bluuebunny/crossref_metadata_2025 huggingface dataset:
Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine
Authors: Dong Wei , Bhide Yoshita , Marsman Sonny , Holtrop Marijke , Meijerhof Tjarko , de Vries‐Idema Jacqueline , de Haan Aalzen , Huckriede Anke
Published: December 2017

Induction of CD8+ cytotoxic T cells (CTLs) to conserved internal influenza antigens, such as nucleoprotein (NP), is a promising strategy for the development of cross‐protective influenza vaccines. However, influenza NP protein alone cannot induce CTL immunity due to its low capacity to activate antigen‐presenting cells (APCs) and get access to the MHC class I antigen processing pathway. To facilitate the generation of NP‐specific CTL immunity the authors develop a novel influenza vaccine consisting of virosomes with the Toll‐like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) and the metal‐ion‐chelating lipid DOGS‐NTA‐Ni incorporated in the membrane. In vitro, virosomes with incorporated MPLA induce stronger activation of APCs than unadjuvanted virosomes. Virosomes modified with DOGS‐NTA‐Ni show high conjugation efficacy for his‐tagged proteins and facilitate efficient uptake of conjugated proteins by APCs. Immunization of mice with MPLA‐adjuvanted virosomes with attached NP results in priming of NP‐specific CTLs while MPLA‐adjuvanted virosomes with admixed NP are inefficient in priming CTLs. Both vaccines induce equally high titers of NP‐specific antibodies. When challenged with heterosubtypic influenza virus, mice immunized with virosomes with attached or admixed NP are protected from severe weight loss. Yet, unexpectedly, they show more weight loss and more severe disease symptoms than mice immunized with MPLA‐virosomes without NP. Taken together, these results indicate that virosomes with conjugated antigen and adjuvant incorporated in the membrane are effective in priming of CTLs and eliciting antigen‐specific antibody responses in vivo. However, for protection from influenza infection NP‐specific immunity appears not to be advantageous.
Manipulation of the sodium‐potassium ratio as a lever for controlling cell growth and improving cell specific productivity in perfusion CHO cell cultures
Authors: Wang Samantha B. , Lee‐Goldman Alexandria , Ravikrishnan Janani , Zheng Lili , Lin Henry
Published: December 2017

Perfusion processes typically require removal of a continuous or semi‐continuous volume of cell culture in order to maintain a desired target cell density. For fast growing cell lines, the product loss from this stream can be upwards of 35%, significantly reducing the overall process yield. As volume removed is directly proportional to cell growth, the ability to modulate growth during perfusion cell culture production thus becomes crucial. Leveraging existing media components to achieve such control without introducing additional supplements is most desirable because it decreases process complexity and eliminates safety and clearance concerns. Here, the impact of extracellular concentrations of sodium (Na) and potassium (K) on cell growth and productivity is explored. High throughput small‐scale models of perfusion revealed Na:K ratios below 1 can significantly suppress cell growth by inducing cell cycle arrest in the G0/1 phase. A concomitant increase in cell specific productivity was also observed, reaching as high as 115 pg/cell/day for one cell line studied. Multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrated similar responses to lower Na:K media, indicating the universal applicability of such an approach. Product quality attributes were also assessed and revealed that effects were cell line specific, and can be acceptable or manageable depending on the phase of the drug development. Drastically altering Na and K levels in perfusion media as a lever to impact cell growth and productivity is proposed.
Computer‐assisted engineering of hyperstable fibroblast growth factor 2
Authors: Dvorak Pavel , Bednar David , Vanacek Pavel , Balek Lukas , Eiselleova Livia , Stepankova Veronika , Sebestova Eva , Kunova Bosakova Michaela , Konecna Zaneta , Mazurenko Stanislav , Kunka Antonin , Vanova Tereza , Zoufalova Karolina , Chaloupkova Radka , Brezovsky Jan , Krejci Pavel , Prokop Zbynek , Dvorak Petr , Damborsky Jiri
Published: December 2017

Fibroblast growth factors (FGFs) serve numerous regulatory functions in complex organisms, and their corresponding therapeutic potential is of growing interest to academics and industrial researchers alike. However, applications of these proteins are limited due to their low stability. Here we tackle this problem using a generalizable computer‐assisted protein engineering strategy to create a unique modified FGF2 with nine mutations displaying unprecedented stability and uncompromised biological function. The data from the characterization of stabilized FGF2 showed a remarkable prediction potential of in silico methods and provided insight into the unfolding mechanism of the protein. The molecule holds a considerable promise for stem cell research and medical or pharmaceutical applications.
A Metal‐Free, Non‐Enzymatic Electrochemical Glucose Sensor with a de‐Bundled Single‐Walled Carbon Nanotube‐Modified Electrode
Authors: Thirumalai Dinakaran , Subramani Devaraju , Shin Bosung , Paik Hyun‐jong , Chang Seung‐Cheol
Published: December 2017

A new metal‐free, non‐enzymatic electrochemical sensor system for the detection of glucose was developed in this study. The developed sensor uses a de‐bundled single‐walled carbon nanotube (SWCNT)‐modified glassy carbon electrode (GCE). SWCNTs were de‐bundled in aqueous solution by adding a synthesized polymer dispersant, sulfonated poly(ether sulfone). The de‐bundled SWCNTs showed two significant characteristics: (1) improvement of the aspect ratio and dispersibility in aqueous solution and (2) suitability for use as a selective and sensitive sensing element in non‐enzymatic glucose sensors. The experimental results clearly demonstrated that the SWCNTs/GCE possesses high electro‐catalytic activity and efficient sensitivity with a stable and faster amperometric response production. Furthermore, interference by ascorbic acid, acetaminophen, uric acid, and dopamine is effectively avoided. Therefore, the proposed approach is favorable for the design and development of non‐enzymatic glucose sensors.
Personality and breast cancer screening in women of the GAZEL cohort study
Authors: Lemogne Cédric , Turinici Monica , Panjo Henri , Ngo Charlotte , Canoui‐Poitrine Florence , Chauvet‐Gelinier Jean‐Christophe , Limosin Frédéric , Consoli Silla M. , Goldberg Marcel , Zins Marie , Ringa Virginie
Published: December 2017

The potential benefit of breast cancer screening is mitigated by the risk of false positives and overdiagnosis, thus advocating for a more personalized approach, based on the individual benefit‐harm balance. Since personality might influence the women's appraisal of this balance, this prospective observational cohort study examined whether it could influence mammography use. A total of 2691 postmenopausal women of the GAZEL Cohort Study completed the Bortner Type A Rating Scale and the Buss and Durkee Hostility Inventory in 1993. Associations between personality scores and subsequent mammography use, self‐reported through up to five triennial follow‐up questionnaires, were estimated with Odds Ratio (OR) and 95% confidence interval (CI) with logistic mixed model regressions, adjusting for age, occupational grade, marital status, family history of breast cancer, age at menarche, age at first delivery, gynecological follow‐up, hormone therapy use, and depressive symptoms. Individual propensity scores were used to weight the analyses to control for potential selection biases. More than 90% of the participants completed at least two follow‐up questionnaires. Type A personality, but not hostility, was associated with mammography use in both univariate (crude OR [95% CI]: 1.62 [1.24–2.11], P < 0.001) and multivariate analyses (OR [95% CI]: 1.46 [1.13–1.90], P < 0.01). Type A personality traits (i.e., sense of time urgency, high job involvement, competitiveness) independently predicted mammography use among postmenopausal women. While paying more attention to the adherence of women with low levels of these traits, clinicians may help those with higher levels to better consider the risks of false positives and overdiagnosis.
Effects of Th17 cells and IL‐17 in the progression of cervical carcinogenesis with high‐risk human papillomavirus infection
Authors: Xue JiSen , Wang YuLi , Chen Cheng , Zhu XueJie , Zhu Hua , Hu Yan
Published: December 2017

The existence of Th17 cells and IL‐17 was recently shown in several types of infectious diseases, but their distribution and functions in cervical lesions with high‐risk human papillomavirus (HPV) infection have not been fully elucidated. In this study, the frequency of Th17 cells in peripheral blood samples obtained from 28 cervical squamous cell carcinoma patients, 26 CIN1 patients, 30 CIN2 patients, 29 CIN3 patients, 25 high‐risk HPV‐infected women with normal cervical cytology, and 30 healthy controls was determined by flow cytometry. Besides, the levels of IL‐17 in peripheral blood samples as well as in supernatant of cervical tissue homogenate were assessed by enzyme‐linked immunosorbent assay (ELISA) simultaneously. We found that during the disease progression of cervical lesions, the proportion of Th17 cells in the total CD4+ cells showed a gradually increased tendency compared with the controls (P < 0.05). Moreover, levels of IL‐17 in serum and supernatant of cervical tissue homogenate showed the same tendency as the proportion of Th17 cells (P < 0.05). When compared in pairs, the levels of IL‐17 in supernatant differed significantly among the study groups and the control group (P < 0.05), but no significant difference was observed in serum (P > 0.05). In conclusions, the results indicate that Th17 cells and IL‐17 may play a role of immune enhancement in the infection of high‐risk HPV especially in the cervical microenvironment, which contribute to the disease progression of its associated cervical lesions.
Antiviral Activity of Faramea hyacinthina and Faramea truncata Leaves on Dengue Virus Type‐2 and Their Major Compounds
Authors: Barboza Rodolfo S. , Valente Ligia M. M. , Wolff Thiago , Assunção‐Miranda Iranaia , Neris Rômulo L. S. , Guimarães‐Andrade Iris P. , Gomes Mário
Published: December 2017

The defatted fractions of the Faramea hyacinthina and F. truncata (Rubiaceae) leaf MeOH extracts showed in vitro non‐cytotoxic and anti‐dengue virus serotype 2 (DENV2) activity in human hepatocarcinoma cell lineage (HepG2). Submitting these fractions to the developed RP‐SPE method allowed isolating the antiviral flavanone (2S)‐isosakuranetin‐7‐O‐β‐d‐apiofuranosyl‐(1→6)‐β‐d‐glucopyranoside (1) from both species and yielded less active sub‐fractions. The new diastereoisomeric epimer pair (2S) + (2R) of 5,3′,5′‐trihydroxyflavanone‐7‐O‐β‐d‐apiofuranosyl‐(1→6)‐β‐d‐glucopyranoside (2a/2b) from F. hyacinthina; the known narigenin‐7‐O‐β‐d‐apiofuranosyl‐(1→6)‐β‐d‐glucopyranoside (3) from both species; rutin (4) and quercetin‐4′‐β‐d‐O‐glucopyranosyl‐3‐O‐rutinoside (5) from F. hyacinthina, and kaempferol‐3‐O‐rutinoside (6), erythroxyloside A (7) and asperuloside (8) from F. truncata have been isolated from these sub‐fractions. Compounds 4 – 8 are reported for the first time in Faramea spp.
Pathological lesions and global DNA methylation in rat prostate under streptozotocin‐induced diabetes and melatonin supplementation
Authors: Gobbo Marina Guimarães , Tamarindo Guilherme Henrique , Ribeiro Daniele Lisboa , de Campos Silvana Gisele Pegorin , Taboga Sebastião Roberto , Góes Rejane Maira
Published: December 2017

Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti‐inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 μg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre‐malignant lesions were assessed. Immunohistochemical assays of α‐actin, cell proliferation (PCNA), Bcl‐2, glutathione S‐transferase (GSTPI), and DNA methylation (5‐methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short‐term diabetes—and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long‐term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.
RNA Characterization by Solid‐State NMR Spectroscopy
Authors: Yang Yufei , Wang Shenlin
Published: December 2017

The structures of RNAs, which play critical roles in various biological processes, provide important clues and insights into the biological functions of these molecules. However, RNA structure determination remains a challenging topic. In recent years, magic‐angle‐spinning solid‐state NMR (MAS SSNMR) has emerged as an alternative technique for structural and dynamic characterization of RNA. MAS SSNMR has been successfully applied to provide atomic‐level structural information about several RNA molecules and RNA–protein complexes. In this Minireview, we give an overview of recent progress in the field of MAS SSNMR based RNA structural characterization, and introduce sample preparation strategies and SSNMR spectroscopic techniques that have been incorporated to identify RNA structural elements. We also highlight a few impressive examples of RNAs that have been investigated extensively by SSNMR. Finally, we briefly discuss future technical trends in the use of MAS SSNMR to facilitate RNA structure determination.
Association between ideal cardiovascular health metrics and risk of cardiovascular events or mortality: A meta‐analysis of prospective studies
Authors: Guo Leilei , Zhang Shangshu
Published: December 2017

Background

Observational studies evaluating the relationship between ideal cardiovascular health (CVH) metrics and risk of cardiovascular (CV) events and mortality yielded inconsistent results.

Hypothesis

Improvement in CVH metrics can result in substantial reductions in the risk of cardiovascular disease (CVD), stroke, and mortality.

Methods

We examined associations between ideal CVH metrics and CV events and mortality by conducting a meta‐analysis of data from prospective cohort studies identified by searching PubMed and Web of Science from their inception to February 2017 and reviewing the reference lists of the retrieved articles.

Results

Thirteen prospective studies involving a total of 193 126 cohort members were included in this meta‐analysis. When comparing the most to the least category of ideal CVH metrics, the overall relative risks (RRs) were 0.54 (95% confidence interval [CI]: 0.41‐0.69) for all‐cause mortality, 0.30 (95% CI: 0.18‐0.51) for CV mortality, 0.22 (95% CI: 0.11‐0.42) for CVD, and 0.33 (95% CI: 0.20‐0.55) for stroke, respectively. A linear dose–response relationship was seen in all‐cause and CV mortality. The risk decreased by 11% and 19% for each increase in ideal CVH metrics. For the analyses of ideal health status in relation to all‐cause and CV mortality, significant results were obtained from smoking, diet, physical activity, plasma glucose levels, and blood pressure.

Conclusions

Ideal CVH status, or even 1 point increase in CVH metrics, can result in substantial reductions in the risk of CVD, stroke, and mortality. Improving metrics of smoking, diet, physical activity, plasma glucose levels, and blood pressure will achieve the highest benefits.
Intended and unintended consequences: Ethics, communication, and prognostic disclosure in pediatric oncology
Authors: Marron Jonathan M. , Cronin Angel M. , Kang Tammy I. , Mack Jennifer W.
Published: December 2017

BACKGROUND

The majority of patients desire all available prognostic information, but some physicians hesitate to discuss prognosis. The objective of the current study was to examine outcomes of prognostic disclosure among the parents of children with cancer.

METHODS

The authors surveyed 353 parents of children with newly diagnosed cancer at 2 tertiary cancer centers, and each child's oncologist. Using multivariable logistic regression, the authors assessed associations between parental report of elements of prognosis discussions with the oncologist (quality of information/communication and prognostic disclosure) and potential consequences of these discussions (trust, hope, peace of mind, prognostic understanding, depression, and anxiety). Analyses were stratified by oncologist‐reported prognosis.

RESULTS

Prognostic disclosure was not found to be associated with increased parental anxiety, depression, or decreased hope. Among the parents of children with less favorable prognoses (<75% chance of cure), the receipt of high‐quality information from the oncologist was associated with greater peace of mind (odds ratio [OR], 5.23; 95% confidence interval [95% CI], 1.81‐15.16) and communication‐related hope (OR, 2.54; 95% CI, 1.00‐6.40). High‐quality oncologist communication style was associated with greater trust in the physician (OR, 2.45; 95% CI, 1.09‐5.48) and hope (OR, 3.01; 95% CI, 1.26‐7.19). Accurate prognostic understanding was less common among the parents of children with less favorable prognoses (OR, 0.39; 95% CI, 0.17‐0.88). Receipt of high‐quality information, high‐quality communication, and prognostic disclosure were not found to be significantly associated with more accurate prognostic understanding.

CONCLUSIONS

The results of the current study demonstrate no evidence that disclosure is associated with anxiety, depression, or decreased hope. Communication processes may increase peace of mind, trust, and hope. It remains unclear how best to enhance prognostic understanding. Cancer 2018;124:1232‐41. © 2017 American Cancer Society.
Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: The FIGHTDIGO study
Authors: Ordan Marie‐Amélie , Mazza Camille , Barbe Coralie , Perrier Marine , Botsen Damien , Renard Yohann , Moreau Johanna , Brasseur Mathilde , Taillière Barbara , Bertin Éric , Bouché Olivier
Published: December 2017

BACKGROUND

Handgrip strength (HGS) is a widely studied noninvasive test. Weak strength (dynapenia) seems to be associated with high morbidity and mortality in different populations, notably oncology populations. Despite this, HGS testing is not used in daily practice in oncology. The study was aimed at evaluating the feasibility and acceptability of HGS testing in patients with digestive cancer treated with ambulatory chemotherapy.

METHODS

In this prospective, single‐center study, enrolled patients were followed for 6 months. Two consecutive bilateral measures were performed with a Jamar dynamometer during each patient's appointments in the unit for intravenous treatment. A questionnaire was completed by patients and medical team members.

RESULTS

There were 203 consecutive patients, and 201 were recruited. In all, 1704 of 1716 measurements (99.3%) were performed, and 201 patients (99.0%) performed at least 1 measure; 190 (94.5%) performed all expected measures. One hundred sixty‐four of 171 participating patients (95.9%) found the test easy to perform, and 167 (97.7%) did not find the test restrictive. All of the 14 medical team members found the test easy to perform, unrestrictive, and undisruptive in their daily practice.

CONCLUSIONS

HGS testing is routinely feasible, inexpensive, and well accepted by patients and medical teams in an ambulatory digestive cancer unit. Cancer 2018;124:1501‐6. © 2017 American Cancer Society.
Implementing The Paris System for Reporting Urinary Cytology results in a decrease in the rate of the “atypical” category and an increase in its prediction of subsequent high‐grade urothelial carcinoma
Authors: Wang Yujing , Auger Manon , Kanber Yonca , Caglar Derin , Brimo Fadi
Published: December 2017

BACKGROUND

In the current study, the authors evaluated the impact of implementing The Paris System for Reporting Urinary Cytology (PSRUC) on the prevalence of various cytological categories and their association with a subsequent diagnosis of high‐grade urothelial carcinoma (HGUC).

METHODS

A comparative study was conducted over the 6‐month period before PSRUC implementation (2013), including 1653 patients and 2371 specimens versus a 6‐month period after implementation of the PSRUC (2016), including 1478 patients and 2392 specimens. The following cytological categories were correlated with the subsequent biopsy result when available (355 cases): negative for HGUC (NHGUC), atypical urothelial cells (AUC), suspicious for HGUC, and HGUC.

RESULTS

Although 18.6% of specimens were diagnosed as AUC in 2013, the percentage was 14.4% in 2016 (P < .0001). Concurrently, the prevalence of the “benign” category increased from 2013 to 2016 (75.4% vs 80%; P < .0001). After implementation of the PSRUC, there was no significant change noted with regard to the association between the categories of NHGUC, suspicious for HGUC, and HGUC and a subsequent HGUC biopsy diagnosis. However, the predictive value of an AUC diagnosis increased from 28.3% to 46.1% (P = .077). Most important, after the implementation of the PSRUC, there was a significant difference noted with regard to the predictive association for HGUC between the NHGUC and AUC groups (13.6% vs 46.1%; P = .003), a difference that was not found to be statistically significant before implementation of the PSRUC (18% vs 28.3%; P = .175).

CONCLUSIONS

There was a much higher risk of HGUC conveyed by AUC cytology after implementation of the PSRUC, justifying more aggressive investigations of patients who receive an AUC diagnosis. Cancer Cytopathol 2018;126:207‐14. © 2017 American Cancer Society.
Synaptic localization of the SUMOylation‐regulating protease SENP5 in the adult mouse brain
Authors: Akiyama Hiroki , Nakadate Kazuhiko , Sakakibara Shin‐ichi
Published: December 2017

Covalent conjugation of small ubiquitin‐like modifiers (SUMOs) or SUMOylation is a reversible post‐translational modification that regulates the stability and function of target proteins. SUMOs are removed from substrate proteins by sentrin/SUMO‐specific proteases (SENPs). Numerous studies have implicated SUMOylation in various physiological and pathological processes in neurons. To understand the functional roles of SUMOylation, it is necessary to determine the distribution of enzymes regulating SUMO conjugation and deconjugation; yet, the localization of SENPs has not been described in detail in intact brain tissue. Here, we report the distribution and subcellular localization of SENP3 and 5 in the adult murine brain. Immunohistochemical analyses revealed the ubiquitous distribution of both SENPs across different brain regions. Within individual cells, SENP3 was confined to the nucleus, consistent with the conventional view that SENPs regulate nuclear events. In contrast, SENP5 was detected in the neuropil but not in cell bodies. Moreover, strong SENP5 immunoreactivity was observed in regions with high numbers of synapses such as the cerebellar glomeruli, suggesting that SENP5 localizes to pre‐ and/or postsynaptic structures. We performed double immunolabeling in cultured neurons and found that SENP5 co‐localized with pre‐ and post‐synaptic markers, as well as a mitochondrial marker. Immunoelectron microscopy confirmed this finding and revealed that SENP5 was localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals. These findings advance the current understanding of the functional roles of SUMOylation in neurons, especially in synaptic regulation, and have implications for future therapeutic strategies in neurodegenerative disorders mediated by mitochondrial dysfunction.
Generalized backpropagation algorithm for training second‐order neural networks
Authors: Fan Fenglei , Cong Wenxiang , Wang Ge
Published: December 2017

The artificial neural network is a popular framework in machine learning. To empower individual neurons, we recently suggested that the current type of neurons could be upgraded to second‐order counterparts, in which the linear operation between inputs to a neuron and the associated weights is replaced with a nonlinear quadratic operation. A single second‐order neurons already have a strong nonlinear modeling ability, such as implementing basic fuzzy logic operations. In this paper, we develop a general backpropagation algorithm to train the network consisting of second‐order neurons. The numerical studies are performed to verify the generalized backpropagation algorithm.
Trainees' self‐evaluation of their development as psychotherapists: An Italian contribution to an international collaborative study on psychotherapy training
Authors: Messina Irene , Gelo Omar C. G. , Sambin Marco , Bianco Francesca , Mosconi Andrea , Fenelli Antonio , Curto Marcello , Gullo Salvo , Orlinsky David
Published: December 2017

This study presents a pilot contribution to the new collaborative, multinational study of psychotherapy trainee development that was undertaken by the Society for Psychotherapy Research Interest Section on Therapist Training and Development (see Orlinsky, Strauss, Rønnestad, et al., ). Although the main project is longitudinal in design, this preliminary study investigated cross‐sectional differences between trainees in different years of training and explored the influence of core training experiences—including supervision and personal therapy—on their perceived development as therapists. Using the trainee current‐progress report that was designed for the Society for Psychotherapy Research Interest Section on Therapist Training and Development project, 90 trainees at 4 different 4‐year training programs in Italy provided self‐evaluations of their development and of their therapeutic work experiences. Perceived development included overall change, progress, deterioration, overcoming past limitations, and realization of potential as a therapist. Therapeutic work experiences were assessed using scales of healing and stressful involvement (Orlinsky & Rønnestad, ). Year in training and support in supervision predicted perceived development and healing involvement, whereas experiencing criticism in supervision was associated with stressful involvement. Having had personal therapy, and especially ratings of benefit from personal therapy, was also associated with perceived development and healing involvement. Results are discussed with regard of their implications for psychotherapy training.
Psychodynamic technique early in treatment related to outcome for depressed patients
Authors: Katz Michael , Hilsenroth Mark J.
Published: December 2017

We examined the relationship between psychodynamic techniques early in treatment with reliable change in depressive symptomatology. Forty‐six patients admitted for individual psychodynamic psychotherapy who received a diagnosis representative of a depressive spectrum disorder were assessed pretreatment and posttreatment through self‐report of depressive symptoms. Videotapes from two early treatment sessions (3rd and 9th) were independently rated on the Comparative Psychotherapy Process Scale for use of psychodynamic‐interpersonal and cognitive–behavioural techniques, with excellent interrater reliability (intraclass correlation coefficient > .75). We found a significant relationship between overall use of psychodynamic technique across early treatment (r = .31,p = .036), as well as specific psychodynamic techniques delivered across early treatment, with change in patient‐reported depressive symptoms. Our findings suggest that focusing on affective experiencing and expression, as well as providing interpretations are particularly helpful early in psychodynamic treatment for depression. Clinical implications and future directions are discussed.
Growth hormone isoform‐differential mass spectrometry for doping control purposes
Authors: Arsene Cristian , Schulze Dirk , Röthke Anita , Thevis Mario , Henrion André
Published: December 2017

Mass spectrometry (MS) allows for monitoring growth hormone (GH) isoform compositions at high specificity. It is demonstrated that this capability can be used to reliably detect alterations as elicited by (putative) doping with 22 kDa‐GH. Sample treatment consists of enzymatic protein cleavage, followed by 2‐step liquid chromatography clean‐up, prior to analysis by MS. The protocol does not depend on antibodies for analyte extraction at any stage. Therefore, MS opens an opportunity for independent confirmation, if combined with the antibody‐based isoform differential test presently used in practice. To check the fitness‐for‐purpose of this concept, GH‐free serum was spiked with pure 22 kDa‐ and 20 kDa‐GH covering a representative range of concentrations (0.5–9.4 μg/L), while the 22kDa fraction was within a range of  80%–85%, or at 100%, the latter simulating an administration of 22 kDa‐GH. Mean deviation of 22 kDa‐fractions found was within less than 3% for samples with total GH>= 1 μg/L . Beyond this, results by antibody‐free isoform‐differential MS, as described, were in line with those of the World Anti‐Doping Agency‐approved antibody‐based test for 18 native sera and 3 positive controls. In this context, relating 22 kDa‐GH to total‐GH rather than 22 kDa+20 kDa was considered as an alternative strategy to earlier approaches. However, 20 kDa‐GH as an additional measurand, next to 22 kDa‐ and total‐GH, provides useful extra information, as it directly indicates the presence or absence of a non‐22 kDa‐GH form.
Effect of glucocorticoid administration on the steroid profile
Authors: Coll Sergi , Matabosch Xavier , Garrostas Lorena , Perez‐Maña Clara , Ventura Rosa
Published: December 2017

The steroid profile (SP) is a powerful tool to detect the misuse of endogenous anabolic androgenic steroids in sports, and it is included in the Athlete Biological Passport (ABP). Glucocorticoids (GCs), which are widely prescribed in sports and only prohibited in competition by systemic routes, inhibit the hypothalamic‐pituitary‐adrenal axis. Since the metabolites monitored in the SP have a partial adrenal origin, their excretion in urine might be altered by GCs consumption. The aim of the present work was to investigate if GCs administered by either systemic or local routes could influence the SP parameters. Three of the most frequently detected GCs in sports (prednisolone, betamethasone, and triamcinolone acetonide) were administered to healthy male and female volunteers (n=40) using different administration routes (topical, oral, and intramuscular administration at different doses). In total, 66 administrations of GCs were performed. Urine samples were collected before and after GCs administration. The SP was measured using gas chromatography‐mass spectrometry. The excretion rates of the SP metabolites decreased after systemic GCs administration. This excretion decrease showed to be associated with the dose and the administration route. However, the individual evaluation of the SP ratios (T/E, A/T, A/Etio, 5αAdiol/5βAdiol, and 5αAdiol/E) led to normal sequences for all the conditions tested. Therefore, GCs administration did not produce misinterpretations on the ABP evaluation. According to these results, GCs administration should not distort the establishment of normal ranges of the SP ratios, and does not need to be considered a confounding factor in the SP evaluation.
Delayed egg‐laying and shortened incubation duration of Arctic‐breeding shorebirds coincide with climate cooling
Authors: Kwon Eunbi , English Willow B. , Weiser Emily L. , Franks Samantha E. , Hodkinson David J. , Lank David B. , Sandercock Brett K.
Published: December 2017

Biological impacts of climate change are exemplified by shifts in phenology. As the timing of breeding advances, the within‐season relationships between timing of breeding and reproductive traits may change and cause long‐term changes in the population mean value of reproductive traits. We investigated long‐term changes in the timing of breeding and within‐season patterns of clutch size, egg volume, incubation duration, and daily nest survival of three shorebird species between two decades. Based on previously known within‐season patterns and assuming a warming trend, we hypothesized that the timing of clutch initiation would advance between decades and would be coupled with increases in mean clutch size, egg volume, and daily nest survival rate. We monitored 1,378 nests of western sandpipers, semipalmated sandpipers, and red‐necked phalaropes at a subarctic site during 1993–1996 and 2010–2014. Sandpipers have biparental incubation, whereas phalaropes have uniparental incubation. We found an unexpected long‐term cooling trend during the early part of the breeding season. Three species delayed clutch initiation by 5 days in the 2010s relative to the 1990s. Clutch size and daily nest survival showed strong within‐season declines in sandpipers, but not in phalaropes. Egg volume showed strong within‐season declines in one species of sandpiper, but increased in phalaropes. Despite the within‐season patterns in traits and shifts in phenology, clutch size, egg volume, and daily nest survival were similar between decades. In contrast, incubation duration did not show within‐season variation, but decreased by 2 days in sandpipers and increased by 2 days in phalaropes. Shorebirds demonstrated variable breeding phenology and incubation duration in relation to climate cooling, but little change in nonphenological components of traits. Our results indicate that the breeding phenology of shorebirds is closely associated with the temperature conditions on breeding ground, the effects of which can vary among reproductive traits and among sympatric species.
Forest composition effect on wildfire pattern and run‐off regime in a Mediterranean watershed
Authors: Ohana‐Levi Noa , Givati Amir , Paz‐Kagan Tarin , Karnieli Arnon
Published: December 2017

Fire may alter land cover throughout the landscape and affect run‐off responses to rainfall events in a burnt watershed. Therefore, the challenge is to understand the interactions between forest composition and fire patterns in a karstic, Mediterranean watershed that affects the run‐off regime. The aim of this research is to improve the understanding of the interactive effects of wildfire and land‐cover change on the rainfall–run‐off relationship in a first‐order watershed. To achieve this goal, satellite imagery, official spatial data, and hydrological modelling were used to study forest composition in relation to extreme fire and to simulate run‐off response for 2 rainfall events. The results show that an extreme wildfire had a greater impact on planted forest, composed mostly of pines, than on native species. Additionally, it was found that the land‐cover alternation due to fire affected the run‐off regime and contributed to an increase in maximum discharge and run‐off volume for the 2 rainfall events by ~39–47%. During the regeneration period, the run‐off response for the 2 rainfall events decreased by ~7.7–9%. Wildfires may impact the run‐off response more profoundly as the plantation of pine trees increases. A greater increase in run‐off response may endanger infrastructure in terms of flooding and affect the population well‐being. Watershed management in areas where afforestation is considered should focus on planting native species that are less flammable rather than introducing combustible pines, thus reducing the hydrologic impacts of land‐cover alteration due to wildfire, especially when climate warms and wildfires become more frequent and intense.
Changes in foliage projective cover and its implications for mapping groundwater dependent vegetation across a precipitation gradient
Authors: Parker Brett M. , Sheldon Fran , Phinn Stuart , Ward Doug
Published: December 2017

Adequate protection of groundwater dependent vegetation (GDV) at the landscape scale (>104 km2) is often hampered as their extent is poorly mapped. Remote sensing data sets have previously been used to delineate GDV by analysing both actual and changes, in green biomass over space and time. The rationale behind such approaches is based on the phenological characteristics of GDV, which often retain greater mean green biomass during dry periods, in comparison to vegetation with access to soil moisture only. However, such methods are hampered by inadequate knowledge about how average annual precipitation, seasonality, and differing water regimes of vegetation communities within a landscape influence green biomass. Therefore, we aimed to test for amount of foliage projective cover (FPC) and variation in FPC as indicators of GDV presence. We assessed differences in the FPC of GDV at 3 sites across a 1,500 mm−1 year−1 precipitation gradient, ranging from arid inland to humid coastal environments in Southern Queensland, Australia. Overall, we found that average annual precipitation had the largest influence on predicting FPC followed by seasonality. During winter in the semi‐arid and humid environments (season with least precipitation), FPC for non‐GDV was higher than subsurface GDV. For our study area, GDV delineation on the basis of higher green biomass than surrounding vegetation was effective when average annual precipitation was less than ~600 mm−1 year−1.
One‐Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base‐Free Rearrangement into Enone Esters: an Autoinductive Mechanism
Authors: Sieng Bora , Maldonado Matias Funes , Romagnoli Carlo , Amedjkouh Mohamed
Published: December 2017

A direct synthesis of γ‐oxo‐α,β‐unsaturated esters has been developed. When heteroaromatic aldehydes are reacted with deprotonated ethyl propiolate, in the presence of Me2Zn or BuLi, the newly formed propargylic alcohol rearranged spontaneously to give the corresponding unsaturated keto ester. Isotope labeling, allenol intermediate trapping and crossover experiments provided insight into the reactive sequence and suggest an autocatalytic mechanism.
Stream channel erosion in a rapidly urbanizing region of the US–Mexico border: documenting the importance of channel hardpoints with Structure‐from‐Motion photogrammetry
Authors: Taniguchi Kristine T. , Biggs Trent W. , Langendoen Eddy J. , Castillo Carlos , Gudino‐Elizondo Napoleon , Yuan Yongping , Liden Douglas
Published: December 2017

Urbanization can lead to accelerated stream channel erosion, especially in areas experiencing rapid population growth, unregulated urban development on erodible soils, and variable enforcement of environmental regulations. A combination of field surveys and Structure‐from‐Motion (SfM) photogrammetry techniques was used to document spatial patterns in stream channel geometry in a rapidly urbanizing watershed, Los Laureles Canyon (LLCW), in Tijuana, Mexico. Ground‐based SfM photogrammetry was used to map channel dimensions with 1 to 2 cm vertical mean error for four stream reaches (100–300 m long) that were highly variable and difficult to survey with a differential GPS. Regional channel geometry curves for LLCW had statistically larger slopes and intercepts compared with regional curves developed for comparable, undisturbed reference channels. Cross‐sectional areas of channels downstream of hardpoints, such as concrete reaches or culverts, were up to 64 times greater than reference channels, with enlargement persisting, in some cases, up to 230 m downstream. Percentage impervious cover was not a good predictor of channel enlargement. Proximity to upstream hardpoint, and lack of riparian and bank vegetation paired with highly erodible bed and bank materials may account for the instability of the highly enlarged and unstable cross‐sections. Channel erosion due to urbanization accounts for approximately 25–40% of the total sediment budget for the watershed, and channel erosion downstream of hardpoints accounts for one‐third of all channel erosion. Channels downstream of hardpoints should be stabilized to prevent increased inputs of sediment to the Tijuana Estuary and local hazards near the structures, especially in areas with urban settlements near the stream channel. Copyright © 2017 John Wiley & Sons, Ltd.
Structural and functional responses of periphyton and macroinvertebrate communities to ferric Fe, Cu, and Zn in stream mesocosms
Authors: Cadmus Pete , Guasch Helena , Herdrich Adam T. , Bonet Berta , Urrea Gemma , Clements William H.
Published: December 2017

Two mesocosm experiments were conducted to examine effects of ferric iron (Fe) and mixtures of ferric Fe with aqueous metals (Cu, Zn) on stream benthic communities. Naturally colonized benthic communities were exposed to a gradient of ferric Fe (0, 0.4, 1.0, 2.5, 6.2, and 15.6 mg/L) that bracketed the current US Environmental Protection Agency water quality criterion value (1.0 mg/L). After 10 d of exposure to ferric Fe, total macroinvertebrate abundance, number of taxa, and abundance of all major macroinvertebrate groups (Ephemeroptera, Plecoptera, Trichoptera, and Diptera) were significantly reduced. Heptageniid mayflies and chironomids were especially sensitive to Fe oxide deposition and were significantly reduced at 0.4 and 1.0 mg/L total Fe, respectively. In a second mesocosm experiment, periphyton and macroinvertebrate communities were exposed to ferric Fe (0.60 mg/L) with or without aqueous Cu and Zn at 2 treatment levels: low (0.01 mg/L Cu + 0.1 mg/L Zn) and high (0.05 mg/L Cu + 0.5 mg/L Zn). In contrast to previous research, we observed no evidence of a protective effect of Fe on toxicity of metals. Growth rates and protein content of periphyton were significantly reduced by both ferric Fe and aqueous metals, whereas abundance of heptageniid mayflies (Cinygmula) and whole community metabolism were significantly reduced by ferric Fe alone. We hypothesize that Fe oxides inhibited algal growth and enhanced metal accumulation, leading to a reduction in the quantity and quality of food resources for grazers. Mesocosm experiments conducted using natural benthic communities provide a unique opportunity to quantify the relative importance of indirect physical effects and to develop a better understanding of the relationship between basal food resources and consumers in natural stream ecosystems. Environ Toxicol Chem 2018;37:1320–1329. © 2017 SETAC
Outcomes after multiple courses of granulocyte colony‐stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial
Authors: Verma Nipun , Kaur Amritjyot , Sharma Ratiram , Bhalla Ashish , Sharma Navneet , De Arka , Singh Virendra
Published: December 2017

Decompensated cirrhosis (DC) carries a high mortality. Liver transplantation (LT) is the treatment of choice; however, the limited availability of donor organs has resulted in high waitlist mortality. The present study investigated the impact of multiple courses of granulocyte‐colony stimulating factor (G‐CSF) with or without growth hormone (GH) in these patients. Sixty‐five patients with DC were randomized to standard medical therapy (SMT) plus G‐CSF 3 monthly plus GH daily (group A; n = 23) or SMT plus G‐CSF (group B; n = 21) or SMT alone (group C; n = 21). The primary outcome was transplant‐free survival (TFS) at 12 months. Secondary outcomes were mobilization of CD34+ cells at day 6 and improvement in clinical scores, liver stiffness, nutrition, episodes of infection, and quality of life (QOL) at 12 months. There was significantly better 12‐month TFS in groups A and B than in group C (P = 0.001). At day 6 of therapy, CD34+ cells increased in groups A and B compared to baseline (P < 0.001). There was a significant decrease in clinical scores, improvement in nutrition, better control of ascites, reduction in liver stiffness, lesser infection episodes, and improvement in QOL scores in groups A and B at 12 months as compared to baseline (P < 0.05). The therapies were well tolerated. Conclusion: Multiple courses of G‐CSF improved 12‐month TFS, mobilized hematopoietic stem cells, improved disease severity scores, nutrition, fibrosis, QOL scores, ascites control, reduced infections, and the need for LT in patients with DC. However, the use of GH was not found to have any additional benefit. (Hepatology 2017).
Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma
Authors: Nepal Chirag , O'Rourke Colm J. , Oliveira Douglas V.N.P. , Taranta Andrzej , Shema Steven , Gautam Prson , Calderaro Julien , Barbour Andrew , Raggi Chiara , Wennerberg Krister , Wang Xin W. , Lautem Anja , Roberts Lewis R. , Andersen Jesper B.
Published: December 2017

Intrahepatic cholangiocarcinoma remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole‐exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, “undetermined”). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, comutation profiles, and enriched pathways. High‐throughput drug repositioning in seven patient‐matched cell lines, chosen to reflect the genetic alterations specific for each patient group, confirmed in silico predictions of subgroup‐specific vulnerabilities linked to enriched pathways. Intriguingly, patients lacking all three mutations (“undetermined”) harbored the most extensive structural alterations, while isocitrate dehydrogenase mutant tumors displayed the most extensive DNA methylome dysregulation, consistent with previous findings. Conclusion: Stratification of intrahepatic cholangiocarcinoma patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epimutational) that influence pharmacologic response in drug repositioning protocols; this genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. (Hepatology 2018).
Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade
Authors: Abe Takumi , Terasaki Masaru
Published: December 2017

Phaitanthrin E was biomimetically synthesized from methyl indole‐3‐carboxylate and methyl anthranilate or anthranilic acid using the ester group as an activating group. The reaction proceeds through NCS‐mediated dearomatization/TFA‐catalyzed protonation of indolenine/C(2) amination/Et3N‐promoted aromatization and cyclization in one‐pot procedure. This method is capable of converting simple biomass materials to phaitanthrin E. The synthesis not only allows assessment of antiproliferative activity, but also affords experimental support for the hypothetical biosynthetic pathway of phaitanthrin E. The resulting phaitanthrin E derivatives were evaluated for in vitro antiproliferative activity against human colorectal cancer cells (DLD‐1). The biogenetic intermediate of phaitanthrin E showed higher antiproliferative activity than the natural product, phaitanthrin E. Furthermore, a concise synthesis of tryptanthrin is also accomplished from indole‐3‐carbaldehyde and methyl anthranilate using the aldehyde group as an activating group.