bluuebunny/crossref_metadata_2025 huggingface dataset:
A new cancer immunotherapy via simultaneous DC‐mobilization and DC‐targeted IDO gene silencing using an immune‐stimulatory nanosystem
Authors: Zhang Yujuan , Fu Jiamin , Shi Yanmei , Peng Shanshan , Cai Ying , Zhan Xuelin , Song Na , Liu Yanling , Wang Zhigang , Yu Yanrong , Wang Yifan , Shi Qiaofa , Fu Yingyuan , Yuan Keng , Zhou Nanjin , Joshi Rakesh , Ichim Thomas E. , Min Weiping
Published: May 2018

The activity of negative immune regulatory molecules, such as indoleamine 2,3‐oxygenase (IDO), significantly attenuates DC (Dendritic cells)‐mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti‐tumor immunity. However, a DC‐targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In our study, we developed a novel DC‐targeted siRNA delivery system, man‐GNR‐siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs. We explored the immunostimulatory man‐GNR‐siIDO nano‐construct in DCs mobilized by Flt3‐L, a receptor‐type tyrosine kinase ligand, for lung cancer immunotherapy. In vivo DC‐targeted gene silencing of IDO resulted in robust anti‐tumor immunity as evidenced by promoting DC maturation, up‐regulating tumor antigen‐specific T‐cell proliferation and enhancing tumor‐specific cytotoxicity. A combinatorial treatment for Lewis Lung Carcinoma (LLC)‐bearing mice, with man‐GNR‐siIDO and Flt3‐L, significantly attenuated tumor growth and delayed tumor formation, suggesting the treatment feasibility of the man‐GNR‐siIDO system in Flt3‐L mobilized DCs in the immunotherapy of lung cancer. Therefore, our study highlights a clinical potential for a first‐in‐class anti‐cancer immunotherapy through simultaneous DC‐mobilization and DC‐targeted gene silencing of IDO with man‐GNR‐siIDO and Flt3‐L treatments.
Association between a pro plant‐based dietary score and cancer risk in the prospective NutriNet‐santé cohort
Authors: Kane‐Diallo Abou , Srour Bernard , Sellem Laury , Deschasaux Mélanie , Latino‐Martel Paule , Hercberg Serge , Galan Pilar , Fassier Philippine , Guéraud Françoise , Pierre Fabrice H. , Kesse‐Guyot Emmanuelle , Allès Benjamin , Touvier Mathilde
Published: May 2018

Diverse plant products (e.g. fruits, vegetables, legumes) are associated with decreased cancer risk at several locations while red and processed meat were found to increase cancer risk. A pro plant‐based dietary score reflecting the relative contribution of consumed plant vs animal products was developed, and was associated with lower overall mortality, type 2 diabetes and cardiovascular disease risk, among omnivorous adults. For the first time, we investigated the prospective associations between this pro plant‐based dietary score and cancer risk. This study included 42,544 men and women of the French NutriNet‐Santé prospective cohort (2009‐2016) aged ≥45 years who completed at least three 24‐hr‐dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific tertiles of pro plant‐based dietary score by multivariable Cox models. In total, 1,591 first primary incident cancer cases were diagnosed during follow‐up, among which 487 breast, 243 prostate, 198 digestive and 68 lung cancers. A higher pro plant‐based dietary score was associated with decreased risks of overall (HRt3vs.t1=0.85; 95% CI 0.76, 0.97; Ptrend =0.02), digestive (HRt3vs.t1=0.68; 95% CI 0.47; 0.99; Ptrend = 0.04) and lung (HRt3vs.t1=0.47; 95% CI 0.25, 0.90; Ptrend =0.02) cancer, though no substantial associations were found for breast or prostate cancers. This large cohort study supports a beneficial role of higher intakes of plant‐based products along with lower intakes of animal products, within a balanced omnivorous diet, regarding primary cancer prevention. These results are consistent with mechanistic evidence from experimental studies.
Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer
Authors: La Manna Sara , Lee Eunmi , Ouzounova Maria , Di Natale Concetta , Novellino Ettore , Merlino Antonello , Korkaya Hasan , Marasco Daniela
Published: May 2018

Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer‐associated inflammation and suppressive immunity leading to enhanced tumor growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N‐terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot‐spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA‐MB‐231‐luci tumors as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumor growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines.
HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation
Authors: Song Xiaojia , Tan Siyu , Wu Zhuanchang , Xu Leiqi , Wang Zehua , Xu Yong , Wang Tixiao , Gao Chengjiang , Gong Yaoqin , Liang Xiaohong , Gao Lifen , Spear Brett T. , Ma Chunhong
Published: May 2018

Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important and complex role in processes leading to HCC. We previously identified the mammalian Zinc fingers and homeoboxes 2 (ZHX2) gene as an HCC‐associated tumor suppressor gene. In the present study, we investigated whether the oncogenic properties of HBV and, more specifically, HBx, involved ZHX2 silencing. Our data indicates that ZHX2 expression is significantly decreased in tumor tissues from HBV‐positive HCC patients and livers from HBV transgenic mice. In vitro and in vivo studies confirmed that HBV‐encoded proteins, particularly HBx, inhibits both the expression and tumor suppression properties of ZHX2. Further analyses identified miR‐155, a well‐known oncomiR in various cancers, as an important link between HBx and ZHX2 inhibition. Increased miR‐155 levels were found in HBV‐positive tumors, livers of HBV transgenic mice and HBx‐overexpressing hepatoma cell lines. MiR‐155 overexpression reduced ZHX2 levels via miR‐155 seed sites in the ZHX2 3′UTR, whereas blocking miR‐155 levels led to increased ZHX2 levels. Taken together, our data indicate that HCC‐promoting properties of HBV may include ZHX2 silencing via a miR‐155 dependent pathway and suggests a novel therapy for HBV‐related HCC.
Tumor progression and metastatic dissemination in ovarian cancer after dose‐dense or conventional paclitaxel and cisplatin plus bevacizumab
Authors: Bizzaro Francesca , Falcetta Francesca , D’Agostini Elisa , Decio Alessandra , Minoli Lucia , Erba Eugenio , Alessandro Peccatori Fedro , Scanziani Eugenio , Colombo Nicoletta , Zucchetti Massimo , Bani Maria Rosa , Ubezio Paolo , Giavazzi Raffaella
Published: May 2018

The efficacy of therapeutic regimens incorporating weekly or every‐3‐weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose‐dense‐equi (every other day to the conventional cumulative dose), or dose‐dense‐high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time‐windows in two patient‐derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short‐term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose‐dense (with/without DDP) was superior to the conventional scheme in a dose‐dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose‐dense‐high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose‐dense‐high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule‐dose of the treatment and help to explain the unclear benefits after bevacizumab.
Prognostic roles for IL‐2‐producing and CD69+T cell subsets in colorectal cancer patients
Authors: Taylor Edward S. , McCall John L. , Shen Shirley , Girardin Adam , Munro Fran M. , Black Michael A. , Ward‐Hartstonge Kirsten A. , Kemp Roslyn A.
Published: May 2018

Tumor infiltrating T cells are a predictor of patient outcome in patients with colorectal cancer (CRC). However, many T cell populations have been associated with both poor and positive patient prognoses, indicating a need to further understand the role of different T cell subsets in CRC. In this study, the T cell infiltrate from the tumor and nontumor bowel (NTB) was examined in 95 CRC patients using flow cytometry and associations with cancer stage and disease recurrence made. Our findings showed that IFN‐γ‐producing T cells were associated with positive patient outcomes, and CD69+ T cells were associated with disease recurrence. Inflammatory (IL‐17) and regulatory T cells were not associated with disease recurrence. Surprisingly, in a second cohort of 32 patients with long‐term clinical follow up data, tumor infiltrating IL‐2‐producing T cells correlated negatively with disease free survival (DFS) and a higher frequency of IL‐2‐producing T cells was found in the NTB of patients with poorly differentiated tumors. These results point toward the possibility of a negative impact of IL‐2 in tumor immune responses, which may influence future immunotherapy treatments in CRC patients.
Low‐dose irradiated mesenchymal stromal cells break tumor defensive properties in vivo
Authors: Stefani Francesca Romana , Eberstål Sofia , Vergani Stefano , Kristiansen Trine A. , Bengzon Johan
Published: May 2018

Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies to overcome tumor resistance are mainly represented by multi‐targeted approaches, and cell vector‐based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow‐derived mesenchymal stromal cells (MSCs), when primed with low‐dose irradiation (irMSCs), undergo changes in their immunogenic and angiogenic capacity and acquire anti‐tumoral properties in a mouse model of glioblastoma (GBM). Following grafting in GL261 glioblastoma, irMSCs migrate extensively and selectively within the tumor and infiltrate predominantly the peri‐vascular niche, leading to rejection of established tumors and cure in 29% of animals. The therapeutic radiation dose window is narrow, with effects seen between 2 and 15 Gy, peaking at 5 Gy. A single low‐dose radiation decreases MSCs inherent immune suppressive properties in vitro as well as shapes their immune regulatory ability in vivo. Intra‐tumorally grafted irMSCs stimulate the immune system and decrease immune suppression. Additionally, irMSCs enhance peri‐tumoral reactive astrocytosis and display anti‐angiogenic properties. Hence, the present study provides strong evidence for a therapeutic potential of low‐dose irMSCs in cancer as well as giving new insight into MSC biology and applications.
Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population‐based case–control study
Authors: Troisi Rebecca , Gulbech Ording Anne , Grotmol Tom , Glimelius Ingrid , Engeland Anders , Gissler Mika , Trabert Britton , Ekbom Anders , Madanat‐Harjuoja Laura , Sørensen Henrik Toft , Tretli Steinar , Bjørge Tone
Published: May 2018

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population‐based case–control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967–2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78–0.97), gestational hypertension (OR 0.90; 95% CI 0.86–0.93) and preeclampsia (OR 0.91; 95% CI 0.88–0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98–1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.
Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer
Authors: Li Jun‐Yan , Jing Ruilin , Wei Hongyi , Wang Minghao , Xiaowei Qi , Liu Haoxi , Jian Liu , Ou Jiang‐Hua , Jiang Wei‐Hua , Tian Fu‐Guo , Sheng Yuan , Li Heng‐Yu , Xu Hong , Zhang Rui‐Shan , Guan Ai‐Hua , Liu Ke , Jiang Hong‐Chuan , Ren Yu , He Jian‐Jun , Huang Weiwei , Liao Ning , Cai Xiangjun , Ming Jia , Ling Rui , Xu Yan , Hu Chun‐Yan , Zhang Jianguo , Guo Baoliang , Ouyang Lizhi , Shuai Ping , Liu Zhenzhen , Zhong Ling , Zeng Zhen , Zhang Ting , Xuan Zhaoling , Tan Xuanni , Liang Junbin , Pan Qinwen , Chen Li , Zhang Fan , Fan Lin‐Jun , Zhang Yi , Yang Xinhua , BoLi Jing , Chen Chongjian , Jiang Jun
Published: May 2018

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
A Summer Program to Assist Diverse, Urban Adolescent Writers in Becoming College and Career Ready
Authors: Ferguson Monica L. , Dole Janice A. , Scarpulla Laura F. , Adamson Sharon L.
Published: May 2018

The authors describe and analyze the strengths and challenges of a 10‐year summer writing program that provides out‐of‐school academic support for adolescent writers who are not yet college and career ready. The two‐week program takes place at the university where faculty and school district English language arts teachers work with approximately 50 students to assist them in constructing argumentative essays. Among the strengths of the program are the research base of the writing instruction and the low teacher–student ratio that allows teachers to provide small‐group and one‐on‐one support for students’ writing. Challenges have related to assisting teachers in understanding and using the writing instructional model and transferring that model into their regular classrooms during the school year.
Comparison between reflectance confocal microscopy and 2‐photon microscopy in early detection of cutaneous radiation injury in a mouse model in vivo
Authors: Jang Won Hyuk , Kwon Soonjae , Shim Sehwan , Jang Won‐Suk , Myung Jae Kyung , Yang Sejung , Park Sunhoo , Kim Ki Hean
Published: May 2018

Cutaneous radiation injury (CRI) is a skin injury caused by high‐dose exposure of ionizing radiation (IR). For proper treatment, early detection of CRI before clinical symptoms is important. Optical microscopic techniques such as reflectance confocal microscopy (RCM) and 2‐photon microscopy (TPM) have been tested as the early diagnosis method by detecting cellular changes. In this study, RCM and TPM were compared in the detection of cellular changes caused by CRI in an in vivo mouse model. CRI was induced on the mouse hindlimb skin with various IR doses and the injured skin regions were imaged longitudinally by both modalities until the onset of clinical symptoms. Both RCM and TPM detected the changes of epidermal cells and sebaceous glands before clinical symptoms in different optical contrasts. RCM detected changes of cell morphology and scattering property based on light reflection. TPM detected detail changes of cellular structures based on autofluorescence of cells. Since both RCM and TPM were sensitive to the early stage CRI by using different contrasts, the optimal method for clinical CRI diagnosis could be either individual methods or their combination.
High‐throughput light sheet tomography platform for automated fast imaging of whole mouse brain
Authors: Yang Xiong , Zhang Qi , Huang Fei , Bai Ke , Guo Yiming , Zhang Yongsheng , Li Ning , Cui Yuting , Sun Pei , Zeng Shaoqun , Lv Xiaohua
Published: May 2018

Acquiring information of the neural structures in the whole‐brain level is vital for systematically exploring mechanisms and principles of brain function and dysfunction. Most methods for whole brain imaging, while capable of capturing the complete morphology of neurons, usually involve complex sample preparation and several days of image acquisition. The whole process including optical clearing or resin embedding is time consuming for a quick survey of the distribution of specific neural circuits in the whole brain. Here, we develop a high‐throughput light‐sheet tomography platform (HLTP), which requires minimum sample preparation. This method does not require optical clearing for block face light sheet imaging. After fixation using paraformaldehyde, an aligned 3 dimensional image dataset of a whole mouse brain can be obtained within 5 hours at a voxel size of 1.30 × 1.30 × 0.92 μm. HLTP could be a very efficient tool for quick exploration and visualization of brain‐wide distribution of specific neurons or neural circuits.
Nanoceria‐loaded injectable hydrogels for potential age‐related macular degeneration treatment
Authors: Wang Kai , Mitra Rajendra Narayan , Zheng Min , Han Zongchao
Published: May 2018

The major purpose of this article is to evaluate oligochitosan coated cerium oxide nanoparticles (OCCNPs) alginate laden injectable hydrogels and their potential treatment for age‐related macular degeneration (AMD). The water soluble OCCNPs were loaded within injectable hydrogels as antioxidative agents. The release of OCCNPs from hydrogel, radical scavenging properties, and biocompatibility were evaluated and calculated in vitro. The effects of OCCNP laden hydrogel downregulating expression of angiogenic proteins and proinflammatory cytokines were quantified in human retinal pigment epithlium‐19 (ARPE‐19) and umbilical endothelium cell lines. The hydrogels behaved with moderate swelling and controllable degradation. The laden OCCNPs were released in a controlled manner in vitro during two months of testing. The OCCNP loaded hydrogels exhibited robust antioxidative properties in oxygen radical absorbance capacity tests and reduced apoptosis in H2O2‐induced ARPE‐19 cells. Furthermore, OCCNP loaded injectable hydrogels are biocompatible and suppressed the ipopolysaccharides‐induced inflammation response in ARPE‐19 cells, and inhibited expression of vascular endothelium growth factor in human ARPE‐19 and umbilical endothelium cell lines. The alginate‐gelatin injectable hydrogel loaded OCCNPs are biocompatible and have high potential in protecting cells from apoptosis, angiogenesis, and production of proinflammatory cytokines in AMD cellular models. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2795–2804, 2018.
Fluoride anion sensing mechanism of a BODIPY‐linked hydrogen‐bonding probe
Authors: Li Yang , Chen Junsheng , Chu Tian‐Shu
Published: May 2018

The sensing mechanism of a fluoride‐anion probe BODIPY‐amidothiourea (1c) has been elucidated through the density functional theory (DFT) and time‐dependent density functional theory (TDDFT) calculations. The theoretical study indicates that in the DMSO/water mixtures the fluorescent sensing has been regulated by the fluoride complex that formed between the probe 1c/two water molecules and the fluoride anion, and the excited‐state intermolecular hydrogen bond (H‐B) plays an important role in the fluoride sensing mechanism. In the first excited state, the H‐Bs of the fluoride complex 1cFH2 are overall strengthened, which induces the weak fluorescence emission. In addition, molecular orbital analysis demonstrates that 1cFH2 has more obvious intramolecular charge transfer (ICT) character in the S1 state than 1cH2 formed between the probe 1c and two water molecules, which also gives reason to the weaker fluorescence intensity of 1cFH2. Further, our calculated UV‐vis absorbance and fluorescence spectra are in accordance with the experimental measurements. © 2018 Wiley Periodicals, Inc.
Partition coefficients of methylated DNA bases obtained from free energy calculations with molecular electron density derived atomic charges
Authors: Lara A. , Riquelme M. , Vöhringer‐Martinez E.
Published: May 2018

Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have also been used to address the accuracy of force fields for various organic compounds and specifically the methylated DNA bases. In this study, atomic charges were derived by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder) directly from the electron density obtained by electronic structure calculations in a vacuum, with an implicit solvation model or with explicit solvation taking the dynamics of the solute and the solvent into account. To test the ability of these charges to describe electrostatic interactions in force fields for condensed phases, the original atomic charges of the AMBER99 force field were replaced with the new atomic charges and combined with different solvent models to obtain the hydration and chloroform solvation free energies by molecular dynamics simulations. Chloroform–water partition coefficients derived from the obtained free energies were compared to experimental and previously reported values obtained with the GAFF or the AMBER‐99 force field. The results show that good agreement with experimental data is obtained when the polarization of the electron density by the solvent has been taken into account, and when the energy needed to polarize the electron density of the solute has been considered in the transfer free energy. These results were further confirmed by hydration free energies of polar and aromatic amino acid side chain analogs. Comparison of the two partitioning methods, Hirshfeld‐I and Minimal Basis Iterative Stockholder (MBIS), revealed some deficiencies in the Hirshfeld‐I method related to the unstable isolated anionic nitrogen pro‐atom used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the MBIS partitioning method accounting for polarization by the implicit solvation model are in good agreement with the experimental values. © 2018 Wiley Periodicals, Inc.
Degradation of tetracyclines and sulfonamides by stevensite‐ and biochar‐immobilized laccase systems and impact on residual antibiotic activity
Authors: García‐Delgado Carlos , Eymar Enrique , Camacho‐Arévalo Raquel , Petruccioli Maurizio , Crognale Silvia , D'Annibale Alessandro
Published: May 2018

BACKGROUND

Stevensite and biochar were investigated to covalently immobilize laccase from Myceliophthora thermophila (MtL) and Pleurotus eryngii (PeL) through the sequential application of aminopropyltriethoxysilane and glutaraldehyde. The immobilized preparations were tested to remove three tetracyclines and six sulfonamides at 0.1 mmol L−1 of each antibiotic. Degradation experiments were conducted both in the absence and in the presence (0.2 mmol L−1) of ABTS, 1‐hydroxybenzotriazol (HBT), syringaldehyde or violuric acid. The residual antibiotic activity was tested towards five bacterial species and a bacterial consortium from wastewater.

RESULTS

Higher values of activity yields (74% and 70.3%) and catalytic capabilities (1426 and 1405 IU g−1) were obtained with PeL on stevensite and biochar than with MtL. Stevensite enabled higher reusability and storage stability than biochar. Best removals of tetracyclines and sulfonamides were obtained with immobilized‐laccase systems coupled to ABTS or syringaldehyde. Immobilized‐laccase/ABTS systems removed 100% of tetracyclines while only chlortetracycline was completely removed in the presence of syringaldehyde. With ABTS, the most effectively removed sulfonamides were sulfathiazole and sulfadiazine (up to 100% and 54%), while syringaldehyde best supported the removal of sulfanilamide, sulfamethazine and sulfamethoxazole (up to 42%, 45% and 46%, respectively). In some cases, an effective antibiotics removal led to either low or no residual antibiotic activity.

CONCLUSION

MtL and PeL were immobilized successfully on biochar and stevensite. The addition of either ABTS or syringaldehyde enhanced significant removals, up to 100%, of tetracyclines and sulfonamides by the immobilized laccase systems. Noteworthy, biochar‐immobilized laccases/ABTS led to complete suppression of the antibiotic activity of tetracyclines. © 2018 Society of Chemical Industry
Evaluation of stress, serum and salivary cortisol, and interleukin‐1β levels in smokers and non‐smokers with chronic periodontitis
Authors: Bawankar Pranjali V. , Kolte Abhay P. , Kolte Rajashri A.
Published: May 2018

Background

Existing literature indicates a positive relationship between stress and chronic periodontitis (CP) but there is limited information on the combined influence of stress and smoking on the progression of periodontal disease. So, the objective of this study was to evaluate the effects of stress, salivary and serum, cortisol and interleukin‐1β levels in smokers with CP.

Methods

Seventy‐five patients equally divided into three groups of healthy controls (Group I), smokers and non‐smokers with CP (Group 2 and Group 3) respectively were evaluated for clinical parameters, biochemical parameters of salivary and serum cortisol and IL‐1β levels via enzyme linked immunosorbent assay (ELISA). Zung's self‐rating depression scale questionnaire was used to determine the stress levels amongst the patients.

Results

Smokers with CP exihibited higher values of probing pocket depth, clinical attachment level, plaque index while lower papillary bleeding index, and gingival index scores as compared to non‐smokers with CP. The salivary cortisol and IL‐1 β were relatively higher as compared to serum values in Group 2 than Group 3. The Group 2 patients revealed higher depression scores as compared to Group 3 patients. The depression scores positively and significantly correlated with the salivary cortisol in Group 2 patients.

Conclusion

The results indicate that smokers with CP exhibit a significantly higher serum and salivary cortisol, IL‐1β, and stress levels and thus they may show an increased risk and periodontal disease severity. Further exploration of relationships between periodontitis and stress is required.
Effect of rearing substrate on growth performance, waste reduction efficiency and chemical composition of black soldier fly (Hermetia illucens) larvae
Authors: Meneguz Marco , Schiavone Achille , Gai Francesco , Dama Andrea , Lussiana Carola , Renna Manuela , Gasco Laura
Published: May 2018

BACKGROUND

Wastes can be used as rearing substrate by black soldier fly (BSF) larvae, the latter being exploitable as a protein source in animal feed. This research aimed to assess the influence of four rearing substrates (Trial 1 (organic wastes): a mixture of vegetable and fruit (VEGFRU) vs. a mixture of fruits only (FRU); Trial 2 (agro‐industrial by‐products): brewery (BRE) vs. winery (WIN) by‐products) on BSF larvae development, waste reduction efficiency and nutritional composition.

RESULTS

If respectively compared to FRU and WIN, VEGFRU and BRE larvae needed less time to reach the prepupal stage (22.0, 22.2, 20.2 and 8.0 days of trial, respectively) and had higher protein content (229.7, 257.3, 312.9 and 395.7 g kg−1 dry matter). The waste reduction index ranged from 2.4 (WIN) to 5.3 g d−1 (BRE). BRE larvae showed the lowest saturated and the highest polyunsaturated fatty acid proportions (612.4 and 260.1 g kg−1 total fatty acids, respectively).

CONCLUSION

Vegetable and fruit wastes and winery by‐products can be used as rearing substrates for BSF larval mass production. Brewery by‐products led to very promising larval performance and nutritional composition. However, given BRE limited availability, low BRE dietary inclusion levels could be used with the purpose of increasing larval performance. © 2018 Society of Chemical Industry
Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model
Authors: Hiraishi Syunsuke , Schol Jordy , Sakai Daisuke , Nukaga Tadashi , Erickson Isaac , Silverman Lara , Foley Kevin , Watanabe Masahiko
Published: May 2018

A multitude of studies has indicated the potential of cell therapy as a method for intervertebral disc (IVD) regeneration. Transplantation of a variety of cells has been assessed and shown capable of deterring the rate of degeneration in animal models and in human clinical trials. In this study, a novel approach using human discogenic nucleus pulposus cells directly from their cryopreserved state was assessed. In an established canine disc degeneration model, the degeneration process was evaluated in IVDs receiving precultured discogenic cells, thawed‐only discogenic cells, and a saline sham injection after induction of degeneration. Degeneration progression was followed over time by the evaluation of the disc height index (DHI). Finally, after 12 weeks, the manipulated and control discs were explanted, histologically stained, and scored. Treated discs demonstrated retained DHI values for all treatment options. Histologic evaluations demonstrated significant improvement of matrix features compared to the sham. Moreover, thawed‐only cells function at least as well as precultured discogenic cells. In short, cell transplantation of human discogenic cells directly from their cryopreserved state can arrest disc height degeneration and maintain histological matrix features in a canine disc degeneration model. The presented work demonstrates the potential of an off‐the‐shelf cell therapy product to treat degenerative disc disease.
Post‐socialist cropland changes and abandonment in Mongolia
Authors: Sankey Temuulen Tsagaan , Massey Richard , Yadav Kamini , Congalton Russell G. , Tilton James C.
Published: May 2018

Large‐scale cropland changes have significant implications for global and national food supply as well as degradation in land resources. We examined cropland dynamics at the national scale in Mongolia over the last three decades using Google Earth Engine cloud computing and 11,360 Landsat satellite images. Our overarching goal was to develop the first comprehensive, high‐resolution maps of Mongolia's cropland extent for two nominal years: 1990 at the peak of the socialist era production and 2014 after major socio‐political and economic regime changes. By comparing the two cropland maps, we estimate cropland changes and identify areas of post‐socialist cropland abandonment. Our cropland classifications produce high overall accuracies (overall weighted, statistical accuracies of 98% and 97%, respectively), and the cropland area estimates compare well with county‐level crop area statistics (R2 = 0.91, p value < .001). We estimate 38% cropland decline in Mongolia throughout the major crop regions but 18% increase in the central region due to increased concentration of crop production. The observed large‐scale cropland abandonment would be expected to result in substantial land conversion to rangelands as well as land degradation in the abandoned fields, including soil erosion, increased contribution to desertification, and reduced species diversity. Future studies can monitor the long‐term trajectory in the abandoned crop fields and recommend targeted restoration strategies.
Impacts of climate change adaptation options on soil functions: A review of European case‐studies
Authors: Hamidov Ahmad , Helming Katharina , Bellocchi Gianni , Bojar Waldemar , Dalgaard Tommy , Ghaley Bhim Bahadur , Hoffmann Christian , Holman Ian , Holzkämper Annelie , Krzeminska Dominika , Kværnø Sigrun H. , Lehtonen Heikki , Niedrist Georg , Øygarden Lillian , Reidsma Pytrik , Roggero Pier Paolo , Rusu Teodor , Santos Cristina , Seddaiu Giovanna , Skarbøvik Eva , Ventrella Domenico , Żarski Jacek , Schönhart Martin
Published: May 2018

Soils are vital for supporting food security and other ecosystem services. Climate change can affect soil functions both directly and indirectly. Direct effects include temperature, precipitation, and moisture regime changes. Indirect effects include those that are induced by adaptations such as irrigation, crop rotation changes, and tillage practices. Although extensive knowledge is available on the direct effects, an understanding of the indirect effects of agricultural adaptation options is less complete. A review of 20 agricultural adaptation case‐studies across Europe was conducted to assess implications to soil threats and soil functions and the link to the Sustainable Development Goals (SDGs). The major findings are as follows: (a) adaptation options reflect local conditions; (b) reduced soil erosion threats and increased soil organic carbon are expected, although compaction may increase in some areas; (c) most adaptation options are anticipated to improve the soil functions of food and biomass production, soil organic carbon storage, and storing, filtering, transforming, and recycling capacities, whereas possible implications for soil biodiversity are largely unknown; and (d) the linkage between soil functions and the SDGs implies improvements to SDG 2 (achieving food security and promoting sustainable agriculture) and SDG 13 (taking action on climate change), whereas the relationship to SDG 15 (using terrestrial ecosystems sustainably) is largely unknown. The conclusion is drawn that agricultural adaptation options, even when focused on increasing yields, have the potential to outweigh the negative direct effects of climate change on soil degradation in many European regions.
J‐difference‐edited MRS measures of γ‐aminobutyric acid before and after acute caffeine administration
Authors: Oeltzschner Georg , Zöllner Helge J. , Jonuscheit Marc , Lanzman Rotem S. , Schnitzler Alfons , Wittsack Hans‐Jörg
Published: May 2018

Purpose

The aim of this study was to investigate potential effects of acute caffeine intake on J‐difference‐edited MRS measures of the primary inhibitory neurotransmitter γ‐aminobutyric acid (GABA).

Methods

J‐difference‐edited Mescher‐Garwood PRESS (MEGA‐PRESS) and conventional PRESS data were acquired at 3T from voxels in the anterior cingulate and occipital area of the brain in 15 healthy subjects, before and after oral intake of a 200‐mg caffeine dose. MEGA‐PRESS data were analyzed with the MATLAB‐based Gannet tool to estimate GABA+ macromolecule (GABA+) levels, while PRESS data were analyzed with LCModel to estimate levels of glutamate, glutamate+glutamine, N‐acetylaspartate, and myo‐inositol. All metabolites were quantified with respect to the internal reference compounds creatine and tissue water, and compared between the pre‐ and post‐caffeine intake condition.

Results

For both MRS voxels, mean GABA+ estimates did not differ before and after caffeine intake. Slightly lower estimates of myo‐inositol were observed after caffeine intake in both voxels. N‐acetylaspartate, glutamate, and glutamate+glutamine did not show significant differences between conditions.

Conclusion

Mean GABA+ estimates from J‐difference‐edited MRS in two different brain regions are not altered by acute oral administration of caffeine. These findings may increase subject recruitment efficiency for MRS studies.
Long Exercise Test in Periodic Paralysis: A Bayesian Analysis
Authors: Simmons Daniel B. , Lanning Julie , Cleland James C. , Puwanant Araya , Twydell Paul T. , Griggs Robert C. , Tawil Rabi , Logigian Eric L.
Published: May 2018

Introduction: The long exercise test (LET) is used to assess the diagnosis of periodic paralysis (PP), but LET methodology and normal “cutoff” values vary. Methods: To determine optimal LET methodology and cutoffs, we reviewed LET data (abductor digiti minimi motor response amplitude, area) from 55 patients with PP (32 genetically definite) and 125 controls. Receiver operating characteristic curves were constructed, and area under the curve (AUC) was calculated to compare (1) peak‐to‐nadir versus baseline‐to‐nadir methodologies and (2) amplitude versus area decrements. Using bayesian principles, we calculated optimal cutoff decrements that achieved 95% posttest probability of PP for various pretest probabilities (PreTPs). Results: AUC was highest for peak‐to‐nadir methodology and equal for amplitude and area decrements. For PreTP ≤ 50%, optimal decrement cutoffs (peak‐to‐nadir) were > 40% (amplitude) or > 50% (area). Discussion: For confirmation of PP, our data endorse the diagnostic utility of peak‐to‐nadir LET methodology using 40% amplitude or 50% area decrement cutoffs for PreTP ≤50%. Muscle Nerve 59:47–54, 2019
Post‐polio syndrome and the late effects of poliomyelitis: Part 2. treatment, management, and prognosis
Authors: Lo Julian K. , Robinson Lawrence R.
Published: May 2018

Post‐polio syndrome (PPS) is characterized by new muscle weakness and/or muscle fatigability that occurs many years after the initial poliomyelitis illness. An individualized approach to rehabilitation management is critical. Interventions may include rehabilitation management strategies, adaptive equipment, orthotic equipment, gait/mobility aids, and a variety of therapeutic exercises. The progression of muscle weakness in PPS is typically slow and gradual; however, there is also variability in both the natural history of weakness and functional prognosis. Further research is required to determine the effectiveness of selected medical treatment. Muscle Nerve 58:760–769, 2018
Postpolio syndrome and the late effects of poliomyelitis. Part 1. pathogenesis, biomechanical considerations, diagnosis, and investigations
Authors: Lo Julian K. , Robinson Lawrence R.
Published: May 2018

Postpolio syndrome (PPS) is characterized by new muscle weakness and/or muscle fatigability that occurs many years after the initial poliomyelitis illness. Many theories exist regarding the pathogenesis of PPS, which remains incompletely understood. In contrast, the late effects of poliomyelitis are often a consequence of biomechanical alterations that occur as a result of polio‐related surgeries, musculoskeletal deformities, or weakness. Osteoporosis and fractures of the polio‐involved limbs are common. A comprehensive clinical evaluation with appropriate investigations is essential to fulfilling the established PPS diagnostic criteria. PPS is a diagnosis of exclusion in which a key clinical feature required for the diagnosis is new muscle weakness and/or muscle fatigability that is persistent for at least 1 year. Electromyographic and muscle biopsy findings including evidence of ongoing denervation cannot reliably distinguish between patients with or without PPS. Muscle Nerve 58:751–759, 2018
Robust topology optimization of phononic crystals with random field uncertainty
Authors: Zhang Xiaopeng , He Jingjie , Takezawa Akihiro , Kang Zhan
Published: May 2018

The uncertain spatial variation of material properties can remarkably affect the band gap characteristics of phononic crystals (PnCs). It is necessary to consider this issue when designing and manufacturing PnC materials/structures. This paper investigates a robust topology optimization method for designing the microstructures of PnCs by considering random‐field material properties. Herein, the spatial distribution of the material properties is first represented by a random field and then discretized into uncorrelated stochastic variables with the expansion optimal linear estimation method; stochastic band gap analysis is then conducted with polynomial chaos expansion. Furthermore, a robust topology optimization formulation of PnCs is proposed on the basis of the relative elemental density, where a weighted objective function handles the compromise of the mean value and standard deviation of the PnC band gap. The band gap response is analyzed, employing the finite element method for each sample of polynomial chaos expansion. In this context, the sensitivities of the stochastic band gap behaviors to the design variables are also derived. Numerical examples demonstrate that the proposed method can generate meaningful optimal topologies of PnCs with a relatively large width and less sensitive band gap. Additionally, the effects of the weight factors in the objective function and the variation coefficient of material properties are discussed.
Effects of consuming a high‐protein diet with or without soy protein during weight loss and maintenance: a non‐inferiority, randomized clinical efficacy trial
Authors: Speaker K. J. , Sayer R. D. , Peters J. C. , Foley H. N. , Pan Z. , Wyatt H. R. , Flock M. R. , Mukherjea R. , Hill J. O.
Published: May 2018

Objective

This 12‐month randomized, non‐inferiority clinical trial sought to determine the impact of consuming soy protein as part of an energy‐restricted, high‐protein diet on weight loss, body composition and cardiometabolic health.

Methods

Seventy‐one adults (58 female) with overweight or obesity (body mass index: 32.9 ± 3.6 kg m−2) were randomly assigned to consume three servings of soy (S) or non‐soy (NS) protein foods per day for 12 months. All participants completed a group‐based behavioural weight loss program lasting 4 months (M4), and follow‐up assessments were completed at month 12 (M12).

Results

Body weight was reduced in both groups at M4 (S: −7.0% ± 5.2%, NS: −7.1% ± 5.7%) and M12 (S: 3.6% ± 5.1%, NS: −4.8% ± 7.3%). Body weight reductions (mean difference [90% confidence interval]) were not different between S and NS at either time point (M4: −0.16% [−1.4, 3.6], P = 0.90; M12: 1.1% [−1.4, 3.6], P = 0.44). Differences in body fat mass loss were not different between S and NS at M4 (0.29 ± 0.84 kg, P = 0.73) or M12 (0.78 ± 1.5 kg, P = 0.59). Weight loss‐induced improvements in cholesterol, triglycerides and blood pressure did not differ between S and NS.

Conclusion

These results indicate that soy‐based protein foods can be effectively incorporated into an energy‐restricted, high‐protein diet for improving body weight, body composition and cardiometabolic health.
Prenatal sonographic description of fetuses affected by pyruvate dehydrogenase or pyruvate carboxylase deficiency
Authors: Egloff Charles , Eldin de Pecoulas Aurelia , Mechler Charlotte , Tassin Mikael , Mairovitz Valerie , Corrizi Frederic , Dussaux Chloe , Boutron Audrey , Simon Isabelle , Guet Agnes , Sibiude Jeanne , Mandelbrot Laurent , Picone Olivier
Published: May 2018

Objective

Pyruvate dehydrogenase deficiency (PDHD) and pyruvate carboxylase deficiency (PCD) are diseases with severe neonatal forms, and their low prevalence makes them difficult to diagnose during pregnancy. Our objective was to describe prenatal ultrasound features that may be suggestive of these diagnoses.

Methods

We analyzed 3 cases from our institution and reviewed 12 published cases of PDHD and 6 cases of PCD, recording all of the ultrasound signs, as well as magnetic resonance findings when available. Because of the small number of cases of PCD, we also included postnatal signs that could have been observed during imaging during pregnancy, for a total of 11 cases of PCD.

Results

We conclude that PDHD can be suggested in the presence of ventriculomegaly or paraventricular cysts, associated with an abnormality of the cerebral parenchyma such as abnormal gyration or involvement of the corpus callosum. Pyruvate carboxylase deficiency can be suggested in the presence of ventriculomegaly, frontal horn impairment associated with subependymal, and paraventricular cysts.

Conclusion

When confronted to the ultrasound abnormalities we described, and after eliminating the most frequent etiologies, a metabolic deficiency should be considered. Furthermore, the hereditary character of these diseases makes that it is important to send the family with genetic advice in particular in case of history of a fetal death in utero or a death neonatal unexplained.