bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world treatment and survival of patients with advanced non-small cell lung Cancer: a German retrospective data analysis
Authors: Hardtstock Fränce , Myers David , Li Tracy , Cizova Diana , Maywald Ulf , Wilke Thomas , Griesinger Frank 
Published: March 2020

Abstract
Background
The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk.

Methods
This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016. Identification of eligible patients took place between 01/01/2012–31/12/2015, to allow for at least 1-year pre-index and follow-up periods. Inpatient and outpatient mutation test procedures after aNSCLC diagnosis were observed. Further, prescribed treatments and OS since first (incident) aNSCLC diagnosis and start of respective treatment lines were described both for all patients and presumed EGFR/ALK/ROS-1-positive patients. Factors associated with OS were analyzed in multivariable Cox regression analysis.

Results
Overall, 1741 aNSCLC patients were observed (mean age: 66·97 years, female: 29·87%). The mutation test rate within this population was 26·31% (n = 458), 26·6% of these patients (n = 122) received a targeted treatment and were assumed to have a positive EGFR/ALK/ROS-1 test result. Most often prescribed treatments were pemetrexed monotherapy as 1 L (21·23% for all and 11·11% for mutation-positive patients) and erlotinib monotherapy as 2 L (25·83%/38·54%). Median OS since incident diagnosis was 351 days in all and 571 days in mutation-positive patients. In a multivariable Cox regression analysis, higher age, a stage IV disease, a higher number of chronic drugs in the pre-index period and no systemic therapy increased the risk of early death since first aNSCLC diagnosis. On the other hand, female gender and treatment with therapies other than chemotherapy were associated with a lower risk of early death.

Conclusions
Despite the introduction of new treatments, the real-world survival prognosis for aNSCLC patients remains poor if measured based on an unselected real-world population of patients. Still, the majority of German aNSCLC patients do not receive a mutation test.
Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study
Authors: Yalcin Suayib , Dane Faysal , Oksuzoglu Berna , Ozdemir Nuriye Yildirim , Isikdogan Abdurrahman , Ozkan Metin , Demirag Guzin Gonullu , Coskun Hasan Senol , Karabulut Bulent , Evrensel Turkkan , Ustaoglu Mehmet Ali , Ozdemir Feyyaz , Turna Hande , Yavuzsen Tugba , Aykan Faruk , Sevinc Alper , Akbulut Hakan , Yuce Deniz , Hayran Mutlu , Kilickap Saadettin 
Published: March 2020

Abstract
Background
Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown.

Methods
A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL.

Results
Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42–0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39–0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms.

Conclusions
Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer.

Trial registration
This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).
Downregulation of S100 calcium binding protein A12 inhibits the growth of glioma cells
Authors: Lu Chunhe , Liu Jia , Yao Mingze , Li Lun , Li Guangyu 
Published: March 2020

AbstractBackgroundS100 calcium binding protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified.MethodsIn the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of S100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by shRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, colony formation assay, transwell assay,flow cytometry assa and western blot.ResultsWe found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT.ConclusionS100A12 plays a vital role in glioma progression, and may be an important regulatory molecule for biological behaviors of glioma cell lines.
The A818–6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer
Authors: Tawfik Doaa , Zaccagnino Angela , Bernt Alexander , Szczepanowski Monika , Klapper Wolfram , Schwab Albrecht , Kalthoff Holger , Trauzold Anna 
Published: March 2020

AbstractBackgroundThe human pancreatic cancer cell line A818–6 can be grown in vitro either as a highly malignant, undifferentiated monolayer (ML) or as three-dimensional (3D) single layer hollow spheres (HS) simulating a benign, highly differentiated, duct-like pancreatic epithelial structure. This characteristic allowing A818–6 cells to switch from one phenotype to another makes these cells a unique system to characterize the cellular and molecular modifications during differentiation on one hand and malignant transformation on the other hand. Ion channels and transport proteins (transportome) have been implicated in malignant transformation. Therefore, the current study aimed to analyse the transportome gene expression profile in the A818–6 cells growing as a monolayer or as hollow spheres.Methods & ResultsThe study identified the differentially expressed transportome genes in both cellular states of A818–6 using Agilent and Nanostring arrays and some targets were validated via immunoblotting. Additionally, these results were compared to a tissue Affymetrix microarray analysis of pancreatic adenocarcinoma patients’ tissues. The overall transcriptional profile of the ML and HS cells confirmed the formerly described mesenchymal features of ML and epithelial nature of HS which was further verified via high expression of E-cadherin and low expression of vimentin found in HS in comparison to ML. Among the predicted features between HS and ML was the involvement of miRNA-9 in this switch. Importantly, the bioinformatics analysis also revealed substantial number (n = 126) of altered transportome genes. Interestingly, three genes upregulated in PDAC tissue samples (GJB2, GJB5 and SLC38A6) were found to be also upregulated in ML and 3 down-regulated transportome genes (KCNQ1, TRPV6 and SLC4A) were also reduced in ML.ConclusionThis reversible HS/ML in vitro system might help in understanding the pathophysiological impact of the transportome in the dedifferentiation process in pancreatic carcinogenesis. Furthermore, the HS/ML model represents a novel system for studying the role of the transportome during the switch from a more benign, differentiated (HS) to a highly malignant, undifferentiated (ML) phenotype.
Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study
Authors: Zhang Zeyu , Zhou Yufan , Hu Kuan , Wang Dong , Wang Zhiming , Huang Yun 
Published: March 2020

AbstractBackgroundIn the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial.MethodsICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated.ResultsThere was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS andP = 0.8004 in OS).ConclusionPNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.
Long non-coding RNA AFAP1-AS1 accelerates the progression of melanoma by targeting miR-653-5p/RAI14 axis
Authors: Liu Fei , Hu Lanting , Pei Yi , Zheng Ke , Wang Wei , Li Shenglong , Qiu Enduo , Shang Guanning , Zhang Jiaming , Zhang Xiaojing 
Published: March 2020

Abstract
Background
Melanoma is the most aggressive skin cancer that derived from pigment cells, accounting for the majority of the skin-cancer-related deaths. Despite great development and evolution have been made in surgery, radiotherapy and adjuvant chemotherapy, the prognosis of melanoma patients exhibited no significant improvement. Long noncoding RNAs (lncRNAs) are frequently dysregulated and involved in the development of cancers. LncRNA AFAP1-AS1 has been explored in various cancers, whereas its role and regulatory mechanism in melanoma are not well understood.

Methods
The expression of AFAP1-AS1 was detected by qRT-PCR. CCK-8, colony formation, transwell and western blot assays were performed to investigate the biological role of AFAP1-AS1 in melanoma. Male BALB/c nude mice were applied for in vivo experiments. The interaction among AFAP1-AS1, miR-653-5p and RAI14 was investigated by RNA pull down, RIP and luciferase reporter assays.

Results
AFAP1-AS1 was highly expressed in melanoma cell lines. Suppression of AFAP1-AS1 impaired cell proliferation, migration, invasion and EMT in melanoma. Moreover, AFAP1-AS1 was a ceRNA of RAI14 by competitively binding with miR-653-5p. Besides, miR-653-5p overexpression or RAI14 inhibition could repress tumor growth. Eventually, rescue assays indicated that the function of AFAP1-AS1 in the cellular process of melanoma was dependent on miR-653-5p and RAI14.

Conclusions
AFAP1-AS1 exerts its oncogenic function in melanoma by targeting miR-653-5p/RAI14 axis.
Preoperative anxiety in adults - a cross-sectional study on specific fears and risk factors
Authors: Eberhart Leopold , Aust Hansjörg , Schuster Maike , Sturm Theresa , Gehling Markus , Euteneuer Frank , Rüsch Dirk 
Published: March 2020

AbstractBackgroundPreoperative anxiety comprising anesthesia and surgery related anxiety is common and perceived by many patients as the worst aspect of the surgical episode. The aim of this study was to identify independent predictors of these three anxieties dimensions and to quantify the relevance of specific fears particularly associated with anesthesia.MethodsThis study was part of a cross-sectional survey in patients scheduled to undergo elective surgery. Anxiety levels were measured with the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Modified numeric rating scales (mNRS, range 0–10) were used to assess the severity of eight selected specific fears which were predominantly analyzed descriptively. Multivariate stepwise linear regression was applied to determine independent predictors of all three anxiety dimensions (APAIS anxiety subscales).Results3087 of the 3200 enrolled patients were analyzed. Mean (SD) total preoperative anxiety (APAIS-A-T, range 4–20) was 9.9 (3.6). High anxiety (APAIS-A-T > 10) was reported by 40.5% of subjects. Mean (SD) levels of concern regarding the eight studied specific fears ranged from 3.9 (3.08) concerning “Anesthesiologist error” to 2.4 (2.29) concerning “Fatigue and drowsiness” with an average of 3.2 (2.84) concerning all specific fears. Ranking of all specific fears according to mean mNRS scores was almost identical in patients with high versus those with low anxiety. Among nine independent predictors of anxiety, only 3 variables (female gender, negative and positive anesthetic experience) independently predicted all three APAIS anxiety subscales. Other variables had a selective impact on one or two APAIS anxiety subscales only. Female gender had the strongest impact on all three APAIS anxiety subscales. Adjusted r2values of the three models were all below 13%.ConclusionsThe high variability of importance assigned to all specific fears suggests an individualized approach is advisable when support of anxious patients is intended. Considering independent predictors of anxiety to estimate each patient’s anxiety level is of limited use given the very low predictive capacity of all three models. The clinical benefit of dividing patients into those with high and low anxiety is questionable.Trial registrationGerman Registry of Clinical Trials (DRKS00016725), retrospectively registered.
Knowledge level of cancer symptoms and risk factors in the Gaza Strip: a cross-sectional study
Authors: Elshami Mohamedraed , Elshami Alaa , Alshorbassi Nabeela , Alkhatib Mohammed , Ismail Iyad , Abu-Nemer Khitam , Hana Mustafa , Qandeel Ahmed , Abdelwahed Ahmed , Yazji Hamza , Abuamro Hisham , Matar Ghadeer , Alsahhar Ahmed , Abolamzi Ahmed , Baraka Obay , Elblbessy Mahmood , Samra Tahani , Bottcher Bettina 
Published: March 2020

Abstract
Background
In low-income settings, cancer is often diagnosed in advanced stages due to late presentation. Good public awareness of cancer signs and symptoms has a positive impact on the time patients take before they present to healthcare professionals. Therefore, this study examined public knowledge of cancer signs and symptoms as well as risk factors in Gaza.

Methods
This was a cross-sectional study. Participants were recruited from adult visitors (≥18 years) to governmental hospitals covering all five governorates of Gaza, and adolescent students (15 to 17 years) from 10 high schools in corresponding locations. An Arabic version of the Cancer Awareness Measure (CAM) was completed in a face-to-face interview. It described demographic data and knowledge of: cancer prevalence, age-related risk, signs and symptoms as well as risk factors both in recall and recognition questions.

Results
Of 3033 participants invited, 2886 completed the CAM (response rate = 95.2%). Adult mean age ± standard deviation was 33.7 ± 11.7 years and that of adolescents was 16.3 ± 0.8 years. Half of the participants (n = 1457, 50.5%) were adolescent (781 females; 53.6%) and 1429 (49.5%) were adult (702 females; 49.1%). About two thirds (n = 1885) thought about cancer as unrelated to age. Only 196 participants (6.8%) identified colorectal cancer as the most common cancer among men. Awareness of cancer signs/symptoms was poor to fair, where ‘lump’ was most commonly recognized (n = 2227, 77.2%) and ‘change of bowel habit’ the least (n = 670, 23.2%). Only 217 participants (7.5%) had a good level of recognizing risk factors with ‘smoking’ being the most identified and ‘eating less than five portions of fruits and vegetables a day’ the least. There was a higher likelihood for adults to identify most cancer signs/symptoms and risk factors than adolescents, except for recalling ‘unexplained pain’, ‘persistent cough/hoarseness’, ‘non-healing ulcer’, ‘smoking’, and ‘eating less than five portions of fruits and vegetables a day’.

Conclusion
Public awareness of cancer signs/symptoms and risk factors needs to improve to facilitate early presentation and diagnosis in Gaza. Combining the delivery of public campaigns with tailored education to population groups, including the youth, may increase their knowledge and maintain its impact.
Epidemiological study on animal bite cases referred to Haji Daii health Center in Kermanshah province, Iran during 2013–2017
Authors: Janatolmakan Maryam , Delpak Mojtaba , Abdi Alireza , Mohamadi Sabah , Andayeshgar Bahare , Khatony Alireza 
Published: March 2020

AbstractBackgroundOver thousands of animal bite cases are reported annually worldwide and in Iran placing a large financial burden on the health and economy. The aim of this study was to evaluate the epidemiology of animal bite cases in Kermanshah, Iran through 2013–2017.MethodsIn this cross-sectional study, 5618 animal bite cases in Kermanshah from 2013 to 2017 were studied. Data were analyzed using descriptive and inferential statistics.ResultsIn the study period, 5618 animal bite cases were found. The prevalence of animal bites was estimated between 42.55–45.66 per100000 populations during 2013–2017. An increasing significant trend was found for prevalence of animal bites (Average annual percent change [AAPC] + 4.9,P-trend< 0.001) over a 5-years’ time period. The mean age of the subjects was 32.7 ± 18.3 years. Of the studied subjects 76.3% were male, and 34% had non-governmental jobs. Dogs were found as the cause of animal bites in 72% of the cases. Of the studied cases, 82% had received rabies vaccination for three times.ConclusionThe results showed an increasing significant trend for animal bites in Kermanshah. Development of interventional programs, such as limiting stray dogs, vaccination of dogs and raising public awareness are essential.
Regional differences in the global burden of age-related macular degeneration
Authors: Xu Xiayan , Wu Jing , Yu Xiaoning , Tang Yelei , Tang Xiajing , Shentu Xingchao 
Published: March 2020

Abstract
Background
Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making.

Methods
Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn’s multiple comparisons test as well as regression analysis.

Results
Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years.

Conclusions
The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.
Coexistence of diffuse panbronchiolitis and sarcoidosis revealed during splenectomy: a case report
Authors: Akaba Tomohiro , Takeyama Kiyoshi , Kondo Mitsuko , Kobayashi Fumi , Okabayashi Asako , Sawada Tatsuo , Tagaya Etsuko 
Published: March 2020

Abstract
Background
Sarcoidosis is a systemic granulomatous disease caused by CD4+ cell-dominant inflammation. Meanwhile, diffuse panbronchiolitis is a chronic inflammatory respiratory disease predominantly caused by CD8+ lymphocytes and neutrophils. Herein, we report a rare case of sarcoidosis in which the clinical presentation had become evident as diffuse panbronchiolitis after splenectomy for sarcoidosis.

Case presentation
A 23-year-old Japanese woman was referred to our hospital due to splenomegaly of unknown etiology. Upon admission, chest computed tomography scan revealed centrilobular and randomly distributed small nodules in both lungs. Bronchoalveolar lavage revealed a high proportion of lymphocytes and a decreased CD4/CD8 ratio. However, the biopsy specimens obtained from both the liver and lungs revealed noncaseating epithelioid granulomas, which confirmed the diagnosis of sarcoidosis. The patient underwent splenectomy due to progressive cytopenia and high risk of splenic rupture. After the surgery, the condition of the patient was consistently good for 3 months. Then, she gradually developed productive cough and dyspnea. Both sinus and chest computed tomography scan revealed chronic paranasal sinusitis and deterioration of centrilobular nodules in both lung fields, respectively. The second bronchoalveolar lavage revealed a high proportion of neutrophils, and the bronchoalveolar lavage fluid tested positive for Hemophilus influenzae. The titer of cold agglutinin was elevated, thereby confirming the diagnosis of diffuse panbronchiolitis. On the basis of the clinical and radiological findings, the condition of the patient improved with low-dose macrolide therapy for 3 months.

Conclusions
The coexistence of sarcoidosis and diffuse panbronchiolitis has not been previously reported, and the hidden profiles of diffuse panbronchiolitis may have been revealed by splenectomy.
Finite elements analysis of the temporomandibular joint disc in patients with intra-articular disorders
Authors: Lai Linfeng , Huang Chenyao , Zhou Fan , Xia Fujian , Xiong Guofeng 
Published: March 2020

Abstract
Background
Intra-articular disorders (ID) or anterior and/or medial displacement of the temporomandibular joint disorder (TMJ) disc are the most common form of TMJ dysfunction (TMD). TMD causes changes in the friction coefficient during TMJ movement. Herein, we provided a three-dimensional (3D) finite-elements model (FEM) including the maxilla, disc, and mandible and evaluated the stress distribution with different friction coefficient.

Methods
Fourteen volunteers without TMD and 20 patients with MRI-diagnosed TMD were selected. CT and MRI data were collected to build the 3D FEA model of the mandible and TMJ disc. Stress distribution with different friction coefficient was measured.

Result
In the normal model, stress distribution on the TMJ disc was 2.07 ± 0.17, 1.49 ± 0.14, and 1.41 ± 0.14 MPa with 0.001, 0.3, and 0.4 friction coefficient, respectively. In the TMD model, stress distribution was 3.87 ± 0.15, 7.23 ± 0.22, and 7.77 ± 0.19 MPa respectively.

Conclusion
When the friction coefficient of the side with anterior displacement increased, stress on the disc, condyle and mandible of the opposite side increased. Simultaneously, stress values of the disc, condyle and mandible were higher than those of the normal lateral joint.