bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA SNHG15 promotes hepatocellular carcinoma progression by sponging miR‐141‐3p
Authors: Ye Junfeng , Tan Ludong , Fu Yu , Xu Hongji , Wen Lijia , Deng Yu , Liu Kai
Published: July 2019

Small nucleolar RNA host gene 15 (SNHG15) is a long noncoding RNA (lncRNA), which promotes progression of multiple cancers. Its specific function in hepatocellular carcinoma (HCC), however, is uncertain. The aims of our study were, therefore, to explore the role of SNHG15 in HCC. SNHG15 and miR‐141‐3p expression were assessed via quantitative real‐time PCR (qRT‐PCR) in 58 paired HCC samples and adjacent matched adjacent normal tissues. CCK‐8 assay, flow cytometric examination, and wound healing/invasion assays were used to respectively assess how SNHG15 influences cell proliferation, the cell cycle, and the migratory and invasive potential of HCC cells. MicroRNA (miRNAs) that targeted SNHG15 was screened by Starbase2.0 and identified by RNA immunoprecipitation and luciferase reporter assays. SNHG15 expression was markedly increased, whereas miR‐141‐3p expression was substantially reduced in HCC cells and tissue samples relative to normal controls. When SNHG15 was knocked down, this resulted in a significant disruption to the proliferation, as well as the invasive and migratory ability of these HCC cells. miR‐141‐3p was also found to be an SNHG15 target in HCC cells. Furthermore, miR‐141‐3p inhibitor partially reversed the observed SNHG15 depletion‐mediated reduction in HCC proliferation, migration, and invasion. By repressing miR‐141‐3p, SNHG15 could modulate zinc finger E‐box binding homeobox 2 (ZEB2) and E2F transcription factor 3 (E2F3) expression, both of which are miR‐141‐3p targets. These finding suggested that SNHG15 promoted HCC progression via negative regulation of miR‐141‐3p, thus identifying a potential novel HCC treatment pathway.
Integrated mRNA‐Seq and miRNA‐Seq analysis of PLCγ2‐overexpressing hepatocarcinoma cells and identification of the associated miRNA‐mRNA network
Authors: Chen Xiaoguang , Zhu Xuemin , Wei Zhiguo , Lv Qiongxia
Published: July 2019

Our previous study has discovered the positive effect of phospholipase Cγ 2 (PLCγ2) on the growth of hepatocarcinoma cells; however, the underlying mechanism is far from being understood. For this reason, this study attempts to identify the differently expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in PLCγ2‐overexpressing hepatocarcinoma cells. The results showed that totally 596 differently‐expressed genes (DEGs) were identified in PLCγ2‐expressed cells, including 314 upregulated and 282 downregulated ones; according to gene ontology analysis, these DEGs were involved in different cellular processes. Concurrently, 34 differently‐expressed miRNAs (DEMs) were also detected in PLCγ2‐expressing hepatocarcinoma cells. Moreover, the integrative analysis of miRNA and mRNA expression profiles identified the potential regulatory network linked to hepatocarcinoma‐related biological processes, including metabolic activity, gene expression, cell cycle, cell migration, and so on. To our knowledge, it is the first study on the effect of PLCγ2 on miRNA and mRNA expressions in hepatocarcinoma cells, and the findings provide new insights into the mechanism supporting the growth‐promoting effect of PLCγ2 in hepatocarcinoma cells.
MicroRNA‐487a‐3p functions as a new tumor suppressor in prostate cancer by targeting CCND1
Authors: Wang Mingming , Yu Wanpeng , Gao Jun , Ma Wenqiang , Frentsch Macro , Thiel Andreas , Liu Mei , Rahman Nafis , Qin Zhihai , Li Xiangdong
Published: July 2019

Prostate cancer (PCa) is one of the major health problems of the aging male. The roles of dysregulated microRNAs in PCa remain unclear. In this study, we mined the public published data and found that miR‐487a‐3p was significantly downregulated in 38 pairs of clinical prostate tumor tissues compared with the normal tissues. We further verified this result by in situ hybridization on tissue chip and quantitative real‐time polymerase chain reaction (qRT‐PCR) in PCa/normal cells. miR‐487a‐3p targeting of cyclin D1 (CCND1) was identified using bioinformatics, qRT‐PCR and western blot analyses. The cellular proliferation, cell cycle, migration, and invasion were assessed by cell counting kit‐8, flow cytometry analysis and transwell assay. We discovered that overexpression of miR‐487a‐3p suppressed PCa cell growth, migration, invasion by directly targeting CCND1. Knockdown of CCND1 in PCa cells showed similar results. Meanwhile, the expression level of CCND1 was significantly upregulated in the PCa tissues and cell lines, which presented negative correlation with the expression of miR‐487a‐3p. More important, we demonstrated significantly reduced growth of xenograft tumors of stable miR‐487a‐3p‐overexpressed human PCa cells in nude mice. Taken together, for the first time, our results revealed that miR‐487a‐3p as a tumor suppressor of PCa could target CCND1. Our finding might reveal miR‐487a‐3p could be potentially contributed to the pathogenesis and a clinical biomarker or the new potential therapeutic target of PCa.
RANKL triggers resistance to TRAIL‐induced cell death in oral squamous cell carcinoma
Authors: Ethiraj Purushoth , Sambandam Yuvaraj , Hathaway‐Schrader Jessica D. , Haque Azizul , Novince Chad M. , Reddy Sakamuri V.
Published: July 2019

Oral squamous cell carcinoma (OSCC) occurs as a malignancy of the oral cavity. RANK ligand (RANKL) is essential for osteoclast formation/bone resorption. Recently, we showed autoregulation of receptor activator of nuclear factor‐κB ligand (RANKL) stimulates OSCC cell proliferation. OSCC cells show resistance to tumor necrosis factor related apoptosis inducing ligand (TRAIL) treatment. Therefore, we hypothesize that RANKL promotes resistance for TRAIL induction of OSCC apoptotic cell death. In this study, SCC14A and SCC74A cells cultured with TRAIL revealed high‐level expression of RANKL which increased resistance to TRAIL inhibition of tumor cell proliferation. RANKL stimulation inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling positive staining in TRAIL‐treated cells. CRISPR/Cas‐9 knockout of RANKL (RANKL‐KO) increased caspase‐9, caspase‐3 activity and cytochrome c release in OSCC cells. RANKL inhibited proapoptotic proteins BAD and BAX expression. TRAIL treatment suppressed the SQSTM1/p62 and RANKL restored the expression. Interestingly, RANKL alone significantly increased proteasome activity. RANKL‐KO in OSCC cells inhibited autophagic activity as evidenced by decreased light chain 3B‐II and beclin‐1 expression. Thus, RANKL stimulation of OSCC tumor cells triggered resistance for TRAIL‐induced OSCC cell death. Taken together, blockade of RANKL may inhibit OSCC tumor progression and enhance the potential of TRAIL induced OSCC tumor cell apoptosis.
Syndecan‐4 involves in the pathogenesis of rheumatoid arthritis by regulating the inflammatory response and apoptosis of fibroblast‐like synoviocytes
Authors: Cai Peian , Lu Zhenhui , Jiang Tongmeng , Wang Zetao , Yang Yifeng , Zheng Li , Zhao Jinmin
Published: July 2019

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the pathogenesis of RA is still unknown. Rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLSs) are of significance in the pathogenesis of RA. In this study, three microarray profiles (GSE55457, GSE55584, and GSE55235) of human joint FLSs from 33 RA patients and 20 normal controls were extracted from the Gene Expression Omnibus Dataset and analyzed to investigate the underlying pathogenesis of RA. As analyzed by the differently expressed genes, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein‐protein interaction network analysis, syndecan‐4 (SDC4), a receptor of multiple cytokines and chemokines, which played a key role in the regulation of inflammatory response, was found to be an essential regulator in RA. To further validate these results, the levels of SDC4, reactive oxygen species (ROS), nitric oxide (NO), inflammation, and apoptosis in RA‐FLSs were examined. SDC4‐silenced RA‐FLSs were also used. The results demonstrated that SDC4 and the level of ROS, NO, and inflammation were highly expressed while the apoptosis was decreased in RA‐FLSs compared with normal FLSs. SDC4 silencing significantly suppressed the levels of ROS, NO, and inflammation; elevated the expression of nuclear factor erythroid 2‐related factor 2; and promoted the apoptosis of RA‐FLSs. Collectively, our results demonstrated a new mechanism of SDC4 in initiating the inflammation and inhibiting the apoptosis of RA‐FLSs and that a potential target for the diagnosis and treatment of RA in the clinic might be developed.
Vascularized gastroepiploic lymph node transfer significantly improves breast cancer‐related lymphedema
Authors: Mousavi Seyed R. , Akbari Mohammad E. , Zarrintan Sina
Published: July 2019

Background

Vascularized lymph node transfer (VLNT) is a surgical treatment for lymphedema. Multiple methods have been described and each has significant disadvantages.

Study Design

We performed VLNT in patients with upper extremity lymphedema resulting from breast cancer surgery. We used lymph nodes of the greater curvature of the stomach (VLNTg). We describe outcomes of the patients suffering from postmastectomy lymphedema who received VLNTg for treatment of lymphedema. Harvest from the periphery of the left gastroepiploic vessel was conducted.

Results

We retrospectively reviewed data of 24 female patients suffering from lymphedema following breast cancer treatment who underwent lymph node transplantation from 2012 to 2017. Axillary lymphadenectomy had been performed in all cases. In 18 patients, upper limb lymphedema was present for at least 1 year (mean = 5.6 years; range, 1–15 years). In 6 patients, it was present for only a few months (mean = 5 months; range, 3–8 months).

Conclusions

The greater curvature of the stomach nodes (VLNTg) is an excellent option for the treatment of upper extremity lymphedema because there is no risk of complications and the scar is easily concealed. Improvement from lymphedema can be expected in a majority of patients.
Use of a self‐contained vacuum‐assisted biopsy system in the assessment of soft tissue tumors
Authors: Simidjiiska‐Belyaeva Maria , Belyaev Orlin , Lehnhardt Marcus , Harati Kamran , Stricker Ingo , Nicolas Volkmar , Daigeler Adrien
Published: July 2019

Background and Objective

This is the first study to compare the safety and efficacy of vacuum‐assisted biopsy (VAB) using a self‐contained hand‐held system compared to those of ultrasound‐guided and computed tomography‐guided core needle biopsy (US‐CNB and CT‐CNB) and to incisional biopsy (IB).

Methods

VAB was performed in an outpatient setting under local anesthesia. Safety, diagnostic accuracy, time, and cost expenditures of biopsy were compared between VAB, US‐CNB, CT‐CNB, and IB in 211 consecutive patients.

Results

VAB was applied in 78 patients, US‐CNB in 51, CT‐CNB in 45, and IB in 37. Patient characteristics did not differ between groups. Sample volume of VAB was 392.5 mm3, 4062 mm
3 for IB, and 25.1 to 34.5 mm
3 for CNB, P < .001. VAB discriminated between malignant and benign lesions with the highest accuracy of 96% and determined sarcoma grading accurately in 95%. VAB and CNB had no complications vs 5% for IB. Duration of VAB was 5 ± 2 minutes, equal to US‐CNB and shorter than CT‐CNB and IB. Expenditures for VAB were higher than for US‐CNB and lower than CT‐CNB and IB.

Conclusion

VAB is an accurate, safe, cost‐effective, and time‐saving outpatient diagnostic procedure for patients with soft‐tissue tumors and presents a viable alternative to IB.
Screening patients at high risk for pancreatic cancer—Is it time for a paradigm shift?
Authors: Lo Winifred , Morris Mackenzie C. , Ahmad Syed A. , Patel Sameer H.
Published: July 2019

Pancreatic cancer remains leading cause of cancer‐related death in the United States. Patients with familial pancreas cancer, hereditary pancreatitis, known genetic mutations, and syndromes are deemed high risk for the development of pancreas cancer. Guidelines exist to help facilitate early diagnosis and treatment and these will be reviewed. Pancreatic cancer remains a leading cause of cancer‐related death in the United States. Patients with familial pancreatic cancer, hereditary pancreatitis, known genetic mutations, and syndromes are deemed high risk for the development of pancreas cancer. Guidelines have been made to help facilitate early diagnosis and treatment for these patients and these will be reviewed. The exact timing of initial screening depends not only on the individual risk factors but consists of endoscopic ultrasound and magnetic resonance cholangiopancreatography. The frequency of screening depends largely on the findings of initial imaging and the patient's clinical status. We suggest that providers make themselves knowledgeable of current screening recommendations and appropriately apply them. Further critical evaluation of ongoing research is necessary to amend these recommendations as more data and genetic testing becomes available.
Screening high risk populations for cancer: Hepatobiliary
Authors: Bailey Amanda , Shah Shimul A.
Published: July 2019

Cancers of the hepatobiliary tract are highly fatal, prompting the need for early detection to provide treatment and decrease the mortality rate. Screening patients for hepatobiliary cancers can provide early detection, but it is not feasible or efficient to screen all patients. Therefore, it is important to consider the known risk factors for each hepatobiliary cancer which creates a smaller population that is amenable to screening.
Predictors of behaviour in solitary fibrous tumours of the pleura surgically resected: Analysis of 107 patients
Authors: Bellini Alice , Marulli Giuseppe , Breda Cristiano , Ferrigno Pia , Terzi Stefano , Lomangino Ivan , Lo Giudice Fabio , Brombin Claudia , Laurino Licia , Pezzuto Federica , Calabrese Fiorella , Rea Federico
Published: July 2019

Objectives

Gold standard therapy for solitary fibrous tumour of the pleura is complete surgical resection. Aims of this retrospective study are to evaluate oncological and surgical outcomes and to verify the clinical reliability of prognostic scores presented in literature.

Methods

Study population: 107 patients surgically treated between 1972 and 2018. Male/female ratio: 1/2.45; median age at surgery: 60 years (range, 19‐80); peduncle lesions 69.8%; visceral pleura origin 72.9%; benign histology 73.8%; median diameter 8 cm (range 1 to 35, 27 cases giant [≥15 cm]).

Results

After a median follow up of 7 years, 12 patients had recurrence. By multivariate analysis, malignant histology (P = .03; HR, 4.17; 95% CI, 1.15‐15.06), origin from parietal pleura (P  = .03; HR, 3.90; 95% CI, 1.08‐14.09), England (P = .002; HR, 1.98; 95% CI, 1.28‐3.07), Diebold (P = .008; HR, 1.96; 95% CI, 1.20‐3.22) and Tapias (P = .003; HR, 1.75; 95% CI, 1.20‐2.53) scores were found independent significant predictors of relapse. Giant tumours were associated with open surgery (P = .003), origin from parietal pleura (P = .011) and intraoperative bleeding (P > .001). Overall 10‐year disease‐free survival (DFS) rate was 81%. Predictors of worst DFS were parietal pleura origin (P = .002), malignant histology (P = .006) and all the prognostic scores.

Conclusions

Malignant histology and origin from parietal pleura were significant predictors of tumour recurrence and worst DFS. The use of current scoring systems can help to predict clinical behaviour. Patients with higher risk of relapse can benefit from closer follow up, prolonged over 10 years.
Use of Memorial Sloan Kettering Cancer Center nomogram to guide intraoperative sentinel lymph node frozen sections in patients with early breast cancer
Authors: Houpu Yang , Fei Xie , Yang Yang , Fuzhong Tong , Peng Liu , Bo Zhou , Lin Cheng , Yingming Cao , Miao Liu , Hongjun Liu , Siyuan Wang , Yuan Peng , Danhua Shen , Shu Wang
Published: July 2019

Background

We implemented selective use of frozen section (FS) to optimize accuracy and cost control in the intraoperative diagnosis of sentinel lymph node (SLN) in patients with breast cancer, guided by the Memorial Sloan Kettering Cancer Center (MSKCC) nodal metastasis risk prediction nomogram.

Methods

Surgical pathology records were reviewed, examining 2582 consecutive biopsies from 2552 patients with breast cancer to compare intraoperative FS diagnoses with postoperative final reports. We calculated sensitivity, specificity, and false‐negative rates (FNRs) for various MSKCC risk levels, also analyzing axillary reoperation rates, with and without FS, and the number needed to treat (NNT) to avoid separate axillary lymph node dissection.

Results

The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3%, respectively. FNR and MSKCC risk level negatively correlated (r = −0.86; P = .002). Axillary reoperation rate significantly declined if FS was done (FS: 4.0%; no FS: 36.4%; P = .002). In grouping patients by quartile of MSKCC risk, axillary reoperation rates were 16.7%, 25.1%, 38.7%, and 58.7% without FS, compared with 4.3%, 3.2%, 5.6%, 3.3% with FS and NNT correspondingly fell from 8.1 to 4.6, 3.0, and 1.8.

Conclusions

A stratified decision‐making algorithm based on the MSKCC risk prediction model improved the effectiveness of FS during SLN biopsy to avoid axillary reoperation.
Appendiceal cancer masked as inflammatory appendicitis in the elderly, not an uncommon presentation (Surveillance Epidemiology and End Results (SEER)‐Medicare Analysis)
Authors: Siddharthan Ragavan V. , Byrne Raphael M. , Dewey Elizabeth , Martindale Robert G. , Gilbert Erin W. , Tsikitis Vassiliki L.
Published: July 2019

Background

The misdiagnosis of appendiceal cancer as inflammatory appendicitis is becoming of greater clinical concern because of the rise of nonoperative management especially in the elder population. To quantify this rate of misdiagnosis, we retrospectively reviewed SEER‐Medicare data.

Methods

The SEER‐Medicare database was reviewed from 2000 to 2014. We identified patients older than 65 years old who were diagnosed with appendiceal cancer and then cross‐referenced them for a diagnosis of inflammatory appendicitis. Demographic data and oncologic stage were collected.

Results

Our results showed that 28.6% of appendiceal cancer patients received an incorrect initial diagnosis of inflammatory appendicitis. Patients older than 75 years of age were more likely to be misdiagnosed than those between ages 65 and 75 (risk ratio [RR]: 0.81; 95% confidence interval: 0.70‐0.93; P = .003). We found that 42% of patients within the misdiagnosis group presented with an earlier stage of disease (stage 1 or 2) compared to 26% of those primarily diagnosed with appendiceal cancer (P < .001).

Conclusion

A significant proportion of patients older than 65 years old with appendiceal cancer were initially misdiagnosed with acute appendicitis. We suggest caution when considering a nonoperative approach for appendicitis in the elderly and follow‐up imaging or an interval appendectomy should be part of the treatment plan.
Long‐term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single‐institutional experience with 1225 cases
Authors: Kyang Lee Shyang , Alzahrani Nayef A. , Valle Sarah J. , Rahman Mohamed K. , Arrowaili Arif , Liauw Winston , Morris David L.
Published: July 2019

Background and Objectives

To review long‐term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC).

Methods

Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database.

Results

The study comprised of 1225 cases, including 687 females (56.1%) and 538 males (43.9%). Diagnoses included CRC (n = 363), followed by HAMN (n = 317), LAMN (n = 297), mesothelioma (n = 101), ovarian cancer (n = 55), and others including gastric, sarcoma, and neuroendocrine tumor (n = 92). The median OS, 5‐ and 10‐year survivals for CRC were 35 months, 33% and 8%, respectively. Patients with LAMN, in relative to HAMN, experienced a higher median OS, 5‐ and 10‐year survivals (248 months vs 63 months; 82% vs 52% and 59% vs 28%). The median OS for mesothelioma was 60 months with 5‐ and 10‐year survivals of 48% and 19%, respectively. In ovarian cancer, the median OS was 30 months with 5‐ and 10‐year survivals of 26% and 10%, respectively. For the remaining histological diagnoses, median OS and 5‐year survival were 28 months and 27%, respectively.

Conclusion

Our large‐cohort data showed that CRS/PIC can provide long‐term survival benefit to patients with PM of gastrointestinal and ovarian origin.
On‐line synergistic stacking in capillary zone electrophoresis featuring field‐amplified sample stacking and micelle to cyclodextrin stacking in the determination of two alkaloids in complicated matrix samples
Authors: Chu Chu , Liu Caijing , Jiang Luyi , Lian Linmin , Li Jing , Li Hanbing , Lv Huawei , Yan Jizhong
Published: July 2019

A novel on‐line synergistic proconcentration strategy coupling field‐amplified sample stacking and micelle to cyclodextrin stacking for cationic analytes in capillary zone electrophoresis has been proposed and applied for the separation and determination of two alkaloids, matrine, and oxymatrine in complicated matrix samples. The approach was performed by the long injection of sample in a low‐conductivity sodium dodecyl benzene sulfonate solution followed by the injection of hydroxypropyl‐β‐cyclodextrin solution in higher conductivity. The stacking mechanism of this method has been expounded and parameters affecting stacking effect have been optimized in our study. Under the optimum experimental conditions, 169‐ and 218‐fold sensitivity improvements were achieved for matrine and oxymatrine when compared with normal injection. Analytical indicators including linearity, limits of detection, and reproducibility (intra‐ and inter‐day relative standard deviations) were evaluated. Moreover, sample matrix effect was studied using compound flavescent sophora and salicylic acid powder and spiked urine samples. The developed method is an attempt for the combination of micelle to cyclodextrin stacking with other stacking methods. It could be a good alternative choice for the determination of alkaloids in a complex sample matrix.
Electrospun scaffolds limit the regenerative potential of the airway epithelium
Authors: Schwartz Cynthia M. , Stack Jacob , Hill Cynthia L. , Lallier Scott W. , Chiang Tendy , Johnson Jed , Reynolds Susan D.
Published: July 2019

Objective

Significant morbidity and mortality are associated with clinical use of synthetic tissue‐engineered tracheal grafts (TETG). Our previous work focused on an electrospun polyethylene terephthalate and polyurethane (PET/PU) TETG that was tested in sheep using a long‐segment tracheal defect model. We reported that graft stenosis and limited epithelialization contributed to graft failure. The present study determined if the epithelialization defect could be attributed to: 1) postsurgical depletion of native airway basal stem/progenitor cells; 2) an inability of the PET/PU‐TETG to support epithelial migration; or 3) compromised basal stem/progenitor cell proliferation within the PET/PU environment.

Study Design

Experimental.

Methods

Basal stem/progenitor cell frequency in sheep that underwent TETG implantation was determined using the clone‐forming cell frequency (CFCF) method. A novel migration model that mimics epithelial migration toward an acellular scaffold was developed and used to compare epithelial migration toward a control polyester scaffold and the PET/PU scaffold. Basal stem/progenitor cell proliferation within the PET/PU scaffold was evaluated using the CFCF assay, doubling‐time analysis, and mitotic cell quantification.

Results

We report that TETG implantation did not decrease basal stem/progenitor cell frequency. In contrast, we find that epithelial migration toward the PET/PU scaffold was significantly less extensive than migration toward a polyester scaffold and that the PET/PU scaffold did not support basal stem/progenitor cell proliferation.

Conclusions

We conclude that epithelialization of a PET/PU scaffold is compromised by poor migration of native tissue‐derived epithelial cells and by a lack of basal stem/progenitor cell proliferation within the scaffold.

Level of Evidence

NA
Nutrient dynamics in submarine groundwater discharge through a coral reef (western Lombok, Indonesia)
Authors: Oehler Till , Bakti Hendra , Lubis Rachmat Fajar , Purwoarminta Ananta , Delinom Robert , Moosdorf Nils
Published: July 2019

Submarine groundwater discharge (SGD) from tropical volcanic islands locally transports significant amounts of terrestrial nutrients into the coastal ocean, which can affect sensitive coastal ecosystems such as coral reefs. In northwestern Lombok, terrestrial submarine groundwater discharges through several submarine springs at the seafloor into a coral reef. In order to understand the transport mechanisms of nutrients from land into the reef, we investigated nutrient fluxes via SGD within the area using a combination of different methods, including recharge estimates in the coastal catchment area, echosounder profiling of the seafloor, discharge measurements, and hydrochemical analyses (stable isotopes of water, radon, and nutrients). Different types of springs can be distinguished based on their morphology. One spring showed a “crater”‐shaped structure while other springs consisted of fissures. Recharge rates in the coastal catchment amounted to 5 L s−1, while discharge rates from the largest spring were 5 L s−1 for total SGD and 2.5 L s−1 for fresh SGD, which is similar to discharge rates from smaller onshore springs at the slopes of a volcano. SGD was in general a source of nutrients such as dissolved silicon (~ 226 mol d−1), phosphate (0.61 mol d−1), or total dissolved nitrogen (13.4 mol d−1). Nitrate concentrations varied among the different springs, probably due to different sources in the hinterland, transformations (e.g., denitrification), or biological uptake during transport from land into the ocean. As nitrate can considerably affect coral reef health, our findings suggest that especially nitrate should be monitored around submarine springs in Indonesia.
Characterization of Laser‐Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy
Authors: Fu Zhibing , Huang Jinhua , Xiang Yaping , Huang Jian , Tang Zhen , Chen Jing , Nelson J. Stuart , Tan Wenbin , Lu Jianyun
Published: July 2019

Background and Objectives

Port wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser‐resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser‐resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM).

Study Design/Materials and Methods

A total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty‐three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed.

Results

We found 44.4% PWS on the extremities (four out of nine subjects) were laser‐resistant, which was significantly higher (P < 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser‐resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P < 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P < 0.001) in the skin when compared with laser‐responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2, P = 0.857) was not correlated to the laser resistance.

Conclusions

Laser‐resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser‐resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Sales promotions for preorder products: The role of time‐of‐release
Authors: Jha Subhash , Deitz George D. , Hart Phillip , Royne Stafford Marla B.
Published: July 2019

Preorder offers are increasingly common for many types of products and services. Sales promotions, such as price discounts and free gifts, are frequently used to raise offer attractiveness and elicit a stronger sales response. Through a series of experiments, we show that a preorder promotion's effectiveness depends on whether it matches the construal level associated with timing of the featured product's release. When a match occurs, it increases consumers’ positive affect leading to higher purchase intention directly or by raising the perceived certainty of new product quality. In addition, we find interesting differences related to promotion type. Specifically, we show that a larger discount promotes low‐level construals, which leads to stronger purchase intentions only when the product is scheduled for near‐future release. Since a gift may elicit either high‐ or low‐level construals, a premium offer of higher perceived value leads to stronger purchase intentions regardless of release timing.
Existence and regularity results of a backward problem for fractional diffusion equations
Authors: Zhou Yong , Wei He Jia , Ahmad Bashir , Huy Tuan Nguyen
Published: July 2019

In this paper, we study a backward problem for an inhomogeneous fractional diffusion equation in a bounded domain. By applying the properties of Mittag‐Leffler functions and the method of eigenvalue expansion, we establish some results about the existence, uniqueness, and regularity of the mild solutions as well as the classical solutions of the proposed problem in a weighted Hölder continuous function space.
Effects of Operating Conditions on the Copolymerization of Castor Oil Maleate–Styrene by Suspension Polymerization
Authors: Maia Dayanne L. H. , Fernandes Fabiano A. N.
Published: July 2019

This work studies the synthesis of copolymers (MACO‐St) of castor oil maleate (MACO) and styrene (St) initiated using benzoyl peroxide (BPO) as free radical initiator through suspension polymerization. The study investigates the effects of temperature (100–140 °C), the molar ratio between styrene and MACO (2:1–4:1), BPO concentration (0.10–0.20 wt%), and water concentration (50–100 wt%) on the molecular weight distribution, thermal stability, viscosity, and biodegradability of the copolymers. Suspension polymerization allows the production of a broad range of number average molecular weight (3465–18 995 g mol−1) and molecular weight distributions with dispersions (Đ) ranging from 1.8 to 4.4. The reaction presents high yields of castor oil into copolymers (>90%), which displays thermal stability up to 200 °C and are highly biodegradable according to the International Organization of Standardization reference.
Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003‐2013
Authors: Wang Stacie S. , Kotecha Rishi S. , Bernard Anne , Blyth Christopher C. , McMullan Brendan J. , Cann Megan P. , Yeoh Daniel K. , Bartlett Adam W. , Ryan Anne L. , Moore Andrew S. , Bryant Penelope A. , Clark Julia , Haeusler Gabrielle M.
Published: July 2019

Background

Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL.

Methods

IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a ‘modified‐possible’ category included.

Results

A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified‐possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8‐11.4%) overall and 23.5% (95% CI 14.5‐32.5%) for relapsed/refractory ALL. For non‐relapsed ALL, the IFI prevalence was significantly higher for children with high‐risk compared to standard‐risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non‐mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI.

Conclusions

IFI is more common in children with high‐risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.
Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience
Authors: Huang Ting‐Huan , Liu Hsi‐Che , Hou Jen‐Yin , Chang Ching‐Yi , Sun Fang‐Ju , Yeh Ting‐Chi
Published: July 2019

Background

In childhood cancer survivors, low bone mineral density (BMD) is a bone‐related consequence. Efficacy of denosumab, an effective therapy for adult patients with osteoporosis, remains unclear in children. This study aimed to investigate denosumab therapy efficacy for low BMD in childhood cancer survivors.

Procedure

Between January 2014 and January 2018, we monitored lumbar BMD of children with cancer using dual‐energy X‐ray absorptiometry after completing chemotherapy with a 6‐month interval. For patients with low BMD, defined as height‐adjusted Z‐scores of BMD < −1.5 in this study, calcium carbonate and vitamin D supplements were initially administered. When low BMD continued for at least 6 months, denosumab therapy was introduced. Calcium and vitamin D supplementation were continued in patients on denosumab. We investigated BMD change and adverse effects during denosumab therapy.

Results

During the study period, 20 patients received denosumab treatment. Mean height‐adjusted Z‐score of BMD before denosumab treatment was −2.68 but increased to −2, −1.96, and −1.33 at 0.5, 1, and 1.5 years after denosumab treatment, respectively (P = .012). In addition, hypocalcemia occurred in 40% (8/20) of patients; three patients had hypocalcemic symptoms with numbness in all four limbs. All hypocalcemic patients, except one patient who died due to relapsed leukemia, recovered well after continuous calcium supplementation.

Conclusions

Denosumab is an effective treatment for low BMD in childhood cancer survivors. However, the complication of hypocalcemia might develop posttreatment.
Preparation, Microstructure and Thermal Property of ZrAl3/Al Composite Fuels
Authors: Hu Aobo , Zou Hui , Shi Wen , Pang Ai‐min , Cai Shuizhou
Published: July 2019

ZrAl3/Al composite fuels (Al‐xZr, x=10, 20, 30, 40, 50, 53 wt.%) were prepared by the non‐consumable arc‐melting technique and close‐coupled gas‐atomization. In order to study the effects of the zirconium content and the oxygen partial pressure on the thermal properties of composite fuels, X‐ray diffraction, scanning electron microscopy, TG‐DTA and DSC were used to characterize the composite fuels, respectively. The result shows that the addition of zirconium leads to the formation of a special structure inside the powder, promoting the oxidation of ZrAl3/Al composite fuels. Besides, non‐selective oxidation of ZrAl3 played an important role in promoting the oxidation process. The oxygen bomb experiment was conducted to evaluate the combustion performance of ZrAl3/Al composite fuels. Oxygen bomb experiments show that the gravimetric combustion enthalpy of the composite fuels decreases linearly with the increase of zirconium content, and increases with the increase of oxygen partial pressure. However, the volumetric combustion enthalpy decreases first and then increases with the increase of zirconium content, and shows a general upward trend when the partial pressure of oxygen reaches 2.5 MPa or more. The pressure curve indicates that the Al‐53Zr composite fuels have the maximum pressure propagation rate (dP/dt)max (which characterizes the maximum flame propagation rate and higher energy releasing rates) in the prepared series of composite fuels. The study demonstrates a complete combustion of ZrAl3/Al composite fuels under high pressure. ZrAl3/Al composite fuels could be considered as a very promising energetic additive in the field of new‐energetic material.
Application of Physiologically‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin
Authors: Willmann Stefan , Frei Matthias , Sutter Gabriele , Coboeken Katrin , Wendl Thomas , Eissing Thomas , Lippert Jörg , Stass Heino
Published: July 2019

Moxifloxacin is a widely used fluoroquinolone for the treatment of complicated intra‐abdominal infections. We applied physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) modeling to support dose selection in pediatric patients. We scaled an existing adult PBPK model to children based on prior physiological knowledge. The resulting model proposed an age‐dependent dosing regimen that was tested in a phase I study. Refined doses were then tested in a phase III study. A popPK analysis of all clinical pediatric data confirmed the PBPK predictions, including the proposed dosing schedule in children, and supported pharmacokinetics‐related safety/efficacy questions. The pediatric PBPK model adequately predicted the doses necessary to achieve antimicrobial efficacy while maintaining safety in the phase I and III pediatric studies. Altogether, this study retroactively demonstrated the robustness and utility of modeling to support dose finding and confirmation in pediatric drug development for moxifloxacin.
Majority Carrier Properties of Single Crystal Cu2−xZnSnSe4 with Varying Copper Composition
Authors: McCandless Brian E. , Bishop Doug , Lloyd Michael
Published: July 2019

The dependence of carrier concentration on copper content in Cu2−xZnSnSe4 single crystals, grown without fluxing agents, is presented over the composition range Cu/(Zn + Sn) of 0.77–0.93 and Zn/Sn from 1.3 (low Cu content) to 1.3 (high Cu content). Single phase mono‐crystals with facets up to 5 mm are synthesized from high‐purity elements and validated using Laue diffraction. A direct optical band gap of 0.98 eV is observed for a crystal with Cu/(Zn + Sn) = 0.85. Van der Pauw–Hall resistance analysis shows decreasing hole concentration, from 1019 cm−3 to 2 × 1015 cm−3, with decreasing copper content over the composition range. Hole mobility varies from 50 cm2 V−1 s−1 to 160 cm2 V−1 s−1, with no dependence on copper concentration. A linear temperature dependence of the Seebeck coefficient is found for all crystals. The Seebeck coefficient–carrier concentration dependence is used to determine the valence band density of states, NV, and corresponding effective mass, μh*. Crystals with Cu/(Zn + Sn) < 0.9 have NV = 4 × 1018 cm−3 and μh* = 0.4 m0 while crystals with elevated copper concentration, Cu/(Zn + Sn) > 0.9, exhibit higher density of states, NV = 3 × 1019 cm−3 and hole effective mass μh* = 0.9 m0. The increased valence band density of states at elevated copper composition is consistent with more Cu–Zn exchange sites contributing to bulk defects and band edge fluctuations. Temperature‐dependent conductivity measurements indicate a transition from metallic‐type to semiconductor‐type conduction at Cu/(Zn + Sn) < 0.9. At lower copper content, for a crystal with Cu/(Zn + Sn) = 0.83 and p = 1017 cm−3 the activation energy for intrinsic conduction is 60 meV. This behavior is attributed to the copper vacancy defect, VCu, and is comparable to reported values obtained in thin films and by first‐principles predictions.
Ultra‐Thin Perovskite Solar Cells Analytical Model Involving Radiative and Nonradiative Carrier Recombination Mechanisms
Authors: Morales-Acevedo Arturo
Published: July 2019

Understanding the reasons for the high efficiencies and open‐circuit voltages of perovskite solar cells is fundamental for achieving performance improvements in the future. Therefore, herein, a perovskite cell model is developed in which both radiative and nonradiative recombination currents are included by two diode equations with ideality factors of 1 and 2, respectively, and then the conversion efficiency dependence on carrier lifetime, perovskite material bandgap, and device thickness is studied, considering these two recombination mechanisms. The capability of the model for the evaluation and prediction of performances of perovskite solar cells is also shown, agreeing very well with current experimental efficiencies for these cells. It avoids complicated numerical solutions for the transport equations and makes use of well‐known analytical expressions for developing a real novel model. This model allows the estimation of the optimum perovskite thickness, and it also helps in determining what should be the required device carrier lifetimes for having increased efficiencies, above the current 23.7% record. It is predicted that (nonradiative) lifetimes larger than 10 μs in the perovskite cell material will not cause any efficiency improvement above the expected limit of 29%. The model agrees well with reported experimental results.
Random effects models for estimation of the probability and time to progression of a continuous biomarker
Authors: Reddy Tarylee , Molenberghs Geert , Bruckers Liesbeth , Njagi Edmund Njeru , Aerts Marc , Willem Schurink Geert
Published: July 2019

Biomarkers play a key role in the monitoring of disease progression. The time taken for an individual to reach a biomarker exceeding or lower than a meaningful threshold is often of interest. Due to the inherent variability of biomarkers, persistence criteria are sometimes included in the definitions of progression, such that only two consecutive measurements above or below the relevant threshold signal that “true” progression has occurred. In previous work, a novel approach was developed, which allowed estimation of the time to threshold using the parameters from a linear mixed model where the residual variance was assumed to be pure measurement error. In this paper, we extend this methodology so that serial correlation can be accommodated. Assuming that the Markov property holds and applying the chain rule of probabilities, we found that the probability of progression at each timepoint can be expressed simply as the product of conditional probabilities. The methodology is applied to a cohort of HIV positive individuals, where the time to reach a CD4 count threshold is estimated. The second application we present is based on a study on abdominal aortic aneurysms, where the time taken for an individual to reach a diameter exceeding 55 mm is studied. We observed that erroneously ignoring the residual correlation when it is strong may result in substantial overestimation of the time to threshold. The estimated probability of the biomarker reaching a threshold of interest, expected time to threshold, and confidence intervals are presented for selected patients in both applications.
Driving factors of the flushing time of bays formed where tributaries enter a reservoir
Authors: Zhao Qian , Mao Jingqiao , Cai Haibin , Dai Huichao
Published: July 2019

Flushing time is an integrative parameter that can represent water exchange capacity and sensitivity to pollution threats. As bays formed where tributaries enter the Three Gorges Reservoir of China have experienced frequent algal blooms over the past decade, we examine the spatially variable flushing time of a typical tributary bay (Xiangxi Bay) by numerical tracer experiments. First, the tracer concentration reduction could be approximated well by a double exponential decay curve, and the local flushing time of Xiangxi Bay is determined using key flushing coefficients. Second, a sensitivity analysis is performed to examine the influence of upstream inflow, temperature difference, wind, water level of the reservoir, and daily water level fluctuation on the spatial variation in local flushing time. Finally, according to local flushing time values and the sensitivity analysis results, the bay can be generally characterized by three zones: riverine, transitional, and mainstream‐influenced zones. In particular, the local flushing times in the riverine zone are mainly affected by the upstream inflow. The difference in temperature between the reservoir mainstream and Xiangxi Bay is the main forcing in the transitional and mainstream‐influenced zones. This study is the first to investigate different driving factors for flushing time in a typical reservoir tributary bay. The findings provide insights on the transport processes in such water bodies, suggesting the possibility of using the longitudinal zonation of flushing time for reservoir management.
Effects of cyclonic plasma deposited organosilicon nano‐coating on 316 stainless steel and its surface characterization
Authors: Wu Li‐Yu , Kuo Yu‐Lin , Chang Kuang‐Hui , Chen Ting‐Hao , Cheng Chou‐Yuan , Liu Yu‐Shuan , Huang Chun
Published: July 2019

Cyclonic atmospheric pressure plasma is developed to synthesize the organosilicon nano‐coating on 316 L stainless steel surface with hexamethyldisilazane (HMDSN) and HMDSN/N2 monomers. The modified 316 L stainless steel surface characteristics of cyclonic plasma deposited organosilicon nano‐coating were evaluated by the static contact angle measurement, FTIR, SEM, AFM, and XPS detections. The chemical analysis with FTIR and XPS depicts that cyclonic plasma deposited nano‐coating obtains the relatively inorganic characteristics. The surface morphological determination with SEM and AFM refers cyclonic plasma deposited 316 L stainless steel surface roughness alteration with switching monomer inputs. This study shows the potential of chamber‐less deposition to create the plasma deposited organosilicon nano‐coating for 316 L stainless.
Exposing {001} Crystal Plane on Hexagonal Ni‐MOF with Surface‐Grown Cross‐Linked Mesh‐Structures for Electrochemical Energy Storage
Authors: Li Yan , Xu Yuxia , Liu Yong , Pang Huan
Published: July 2019

Hexagonal nickel‐organic framework (Ni‐MOF) [Ni(NO3)2·6H2O, 1,3,5‐benzenetricarboxylic acid, 4‐4′‐bipyridine] is fabricated through a one‐step solvothermal method. The {001} crystal plane is exposed to the largest hexagonal surface, which is an ideal structure for electron transport and ion diffusion. Compared with the surrounding rectangular crystal surface, the ion diffusion length through the {001} crystal plane is the shortest. In addition, the cross‐linked porous mesh structures growing on the {001} crystal plane strengthen the mixing with conductive carbon, inducing preferable conductivity, as well as increasing the area of ion contact and the number of active sites. These advantages enable the hexagonal Ni‐MOF to exhibit excellent electrochemical performance as supercapacitor electrode materials. In a three‐electrode cell, specific capacitance of hexagonal Ni‐MOF in the 3.0 m KOH electrolyte is 977.04 F g−1 and remains at the initial value of 92.34% after 5,000 cycles. When the hexagonal Ni‐MOF and activated carbon are assembled into aqueous devices, the electrochemical performance remains effective.