bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal cancer screening behaviors of general surgeons and first-degree family members: a survey-based study
Authors: Celik Suleyman Utku , Cay Hasan Gorkem , Bayrakdar Ersin , Ince Aysima , Ince Esra Nur , Celik Yasemin , Yucel Yunus Emre , Koc Mehmet Ali , Ersoz Siyar , Akyol Cihangir
Published: November 2019

Background

Colorectal cancer (CRC) screening rates are low in the general population and among health care providers. The aim of this study was to evaluate the CRC screening practices of general surgeons who provide specialized diagnostic testing and CRC treatment and to examine the CRC screening behaviors of their first-degree family members.

Methods

A cross-sectional survey was conducted among general surgeons who attended the 21st National Surgical Congress in Turkey held from April 11th to 15th, 2018. The survey included items on demographics, screening-related attitude, CRC screening options, barriers to CRC screening, and surgeons’ annual volumes of CRC cases.

Results

A total of 530 respondents completed the survey. Almost one-third of the responding surgeons (29.4%, n = 156) were aged over 50 years, among whom approximately half (47.1%, n = 74) reported having undergone CRC screening and preferring a colonoscopy as the screening modality (78.4%). Among general surgeons aged 50 years and older, high-volume surgeons (≥25 CRC cases per year) were more likely to undergo screening compared with low-volume surgeons (< 25 CRC cases per year). The respondents aged below 50 years reported that 56.1% (n = 210) of their first-degree relatives were up-to-date with CRC screening, mostly with colonoscopy. Compared to low-volume surgeons aged below 50 years, high-volume surgeons’ first-degree relatives were more likely to be up-to-date with CRC screening.

Conclusion

The survey results demonstrated that routine screening for CRC among surgeons and/or their first-degree relatives is currently not performed at the desired level. However, high-volume surgeons are more likely to participate in routine screening.
Relationship between meaning in life and death anxiety in the elderly: self-esteem as a mediator
Authors: Zhang Jiaxi , Peng Jiaxi , Gao Pan , Huang He , Cao Yunfei , Zheng Lulu , Miao Danmin
Published: November 2019

Background

Death anxiety is a common phenomenon in all societies. Older adults may be more prone to death anxiety than their younger counterparts; however, death anxiety among older adults is not well understood. This study explores the relationship between meaning in life, self-esteem, and death anxiety in senior citizens in China.

Methods

A total of 283 older adults participated in this study; data were collected via the Meaning in Life Questionnaire, the Rosenberg Self-Esteem Scale, and the Death Anxiety Scale.

Results

Results show that the dimensions of meaning in life, presence of meaning (r = − 0.43,p < 0.01), search for meaning (r = − 0.31,p < 0.01), and self-esteem (r = − 0.54,p < 0.01) were each negatively correlated with death anxiety. Regression analysis reveals that meaning in life significantly predicted self-esteem and death anxiety (F = 45.70,p < 0.01; R2 = 0.33). Path analysis indicated that self-esteem either completely or partially mediated the effects of meaning in life on death anxiety in older adults.

Conclusions

Overall, meaning in life appears to be significantly correlated with death anxiety in older adults, and self-esteem can mediate this effect.
Hospitalized elder abuse in Iran: a qualitative study
Authors: Naderi Zeinab , Gholamzadeh Sakineh , Zarshenas Ladan , Ebadi Abbas
Published: November 2019

Background

Elder abuse is a serious violation of human rights and a worldwide issue. Upon hospital admission, elderly patients become vulnerable and susceptible to abuse. Understanding the issues perceived as abuse by the elderly patients and their family members allows us to identify, manage, and prevent elder abuse; especially in hospital settings. The present study aimed to identify and describe the abuse of hospitalized elders from the perspective of patients and their family members.

Methods

The present exploratory qualitative study was conducted from October 2017 to September 2018 at six different teaching hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The target population was elderly patients in different wards across various hospitals and their family members. Based on the purposive sampling method, 16 hospitalized elderly patients and 11 family members were recruited and interviewed. The data were analyzed using the inductive content analysis method in accordance with the process described by Elo and Kyngas (J Adv Nurs 62:107–15, 2008).

Results

Based on the analysis of the interview data, four main categories were extracted and classified as Micro-level, Meso-level, Exo-level, and Macro-level issues.

Conclusion

Hospitalized elder abuse is a multi-dimensional phenomenon caused by personal and professional factors as well as issues related to the inadequate physical environment and organizational structure. To prevent the occurrence of elderly abuse, it is recommended to train hospital staff, rearrange the physical environment, reform the organizational structure, and better plan and manage the financial, physical, and human resources.
SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model
Authors: Liu Guangjie , Li Youjia , Qin Li , Yan Yongxiang , Ye Yijian , Chen Yue , Huang Cuizhu , Zhao Siting , Yao Yongchao , Su Zhong , Chen Xiaoping
Published: November 2019

Background

The co-occurrence of human immunodeficiency virus (HIV) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. Although epidemiological studies have shown the impact of HIV infection on malaria, the mechanism(s) are not yet fully understood. Using a Chinese rhesus macaque coinfection model with simian immunodeficiency virus (SIV) and Plasmodium cynomolgi (Pc) malaria, we investigated the effect of concurrent SIV infection on the course of malaria and the underlying immunological mechanism(s).

Methods

We randomly assigned ten Chinese rhesus monkeys to two groups based on body weight and age. The SIV-Pc coinfection animals (S + P group) were infected intravenously with SIVmac251 eight weeks prior to malaria infection, and the control animals (P group) were infected intravenously with only Pc-infected red blood cells. After malaria was cured with chloroquine phosphate, we also initiated a secondary malaria infection that lasted 4 weeks.

We monitored body weight, body temperature and parasitemia, measured SIV viral loads, hemoglobin and neopterin, and tracked the CD4+, CD8+, and CD4+ memory subpopulations, Ki67 and apoptosis by flow cytometry. Then, we compared these parameters between the two groups.

Results

The animals infected with SIV prior to Pc infection exhibited more severe malaria symptoms characterized by longer episodes, higher parasitemia, more severe anemia, greater body weight loss and higher body temperature than the animals infected with Pc alone. Concurrent SIV infection also impaired immune protection against the secondary Pc challenge infection. The coinfected animals showed a reduced B cell response to Pc malaria and produced lower levels of Pc-specific antibodies. In addition, compared to the animals subjected to Pc infection alone, the animals coinfected with SIV and Pc had suppressed total CD4+ T cells, CD4+CD28highCD95high central memory T cells, and CD4+CD28lowCD95− naïve T cells, which may result from the imbalanced immune activation and faster CD4+ T cell turnover in coinfected animals.

Conclusions

SIV infection aggravates malaria physiologically and immunologically in Chinese rhesus monkeys. This nonhuman primate SIV and Pc malaria coinfection model might be a useful tool for investigating human HIV and malaria coinfection and developing effective therapeutics.
Genomic epidemiology supports multiple introductions and cryptic transmission of Zika virus in Colombia
Authors: Black Allison , Moncla Louise H. , Laiton-Donato Katherine , Potter Barney , Pardo Lissethe , Rico Angelica , Tovar Catalina , Rojas Diana P. , Longini Ira M. , Halloran M. Elizabeth , Peláez-Carvajal Dioselina , Ramírez Juan D. , Mercado-Reyes Marcela , Bedford Trevor
Published: November 2019

Background

Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia.

Methods

We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia.

Results

We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 – Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela.

Conclusions

Similarly to genomic epidemiological studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. More accurately dating when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.
Spectrum of clinical and radiographic findings in patients with diagnosis of H1N1 and correlation with clinical severity
Authors: Schoen Karla , Horvat Natally , Guerreiro Nicolau F. C. , de Castro Isac , de Giassi Karina S.
Published: November 2019

Background

The aim of this study was to evaluate the correlation between clinical and imaging findings with a worse clinical outcome in patients with a confirmed diagnosis of H1N1 influenza A virus.

Methods

Patients with a positive viral test for influenza A H1N1 in 2016 and chest radiography (CR) and/or computed tomography (CT) results had clinical and imaging data reviewed. Hospitalization, admission to the intensive care unit or death were defined as worse clinical outcomes. The association between clinical and imaging features and the worse outcome was calculated in a logistical regression model.

Results

Eighty of 160 (50%) patients were men, with a mean age of 43 ± 19 years. The most common symptoms were as follows: flu-like symptoms 141/160 (88%), dyspnea (25/160, 17%), and thoracic pain (7/160, 5%). Abnormalities on CR were detected in 8/110 (7%) patients, and 43/59 (73%) patients had an abnormal CT. The following variables were associated with worse clinical outcomes: the presence of diabetes mellitus (DM), hypertension, dyspnea, thoracic pain, abnormal CR or CT regardless of the type of finding, CT with consolidation or ground glass opacity.

Conclusions

The presence of DM, hypertension, dyspnea, thoracic pain, or an abnormal CR or CT on admission were associated with worse clinical outcomes in patients with H1N1 influenza A virus infection. Thus, the use of readily accessible clinical and imaging features on admission may have a role in the evaluation of patients with H1N1 infection.
The 2017–2018 influenza season in Bucharest, Romania: epidemiology and characteristics of hospital admissions for influenza-like illness
Authors: Drăgănescu Anca , Săndulescu Oana , Florea Dragoș , Vlaicu Ovidiu , Streinu-Cercel Anca , Oțelea Dan , Luminos Monica Luminița , Aramă Victoria , Abrudan Sorin , Streinu-Cercel Adrian , Pițigoi Daniela
Published: November 2019

Background

Seasonal influenza causes a considerable burden to healthcare services every year. To better measure the impact of severe influenza cases in Romania, we analyzed active surveillance data collected during the 2017–2018 season from patients admitted for influenza-like illness (ILI) at a tertiary care hospital in Bucharest.

Methods

Patients admitted for acute ILI were included if they were resident in the Bucharest-Ilfov region, had been hospitalized for at least 24 h, and had onset of symptoms within 7 days before admission. Patient demographics, healthcare use, vaccination status, and outcome data were collected by questionnaire or by searching clinical records. Respiratory swabs were also obtained from each patient to confirm influenza A (A/H1 and A/H3 subtypes) or influenza B (Yamagata and Victoria lineages) infection by real-time reverse-transcription polymerase chain reaction assay.

Results

The study included 502 patients, many (45.2%) of whom were aged < 5 years. Overall, 108 patients (21.5%) had one or more comorbidities. Seventeen adults aged 18–64 years (3.4%) had been vaccinated against influenza. Patients were hospitalized for a median of 5 days and most (90.4%) were prescribed antiviral treatment. More than one-half of the patients (n = 259, 51.6%) were positive for influenza. Most influenza cases were caused by B viruses (172/259, 66.4%), which were mostly of the B/Yamagata lineage (85 of 94 characterized, 90.4%). Most of the subtyped A viruses were A/H1 (59/74, 79.7%). A/H1 viruses were frequently detected in influenza-positive admissions throughout the 2017–2018 season, whereas the predominant B/Yamagata viruses were detected around the middle of the season, with a peak in cases at week 7 of 2018. Eleven patients were admitted to an intensive care unit; of these, one patient with confirmed B/Yamagata infection died.

Conclusions

These results show that seasonal influenza results in considerable hospitalization in Bucharest-Ilfov, Romania and suggest vaccine coverage should be extended, especially to the youngest age groups. The data from this study should help inform and optimize national influenza healthcare policies.
Risk factors of 90-day rehospitalization following discharge of pediatric patients hospitalized with mycoplasma Pneumoniae pneumonia
Authors: Wang Le , Feng Zhishan , Shuai Jinfeng , Liu Jianhua , Li Guixia
Published: November 2019

Background

Among pediatric patients hospitalized for Mycoplasma pneumoniae pneumonia (MPP), the risk factors for 90-day readmission after discharge is undefined.

Methods

We conducted a retrospective observational study of patients <14 years of age who were discharged with a diagnosis of MPP between January 2016 and February 2017. We collected clinical, laboratory and radiographic variables at the time of initial admission. We assessed pneumonia-related readmission within 90-day after discharge. Risk factors independently associated with rehospitalization were identified using multiple logistic regression models.

Results

Of the 424 MPP hospitalizations, 48 (11.3%) were readmitted within 90 days and were mainly diagnosed with pneumonia. Patients with younger age or coinfection with influenza A were more likely to be readmitted. In addition, compared with children without readmission, the readmission ones showed different clinical and laboratory characteristics at the index hospital admission. Multiple logistic regression analysis identified age (OR 0.815, 95%CI 0.706–0.940) and body temperature (OR 0.659, 95%CI 0.518–0.839) were significantly associated with lower risk of 90-day readmission. Coinfection with influenza was independently associated with a greater likelihood of 90-day readmission (OR 4.746, 95%CI 1.191–18.913).

Conclusions

Readmission after MPP are common and is related to patients’ age, body temperature and influenza A coinfection during initial hospital stay, indicating potential targets could be noticed to reduce the rehospitalization after pediatric MPP.
Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: a prospective controlled study according to the Sepsis-3 definitions
Authors: Song Juhyun , Park Dae Won , Moon Sungwoo , Cho Han-Jin , Park Jong Hak , Seok Hyeri , Choi Won Seok
Published: November 2019

Background

This study investigated the clinical value of interleukin-6 (IL-6), pentraxin 3 (PTX3), and procalcitonin (PCT) in patients with sepsis and septic shock diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Methods

Serum levels of IL-6, PTX3, and PCT were measured in 142 enrolled subjects (51 with sepsis, 46 with septic shock, and 45 as controls). Follow-up IL-6 and PTX3 levels were measured in patients with initial septic shock within 24 h of hospital discharge. Optimal cut-off values were determined for sepsis and septic shock, and prognostic values were evaluated.

Results

Serum IL-6 levels could discriminate sepsis (area under the curve [AUC], 0.83–0.94, P <  0.001; cut-off value, 52.60 pg/mL, 80.4% sensitivity, 88.9% specificity) from controls and could distinguish septic shock (AUC, 0.71–0.89; cut-off value, 348.92 pg/mL, 76.1% sensitivity, 78.4% specificity) from sepsis. Twenty-eight-day mortality was significantly higher in the group with high IL-6 (≥ 348.92 pg/mL) than in the group with low IL-6 (< 348.92 pg/mL) (P = 0.008). IL-6 was an independent risk factor for 28-day mortality among overall patients (hazard ratio, 1.0004; 95% confidence interval, 1.0003–1.0005; p = 0.024). In septic shock patients, both the initial and follow-up PTX3 levels were consistently significantly higher in patients who died than in those who recovered (initial p = 0.004; follow-up P <  0.001).

Conclusions

The diagnostic and prognostic value of IL-6 was superior to those of PTX3 and PCT for sepsis and septic shock.
Association of PD-1 polymorphisms with the risk and prognosis of lung adenocarcinoma in the northeastern Chinese Han population
Authors: Huang Kun , Hu Erqiang , Li Wan , Lv Junjie , He Yuehan , Deng Gui , Xiao Jinling , Yang Chengcheng , Zhao Xinyu , Chen Lina , Wang Xinyan
Published: November 2019

Background

Lung cancer is a leading cause of death from cancer worldwide, especially non-small cell lung cancer (NSCLC). The marker of progression in lung adenocarcinoma, the main type of NSCLC, has been rarely studied. Programmed death 1 (PD-1) is an effective drug target for the treatment of NSCLC. Our study aimed to examine the PD-1 role in the disease process. The study of the effect of polymorphisms on the progression of lung adenocarcinoma in the Han population of Northeast China may provide a valuable reference for the research and application of these drugs.

Methods

Chi-square test, Wilcoxon rank sum test, and classification efficiency assessment were used to test SNPs of PD-1 in 287 patients and combined with clinical information.

Results

We successfully identified biomarkers (rs2227981, rs2227982, and rs3608432) that could distinguish between lung adenocarcinoma patients of early stages and late stages. Multiple clinical indicators showed significant differences among different SNPs and cancer stages. Furthermore, this gene was confirmed to effectively distinguish the stages of lung adenocarcinoma with RNA-seq data in TCGA.

Conclusions

Out study indicated that the PD-1 gene and the SNPs on it could be used as markers for distinguishing lung adenocarcinoma staging in the Northeast Han population. Our investigation into the link between PD-1 polymorphisms and lung adenocarcinoma would help to provide guidance for the treatment and prognosis of lung adenocarcinoma.
Advanced neoplasia in Veterans at screening colonoscopy using the National Cancer Institute Risk Assessment Tool
Authors: Musselwhite Laura W. , Redding Thomas S. , Sims Kellie J. , O’Leary Meghan C. , Hauser Elizabeth R. , Hyslop Terry , Gellad Ziad F. , Sullivan Brian A. , Lieberman David , Provenzale Dawn
Published: November 2019

Background

Adapting screening strategy to colorectal cancer (CRC) risk may improve efficiency for all stakeholders however limited tools for such risk stratification exist. Colorectal cancers usually evolve from advanced neoplasms that are present for years. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool, which calculates future risk of CRC, to determine whether it could be used to predict current advanced neoplasia (AN) in a veteran cohort undergoing a baseline screening colonoscopy.

Methods

This was a prospective assessment of the relationship between future CRC risk predicted by the NCI tool, and the presence of AN at screening colonoscopy. Family, medical, dietary and physical activity histories were collected at the time of screening colonoscopy and used to calculate absolute CRC risk at 5, 10 and 20 years. Discriminatory accuracy was assessed.

Results

Of 3121 veterans undergoing screening colonoscopy, 94% had complete data available to calculate risk (N = 2934, median age 63 years, 100% men, and 15% minorities). Prevalence of AN at baseline screening colonoscopy was 11 % (N = 313). For tertiles of estimated absolute CRC risk at 5 years, AN prevalences were 6.54% (95% CI, 4.99, 8.09), 11.26% (95% CI, 9.28-13.24), and 14.21% (95% CI, 12.02-16.40). For tertiles of estimated risk at 10 years, the prevalences were 6.34% (95% CI, 4.81-7.87), 11.25% (95% CI, 9.27-13.23), and 14.42% (95% CI, 12.22-16.62). For tertiles of estimated absolute CRC risk at 20 years, current AN prevalences were 7.54% (95% CI, 5.75-9.33), 10.53% (95% CI, 8.45-12.61), and 12.44% (95% CI, 10.2-14.68). The area under the curve for predicting current AN was 0.60 (95% CI; 0.57-0.63, p < 0.0001) at 5 years, 0.60 (95% CI, 0.57-0.63, p < 0.0001) at 10 years and 0.58 (95% CI, 0.54-0.61, p < 0.0001) at 20 years.

Conclusion

The NCI tool had modest discriminatory function for estimating the presence of current advanced neoplasia in veterans undergoing a first screening colonoscopy. These findings are comparable to other clinically utilized cancer risk prediction models and may be used to inform the benefit-risk assessment of screening, particularly for patients with competing comorbidities and lower risk, for whom a non-invasive screening approach is preferred.
System-based approaches as prognostic tools for glioblastoma
Authors: Salvucci Manuela , Zakaria Zaitun , Carberry Steven , Tivnan Amanda , Seifert Volker , Kögel Donat , Murphy Brona M. , Prehn Jochen H. M.
Published: November 2019

Background

The evasion of apoptosis is a hallmark of cancer. Understanding this process holistically and overcoming apoptosis resistance is a goal of many research teams in order to develop better treatment options for cancer patients. Efforts are also ongoing to personalize the treatment of patients. Strategies to confirm the therapeutic efficacy of current treatments or indeed to identify potential novel additional options would be extremely beneficial to both clinicians and patients. In the past few years, system medicine approaches have been developed that model the biochemical pathways of apoptosis. These systems tools incorporate and analyse the complex biological networks involved. For their successful integration into clinical practice, it is mandatory to integrate systems approaches with routine clinical and histopathological practice to deliver personalized care for patients.

Results

We review here the development of system medicine approaches that model apoptosis for the treatment of cancer with a specific emphasis on the aggressive brain cancer, glioblastoma.

Conclusions

We discuss the current understanding in the field and present new approaches that highlight the potential of system medicine approaches to influence how glioblastoma is diagnosed and treated in the future.
Cytokeratin 7-negative and GATA binding protein 3-negative breast cancers: Clinicopathological features and prognostic significance
Authors: Lu Shaolei , Yakirevich Evgeny , Wang Li Juan , Resnick Murray B. , Wang Yihong
Published: November 2019

Background

Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.

Methods

This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.

Results

CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.

Conclusions

This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.
EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma
Authors: Xue Liqiong , Yan Hongzhu , Chen Ying , Zhang Qifa , Xie Xin , Ding Xiaoying , Wang Xiaojing , Qian Zhongqing , Xiao Feng , Song Zhiyi , Wu Yijie , Peng Yongde , Xu Huanbai
Published: November 2019

Background

The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. Therefore, novel potential therapeutic targets for PTC are urgently needed. Enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to PRC2, plays important roles in epigenetic silencing and cell cycle regulation. EZH2 overexpression has been found in several malignant tumor tissues, while its expression and function in PTC are largely unknown.

Methods

Sixty-five cases of PTC tissue confirmed by pathology and 30 cases of normal thyroid tissue adjacent to PTC tissue were collected from patients undergoing surgical treatment, between February 2003 and February 2006. We investigated the clinic pathologic significance of EZH2 expression using Realtime-PCR and IHC in 65 human PTC tissues and 30 normal thyroid tissue samples. The EZH2 expression in human PTC cell lines (K1 and W3) and the normal thyroid follicular epithelial cell line Nthy-ori 3–1 was analyzed by Western blotting and Realtime PCR. The expressions of ERα and ERβ in cell lines were analyzed by Realtime PCR.The tumor cell biological behavior was evaluated by CCK8 assay, colony formation assay, transwell migration assay and xenograft tumors model.

Results

Higher rate of EZH2 expression was found in PTC tissues than in normal thyroid tissues, EZH2 expression is associated with lymph node metastasis and recurrent. Inhibition of EZH2 in PTC cell lines downregulates cellular proliferation and migration. PTC is a disease with high incidence of female and E2-ERα upregulates EZH2 expression.

Conclusions

These results suggest a potential role of EZH2 for the PTC growth and metastasis. As a novel therapy, a pharmacological therapy targeting EZH2 has full potential in treatment of PTC.
The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer
Authors: Wang Ru , Zhu Yayun , Liu Xiaoxu , Liao Xiaoqin , He Jianjun , Niu Ligang
Published: November 2019

Background

The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites.

Methods

Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors.

Results

A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors.

Conclusion

Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.
Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience
Authors: Santoro A. , Piermattei A. , Inzani F. , Angelico G. , Valente M. , Arciuolo D. , Spadola S. , Martini M. , Fanfani F. , Fagotti A. , Gallotta V. , Scambia G. , Zannoni G. F.
Published: November 2019

Background

The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging.

Methods

A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement.

Results

Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively.

Conclusions

The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.
MiR-155 promotes anaplastic thyroid cancer progression by directly targeting SOCS1
Authors: Zhang Wei , Ji Wenyue , Zhao Xudong
Published: November 2019

Background

Anaplastic thyroid cancer (ATC) is considered to be a rare type of thyroid cancer but takes up the most important proportion of thyroid cancer-related deaths. Therefore, the development of molecular targeted therapy is an exciting strategy in the management of ATC.

Methods

miR-155 and SOCS1 expression were measured by qRT-PCR as well as western blot analysis. 8305c and FRO cells were transfected and cultured for apoptosis assays, transwell, MTT on miR-155 or SOCS1 suppression and overexpression. Dual-luciferase reporter assays and SOCS1 restoration experimentswas implemented for define the relation between SOCS1 and miR-155. In addition, the correlation between miR-155 expression and patients’ clinicopathological features were also explored.

Results

Aberrant miR-155 and SOCS1 expression and inverse correlation were found in ATC samples. In addition, it indicated that miR-155 expression correlated with cervical metastasis as well as extrathyroidal invasion. Moreover, we demonstrated that miR-155 inhibited 8305c and FRO cells apoptosis, promoted proliferation, invasion and migration. Furthermore, miR-155 inhibition was associated with a significant overexpression of SOCS1. Additionally, luciferase reporter assays presented that miR-155 could bind to SOCS1 3′-UTR, influencing its stability negatively and finally lowering SOCS1 levels. Moreover, it was illustrated that the impacts of miR-155 suppression were reversed by the inhibition of SOCS1 on cell proliferation, apoptosis as well as invasion.

Conclusions

Aberrant miR-155/SOCS1 expression has been included in ATC progression: miR-155 overexpression leads to SOCS1 suppression and develops ATC progression. Thus, miR-155 has been considered to be an underlying therapeutic target for ATC.
Serum fibroblast growth factor 19 serves as a potential novel biomarker for hepatocellular carcinoma
Authors: Maeda Takahiro , Kanzaki Hiroaki , Chiba Tetsuhiro , Ao Junjie , Kanayama Kengo , Maruta Susumu , Kusakabe Yuko , Saito Tomoko , Kobayashi Kazufumi , Kiyono Soichiro , Nakamura Masato , Ogasawara Sadahisa , Suzuki Eiichiro , Ooka Yoshihiko , Nakamoto Shingo , Nakagawa Ryo , Muroyama Ryosuke , Kanda Tatsuo , Maruyama Hitoshi , Kato Naoya
Published: November 2019

Background

Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).

Methods

The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.

Results

The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called “double negative HCC”) exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.

Conclusion

Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.
Can ELABELA be a novel target in the treatment of chronic lymphocytic leukaemia?
Authors: Acik Didar Yanardag , Bankir Mehmet , Baylan Filiz Alkan , Aygun Bilal
Published: November 2019

Background

It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum ELABELA levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment.

Methods

Forty two untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FİNLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer’s instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels.

Results

In our study, we found that serum ELA levels were significantly higher in patients with CLL.

Conclusions

This study highlights that ELA targeting may be a potential therapeutic option for treating CLL.
Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study
Authors: Lakatos Andrea , Kolossváry Márton , Szabó Miklós , Jermendy Ágnes , Barta Hajnalka , Gyebnár Gyula , Rudas Gábor , Kozák Lajos R.
Published: November 2019

Background

Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.

Methods

A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.

Results

MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.

Conclusion

HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.
Sex-related change in BMI of 15- to 16-year-old Norwegian girls in cross-sectional studies in 2002 and 2017
Authors: Bjertnaes Asborg A. , Grundt Jacob H. , Juliusson Petur B. , Markestad Trond J. , Strand Tor A. , Holten-Andersen Mads N.
Published: November 2019

Background

The prevalence of overweight and obesity (OWOB) has stabilized in some countries, but a portion of children with high body mass index (BMI) may have become heavier. This study aimed to describe the distributions of BMI and the point prevalence of OWOB in Norwegian adolescents in 2002 and 2017.

Methods

A cross-sectional study involving 15- to 16-year-old adolescents in Oppland, Norway, was undertaken in 2002 and 2017. We calculated their BMI, BMI z-scores (BMIz), and the prevalence of OWOB.

Results

The mean BMI increased from 20.7 to 21.4 (p < 0.001) for girls but remained unchanged at 21.5 vs 21.4 (p = 0.80) for boys. The prevalence of OWOB increased from 9 to 14% among girls (difference 5, 95% CI: 2, 8) and from 17 to 20% among boys (difference 3, 95% CI: − 1, 6%). The BMI density plots revealed similar shapes at both time points for both sexes, but the distribution for girls shifted to the right from 2002 to 2017.

Conclusion

Contrary to previous knowledge, we found that the increase in OWOB presented a uniform shift in the entire BMI distribution for 15–16-year-old Norwegian girls and was not due to a larger shift in a specific subpopulation in the upper percentiles.
A review of changes to the attention deficit/hyperactivity disorder age of onset criterion using the checklist for modifying disease definitions
Authors: Sanders Sharon , Thomas Rae , Glasziou Paul , Doust Jenny
Published: November 2019

Background

Widening definitions of health conditions have the potential to affect millions of people and should only occur when there is strong evidence of benefit. In the last version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the DSM-5 Committee changed the Attention Deficit Hyperactivity Disorder (ADHD) age of onset criterion in two ways: raising the age of symptom onset and removing the requirement for symptoms to cause impairment. Given concerns about ADHD prevalence and treatment rates, we aimed to evaluate the evidence available to support these changes using a recently developed Checklist for Modifying Disease Definitions.

Methods

We identified and analysed research informing changes to the DSM-IV-TR ADHD age of onset criterion. We compared this evidence to the evidence recommended in the Checklist for Modifying Disease Definitions.

Results

The changes to the DSM-IV-TR age of onset criterion were based on a literature review (publicly available as a 2 page document with online table of included studies), which we appraised as at high risk of bias. Estimates of the change in ADHD prevalence resulting from change to the age of onset criterion were based on a single study that included only a small number of children with ADHD (n = 68) and only assessed the impact of change to the age component of the criterion. No evidence was used by, or available to the Committee regarding the impact on prevalence of removal of the requirement for impairment, or the effect of the criterion changes on diagnostic precision, the prognosis of, or the potential benefits or harms for individuals diagnosed by the new, but not old criterion.

Conclusions

The changes to the age of onset criterion were based on minimal research evidence that suffered from either high risk of bias or poor applicability. The minimal documentation available makes it difficult to judge the rigor of the process behind the criterion changes. Use of the Checklist for Modifying Disease Definitions would assist future proposed modifications of the DSM ADHD criteria, provide guidance on the studies needed to inform potential changes and would improve the transparency and documentation of the process.
Measuring and correcting bias in indirect estimates of under-5 mortality in populations affected by HIV/AIDS: a simulation study
Authors: Quattrochi John , Salomon Joshua A. , Hill Kenneth , Castro Marcia C.
Published: November 2019

Background

In populations that lack vital registration systems, under-5 mortality (U5M) is commonly estimated using survey-based approaches, including indirect methods. One assumption of indirect methods is that a mother’s survival and her children’s survival are not correlated, but in populations affected by HIV/AIDS this assumption is violated, and thus indirect estimates are biased. Our goal was to estimate the magnitude of the bias, and to create a predictive model to correct it.

Methods

We used an individual-level, discrete time-step simulation model to measure how the bias in indirect estimates of U5M changes under various fertility rates, mortality rates, HIV/AIDS rates, and levels of antiretroviral therapy. We simulated 4480 populations in total and measured the amount of bias in U5M due to HIV/AIDS. We also developed a generalized linear model via penalized maximum likelihood to correct this bias.

Results

We found that indirect methods can underestimate U5M by 0–41% in populations with HIV prevalence of 0–40%. Applying our model to 2010 survey data from Malawi and Tanzania, we show that indirect methods would underestimate U5M by up to 7.7% in those countries at that time. Our best fitting model to correct bias in U5M had a root median square error of 0.0012.

Conclusions

Indirect estimates of U5M can be significantly biased in populations affected by HIV/AIDS. Our predictive model allows scholars and practitioners to correct that bias using commonly measured population characteristics. Policies and programs based on indirect estimates of U5M in populations with generalized HIV epidemics may need to be reevaluated after accounting for estimation bias.