bluuebunny/crossref_metadata_2025 huggingface dataset:
HPV self‐sampling acceptability and preferences among women living with HIV in Botswana
Authors: Kohler Racquel E. , Elliott Tamara , Monare Barati , Moshashane Neo , Ramontshonyana Kehumile , Chatterjee Pritha , Ramogola‐Masire Doreen , Morroni Chelsea
Published: September 2019

Objective

To assess the acceptability and preferences of HPV screening with self‐sampling and mobile phone results delivery among women living with HIV (WLWH) in Botswana, as an alternative to traditional speculum screening.

Methods

WLWH aged 25 years or older attending an infectious disease clinic in Gaborone were enrolled in a cross‐sectional study between March and April 2017. Women self‐sampled with a flocked swab, had a speculum exam, and completed an interviewer‐administered questionnaire about screening acceptability, experiences, and preferences.

Results

Of the 104 WLWH recruited, 98 (94%) had a history of traditional screening. Over 90% agreed self‐sampling was easy and comfortable. Ninety‐five percent were willing to self‐sample again; however, only 19% preferred self‐sampling over speculum exam for future screening. Preferences differed by education and residence with self‐sampling being considered more convenient, easier, less embarrassing, and less painful. Speculum exams were preferred because of trust in providers’ skills and women's low self‐efficacy to sample correctly. Almost half (47%) preferred to receive results via mobile phone call. Knowledge of cervical cancer did not affect preferences.

Conclusion

HPV self‐sampling is acceptable among WLWH in Botswana; however, preferences vary. Although self‐sampling is an important alternative to traditional speculum screening, education and support will be critical to address women's low self‐efficacy to self‐sample correctly.
Tutorials in Clinical Research, Part VI: Descriptive Statistics
Authors: Neely J. Gail , Stewart Michael G. , Hartman James M. , Forsen James W. , Wallace Mark S.
Published: September 2019

Objectives: This is the sixth in a series of Tutorials in Clinical Research. The objectives of this tutorial are to produce a brief, step‐by‐step, user‐friendly atlas with clinical scenarios and illustrative examples to serve as ready references and, it is hoped, to open an inviting door to understanding statistics. Study Design: Tutorial. Methods: The authors met weekly for 6 months discussing clinical research articles and the applied statistics. Liberal use of reference texts and discussion focused on constructing a tutorial that is factual as well as easy to read and understand. Results: The tutorial is organized into five sections: Overview, Key to Descriptive Summaries, Steps in Summarizing Descriptive Data, Understanding the Summaries of Specific Data Types, and Understanding Scope or Dispersion of Data. Conclusions: Assessing the validity of medical studies requires a working knowledge of statistics; however, obtaining this knowledge need not be beyond the ability of the busy surgeon. Desire is the only limiting factor. We have tried to construct an accurate, basic, easy‐to‐read‐and‐apply introduction to the task of summarizing the characteristics of a single variable. This is known as descriptive statistics. Key Words: Research and methods, research design, clinical protocols, statistics and methods.
The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers
Authors: Gang Wang , Yu‐Zhu Wang , Yang Yu , Feng Shi , Xing‐Li Fu , Heng Zhang
Published: September 2019

Transcription factors (TFs) like a nuclear factor of activated T‐cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor‐associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T‐cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll‐like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by‐product that affect T‐cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient‐personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T‐cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC.
miR‐125a‐3p suppresses the growth and progression of papillary thyroid carcinoma cell by targeting MMP11
Authors: Song Min , Wang Na , Li Zhen , Zhang Yanfang , Zheng Yingying , Yi Pengfei , Chen Jing
Published: September 2019

The dysregulation of miR‐125a‐3p has been observed in multiple tumor types. Nevertheless, the function of miR‐125a‐3p in papillary thyroid carcinoma (PTC) is yet to be explored. Herein, we find that miR‐125a‐3p is markedly downregulated in PTC tissues, and its level is inversely related to the histological grade of PTC. Upregulation of miR‐125a‐3p suppresses the pulmonary metastatic ability as well as the tumor growth of PTC cell in vivo. Consistently, the colony formation ability and other metastasis‐related traits of PTC cell are inhibited by miR‐125a‐3p transfection in vitro. In addition, we identify that matrix metalloprotease 11 (MMP11) is the direct target gene of miR‐125a‐3p, and that miR‐125a‐3p inhibits cell viability, migration, and invasiveness of PTC cell by reducing MMP11 expression in vitro. Together, these data testify that the miR‐125a‐3p/MMP11 axis plays vital roles in the growth and progression of human PTC cells.
ShRNA‐mediated matrix metalloproteinase‐2 gene silencing protects normal cells and sensitizes cancer cells against ionizing‐radiation induced damage
Authors: Shailender Gugalavath , Patanla Kiranmayi , Malla Rama Rao
Published: September 2019

Introduction

Ionizing radiation (IR) affects healthy tissues during the treatment of cancer radiation therapy and other nuclear and radiological accidents. Some natural compounds showed nonspecific radioprotective activity with severe side effects. The present study is aimed to develop potent and specific radioprotective short hairpin RNA (shRNA), which selectively protects normal cells from IR by specifically targeting matrix metalloproteinases (MMP‐2).

Results

IR reduced the viability of human normal dermal fibroblasts (HDFs) in a dose‐response manner. It enhanced the expression of MMP‐2 at 10 Gy. Plasmid MMP‐2shRNA (pMMP‐2) reduced the IR (10 Gy) induced cytotoxicity analyzed by lactate dehydrogenase (LDH) assay, normalized IR induced cellular and morphological changes with enhanced the clonogenicity in 48 hours at 2 µg/mL. It reduced the ROS generation, released HDFs from G2/M arrest and rescued from apoptosis analyzed by DCFDA dye, cell cycle analysis by PI stain and annexin V assay, respectively. pMMP‐2 also modulates the expression of EGFR and reduced IR induced expression of DNA damage response protein, ATM and increased the expression of repair proteins, KU70/KU80, and RAD51. In addition, decreased the expression of cell cycle regulatory proteins cyclin‐dependent kinases (CDK1) and Cyclin B as well as proapoptotic proteins BAX, caspase‐3, and Cytochrome‐C and increased the expression of survival protein, Bcl‐2. In contrary pMMP‐2 decreased the LDH activity, survival fraction and blocked G2/M phase of cell cycle and increased apoptosis in MCF‐7 cells. In addition, decreased the expression of EGFR, proapoptotic BAX and DNA repair proteins ATM, KU70/80 and RAD51, increased expression of cyclinB as well as CDK1.

Conclusion

Results conclude that pMMP‐2 protected HDFs from IR and sensitized the MCF‐7 cells. Therefore, pMMP‐2 can be employed for better treatment of radiation accidents and during the treatment of radiotherapy.
Tackling endothelium remodeling in cardiovascular disease
Authors: Guľašová Zuzana , Guerreiro Susana G. , Link Rene , Soares Raquel , Tomečková Vladimíra
Published: September 2019

Endothelial dysfunction is considered an early marker of atherosclerosis. Herein, we address the molecular mechanisms affecting endothelium remodeling in disease. Vascular calcification is highly prevalent in patients with ischemic cardiovascular disease, cerebrovascular disorder, and renal failure, being a common feature in aging, diabetes, dyslipidemia, abnormal valve biomechanics, end‐stage renal disease and atherosclerosis, a major cause of mortality and morbidity. Oxidative stress promotes calcification of vascular smooth muscle cells (SMC) by increasing osteogenic transcription factors expression and activity in atherosclerotic plaques. Various markers of osteogenic differentiation are expressed by SMC in calcified atherosclerotic lesions. Interestingly, decreased levels of some bone factors and microRNAs accelerate vascular calcification and injured tissue regeneration. Another key player in endothelial remodeling is amino acids metabolism. Branched‐chain amino acids are catabolized in several nonhepatic tissues including cardiac muscle. Immune activation and inflammation in cardiovascular disease patients associate with higher phenylalanine/tyrosine ratios. Understanding the whole process that underlies endothelium dysfunction is of paramount importance for the development of new therapeutic approaches.
Accumulation of sphingomyelin in Niemann‐Pick disease type C cells disrupts Rab9‐dependent vesicular trafficking of cholesterol
Authors: Wanikawa Masahiro , Nakamura Hiroyuki , Emori Shunsuke , Hashimoto Naohiro , Murayama Toshihiko
Published: September 2019

Niemann‐Pick disease type C (NPC) is a genetic disorder in which patient cells have endosomal/lysosomal accumulation of cholesterol and sphingolipids. However, the relationship between sphingolipids and cholesterol accumulation in NPC cells has not been established. Here, we investigated the role of sphingomyelin (SM) on the accumulation of cholesterol in NPC cells. Reduction of SM by inhibition of the ceramide transfer protein CERT decreased the cholesterol accumulation in NPC cells. The accumulation of SM in NPC cells inhibited the transport of cholesterol to the endoplasmic reticulum. Overexpression of Rab9 in NPC cells reduced the cholesterol accumulation, which was recovered by treatment with SM. In NPC cells that overexpressed a Rab9 constitutively active mutant, SM treatment did not lead to the cholesterol accumulation. These results indicate that SM negatively regulates the Rab9‐dependent vesicular trafficking of cholesterol, and a reduction in SM levels in NPC cells recovers the Rab9‐dependent vesicular trafficking defect.
Network‐based analysis reveals novel gene signatures in the peripheral blood of patients with sporadic nonsyndromic thoracic aortic aneurysm
Authors: Xu Heng , Chen Shanshan , Zhang Hao , Zou Yanqiang , Zhao Jing , Yu Jizhang , Le Sheng , Cui Jikai , Jiang Lang , Wu Jie , Xia Jiahong
Published: September 2019

Thoracic aortic aneurysm (TAA), a serious cardiovascular disease that causes morbidity and mortality worldwide. At present, few biomarkers can accurately diagnose the appearance of TAA before dissection or rupture. Our research has the intention to investigate the developing applicable biomarkers for TAA promising clinically diagnostic biomarkers or probable regulatory targets for TAA. In our research, we built correlation networks utilizing the expression profile of peripheral blood mononuclear cell obtained from a public microarray data set (GSE9106). Furthermore, we chose the turquoise module, which has the strongest significance with TAA and was further analyzed. Fourteen genes that overlapped with differentially expressed proteins in the medial aortic layer were obtained. Subsequently, we verified the results applying quantitative polymerase chain reaction (Q‐PCR) to our clinical specimen. In general, the Q‐PCR results coincide with the majority of the expression profile. Fascinatingly, a notable change occurred in CLU, DES, MYH10, and FBLN5. In summary, using weighted gene coexpression analysis, our study indicates that CLU, DES, MYH10, and FBLN5 were identified and validated to be related to TAA and might be candidate biomarkers or therapeutic targets for TAA.
Dysbiotic 1‐carbon metabolism in cardiac muscle remodeling
Authors: George Akash K. , Singh Mahavir , Pushpakumar S. , Homme Rubens P. , Hardin Shanna J. , Tyagi Suresh C.
Published: September 2019

Unless there is a genetic defect/mutation/deletion in a gene, the causation of a given disease is chronic dysregulation of gut metabolism. Most of the time, if not always, starts within the gut; that is what we eat. Recent research shows that the imbalance between good versus bad microbial population, especially in the gut, causes systemic diseases. Thus, an appropriate balance of the gut microbiota (eubiosis over dysbiosis) needs to be maintained for normal health (Veeranki and Tyagi, 2017, Journal of Cellular Physiology, 232, 2929–2930). However, during various diseases such as metabolic syndrome, inflammatory bowel disease, diabetes, obesity, and hypertension the dysbiotic gut environment tends to prevail. Our research focuses on homocysteine (Hcy) metabolism that occupies a center‐stage in many biochemically relevant epigenetic mechanisms. For example, dysbiotic bacteria methylate promoters to inhibit gene activities. Interestingly, the product of the 1‐carbon metabolism is Hcy, unequivocally. Emerging studies show that host resistance to various antibiotics occurs due to inverton promoter inhibition, presumably because of promoter methylation. This results from modification of host promoters by bacterial products leading to loss of host's ability to drug compatibility and system sensitivity. In this study, we focus on the role of high methionine diet (HMD), an ingredient rich in red meat and measure the effects of a probiotic on cardiac muscle remodeling and its functions. We employed wild type (WT) and cystathionine beta‐synthase heterozygote knockout (CBS+/−) mice with and without HMD and with and without a probiotic; PB (Lactobacillus) in drinking water for 16 weeks. Results indicate that matrix metalloproteinase‐2 (MMP‐2) activity was robust in CBS+/− fed with HMD and that it was successfully attenuated by the PB treatment. Cardiomyocyte contractility and ECHO data revealed mitigation of the cardiac dysfunction in CBS+/− + HMD mice treated with PB. In conclusion, our data suggest that probiotics can potentially reverse the Hcy‐meditated cardiac dysfunction.
Physiologically Based Pharmacokinetic Models to Predict Maternal Pharmacokinetics and Fetal Exposure to Emtricitabine and Acyclovir
Authors: Liu Xiaomei I. , Momper Jeremiah D. , Rakhmanina Natella , van den Anker John N. , Green Dionna J. , Burckart Gilbert J. , Best Brookie M. , Mirochnick Mark , Capparelli Edmund V. , Dallmann André
Published: September 2019

Pregnancy is associated with physiological changes that may impact drug pharmacokinetics (PK). The goals of this study were to build maternal‐fetal physiologically based pharmacokinetic (PBPK) models for acyclovir and emtricitabine, 2 anti(retro)viral drugs with active renal net secretion, and to (1) evaluate the predicted maternal PK at different stages of pregnancy; (2) predict the changes in PK target parameters following the current dosing regimen of these drugs throughout pregnancy; (3) evaluate the predicted concentrations of these drugs in the umbilical vein at delivery; (4) compare the model performance for predicting maternal PK of emtricitabine in the third trimester with that of previously published PBPK models; and (5) compare different previously published approaches for estimating the placental permeability of these 2 drugs. Results showed that the pregnancy PBPK model for acyclovir predicted all maternal concentrations within a 2‐fold error range, whereas the model for emtricitabine predicted 79% of the maternal concentrations values within that range. Extrapolation of these models to earlier stages of pregnancy indicated that the change in the median PK target parameters remained well above the target threshold. Concentrations of acyclovir and emtricitabine in the umbilical vein were overall adequately predicted. The comparison of different emtricitabine PBPK models suggested an overall similar predictive performance in the third trimester, but the comparison of different approaches for estimating placental drug permeability revealed large differences. These models can enhance the understanding of the PK behavior of renally excreted drugs, which may ultimately inform pharmacotherapeutic decision making in pregnant women and their fetuses.
Population Pharmacokinetics of Talazoparib in Patients With Advanced Cancer
Authors: Yu Yanke , Durairaj Chandrasekar , Shi Haihong , Wang Diane D.
Published: September 2019

Poly(ADP‐ribose) polymerase (PARP) inhibitors have been developed to treat cancers associated with somatic BRCA mutations and germline genetic aberrations involved in the DNA damage response. The efficacy, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profile of talazoparib, a potent small‐molecule PARP inhibitor, was established in 4 clinical studies in cancer patients (2 phase 1 studies PRP‐001 and PRP‐002, the phase 2 ABRAZO trial, and the phase 3 EMBRACA trial). The current study aimed to describe the population PK of talazoparib and identify covariates that affect talazoparib PK in patients with advanced cancers using pooled data from these 4 studies. Talazoparib PK was well characterized by a 2‐compartment model with first‐order absorption and absorption lag time. Based on covariate analysis, no dose adjustment for talazoparib is required based on a patient's age, sex, baseline body weight, Asian race, the presence of mild renal or hepatic impairment, or use of acid‐reducing agents. A reduced 0.75‐mg daily dose is recommended for patients taking a potent P‐glycoprotein inhibitor and those with moderate renal impairment. Insufficient data were available to establish dosing recommendations for patients with severe renal and moderate or severe hepatic impairment. The PK of a single 1‐mg talazoparib capsule is comparable with 4 0.25‐mg capsules. Talazoparib can be taken with or without food. These data provide support for dosing recommendations and labeling information for talazoparib.
The interactions of an algae–fungi symbiotic system influence nutrient removal from synthetic wastewater
Authors: Jiang Mengqi , Li Huimin , Zhou Yanping , Zhang Jibiao
Published: September 2019

BACKGROUND

Algae–bacteria symbiotic system has attracted much attention in the fields of nutrients removal from wastewater. Fungi has also been demonstrated to promote the cultivation of microalgae. However, capability and mechanism of algae–fungi symbiotic system for nutrient removal remains unclear.

RESULTS

This study assessed the removal efficiencies of an algae–fungi symbiotic system of Chlorella variabilis NC64A and Ganoderma lucidum for chemical oxygen demand (CODcr), total nitrogen (TN), total phosphorus (TP), and ammonia nitrogen (NH3‐N) from synthetic wastewater. The highest levels of dry cell weight (DCW), chlorophyll‐a (Chl‐a), and enzyme activity in the algae–fungi symbiotic system were obtained at an algae–fungi mass ratio of 1:3. At this ratio, the system on the tenth day removed 75.5%, 76.7%, 74.7%, and 90.0% of CODcr, TN, TP, and NH3‐N, respectively. Maximum values of both DCW (0.89 g L−1) and Chl‐a (2885 mg L−1) were achieved on day 6. Chlorella variabilis NC64A and G. lucidum coexisted as an algae–fungi consortium, in which G. lucidum exerted pressure on C. variabilis NC64A via enzymatic hydrolysis of cellulose in algal cell walls.

CONCLUSION

Algae–fungi interactions have the tendency to establish symbiosis and a fully autotrophic system without the need for an additional carbon source. © 2019 Society of Chemical Industry
Feasibility of the lidocaine injection method during esophageal endoscopic submucosal dissection
Authors: Yoshizaki Tetsuya , Obata Daisuke , Ueda Chise , Katayama Norio , Aoki Yasuhiro , Okamoto Norihiro , Hashimura Hiroki , Matsumoto Masanori , Takagi Megumi , Ikeoka Seitaro , Yoshida Ryutaro , Momose Kenji , Eguchi Takaaki , Yamashita Hiroshi , Okada Akihiko
Published: September 2019

Background and Aim

Esophageal endoscopic submucosal dissection (ESD) is often technically difficult due to intraoperative body movements. The level of sedation can be increased to suppress body movements, but this may not be successful in all cases. Using local analgesics for submucosal injection during ESD may aid in conscious sedation. This study evaluated the feasibility of the lidocaine injection method (LIM) during esophageal ESD.

Methods

Twenty‐nine patients with superficial esophageal cancer were enrolled in this study at Osaka Saiseikai Nakatsu Hospital, and 1% lidocaine + 0.4% hyaluronate sodium was injected into the submucosa underneath the lesion during esophageal ESD. The main outcome was body movements that disturbed the procedure.

Results

Most patients were male (90%), with a median age of 70 years (interquartile range [IQR]: 66–75 years old), and the median lesion size was 17 mm (IQR: 12–21 mm). The median injection volume of lidocaine was 70 mg (IQR: 55–79 mg). All lesions were successfully removed en bloc. In all cases, there were no body movements that disturbed the procedure. Regarding adverse events of sedation, five patients (17%) had hypotension, four patients (14%) had bradycardia, and seven patients (24%) had hypoxemia during ESD. Convulsions or arrhythmia as adverse events associated with lidocaine were not observed.

Conclusions

Esophageal ESD with LIM did not cause body movements that disturbed the procedure. LIM may help create a stable conscious sedation method for esophageal ESD.
TLR4 mediates alveolar bone resorption in experimental peri‐implantitis through regulation of CD45+ cell infiltration, RANKL/OPG ratio, and inflammatory cytokine production
Authors: Deng Shu , Hu Yang , Zhou Jing , Wang Yufeng , Wang Yuguang , Li Sicong , Huang Grace , Peng Cheng , Hu Anka , Yu Qing , Han Xiaozhe
Published: September 2019

Background

The present study was to determine the role of Toll‐like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model of Porphyromonas gingivalis‐associated ligature‐induced peri‐implantitis.

Methods

Smooth surface titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in Wild‐type (WT) and TLR4−/− (TLR4 KO) mice. Silk ligatures immersed with P. gingivalis were tied around the implants 4 weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses, and gingival mRNA expression levels of cytokines were assessed by micro‐computed tomography, tartrate‐resistant acid phosphatase (TRAP) staining, immunobiological examination and Real‐time quantitative polymerase chain reaction, respectively.

Results

In both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared with control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared with that in WT mice. Receptor activator of nuclear factor‐kappa B ligand /osteoprotegerin (RANKL/OPG) ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL‐1β, IFN‐γ, and 1L‐17 were significantly increased in TLR4 KO mice.

Conclusion

This study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature‐induced peri‐implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production.
Social media conflicts during the financial crisis: Managerial implications for retail banks
Authors: Dineva Denitsa , Lu Xiaoming , Breitsohl Jan
Published: September 2019

Social media can be used proactively to disseminate accurate corporate information and address undesirable consumer behaviors online in order to help counteract negativity in the business environment in the wake of a financial crisis. Social media thus has become a popular open forum for financial institutions such as retail banks to engage in corporate dialogue with consumers. We recommend that financial services firms preemptively use their social media‐based online communities in order to disseminate accurate corporate information in times of a financial crisis. Particularly, firms can choose between a range of reactive and proactive strategies to manage social conflict in the wake of a financial crisis.
Questionable Dystonia in Essential Tremor Plus: A Video‐Based Assessment of 19 Patients
Authors: Pandey Sanjay , Bhattad Sonali
Published: September 2019

View Supplementary Video 1
The effect of cognitive load on economic decisions
Authors: Blaywais Reut , Rosenboim Mosi
Published: September 2019

In the current study, we examine how cognitive load affects economic decision‐making. We asked participants to bid for lottery tickets with and without an alternative income. We demonstrate that the tendency to ignore opportunity costs is stronger under a greater cognitive load. Furthermore, cognitive load causes participants to invest fewer cognitive efforts in choice tasks and take more risks.
Comparisons in long‐term clinical outcomes among patients with upper or lower extremity lymphedema treated with diverse vascularized lymph node transfer
Authors: Ciudad Pedro , Manrique Oscar J. , Bustos Samyd S. , Coca John J. P. , Chang Chang‐Cheng , Shih Pin‐Keng , Nicoli Fabio , Lo Torto Federico , Agko Mouchammed , Huang Tony C.‐T. , Maruccia Michele , Chen Hung‐Chi
Published: September 2019

Background

Vascularized lymph node transfer (VLNT) is an emerging surgical treatment for lymphedema. However, literature‐comparing outcomes of upper limb lymphedema (ULL) and lower limb lymphedema (LLL) is limited. Hence, the aim of this study is to compare the long‐term clinical outcomes on ULL versus LLL in patients treated with VLNT.

Methods

A retrospective study retrieving data from patients with International Society of Lymphology (ISL) stages II–III who underwent different VLNTs from July 2010 to July 2016 in our institution was performed. Demographics preoperatively, and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) preoperatively and postoperatively were recorded. Clinical outcomes by extremity were also analyzed.

Results

A total of 83 patients with lymphedema (ULL: n = 30, LLL: n = 53) were included. Mean follow‐up time was 32.8 months (range 24–49 months). Mean circumference reduction was higher in patients with ULL compared to with LLL (28.6 ± 8.6 vs. 22.3 ± 10.1, p < .001), and for patients with secondary lymphedema (24.8 ± 9.6, p < .001) than for patients with primary lymphedema (18.9 ± 14, p > .05). Infectious episodes per year preoperative and postoperative showed that LLL patients had higher reduction on infection rate compared with ULL patients (2.4 ± 1.1 vs. 1.9 ± 1.2, p < .001).

Conclusion

VLNT is a promising surgical treatment option for patients with lymphedema. This study suggests that VLNT may have a more beneficial outcome in patients with ULL and with secondary lymphedema.
Bismuth‐doped compound germanate glass microsphere lasing in the near‐infrared region
Authors: Liang Haidong , Wang Xin , Yu Jibo , Yang Wenlei , Lewis Elfed , Wang Pengfei
Published: September 2019

A bismuth‐doped compound glass‐based microsphere laser is reported. The fluorescence luminescence of the bismuth‐doped compound glass is measured over an ultra‐broad wavelength range of 1100 to 1700 nm excited using an 808 nm pumping source. The glass microsphere was fabricated using a CO2 laser heating the fiber near its melting temperature, and when coupled with the tapered silica fiber, yielded the 1310 nm laser emission pumped using an 808 nm laser diode. The 245 μW––low absorbed pumping threshold of the microsphere, 3.57 μW laser output and the tunable multiple wavelength emissions demonstrate great potential applications for use in near infrared broadband fiber amplifiers and tunable lasers.
MiR‐8‐3p regulates hyperthermia‐induced lactate secretion by targeting PPP2R5B in boar Sertoli cells
Authors: Hu Yu , Deng Jie , Tian Ke , Yang Wei‐Rong , Luo Nan‐Jian , Lian Yu , Gan Lu , Tang Xing‐Yi , Luo Hong‐Yan , Zhang Jiao‐Jiao , Wang Xian‐Zhong
Published: September 2019

Lactate produced by glycolysis in Sertoli cells (SCs) is the main energy substrate for developing germ cells and plays a vital role in spermatogenesis. MicroRNAs (miRNAs) function as posttranscriptional regulators of gene expression in biological processes. We have previously shown that hyperthermia (43°C, 30 min) promotes lactate secretion by inhibiting phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK) in cultured immature boar SCs. However, it is unclear whether miRNAs are involved in AMPK‐modulated glycolysis in SCs. In the present study, we identified 349 miRNAs (227 upregulated and 122 downregulated) in hyperthermia‐treated boar SCs by next‐generation high‐throughput RNA sequencing. MiR‐8‐3p, which was found to be a novel upregulated miRNA in hyperthermia‐treated SCs, suppressed the expression of AMPK upstream genes (protein phosphatase 2 subunit B, PPP2R5B), and further downregulated the expression of p‐AMPK. The miR‐8‐3p mimic upregulated expression of glucose transporter 3, lactate dehydrogenase A and monocarboxylate transporter 1, and increased lactic acid dehydrogenase activity, lactate secretion, and ATP depletion in SCs; the miR‐8‐3p inhibitor had the opposite effects on these parameters. Our findings indicate that miR‐8‐3p acts as a novel regulator of AMPK‐modulated lactate secretion by targeting PPP2R5B in hyperthermic boar SCs.
An Integrated Pest Management Tactic for Quagga Mussels: Site-Specific Application of Fish Biological Control Agents
Authors: Culver Carolynn S. , Ginther Samuel C. , Daft Daniel , Johnson Leigh T. , Brooks Andrew J.
Published: September 2019

The quagga mussel Dreissena bugensis is a harmful aquatic pest that invaded the southwestern USA in 2007. Challenges with managing this pest have been encountered because the invaded systems are primarily open-water sources used for human consumption and/or are connected to freshwater habitats containing threatened and endangered species. Existing chemical and physical control methods are undesirable, and the use of some methods is restricted or prohibited because they pose risks to humans and ecosystems more broadly. To address this problem, we investigated the efficacy of using resident fishes as biocontrol agents for managing different life stages of quagga mussels on different spatial scales in a site-specific manner. We conducted field experiments to test whether planktivorous Bluegill Lepomis macrochirus reduced mussel infestations on substrates of varying orientations in small and large pens through predation on larval mussels. We also performed an experiment to evaluate whether carnivorous Redear Sunfish L. microlophus reduced mussel infestations established on substrates of varying orientations in small pens through predation on juvenile and adult mussels. Bluegill significantly reduced mussel infestations on all substrates in the pens through predation on larvae and small juvenile mussels. Redear Sunfish reduced existing juvenile and adult mussel populations in some cases, with consumption varying among individuals and substrate orientations. Our results indicate that fishes, specifically Bluegill, may represent effective site-specific biocontrol agents for quagga mussels, reducing impacts on targeted infrastructure (e.g., water towers, docks, and pipes) and habitats having different surface orientations by controlling more than one life stage of the pest. Development of an integrated pest management strategy that considers application of this tactic in combination with others would undoubtedly improve the management of quagga mussels—and potentially that of congeneric zebra mussels D. polymorpha—within lake and reservoir ecosystems.
Elementary school teachers’ preferences for school‐based interventions for students with emotional and behavioral problems
Authors: Egan Theresa E. , Wymbs Frances A. , Owens Julie Sarno , Evans Steven W. , Hustus Chelsea , Allan Darcey M.
Published: September 2019

Teachers’ adoption and implementation of evidence‐based programs is often limited. Program characteristics may be important facilitators or barriers of use, yet little is known about which attributes influence teacher decisions. Using a discrete choice experiment with a sample of general education elementary teachers (N = 230), we examined (a) preference for attributes of school‐based interventions, (b) relative preference for three intervention packages with experimentally manipulated characteristics, and (c) teacher characteristics related to the above preference profiles. Intervention outcomes were the most important characteristics in teachers’ intervention decisions. Most teachers’ responses suggested preference for a social and emotional learning program (57.9%) or school‐based consultation for behavioral interventions (35.8%); a small group of teachers preferred a general support intervention (5.8%). Teachers preferring the general support intervention reported greater mental health symptoms, lower mental health literacy and lower confidence in program effectiveness than peers preferring other interventions. Implications for intervention development and future directions are discussed.
Lignin, a biomass crosslinker, in a shape memory polycaprolactone network
Authors: Liu Hailing , Mohsin Nuverah , Kim Sundol , Chung Hoyong
Published: September 2019

This work reports a new direction of natural lignin valorization, which utilizes lignin to produce crosslinked polycaprolactone (PCL) via a straightforward synthesis. Lignin's hydroxyl groups of its multibranched phenolic structure allow lignin to serve as crosslinkers, whereas the aromatic groups serve as hard segments. The modified natural lignin containing alkene terminals is crosslinked with a thiol‐terminal PCL via Ru‐catalyzed photoredox thiol‐ene reaction. The high rate of gel contents measured for all crosslinked polymers, with the least being 84% of gel content, indicates efficient crosslinking. The prepared flat rectangular shape lignin‐crosslinked PCL sample demonstrates rapid thermal responsive shape memory behavior at 10 °C and 80 °C showing interconversion between a permanent and temporary shape. The melting temperature of the lignin‐crosslinked PCL is tunable by varying the percent weight of lignin. The 11, 21, and 30 wt % lignin demonstrated Tm of 42 °C, 35 °C, and 26 °C, respectively. The role of lignin as a crosslinker presented in this work suggests that lignin can serve as an efficient biomass‐based functional additive to polymers. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2121–2130
Effect of P21‐activated kinase 1 (PAK‐1) inhibition on cancer cell growth, migration, and invasion
Authors: Najahi‐Missaoui Wided , Quach Nhat D. , Jenkins Amber , Dabke Isha , Somanath Payaningal R. , Cummings Brian S.
Published: September 2019

P21‐activated kinase‐1 (PAK‐1) is a serine/threonine kinase involved in multiple signaling pathways that mediate cellular functions such as cytoskeletal motility, cell proliferation, and survival. PAK‐1 expression is altered in various cancers, including prostate and breast. Our recent studies showed that prostate cancer cells expressing higher levels of PAK‐1 were resistant to the cytotoxic effects of the PAK‐1 inhibitor, inhibitor targeting PAK‐1 activation‐3 (IPA‐3), compared to those with lower expression. This study expanded these findings to other cancers (breast and melanoma) by testing the hypothesis that genetic and pharmacological inhibition of PAK‐1 alters cell growth, migration, and invasion in prostate, breast, and skin cancer cell lines. We also tested the specificity of IPA‐3 for PAK‐1 and the hypothesis that gene silencing of PAK‐1 altered the efficacy of sterically stabilized liposomes (SSL) containing IPA‐3 (SSL‐IPA‐3). PAK‐1 expression was identified in four different breast cancer cell lines, and in a melanoma cell line. The expression of PAK‐1 correlated to the IC50 of IPA‐3 as measured by MTT staining. PAK‐1 inhibition using shRNA correlated with decreased cell migration and invasion in prostate cancer DU‐145 and breast cancer MCF‐7 cells. Decreased migration and invasion also correlated to decreased expression of E‐cadherin and alterations in C‐X‐C Chemokine Receptor type 4 and Homing Cell Adhesion Molecule expression. PAK‐1 inhibition increased the cytotoxicity of IPA‐3, and the cytotoxicity of SSL‐IPA‐3 to levels comparable to that of free drug. These data demonstrate that both pharmacological and molecular inhibition of PAK‐1 decreased growth in prostate, breast, and melanoma cancer cell lines, and increased the toxicity of IPA‐3 and its liposomal formulation. These data also show the specificity of IPA‐3 for PAK‐1, are some of the first data suggesting that IPA‐3 is a therapeutic treatment for breast cancer and melanoma, and demonstrate the efficacy of liposome‐encapsulated IPA‐3 in breast cancer cells.
Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70
Authors: Russo Alessandra , Cardile Venera , Avola Rosanna , Graziano Adriana , Montenegro Iván , Said Bastian , Madrid Alejandro
Published: September 2019

Isocordin 1 and a series of 4‐oxyalkyl‐isocordoin analogues 2–8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively. These analogues, 4, 5, and 6, also induced an apoptotic response at 12.5‐ and 25‐μM concentrations. They inhibited the expression of antiapoptotic proteins Bcl‐2 and Hsp70, a critical factor that promotes tumour cell survival. In contrast, Bax and caspase‐9 expression, and caspase‐3 enzyme resulted activated. These results were correlated to a DNA fragmentation typical of apoptosis and an increase of intracellular reactive oxygen species (ROS) levels. Alternatively, at higher concentration (50 μM), when the capacity of the cells to sustain Hsp70 synthesis is reduced, our results seem to indicate that necrosis was induced by a further increase in ROS production. Therefore, the central finding in the present study is that these molecules downregulates Hsp70 expression. Altogether, these results suggest that 4‐oxyalkyl‐isocordoin analogues 4, 5, and 6 deserve to be deeply investigated for a possible application as Hsp70 inhibitor in the management of melanoma.
High performance and safe flight of full‐scale helicopters from takeoff to landing with an ensemble of planners
Authors: Choudhury Sanjiban , Dugar Vishal , Maeta Silvio , MacAllister Brian , Arora Sankalp , Althoff Daniel , Scherer Sebastian
Published: September 2019

Autonomous flight of unmanned full‐size rotor‐craft has the potential to enable many new applications. However, the dynamics of these aircraft, prevailing wind conditions, the need to operate over a variety of speeds and stringent safety requirements make it difficult to generate safe plans for these systems. Prior work has shown results for only parts of the problem. Here we present the first comprehensive approach to planning safe trajectories for autonomous helicopters from takeoff to landing. Our approach is based on two key insights. First, we compose an approximate solution by cascading various modules that can efficiently solve different relaxations of the planning problem. Our framework invokes a long‐term route optimizer, which feeds a receding‐horizon planner which in turn feeds a high‐fidelity safety executive. Secondly, to deal with the diverse planning scenarios that may arise, we hedge our bets with an ensemble of planners. We use a data‐driven approach that maps a planning context to a diverse list of planning algorithms that maximize the likelihood of success. Our approach was extensively evaluated in simulation and in real‐world flight tests on three different helicopter systems for duration of more than 109 autonomous hours and 590 pilot‐in‐the‐loop hours. We provide an in‐depth analysis and discuss the various tradeoffs of decoupling the problem, using approximations and leveraging statistical techniques. We summarize the insights with the hope that it generalizes to other platforms and applications.
Energy poverty: A macrolevel perspective
Authors: Primc Kaja , Slabe‐Erker Renata , Majcen Boris
Published: September 2019

The growing unpredictability of energy poverty requires a different policy approach. Yet studies focus on the microlevel drivers, leaving the roles of macroeconomic perspective and climate understudied. Studying the latter is important though, because well‐planned policies can fail if the causes of energy poverty and their interrelations remain unclear. This research submits data collected from 28 EU member states to fuzzy‐set qualitative comparative analysis and offers new evidence concerning the relationship between energy poverty and macrolevel drivers. Our results suggest that states with a mild climate, low or average GDP, and high energy prices have high levels of energy poverty. Likewise, states located in colder climates with low or average GDP, the energy‐policy focus, and nonhigh energy prices tend to be energy poor. Moreover, the results show that two configurations lead to absence of energy poverty. To develop and implement effective policies, it is vital to understand these configurations.
Synergistic Control of Structural Disorder and Surface Bonding Nature to Optimize the Functionality of Manganese Oxide as an Electrocatalyst and a Cathode for Li–O2 Batteries
Authors: Jin Xiaoyan , Park Mihui , Shin Seung‐Jae , Jo Yujin , Kim Min Gyu , Kim Hyungjun , Kang Yong‐Mook , Hwang Seong‐Ju
Published: September 2019

An efficient way to improve the electrocatalyst and Li–O2 battery performances of metal oxide is developed by an exquisite synergistic control over structural disorder and surface bonding nature. The effects of amorphous nature and surface chemical environment on the functionalities of metal oxide are systematically investigated with well‐crystalline and amorphous MnO2 nanocrystals with/without surface anchoring of highly oxidized iodate clusters. The amorphous MnO2 nanocrystal containing anchored iodate clusters shows much better performance as an oxygen evolution electrocatalyst and cathode catalyst for Li–O2 batteries than both iodate‐free amorphous and well‐crystalline homologues, underscoring the remarkable advantage of simultaneous enhancement of structural disorder and surface electron density. In situ X‐ray absorption spectroscopic analysis demonstrates the promoted formation of double (MnO) bond, a critical step of oxygen evolution reaction, upon amorphization caused by the poor orbital overlap inside highly disordered crystallites. The beneficial effects of iodate anchoring and amorphization on electrocatalyst functionality are attributable to the alteration of surface bonding character, stabilization of Jahn–Teller active Mn3+ species, and enhanced charge transfer of interfaces. The present study underscores that fine‐tuning of structural disorder and surface bonding nature provides an effective methodology to explore efficient metal oxide‐based electrocatalysts.
Early Lithium Plating Behavior in Confined Nanospace of 3D Lithiophilic Carbon Matrix for Stable Solid‐State Lithium Metal Batteries
Authors: Huang Shaobo , Yang Hao , Hu Jiangkui , Liu Yongchang , Wang Kexin , Peng Hailin , Zhang Hao , Fan Li‐Zhen
Published: September 2019

Considerable efforts are devoted to relieve the critical lithium dendritic and volume change problems in the lithium metal anode. Constructing uniform Li+ distribution and lithium “host” are shown to be the most promising strategies to drive practical lithium metal anode development. Herein, a uniform Li nucleation/growth behavior in a confined nanospace is verified by constructing vertical graphene on a 3D commercial copper mesh. The difference of solid‐electrolyte interphase (SEI) composition and lithium growth behavior in the confined nanospace is further demonstrated by in‐depth X‐ray photoelectron spectrometer (XPS) and line‐scan energy dispersive X‐ray spectroscopic (EDS) methods. As a result, a high Columbic efficiency of 97% beyond 250 cycles at a current density of 2 mA cm−2 and a prolonged lifespan of symmetrical cell (500 cycles at 5 mA cm−2) can be easily achieved. More meaningfully, the solid‐state lithium metal cell paired with the composite lithium anode and LiNi0.5Co0.2Mn0.3O2 (NCM) as the cathode also demonstrate reduced polarization and extended cycle. The present confined nanospace–derived hybrid anode can further promote the development of future all solid‐state lithium metal batteries.
Deciphering the Interface of a High‐Voltage (5 V‐Class) Li‐Ion Battery Containing Additive‐Assisted Sulfolane‐Based Electrolyte
Authors: Lu Di , Xu Gaojie , Hu Zhiwei , Cui Zili , Wang Xiao , Li Jiedong , Huang Lang , Du Xiaofan , Wang Yantao , Ma Jun , Lu Xiaolan , Lin Hong‐Ji , Chen Chien‐Te , Nugroho Agustinus Agung , Tjeng Liu Hao , Cui Guanglei
Published: September 2019

Next generation high energy density lithium‐ion batteries have aroused great interests worldwide. Herein, in a high‐voltage (5 V‐class) LiNi0.5Mn1.5O4/MCMB (graphitic mesocarbon microbeads) battery system using 1 m lithium difluoro(oxalate)borate/sulfolane, tris(trimethylsilyl) phosphite (TMSP) additive is added to significantly improve room/high temperature cycling performances. The unchanged X‐ray diffraction patterns suggest the bulk crystal structure of cycled MCMB anode and LiNi0.5Mn1.5O4 cathode are well preserved. Moreover, soft X‐ray absorption spectroscopy (XAS) taken from bulk sensitive fluorescence‐yield (FY) mode reveals the unchanged bulk electronic structure of cycled LiNi0.5Mn1.5O4 cathode. Therefore, it is concluded that only interface instability contributes to capacity fading of full‐cells. However, electrode/electrolyte interface and corresponding interfacial reaction processes are always “enigmatic.” First, X‐ray photoelectron spectroscopy (XPS) and in situ differential electrochemical mass spectrometry (DEMS) are used to more accurately decipher the TMSP additive action mechanism in MCMB/electrolyte interfacial reaction processes, by identifying the interfacial solid and gas byproducts, respectively. Then, the crucial role of TMSP additive in modifying cathode/electrolyte interface is revealed by XPS and soft XAS taken from surface sensitive total electron yield (TEY) mode. This paper provides valuable perspectives for formulating novel electrolytes, and for more accurately depicting additive action mechanism in “enigmatic” electrode/electrolyte interfacial reaction processes.