bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen‐Bond Cyclization Programming of Ultrasensitive Esters and Its Application in Gene Delivery
Authors: Li Shengran , Yan Xinxin , Qu Yangchun , Wang Wenliang , Chen Binggang , Ma Xiaojing , Liu Sanrong , Yu Xifei
Published: May 2019

The ester bond as a universal linker has recently been applied in gene delivery systems owing to its efficient gene release by electrostatic repulsion after its cleavage. However, the ester bond is nonlabile and is difficult to cleave in cells. This work reports a method in which a secondary amine was introduced to the β‐position of the ester bond to generate a hydrogen‐bond cyclization (HBC) structure that can make the ester bond hydrolysis ultrafast. A series of molecules comprising ultrasensitive esters that can be activated by H2O2 were synthesized, and it was found that those able to form an HBC structure showed complete ester hydrolysis within 5 h in both water and phosphate‐buffered saline solution, which was several times faster than other methods reported. Then, a series of amphiphilic poly(amidoamine) dendrimers were constructed, comprising the ultrasensitive ester groups for gene delivery; it was found that they could effectively release genes under quite a low concentration of H2O2 (<200 μm) and transport them into the nucleus within 2 h in Hela cells with high safety. Their gene transfection efficiencies were higher than that of PEI25k. The results demonstrated that the hydrogen‐bond‐induced ultrasensitive esters could be powerfully applied to construct gene delivery systems.
Divergent Synthesis of Oxa‐Cyclic Nitrones through Gold(I)‐Catalyzed 1,3‐Azaprotio Transfer of Propargylic α‐Ketocarboxylate Oximes: Experimental and DFT Studies
Authors: Wang Chunhong , Cui Qi , Zhang Zhixin , Yao Zhu‐Jun , Wang Shaozhong , Yu Zhi‐Xiang
Published: May 2019

1,3‐Azaprotio transfer of propargylic α‐ketocarboxylate oximes, a new type of alkynyl oximes featuring an ester tether, has been explored by taking advantage of gold catalysis. The incorporation of an oxygen atom to the chain of alkynyl oximes led to the formation of two different oxa‐cyclic nitrones. It was found that internal alkynyl oximes with an E‐configuration deliver five‐membered nitrones, whereas terminal alkynyl oximes with an E‐configuration afford six‐membered nitrones. DFT calculations on four possible pathways supported a stepwise formation of C−N and C−H bonds, in which a 1,3‐acyloxy‐migration competes with the 1,3‐azaprotio‐transfer, especially in the case of internal alkynyl oximes. The relative nucleophilic properties of oxygen in the carbonyl group and the nitrogen in the oxime, the electronic effects of alkynes, and the influence of the ring system have been investigated computationally.
CuII and AuIII Complexes with Glycoconjugated Dithiocarbamato Ligands for Potential Applications in Targeted Chemotherapy
Authors: Pettenuzzo Nicolò , Brustolin Leonardo , Coltri Elisa , Gambalunga Alberto , Chiara Federica , Trevisan Andrea , Biondi Barbara , Nardon Chiara , Fregona Dolores
Published: May 2019

This work is focused on the synthesis, characterization, and preliminary biological evaluation of bio‐conjugated AuIII and CuII complexes with the aim of overcoming the well‐known side effects of chemotherapy by improving the selective accumulation of an anticancer metal payload in malignant cells. For this purpose, carbohydrates were chosen as targeting agents, exploiting the Warburg effect that accounts for the overexpression of glucose‐transporter proteins (in particular GLUTs) in the phospholipid bilayer of most neoplastic cells. We linked the dithiocarbamato moiety to the C1 position of three different monosaccharides: d‐glucose, d‐galactose, and d‐mannose. Altogether, six complexes with a 1:2 metal‐to‐ligand stoichiometry were synthesized and in vitro tested as anticancer agents. One of them showed high cytotoxic activity toward the HCT116 colorectal human carcinoma cell line, paving the way to future in vivo studies aimed at evaluating the role of carbohydrates in the selective delivery of whole molecules into cancerous cells.
Pathologic staging changes in oral cavity squamous cell carcinoma: Stage migration and implications for adjuvant treatment
Authors: Lee Nicholas C. J. , Eskander Antoine , Park Henry S. , Mehra Saral , Burtness Barbara A. , Husain Zain
Published: May 2019

Background

The eighth edition of the AJCC Cancer Staging Manual (AJCC 8) incorporates depth of invasion (DOI) into the pathologic tumor (pT) classification and pathologic extranodal extension (pENE) into the pathologic nodal (pN) classification for oral cavity squamous cell carcinoma (OCSCC). This study evaluated the incidence and prognostic importance of stage migration as a result of these changes in the AJCC 8 staging system.

Methods

From the National Cancer Database, cohorts were identified from patients with OCSCC undergoing definitive surgery between 2004 and 2013 for pT (n = 7184), pN (n = 13,627), and pathologic stage (pStage) analysis (n = 5580).

Results

DOI and pENE were prognostic in all groups except for pN3 according to the seventh edition of the AJCC Cancer Staging Manual (AJCC 7). Upstaging was seen in 12.4% of patients for the pT classification, in 13.3% for the pN classification, and in 24.8% for the overall pStage grouping. Notably, upstaging led to similar or improved 5‐year overall survival (OS) for every AJCC 8 pT/N classification except pStage IVB. Patients with AJCC 7 pT1 tumors that were upstaged to AJCC 8 pT3 tumors had improved OS in comparison with the remainder of the pT3 group (71.7% vs 43.7%; P < .0001). A multivariable analysis of upstaged pT3N0 patients demonstrated a reduced risk of death with the receipt of postoperative radiotherapy (PORT; hazard ratio, 0.56; 95% confidence interval, 0.33‐0.95; P = .03).

Conclusions

Upstaging is common in AJCC 8, and patients with upstaged tumors demonstrate improved survival; these factors should be kept in mind when one is interpreting data with the new staging system. PORT may reduce deaths among newly upstaged pT3N0 patients, and further study is needed in this area.
Patient‐reported and clinician‐reported chemotherapy‐induced peripheral neuropathy in patients with early breast cancer: Current clinical practice
Authors: Nyrop Kirsten A. , Deal Allison M. , Reeder‐Hayes Kathryn E. , Shachar Shlomit S. , Reeve Bryce B. , Basch Ethan , Choi Seul Ki , Lee Jordan T. , Wood William A. , Anders Carey K. , Carey Lisa A. , Dees Elizabeth C. , Jolly Trevor A. , Kimmick Gretchen G. , Karuturi Meghan S. , Reinbolt Raquel E. , Speca JoEllen C. , Muss Hyman B.
Published: May 2019

Background

In the current study, the authors investigated the incidence of moderate to severe chemotherapy‐induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient‐reported and clinician‐assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified.

Methods

Patients completed a Patient‐Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy.

Results

The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti–human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti‐HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient‐reported and clinician‐assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient‐reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06‐2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72‐4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37‐0.887 [P = .01]) was found to be associated with lower CIPN severity.

Conclusions

The discrepancy between patient‐reported and clinician‐assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose‐limiting, and potentially disabling side effect of chemotherapy.
Chirality and Excited State Proton Transfer: From Sensing to Asymmetric Synthesis
Authors: Posey Victoria , Hanson Kenneth
Published: May 2019

Excited state proton transfer (ESPT) is a unique photochemical process where the electron density shift of a molecule in the excited state dramatically decreases the pKa value of a proton donor site. A majority of ESPT research to date has focused on achiral molecules but there is growing interest in understanding/harnessing ESPT to/from chiral molecules. This review summarizes and critically examines the literature to date describing the role of ESPT in enantioselective fluorescence sensing, asymmetric synthetic organic chemistry, and photoisomerization of chiral molecules. Our goal is to show that despite ESPT of chiral molecules being a relatively new pursuit, there has been significant progress and even greater potential for ESPT in these and other applications yet to be realized.
Condensation of laser‐produced gold plasma during expansion and cooling in a water environment
Authors: Petrov Yu.V. , Inogamov N.A. , Zhakhovsky V.V. , Khokhlov V.A.
Published: May 2019

Physical processes involved in laser ablation in liquid (LAL) are studied using a gold target irradiated through transparent water. During and after irradiation, the heated material from the surface of a target produces a plume that expands into liquid‐forming nanoparticles (NPs). The LAL method of NP production is ecologically much cleaner than others. A better understanding of the processes associated with complicated hydrodynamic phenomena leading to LAL is important for controlled manufacturing. We consider laser pulses with different durations τL covering fifth orders of magnitudes ranging from 0.1 ps to 0.5 ns and large absorbed fluences Fabs near optical breakdown of liquid. It is shown that the trajectory of the contact boundary with liquid at the middle and late stages after passing the maximum intensity of the longest pulse is rather similar for very different pulse durations if energies Fabs are comparable. We trace how hot (in a few eV range) dense gold plasma expands, cools down, intersects a saturation curve, and condenses into NPs appearing first inside the water‐gold diffusively mixed intermediate layer where gold vapour has the lowest temperature. Later, the pressure around the gold‐water contact drops down below the critical pressure for water. As a result, the nanoparticles find themselves in gaseous water bubble where density of water gradually decreases to 10−4 − 10−5  g/cm3 at maximum bubble expansion.
Understory plant composition and nitrogen transformations resistant to changes in seasonal precipitation
Authors: Ploughe Laura W. , Dukes Jeffrey S.
Published: May 2019

Climate change has increased global mean surface temperatures and altered hydrological processes, and projections suggest that these changes will accelerate. As seasonal precipitation patterns change, so will the soil resources available for plants. In the midwestern United States, winter temperatures and precipitation are expected to increase, while snowfall is expected to be reduced. Reduced snowpack could lead to greater frost damage and alter the timing and amount of plant available resources at the start of the growing season. In the summer, precipitation is expected to decrease, and variability is expected to increase, creating longer and more frequent dry periods. In temperate forests, herbaceous understory plants and woody plants in early developmental stages are expected to be highly sensitive to changes in abiotic conditions. Here, we study how seasonal changes in precipitation affect the timing and availability of resources in a temperate deciduous forest. Further, we examine how changes in abiotic conditions influence understory composition and woody plant recruitment. We established a fully factorial experiment that manipulated winter snowfall and summer precipitation to create wet, dry, and control (ambient) conditions in a temperate deciduous forest near West Lafayette, Indiana, USA. We found that large changes in winter and summer precipitation appeared to affect forest processes independently of one another, and changes in seasonal precipitation altered understory composition minimally and had little to no effect on mineralization rates. The recruitment of woody plant species may be more sensitive to altered precipitation, as snow removal lowered germination rates and wet summer conditions lowered relative growth of a woody plant species, Lindera benzoin. In general, though, ecological processes in this forest understory were relatively resistant to change, at least in the short timeframe of this experiment.
TCR‐induced alteration of primary MHC peptide anchor residue
Authors: Madura Florian , Rizkallah Pierre J. , Legut Mateusz , Holland Christopher J. , Fuller Anna , Bulek Anna , Schauenburg Andrea J. , Trimby Andrew , Hopkins Jade R. , Wells Stephen A. , Godkin Andrew , Miles John J. , Sami Malkit , Li Yi , Liddy Nathaniel , Jakobsen Bent K. , Loveridge E. Joel , Cole David K. , Sewell Andrew K.
Published: May 2019

The HLA‐A*02:01‐restricted decapeptide EAAGIGILTV, derived from melanoma antigen recognized by T‐cells‐1 (MART‐1) protein, represents one of the best‐studied tumor associated T‐cell epitopes, but clinical results targeting this peptide have been disappointing. This limitation may reflect the dominance of the nonapeptide, AAGIGILTV, at the melanoma cell surface. The decapeptide and nonapeptide are presented in distinct conformations by HLA‐A*02:01 and TCRs from clinically relevant T‐cell clones recognize the nonapeptide poorly. Here, we studied the MEL5 TCR that potently recognizes the nonapeptide. The structure of the MEL5‐HLA‐A*02:01‐AAGIGILTV complex revealed an induced fit mechanism of antigen recognition involving altered peptide–MHC anchoring. This “flexing” at the TCR–peptide–MHC interface to accommodate the peptide antigen explains previously observed incongruences in this well‐studied system and has important implications for future therapeutic approaches. Finally, this study expands upon the mechanisms by which molecular plasticity can influence antigen recognition by T cells.
Synthesis of MoO3/polypyrrole nanocomposite and its adsorptive properties toward cadmium(II) and nile blue from aqueous solution: Equilibrium isotherm and kinetics modeling
Authors: Siddiqui Mohammad Fuzail , Khan Equbal A. , Alam Khan Tabrez
Published: May 2019

Molybdenum trioxide/polypyrrole (MoO3/Ppy) nanocomposite was prepared via oxidative polymerization of pyrrole monomer with MoO3 nanoparticles. The adsorption of Cd+2 and nile blue (NB) onto the nanocomposite was investigated in terms of various process parameters. The characterization of MoO3/Ppy nanocomposite was carried out by Fourier transform‐infrared spectroscopy, X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy dispersive X‐ray spectroscopy. Higher R2 (0.992–0.997 for Cd+2 and 0.997–0.998 for NB) and lower standard error of estimation values (1.04–1.82 for Cd+2 and 0.87–1.07 for NB) for Freundlich isotherm highlighted the multilayer adsorption onto heterogeneous nanocomposite surface. The higher Qm values at 323 K for Cd+2 (181 mg/g) and NB (189 mg/g) compared to many reported adsorbents proved the adsorptive superiority of MoO3/Ppy. The energy of adsorption (E) values from Dubinin–Radushkevich model was 1.26–1.38 and 1.36–1.44 kJ/mol for Cd+2 and NB, respectively, suggesting physical adsorption. Pseudo‐second order kinetic model governed the adsorption of Cd+2 and NB with intraparticle and liquid film diffusion controlling the mechanism. The negative ΔG values (8.4–9.4 kJ/mol) and positive ΔH values (2.5–6.1 kJ/mol) implied spontaneous and endothermic adsorption process. The positive ΔS values (0.036–0.048 kJ/mol/K) indicated increased randomness at MoO3/Ppy‐Cd+2 or NB interface. The MoO3/Ppy nanocomposite proved to be suitable and efficient adsorbent for sequestering of Cd+2 and NB from aqueous solution.
Influence of prior pH and thermal stresses on thermal tolerance of foodborne pathogens
Authors: Kim Chyer , Bushlaibi Mariam , Alrefaei Rana , Ndegwa Eunice , Kaseloo Paul , Wynn Crystal
Published: May 2019

Improper food processing is one of the major causes of foodborne illness. Accurate prediction of the thermal destruction rate of foodborne pathogens is therefore vital to ensure proper processing and food safety. When bacteria are subjected to pH and thermal stresses during growth, sublethal stresses can occur that may lead to differences in their subsequent tolerance to thermal treatment. As a preliminary study to test this concept, the current study evaluated the effect of prior pH and thermal stresses on thermal tolerance of Salmonella and Staphylococcus using a tryptic soy broth supplemented with yeast extract. Bacteria incubated at three pH values (6.0, 7.4, and 9.0) and four temperatures (15, 25, 35, and 45°C) for 24 hr were subjected to thermal treatments at 55, 60, and 65°C. At the end of each treatment time, bacterial suspensions were surface‐plated on standard method agar for quantification of bacterial survival and further calculation of the thermal death decimal reduction time (D‐value) and thermal destruction temperature (z‐value). The effect of pH stress alone during the incubation on the thermal tolerance of both bacteria was generally insignificant. An increasing pattern of D‐value was observed with the increment of thermal stress (incubation temperature). The bacteria incubated at 35°C required the highest z‐value to reduce the 90% in D‐values. Staphylococcus mostly displayed higher tolerance to thermal treatment than Salmonella. Although further research is needed to validate the current findings on food matrices, findings in this study clearly affirm that adaptation of bacteria to certain stresses may reduce the effectiveness of preservation procedures applied during later stage of food processing and storage.
Evaluation of nutritional value ofAsystasia mysorensisandSesamum angustifoliaand their potential contribution to human health
Authors: Maina Ernest G. , Madivoli Edwin S. , Ouma Josephine A. , Ogilo Joel K. , Kenya Jackson M.
Published: May 2019

Wild indigenous vegetables make considerable contributions to food baskets among subsistence farmers in sub‐Saharan Africa. The aim of this study was to evaluate the proximate analysis, mineral composition, vitamin C content, β‐carotene content, and GC‐MS profile of crude methanolic extracts ofAsystasia mysorensisandSesamum angustifolia. Crude extracts obtained through sequential extraction using ethyl acetate and methanol were screened for the presence of secondary metabolites. Functional groups present were determined with a Shimadzu FT‐IR spectrophotometer, while β‐carotene content and ascorbic acid content were evaluated using a Shimadzu HPLC and Shimadzu UV‐VIS spectrophotometer, respectively. Secondary metabolites present in the extracts were determined qualitatively using a Shimadzu GC‐MS system equipped with a NIST spectral database. From the results obtained, the two plants could supply the recommended daily requirement for micronutrient and vitamin C content needed for a healthy diet. The total phenolic and flavonoid contents inS. amgustifoliawere higher as compared toA. myorensis;hence, their consumption is highly beneficial as some compounds identified in the GC‐MS profile have been reported to have medicinal properties. The findings on the mineral and chemical composition, GC‐MS profile ofA. mysorensisandS. angustifoliaindicate that their consumption may provide the recommended nutritional requirements needed for a healthy diet.
Evaluation of the 3D fractal dimension as a marker of structural brain complexity in multiple‐acquisition MRI
Authors: Krohn Stephan , Froeling Martijn , Leemans Alexander , Ostwald Dirk , Villoslada Pablo , Finke Carsten , Esteban Francisco J.
Published: May 2019

Fractal analysis represents a promising new approach to structural neuroimaging data, yet systematic evaluation of the fractal dimension (FD) as a marker of structural brain complexity is scarce. Here we present in‐depth methodological assessment of FD estimation in structural brain MRI. On the computational side, we show that spatial scale optimization can significantly improve FD estimation accuracy, as suggested by simulation studies with known FD values. For empirical evaluation, we analyzed two recent open‐access neuroimaging data sets (MASSIVE and Midnight Scan Club), stratified by fundamental image characteristics including registration, sequence weighting, spatial resolution, segmentation procedures, tissue type, and image complexity. Deviation analyses showed high repeated‐acquisition stability of the FD estimates across both data sets, with differential deviation susceptibility according to image characteristics. While less frequently studied in the literature, FD estimation in T2‐weighted images yielded robust outcomes. Importantly, we observed a significant impact of image registration on absolute FD estimates. Applying different registration schemes, we found that unbalanced registration induced (a) repeated‐measurement deviation clusters around the registration target, (b) strong bidirectional correlations among image analysis groups, and (c) spurious associations between the FD and an index of structural similarity, and these effects were strongly attenuated by reregistration in both data sets. Indeed, differences in FD between scans did not simply track differences in structure per se, suggesting that structural complexity and structural similarity represent distinct aspects of structural brain MRI. In conclusion, scale optimization can improve FD estimation accuracy, and empirical FD estimates are reliable yet sensitive to image characteristics.
Widespread and lateralized social brain activity for processing dynamic facial expressions
Authors: Sato Wataru , Kochiyama Takanori , Uono Shota , Sawada Reiko , Kubota Yasutaka , Yoshimura Sayaka , Toichi Motomi
Published: May 2019

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.
Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production by Micro‐RNA 155 in Alcoholic Liver Disease
Authors: Babuta Mrigya , Furi Istvan , Bala Shashi , Bukong Terence N. , Lowe Patrick , Catalano Donna , Calenda Charles , Kodys Karen , Szabo Gyongyi
Published: May 2019

Cellular homeostais, that is normally maintained through autophagy, is disrupted in alcoholic liver disease (ALD). Because autophagy and exosome biogenesis share common elements, we hypothesized that increased exosome production in ALD may be linked to disruption of autophagic function. We found impaired autophagy both in ALD and alcoholic hepatitis (AH) mouse models and human livers with ALD as indicated by increased hepatic p62 and LC3‐II levels. Alcohol reduced autophagy flux in vivo in chloroquine‐treated mice as well as in vitro in hepatocytes and macrophages treated with bafilomycin A. Our results revealed that alcohol targets multiple steps in the autophagy pathway. Alcohol‐related decrease in mechanistic target of rapamycin (mTOR) and Ras homolog enriched in brain (Rheb), that initiate autophagy, correlated with increased Beclin1 and autophagy‐related protein 7 (Atg7), proteins involved in phagophore‐autophagosome formation, in ALD. We found that alcohol disrupted autophagy function at the lysosomal level through decreased lysosomal‐associated membrane protein 1 (LAMP1) and lysosomal‐associated membrane protein 2 (LAMP2) in livers with ALD. We identified that micro‐RNA 155 (miR‐155), that is increased by alcohol, targets mTOR, Rheb, LAMP1, and LAMP2 in the authophagy pathway. Consistent with this, miR‐155‐deficient mice were protected from alcohol‐induced disruption of autophagy and showed attenuated exosome production. Mechanistically, down‐regulation of LAMP1 or LAMP2 increased exosome release in hepatocytes and macrophages in the presence and absence of alcohol. These results suggested that the alcohol‐induced increase in exosome production was linked to disruption of autophagy and impaired autophagosome and lysosome function. Conclusion: Alcohol affects multiple genes in the autophagy pathway and impairs autophagic flux at the lysosome level in ALD. Inhibition of LAMP1 and LAMP2 promotes exosome release in ALD. We identified miR‐155 as a mediator of alcohol‐related regulation of autophagy and exosome production in hepatocytes and macrophages.
APOBEC‐mediated DNA alterations: A possible new mechanism of carcinogenesis in EBV‐positive gastric cancer
Authors: Bobrovnitchaia Irina , Valieris Renan , Drummond Rodrigo D. , Lima Joao P. , Freitas Helano C. , Bartelli Thais F. , de Amorim Maria G. , Nunes Diana N. , Dias‐Neto Emmanuel , da Silva Israel T.
Published: May 2019

Mechanisms of viral oncogenesis are diverse and include the off‐target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single‐strand DNA editing capability of APOBECs represent a well‐conserved viral infection response that can also cause untoward mutations in the host DNA. Here we show, after evaluating somatic single‐nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA‐expression and the APOBEC‐mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC mutations preferentially occurring in the genomic loci of the most active transcripts. This EBV infection and APOBEC3 mutation‐signature axis were confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV‐induced gastric carcinogenesis. After further validation, this EBV‐APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.
Protective role of luteolin against bisphenol A‐induced renal toxicity through suppressing oxidative stress, inflammation, and upregulating Nrf2/ARE/ HO‐1 pathway
Authors: Alekhya Sita Gadamsetty Jaya , Gowthami Motati , Srikanth Gadiparthi , Krishna M. Murali , Rama Sireesha Kokkiligadda , Sajjarao Mounika , Nagarjuna Kandru , Nagarjuna Mukkamulla , Chinnaboina Gopala Krishna , Mishra Anurag , SreeHarsha Nagaraja
Published: May 2019

For the development of renal diseases, oxidative stress (OS) is reasoned to be one of the risk factors. For the treatment or prevention of the renal disease, the use of antioxidants could be a hopeful therapeutic mediation as they retard or block the oxidative reaction along with the inflammatory process. Luteolin (Lut) is a plant flavonoid, a pharmacologically active component normally found in glycosylated forms in basic perilla leaf, green pepper, celery, seed, honeysuckle bloom, and chamomile blossom; it exhibits antioxidant activity. In this investigation, we explored the nephroprotective activity of Lut on bisphenol A (BPA)‐induced nephron toxicity in rats. Orally administering Lut (100 and 200 mg/kg) diminished BPA‐induced anomalies in the kidney, blood urea nitrogen, creatinine, and serum uric acid levels. Lut therapy reduced the BPA‐influenced generation of inflammatory mediators, inclusive of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. This was coupled with significant improvement in kidney histopathologic features. Lut enhanced the nuclear factor‐like 2 (Nrf2) and heme oxygenase 1 (HO‐1) expression, which showed protection against OS induced by BPA. The current outcomes of the study showed that Lut has a strong reactive oxygen species scavenging property and potentially decreases the lipid peroxidation as well as inhibits DNA damage in renal toxicity induced by BPA. In conclusion, the potential antioxidant effect of Lut may be because of its modulatory effect on the Nrf2/antioxidant response element (ARE)/HO‐1 pathway, which means it protects the kidney from BPA‐induced oxidative injury. © 2019 IUBMB Life, 2019
Cell‐surface‐bound circulating DNA in the blood: Biology and clinical application
Authors: Tamkovich Svetlana , Laktionov Pavel
Published: May 2019

Cell‐surface‐bound extracellular DNA (csbDNA) is present on the outer membrane of blood cells, including both red blood cells and leukocytes. Although less well characterized than cell‐free DNA (cfDNA) in plasma and serum, leukocyte and red blood cell csbDNA form a considerable fraction of the blood extracellular nucleic acids pool, with typically at least comparable amount of DNA occurring bound to the outer surface of cells as compared with circulating free DNA in plasma. The cellular origin of csbDNA is not clear; however, as with cfDNA, in patients with cancer a proportion is derived from the tumor, thus making it potentially a useful source of DNA for cancer diagnosis, prognosis, and monitoring. © 2019 IUBMB Life, 71(9):1201–1210, 2019
Trabecular architecture in the humeral metaphyses of non‐avian reptiles (Crocodylia, Squamata and Testudines): Lifestyle, allometry and phylogeny
Authors: Plasse Martial , Amson Eli , Bardin Jérémie , Grimal Quentin , Germain Damien
Published: May 2019

The lifestyle of extinct tetrapods is often difficult to assess when clear morphological adaptations such as swimming paddles are absent. According to the hypothesis of bone functional adaptation, the architecture of trabecular bone adapts sensitively to physiological loadings. Previous studies have already shown a clear relation between trabecular architecture and locomotor behavior, mainly in mammals and birds. However, a link between trabecular architecture and lifestyle has rarely been examined. Here, we analyzed trabecular architecture of different clades of reptiles characterized by a wide range of lifestyles (aquatic, amphibious, generalist terrestrial, fossorial, and climbing). Humeri of squamates, turtles, and crocodylians have been scanned with microcomputed tomography. We selected spherical volumes of interest centered in the proximal metaphyses and measured trabecular spacing, thickness and number, degree of anisotropy, average branch length, bone volume fraction, bone surface density, and connectivity density. Only bone volume fraction showed a significant phylogenetic signal and its significant difference between squamates and other reptiles could be linked to their physiologies. We found negative allometric relationships for trabecular thickness and spacing, positive allometries for connectivity density and trabecular number and no dependence with size for degree of anisotropy and bone volume fraction. The different lifestyles are well separated in the morphological space using linear discriminant analyses, but a cross‐validation procedure indicated a limited predictive ability of the model. The trabecular bone anisotropy has shown a gradient in turtles and in squamates: higher values in amphibious than terrestrial taxa. These allometric scalings, previously emphasized in mammals and birds, seem to be valid for all amniotes. Discriminant analysis has offered, to some extent, a distinction of lifestyles, which however remains difficult to strictly discriminate. Trabecular architecture seems to be a promising tool to infer lifestyle of extinct tetrapods, especially those involved in the terrestrialization.
2019 HRS/EHRA/APHRS/LAHRS focused update to 2015 expert consensus statement on optimal implantable cardioverter‐defibrillator programming and testing
Authors: Stiles Martin K. , Fauchier Laurent , Morillo Carlos A. , Wilkoff Bruce L.
Published: May 2019

The 2015 HRS/EHRA/APHRS/SOLAECE Expert Consensus Statement on Optimal Implantable Cardioverter‐Defibrillator Programming and Testing provided guidance on bradycardia programming, tachycardia detection, tachycardia therapy, and defibrillation testing for implantable cardioverter‐defibrillator (ICD) patient treatment. The 32 recommendations represented the consensus opinion of the writing group, graded by Class of Recommendation and Level of Evidence. In addition, Appendix B provided manufacturer‐specific translations of these recommendations into clinical practice consistent with the recommendations within the parent document. In some instances, programming guided by quality evidence gained from studies performed in devices from some manufacturers was translated such that this programming was approximated in another manufacturer's ICD programming settings. The authors found that the data, although not formally tested, were strong, consistent, and generalizable beyond the specific manufacturer and model of ICD. As expected, because these recommendations represented strategic choices to balance risks, there have been reports in which adverse outcomes were documented with ICDs programmed to Appendix B recommendations. The recommendations have been reviewed and updated to minimize such adverse events. Notably, patients who do not receive unnecessary ICD therapy are not aware of being spared potential harm, whereas patients in whom their ICD failed to treat life‐threatening arrhythmias have their event recorded in detail. The revised recommendations employ the principle that the randomized trials and large registry data should guide programming more than anecdotal evidence. These recommendations should not replace the opinion of the treating physician who has considered the patient's clinical status and desired outcome via a shared clinical decision‐making process.
The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration
Authors: Wang Hua‐Cong , Jin Cang‐Hai , Kong Jie , Yu Tao , Guo Jian‐Wei , Hu You‐Gu , Liu Yong
Published: May 2019

The present study determines whether the in vivo injection of TGFβ1 and CTGF mediated by AAV2 to transfect nucleus pulposus cells in degenerative lumbar discs can reverse the biological effects of rhesus lumbar disc degeneration. A total of 42 lumbar discs obtained from six rhesus monkeys were classified into three groups: experimental group, control group, and blank group. Degenerative lumbar discs were respectively injected with double gene‐transfected human nucleus pulposus cells using minimally invasive techniques. Immumohistochemical staining, RT‐PCR, and western blot were performed to observe the biological effects of double gene‐transfected human nucleus pulposus cells in degenerative lumbar discs on rhesus lumbar disc degeneration. At 4, 8, and 12 weeks after the transplantation of nucleus pulposus cells, the expression levels of TGF‐ß1, CTGF, proteoglycan mRNA, and type‐II collagen were detected by RT‐PCR. The values of immumohistochemical staining and RT‐PCR in the experimental group increased at 8 weeks, decreased with time at 12 weeks, and remained greater than the values in the control group, and the differences were statistically significant (P < .05). The western blot revealed that the values in the experimental group decreased with time, but remained greater than those in the PBS control group and blank control group, and the differences were statistically significant (P < .05). The double gene‐transfection of human nucleus pulposus cells in degenerative lumbar discs mediated by rAAV2 can be continuously expressed in vivo after transplantation in lumbar discs of rhesus monkeys, and promotes the synthesis of proteoglycan and type II collagen, achieving the treatment purpose.
The rising rate of nonsmokers among laryngeal carcinoma patients: Are we facing a new disease?
Authors: Shoffel‐Havakuk Hagit , O'Dell Karla , Johns Michael M. , Reder Lindsay , Popova Margarita , Halperin Doron , Feldberg Edit , Lahav Yonatan
Published: May 2019

Objectives/Hypothesis

Laryngeal squamous cell carcinoma (SCC) is strongly associated with tobacco smoking. With the rising awareness of tobacco's adverse health effects, we have witnessed a global decrease in tobacco use. Nevertheless, laryngeal SCC remains prevalent and includes a subset of patients lacking the traditional risk factors.

Study Design

A two‐center retrospective cohort.

Methods

Medical records of patients diagnosed with laryngeal SCC between 2009 and 2016 were reviewed. Data collected included demographics, smoking status, and tumor site. Patients who have never smoked were designated as nonsmokers.

Results

The study included 330 patients with laryngeal SCC, of whom 75 (22.7%) were nonsmokers; this rate was relatively similar for each of the two institutions independently (21.9% and 25%). There were 285 patients with glottic SCC and 45 with supraglottic SCC. All nonsmoking patients in this cohort had glottic SCC, representing 26.3% (75/285) of the glottic SCC cases. The rate of female patients was significantly higher among nonsmokers. Of the patients with glottic SCC, females represented 25.3% (19/75) of the nonsmokers compared with 12.4% (26/210) of the smokers (P = .008). Mean age at diagnosis was 60.2 ± 17.5 years for nonsmoking glottic SCC patients and 63.6 ± 12.4 years for smokers (P = .280). However, nonsmokers demonstrated a distinct age distribution pattern. Nonsmoking females with glottic SCC demonstrated a bimodal age distribution pattern; 73.7% (14/19) were age <40 years or >75 years at diagnosis.

Conclusions

The rate of laryngeal SCC in nonsmokers is higher than what has previously been reported, representing a growing proportion, and may suggest a shift in etiology. Knowing that laryngeal SCC in nonsmokers predominantly affects the glottis, and that females and age extremities are more vulnerable, the traditional screening paradigm should be revised.

Level of Evidence

4

Laryngoscope, 130:E108–E115, 2020
Incorporation of Very Insoluble Monomers in Waterborne Coatings
Authors: Boscán Freddy , Meeuwisse Marcel , Mestach Dirk , Paulis Maria , Barandiaran Maria Jesus , Bohórquez Silfredo Javier
Published: May 2019

The benefits of polymerizing very insoluble monomers in aqueous media, avoiding the use of energy‐intensive procedures, by implementing two novel synthesis techniques based on the emulsifier combination in emulsion polymerization and on miniemulsification by phase inversion temperature are investigated. The performance of standalone polymers consisting of monomers, namely lauryl methacrylate, isobornyl acrylate, and 1H,1H,2H,2H‐perfluorodecyl acrylate, and of formulated binders with these monomers incorporated either through blending or in situ polymerization, is evaluated with special emphasis on their water‐barrier properties (e.g., uptake, whitening, immersion, and vapor resistance) and on their chemical resistance. The performance of the standalone polymers is found to be similar to that of polymers prepared by high‐shear miniemulsion polymerization, while the performance of the formulated binders is generally superior to a commercial coating formulation based on a binder recommended for water resistance.
Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade
Authors: Marras Connie , Canning Colleen G. , Goldman Samuel M.
Published: May 2019

There is evidence from observational studies for a role of a number of environmental exposures and lifestyle habits in modulating the risk for Parkinson's disease. Environmental and lifestyle associations, if causal, represent opportunities for Parkinson's disease prevention or disease modification at individual and population levels. In the past decade, additional evidence has been published that improves causal inference and/or enhances our understanding of the complexity of these associations. A number of gene–environment interactions have been elucidated, and our understanding of the roles of physical activity, pesticide and other chemical exposures, dietary habits, emotional stress, head injury, and smoking has been refined. In the next decade, better techniques will help us to close the gaps in our knowledge, including taking into account Parkinson's disease heterogeneity and gene and risk factor interactions in observational studies. To do this, larger datasets, global consortia, genomewide environment interaction studies, prospective studies throughout the lifespan, and improvements in the methodology of clinical trials of physical activity will be key. Despite the caveats of observational studies, a number of low‐risk and potentially high‐yield recommendations for lifestyle modification could be made to minimize the individual and societal burdens of Parkinson's disease, including dietary modifications, increasing physical activity, and head injury avoidance. Furthermore, a reduction in pesticide use could have a major impact on global health related to and beyond Parkinson's disease. Given the increasing prevalence of this disorder, formulating and promoting these recommendations should be a high priority. © 2019 International Parkinson and Movement Disorder Society
Strip Spawning Methodology for Captive Propagation of Broadcast-Spawning Cyprinids in the Great Plains
Authors: Urbanczyk Aaron C , Woodley Christa M , Wilde Gene R
Published: May 2019

In the summer of 2011, large parts of Texas and Oklahoma experienced their worst drought in recorded history. Most of the rivers and streams in this region are inhabited by cyprinids that broadcast semibuoyant pelagic ova. These fish depend on flowing water for the hormonal cues that induce spawning and to allow ova to develop and hatch as they float downstream. During the drought, the Brazos and Canadian rivers, Texas, were reduced to isolated streambed pools. Monitoring efforts concluded that pelagic, broadcast-spawning cyprinids experienced complete reproductive failure in the Brazos River and had very little spawning success in the Canadian River. Personnel from the Texas Parks and Wildlife Department, U.S. Fish and Wildlife Service, and Texas Tech University began salvage operations in both rivers in September 2011 to ensure the survival of imperiled cyprinids. In spring 2012, standard captive propagation techniques were used with several species of cyprinids, with little success. As a result, we developed new techniques for four species of pelagic, broadcast-spawning cyprinids from the Brazos and Canadian rivers that could greatly increase hatchery program efficacy.
Magnetic resonance imaging as an assessment tool following intervention with an AdVance XP suburethral sling for postprostatectomy urinary incontinence
Authors: Collado Serra Argimiro , Pelechano Gómez Paula , Martin Isabel , Dominguez‐Escrig Jose , Alberich‐Bayarri Ángel , Barrios María , Cervera Deval José , Rubio‐Briones José
Published: May 2019

Aims

The aim of this study was to compare magnetic resonance imaging (MRI) parameters in patients with mild incontinence after radical prostatectomy, who had undergone treatment with a suburethral sling. The objective was to compare patients who had been successfully treated with unsuccessful patients.

Methods

This observational cohort study at a single institution evaluated consecutive patients treated with an AdVance XP sling. MRI was performed using a 1.5 Tesla system. Preoperative urodynamic assessment and flexible cystoscopy were performed. The qualitative analysis was based on sling indentation (complete vs incomplete). The quantitative analysis comprised the following three parameters: the sling‐pubis distance, the thickness of the proximal urethral bulb, and the sling backward distance (SBD), defined as the distance between the prolongation of a line through the major axis of the pubis (the line‐segment joining the vertices of the pubis) and the sling indentation. The primary outcome was pad count at 3 months; cure as zero pads. A logistic univariate regression model was employed to assess the potential predictors of successful outcomes. An adjusted multivariate logistic regression model using the significant univariate factors was developed.

Results

Of the 83 patients enrolled, the univariate analysis revealed a relationship between failure and adverse urodynamics and between success and sling indentation, thickness of the proximal bulb and SBD. Only the association with SBD persisted in the multivariate analysis.

Conclusions

MRI revealed a strong relationship between proper positioning of the sling (small SBD) and continence outcome. These data have important implications for a second surgery following initial sling failure.
Ylide‐Functionalization via Metalated Ylides: Synthesis and Structural Properties
Authors: Schwarz Christopher , Scherpf Thorsten , Rodstein Ilja , Weismann Julia , Feichtner Kai‐Stephan , Gessner Viktoria H.
Published: May 2019

The α‐metallated ylides [Ph3P−C−Z]−M+ (with Z=SO2Tol or CN and M=Na or K) were used as versatile nucleophiles for the facile access to ylide‐substituted compounds. Halogenations, alkylations, carbonylations and functionalization reactions with main group element halides were easily accomplished by simple trapping reactions with the appropriate electrophiles. X‐ray crystallographic studies of all compounds – including the first structures of α‐fluorinated P‐ylides – showed remarkable differences in the ylide backbone depending on the substituents. In the fluorinated compounds, a change from a fully planar to a pyramidalized ylidic carbon centre was observed despite the strongly anion‐stabilizing ability of the yldiide substituent. π‐Donation from the ylide substituent also resulted in geometric restrictions depending on the steric and electronic properties of the introduced substituents.