91%), men (92%), and patients meeting NCCN criteria based on family history of male breast cancer (78%) and prostate cancer (87%). We observed a higher testing rate in patients treated by physicians with a genetic counselor in their practice (95% versus 91%).

Conclusions
Adherence to NCCN BRCA testing guidelines is high in this group of predominantly medical oncologists with extensive experience, with a high proportion having a genetic counselor in practice. Testing rates can be improved in patients with risk factors related to male relatives. High level of compliance to guidelines in a community setting is possible with a delivery model for genetic counseling and testing.
ECMO use in COVID-19: lessons from past respiratory virus outbreaks—a narrative review
Authors: Cho Hwa Jin , Heinsar Silver , Jeong In Seok , Shekar Kiran , Li Bassi Gianluigi , Jung Jae Seung , Suen Jacky Y. , Fraser John F. 
Published: June 2020

AbstractThe spread of coronavirus disease 2019 (COVID-19) continues to grow exponentially in most countries, posing an unprecedented burden on the healthcare sector and the world economy. Previous respiratory virus outbreaks, such as severe acute respiratory syndrome (SARS), pandemic H1N1 and Middle East respiratory syndrome (MERS), have provided significant insights into preparation and provision of intensive care support including extracorporeal membrane oxygenation (ECMO). Many patients have already been supported with ECMO during the current COVID-19 pandemic, and it is likely that many more may receive ECMO support, although, at this point, the role of ECMO in COVID-19-related cardiopulmonary failure is unclear. Here, we review the experience with the use of ECMO in the past respiratory virus outbreaks and discuss potential role for ECMO in COVID-19.
The effectiveness of peer and community health worker-led self-management support programs for improving diabetes health-related outcomes in adults in low- and-middle-income countries: a systematic review
Authors: Werfalli Mahmoud , Raubenheimer Peter J. , Engel Mark , Musekiwa Alfred , Bobrow Kirsten , Peer Nasheeta , Hoegfeldt Cecilia , Kalula Sebastiana , Kengne Andre Pascal , Levitt Naomi S. 
Published: June 2020

Abstract
Objective
Community-based peer and community health worker-led diabetes self-management programs (COMP-DSMP) can benefit diabetes care, but the supporting evidence has been inadequately assessed. This systematic review explores the nature of COMP-DSMP in low- and middle-income countries’ (LMIC) primary care settings and evaluates implementation strategies and diabetes-related health outcomes.

Methods
We searched the Cochrane Library, PubMed-MEDLINE, SCOPUS, CINAHL PsycINFO Database, International Clinical Trials Registry Platform, Clinicaltrials.gov, Pan African Clinical Trials Registry (PACTR), and HINARI (Health InterNetwork Access to Research Initiative) for studies that evaluated a COMP-DSMP in adults with either type 1 or type 2 diabetes in World Bank-defined LMIC from January 2000 to December 2019. Randomised and non-randomised controlled trials with at least 3 months follow-up and reporting on a behavioural, a primary psychological, and/or a clinical outcome were included. Implementation strategies were analysed using the standardised implementation framework by Proctor et al. Heterogeneity in study designs, outcomes, the scale of measurements, and measurement times precluded meta-analysis; thus, a narrative description of studies is provided.

Results
Of the 702 records identified, eleven studies with 6090 participants were included. COMP-DSMPs were inconsistently associated with improvements in clinical, behavioural, and psychological outcomes. Many of the included studies were evaluated as being of low quality, most had a substantial risk of bias, and there was a significant heterogeneity of the intervention characteristics (for example, peer definition, selection, recruitment, training and type, dose, and duration of delivered intervention), such that generalisation was not possible.

Conclusions
The level of evidence of this systematic review was considered low according to the GRADE criteria. The existing evidence however does show some improvements in outcomes. We recommend ongoing, but well-designed studies using a framework such as the MRC framework for the development and evaluation of complex interventions to inform the evidence base on the contribution of COMP-DSMP in LMIC.