bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in the process and outcome indicators of type 2 diabetes care: a cohort study from Eastern Finland, 2012–2017
Authors: Lamidi Marja-Leena , Wikström Katja , Inglin Laura , Rautiainen Päivi , Tirkkonen Hilkka , Laatikainen Tiina 
Published: December 2020

Abstract
Background
Evidence-based guidelines include concrete treatment targets that can be used as process and outcome indicators in the evaluation of the quality of healthcare services and diabetes care. Quality improvement can be evaluated by monitoring longitudinal trends in the care indicators on the system level. The aim of this study is to describe trends in the processes and outcomes of care among people with type 2 diabetes in North Karelia, Finland.

Methods
The data consist of all adults with type 2 diabetes (identified from the EHRs using ICD-10 codes) who used primary or specialized care services in North Karelia during 2012–2017. The diabetes care was evaluated using the measurement activity, treatment levels, and the achievement of the treatment targets for HbA1c and LDL as care indicators. Logistic and linear models with generalized estimating equations were used to assess the differences between years, sexes, and age groups.

Results
The proportion of patients with annual measurement varied between 75.8 and 78.1% for HbA1c and between 67.4 and 69.1% for LDL during a five-year follow-up. The changes in average levels were moderate: a 0.2% (2 mmol/mol) increase for HbA1c and a 0.1 mmol/l decrease for LDL. Anyway, the proportion of patients meeting the treatment target for HbA1c decreased from 72.7 to 67.3% (age-adjusted decrease: 5.7%p, 95% CI: 4.5–6.9) and for LDL it increased from 53.4 to 59.5% (age-adjusted increase: 5.6%p, 95% CI: 4.2–7.0). Women were measured and met the HbA1c target level more often compared with men. Conversely, men met the LDL target level more often than women, and the age-adjusted difference between sexes increased smoothly from 7.9%p to 11.7%p.

Conclusions
The achievements in relation to type 2 diabetes care in North Karelia are very good, but no major improvement was observed during follow-up. HbA1c levels had a rising tendency and LDL levels declining tendency indicating quality improvement in LDL management, but challenges in further improvement in glucose control.
High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis
Authors: van der Zalm M. M. , Walters E. , Claassen M. , Palmer M. , Seddon J. A. , Demers A.M. , Shaw M. L. , McCollum E. D. , van Zyl G. U. , Hesseling A. C. 
Published: December 2020

AbstractBackgroundThe presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up.MethodsIn an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8.ResultsSeventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0–48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8.ConclusionsWe found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.
Urine collection in cervical cancer screening – analytical comparison of two HPV DNA assays
Authors: Tranberg Mette , Jensen Jørgen Skov , Bech Bodil Hammer , Andersen Berit 
Published: December 2020

Abstract
Background
To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures.

Methods
One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference.

Results
With the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure.

Conclusions
Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.
Revealing two dynamic dengue epidemic clusters in Thailand
Authors: Lim Jue Tao , Han Yiting , Dickens Borame Sue Lee , Choo Esther Li Wen , Chew Lawrence Zheng Xiong , Cook Alex R. 
Published: December 2020

AbstractBackgroundThailand is home to around 69 million individuals. Dengue is hyper-endemic and all 4 serotypes are in active circulation in the country. Dengue outbreaks occur almost annually within Thailand in at least one province but the spatio-temporal and environmental interface of these outbreaks has not been studied.MethodsWe develop Bayesian regime switching (BRS) models to characterize outbreaks, their persistence and infer their likelihood of occurrence across time for each administrative province where dengue case counts are collected. BRS was compared against two other classification tools and their agreement is assessed. We further examine how these spatio-temporal clusters of outbreak clusters arise by comparing reported dengue case counts, urban population, urban land cover, climate and flight volumes on the province level.ResultsTwo dynamic dengue epidemic clusters were found nationally. One cluster consists of 47 provinces and is highly outbreak prone. Provinces with a large number of case counts, urban population, urban land cover and incoming flight passengers are associated to the epidemic prone cluster of dengue. Climate has an effect on determining the probability of outbreaks over time within provinces, but have less influence on whether provinces belong to the epidemic prone cluster. BRS found high agreement with other classification tools.ConclusionsImportation and urbanization drives the risk of outbreaks across regions strongly. In provinces estimated to have high epidemic persistence, more resource allocation to vector control should be applied to those localities as heightened transmission counts are likely to occur over a longer period of time. Clustering of epidemic and non-epidemic prone areas also highlights the need for prioritization of resource allocation for disease mitigation over provinces in Thailand.
Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial
Authors: Pericot-Valverde Irene , Heo Moonseong , Akiyama Matthew J. , Norton Brianna L. , Agyemang Linda , Niu Jiajing , Litwin Alain H. 
Published: December 2020

Abstract
Background
Cigarette smoking has emerged as a leading cause of mortality among people with hepatitis C virus (HCV). People who inject drugs (PWID) represent the largest group of adults infected with HCV in the US. However, cigarette smoking remains virtually unexplored among this population. This study aimed at (1) determining prevalence and correlates of cigarette smoking among HCV-infected PWID enrolled in opiate agonist treatment programs; (2) exploring the association of smoking with HCV treatment outcomes including adherence, treatment completion and sustained virologic response (SVR); and 3) exploring whether cigarette smoking decreased after HCV treatment.

Methods
Participants were 150 HCV-infected PWID enrolled in a randomized clinical trial primarily designed to test three intensive models of HCV care. Assessments included sociodemographics, presence of chronic health and psychiatric comorbidities, prior and current drug use, quality of life, and HCV treatment outcomes.

Results
The majority of the patients (84%) were current cigarette smokers at baseline. There was a high prevalence of psychiatric and medical comorbidities in the overall sample of PWID. Alcohol and cocaine use were identified as correlates of cigarette smoking. Smoking status did not influence HCV treatment outcomes including adherence, treatment completion and SVR. HCV treatment was not associated with decreased cigarette smoking.

Conclusions
The present study showed high prevalence of cigarette smoking among this population as well as identified correlates of smoking, namely alcohol and cocaine use. Cigarette smoking was not associated with HCV treatment outcomes. Given the detrimental effects that cigarette smoking and other co-occurring, substance use behaviors have on HCV-infected individuals’ health, it is imperative that clinicians treating HCV also target smoking, especially among PWID. The high prevalence of cigarette smoking among PWID will contribute to growing morbidity and mortality among this population even if cured of HCV. Tailored smoking cessation interventions for PWID along with HCV treatment may need to be put into clinical practice.

Trial registration
NCT01857245. Registered May 20, 2013.
Idiopathic multicentric Castleman disease with Sjögren’s syndrome and secondary membranous nephropathy: a case report and review of the literature
Authors: Pan Yuejuan , Cui Zhuan , Wang Song , Zheng Danxia , Deng Zhenling , Tian Xinyu , Guo Hongxia , Bao Wenhan , Zhou Sijia , Wang Yue 
Published: December 2020

Abstract
Background
Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren’s syndrome (SS) and secondary membranous nephropathy (SMN).

Case presentation
A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were “reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia”. Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission.

Conclusions
Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.
Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry
Authors: Stuchiner Tamela , Lucas Lindsay , Baraban Elizabeth , Spinelli Kateri J. , Chen Chiayi , Smith Alden , Hashemi Lobat , Cohan Stanley 
Published: December 2020

Abstract
Background
Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period.

Methods
Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable.

Results
Among 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: − 0.41; [95% confidence interval CI: − 3.3-2.4]; p = 0.78) or psychological (mean difference: − 0.23; [95% CI, − 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status.

Conclusions
MS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.
EZH2 inhibitors reverse resistance to gefitinib in primary EGFR wild-type lung cancer cells
Authors: Gong Hao , Li Yongwen , Yuan Yin , Li Weiting , Zhang Hongbing , Zhang Zihe , Shi Ruifeng , Liu Minghui , Liu Chao , Chen Chen , Liu Hongyu , Chen Jun 
Published: December 2020

Abstract
Background
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In traditional anti-cancer therapy, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been proven to be beneficial for patients with EGFR mutations. However, patients with EGFR wild-type NSCLC were usually not respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2) is a key molecular in the PRC2 complex and plays an important role in epigenetic regulation and is overexpressed in variant tumors. EZH2 inhibitors have been reported to sensitize variant tumor cells to anticancer drugs. This study aimed to investigate whether the EZH2 inhibitors, GSK343 and DZNep when combined with gefitinib can reverse EGFR-TKIs resistance in EGFR wild-type NSCLC cells.

Methods
The RNA-sequencing data of patients with NSCLC [502 patients with lung squamous cell carcinoma, including 49 paracancerous lung tissues and 513 patients with lung adenocarcinoma (LUAD), including 59 paracancerous lung tissues] from the Cancer Genome Atlas (TCGA), were analyzed for EZH2 expression. EZH2 expression was verified in 40 NSCLC tissue cancer samples and their corresponding paracancerous tissues from our institute (TJMUGH) via RT-PCR. A549 and H1299 cells treated with siRNA or EZH2 inhibitors were subjected to cell viability and apoptosis analyses as well to EGFR pathway proteins expression analyses via western blotting.

Results
EZH2 was upregulated in human NSCLC tissues and correlated with poor prognosis in patients with LUAD based on data from both TCGA and TJMUGH. Both GSK343 and DZNep sensitized EGFR wild-type LUAD cells (A549 and H1299) to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and by inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted a stronger inhibitory effect on tumor activity, cell proliferation and cell migration than single drug administration in vitro and in vivo.

Conclusions
These data suggest that the combination of EZH2 inhibitors with EGFR-TKIs may be an effective method for treating NSCLC-patients with EGFR-wild type, who do not want to undergo traditional treatment with chemotherapy.
A single-arm, phase 2 study of adjuvant chemotherapy with oral tegafur-uracil for pathologically lymphovascular invasion positive stage IA non-small cell lung cancer: LOGIK0602 study
Authors: Tsuchiya Tomoshi , Kamohara Ryotaro , Muraoka Masashi , Nagayasu Takeshi , Saeki Sho , Takenoyama Mitsuhiro , Suzuki Makoto , Inada Kazuo , Tokunaga Shoji , Hayashi Tomayoshi , Urabe Shogo , Koga Takaomi , Akamine Shinji , Sugio Kenji 
Published: December 2020

Abstract
Background
Lymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC.

Methods
Patients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012.

Results
Among the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered.

Conclusion
A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC.

Trial registration
UMIN identifier: UMIN000005921; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).
Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Yu Ho-Min , Kim Do Kyoung , Seo Hye Jin , Lee Yoo Jin , Cheon Jaekyung , Koh Su Jin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol 
Published: December 2020

Abstract
Background
Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death in AML cells. Therefore, we investigated combination effects of radotinib and Ara-C on AML in this study.

Methods
Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed.

Results
The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI–CDK–cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo. Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells.

Conclusions
Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.