bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of S‐1 on survival outcomes in 838 patients with advanced pancreatic cancer: A 7‐year multicenter observational cohort study in Taiwan
Authors: Lai Hsiang‐Lan , Chen Yen‐Yang , Lu Chang‐Hsien , Hung Chia‐Yen , Kuo Yung‐Chia , Chen Jen‐Shi , Hsu Hung‐Chih , Chen Ping‐Tsung , Chang Pei‐Hung , Hung Yu‐Shin , Chou Wen‐Chi
Published: April 2019

Objective

Studies have rarely explored the efficacy of S‐1 in treating advanced pancreatic cancer outside Japan. This study compared the survival outcomes of patients with advanced pancreatic cancer treated with S‐1 with the survival outcomes of those without S‐1 treatment before and after S‐1 reimbursement was introduced in Taiwan in June of 2014.

Method

We retrospectively analyzed 838 patients with locally advanced or metastatic pancreatic cancer who underwent palliative chemotherapy from 2010 to 2016 at 4 institutes in Taiwan. For survival analysis, patients were categorized into two groups according to whether they received S‐1 treatment as palliative chemotherapy after diagnosis: (a) S‐1‐treated (n = 335) and (b) non‐S‐1‐treated (n = 503) groups.

Results

The median overall survival was longer in the S‐1‐treated group than in the non‐S‐1‐treated group (10.7 vs 6.0 mo, P < 0.001). Subgroup survival analyses showed that the S‐1‐treated group had more favorable outcomes than the non‐S‐1‐treated group in terms of stage III (19.6 vs 10.1 mo, P < 0.001) and stage IV (8.5 vs 5.3 mo, P < 0.001) disease. The disease control rates were 43.6% and 32.8% (P < 0.001) in patients treated with and without S‐1 in the first‐line setting, respectively. In multivariate analysis, exposure to S‐1 treatment was an independent prognosticator for survival.

Conclusion

Our results support the clinical use of S‐1 as the treatment of choice for patients with locally advanced or metastatic pancreatic cancer, particularly in resource‐limited situations.
Solubilizing Trityl‐Type Tag To Synthesize Asx/Glx‐Containing Peptides
Authors: Tsuda Shugo , Masuda Shun , Yoshiya Taku
Published: April 2019

A novel solubilizing tag system for Asp/Asn/Glu/Gln‐containing peptides is described. In this method, an Asp/Glu[Dbz‐Cys‐NH2]‐containing peptide (Dbz: 3,4‐diaminobenzoic acid) is first synthesized through fluorenylmethyloxycarbonyl (Fmoc) solid‐phase peptide synthesis. The solubilizing moiety containing an oligo‐Lys group is then attached to the peptide in hexafluoroisopropanol through a trityl anchor to afford a hydrophilic tagged peptide. To detach the solubilizing tag, the Dbz moiety of the tagged peptide is activated with NaNO2, and the Asp/Asn/Glu/Gln‐containing peptide is obtained through hydrolysis or ammonolysis. This synthetic approach proved to be compatible with native chemical ligation, and amyloid β‐protein 1–42 was successfully synthesized by the solubilizing‐tag‐aided native chemical ligation–desulfurization method.
Modular Microfluidic Paper‐Based Devices for Multi‐Modal Cascade Catalysis
Authors: Andersen Nalin I. , Artyushkova Kateryna , Matanović Ivana , Seow Chavez Madelaine , Hickey David P. , Abdelloui Sofiene , Minteer Shelley D. , Atanassov Plamen
Published: April 2019

The integration of different catalytic modalities to control precursors, intermediates, and products requires a method for understanding these complex systems. A modular analytical platform is presented here that allows for catalytic conversion reactions and the delivery of catalytically transformed analytes to subsequent surface enhanced Raman scattering (SERS) detection zones. The paper‐based platforms are compatible for studying biochemical conversion reactions and electrochemical transformations. The full oxidation of glycerol to carbon dioxide follows a cascade reaction of 9 steps, chosen to illustrate the use of a molecular, biological, and metallic catalyst. Designated catalytic reaction zones and SERS detection zones integrated into the pores of paper at specific locations allows all of the reactions to take place within the pores of the analytical platform. Multiple chemical reactions were performed in sequence and the SERS spectra of the resulting intermediates and products were measured.
Nitrogen‐Doped Carbon Nanosheets Encapsulating Cobalt Nanoparticle Hybrids as High‐Performance Bifunctional Electrocatalysts
Authors: Zheng Dandan , Ci Suqin , Cai Pingwei , Wang Genxiang , Wen Zhenhai
Published: April 2019

Developing efficient and low‐cost catalysts with excellent catalytic activities for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is of significance for large‐scale commercial applications in rechargeable Zn−air batteries and fuel cells. Herein, we develop a simple, mild and efficient method to synthesize a hybrid of N‐doped carbon nanosheets encapsulating cobalt nanoparticles (Co@NCNSs), which shows favorable catalytic properties toward both ORR and OER with high activity and good stability. The optimized hybrids (Co@NCNSs‐900) exhibit an onset potential of 0.95 V vs. reversible hydrogen electrode (RHE) and a half‐wave potential of 0.85 V vs. RHE for the ORR, and an onset potential of 1.51 V vs. RHE, a potential of 1.59 V vs. RHE at 10 mA cm−2 for the OER, as well as an oxygen electrode activity parameter (ΔE) of 0.802 V in alkaline electrolyte. Moreover, the Zn−air battery with the Co@NCNSs‐900 as the cathode catalyst outperforms that with the commercial Pt/C as cathode catalyst in terms of the maximum power density and stability, showing great prospects in renewable energy applications.
Population Modeling Highlights Drug Disposition Differences Between Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate in the Blood and Semen
Authors: Greene Stephen A. , Chen Jingxian , Prince Heather M. A. , Sykes Craig , Schauer Amanda P. , Blake Kimberly , Nelson Julie A. E. , Gay Cynthia L. , Cohen Myron S. , Dumond Julie B.
Published: April 2019

Understanding antiretroviral disposition in the male genital tract, a distinct viral compartment, can provide insight for the eradication of HIV. Population pharmacokinetic modeling was conducted to investigate the disposition of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine and their metabolites in blood and semen. Blood plasma and seminal plasma (SP) concentrations of tenofovir and emtricitabine were measured, as were tenofovir‐diphosphate and emtricitabine‐triphosphate concentrations in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells. Sequential compartmental modeling described drug disposition in blood and semen. Our modeling suggests slower elimination of apparent tenofovir‐diphosphate PBMC and faster elimination of tenofovir SP after administration of TAF compared with TDF, likely reflecting flip‐flop kinetics. Additionally, TAF metabolism to tenofovir appeared slower in semen compared with blood; however, SP elimination of TAF‐derived tenofovir appeared faster than its blood plasma elimination. These findings provide valuable insight for further mechanistic study of cellular entry and drug metabolism in the male genital tract.
Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila
Authors: Politano Stephen F. , Salemme Ryan R. , Ashley James , López‐Rivera Javier A. , Bakula Toren A. , Puhalla Kathryn A. , Quinn John P. , Juszczak Madison J. , Phillip Lauren K. , Carrillo Robert A. , Vanderzalm Pamela J.
Published: April 2019

The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine‐threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.
Genetic diversity and genetic structure of Decalobanthus boisianus in Hainan Island, China
Authors: Jiang Huan , Long Wenxing , Zhang Hui , Mi Chengneng , Zhou Tao , Chen Zongzhu
Published: April 2019

Decalobanthus boisianus is a native plant of Hainan Island, China, which has caused considerable damage to tropical forest ecosystems in recent decades. Understanding the genetic diversity and structure of this species can facilitate uncovering the molecular mechanism of its invasive ability. Here, we collected 77 individuals of D. boisianus spanning 8 distribution areas with a gradient of human disturbance intensity (i.e., low, moderate, and high disturbance intensity groups) to assess patterns of genetic diversity and structure using inter simple sequence repeat (ISSR) markers. We found that a total of 220 loci were scored with 13 primers using ISSR methods, and that 198 loci were polymorphic. The genetic diversity of D. boisianus among these eight forests decreased with increasing human disturbance intensity. Over 70% of the total genetic variation was present within populations, while less than 30% of variation was found among populations. There was a high gene flow (1.27) among them due to a lack of effective geographic barriers. The mean Nei's genetic distance of D. boisianus populations was found to be relatively small (i.e., 0.07), and the average genetic similarity of the eight populations was high (i.e., 0.93). Our findings indicate that the genetic diversity of D. boisianus correlated to human disturbance density, and that D. boisianus populations in Hainan Island have frequent gene exchange. We suggest that reduce deforestation to decrease human disturbance may be a good way to prevent the invasion of D. boisianus.
Janzen‐Connell effects in a forest BEF experiment: Strong distance‐dependent seedling establishment of multiple species
Authors: Germany Markus S. , Bruelheide Helge , Erfmeier Alexandra
Published: April 2019

The Janzen‐Connell (JC) hypothesis is a major ecological explanation for high species richness, in particular in tropical forest ecosystems. Central components of the JC hypothesis are noncompetitive effects of distance and density dependence, two drivers that contribute independently to species coexistence, but are ultimately linked in the field. However, although numerous studies provide evidence for either distance‐ or density‐dependent effects based on observational data, experimental testing of simultaneous and interactive effects of distance and density has rarely been conducted, especially in a comprehensive multispecies approach. Here, we make use of the forest Biodiversity‐Ecosystem Functioning project (BEF) –China to estimate distance‐ and density‐dependent effects in a reciprocal tree seedling transplant experiment of 11 tree species. We deployed 13,490 juveniles of all 11 species in their own (home) and in all foreign monocultures (away), as well as at three different levels of planting density, thereby testing for distance and density effects, respectively. In addition, to quantify the amount to which density effects were brought about by potential additional effects of intraspecific competition, we set up a common garden experiment with different levels of planting density, where an additional “shadow” treatment controlled for effects of canopy shading. Although the “away” and “high‐density” treatments significantly impaired the performance and productivity of seedlings, leaf damage and survival was exclusively affected by either the home/away or the density treatment, respectively. Negative density‐dependent effects on leaf damage were less pronounced in the “home” treatment, showing that the effects were not additive. In addition, results obtained in the Common Garden Experiment showed that negative effects of high density may be also brought about by intraspecific competition as an alternative density‐responsive mechanism and less by true JC effects. Overall, our results provide strong support on a multispecies basis for the influence of host‐specific effects already operating in early stages of a forest plantation. However, they also emphasize the need to account appropriately for potential additional density‐responsive mechanisms such as intraspecific competition or microenvironmental conditions when addressing the role of JC effects for species coexistence.
Divergent Synthesis of Multisubstituted Unsymmetric Pyrroles and Pyrrolin‐4‐ones from Enamino Esters via Copper‐Catalyzed Aerobic Dimerization
Authors: Chen Zhi‐Wei , Zheng Lei , Liu Jin
Published: April 2019

A facile synthetic method to access multisubstituted unsymmetric pyrrole and pyrrolin‐4‐one derivatives is disclosed. In the presence of Cu(OAc)2 and KOAc, substituted pyrrole derivatives are produced in good yields (up to 93 %) through oxidative cyclization of enamino esters. Meanwhile, using CuCl2 and TFA (trifluoroacetic acid), pyrrolin‐4‐one derivatives are obtained in excellent yields (up to 94 %) through 1,2‐aryl migration. A wide range of functional groups have been tolerated, and a reliable method for the synthesis of valuable multisubstituted pyrroles and pyrrolin‐4‐ones has been developed.
Synthesis of Sulfur‐Hybridized Pyracylene and the Unexpected Phenyl Shift Mediated Rearrangement of Scholl Reaction
Authors: Liu Shuli , Huang Chengting , Zhang Jing , Tian Siyu , Li Chang , Fu Nina , Wang Lianhui , Zhao Baomin , Huang Wei
Published: April 2019

We present herein a strategy towards the straightforward synthesis of a novel sulfur‐hybridized pyracylene, tetraceno[5,6‐bc:11,12‐b'c']dithiophene (TDT) derivatives, via 2‐fold FeCl3‐mediated Scholl reaction. Surprisingly, the substituents on the precursors will guide the synthetic route, when the substituents were bromo‐ or phenyl‐, quantitatively debromination or phenyl ring shift mediated rearrangement were observed respectively, the rearrangement products were identified by the HR‐Mass and 2D NMR analyses. Additionally, a retrosynthetic method was adopted to confirm the unexpected reaction results in rearrangement of Scholl reaction.
Tuning the Catalytic Performance of Novel Composites Based on ZIF‐8 and Nafen through Dimensional and Concentration Effects in the Synthesis of Propylene Glycol Methyl Ether
Authors: Timofeeva Maria N. , Paukshtis Evgeniy A. , Panchenko Valentina N. , Shefer Kristina I. , Isaeva Vera I. , Kustov Leonid M. , Gerasimov Evgeniy Yu.
Published: April 2019

Zeolitic imidazolate framework (ZIF‐8, Zn(2‐meIm)2) and composites based on ZIF‐8 and alumina nanofibers (NafenTM), i.e. ZIF‐8/Nafen, were demonstrated to be efficient heterogeneous catalysts for the reaction of methanol with propylene oxide to produce propylene glycol methyl ether (PGME), which is a member of the family of glycol ether solvents used for a wide variety of consumer products and industrial applications. Both the reaction rate and the selectivity toward PGME were found to decrease with increasing crystal size of the ZIF‐8 material, which was related to the change in the number of basic sites and their accessibility. The investigation of ZIF‐8/Nafen composites revealed the dependence of their catalytic performance on the amount of the ZIF‐8 component. In particular, the activity was affected by the crystal size of the ZIF‐8 material and the nature of acid‐base sites in its framework.
Sorafenib Induces Pyroptosis in Macrophages and Triggers Natural Killer Cell–Mediated Cytotoxicity Against Hepatocellular Carcinoma
Authors: Hage Carina , Hoves Sabine , Strauss Léanne , Bissinger Stefan , Prinz Ylva , Pöschinger Thomas , Kiessling Fabian , Ries Carola H.
Published: April 2019

Antiangiogenic and cytotoxic effects are considered the principal mechanisms of action of sorafenib, a multitarget kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC). We report that sorafenib also acts through direct immune modulation, indispensable for its antitumor activity. In vivo cell depletion experiments in two orthotopic HCC mouse models as well as in vitro analysis identified macrophages (MΦ) as the key mediators of the antitumoral effect and demonstrate a strong interdependency of MΦ and natural killer (NK) cells for efficient tumor cell killing. Caspase 1 analysis in sorafenib‐treated MΦ revealed an induction of pyroptosis. As a result, cytotoxic NK cells become activated when cocultured with sorafenib‐treated MΦ, leading to tumor cell death. In addition, sorafenib was found to down‐regulate major histocompatibility complex class I expression of tumor cells, which may reduce the tumor responsiveness to immune checkpoint therapies and favor NK‐cell response. In vivo cytokine blocking revealed that sorafenib efficacy is abrogated after inhibition of interleukins 1B and 18. Conclusion: We report an immunomodulatory mechanism of sorafenib involving MΦ pyroptosis and unleashing of an NK‐cell response that sets it apart from other spectrum kinase inhibitors as a promising immunotherapy combination partner for the treatment of HCC.
External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation
Authors: Levitsky Josh , Asrani Sumeet K. , Abecassis Michael , Ruiz Richard , Jennings Linda W. , Klintmalm Goran
Published: April 2019

In patients with end‐stage liver disease, the ability to predict recovery of renal function following liver transplantation (LT) remains elusive. However, several important clinical decisions depend on whether renal dysfunction is recoverable after LT. We used a cohort of patients undergoing LT to independently validate a published pre‐LT model predictive of post‐transplant renal recovery (Renal Recovery Assessment at Liver Transplant [REVERSE]: high osteopontin [OPN] and tissue inhibitor of metalloproteinases‐1 [TIMP‐1] levels, age < 57, no diabetes). Serum samples pre‐LT and 4‐12 weeks post‐LT (n = 117) were analyzed for kidney injury proteins from three groups of recipients: (1) estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 prior to and after LT (irreversible acute kidney injury [AKI]), (2) eGFR < 30 mL/minute/1.73 m2 prior to LT and >50 mL/minute/1.73 m2 after LT (reversible AKI [rAKI]) (3) eGFR > 50 mL/minute/1.73 m2 prior to and after LT (no AKI). In patients with elevated pre‐LT serum levels of OPN and TIMP‐1, recovery of renal function correlated with decreases in the level of both proteins. At 4 weeks post‐LT (n = 77 subset), the largest decline in OPN and TIMP‐1 was seen in the rAKI group. Validation of the REVERSE model in this independent data set had high area under the curve (0.78) in predicting full post‐LT renal recovery (sensitivity 0.86, specificity 0.6, positive predictive value 0.81, negative predictive value 0.69). Our eGFR findings were confirmed using measured GFR. Conclusion: The REVERSE model, derived from an initial training set combining plasma biomarkers and clinical characteristics, demonstrated excellent external validation performance characteristics in an independent patient cohort using serum samples. Among patients with kidney injury pre‐LT, the predictive ability of this model may prove beneficial in clinical decision‐making both prior to and following transplantation.
TRPC channels are not required for graded persistent activity in entorhinal cortex neurons
Authors: Egorov Alexei V. , Schumacher Dagmar , Medert Rebekka , Birnbaumer Lutz , Freichel Marc , Draguhn Andreas
Published: April 2019

Adaptive behavior requires the transient storage of information beyond the physical presence of external stimuli. This short‐lasting form of memory involves sustained (“persistent”) neuronal firing which may be generated by cell‐autonomous biophysical properties of neurons or/and neural circuit dynamics. A number of studies from brain slices reports intrinsically generated persistent firing in cortical excitatory neurons following suprathreshold depolarization by intracellular current injection. In layer V (LV) neurons of the medial entorhinal cortex (mEC) persistent firing depends on the activation of cholinergic muscarinic receptors and is mediated by a calcium‐activated nonselective cation current (ICAN). The molecular identity of this conductance remains, however, unknown. Recently, it has been suggested that the underlying ion channels belong to the canonical transient receptor potential (TRPC) channel family and include heterotetramers of TRPC1/5, TRPC1/4, and/or TRPC1/4/5 channels. While this suggestion was based on pharmacological experiments and on effects of TRP‐interacting peptides, an unambiguous proof based on TRPC channel‐depleted animals is pending. Here, we used two different lines of TRPC channel knockout mice, either lacking TRPC1‐, TRPC4‐, and TRPC5‐containing channels or lacking all seven members of the TRPC family. We report unchanged persistent activity in mEC LV neurons in these animals, ruling out that muscarinic‐dependent persistent activity depends on TRPC channels.
Exploring Australian residents cycling engagement – Differences in self‐reported cycling behaviour between urban and rural dwelling Queenslanders
Authors: King Jemma C. , Franklin Richard C. , Devine Sue , Watt Kerrianne , Leggat Peter A.
Published: April 2019

Issue addressed

Cycling participation rates in Australia and Queensland remain low. Rural residents typically do not have distinct cycling infrastructure available for use. Investigating current cycling participation and barriers to cycling engagement will inform future work to promote cycling engagement.

Methods

Data were collected through the inclusion of cycling‐related questions in the 2012 Queensland Social Survey.

Results

The majority of the sample had not cycled in the previous 12 months (66%; n = 831). Significantly more rural residents reported not cycling due to environmental concerns (P < 0.05) and preferring other modes of transport or exercise (P < 0.01). Rural cyclists (31.4%; n = 113) had higher levels of cycling engagement in the previous week (41.6% to 32.6% urban; χ2 = 7.83; n = 420; P < 0.05) but lower cycling durations than urban cyclists (41.6% rural residents cycling for 30+ minutes vs 57.4% urban residents; χ2 = 8.25; n = 418; P < 0.01). Rural cycling engagement was independently associated with being male (OR = 2.34; 95% CI = 1.40‐3.91); sufficient physical activity engagement (OR = 1.86; 95% CI = 1.10‐3.15); and having children at place of residence (1‐2 children: OR = 3.21; 95% CI = 1.88‐5.49; 3+ children: OR = 3.01; 95% CI = 1.17‐7.75).

Conclusions

One‐third of all adults cycled in the previous 12 months irrespective of location; however reasons for not cycling varied by urban/rural location. Results indicate that environmental factors appear to be inhibiting cycling participation in rural areas. Advocating for government commitment for infrastructure development to support safe cycling across Queensland including outside of metropolitan areas is required.

So what?

This research explores self‐reported cycling engagement amongst a sample of urban and rural dwelling Queenslanders. Differences in cycling exposure and reasons for lack of engagement offer insights into what may encourage greater cycling participation.
A multiobjective thermodynamic optimization of a nanoscale Stirling engine operated with Maxwell‐Boltzmann gas
Authors: Shah Priyank , Saliya Pankaj , Raja Bansi , Patel Vivek
Published: April 2019

Recent developments in nanotechnology provided an opportunity to solve many complex problems in the field of energy. Performance investigation of the nanoscale thermal cycles can prove crucial in the development of efficient and less polluting energy system. Due to the influence of boundary phenomenon and quantum degeneracy effects, a nanoscale engine performs according to statistical quantum thermodynamics instead of classical thermodynamics. In this study, a nanoscale Stirling engine operating on an ideal Maxwell‐Boltzmann gas is investigated for multiobjective optimization. Optimization problem of Stirling cycle is formed considering the thermal efficiency, ecological coefficient of performance and entropy generation. An application example of a nanoscale Stirling engine is presented and solved using Heat Transfer Search algorithm. Maxwell‐Boltzmann gas restricted in a finite domain is studied and the effect of different parameters, such as surface area ratio, volume ratio, and temperature ratio of the domain, is investigated. Sensitivity analysis is carried out to identify the effect of design variables on the performance parameters. Further, influence of the source temperature and the number of particles of working fluid on the objective functions is studied and presented.
Trends in frequency and outcome of high‐risk breast lesions at core needle biopsy in women recalled at biennial screening mammography, a multiinstitutional study
Authors: Luiten Jacky D. , Korte Bram , Voogd Adri C. , Vreuls Willem , Luiten Ernest J.T. , Strobbe Luc J. , Rutten Matthieu J.C.M. , Plaisier Menno L. , Lohle Paul N. , Hooijen Marianne J.H. , Tjan‐Heijnen Vivianne C.G. , Duijm Lucien E.M.
Published: April 2019

Between January 1, 2011, and December 31, 2016, we studied the incidence, management and outcome of high‐risk breast lesions in a consecutive series of 376,519 screens of women who received biennial screening mammography. During the 6‐year period covered by the study, the proportion of women who underwent core needle biopsy (CNB) after recall remained fairly stable, ranging from 39.2% to 48.1% (mean: 44.2%, 5,212/11,783), whereas the proportion of high‐risk lesions at CNB (i.e., flat epithelial atypia, atypical ductal hyperplasia, lobular carcinoma in situ and papillary lesions) gradually increased from 3.2% (25/775) in 2011 to 9.5% (86/901) in 2016 (p < 0.001). The mean proportion of high‐risk lesions at CNB that were subsequently treated with diagnostic surgical excision was 51.4% (169/329) and varied between 41.0% and 64.3% through the years, but the excision rate for high‐risk lesions per 1,000 screens and per 100 recalls increased from 0.25 (2011) to 0.70 (2016; p < 0.001) and from 0.81 (2011) to 2.50 (2016; p < 0.001), respectively. The proportion of all diagnostic surgical excisions showing in situ or invasive breast cancer was 29.0% (49/169) and varied from 22.2% (8/36) in 2014 to 38.5% (5/13) in 2011. In conclusion, the proportion of high‐risk lesions at CNB tripled in a 6‐year period, with a concomitant increased excision rate for these lesions. As the proportion of surgical excisions showing in situ or invasive breast cancer did not increase, a rising number of screened women underwent invasive surgical excision with benign outcome.
Astragaloside attenuates lipopolysaccharide‐induced cell apoptosis in human gingiva cells via MAPK signaling pathway
Authors: Shen Xionghu , Sun Honghua , Cui Hai , Jin Yongmin , Jin Wenbo , Cui Xian , Guo Jie
Published: April 2019

Subjects

The aim of this study was to research the antiapoptotic effect of astragaloside, the principal component of Astragalus membranaceus (Fisch) Bge, in human gingiva cells induced by lipopolysaccharide (LPS).

Methods

According to the treatment, human gingiva cells were divided into five groups, including (1) control group without drug treatment; (2) imitating group, treated with LPS (10 μg·mL−1) alone; (3) low group, treated with LPS and 50 μmol·L
−1 astragaloside; (4) medium group, treated with LPS and 100 μmol·L
−1 astragaloside; and (5) high group, treated with LPS and 150 μmol·L
−1 astragaloside. Cell proliferation and apoptosis were investigated using MTT assay and flow cytometry, respectively. Apoptosis and mitogen‐activated protein kinase associated proteins were determined using Western blot analysis.

Results

LPS significantly suppressed the proliferation of human gingiva cells, but astragaloside obviously attenuated this change with a dose‐dependent manner. LPS significantly promoted the apoptosis of human gingiva cells, but astragaloside treatments significantly attenuated this change with a dose‐dependent manner. In addition, LPS could significant upregulated the expression of P‐p38, P‐JNK, Bax, and caspase‐3.

Conclusion

Astragaloside preformed a promising antiapoptotic role in apoptosis of human gingiva cells induced by LPS. This finding might provide us with a novel therapeutic method in tooth protection.
miR‐143 inhibits proliferation and metastasis of nasopharyngeal carcinoma cells via targeting FMNL1 based on clinical and radiologic findings
Authors: Cui Fusheng , Ji Yuqing , Wang Man , Gao Fengxiao , Li Yongcai , Li Xueshen
Published: April 2019

Mounting evidence has reported that microRNA‐143 (miR‐143) is involved in the development of multiple cancers. To investigate the underlying mechanisms of miR‐143 regulating proliferation and metastasis in nasopharyngeal carcinoma (NPC) cells, we evaluated the levels of miR‐143 and formin‐like protein 1 (FMNL1) in NPC tissues. The results of qRT‐PCR and Western blot analysis showed that the expression of miR‐143 was decreased, while FMNL1 was increased in NPC tissues. The expression of miR‐143 was significantly elevated in NPC cells compared with that of human nasopharyngeal epithelial cells. The results of MiRcode prediction, dual‐luciferase reporter, and Western blot analysis assays indicated that miR‐143 negatively regulated the expression of FMNL1 (r2 = 0.4365P = 0.0001). Overexperssion of miR‐143 or FMNL1 knockdown inhibited cell proliferation, migration, and invasion in NPC cells (P < 0.05). Ectopic expression of FMNL1 undermined the inhibition effect of miR‐143 on proliferation, migration, and invasion in NPC cells. The findings of this study revealed that miR‐143 functioned as a tumor suppressor and inhibited the NPC progression by targeting FMNL1.
Retracted: Nimotuzuma restrains proliferation and induces apoptosis in human osteosarcoma cells by regulation of EGFR/PI3K/AKT signal pathway
Authors: Liu Meihan , Zhang Jingzhe , Dong Hang , Wang Wenjun
Published: April 2019

Osteosarcoma (OS) is a conversant malignant bone tumor, commonly occurs in children and adolescents. Nimotuzuma is an epidermal growth factor receptor (EGRF) monoclonal antibody agent, which has been exploited in varied solid tumors. Nevertheless, the functions of Nimotuzuma in OS remain blurry. We attempted to disclose the impacts of Nimotuzuma on OS cells proliferation and apoptosis. OS MG‐63 and U2OS cells were stimulated with the disparate doses of Nimotuzuma. Then, cell viability, cell cycle, and apoptosis were appraised through executing CCK‐8 and flow cytometry assays. Moreover, the change of mitochondrial membrane potential (ΔΨm) was estimated via JC‐1 fluorescent probe to further probe the impacts of Nimotuzuma on cell apoptosis. The proteins of cell apoptosis, cell cycle, and EGFR/PI3K/AKT were appraised via western blot. Eventually, Nimotuzuma together EGRF or PI3K inhibitor (LY294002) were utilized to dispose MG‐63 to further uncover the latent mechanism. We found that Nimotuzuma remarkably repressed cell viability at a time‐ and dose‐dependent manners in MG‐63 and U2OS cells. The percentage of the S phase cells was evidently reduced by Nimotuzuma through regulating P21, Cyclin E1, and Cyclin D1. In addition, Nimotuzuma obviously evoked cell apoptosis, meanwhile elevated Bid, Bax, and cleaved‐caspase‐3. Further exploration showed that Nimotuzuma decreased ΔΨm in a dose‐dependent manner in MG‐63 and U2OS cells. Besides, we discovered the repressive functions of Nimotuzuma in OS cells proliferation and apoptosis via hindering the EGFR/PI3K/AKT pathway. These investigations testified that Nimotuzuma repressed cell growth by restraining the EGFR/PI3K/AKT pathway in OS cells, hinting the antitumor activity of Nimotuzuma in OS.
Creative Potential and Multicultural Experiences: The Mediating Role of Creative Self‐Efficacy
Authors: Puente‐Diaz Rogelio , Toptas Seda Dilan , Cavazos‐Arroyo Judith , Wimschneider Christine , Brem Alexander
Published: April 2019

In two studies, one in Mexico and another one in Germany, we examined the indirect influence of self‐reported multicultural experience on creative potential, through its influence on creative self‐efficacy, and its direct influence on creative personal identity. In both studies, business students from Mexico and Germany completed a battery of questionnaires assessing creative self‐efficacy (with two different operationalizations), creative personal identity, multicultural experiences, and a divergent thinking task designed to generate ideas to solve two different business problems. Structural equation modeling was used to test our hypotheses. Results from both studies found a positive relationship between self‐reported multicultural experiences and creative personal identity. Similarly, multicultural experiences had an indirect, positive relationship with originality scores from a divergent thinking task, through its influence on creative self‐efficacy. Hence, the positive influence of multicultural experience on creative potential, through creative self‐efficacy, was established in two countries and with different operationalizations, trait like versus state like, of creative self‐efficacy. The implications of the results were discussed.
Risks of substance uses, alcohol flush response, Helicobacter pylori infection and upper digestive tract diseases—An endoscopy cross‐sectional study
Authors: Chuang Yun‐Shiuan , Wu Meng‐Chieh , Wang Yao‐Kuang , Chen Yi‐Hsun , Kuo Chao‐Hung , Wu Deng‐Chyang , Wu Ming‐Tsang , Wu I‐Chen
Published: April 2019

This study examines the effects of environmental hazards, including tobacco, alcohol/alcohol flush response, areca nut, and Helicobacter pylori (H pylori) infection on upper digestive diseases. This is a multi‐hospital‐based endoscopy‐survey cross‐sectional study. Subjects were received upper endoscopies in outpatient clinics at four hospitals in Taiwan between 2008 and 2013. Biopsy‐based methods or urea breath test were used confirm the status of H pylori infection. In total, 8135 subjects were analyzed. Higher cumulative amounts of alcohol consumption were at higher risk of Barrett's esophagus and esophageal squamous cell carcinoma (ESCC), higher cumulative amounts of tobacco consumption were at higher risk of peptic ulcer, and higher cumulative amounts of areca nut consumption were at higher risk of duodenitis. Alcohol flush response was significant risk for reflux esophagitis and Barrett's esophagus (adjusted odds ratio [aOR] = 1.18 and 1.32, 95% confidence interval [CI] = 1.07‐1.31 and 1.06‐1.65, respectively). H pylori infection was inversely associated with ESCC risk (aOR = 0.20, 95% CI = 0.10‐0.40). In addition, H pylori infection was consistently and significantly risk factors for gastrointestinal diseases, including peptic ulcer, gastric adenocarcinoma, and duodenitis (aOR = 5.51, 1.84, and 2.10, 95% CI = 4.85‐6.26, 1.03‐3.26, and 1.71‐2.56, respectively). Besides the cumulative risk of alcohol, tobacco, and areca nut for Barrett's esophagus, ESCC, and peptic ulcer, respectively, presence of facial flushing was the significant risk for reflux esophagitis and Barrett's esophagus. H pylori infection was positively associated with peptic ulcer, gastric adenocarcinoma, and duodenitis, but inversely associated with ESCC.
Dopamine drives binge‐like consumption of a palatable food in experimental Parkinsonism
Authors: Mineo Désirée , Cacace Fabrizio , Mancini Maria , Vannelli Anna , Campanelli Federica , Natale Giuseppina , Marino Gioia , Cardinale Antonella , Calabresi Paolo , Picconi Barbara , Ghiglieri Veronica
Published: April 2019

Background

Prolonged dopaminergic replacement therapy in PD results in pulsatile dopamine receptors stimulation in both dorsal and ventral striatum causing wearing off, motor fluctuations, and nonmotor side effects such as behavioral addictions. Among impulse control disorders, binge eating can be easily modeled in laboratory animals.

Objectives

We hypothesize that manipulation of dopamine levels in a 6‐hydroxydopamine–lesioned rats, as a model of PD characterized by a different extent of dopamine denervation between dorsal and ventral striatum, would influence both synaptic plasticity of the nucleus accumbens and binge‐like eating behavior.

Methods

Food preference, food intake, and weight gain were monitored in sham‐operated and unilaterally lesioned rats, subjected to a modified version of Corwin's limited access protocol, modelling binge eating disorder. Electrophysiological properties and long‐term potentiation of GABAergic spiny projection neurons of the nucleus accumbens core were studied through ex vivo intracellular and patch‐clamp recordings from corticostriatal slices of naïve and l‐dopa–treated rats.

Results

Sham‐operated animals with intact nucleus accumbens core plasticity reliably developed food‐addiction–like behavior when exposed to intermittent access to a highly palatable food. In contrast, parkinsonian rats were unresponsive to such restriction regimens, and also plasticity was lost in ventral spiny neurons. Chronic l‐dopa reestablished long‐term potentiation and compulsive eating, but with a different temporal dynamic that follows that of drug administration.

Conclusions

Our data indicate that endogenous and exogenous dopamine drive binge‐like consumption of a palatable food in healthy and parkinsonian rats with distinct temporal dynamics, providing new insights into the complexity of l‐dopa effects on the mesolimbic dopaminergic system. © 2019 International Parkinson and Movement Disorder Society
Genetic silencing of striatal CaV1.3 prevents and ameliorates levodopa dyskinesia
Authors: Steece‐Collier Kathy , Stancati Jennifer A. , Collier Nicholas J. , Sandoval Ivette M. , Mercado Natosha M. , Sortwell Caryl E. , Collier Timothy J. , Manfredsson Fredric P.
Published: April 2019

Background

Levodopa‐induced dyskinesias are an often debilitating side effect of levodopa therapy in Parkinson's disease. Although up to 90% of individuals with PD develop this side effect, uniformly effective and well‐tolerated antidyskinetic treatment remains a significant unmet need. The pathognomonic loss of striatal dopamine in PD results in dysregulation and disinhibition of striatal CaV1.3 calcium channels, leading to synaptopathology that appears to be involved in levodopa‐induced dyskinesias. Although there are clinically available drugs that can inhibit CaV1.3 channels, they are not adequately potent and have only partial and transient impact on levodopa‐induced dyskinesias.

Methods

To provide unequivocal target validation, free of pharmacological limitations, we developed a CaV1.3 shRNA to provide high‐potency, target‐selective, mRNA‐level silencing of striatal CaV1.3 channels and examined its ability to impact levodopa‐induced dyskinesias in severely parkinsonian rats.

Results

We demonstrate that vector‐mediated silencing of striatal CaV1.3 expression in severely parkinsonian rats prior to the introduction of levodopa can uniformly and completely prevent induction of levodopa‐induced dyskinesias, and this antidyskinetic benefit persists long term and with high‐dose levodopa. In addition, this approach is capable of ameliorating preexisting severe levodopa‐induced dyskinesias. Importantly, motoric responses to low‐dose levodopa remained intact in the presence of striatal CaV1.3 silencing, indicating preservation of levodopa benefit without dyskinesia liability.

Discussion

The current data provide some of the most profound antidyskinetic benefit reported to date and suggest that genetic silencing of striatal CaV1.3 channels has the potential to transform treatment of individuals with PD by allowing maintenance of motor benefit of levodopa in the absence of the debilitating levodopa‐induced dyskinesia side effect. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Projected changes in drought characteristics over the Western Cape, South Africa
Authors: Naik Myra , Abiodun Babatunde J.
Published: April 2019

The devastating socioeconomic impacts of recent droughts in the Western Cape have intensified the quest for future drought mitigation measures. While ongoing global warming may increase atmospheric evaporative demand and worsen drought conditions, most studies on drought in the Western Cape have overlooked the role of potential evapotranspiration (PET). The present study examines the role of PET on future drought characteristics, focusing on four river catchments. Two drought indices, the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI), were analysed. The capability of the Co‐ordinated Regional Downscaling Experiment simulations to reproduce the drought characteristics was evaluated by comparing present‐day climate simulations with observations. The impacts of different global warming levels (GWLs) on the SPI and SPEI projections were assessed using self‐organizing map (SOM) classifications. The results project that a robust drying signal across the Western Cape, but the magnitudes of the projections, which vary across the river catchments, increase with the GWLs. The changes in the drought intensity and frequency are weaker when using the SPI than the SPEI, suggesting that SPI projections may underestimate the influence of global warming on drought because they do not account for the influence of PET. The SOM classification confirms the differences between the two drought indices reveals the drought patterns that are not seen in the drought ensemble means. Nevertheless, the study underscores the need to mitigate future drought impacts over the Western Cape, but with careful consideration on the drought index used in characterizing the droughts.
Multi‐subtype classification model for non‐small cell lung cancer based on radiomics: SLS model
Authors: Liu Jian , Cui Jingjing , Liu Fei , Yuan Yixuan , Guo Feng , Zhang Guanglei
Published: April 2019

Purpose

Histological subtypes of non‐small cell lung cancer (NSCLC) are crucial for systematic treatment decisions. However, the current studies which used noninvasive radiomic methods to classify NSCLC histology subtypes mainly focused on two main subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC), while multi‐subtype classifications that included the other two subtypes of NSCLC: large cell carcinoma (LCC) and not otherwise specified (NOS), were very few in the previous studies. The aim of this work was to establish a multi‐subtype classification model for the four main subtypes of NSCLC and improve the classification performance and generalization ability compared with previous studies.

Methods

In this work, we extracted 1029 features from regions of interest in computed tomography (CT) images of 349 patients from two different datasets using radiomic methods. Based on “three‐in‐one” concept, we proposed a model called SLS wrapping three algorithms, synthetic minority oversampling technique, ℓ2,1‐norm minimization, and support vector machines, into one hybrid technique to classify the four main subtypes of NSCLC: SCC, ADC, LCC, and NOS, which could cover the whole range of NSCLC.

Results

We analyzed the 247 features obtained by dimension reduction, and found that the extracted features from three methods: first order statistics, gray level co‐occurrence matrix, and gray level size zone matrix, were more conducive to the classification of NSCLC subtypes. The proposed SLS model achieved an average classification accuracy of 0.89 on the training set (95% confidence interval [CI]: 0.846 to 0.912) and a classification accuracy of 0.86 on the test set (95% CI: 0.779 to 0.941).

Conclusions

The experiment results showed that the subtypes of NSCLC could be well classified by radiomic method. Our SLS model can accurately classify and diagnose the four subtypes of NSCLC based on CT images, and thus it has the potential to be used in the clinical practice to provide valuable information for lung cancer treatment and further promote the personalized medicine.
Multiple interleaved mode saturation (MIMOSA) for B1+ inhomogeneity mitigation in chemical exchange saturation transfer
Authors: Liebert Andrzej , Zaiss Moritz , Gumbrecht Rene , Tkotz Katharina , Linz Peter , Schmitt Benjamin , Laun Frederik B. , Doerfler Arnd , Uder Michael , Nagel Armin M.
Published: April 2019

Purpose

To mitigate inhomogeneity in quantitative CEST MRI at ultra‐high magnetic field strengths (B0 ≥ 7 Tesla) using a parallel transmit system.

Methods

Multiple interleaved mode saturation employs interleaving of 2 complementary phase sets during the saturation pulse train. Phase differences of 45° (first mode) and 90° (second mode) between 2 adjacent transmitter coil channels are used. The influence of the new saturation scheme on the CEST contrast was analyzed using Bloch‐McConnell simulations. The presented method was verified in phantom and in vivo measurements of the healthy human brain. The relayed nuclear Overhauser effect was evaluated, and the inverse magnetic transfer ratio metric was calculated. Results were compared to a published correction method. All measurements were conducted on a whole‐body 7 Tesla MRI system using an 8 transmitter and 32 receiver channel head coil.

Results

Simulations showed that the inverse magnetic transfer ratio metric contrast of relayed nuclear Overhauser effect shows a smaller dependency on the relative amplitudes of the 2 different modes than the contrasts of Cr and amide proton transfer. Measurements of an egg white phantom showed markedly improved homogeneity compared to the uncorrected inverse magnetic transfer ratio metric (relayed nuclear Overhauser effect) images and slightly improved results compared to corrected images. In vivo multiple interleaved mode saturation images showed similar contrast compared to corrected images.

Conclusion

Multiple interleaved mode saturation can be used as a simple method to mitigate inhomogeneity effects in CEST MRI at ultra‐high magnetic field strengths. Compared to previous correction methods, acquisition time can be reduced because an additional scan, usually required for correction, can be omitted.
A polyhedral analysis of the capacitated edge activation problem with uncertain demands
Authors: Mattia Sara
Published: April 2019

The capacitated edge activation problem consists of activating a minimum cost set of capacitated edges to ensure the routing of some traffic demands. If the demands are subject to uncertainty, we speak of the robust capacitated edge activation problem. We consider a capacity formulation of the problem and investigate, from a polyhedral perspective, the similarities and the differences between the robust capacitated edge activation and the robust network loading polyhedron, as well as between the polyhedra corresponding to different routing and flows policies.