bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic predictive value of the Bladder EpiCheck test in the follow‐up of patients with non–muscle‐invasive bladder cancer
Authors: Trenti Emanuela , D'Elia Carolina , Mian Christine , Schwienbacher Christine , Hanspeter Esther , Pycha Alexander , Kafka Mona , Degener Stephan , Danuser Hansjörg , Roth Stephan , Pycha Armin
Published: June 2019

Background

The objective of this study was to evaluate the diagnostic accuracy of the Bladder EpiCheck test in the follow‐up of patients with non–muscle‐invasive bladder cancer (NMIBC) and to compare it with the accuracy of urinary cytology, cystoscopy, and/or histology.

Methods

In total, 243 patients were enrolled in the current study. Patients were evaluated by voided urine cytology, by the Bladder EpiCheck test, and by white‐light cystoscopy.

Results

Overall sensitivity was 33.3% for cytology, 62.3% for Bladder EpiCheck, and 66.7% for the 2 tests combined. The sensitivity of cytology increased from 7.7% in low‐grade (LG) tumors to 66.6% in high‐grade (HG) tumors; whereas, for the Bladder EpiCheck test, the sensitivity was 46.1% in LG tumors and 83.3% in HG tumors. Combined cytology and Bladder EpiCheck testing yielded an overall sensitivity of 56.4% for LG tumors and 90% for HG tumors. Overall specificity was 98.6% for cytology, 86.3% for Bladder EpiCheck, and 85.6% for the 2 tests combined. The positive predictive value was 92% for cytology and 68.2% for Bladder EpiCheck. For the 2 tests combined, it was 68.6%. The negative predictive value was similar for the 2 tests: 75.8% for cytology, 82.9% for Bladder EpiCheck, and 84.5% for the 2 tests combined.

Conclusions

The sensitivity of the Bladder EpiCheck test was significantly higher than that of cytology. The test performed very well in terms of specificity but could not reach the high value of cytology. The positive predictive value was higher for Bladder EpiCheck, whereas the negative predictive value was approximately the same for both tests.
Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations
Authors: Kaur Sarabjeet , Sharma Purshotam , Wetmore Stacey D.
Published: June 2019

The front cover artwork is provided by the groups of Dr. Purshotam Sharma (Panjab University) and Prof. Stacey Wetmore (University of Lethbridge). The image highlights the plausible relevance of cyanuric acid and 2,4,6‐triaminopyrimidine as nucleobases of prebiotic RNA assemblies. Read the full text of the Article at 10.1002/cphc.201900237.
The power to detect regional declines in common bird populations using continental monitoring data
Authors: Baker D. J. , Clarke R. H. , McGeoch M. A.
Published: June 2019

Anthropogenic environmental change is driving the rapid loss of biodiversity. Large declines in the abundance of historically common species are now emerging as a major concern. Identifying declining populations through long‐term biodiversity monitoring is vital for implementing timely conservation measures. It is, therefore, critical to evaluate the likelihood that persistent long‐term population trends of a given size could be detected using existing monitoring data and methods. Here, we test the power to detect declines in Australia's common landbirds using long‐term citizen science monitoring. We use spatially explicit simulations of occupancy dynamics and virtual sampling, designed to mimic bird monitoring in better‐sampled regions of Australia, to assess likely power in these data to detect trends relevant for conservation. We predict the statistical power for 326 common species that meet minimum requirements for monitoring data across 10 regions of Australia, estimating the number of species for which we would have a high (≥80%) chance of detecting declines of different sizes. The power to detect declines of ≥30% per decade was predicted to be high for at least one‐third of the common species in 7 of 10 regions, with a total of 103 (32% of 326) unique species sufficiently monitored in at least one region. These species spanned 12 taxonomic orders, four orders of magnitude in body mass, and a broad diversity of dietary guilds, suggesting the current species pool will likely serve as robust indicators for a broad range of environmental states and pressures. Power was strongly affected by species' detectability, and power to detect even large declines was negligible when species are detected on ≤50% of visits to an occupied site. Predicted power for many species fell just short of the 80% threshold in one or more regions, which suggests an increase in effort targeting these species could greatly enhance the species and regional representation of these data. Against the backdrop of unprecedented biodiversity losses, this study shows how critical evaluation of existing monitoring schemes is valuable both for assessing the contribution of citizen science schemes to biodiversity monitoring and for designing strategic monitoring to significantly improve the knowledge these schemes provide.
Rh2(esp)2‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines
Authors: Zhukovsky Daniil , Dar'in Dmitry , Krasavin Mikhail
Published: June 2019

Decomposition of α‐diazo‐γ‐butyrolactams in the presence of aromatic and heteroaromatic amines, under Rh2(esp)2 catalysis, led to corresponding α‐arylamino‐γ‐butyrolactams, which are of significant value for medicinal chemistry. The reaction scope encompasses primary as well as secondary, diversely substituted anilines and heteroaromatic amines. Insertion into the anilinic amino group was shown to be selective over amide and sulfonamide N–H insertion.
Cornea nerve fibre state determines analgesic response to tapentadol in fibromyalgia patients without effective endogenous pain modulation
Authors: van de Donk Tine , van Velzen Monique , Dahan Albert , Niesters Marieke
Published: June 2019

Background

Tapentadol is a centrally acting analgesic with μ‐agonistic activity combined with noradrenaline reuptake inhibition. Its mechanism of action relies on improvement of descending pain inhibition. In the current study, tapentadol's ability to enhance conditioned pain modulation (CPM, an experimental measure of descending pain inhibition) was evaluated in fibromyalgia patients with absent or reduced CPM responses.

Methods

A total of 34 fibromyalgia patients completed this double‐blind trial. Patients were randomized to receive treatment with tapentadol sustained‐release or placebo for a 3‐month period with 1‐month follow‐up. At baseline, the cornea nerve fibre state (CNFS) was quantified to determine the presence of nerve fibre pathology and assess its value in the prediction of the analgesic response.

Results

Tapentadol significantly increased CPM responses during treatment with an average increase from baseline of 20.5 ± 12.5% (tapentadol) versus 3.0 ± 11.2% (placebo; p = 0.042). No treatment effect was observed for the absolute pain scores, however, analgesia responder rate analyses demonstrated a treatment effect in favour of tapentadol. Pain relief (a reduction in pain score ≥ 30%) was predicted by the presence of a normal CNFS (p = 0.035). Patients with an abnormal CNFS had no analgesic effect from tapentadol despite an increase in CPM.

Conclusions

In chronic pain patients with fibromyalgia, the increase in endogenous pain inhibition by tapentadol was translated into analgesia in patients with a normal CNFS. In those with abnormal CNFS, tapentadol treatment was without analgesic effect.

Significance

In this double‐blind randomized placebo‐controlled trial, we showed that tapentadol significantly enhanced the descending pain inhibition in fibromyalgia patients. Tapentadol‐induced pain relief was only present in patients with a normal CNFS.
Evaluating Sustainability: Controversies, Challenges, and Opportunities
Authors: Julnes George
Published: June 2019

Sustainability has long been a concern with regard to overpopulation and resource shortages. The concept became used in evaluation because of the observations that many programs have difficulties being sustained after initial start‐up funding expired. Now sustainability is a central concern due to the crisis of climate change. This chapter provides a foundation for this issue on evaluating sustainability by reviewing the evolving understandings of “sustainability” as it relates to evaluation, developing the argument that sustainability, and evaluating sustainability, is better viewed in process versus outcome terms, and summarizing some of the challenges and opportunities that wait to be addressed.
Supporting Transitions to Sustainability: Evaluation for Managing Processes in the Public Interest
Authors: Julnes George
Published: June 2019

Sustainability as a goal is often a major consideration in policy debates and is becoming more so in the field of evaluation. This rising profile, however, creates challenges because the contexts where sustainability is evaluated can be complex in ways that standard evaluation is less equipped to address. After addressing conditions that add to this complexity, recommendations are made to counter three problems. First, with a traditional focus on support for achieving outcomes, evaluators have tended to neglect support for managing processes. Second, with the largely accepted goal of influencing selected outcomes, evaluators have tended to neglect influencing established systems and so have been less prepared to support managing transitions from unsustainable to sustainable practices. Third, judging the value of public initiatives involves assumptions that, when applied to sustainability, can result in overly narrow and biased understandings of the public interest.
RETRACTED: Impact of drying methods on composition and functional properties of date powder procured from different cultivars
Authors: Raza Nighat , Arshad Muhammad U. , Anjum Faqir M. , Saeed Farhan , Maan Abid A. , Bader Ul Ain Huma
Published: June 2019

The present study was designed to evaluate the effect of two different drying methods, that is, spray drying and oven drying on physicochemical and nutritional attributes of date flesh powder of dhakki, aseel, and rabi varieties. Date powders were prepared using mixture of maltodextrin and acacia gum (50:50) as drying aid at the rate of 0.4 kg per 1.0 kg of date fruits (dry weight basis). The oven‐drying conditions were 60°C for 48 hr, whereas in spray drying, flow rate of 30 ml/min at 150°C was maintained. Date powder was obtained in both treatments from three varieties. Nutritional profile in all six powders was explored specifically with quantification of sugars using HPLC‐RI, followed by physicochemical characterization. The total phenolic compounds, color (L*a*b* values), hygroscopicity, bulk density, wettability, solubility index, and glass transition temperatures (using differential scanning calorimetry, DSC), were determined for the date powders. The nutritional profile and total phenolic contents and sugars (sucrose, fructose, and glucose) were significantly different for the varieties, while treatments showed insignificant effect. The physicochemical characteristics of date powder varied significantly with respect to the date varieties. The colored values were affected due to treatments also, and the spray‐dried powders showed better color values. The drying methods also showed effects in some parameters such as wettability time. Similarly, bulk density was different in both treatments for rabi and aseel. The glass transition temperatures were significantly varied in varieties due to difference in sugar contents, but within the treatments, they remain unaffected. The highest glass transition temperature of spray‐dried rabi was 53.2 ± 1.31°C.
Block trades in options markets
Authors: Gousgounis Eleni , Srinivasan Sayee
Published: June 2019

Block trading, which was sparse before the reduction of the minimum permissible block size threshold in October 2012, currently accounts for about 30% of the trading volume in WTI crude oil options. Block orders share similar characteristics to those routed at the pit, but they have lower information content and face higher execution costs, due to high search costs. However, our results show that such block orders would have been costlier to execute at the pit, which suggests that some pit order flow may have migrated to the upstairs market, contributing to the eventual demise of energy options pits.
Das Setzungsverhalten von vibrationsverdichteten, rolligen Böden
Authors: Massarsch Karl Rainer
Published: June 2019

Vibrationsverdichtung wird oft zur Verminderung von Setzungen in rolligen Böden angewendet. Die Drucksonde CPT und der Flachdilatometer DMT eignen sich besonders zur Planung und Durchführung von Vibrationsverdichtungsprojekten, da sowohl die Bodensteifigkeit als auch die Änderung der Horizontalspannungen gemessen werden können. Der Spannungspfad bei der Vibrationsverdichtung beschreibt die permanente Erhöhung der Horizontalspannung und den dadurch entstandenen Vorbelastungseffekt. Ein Verfahren wird vorgestellt, wie aus der Erhöhung der Horizontalspannung der Vorbelastungsgrad abgeschätzt werden kann. Das Setzungsverhalten von normalkonsolidierten Böden wird beschrieben. Das Tangentenmodulverfahren kann zur Setzungsberechnung vor und nach der Verdichtung verwendet werden. Die Modulzahl sowie der Vorbelastungsgrad können aus Feldversuchen mit CPT und DMT abgeschätzt werden. Die Anwendung von CPT‐ und DMT‐Untersuchungen zur Festlegung von setzungsbezogenen Verdichtungskriterien wird beschrieben. Die Setzungsberechnung vor und nach der Vibrationsverdichtung wird anhand eines Fallbeispiels geschildert, bei dem ein schluffiger Sandboden mittels VibroWing‐Verfahren und Vibrationsplatte verdichtet wurde.
The Miocene Shuangyashan basalts in northeast China: Implications for the origin of Cenozoic basalts in northeast Asia
Authors: Zhang Lei , Chen Jia‐fu , Shi Xing‐jun
Published: June 2019

Cenozoic basalts are widespread in northeast Asia, and their origins have been accepted as the products of different mantle end‐members. A combined study of elemental and isotopic geochemistry was carried out on Miocene basalt from the Shuangyashan Basin (Northeast China) to investigate the contributions of the various mantle end‐members. The Shuangyashan basalts are alkali trachybasalt (SiO2 = 49.8–50.8 wt%, Na2O + K2O = 5.45–6.09 wt%) in composition, with micro‐porphyritic texture. The phenocryst is euhedral olivine, and the matrix is composed of plagioclase, clinopyroxene, olivine, and ilmenite. The basalt shows slightly high MgO (6.80–7.22 wt%), Mg# (Mg2+ × 100/(Mg2+ + Fe2+), 63.0–64.8), and Ti/Y ratios (515–597) as well as extremely low Rb/Ba (0.08–0.10), Rb/Sr (0.04–0.06), and La/Nb (0.57–0.62) ratios. The elemental and isotopic geochemistry indicates that the basalt has experienced no or negligible crustal contamination. The small variations in basalt composition are controlled by fractional crystallization of olivine and clinopyroxene. The Sr (initial 87Sr/86Sr = 0.70507–0.70516), Nd (εNd(t) = 4.13–4.33), and Hf (εHf(t) = 9.24–12.1) isotopes show that the basalt has been affected by the EM2 (enriched mantle 2) in spinel peridotite lithospheric mantle. Meanwhile, the basalt shows relatively high REE fractionation (La/Yb = 14.9–16.6), suggesting it may be generated from the garnet peridotite. Therefore, the basalt could be originated from garnet peridotite in the lowest lithospheric mantle or asthenosphere and overprinted by the lithospheric EM2. Based on the compiled data from the literature, Sr–Nd isotope and trace element composition of the basalts from western northeast China, eastern northeast China, and Japanese islands are different from each other. Basalts from western northeast China are characterized by low 143Nd/144Nd, high 87Sr/86Sr ratios, and extremely high La/Yb ratio (mean is about 71), indicating that their origin is an EM1 (enriched mantle 1) in garnet‐bearing mantle. Basalts from eastern northeast China and Japanese islands show large variation of La/Yb ratios (1.2–34), showing that both have contributions from spinel and garnet peridotites. In eastern northeast China, basalts exhibit a roughly negative correlation between 87Sr/86Sr and La/Yb ratios. It is speculated that the asthenospheric mantle there is dominated by DM while the lithospheric mantle contains not only DM but also EM1 and EM2. In Japanese islands, (87Sr/86Sr)i ratios of basalts vary more greatly at low La/Yb (<10) than at high La/Yb ratios (>20), and high (87Sr/86Sr)i ratios (>0.7045) can only be observed at high La/Yb ratios (>20). Both the spinel and garnet peridotite mantle beneath Japanese islands have been significantly metasomatized by the subduction‐related fluid/melt.
Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial
Authors: Gluz Oleg , Kolberg‐Liedtke Cornelia , Prat Aleix , Christgen Matthias , Gebauer Daniel , Kates Ronald , Paré Laia , Grischke Eva‐Maria , Forstbauer Helmut , Braun Michael , Warm Mathias , Hackmann John , Uleer Christoph , Aktas Bahriye , Schumacher Claudia , Kuemmel Sherko , Wuerstlein Rachel , Pelz Enrico , Nitz Ulrike , Kreipe Hans Heinrich , Harbeck Nadia
Published: June 2019

In the neoadjuvant WSG‐ADAPT‐TN trial, 12‐week nab‐paclitaxel + carboplatin (nab‐pac/carbo) was highly effective and superior to nab‐paclitaxel + gemcitabine (nab‐pac/gem) in triple‐negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 × nab‐pac 125 mg/m2 (plus carbo AUC2 or gem 1,000 mg/m2 d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow‐up. Basal‐like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki‐67 (IHC; p < 0.001). For nab‐pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab‐pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event‐free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal‐like subtype, higher Ki‐67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.
Self‐assembling amyloid‐like peptides as exogenous second harmonic probes for bioimaging applications
Authors: Ni Ming , Zhuo Shuangmu , Iliescu Ciprian , So Peter T. C. , Mehta Jodhbir S. , Yu Hanry , Hauser Charlotte A. E.
Published: June 2019

Amyloid‐like peptides are an ideal model for the mechanistic study of amyloidosis, which may lead to many human diseases, such as Alzheimer disease. This study reports a strong second harmonic generation (SHG) effect of amyloid‐like peptides, having a signal equivalent to or even higher than those of endogenous collagen fibers. Several amyloid‐like peptides (both synthetic and natural) were examined under SHG microscopy and shown they are SHG‐active. These peptides can also be observed inside cells (in vitro). This interesting property can make these amyloid‐like peptides second harmonic probes for bioimaging applications. Furthermore, SHG microscopy can provide a simple and label‐free approach to detect amyloidosis. Lattice corneal dystrophy was chosen as a model disease of amyloidosis. Morphological difference between normal and diseased human corneal biopsy samples can be easily recognized, proving that SHG can be a useful tool for disease diagnosis.
Salidroside ameliorated hypoxia‐induced tumorigenesis of BxPC‐3 cells via downregulating hypoxia‐inducible factor (HIF)‐1α and LOXL2
Authors: Chen Xiaoping , Kou Yubin , Lu Yunsong , Pu Yumei
Published: June 2019

Herein, we found that salidroside suppressed hypoxia‐inducible factor 1 alpha (HIF‐1α) and lysyl oxidase‐like protein 2 (LOXL2) within human pancreatic cancer BxPC‐3 cells cultured both under normoxia and hypoxia condition. To investigate the effect of salidroside on tumorigenesis of BxPC‐3 cells and whether HIF‐1α and LXCL2 were involved in this process, cells transfected with or without LOXL2 overexpression vector, were treated with 50 μg/mL of salidroside or 50 μM of KC7F2 (a HIF‐1α inhibitor) under hypoxia. Cell viability and invasion were assessed using CCK‐8 and Transwell chamber assay, respectively. Expression of E‐cadherin and matrix metalloproteinase 2/9 (MMP 2/9) was determined, by Western blot analysis, to assess cell mobility at molecular levels. We confirmed that hypoxia increased LOXL2 and induced tumorigenesis of BxPC‐3 cells, as evidenced by promoted cell proliferation and invasion, enhanced MMP2/9 while reduced E‐cadherin. Interestingly, hypoxia‐induced carcinogenesis was significantly retarded by both salidroside and KC7F2, however, enhanced with LOXL2 overexpression. Besides, salidroside and KC7F2 reduced LOXL2, and reversed the tumorigenesis of BxPC‐3 cells induced by LOXL2 overexpression. Given the inhibitory effect of salidroside on HIF‐1α expression, our data suggested that: (1) LOXL2 was the mechanism, whereby salidroside and KC7F2 showed inhibitory effect on cancer progression of BxPC‐3 cells; (2) salidroside exerted its anticancer effect, most likely, by a HIF‐1α/LOXL2 pathway. In conclusion, salidroside was a novel therapeutic drug in pancreatic cancer, and downregulation of HIF‐1α and LXCL2 was the underlying mechanism.
Right ventricle may be involved in regional diastolic dysfunction earliest in primary hypertension patients
Authors: Zhang Xiujin , Wu Cai‐e , Ye Ping , Sheng Li , Luo Leiming
Published: June 2019

Background

Impaired ventricular diastolic function is common in hypertensive patients and is one of the major causes of heart failure. Both left and right ventricle diastolic dysfunction have been reported, but the order of involvement is not clear.

Method

A total of 161 primary hypertensive patients and 40 healthy volunteers were enrolled. Pulsed wave tissue Doppler was used to measure regional diastolic dysfunction (defined as early peak diastolic [Em] and late diastolic [Am] velocity ratios (Em/Am) < 1) at right ventricular tricuspid valve annulus lateral side (RAVP1), right ventricular tricuspid valve annulus septum side (RAVP2), left ventricular mitral valve annulus septum side (LAVP1) and left ventricular mitral annulus lateral side (LAVP2).

Results

The prevalence of regional diastolic dysfunction at RAVP1, RAVP2, LAVP1, and LAVP2 was all higher in the hypertensive group (P < .001 for all). In both the hypertensive group and the control group, more cases were presented with RAVP1 diastolic dysfunction, while the least number of cases had LAVP2 diastolic dysfunction. In patients with stage 1 hypertension, most cases had RAVP1, or RAVP1 and RAVP2/LAVP1 diastolic dysfunction, while in patients with more advanced hypertension stages, significantly more cases had both RAVP1 and LAVP2, or all four locations diastolic dysfunction (P < .001). A similar trend was observed in patients with longer hypertension duration (duration of 6‐9.9 years and 10‐18 years compared with 2‐5.9 years of duration, P < .001).

Conclusions

With a more advanced stage and longer duration of hypertension, the range of regional diastolic dysfunction increased, showing a trend from the right ventricular wall, to the septum and left the ventricular wall. In primary hypertension, regional diastolic dysfunction in the right ventricle might happen earlier than that in the septum and the left ventricle.
Joint detection of claudin‐1 and junctional adhesion molecule‐A as a therapeutic target in oral epithelial dysplasia and oral squamous cell carcinoma
Authors: Upadhaya Puja , Barhoi Dharmeswar , Giri Anirudha , Bhattacharjee Abhinandan , Giri Sarbani
Published: June 2019

Abnormal expression of claudin‐1 (CLDN‐1) and junctional adhesion molecule‐A (JAM‐A) has been described in certain malignancies but their clinical relevance is poorly understood. The present study aims to elucidate the role of CLDN‐1 and JAM‐A in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Changes in the expression of these proteins were identified immunohistochemically on tissue sections from patients with OED and OSCC and compared with control. A correlation between the expression level of proteins and clinicopathological features was analyzed by Pearson's correlation χ2 test. The survival curve of the follow‐up data was estimated by the Kaplan‐Meier method followed by the log‐rank test. CLDN‐1 and JAM‐A were highly expressed in OED and OSCC tissues when compared to control. Also, delocalization of CLDN‐1 from the membrane to the cytoplasm to the nucleus was observed as the cell proceeds from normal to malignancy. Increased expression of CLDN‐1 and JAM‐A in both OED and OSCC were concomitant with histological grades. In addition, increased JAM‐A was associated with perineural invasion of cancer cells. A positive correlation between the expression level of proteins was observed in OED (r = 0.733) and OSCC (r = 0.577). Kaplan‐Meier analysis in patients with OSCC showed that the survival rate was lower in patients with high CLDN‐1 and high JAM‐A expression compared to low expressed patients. To conclude, the elevated level and delocalization of CLDN‐1 and JAM‐A suggest their use as tumor markers. A positive correlation between CLDN‐1 and JAM‐A suggests joint detection of these proteins as a future diagnostic tool in oral precancerous and cancerous conditions.
Centaurea cyanus extracted 13‐O‐acetylsolstitialin A decrease Bax/Bcl‐2 ratio and expression of cyclin D1/Cdk‐4 to induce apoptosis and cell cycle arrest in MCF‐7 and MDA‐MB‐231 breast cancer cell lines
Authors: Keyvanloo Shahrestanaki Mohammad , Bagheri Mahboobeh , Ghanadian Mustafa , Aghaei Mahmoud , Jafari Seyyed Mehdi
Published: June 2019

Natural products are considered recently as one of the source for production of efficient therapeutical agents for breast cancer treatment. In this study, a sesquiterpene lactone, 13‐O‐acetylsolstitialin A (13ASA), isolated from Centaurea cyanus, showed cytotoxic activities against MCF‐7 and MDA‐MB‐231 breast cancer cell lines using standard 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. To find the mechanism of action of cytotoxicity, annexin V/propidium iodide (PI) staining was performed for evaluation of apoptosis. This process was further confirmed by immunoblotting of anti‐ and proapoptotic, Bcl‐2 and Bax, proteins. Cell cycle arrest was evaluated by measurement of fluorescence intensity of PI dye and further confirmed by immunoblotting of Cdk‐4 and cyclin D1. Mitochondrial transmembrane potential (ΔΨm) and generation of reactive oxygen species (ROS) were measured using the JC‐1 and DCFDA fluorescence probes, respectively. These experiments showed that 13ASA is a potent cytotoxic agent, which activates apoptosis‐mediated cell death. In response to this compound, Bax/Bcl‐2 ratio was noticeably increased in MCF‐7 and MDA‐MB‐231 cells. Moreover, 13ASA induced cell cycle arrest at subG1 and G1 phases by decreasing protein levels of cyclin D1 and Cdk‐4. It was done possibly through the decrease of ΔΨm and increase of ROS levels which induce apoptosis. In conclusion, this study mentioned that 13ASA inhibit the growth of MCF‐7 and MDA‐MB‐231 breast cancer cell lines through the induction of cell cycle arrest, which triggers apoptotic pathways. 13ASA can be considered as a susceptible compound for further investigation in breast cancer study.
The RyR–ClCa–VDCC axis contributes to spontaneous tone in urethral smooth muscle
Authors: Feng Mei , Wang Zhaoyang , Liu Zheng , Liu Donghai , Zheng Kaizhi , Lu Ping , Liu Chuanyong , Zhang Min , Li Jingxin
Published: June 2019

Current therapies including pharmaceutical intervention and surgery have limited efficacy on stress urinary incontinence (SUI). One type of SUI is due to low intraurethral pressure caused by the disabled contraction of urethral smooth muscle (USM). However, the molecular mechanisms underlying the motility of USM remain unknown. Here, we show that USM represents spontaneous tone after stretching in humans and mice. Deletion of TMEM16A in the smooth muscle of mice abolishes spontaneous urethral tone. Furthermore, ClCa currents and [Ca2+]i in TMEM16ASMKO mice were largely impaired. Inhibitors of ryanodine receptor (RyR), TMEM16A encoded calcium‐activated chloride channel (ClCa) and L‐type voltage‐dependent calcium channel (VDCC) fully prevented spontaneous tone accompanied by a significant decrease of intracellular calcium concentration ([Ca2+]i). In summary, RyR–ClCa–VDCC signaling contributes to spontaneous USM tone. This finding may provide a new promising approach for women with stress SUI who reject surgery.
Autophagy regulation and its role in normal and malignant hematopoiesis
Authors: Shahrabi Saeid , Paridar Mostafa , Zeinvand‐Lorestani Marzieh , Jalili Arsalan , Zibara Kazem , Abdollahi Mohammad , Khosravi Abbas
Published: June 2019

Autophagy, the molecular machinery of self‐eating, plays a dual role of a tumor promoter and tumor suppressor. This mechanism affects different clinical responses in cancer cells. Autophagy is targeted for treating patients resistant to chemotherapy or radiation. Limited reports investigate the significance of autophagy in cancer therapy, the regulation of hematopoietic and leukemic stem cells and leukemia formation. In the current review, the role of autophagy is discussed in various stages of hematopoiesis including quiescence, self‐renewal, and differentiation.
Future changes in five extreme precipitation indices in the lowlands of Romania
Authors: Harpa Gabriela‐Victoria , Croitoru Adina‐Eliza , Djurdjevic Vladimir , Horvath Csaba
Published: June 2019

This paper presents the results of a study focused on the projected changes in extreme precipitation indices in Romania during three future periods: 2021–2040, 2041–2070, and 2071–2100. We investigated changes in future climate based on historical and modelled data sets of daily precipitation. We compared the values calculated for the three future periods with those obtained for the historical reference period 1961–1990. The historical observation data recorded at 30 weather stations and data extracted from six regional climate model outputs (ALADIN53, CCLM4‐8‐17, RACMO22E, RCA4, REMO2009, and WRF331F) under moderate (RCP4.5) and pessimistic (RCP8.5) scenarios were employed. Five indices established by the Expert Team for Climate Change Detection Monitoring and Indices were analysed: consecutive dry days, consecutive wet days, heavy precipitation days, very heavy precipitation days, and annual total wet‐day precipitation. The series of indices were generated using ClimPACT2 software. Based on bias correction methods, the quality of the modelled data considerably increased, and the errors obtained for the daily precipitation varied in the range of ±0.05 to ±1.22 mm/day. The main findings revealed an increase in three of the extreme precipitation indices based on all models considered compared to the historical period. The most important increase (more than 50%) compared to the historical period was detected in the frequency of very heavy precipitation days and the annual total wet‐day precipitation. They were followed by the heavy precipitation days index. The consecutive dry days index indicated mainly no change or a slow decrease, while inconsistencies among the results of regional climate models were detected for the consecutive wet days index. For all indices except the consecutive dry days index, the ALADIN53 and WRF331F models provided the highest projected values for both scenarios. The dispersion of values obtained as model output for each location was higher for RCP8.5 than for RCP4.5.
Whole unripe plantain (Musa paradisiaca L.) as raw material for bioethanol production
Authors: Alonso‐Gómez Leonardo A , Heredia‐Olea Erick , Serna‐Saldivar Sergio O , Bello‐Pérez Luis A
Published: June 2019

BACKGROUND

The use of byproducts such as rejected plantain with final disposition problems and conversion processes with ‘green’ technologies are important research topics. Bioethanol production from crops with a high content of fermentable sugars is an alternative to that from traditional crops (corn and sugar cane). The aim of this work was to study the use of whole (peel and pulp) unripe plantain (WP) for bioethanol production.

RESULTS

Lab‐scale liquefaction and saccharification of both materials released mainly three carbohydrates, glucose (9.02 mg g−1), maltose (0.45 mg g−1) and xylose (0.25 mg g−1). The WP saccharification required the use of pectinase and cellulase because of the high amounts of pectin and cellulose associated with the peel. Fermentation for 11 h produced similar ethanol concentration for both samples, but at the end of fermentation (32 h), the ethanol production was higher in the WP (58.6 mL L−1) compared with the plantain pulp (PP) (45.5 mL L−1). The theoretical ethanol yield was lower with WP (67%) than with PP (90%).

CONCLUSION

WP can be an alternative raw material for bioethanol production. © 2019 Society of Chemical Industry
Amylose‐Coated Biohybrid Microgels by Phosphorylase‐Catalyzed Grafting‐From Polymerization
Authors: Gau Elisabeth , Flecken Franziska , Belthle Thomke , Ambarwati Masyitha , Loos Katja , Pich Andrij
Published: June 2019

Herein, the synthesis of amylose‐coated, temperature‐responsive poly(N‐vinylcaprolactam) (VCL)‐based copolymer microgels by enzyme‐catalyzed grafting‐from polymerization with phosphorylase b from rabbit muscle is reported. The phosphorylase is able to recognize the oligosaccharide maltoheptaose as primer and attach glucose units from the monomer glucose‐1‐phosphate to it, thereby forming amylose chains while releasing inorganic phosphate. Therefore, to enable the phosphorylase‐catalyzed grafting‐from polymerization of glucose‐1‐phosphate from the PVCL‐based microgels, the maltoheptaose primer is covalently attached to the microgel in the first synthesis step. This is realized by adding N‐(2‐aminoethyl)methacrylamide (AEMAA) as a comonomer to the PVCL microgel to integrate primary amino groups and subsequent coupling of maltoheptaonolactone. Both the PVCL/AEMAA microgel as well as the obtained microgel–maltoheptaose construct are characterized in detail by dynamic light scattering, electrophoretic mobility measurements, IR spectroscopy, and atomic force microscopy. From the microgel–maltoheptaose construct, the grafting‐from polymerization of glucose‐1‐phosphate is performed by the addition of phosphorylase b. Atomic force microscopy images clearly demonstrate the formation of an amylose shell around the microgels. The developed amylose‐coated microgels open up promising application possibilities, for example, as colloidal scavengers, since amylose helices can serve as host molecules for inclusion of hydrophobic guest molecules.
Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway
Authors: Ou Yang , Ren Haifeng , Zhao Rongrong , Song Le , Liu Zhengxia , Xu Wenting , Liu Yakun , Wang Siying
Published: June 2019

The Helicobacter pylori (H. pylori) cytotoxin‐associated gene A (CagA) and Krüppel‐like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA‐mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori‐positive GC cells compared with the H. pylori‐negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR‐155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR‐155 in GES‐1 promoted epithelial‐mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR‐155/KLF4 signaling pathway provided a new insight into the development and treatment of GC.
Fast quantitative 2D NMR for metabolomics and lipidomics: A tutorial
Authors: Martineau Estelle , Dumez Jean‐Nicolas , Giraudeau Patrick
Published: June 2019

Nuclear magnetic resonance (NMR) is a well‐known analytical technique for the analysis of complex mixtures. Its quantitative capability makes it ideally suited to metabolomics or lipidomics studies involving large sample collections of complex biological samples. To overcome the ubiquitous limitation of spectral overcrowding when recording 1D NMR spectra on such samples, the acquisition of 2D NMR spectra allows a better separation between overlapped resonances while yielding accurate quantitative data when appropriate analytical protocols are implemented. Moreover, the experiment duration can be considerably reduced by applying fast acquisition methods. Here, we describe the general workflow to acquire fast quantitative 2D NMR spectra in the “omics” context. It is illustrated on three representative and complementary experiments: UF COSY, ZF‐TOCSY with nonuniform sampling, and HSQC with nonuniform sampling. After giving some details and recommendations on how to apply this protocol, its implementation in the case of targeted and untargeted metabolomics/lipidomics studies is described.
Outcome in radiographic complete regression of unresectable head and neck cancer with carotid artery encasement from induction chemotherapy followed by concurrent chemoradiotherapy: Case reports
Authors: Ampil Federico , Takalkar Amol , Sangster Guillermo , Richards Troy
Published: June 2019

Little is known about the effects of non‐operative treatment for unresectable head and neck cancer with carotid artery encasement. While induction chemotherapy followed by concurrent chemoradiotherapy/sequential chemoradiotherapy is usually recommended for this disease entity, conclusive evidence regarding the benefit achieved from such therapeutic intervention remains sparse. The authors describe two cases of head and neck cancer with carotid artery encasement managed by induction chemotherapy followed by concurrent chemoradiotherapy, and review the literature. Despite the complete disappearance of the locally advanced tumor after the sequential chemoradiotherapy, recurrence and progression of tumor subsequently developed. The untoward event was believed to be due to the prolongation of the overall treatment time and the radiotherapy course. It is surmised that the continued use of sequential chemoradiotherapy in the management of head and neck cancer with carotid artery encasement can be justified, provided it is aggressive, timely, and without undue prolongations.
The crystal structure of Klebsiella pneumoniae FeoA reveals a site for protein‐protein interactions
Authors: Linkous Richard O. , Sestok Alexandrea E. , Smith Aaron T.
Published: June 2019

In order to establish infection, pathogenic bacteria must obtain essential nutrients such as iron. Under acidic and/or anaerobic conditions, most bacteria utilize the Feo system in order to acquire ferrous iron (Fe2+) from their host environment. The mechanism of this process, including its regulation, remains poorly understood. In this work, we have determined the crystal structure of FeoA from the nosocomial agent Klebsiella pneumoniae (KpFeoA). Our structure reveals an SH3‐like domain that mediates interactions between neighboring polypeptides via hydrophobic intercalations into a Leu‐rich surface ridge. Using docking of a small peptide corresponding to a postulated FeoB partner binding site, we demonstrate that KpFeoA can assume both “open” and “closed” conformations, controlled by binding at this Leu‐rich ridge. We propose a model in which a “C‐shaped” clamp along the FeoA surface mediates interactions with its partner protein, FeoB. These findings are the first to demonstrate atomic‐level details of FeoA‐based protein‐protein interactions and provide a framework for testing FeoA‐FeoB interactions, which could be exploited for future antibiotic developments.
Detection of Sulfur‐Related Defects in Sulfur Diffused n‐ and p‐Type Si by DLTS
Authors: Gwozdz Katarzyna , Kolkovsky Vladimir , Weber Joerg , Yakovleva Anastasia A. , Astrov Yuri A.
Published: June 2019

Sulfur is diffused into Czochralski (CZ) and Float‐Zone (FZ) silicon wafers at 1200 °C for 30 h. After diffusion, the wafers are slowly cooled in air. Several defect levels are observed by deep level transient spectroscopy (DLTS) in n‐ and p‐type samples. All defects levels are related to sulfur defects, but none could be identified with the donor and double donor states of substitutional S or molecular S2. Additional annealing of the samples at 300 °C generates four DLTS levels in n‐type Si and no peaks in p‐type Si. The enhancement of the emission rate with the electrical field confirm their donor and double donor‐like behavior. The authors identify the four DLTS levels in the annealed n‐type Si samples with the different charge states of monoatomic S and molecular S2 (S0, S+, S20, and S2+) defects in Si. Hydrogenation of the annealed samples by wet chemical etching results in a reduction of the intensity of S0, S+, S20, and S2+ due to a passivation of these defects. The authors did not observe any electrically active SH‐complexes in the hydrogenated samples.
Electrically Active Copper–Nickel Complexes in p‐Type Silicon
Authors: Yarykin Nikolai , Weber Jörg
Published: June 2019

The interaction of substitutional copper atoms (Cus) with interstitial nickel (Nii) or copper (Cui) in crystalline p‐type Si is investigated by DLTS. The mobile interstitial species are introduced at near‐room temperatures by etching in Ni‐ or Cu‐contaminated KOH aqueous solutions. The Cui in‐diffusion is confirmed by the formation of several deep level complexes including the photoluminescence CuPL center which is known to be a Cus atom decorated with three Cui species. The Nii in‐diffusion results in the appearance of three novel electrically active Cu‐Ni complexes; two of them are unstable at room temperature and transform into the third center which possesses a level at 0.16 eV above the top of the valence band. The deep‐level depth profiles below the etched surface affirm that all three Cu‐Ni complexes are formed on the base of one Cus atom by means of addition at least one Nii and one or more Cui species.
Persistent precipitation extremes in the Yangtze River Valley prolonged by opportune configuration among atmospheric teleconnections
Authors: Chen Yang , Zhai Panmao , Liao Zhen , Li Lei
Published: June 2019

This study investigates whether and how three synoptic‐scale teleconnections, i.e. East Asia/Pacific teleconnection (EAP), Silk‐Road teleconnection (SR) and Eurasia teleconnection (EU), induce persistent precipitation extremes (PPEs) in the Yangtze River Valley. Results show that only the EAP teleconnection has the potential of independently incurring PPEs; while the other two teleconnections' influences on PPEs need to be exerted via their liaison with the EAP pattern. Cases are accordingly grouped into two subsets, i.e. single EAP‐PPEs and three teleconnection–PPEs. In both groups, the EAP teleconnection evolves following a similar pathway that poleward energy dispersion dynamically links a westward‐extended subtropical high, a deepened midlatitude trough and the Okhotsk blocking. EAP‐induced circulation anomalies enhance low‐level convergences and upper‐level divergences, convey exceptionally abundant moisture, and hence give birth to a quasi‐stationary front leading to PPEs in the Yangtze River Valley. Despite similarities, PPEs last noticeably longer in the three‐teleconnection context. The EU teleconnection‐related downstream energy dispersion at higher latitudes favours both earlier establishment and latter decay of the Okhotsk blocking. Constructed meridional flows at mid–high latitudes continuously steer migratory disturbances southeastward into the EAP trough. The SR plays a bigger role during the latter half of PPE life span (3 days after onset) via stimulating new cyclonic disturbances that largely overlap with the EAP trough spatially. Moreover, EU‐ and SR‐excited disturbances could effectively extract baroclinic and barotropic energy from local mean flows to replenish components of the EAP tripole pattern, which therefore survives longer and prolongs PPEs by several days.
Children's Literacy Experiences in Low‐Income Families: The Content of Books Matters
Authors: Luo Rufan , Tamis‐LeMonda Catherine S. , Mendelsohn Alan L.
Published: June 2019

The authors examined children's access to books in 153 four‐year‐olds from low‐income, U.S. ethnic‐minority families. Mothers reported on the number of books available to their children and the variety of books their children had, such as concept books about letters, numbers, and shapes and narrative books about cultural beliefs and relationships. Mothers also reported on the frequency of mother–child book‐sharing interactions. The authors coded characteristics of book‐sharing interactions from videos of mother–child sharing of a wordless book. Most children had a variety of concept books but few narrative books. Children who were later born and who had English‐speaking (vs. Spanish‐speaking) parents had a greater variety of narrative books than did their counterparts, and children living with their father and mother had a greater variety of narrative and concept books than those who did not reside with their father. The variety of narrative books predicted children's narrative contributions during book sharing through the mediator of mothers’ questions about the story. In contrast, the variety of concept books predicted children's referential contributions (e.g., “That's a tree”) through the mediator of mothers’ referential questions (e.g., “What's that?”). Household composition, home language use, and the content of books shape the early literacy experiences of children from low‐income, ethnic‐minority families.
Preparation and Characterization of Highly Flexible, Free‐Standing, Three‐Dimensional and Rough NiMOF/rGO Composite Paper Electrode for Determination of Catechol
Authors: Kıranşan Kader Dağcı
Published: June 2019

The flexible, free‐standing and durable highly rough nickel metal‐organic framework/reduced graphene oxide (NiMOF/rGO) composite paper electrode was prepared with a simple electrochemical deposition of NiMOF structures on the surface of the rGO paper electrode. NiMOF/rGO composite paper electrode was characterized by using scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), Raman spectroscopy and electrochemical impedance spectroscopy (EIS) techniques. As‐prepared NiMOF/rGO composite paper was used in the electrochemical detection of catechol (CC). The rough and flower‐like three‐dimensional (3D) NiMOF nanostructures on the rGO paper electrode surface greatly increased the catalytic performance of the paper electrode by providing a large active surface area. CC was detected on NiMOF/rGO composite paper in a very wide linear range from 0.02 to 760 μM, a low detection limit of 1.8 nM (S/N=3), with a high sensitivity of 0.158 mA μM cm−2 and very high selectivity, especially in the presence of phenol‐derived materials. Furthermore, it was determined that NiMOF/rGO composite paper also had high stability, flexibility, and durability, which may enable this material to be used in‐vivo applications.