bluuebunny/crossref_metadata_2025 huggingface dataset:
CAIX is a predictor of pathological complete response and is associated with higher survival in locally advanced breast cancer submitted to neoadjuvant chemotherapy
Authors: Alves Wilson Eduardo Furlan Matos , Bonatelli Murilo , Dufloth Rozany , Kerr Lígia Maria , Carrara Guilherme Freire Angotti , Costa Ricardo Filipe Alves da , Scapulatempo-Neto Cristovam , Tiezzi Daniel , Vieira René Aloísio da Costa , Pinheiro Céline
Published: November 2019

Background Locally advanced breast cancer often undergoes neoadjuvant chemotherapy (NAC), which allows in vivo evaluation of the therapeutic response. The determination of the pathological complete response (pCR) is one way to evaluate the response to neoadjuvant chemotherapy. However, the rate of pCR differs significantly between molecular subtypes and the cause is not yet determined. Recently, the metabolic reprogramming of cancer cells and its implications for tumor growth and dissemination has gained increasing prominence and could contribute to a better understanding of NAC. Thus, this study proposed to evaluate the expression of metabolism-related proteins and its association with pCR and survival rates. Methods The expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4, respectively), cluster of differentiation 147 (CD147), glucose transporter-1 (GLUT1) and carbonic anhydrase IX (CAIX) was analyzed in 196 locally advanced breast cancer samples prior to NAC. The results were associated with clinical-pathological characteristics, occurrence of pCR, disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Results The occurrence of pCR was higher in the group of patients whith tumors expressing GLUT1 and CAIX than in the group without expression (27.8% versus 13.1%, p = 0.030 and 46.2% versus 13.5%, p = 0.007, respectively). Together with regional lymph nodes staging and mitotic staging, CAIX expression was considered an independent predictor of pCR. In addition, CAIX expression was associated with DFS and DSS (p = 0.005 and p = 0.012, respectively). Conclusions CAIX expression was a predictor of pCR and was associated with higher DFS and DSS in locally advanced breast cancer patients subjected to NAC.
Single-session esophagogastroduodenoscopy and endoscopic ultrasound using a forward-viewing radial scan ultrasonic endoscope
Authors: Uchida Daisuke , Kato Hironari , Matsumoto Kazuyuki , Ishihara Yuki , Matsumi Akihiro , Saragai Yosuke , Takada Saimon , Yabe Shuntaro , Muro Shinichiro , Tomoda Takeshi , Horiguchi Shigeru , Okada Hiroyuki
Published: November 2019

Background and Aims Endoscopic ultrasound is useful for obtaining high-resolution images of pancreaticobiliary diseases, but is not readily available for physical checkups. In this study, we evaluated the safety and efficacy of single-session esophagogastroduodenoscopy and endoscopic ultrasound in the detection of upper-gastrointestinal and pancreaticobiliary diseases using a forward-viewing radial scan ultrasonic endoscope. Methods A total of 148 patients who were scheduled for upper-gastrointestinal screening using an endoscope were prospectively included. All patients were examined by EUS in combination with EGD using a forward-viewing radial scan ultrasonic endoscope. The primary endpoint was the safety of the procedures. The secondary endpoints were the prevalence of diseases, the basal imaging capability of EUS, the procedure time, total dose of propofol, and the correlation between background factors and the prevalence of pancreatic disease. The imaging capability at each region was scored as 0 (invisible) to 2 (sufficient visualization to evaluate the organs). Results Intraoperative hypotension occurred as an adverse event of intravenous anesthesia in one patient. There were 82 pancreaticobiliary findings and 165 upper-gastrointestinal findings (malignancy not included). Follicular lymphoma of the intra-abdominal lymph nodes was detected in one patient. The mean imaging scores of each section were 1.95 (pancreatic head and papilla), 2.0 (pancreatic body), 1.99 (pancreatic tail), and 1.89 (common bile duct and gallbladder). Age, history of diabetes mellitus, and smoking history were significantly associated with the prevalence of pancreatic diseases. Conclusion The simultaneous performance of EGD and EUS using a new ultrasonic endoscope is tolerable and safe for upper-gastrointestinal and pancreaticobiliary screening.
The growing use of the WHO Safe Childbirth Checklist: Lessons learned at the Yaounde Gyneco-Obstetric and Pediatric Hospital, Cameroon
Authors: DOHBIT Julius Sama , WOKS Namanou Ines Emma , KOUDJINE Carlin Héméry , TAFEN Willy , FOUMANE Pascal , ASSUMPTA Lucienne BELLA , OGU Rosemary Nkemdilim , III Fru Fobuzshi ANGWAFO
Published: November 2019

Background: Safe childbirth remains a daunting challenge, particularly in low-resource settings where most pregnancy-related deaths occur. Cameroon’s maternal mortality rate, estimated at 782 per 100,000 live births in 2011 is significantly high. Adherence to good practice standards by birth attendants is key to improving pregnancy outcomes. The WHO Safe Childbirth checklist was designed as a tool to improve the quality of care provided to women giving birth. This checklist was implemented at the Yaounde Gyneco-Obsteric and Pediatric Hospital. Quantitative and qualitative assessment of its utilization is essential to secure a change in attitudes and practice and engender improvement in maternal health. Objective: Evaluate the change in attitudes and practice of nurses and compare outcomes in cases where it was and was not used, 6 months after introduction of the safe childbirth checklist in a maternity setting. Methods: A cross sectional and retrospective study was conducted over a 6 month period (January – June 2018). Predesigned questionnaires were used to collect qualitative data on the checklist from personnel of the maternity and another data collection form used to extract information from patient records. Data analysis was done using SPSS version 23.0. Chi square test was used to compare categorical variables, while the student test was used to compare continuous variables. Results: Of the 1001 files retrieved from the archives, 25 were excluded. The checklist was used in 828/976 (84.8%) files. We observed an increasing trend in the usage rate, with a peak at 93.9% recorded during the last 2 months. Pages 2 and 3 were least completed, in <10% of cases during the first 5 months. Fewer cases of pre-eclampsia and eclampsia were associated with the use of the checklist, compared to patients in whom the checklist was not used (2·1% Vs 5·4%, p = 0·017). Fifty percent of the staff reported that the checklist increased workload while 37.5% mentioned laziness and absence of checklists in some files as a hindrance to its proper use. Conclusion: The use of the safe childbirth checklist improved progressively with a simultaneous reduction in obstetrical and neonatal complications overtime.
Inflammation biomarker discovery in Parkinson's disease and atypical parkinsonisms
Authors: Santaella Anna , Kuiperij H. Bea , Rumund Anouke van , Esselink Rianne A.J. , Gool Alain J. van , Bloem Bas R. , Verbeek Marcel
Published: November 2019

Background: Parkinson’s disease (PD) and atypical parkinsonisms (APD) have overlapping symptoms challenging an early diagnosis. Diagnostic accuracy is important because PD and APD have different prognosis and response to treatment. We aimed to identify diagnostic inflammatory biomarkers of PD and APD in cerebrospinal fluid (CSF) using the multiplex proximity extension assay (PEA) technology and to study possible correlations of biomarkers with disease progression.

Methods: CSF from a longitudinal cohort study consisting of PD and APD patients (PD, n = 44; multiple system atrophy (MSA), n = 14; vascular parkinsonism (VaP), n = 9; and PD with VaP, n = 7) and controls (n = 25) were analyzed.

Results: Concentrations of CCL28 were elevated in PD compared to controls (p = 0.0001). Five other biomarkers differentiated both MSA and PD from controls (p < 0.05) and 10 biomarkers differentiated MSA from controls, of which two proteins, i.e. beta nerve growth factor (β-NGF) and Delta and Notch like epidermal growth factor-related receptor (DNER), were also present at lower levels in MSA compared to PD (both p = 0.032). Two biomarkers (MCP-1 and MMP-10) positively correlated with PD progression (rho > 0.650; p < 0.01).

Conclusions: PEA technique identified potential new CSF biomarkers to help to predict the prognosis of PD. Also, we identified new candidate biomarkers to distinguish MSA from PD.
Genomic and evolutionary features of two AHPND positive Vibrio parahaemolyticus strains isolated from shrimp (Penaeus monodon) of south-west Bangladesh
Authors: Ahmmed Shawon , Khan Md. Abdullah-Al-Kamran , Eshik Md. Mostavi Enan , Punom Nusrat Jahan , Islam Abul B.M.M.K. , Rahman Mohammad Shamsur
Published: November 2019

Background Due to its rapid lethal effect in the early development stage of shrimp, acute hepatopancreatic necrosis disease (AHPND) has been causing great economic losses, since its first outbreak in southeast China in 2009. Vibrio parahaemolyticus, carrying the pirA and pirB toxin genes is known to cause AHPND in shrimp. The overall objective of this study was to sequence the whole genome of AHPND positive V. parahaemolyticus strains isolated from shrimp (Peneaus monodon) of the south-west region of Bangladesh in 2016 and 2017 and characterize the genomic features and emergence pattern of this marine pathogen. Results Two targeted AHPND positive V. parahaemolyticus strains were confirmed using PCR with 16S rRNA, ldh, AP3 and AP4 primers. The assembled genomes of strain MSR16 and MSR17 were comprised of a total of 5,393,740 bp and 5,241,592 bp, respectively. From annotation, several virulence genes involved in chemotaxis and motility, EPS type II secretion system, Type III secretion system-1 (T3SS-1) and its secreted effectors, thermolabile hemolysin were found in both strains. Importantly, the ~69 kb plasmid was identified in both MSR16 and MSR17 strains containing the two toxin genes pirA and pirB. Antibiotic resistance genes were predicted against β-lactam, fluoroquinolone, tetracycline and macrolide groups in both MSR16 and MSR17 strains. Conclusions The findings of this research may facilitate the tracking of pathogenic and/or antibiotic-resistant V. parahaemolyticus isolates between production sites, and the identification of candidate strains for the production of vaccines as an aid to control of this devastating disease. Also, the emergence pattern of this pathogen can be highlighted to determine the characteristic differences of other strains found all over the world.
An alarming rise of non-albicans Candida species and uncommon yeasts in the clinical samples; a combination of various molecular techniques for identification of etiologic agents
Authors: Taei Mohireh , Chadeganipour Mostafa , Mohammadi Rasoul
Published: November 2019

Objective: Yeasts are unicellular microorganisms may cause systemic infection in immunocompromised patients. The aim of this study was to identify yeast strains isolated from clinical specimens using molecular techniques. Results: A total of 202 yeast strains isolated from 341 clinical samples between February 2017 and May 2019. All clinical isolates were identified using phenotypic and molecular tests including PCR-RFLP, duplex-PCR, multiplex-PCR, and PCR-sequencing. The most yeast fungal isolates were obtained from urine (66.8%), nail (9.4%), skin lesion (7.9%), bronchoalveolar lavage (5.9%), and blood (3.9%). One hundred and twenty-one Candida species were identified as non- albicans versus 76 Candida albicans. Trichosporon asahii, and Pichia terricola were uncommon non- Candida yeasts isolated from urine samples. For the first time, we isolated P. terricola as etiological agent of urinary tract infection in a pregnant female. Since Candida species show different levels of resistance to antifungal agents, precise identification of clinical isolates is critical for better treatment of infection.
Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model
Authors: Wang Benfan , Li Qinyan , Wang Jinyan , Zhao Siting , Nashun Bayaer , Qin Li , Chen Xiaoping
Published: November 2019

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of effective treatment results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model. Methods: A study was conducted to investigate the inhibitory effect of Plasmodium infection on hepatocellular carcinoma in mice, and chip analysis techniques were used to find possible signal regulation mechanisms. Results: we report that Plasmodium infection efficiently inhibited tumor progression and prolonged survival in tumor-bearing mice in a murine implanted hepatoma model. The inhibition of tumor progression by Plasmodium infection is related to the suppression of tumor angiogenesis within the tumor tissue and the decreased infiltration of tumor-associated macrophages (TAMs). Further study demonstrated that TAM-produced matrix metalloprotease 9 (MMP-9) contributed to tumor angiogenesis in the tumor tissue and that the reduced expression of MMP-9 in TAMs mediated by parasite infection resulted in the suppression of tumor angiogenesis. A mechanistic study revealed that the Plasmodium-derived hemozoin (HZ) that accumulated in TAMs inhibited IGF-1 signaling through the PI3-K and MAPK signaling pathways, which led to decreased expression of MMP-9 in TAMs. Conclusions: Our study suggests that this novel method of inhibiting tumor angiogenesis by Plasmodium infection is of high importance for developing new therapies for cancer patients.
LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation
Authors: Yang Feng-lian , Wei Yu-xia , Liao Bi-yun , Wei Gui-jiang , Qin Hai-mei , Pang Xiao-xia , Wang Jun-li
Published: November 2019

Background In recent years, there has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC).. We aim to delve into the position of lncRNA HOTAIR, together with EZH2, E-cadherin and H3K27me3 in NPC and explore the related mechanisms. Methods RT-qPCR and western blot analysis were carried out for detecting lncRNA HOTAIR, EZH2, E-cadherin and H3K27me3 expression in NPC tissues and cells. Moreover, the correlations between lncRNA HOTAIR and EZH2 expression and the clinicopathological characteristics and prognosis of patients with NPC were observed. NPC cell biological functions were examined through gain-of and loss-of function assays. RIP and ChIP assays were applied to detect whether lncRNA HOTAIR in NPC cells could regulate E-cadherin by recruiting EZH2 to mediate trimethylation of H3K27. Results LncRNA HOTAIR, EZH2, and H3K27me3 were richly expressed in NPC tissues and cells, and E-cadherin was lowly expressed. The prognosis of patients with overexpression of lncRNA HOTAIR and EZH2 was worse than that of patients with theirs low expression. Down-regulation of either HOTAIR or EZH2 inhibited cell proliferation, promoted apoptosis, suppressed migration and invasion and inhibited tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. Conclusion Our study suggests that lncRNA HOTAIR inhibits the expression of E-cadherin by stimulating the trimethylation of H3K27 by histone methylase EZH2 to promote cell migration, proliferation, and inhibit apoptosis of NPC cells.
PTPN3 inhibits the growth and metastasis of clear cell renal cell carcinoma via inhibition of PI3K/AKT signaling
Authors: Peng Xing-Si , Yang Jun-Ping , Qiang Yuan-Yuan , Sun Rui , Cao Yun , Zhou Fang-Jian , Zheng Li-Sheng , Peng Li-Xia , Lang Yan-Hong , Li Chang-Zhi , Mei Yan , Meng Dong-Fang , Liu Zhi-Jie , Wang Ming-Dian , Huang Bi-Jun , Qian Chao-Nan
Published: November 2019

Background: The underlying molecular mechanism driving clear cell renal cell carcinoma (ccRCC) progression is not fully understood. The significant downregulation of protein tyrosine phosphatase non-receptor type 3 (PTPN3) expression in the tumor tissues suggested its protective role in ccRCC progression. Methods: Immunohistochemical analysis of PTPN3 protein in 172 ccRCC tissue revealed that PTPN3 expression was an independent, favorable prognostic factor for overall survival ( P = 0.0343) and distant metastasis-free survival ( P = 0.0166) of patients. The ccRCC cell lines SN12C, 1932, ACHN and Caki-1 were used to evaluate, both in vitro and in vivo , the biological roles of PTPN3. Results: We observed that overexpression of PTPN3 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. In contrast, the knocking down of PTPN3 elicited opposite effects. PTPN3 overexpression suppressed xenograft tumor growth and lung metastasis in vivo mice models. PTN3 inhibited tumor cell motility by suppressing the phosphorylation of AKT, and subsequently inactivating the PI3K/AKT signaling pathway of ccRCC cells. Further, the inhibition of phospho-AKT Thr308 and phospho-AKT Ser473 reversed PTPN3 induced-silencing in tumor cell migration. Our work revealed that the overexpression of PTPN3 could suppress kidney cancer progression by negatively regulating the AKT signaling pathway, and served as a favorable prognostic factor in ccRCC patients. Conclusions: Our findings provided insight that PTPN3 could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC.
Seed-resident microbiomes of leguminous and gramineous grasses are related to host stress tolerance
Authors: Dai Ya , Li Xin-Yu , Wang Yan , Li Cai-Xia , He Yuan , Lin Hong-Hui , Wang Tao , Ma Xin-Rong
Published: November 2019

Background: The grasses in adverse environment such as Qinghai-Tibet Plateau are hypothesized to survive the harsh climate in part upon their seed-borne microorganisms, and yet the characteristics of the grass seed microbial communities remain undetermined. Here, we assessed the seed microbial communities of three native gramineous grass species (Avena sativa, Elymus sibiricus and Elymus dahuricus) and four candidate legumes (Vicia villosa, Trifolium repens, Trifolium pretense and Medicago sativa) on the Qinghai-Tibet Plateau by high-throughput sequencing. Results: A total of 1,013 bacterial operational taxonomic units (OTUs) and 922 fungal OTUs were observed. The OTUs that shared in all the samples were in high abundance but with different relative abundances. The majority of bacterial sequences were assigned to Proteobacteria (54~90%) and Firmicutes (5~41%), and the fungal communities were mainly composed of Ascomycota (23~96%) and Basidiomycota (2~11%). The fungal communities were more affected by host genetic distance than bacteria. The three gramineous grasses were speculated to survive the adversity partly due to their high abundance of beneficial bacteria like Pantoea or Bacillus, and non-pathogenic fungi like Candida or unclassified Helotiaceae. Also enriched with these potential beneficial taxa, the four leguminous grasses may be competent to adapt the Qinghai-Tibet Plateau stress. Furthermore, the higher tolerance grasses (Elymus sibiricus and Elymus dahuricus) possessed a greater number of growth-promoting and tolerance bacterial and non-pathogenic fungi. Conversely, the less tolerance grass Medicago sativa contained lower levels of such microorganisms, and showed higher abundance of pathogenic taxa. Furthermore, the isolated Bacillus subtilis or Pantoea agglomerans could more probably promote seeding growth of hosts with lower abundance of them, while inhibit if the endo-abundance of was high. Conclusions: Seed-resident microbiome structure of the four cold-tolerance legumes and three Qinghai-Tibet Plateau gramineae is host dependent and related to stress resistance. It also has a strong influence on the response of seedlings to biological seed treatments. This study provides valuable data for studying plant resilience, identifying more biocontrol strains, maximizing microbial functions in ‘smart farming’ practices.
Healthy adult vegetarians have better renal function than matched omnivores: a cross sectional study in China.
Authors: Xu Kaijie , Cui Xueying , Wang Bian , Tang Qingya , Cai Jianfang , Shen Xiuhua
Published: November 2019

Background Appropriate diet is an important determinant of kidney health. However, the association between vegetarian diets and renal function is unclear.Object We aimed to study the association between vegetarian diets and renal function in healthy adults.Design A total of 269 vegetarians (aged 34.5±8.7 years) and 269 sex- and age-matched nonvegetarian omnivores were enrolled in this cross-sectional study. Basic characteristics as well as daily dietary intakes were assessed by face-to-face interviews. Blood samples were collected, and renal function was assessed by measuring blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA) and estimated glomerular filtration rate (eGFR). Blood pressure, fasting blood glucose and blood lipid profiles were also assessed.Results The average age of the vegetarians was 35.4±8.6 years, 82.2% of whom were female. We evaluated the association between vegetarian diets and renal function by using multivariate analysis. Compared with omnivores, vegetarians had lower BUN (β= -0.63, 95% CI: -0.88 to -0.38), SCr (β= -2.07, 95% CI: -4.21 to -0.061), UA (β= -15.17, 95% CI: -27.81 to -2.53) and higher eGFR levels (β= 4.09, 95% CI: 0.23 to 7.96) after adjusting for sex, age, BMI, physical activity, alcohol consumption, smoking status, LDL, HDL, systolic pressure and fasting blood glucose. Further analysis of food composition and renal function showed that dietary fiber intake was significantly negatively associated with BUN [β= -0.02, 95% CI:(-0.03, 0.00)], SCr [β= -0.14, 95% CI:(-0.25, 0.04)], and UA [β= -0.72, 95% CI:(-1.36, 0.07)] and positively associated with eGFR [β= 0.20, 95% CI:(0.00, 0.40)].Conclusions Healthy adult vegetarians have better renal function than omnivores, and the higher dietary fiber intake associated with vegetarian diets may contribute to the protective effect on renal function.
Adequacy and complication rates of percutaneous renal biopsy with 18- vs. 16-gauge needles in native kidneys in Chinese individuals.
Authors: Xie Weiji , Xu Jing , Xie Yi , Lin Zhijun , Xu Xiaochang , Zhang Xia Lan , Zhang Yimin
Published: November 2019

Background The study aims to compare the adequacy, complication rate and pathological classification when using 18G vs. 16G needles to perform renal biopsy with ultrasound-guidedance on native kidneys in Chinese individuals.Methods We retrospectively analyzed the number of glomeruli, adequate sample rates, complication rates and pathological classification in 270 patients with the use of 18G or 16G needles from January 2011 to May 2017 and verified whether the needle gauge affected the disease diagnosis.Results A total of 270 kidney biopsies were performed. Among them,72 were performed with 18G needles, and 198 were performed with 16G needles. There was no difference in the number of glomeruli under light microscope using 18G relative to 16G needles (24±11 vs. 25±11, p=0.265), whereas more glomeruli were found in the 16G group than in the 16G group using immunofluorescence microscopy (3±2 vs. 5±3, p<0.05). There was no significant difference in the adequate sample rates between the 18G group and the 16G group (90.28% vs. 93.94%, p=0.298). Minor complications including the incidence of lumbar or abdominal pain (4.17% vs. 7.07%, p = 0.57), gross hematuria (4.17% vs. 3.54%, p = 0.729), and perinephric hematoma without symptoms (4.17% vs. 1.52%, p = 0.195), were not significantly different between the 18G and 16G groups. In the 16G group, 2 cases of serious complications occurred: severe gross hematuria requiring blood transfusion and retroperitoneal hematoma requiring surgery. No serious complications were observed in the 18G group, although there was no significant difference in serious complications rates between the 18G and 16G groups (0% vs. 1.02%, p = 1).Conclusion There was no significant difference in the number of glomeruli, adequate sample rates, or complication rates when using 18G or 16G needles to perform renal biopsy, and the use of an 18G needle with a smaller diameter did not affect the pathological diagnosis or classification of IgA nephropathy and lupus nephritis.
Germline BRCA, Chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer
Authors: Lee Yong Jae , Kim Hyun-Soo , Rim John Hoon , Lee Jung-Yun , Nam Eun Ji , Kim Sang Wun , Kim Sunghoon , Kim Young Tae
Published: November 2019

Background To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Methods We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. Results BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) ( P = 0.949) or overall survival (OS) ( P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS ( P = 0.030) and OS ( P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS ( P = 0.0344) and OS ( P = 0.043) than wild-type BRCA genotype patients. Conclusion In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.
Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis
Authors: Qu Nanfang , Jiang Haixing , Qin Sanyu , Zhang Xuemei , Liu Zhengchun , Tan Chao , Wen Guiqiong
Published: November 2019

Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.
Association of Helicobacter Pylori babA2 gene and Gastric Cancer Risk: A Meta-analysis
Authors: Kpoghomou Marce-Amara , Wang jinchen , Wang Tianpei , Jin Guangfu
Published: November 2019

Background The association of H. pylori babA2 gene with gastric cancer (GC) was proposed by several studies, but the results have been inconsistent. Objective of this meta-analysis was to investigate the association of Helicobacter pylori (H. pylori ) babA2 gene and gastric cancer (GC) risk.Methods Studies evaluated the association between H. pylori babA2 gene and GC risk were collected from PubMed databases. A meta-analysis of case-control studies was used. The pooled ORs with 95% CIs were used to calculate the effect of H. pylori babA2 gene effect on GC risk.Results Twenty studies were identified with a total of 747 GC and 1597 controls. Infection with H. pylori babA2 gene was associated with an increased risk of GC by 1.46 fold (95% CI: 1.19-1.77, P=0.001) . In subgroup analysis, borderline association was found among South American and strong association was found among Asian population, with pooled OR of 1.38 (95% CI: 0.97-1.95, P=0.068 ) and 1.50 (95% CI: 1.16-1.93, P=0.002 ) respectively.Conclusions This meta-analysis validated that H. pylori babA2 gene may be associated with increased risk of GC. And positive association was found among Asian population.
Metabolic Profile Of Leukemia Cells Influences Treatment Efficacy Of L‑Asparaginase
Authors: Hlozkova Katerina , Pecinova Alena , Reguera David Pajuelo , Simcikova Marketa , Hovorkova Lenka , Rejlova Katerina , Artieda Natividad Alquezar , Zaliova Marketa , Mracek Tomas , Stary Jan , Trka Jan , Starkova Julia
Published: November 2019

Background Effectiveness of L-asparaginase administration in acute lymphoblastic leukemia treatment is mirrored in overall outcome of patients. Generally, leukemia patients differ in their sensitivity to L-asparaginase; however, the mechanism underlying their inter-individual differences is still not fully understood. We have previously shown that L-asparaginase rewires the biosynthetic and bioenergetic pathways of leukemia cells to activate both anti-leukemic and pro-survival processes. Herein, we investigated the relationship between the metabolic profile of leukemia cells and their sensitivity to currently used cytostatic drugs.Methods Altogether, 19 leukemia cell lines and primary leukemia cells from 11 patients were used. Glycolytic function and mitochondrial respiration were measured using Seahorse bioanalyzer. Sensitivity to cytostatics was measured using MTS assay and/or absolute count and flow cytometry. Mitochondrial membrane potential was determined as TMRE fluorescence.Results We characterized the basal metabolic state of the cells derived from different leukemia subtypes using cell lines and primary samples and assessed their sensitivity to cytostatic drugs. We found that leukemia cells cluster into distinct groups according to their metabolic profile, which is mainly driven by their hematopoietic lineage of origin from which they derived. However, majority of lymphoid leukemia cell lines and patients with lower sensitivity to L-asparaginase clustered regardless their hematopoietic phenotype together with myeloid leukemias. Furthermore, we observed a correlation of specific metabolic parameters with sensitivity to L-asparaginase. Greater ATP-linked respiration and lower basal mitochondrial membrane potential in cells significantly correlated with higher sensitivity to L-asparaginase. No such correlation was found in other tested cytostatic drugs.Conclusions These data support the prominent role of the cell metabolism in the treatment effect of L-asparaginase. Based on these findings metabolic profile could identify leukemia patients with lower sensitivity to L-asparaginase with no specific genetic characterization.
CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy
Authors: Tong Yilin , Zhao Yan , Shan Zexing , Zhang Jianjun
Published: November 2019

Background: Serum tumor markers are of great importance in diagnosis, prognostic predicting and recurrence monitoring in gastrointestinal malignancy, including AFU, AFP, CEA, CA199, CA125 and CA724. However, their significances in gastric cancer (GC) patients with neoadjuvant therapy (NCT) are still uncertain. The aim of this study is to evaluate the predictive value of these six tumor markers in locally advanced GC patients with NCT and curative surgery. Methods: 290 locally advanced GC patients with NCT and D2 radical gastrectomy were retrospectively analyzed. Their tumor markers before (pre-) and after (post-) NCT and pathological characters were exacted from the database in our hospital. The optimal cutoff values of six tumor markers were calculated by ROC and Youden index. Their predictive significances were analyzed and survival curves on overall survival (OS) were obtained by Kaplan-Meier method. Associations between categorical variables were explored by Chi-square test or Fisher's exact method. Multivariate analyses were performed by Cox regression model. Results: Not only the pre- and post- CA199, CA125 and CA724 could predict the overall survival respectively, but also the changes (diff-) between post- and pre- groups were related to the prognosis (P < 0.05). In multivariable analysis, only pre- (P = 0.016) and post-CA724 (P = 0.033) remained significant, and the significance of diff-CA724 was on borderline (P = 0.085). Besides, pre- and post-CA199, CA125 and CA724 were associated with the metastasis of lymph node (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (P < 0.05). Post-CA724 was related to the invasion of vascular or lymphatic vessels (P = 0.019), and pre-CA724 was nearly remarkable (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05). Conclusions: CA724 is an independent factor to prognosis, and could be used to predict the ypN and ypTNM stage in locally advanced GC patients undergone NCT and curative resection.
Multiple hepatoid gastric adenocarcinoma: A case report and literature review
Authors: Zhu Ce , Chen Xiaodong , Zhao Zhiguang , Chen Jian , Shen Xian
Published: November 2019

Background Hepatoid gastric adenocarcinoma (HGAC) is a rare gastric malignancy that exhibits the characteristics of differentiated hepatocellular carcinoma and gastric adenocarcinoma. Most cases of HGAC are also accompanied by an elevated serum alpha-fetoprotein (AFP) concentration. Here, we report a rare case of HGAC involving two primary lesions.Case presentation A 61-year-old man presented at our institution with the complaint of upper abdominal pain. An examination revealed a significantly elevated serum AFP concentration. Abdominal computed tomography revealed a gastric tumour with enlarged peripheral lymph nodes and a cavernous haemangioma in the right anterior hepatic lobe. The patient underwent distal gastrectomy, and postoperative histopathology revealed two hepatoid gastric adenocarcinomas. Immunohistochemically, the tumours were positive for AFP, hepatocyte and chromogranin A (CgA), with a Ki67 index >90%. Following a postoperative diagnosis of HGAC, the patient was treated with a chemotherapy regimen of oxaliplatin combined with capecitabine. At the 6-month follow-up, the patient’s serum AFP concentration returned to the normal level. No signs of recurrence were detected.Conclusions Compared with other gastric cancers, HGAC tends to be more malignant and invasive, with a poor prognosis. These tumours are also prone to liver metastasis,but for which without liver metastasis may have a better prognosis. We hope that our experience with this extremely rare case of HGAC involving two different primary lesions without liver metastasis, as well as our literature review and summary of the etiological mechanism, pathological features, treatment and prognosis, will help improve the diagnosis and treatment of HGAC.
Prognosis and Expanded Definition of Pregnancy-associated Breast Cancer: A Dose-Response Meta-Analysis
Authors: Shao Chunchun , Yu Zhi Gang , Xiao Juan , Liu Li Yuan , Hong Fan Zhen , Zhang Yuan , Jia Hong Ying
Published: November 2019

Background Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or postpartum period. Deﬁnitions of the duration in the postpartum have controversial and this variability may led to diverse results on the prognosis. Moreover, evidence on the dose-response association between the time from last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. Methods We systematically searched PubMed, Embase, and the Cochrane Database for observational studies about the prognosis of PABC published up to June 1, 2019. We estimated summary adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosed time, PABC definition, geographic region, year of publication and the way of HR estimate were performed. Additionally, the dose–response analysis was conducted by using the variance weighted least-squares regression (vwls) trend estimation. Results A total of 54 articles (76 studies) were included in our study. PABC is associated with poor prognosis on overall survival (OS), disease-free survival (DFS) and cause-special survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a non-linear association between the time from last pregnancy to breast cancer diagnosis and overall mortality ( P <0.001). Compared with nulliparous women, PABC had a HR for all cause death that peaked at 1.62 (95% CI, 1.46-1.80) at 28 months since last pregnancy, starting from 78 months since last pregnancy became insignificant 1.07(95%CI, 0.99-1.26). It suggested that the definition of PABC should be extended to include cases diagnosed up to about six-years postpartum (78 months since last pregnancy) in order to capture this ongoing increased risk. Conclusion This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include cases diagnosed up to about six-years postpartum.
Value of preoperative neutrophil-to-lymphocyte ratio in predicting thyroid cancer in intermediate category fine needle aspiration pathology: retrospective study
Authors: Ozdenkaya Yasar , Basim Pelin , Olmuscelik Oktay , Arslan Naciye Cigdem
Published: November 2019

Background The management of thyroid nodules with intermediate category of the Bethesda System for Reporting Thyroid Cancer (TBSRTC) is still debatable. Aim of this study is to investigate the diagnostic accuracy of neutrophil-to-lymphocyte ratio (NLR) in detecting cancer in intermediate TBSRTC categories.Methods Data of the patients who underwent thyroidectomy between 2012 and 2018 were analyzed retrospectively. Demographic characteristics, complete blood count, TSH value, TBSRTC categories and postoperative pathology of the patients were collected. The association with preoperative NLR and postoperative pathology was assessed.Results Of 146 patients included in the study, 57 (39%) were in TBSRTC III, IV and V category. The mean NLR in this subgroup was 2.1±0.8 and similar between TBSRTC III, IV and IV groups (p=0.737). Thyroid cancer was detected in 38 (66.7%) patients. The mean NLR was 2.4±0.8 in thyroid cancers and significantly higher when compared with patients with benign postoperative pathology (1.6±0.4, p=0.014). There was a significant difference between papillary and follicular cancer; the mean NLR was 2.3±0.8 in papillary cancer and 2.6±0.7 in follicular cancer patients (p=0.005). The cut-off value of NLR for predicting cancer at 89% sensitivity and 53% specificity was 1.6 (Area under curve: 0.769, 95% confidence interval: 0.643-0.895, p=0.001).Conclusions Preoperative NLR is elevated in patients with thyroid cancer in intermediate TBSRTC categories. Despite low diagnostic accuracy, considering its availability and low costs, NLR has merit for further studies.
Neck Lymph Node Metastasis Detection in Patients with Differentiated Thyroid Carcinoma (DTC) in Long-Term Follow-up: a ¹³¹I-SPECT/CT Study
Authors: Spanu Angela , Nuvoli Susanna , Marongiu Andrea , Gelo Ilaria , Mele Luciana , Piras Bastiana , Madeddu Giuseppe
Published: November 2019

Background: The prognostic importance of neck lymph node (LN) metastases in differentiated thyroid carcinoma (DTC) is controversial even if their presence at surgery often correlates with tumor recurrences that it is mandatory to identify. To this purpose, in the present study, we used 131 I-SPECT/CT as diagnostic imaging procedure. Methods: We retrospectively evaluated 224 consecutive DTC patients already submitted to total thyroidectomy and radioiodine therapy, all of them with ascertained neck radioiodine-avid foci at ¹³¹I-SPECT/CT during long-term follow-up; at surgery, 62 patients were classified at high risk (H), 64 at low risk (L), 98 at very low risk. All patients underwent ¹³¹I-Whole body scan (WBS) followed by SPECT/CT. Result: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter it pinpointed 26 LN metastases, 18 residues and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients,T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or <2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5 % of patients, a more correct patient classification changing therapeutic approach in 30.3 % of cases and identified WBS false positive findings in 8% of cases. Conclusion: ¹³¹I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving WBS performance. SPECT/CT routine use is suggested, its role being particularly significant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.
Do Africans really need to go overseas for Phaco training? Performance audit of a locally trained phaco surgeon in rural Kenya
Authors: Niyonzima Jean Claude , Gichuhi Stephen , Sitati Sarah , Ollando Ernest
Published: November 2019

Purpose: To audit phacoemulsification cataract surgeries performed independently after a short - term training completed in a rural hospital in Kenya, and to benchmark the outcomes against WHO recommendations. Methods: This retrospective case-series study recruited patients who had had phacoemulsification cataract surgery at Sabatia Eye Hospital from January to December 2018. All the surgeries were performed by a single surgeon following a brief training in the same center. Data were collected retrospectively using a detailed questionnaire. Results: Of the one hundred and twenty eyes operated on during this period, one-hundred and sixteen eyes of 86 patients met the inclusion criteria. The mean age was 62 years and the majority of the eyes (83.6%) had vision less than 6/18 preoperatively. Co-morbidities included diabetic retinopathy (3.4%), age-related macular degeneration (2.6%), trauma (1.7%) and glaucoma (0.9%). Surgical complications were not severe enough to affect the final best-corrected visual acuity, unlike the comorbidities that were negatively correlated with visual outcomes (p-value< 0.001). Good outcomes were 81% against a WHO target of 80% for uncorrected visual acuity category, and 96.6% in the best-corrected visual acuity category against a target of 90%. The Royal College of Ophthalmology database of cataract surgery outcomes and the European Registry of Quality Outcomes for cataract and refractive surgery had comparable results. Conclusions: This local training model was based on apprenticeship and skills transfer. It can achieve high-quality visual outcomes meeting WHO recommendations.
Countertransference feelings and personality disorders: A psychometric evaluation of a brief version of the Feeling Word Checklist (FWC-12)
Authors: Breivik Randi , Wilberg Theresa , Evensen Julie , Røssberg Jan Ivar , Dahl Hanne Sofie , Pedersen Geir A. Feigum
Published: November 2019

Background The Feeling Word Checklist (FWC) is a self-report questionnaire designed to measure therapists’ countertransference (CT) feelings. The primary aim of the study was to evaluate the psychometric properties of a brief version of the Feeling Word Checklist comprising twelve feeling words (FWC-12). The second aim was to validate the factor structure by examining the associations between the FWC-12 factors, patients’ personality pathology and therapeutic alliance (TA). Methods Therapists at 13 different outpatient units within the Norwegian Network of Personality Disorders completed the FWC-12 every 6 months during the course of treating a patient with a personality disorder (PD), over a period of up to 2.5 years. A large sample of patients with personality pathology participated in the study. The data were analysed with exploratory (EFA) and confirmatory (CFA) factor analysis. Internal consistency was estimated using Cronbach’s alpha. The Structured Clinical Interview for DSM-IV – Axis II (SCID II) and Mini International Neuropsychiatric Interview (MINI) were used as diagnostic instruments, and patient-rated TA was assessed using the Working Alliance Inventory (WAI-SR). Results Factor analyses revealed three clinically meaningful factors: Inadequate, Idealised and Confident. These factors had acceptable psychometric properties. Most notably, a number of borderline PD criteria correlated positively with the factors Inadequate and Idealised, and negatively with the factor Confident. All the factors correlated significantly with at least one of the WAI-SR subscales. Conclusions The FWC-12 measures three clinically meaningful aspects of therapists’ CT feelings. This brief version of the FWC seems satisfactory for use in further research and in clinical contexts. Keywords: Countertransference, Feeling Word Checklist, factor analysis, personality disorder, psychometrics