bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma
Authors: Mou Yanhua , Wu Jinchun , Zhang Yao , Abdihamid Omar , Duan Chaojun , Li Bin 
Published: January 2021

Abstract
Background
Clear cell renal cell carcinoma is susceptible to ferroptosis, and immunotherapy is recently recommended as a priority for the initial treatment of metastatic clear cell renal carcinoma. Increased ferroptosis and immune activation can synergistically reinforce each other in killing cancer cells. NCOA4 depletion can eliminate iron accumulation and thus weaken ferroptosis. Here, we aim to identify and validate the association between NCOA4 expression, clinicopathologic characteristics, and overall survival in ccRCC by using The Cancer Genome Atlas and Gene Expression Omnibus databases. We further analyze the interacted proteins of NCOA4 and infiltrated immune cells via TIMER and GEPIA databases.

Methods
NCOA4 expression in clear cell renal carcinoma (ccRCC) tissues and normal adjacent tissues in The Cancer Genome Atlas (TCGA) data were primarily screened, and further validated in another independent cohort from the gene expression omnibus (GEO) database and human protein atlas. The relationships of NCOA4 expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which NCOA4 interacted were also built using the online STRING website. Meanwhile, we use TIMER and GEPIA databases to investigate the relationships between NCOA4 expression and infiltrated immune cells and their corresponding gene marker sets.

Results
Contrast to normal tissue, NCOA4 expression was lower in ccRCC tumor tissue(p < 0.05). Lower NCOA4 expression was closely associated with high-grade malignancy and advanced TNM stage. Univariate and multivariate analysis indicated the overall survival of ccRCC cases with low NCOA4 level is shorter than those of patients with high NCOA4 expression (p < 0.05). FTL and FTH1 were the important proteins interacting with NCOA4. ccRCC with NCOA4 deficiency presented the paucity of infiltrated immune cells and their matching marker sets, including CD8+ T cells.

Conclusion
Deficient NCOA4 expression was related to disease progression and poor prognosis, as well as impaired infiltration of immune cells in ccRCC.
Actual long-term survival after resection of stage III soft tissue sarcoma
Authors: Lee Do Weon , Kim Han-Soo , Han Ilkyu 
Published: January 2021

AbstractBackgroundActuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS.MethodsWe retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years.ResultsMultivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95,p = 0.047], histological grade of 2 (OR 8.12,p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25,p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival.ConclusionsActual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.
IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy
Authors: Kim Su Jin , Lee Seung Uk , Kang Min Seung , Ahn Jung Hyo , Shin Jonghoon , Park Choul Yong , Lee Ji Eun 
Published: January 2021

Abstract
Background
We report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement.

Case presentation
A 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years.

Conclusions
This case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.
Psychometric properties of the Norwegian version of the Patient Health Questionnaire-9 (PHQ-9) in a large female sample of adults with and without eating disorders
Authors: Wisting Line , Johnson Sverre Urnes , Bulik Cynthia M. , Andreassen Ole A. , Rø Øyvind , Bang Lasse 
Published: January 2021

Abstract
Background
Internationally, the Patient Health Questionnaire-9 (PHQ-9) is commonly used to assess the frequency and severity of depressive symptoms. However, psychometric properties of the Norwegian version of the PHQ-9 have only been assessed in adolescents. We present normative data for women and an evaluation of the psychometric properties (internal consistency, convergent validity, and factor structure) of the Norwegian PHQ-9 among women with and without eating disorders (ED).

Methods
In this case-control study, a total of 793 females aged 18–78 years (mean 30.39; SD 9.83) completed an online self-report assessment. Measures included the ED100K and Eating Disorder Examination Questionnaire (EDE-Q) to assess ED psychopathology, and the Generalized Anxiety Disorder (GAD) scale and Difficulties in Emotion Regulation Scale Short Form (DERS-SF) to assess symptoms of anxiety and emotion regulation deficits. Participants were categorized into three groups, i.e., previous ED (19.7%, n = 148), current ED (36.3%, n = 272), and no history of ED (44.0%, n = 330), based on self-reported scores on the ED 100 K and the EDE-Q.

Results
Mean PHQ-9 total score for those with a previous history of ED was 10.67 (SD 6.33), for those with a current ED 16.61 (SD 5.84), and for those with no lifetime history of ED 6.83 (SD 5.58). Excellent internal consistency was demonstrated by Cronbach’s alpha’s for individuals with a previous ED (.88), for individuals with a current ED (.86), and for individuals with no history of ED (.88). Acceptable convergent validity was indicated based on significant correlations between the PHQ-9 and GAD-7 and DERS-SF. Confirmatory Factor Analyses revealed a mediocre fit for a one-factor structure of the PHQ-9, regardless of diagnostic status.

Conclusions
The psychometric properties of the Norwegian version of the PHQ-9 are acceptable across females with and without ED, and the PHQ-9 can be recommended for use in clinical ED settings and for people without mental disorders.
Constructing a malaria-related health service readiness index and assessing its association with child malaria mortality: an analysis of the Burkina Faso 2014 SARA data
Authors: Millogo Ourohiré , Doamba Jean E. O. , Sié Ali , Utzinger Jürg , Vounatsou Penelope 
Published: January 2021

Abstract
Background
The Service Availability and Readiness Assessment surveys generate data on the readiness of health facility services. We constructed a readiness index related to malaria services and determined the association between health facility malaria readiness and malaria mortality in children under the age of 5 years in Burkina Faso.

Methods
Data on inpatients visits and malaria-related deaths in under 5-year-old children were extracted from the national Health Management Information System in Burkina Faso. Bayesian geostatistical models with variable selection were fitted to malaria mortality data. The most important facility readiness indicators related to general and malaria-specific services were determined. Multiple correspondence analysis (MCA) was employed to construct a composite facility readiness score based on multiple factorial axes. The analysis was carried out separately for 112 medical centres and 546 peripheral health centres.

Results
Malaria mortality rate in medical centres was 4.8 times higher than that of peripheral health centres (3.5% vs. 0.7%, p < 0.0001). Essential medicines was the domain with the lowest readiness (only 0.1% of medical centres and 0% of peripheral health centres had the whole set of tracer items of essential medicines). Basic equipment readiness was the highest. The composite readiness score explained 30 and 53% of the original set of items for medical centres and peripheral health centres, respectively. Mortality rate ratio (MRR) was by 59% (MRR = 0.41, 95% Bayesian credible interval: 0.19–0.91) lower in the high readiness group of peripheral health centres, compared to the low readiness group. Medical centres readiness was not related to malaria mortality. The geographical distribution of malaria mortality rate indicate that regions with health facilities with high readiness show lower mortality rates.

Conclusion
Performant health services in Burkina Faso are associated with lower malaria mortality rates. Health system readiness should be strengthened in the regions of Sahel, Sud-Ouest and Boucle du Mouhoun. Emphasis should be placed on improving the management of essential medicines and to reducing delays of emergency transportation between the different levels of the health system.
The potential role of local pharmacies to assess asthma control: an Italian cross-sectional study
Authors: Caminati M. , Cegolon L. , Bacchini M. , Segala N. , Dama A. , Bovo C. , Olivieri B. , Furci F. , Senna G. 
Published: January 2021

Abstract
Background
Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay between secondary and primary care services as an effective strategy to control the disease, community pharmacies’ are seldom involved in asthma control assessment.
The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies within the health district of the city of Verona (Veneto Region, North-Eastern Italy).

Methods
A call for participation was launched through the Pharmacists’ Association of Verona. Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI).

Results
Fifty-seven community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. Most patients (92%) self-reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR = 0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT< 16 compared to those not taking medications regularly.

Conclusions
Overall, our findings highlighted an unsatisfactory asthma control in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.
Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors
Authors: Tsukamoto Shinji , Tanzi Piergiuseppe , Mavrogenis Andreas F. , Akahane Manabu , Kido Akira , Tanaka Yasuhito , Cesari Marilena , Donati Davide Maria , Longhi Alessandra , Errani Costantino 
Published: January 2021

AbstractBackgroundThis study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors.MethodsWe retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up.ResultsAn event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p= 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23–30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19–29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p= 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p= 0.976).ConclusionUpfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.
Response to ‘Methodological flaws on “manual therapy for the pediatric population: a systematic review” by Prevost et al. (2019)’
Authors: Pohlman Katherine A. , Anderson Kristian , Carleo Beth , Gleberzon Brian 
Published: January 2021

AbstractCorrespondence from Yu et al. identify methodological issues with the systematic review of manual therapy for pediatric manuscript. Like any research study, limitations are important for readers to keep in consideration when reviewing study findings. The primary authors maintain full confidence in the use of the review to provide practicing clinicians with a comprehensive overview of the limited and low-quality available evidence regarding manual therapies for the pediatric patient.
Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress
Authors: Zhuang Sujing , Liu Baogui , Guo Shifeng , Xue Yanzhong , Wu Lin , Liu Shiqi , Zhang Chunling , Ni Xiuyan 
Published: January 2021

Abstract
Background
Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown.

Methods
Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay.

Results
GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65.

Conclusions
GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.
Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation
Authors: Hsu Yaw-Wen , Hsu Fu-Fei , Chiang Ming-Tsai , Tsai Dong-Lin , Li Fu-An , Angata Takashi , Crocker Paul R. , Chau Lee-Young 
Published: January 2021

AbstractBackgroundThe accumulation of lipid-laden macrophages, foam cells, within sub-endothelial intima is a key feature of early atherosclerosis. Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. Whether Siglec-E expression on macrophages impacts foam cell formation and atherosclerosis remains to be established.MethodsApoE-deficient (apoE−/−) and apoE/Siglec-E-double deficient (apoE−/−/Siglec-E−/−) mice were placed on high fat diet for 3 months and their lipid profiles and severities of atherosclerosis were assessed. Modified low-density lipoprotein (LDL) uptake and foam cell formation in wild type (WT) and Siglec-E−/−- peritoneal macrophages were examined in vitro. Potential Siglec-E-interacting proteins were identified by proximity labeling in conjunction with proteomic analysis and confirmed by coimmunoprecipitation experiment. Impacts of Siglec-E expression and cell surface sialic acid status on oxidized LDL uptake and signaling involved were examined by biochemical assays.ResultsHere we show that genetic deletion of Siglec-E accelerated atherosclerosis without affecting lipid profile in apoE−/−mice. Siglec-E deficiency promotes foam cell formation by enhancing acetylated and oxidized LDL uptake without affecting cholesterol efflux in macrophages in vitro. By performing proximity labeling and proteomic analysis, we identified scavenger receptor CD36 as a cell surface protein interacting with Siglec-E. Further experiments performed in HEK293T cells transiently overexpressing Siglec-E and CD36 and peritoneal macrophages demonstrated that depletion of cell surface sialic acids by treatment with sialyltransferase inhibitor or sialidase did not affect interaction between Siglec-E and CD36 but retarded Siglec-E-mediated inhibition on oxidized LDL uptake. Subsequent experiments revealed that oxidized LDL induced transient Siglec-E tyrosine phosphorylation and recruitment of SHP-1 phosphatase in macrophages. VAV, a downstream effector implicated in CD36-mediated oxidized LDL uptake, was shown to interact with SHP-1 following oxidized LDL treatment. Moreover, oxidized LDL-induced VAV phosphorylation was substantially lower in WT macrophages comparing to Siglec-E−/−counterparts.ConclusionsThese data support the protective role of Siglec-E in atherosclerosis. Mechanistically, Siglec-E interacts with CD36 to suppress downstream VAV signaling involved in modified LDL uptake.
HCG11 up-regulation induced by ELK4 suppressed proliferation in vestibular schwannoma by targeting miR-620/ELK4
Authors: Long Ruiqing , Liu Zhuohui , Li Jinghui , Zhang Yuan , Yu Hualin 
Published: January 2021

AbstractBackgroundVestibular schwannoma (VS) is a kind of benign tumor deriving from the acoustic nerve sheath. Substantial long non-coding RNAs (lncRNAs) were illustrated to have crucial roles in multiple cancers. However, few lncRNAs were elucidated in VS.MethodsHCG11, miR-620 and ELK4 expression were tested by RT-qPCR. Gain-of-function experiments were conducted to confirm the effect of HCG11 on VS.ResultsHCG11 possessed a low expression in VS cell lines. Overexpression of HCG11 repressed cell proliferation but accelerated apoptosis of VS cells. Moreover, we identified ELK4 stimulated the transcription of HCG11 and their affinity was verified by ChIP assays. MiR-620 was chosen to be a target of HCG11 and it was tested to have a high expression in VS cell lines. Moreover, depletion of miR-620 could inhibit cell proliferative ability while fostering apoptosis rate of VS cells. ELK4 was low expressed in VS cell lines and knockdown of ELK4 could rescue the effects made by HCG11 overexpression on progression of VS.ConclusionsHCG11 could inhibit the growth of VS by targeting miR-620/ELK4 in VS cells. HCG11 was a novel therapeutic target for VS treatment.