bluuebunny/crossref_metadata_2025 huggingface dataset:
A reference genome of the Chinese hamster based on a hybrid assembly strategy
Authors: Rupp Oliver , MacDonald Madolyn L. , Li Shangzhong , Dhiman Heena , Polson Shawn , Griep Sven , Heffner Kelley , Hernandez Inmaculada , Brinkrolf Karina , Jadhav Vaibhav , Samoudi Mojtaba , Hao Haiping , Kingham Brewster , Goesmann Alexander , Betenbaugh Michael J. , Lewis Nathan E. , Borth Nicole , Lee Kelvin H.
Published: April 2018

Accurate and complete genome sequences are essential in biotechnology to facilitate genome‐based cell engineering efforts. The current genome assemblies for Cricetulus griseus, the Chinese hamster, are fragmented and replete with gap sequences and misassemblies, consistent with most short‐read‐based assemblies. Here, we completely resequenced C. griseus using single molecule real time sequencing and merged this with Illumina‐based assemblies. This generated a more contiguous and complete genome assembly than either technology alone, reducing the number of scaffolds by >28‐fold, with 90% of the sequence in the 122 longest scaffolds. Most genes are now found in single scaffolds, including up‐ and downstream regulatory elements, enabling improved study of noncoding regions. With >95% of the gap sequence filled, important Chinese hamster ovary cell mutations have been detected in draft assembly gaps. This new assembly will be an invaluable resource for continued basic and pharmaceutical research.
Non‐Newtonian rheology in suspension cell cultures significantly impacts bioreactor shear stress quantification
Authors: Wyma Alex , Martin‐Alarcon Leonardo , Walsh Tylor , Schmidt Tannin A. , Gates Ian D. , Kallos Michael S.
Published: April 2018

The fields of regenerative medicine and tissue engineering require large‐scale manufacturing of stem cells for both therapy and recombinant protein production, which is often achieved by culturing cells in stirred suspension bioreactors. The rheology of cell suspensions cultured in stirred suspension bioreactors is critical to cell growth and protein production, as elevated exposure to shear stress has been linked to changes in growth kinetics and genetic expression for many common cell types. Currently, little is understood on the rheology of cell suspensions cultured in stirred suspension bioreactors. In this study, we present the impact of three common cell culture parameters, serum content, cell presence, and culture age, on the rheology of a model cell line cultured in stirred suspension bioreactors. The results reveal that cultures containing cells, serum, or combinations thereof are highly shear thinning, whereas conditioned and unconditioned culture medium without serum are both Newtonian. Non‐Newtonian viscosity was modeled using a Sisko model, which provided insight on structural mechanisms driving the rheological behavior of these cell suspensions. A comparison of shear stress estimated by using Newtonian and Sisko relationships demonstrated that assuming Newtonian viscosity underpredicts both mean and maximum shear stress in stirred suspension bioreactors. Non‐Newtonian viscosity models reported maximum shear stresses exceeding those required to induce changes in genetic expression in common cell types, whereas Newtonian models did not. These findings indicate that traditional shear stress quantification of cell or serum suspensions is inadequate and that shear stress quantification methods based on non‐Newtonian viscosity must be developed to accurately quantify shear stress.
High wrist ratio is a risk factor for carpal tunnel syndrome
Authors: Ozcakir S. , Sigirli D. , Avsaroglu H.
Published: May 2018

Carpal tunnel syndrome (CTS) is the most common upper extremity entrapment neuropathy and various risk factors have been implicated in the etiology. In this study, we aimed to determine whether anthropometric measurements are independent risk factors for CTS. Patients with symptoms of CTS (n = 27) and asymptomatic controls (n = 27) were enrolled following electrophysiological confirmation. Body mass index (BMI) was recorded and anthropometric measurements of the hand were made by a digital caliper. BMI, wrist width, wrist depth, palm length, hand width, wrist ratio, wrist/palm ratio, and wrist/hand ratio were significantly higher in the CTS group. BMI, wrist ratio, wrist/palm ratio, and wrist/hand ratio were independent variables in the logistic regression analysis; wrist ratio was the only significant predictor of CTS. Patients with a wrist ratio higher than 0.69 were 8.2 times more likely to have CTS. This study suggests that wrist ratio may be considered as an independent risk factor for CTS. Clin. Anat. 31:698–701, 2018. © 2018 Wiley Periodicals, Inc.
A novel plasma circular RNA circFARSA is a potential biomarker for non‐small cell lung cancer
Authors: Hang Dong , Zhou Jing , Qin Na , Zhou Wen , Ma Hongxia , Jin Guangfu , Hu Zhibin , Dai Juncheng , Shen Hongbing
Published: May 2018

Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non‐small cell lung cancer (NSCLC). We used RNA sequencing (RNA‐seq) and quantitative real‐time PCR to explore cancer‐related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA‐seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5–7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients’ plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR‐330‐5p and miR‐326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy.
The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH‐like 2‐Heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) Biosynthesis Enzyme PqsBC
Authors: Witzgall Florian , Depke Tobias , Hoffmann Michael , Empting Martin , Brönstrup Mark , Müller Rolf , Blankenfeldt Wulf
Published: May 2018

Pseudomonas aeruginosa is a bacterial pathogen that causes life‐threatening infections in immunocompromised patients. It produces a large armory of saturated and mono‐unsaturated 2‐alkyl‐4(1H)‐quinolones (AQs) and AQ N‐oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β‐ketoacyl‐acyl‐carrier protein synthase III (FabH)‐like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2‐heptyl‐4(1H)‐quinolone (HHQ), by condensing octanoyl‐coenzyme A (CoA) with 2‐aminobenzoylacetate (2‐ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium‐chain acyl‐CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono‐unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl‐binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH‐enzymes, for which such structural transitions have been postulated but have never been observed.
Aptamer‐Functionalized Magnetic Conjugated Organic Framework for Selective Extraction of Traces of Hydroxylated Polychlorinated Biphenyls in Human Serum
Authors: Jiang Dandan , Hu Tingting , Zheng Haijiao , Xu Guoxing , Jia Qiong
Published: May 2018

A solid‐phase extraction adsorbent based on an aptamer‐functionalized magnetic conjugated organic framework (COF) was developed for selective extraction of traces of hydroxylated polychlorinated biphenyls. This material has advantages such as superparamagnetism of the magnetic core, high surface area and porous structure of the COF, and high specific affinity of the aptamer. In combination with HPLC‐MS, the aptamer‐functionalized magnetic COF was used for the capture of hydroxy‐2′,3′,4′,5,5′‐pentachlorobiphenyl in human serum. The method provided a linear range of 0.01–40 ng mL−1 with a good correlation coefficient (R2=0.9973). The limit of detection was as low as 2.1 pg mL−1. Furthermore, the material showed good reusability and could be applied in at least ten extraction cycles with recoveries greater than 90 %.
Selective On/Off‐Nitroxides as Radical Probes to Investigate Non‐radical Enzymatic Activity by Electron Paramagnetic Resonance
Authors: Duttagupta Indranil , Jugniot Natacha , Audran Gérard , Franconi Jean‐Michel , Marque Sylvain R. A. , Massot Philippe , Mellet Philippe , Parzy Elodie , Thiaudière Eric , Vanthuyne Nicolas
Published: May 2018

A nitroxide carrying a peptide specific to the binding pocket of the serine proteases chymotrypsin and cathepsin G is prepared. This peptide is attached as an enol ester to the nitroxide. Upon enzymatic hydrolysis of the peptide, the enol ester moiety is transformed into a ketone moiety. This transformation affords a difference of 5 G in phosphorus hyperfine coupling constant between the electronic paramagnetic resonance (EPR) signals of each nitroxide. This property is used to monitor the enzymatic activity of chymotrypsin and cathepsin G by EPR. Michaelis constants were determined and match those reported for conventional optical probes.
Functionalization of Bambusurils by a Thiol–Ene Click Reaction and a Facile Method for the Preparation of Anion‐Free Bambus[6]urils
Authors: Azazna Djamille , Lafosse Marine , Rivollier Julie , Wang Jialan , Cheikh Imen Ben , Meyer Michel , Thuéry Pierre , Dognon Jean‐Pierre , Huber Gaspard , Heck Marie‐Pierre
Published: May 2018

Sulfide‐functionalized bambus[4]urils ((RS)8BU[4]) and bambus[6]urils ((RS)12BU[6]) were synthesized through thiol–ene click coupling reactions (TEC) of allylbambus[n]urils. Thiosugars were grafted to BU[4] and BU[6]. Synthesis of BU[6] derivatives always requires the use of a template anion (iodide, chloride, or bromide), which is enclosed in the cavity of BU[6]. We show that this anion influences the reactivity of bambus[6]urils. An encapsulated iodide makes allyl functions of allyl12BU[6] less reactive towards TEC and hydrogenation reactions in comparison to the corresponding chloride or bromide inclusion complexes. This is critical for the chemical reactivity of BU[6] and even more to determine their anion‐binding properties. We report a new, facile and fast method using AgSbF6 to prepare anion‐free BU[6]. NMR spectroscopic methods were used to estimate association constants of these new empty BU[6] with different anions. Quantum chemical calculations were employed to rationalize the observed results. These new functionalized bambusuril scaffolds in alternate conformations could find applications as multivalent binders.
The evolution of dasatinib dosage over the years and its relevance to other anticancer medications
Authors: Schiffer Charles A.
Published: May 2018

A lower dose of 50 mg of dasatinib is effective when used as the initial treatment of patients with chronic‐phase chronic myeloid leukemia. This observation has implications for dose and schedule considerations for other anticancer drugs. See also pages 2740‐7.
Risk factors for locoregional disease recurrence after breast‐conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta‐analysis
Authors: Valachis Antonios , Mamounas Eleftherios P. , Mittendorf Elizabeth A. , Hayashi Naoki , Ishitobi Makoto , Natoli Clara , Fitzal Florian , Rubio Isabel T. , Tiezzi Daniel G. , Shin Hee‐Chul , Anderson Stewart J. , Hunt Kelly K. , Matsuda Naoko , Ohsumi Shozo , Totomi Athina , Nilsson Cecilia
Published: May 2018

BACKGROUND

Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast‐conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT.

METHODS

Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1‐stage meta‐analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively.

RESULTS

A total of 9 studies (4125 patients) provided their data sets. The 10‐year LR rate was 6.5%, whereas the 10‐year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor‐negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low‐risk, intermediate‐risk, and high‐risk group with 10‐year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low‐risk, intermediate‐risk, and high‐risk group with 10‐year LRR rates of 3.2%, 10.1%, and 24.1%, respectively.

CONCLUSIONS

BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy‐to‐use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow‐up. Cancer 2018;124:2923‐30. © 2018 American Cancer Society.
Transformation of Indium and Gallium Metal into Mixed Group 11/13 Ternary Sulfide Nanoparticles by Using a Dithioic Acid
Authors: Senevirathna Dimuthu C. , Spiccia Leone , Werrett Melissa V. , Andrews Philip C.
Published: April 2018

Heterobimetallic Group 11/13 sulfide nanoparticles (AgInS2, CuInS2, Ag9GaS6, and CuGaS2) are formed by treatment of [M(S2CAr)3] (M=Ga or In) with either AgNO3 or CuCl under mild conditions. The intermediary gallium or indium tris(aryldithioate) complexes are easily prepared by stirring the appropriate metal and aryldithioc acid at room temperature. Overall, this two‐step process is a simple solution‐based method for transforming Ga and In metal into valuable ternary metallosulfide nanoparticles at relatively low temperatures.
A therapist version of the Alliance Negotiation Scale
Authors: Doran Jennifer M. , Gómez‐Penedo Juan Martín , Safran Jeremy D. , Roussos Andrés
Published: May 2018

The aim of the current study was to design and evaluate a therapist version of the Alliance Negotiation Scale (ANS). The ANS was created in order to operationalize the construct of dyadic negotiation in psychotherapy and to augment existing conceptualizations of the working alliance. The ANS has existed only as a client self‐report form since its inception and has demonstrated promise as a psychotherapy process measure. This research intended to develop a complementary therapist self‐report version of the measure. The scale creation process is discussed in detail, and the results of a preliminary psychometric investigation are reported. The ANS‐Therapist version (ANS‐T) was developed using a sample of therapists (n = 114) through a principal components analysis procedure. The ANS‐T contains 9 unidimensional items and was moderately correlated with therapist‐reported working alliance (r = .468). The results of the study support the composition of the ANS‐T and provide initial support for the reliability and validity of the measure.
Mode selection schemes for unicasting device‐to‐device communications supported by network coding
Authors: Fodor Gabor
Published: May 2018

Device‐to‐device (D2D) communication in a cellular spectrum increases the spectral and energy efficiency of local communication sessions, while also taking advantage of accessing licensed spectrum and higher transmit power levels than when using unlicensed bands. To realize the potential benefits of D2D communications, appropriate mode selection algorithms that select between the cellular and D2D communication modes must be designed. On the other hand, physical‐layer network coding (NWC) at a cellular base station—which can be used without D2D capability—can also improve the spectral efficiency of a cellular network that carries local traffic. In this paper, we ask whether cellular networks should support D2D communications, physical‐layer NWC, or both. To this end, we study the performance of mode selection algorithms that can be used in cellular networks that use physical‐layer NWC and support D2D communications. We find that the joint application of D2D communication and NWC scheme yields additional gains compared with a network that implements only one of these schemes, provided that the network implements proper mode selection and resource allocation algorithms. We propose 2 mode selection schemes that aim to achieve high signal‐to‐interference‐plus‐noise ratio and spectral efficiency, respectively, and take into account the NWC and D2D capabilities of the network.
Lack of transformation zone in cervical Pap tests, should it be a concern? A quality assurance initiative
Authors: Polanco Jacome Evelyn Carolina , Maerki Jennifer , Chau Karen , Akerman Meredith , Sajjan Sujata , Klein Melissa , Gimenez Cecilia , Laser Alice , Das Kasturi
Published: May 2018

Background

Bethesda guidelines do not require presence of transformation zone (TZ) for a cervical Pap test to be deemed adequate. However, clinicians are concerned with specimens that are reported to lack TZ.

Methods

We analyzed 566 ThinPrep cases reported as negative for intraepithelial lesion or malignancy (NILM) with no cervical abnormality detected in previous 4 years (2007–2011). These cases were divided into two cohorts; those with TZ (ETZ) and those without TZ (NTZ). Patients' age, HPV status, time of sample collection (>14 days after last menstrual period), subsequent management, interval of subsequent Pap test (<1, 1–3, and >3 years), and result of subsequent examination were compared over a 5‐year period.

Results

The rate of abnormal Pap test on 5 year follow‐up was not statistically significant (P < .9520) between cohorts. Our data demonstrates lack of statistical significance between the variables studied. Five year follow‐up of all abnormal Pap smears were analyzed (93% ETZ and 7% NTZ). Of the ETZ group, 25% ASCUS remained as ASCUS and 75% were reported as NILM in subsequent Pap smears. Additionally, 75% of the LSIL were subsequently reported as NILM and 25% reported as ASCUS. One patient reported as HSIL underwent hysterectomy. Two Pap smears performed two years after surgery were negative. Within the NTZ group, one case of ASCUS was NILM upon follow‐up.

Conclusion

Pap smears with NTZ were not at a higher risk for subsequent detection of cervical abnormalities, making earlier repeat testing unnecessary. Rescreening cases without TZ is neither cost effective nor necessary.
Fluorescence in situ hybridization analysis on cytologic smears: An accurate and efficient method in the diagnosis of melanotic Xp11 translocation renal cancer
Authors: Gupta Alia , Micale Mark , Bernacki Kurt D.
Published: May 2018

Melanotic Xp11 translocation renal cancer is a rare category of MiTF/TFE3 neoplasms morphologically resembling Xp11 translocation renal cell carcinoma, Xp11 translocation perivascular epithelioid cell tumor, and melanoma. The diagnosis requires demonstration of TFE3 gene rearrangement, by either fluorescence in situ hybridization (FISH) at the Xp11.2 locus or by TFE3 immunohistochemistry. As cytology smears can be useful adjuncts in cytogenetic and molecular testing, we demonstrate TFE3 rearrangement by FISH analysis on cytologic smears in melanotic Xp11 translocation renal cancer. An 18‐year‐old girl presented with a large right renal mass. Intraoperative scrape smears were performed on suspicious aortocaval lymph nodes. A subset of smears was stained (Papanicolaou and DiffQuik). Morphologically, the neoplastic cells exhibited abundant clear vacuolated cytoplasm and moderate to marked nuclear pleomorphism. Unstained and destained smears were examined for TFE3 rearrangement by FISH. Positive TFE3 FISH results on formalin‐fixed paraffin‐embedded tissue correlated with the positive FISH findings of TFE3 gene rearrangement on cytologic smears. Therefore, the diagnosis of melanotic Xp11 translocation renal cancer was rendered. In Xp11 translocation associated neoplasms, FISH analysis on cytologic smears can be an efficient, accurate, and cost‐effective method for evaluating TFE3 rearrangement.
The acceptability, feasibility, and possible benefits of a neurobiologically‐informed 5‐day multifamily treatment for adults with anorexia nervosa
Authors: Wierenga Christina E. , Hill Laura , Knatz Peck Stephanie , McCray Jason , Greathouse Laura , Peterson Danika , Scott Amber , Eisler Ivan , Kaye Walter H.
Published: May 2018

Objective

Novel treatments for adults with anorexia nervosa (AN) are lacking. Recent scientific advances have identified neurobiologically‐driven temperament contributors to AN symptoms that may guide development of more effective treatments. This preliminary study evaluates the acceptability, feasibility and possible benefits of a multicenter open trial of an intensive 5‐day neurobiologically‐informed multifamily treatment for adults with AN and their supports (SU). The temperament‐focused treatment combines psychoeducation of AN neurobiology and SU involvement to develop skills to manage traits contributing to disease chronicity.

Method

Fifty‐four adults with AN and at least one SU (n = 73) received the 5‐day treatment. Acceptability, feasibility, and attrition were measured post‐treatment. Clinical outcome (BMI, eating disorder psychopathology, family function) was assessed post‐treatment and at >3‐month follow‐up.

Results

The treatment had low attrition, with only one drop‐out. Patients and SU rated the intervention as highly acceptable, and clinicians reported good feasibility. At post‐treatment, patients demonstrated significantly increased BMI, reduced eating disorder psychopathology, and improved family function. Benefits were maintained in the 39 patients who completed follow‐up assessment, with 62% reporting full or partial remission.

Discussion

Preliminary results are promising and suggest this novel treatment is feasible and acceptable. To establish treatment efficacy, fully‐powered randomized controlled trials are necessary.
Quantifying natural seasonal variation in mutation parameters with mutation accumulation lines
Authors: Rutter Matthew T. , Roles Angela J. , Fenster Charles B.
Published: May 2018

Mutations create novel genetic variants, but their contribution to variation in fitness and other phenotypes may depend on environmental conditions. Furthermore, natural environments may be highly heterogeneous. We assessed phenotypes associated with survival and reproductive success in over 30,000 plants representing 100 mutation accumulation lines of Arabidopsis thaliana across four temporal environments at a single field site. In each of the four assays, environmental variance was substantially larger than mutational variance. For some traits, whether mutational variance was significantly varied between seasons. The founder genotype had mean trait values near the mean of the distribution of the mutation accumulation lines in all field experiments. New mutations also contributed more phenotypic variation than would be predicted, given phenotypic and sequence‐level divergence among natural populations of A. thaliana. The combination of large environmental variance with a mean effect of mutation near zero suggests that mutations could contribute substantially to standing genetic variation.
Relating species richness to the structure of continuous landscapes: alternative methodological approaches
Authors: Gallardo‐Cruz José Alberto , Hernández‐Stefanoni José Luis , Moser Dietmar , Martínez‐Yrizar Angelina , Llobet Sergi , Meave Jorge A.
Published: May 2018

Numerous studies have focused on the relationship between landscape structure and plant diversity based on the patch‐mosaic landscape paradigm, by deriving structural data from classified images. Since the use of discrete classes poses limitations for predicting biodiversity patterns in complex, low human‐impacted ecosystems, two alternative methods have been used to analyze changes of landscape attributes in a continuum: moving‐window metrics and surface metrics (image texture). Here, we compare these two approaches for predicting richness of all plant species, legume species, legume trees, legume shrubs, legume forbs, and legume climbers across a tropical landscape in Mexico, based on the records of vascular plants in 250 10 × 10 m plots. Multiple regression and variance partitioning methods were used to analyze the effects of the two landscape descriptors (moving‐window and surface metrics), scale (400‐ and 200‐m moving‐window sides), and space (based on the extraction of principal coordinates of neighbor matrices’ vectors) on species richness. The predictive power of all metrics was relatively small for total species richness, but generally higher for legume species. For legume forbs, surface metrics‐based models indicated a direct association between species richness and landscape homogeneity. Moving‐window metrics were highly sensitive to the biological group and to spatial scale, likely due to a leftover effect of image classification procedures. Conversely, surface metrics were more independent from scale and taxonomy. Attempts to predict species richness in highly diverse, low human‐impacted tropical ecosystems more rapidly and accurately should better rely on surface metrics rather than on moving‐window metrics, in line with the continuous landscape paradigm.
A modified trait‐based framework for assessing the resilience of ecosystem services provided by coral reef communities
Authors: Carturan Bruno S. , Parrott Lael , Pither Jason
Published: May 2018

Climate change and other anthropogenic disturbances are having dramatic impacts on tropical coral reefs and the ecosystem services they provide. Anticipating change in ecosystem services is a pressing challenge that requires understanding how species respond to an environmental change, and how they contribute to ecosystem services. Building on analogous efforts by plant ecologists, we propose a trait‐based framework that aims to predict the resistance and recovery of coral ecosystem services against both pulse and press disturbances. The framework involves identifying effect, resistance, and recovery traits across coral species and using these to ascertain how species might (1) contribute to a service, (2) resist disturbance, and (3) recover after the disturbance. By identifying trait functional overlaps and quantifying correlations among the trait types, the framework can yield a better understanding of the potential mechanistic links between community assembly, ecosystem dynamics, and ecosystem functioning. We demonstrate the utility of the framework by applying it to a virtual scenario, implemented via simulation, in which habitat provisioning is the focal ecosystem service, and cyclones and bleaching events are the disturbances of interest. This demonstration required us to assemble an extensive dataset of relevant traits—a process that revealed key gaps in the coral trait database and in our understanding of coral functional ecology. The framework can provide predictive power for the resilience of ecosystem services and can also help identify crucial knowledge gaps, research objectives, and strategies for applying a trait‐based approach to advancing coral reef science and conservation.
How can mortality increase population size? A test of two mechanistic hypotheses
Authors: McIntire Kristina M. , Juliano Steven A.
Published: May 2018

Overcompensation occurs when added mortality increases survival to the next life‐cycle stage. Overcompensation can contribute to the Hydra effect, wherein added mortality increases equilibrium population size. One hypothesis for overcompensation is that added mortality eases density dependence, increasing survival to adulthood (“temporal separation of mortality and density dependence”). Mortality early in the life cycle is therefore predicted to cause overcompensation, whereas mortality later in the life cycle is not. Another hypothesis for overcompensation is that threat of mortality (e.g., from predation) causes behavioral changes that reduce overexploitation of resources, allowing resource recovery, and increasing production of adults (“prudent resource exploitation”). Behaviorally active predation cues alone are therefore predicted to cause overcompensation. We tested these predictions in two experiments with larvae of two species ofAedes. As predicted, early mortality yielded greater production of adults, and of adult females, and greater estimated rate of population increase than did later mortality. Addition of water‐borne predation cues usually reduced browsing on surfaces in late‐stage larvae, but contrary to prediction, resulted in neither significantly greater production of adult mosquitoes nor significantly greater estimated rate of increase. Thus we have strong evidence that timing of mortality contributes to overcompensation and the Hydra effect in mosquitoes. Evidence that predation cues alone can result in overcompensation via prudent resource exploitation is lacking. We expect the overcompensation in response to early mortality will be common in organisms with complex life cycles, density dependence among juveniles, and developmental control of populations.
Beyond neutrality: disentangling the effects of species sorting and spurious correlations in community analysis
Authors: Clappe Sylvie , Dray Stéphane , Peres‐Neto Pedro R.
Published: May 2018

The methods of direct gradient analysis and variation partitioning are the most widely used frameworks to evaluate the contributions of species sorting to metacommunity structure. In many cases, however, species are also driven by spatial processes that are independent of environmental heterogeneity (e.g., neutral dynamics). As such, spatial autocorrelation can occur independently in both species (due to limited dispersal) and the environmental data, leading to spurious correlations between species distributions and the spatialized (i.e., spatially autocorrelated) environment. In these cases, the method of variation partitioning may present high Type I error rates (i.e., reject the null hypothesis more often than the pre‐established critical level) and inflated estimates regarding the environmental component that is used to estimate the importance of species sorting. In this paper, we (1) demonstrate that metacommunities driven by neutral dynamics (via limited dispersal) alone or in combination with species sorting leads to inflated estimates and Type I error rates when testing for the importance of species sorting; and (2) propose a general and flexible new variation partitioning procedure to adjust for spurious contributions due to spatial autocorrelation from the environmental fraction. We used simulated metacommunity data driven by pure neutral, pure species sorting, and mixed (i.e., neutral + species sorting dynamics) processes to evaluate the performances of our new methodological framework. We also demonstrate the utility of the proposed framework with an empirical plant dataset in which we show that half of the variation initially due to the environment by the standard variation partitioning framework was due to spurious correlations.
Sulfonyl Fluorides (SFs): More Than Click Reagents?
Authors: Chinthakindi Praveen K. , Arvidsson Per I.
Published: May 2018

Sulfonyl fluoride (SF) containing substances are currently attracting enormous attention among practitioners of both chemical biology and synthetic organic chemistry. The groups of Jones and Liskamp have demonstrated the potential of sulfonyl fluorides as selective covalent inhibitors in studies related to drug discovery and chemical biology, respectively, in the last few years. The Sharpless group has extended the repertoire of “click‐reactions” to those involving sulfonyl fluorides, that is, sulfur–fluoride exchange (SuFEx), a development that quickly triggered the interest in this functional group in the community of synthetic organic chemists. In this microreview, we aim to give an account of the synthetic chemistry surrounding sulfonyl fluoride containing substances from a historical perspective to present day developments.
Stereocontrolled Synthesis of 2‐Fluorinated C‐Glycosides
Authors: Sadurní Anna , Gilmour Ryan
Published: May 2018

A systematic study of the addition of C‐based nucleophiles to fluorinated lactones based on 2‐deoxy‐2‐fluoro‐d‐pyranoses is disclosed. This high yielding, α‐selective process was found to be independent on the nature or configuration [(R)‐C(sp3)–F, (S)‐C(sp3)–F] of the substituent at C2. Representative, fluorinated analogues of Trehalose, Carminic acid, and the spirocyclic cores of Tofogliflozin and Papulacandin D are also reported. These glycomimics constitute a valuable series of 19F NMR active probes for application in structural biology.
Region‐specific deletions of the glutamate transporter GLT1 differentially affect nerve injury‐induced neuropathic pain in mice
Authors: Zhao Zhuoyang , Hiraoka Yuichi , Ogawa Hiroshi , Tanaka Kohichi
Published: May 2018

Glutamate is a major excitatory neurotransmitter and plays an important role in neuropathic pain, which is frequently caused by nerve damage. According to recent studies, nerve injury induces changes in glutamatergic transmission in the spinal cord and several supraspinal regions, including the periaqueductal gray (PAG). Among glutamate signaling components, accumulating evidence suggests that the glial glutamate transporter GLT1 plays a critical role in neuropathic pain. Indeed, GLT1 expression is reduced in the spinal cord but increased in the PAG after nerve injury, suggesting that the role of GLT1 in neuropathic pain may vary according to the brain region. In this study, we generated PAG‐specific and spinal cord‐specific GLT1 knockout mice. Nerve injury‐induced neuropathic pain was enhanced in spinal cord‐specific GLT1 knockout mice but alleviated in PAG‐specific GLT1 knockout mice. Thus, nerve injury may enhance glutamatergic neurotransmission from primary sensory neurons to the post‐synaptic dorsal horn following downregulation of GLT1 in the spinal cord and result in inadequate descending pain inhibition caused by GLT1 upregulation in the PAG, resulting in neuropathic pain. In addition, ceftriaxone upregulated GLT1 expression in the spinal cord, but not the PAG, of control mice and attenuated tactile hypersensitivity in nerve‐injured control mice but not in nerve‐injured spinal cord‐specific GLT1 knockout mice. Based on these results, the anti‐neuropathic pain effect of ceftriaxone is mediated by the upregulation of GLT1 expression in the spinal cord. Thus, selective upregulation of spinal GLT1 and/or downregulation of GLT1 in the PAG represents a potentially novel strategy for the treatment of neuropathic pain.
A systematic review of effort‐reward imbalance among health workers
Authors: Nguyen Van Huy , Dinh Le Mai , Nguyen Van Thanh , Nguyen Ngoc Dung , Tran Thi Ngoc Anh , Nguyen The Phuong
Published: May 2018

The purpose of this article is to systematically collate effort‐reward imbalance (ERI) rates among health workers internationally and to assess gender differences. The effort‐reward (ER) ratio ranges quite widely from 0.47 up to 1.32 and the ERI rate from 3.5% to 80.7%. Many studies suggested that health workers contribute more than they are rewarded, especially in Japan, Vietnam, Greece, and Germany—with ERI rates of 57.1%, 32.3%, 80.7%, and 22.8% to 27.6%, respectively. Institutions can utilize systems such as the new appraisal and reward system, which is based on performance rather than the traditional system, seniority, which creates a more competitive working climate and generates insecurity. Additionally, an increased workload and short stay patients are realities for workers in a health care environment, while the structure of human resources for health care remains inadequate. Gender differences within the ER ratio can be explained by the continued impact of traditional gender roles on attitudes and motivations that place more pressure to succeed for men rather than for women. This systematic review provides some valued evidence for public health strategies to improve the ER balance among health workers in general as well as between genders in particular. An innovative approach for managing human resources for health care is necessary to motivate and value contributions made by health workers.
Single‐incision laparoscopic abdominal cerclage placement: A retrospective study of single‐port and robotic single‐port versus multiport laparoscopy
Authors: Zhang Yiming , Gandhi Manisha , Birchall Courtney , Guan Xiaoming
Published: May 2018

Single‐incision laparoscopic surgery is a potential alternative method for abdominal cerclage placement before conception in women needing this intervention.
TSFDC: A trading strategy based on forecasting directional change
Authors: Bakhach Amer M. , Tsang Edward P.K. , Raju Chinthalapati V.L.
Published: May 2018

Directional Change (DC) is a technique to summarize price movements in a financial market. According to the DC concept, data is sampled only when the magnitude of price change is significant according to the investor. In this paper, we develop a contrarian trading strategy named TSFDC. TSFDC is based on a forecasting model which aims to predict the change of the direction of market's trend under the DC context. We examine the profitability, risk and risk‐adjusted return of TSFDC in the FX market using eight currency pairs. The results suggest that TSFDC outperforms the buy and hold approach and another DC‐based trading strategy.
Near infrared low‐level laser therapy and cell proliferation: The emerging role of redox sensitive signal transduction pathways
Authors: Migliario Mario , Sabbatini Maurizio , Mortellaro Carmen , Renò Filippo
Published: May 2018

Lasers devices are widely used in various medical fields (eg, surgery, dermatology, dentistry, rehabilitative medicine, etc.) for different applications, ranging from surgical ablation of tissues to biostimulation and pain relief. Laser is an electromagnetic radiation, which effects on biological tissues strongly depends on a number of physical parameters. Laser wavelength, energy output, irradiation time and modality, temperature and tissue penetration properties have to be set up according to the clinical target tissue and the desired effect. A less than optimal operational settings, in fact, could result in a null or even lethal effect. According to the first law of photobiology, light absorption requires the presence of a specific photoacceptor that after excitation could induce the activation of downstream signaling pathways. Low‐level lasers operating in the red/near infrared portion of the light spectra are generally used for biostimulation purposes, a particular therapeutic application based on the radiant energy ability to induce nonthermal responses in living cells. Biostimulation process generally promotes cell survival and proliferation. Emerging evidences support a low‐level laser stimulation mediated increase in “good” reactive oxygen species, able to activate redox sensitive signal transduction pathways such as Nrf‐2, NF‐kB, ERK which act as key redox checkpoints.
A comparison of the bone regeneration and soft‐tissue‐formation capabilities of various injectable‐grafting materials in a rabbit calvarial defect model
Authors: Chen Chih‐Long , Tien Han‐Wen , Chuang Chia‐Hui , Chen Ying‐Chieh
Published: May 2018

Restoring adequate blood supply is essential to the success of bone repair and augmentation procedures in craniofacial surgery. Nevertheless, the manner by which the incorporation of collagen gels (which can potentially induce angiogenesis), particulated deproteinized bovine bone grafts, or a combination of both can accelerate or delay bone regeneration in a clinical setting remains controversial. The objective of this study was to evaluate radiographically and histologically the capacity and functionality of particulated bone grafts and collagen gels on bone ossification and soft tissue formation in a rabbit calvarial defect. Bilateral calvarial defects in adult white New Zealand rabbits were filled or left either unfilled with bone grafts (DBBM), collagen gels (Gel), or a combination of both (DBBM + Gel). The defects were allowed to heal for 1, 2, and 6 months postoperatively before termination. Healing and regeneration patterns were assessed by 3D µCT and histological methods, and the biomechanical properties of regenerated tissue constructs were investigated and compared with autogenous calvarial bone. Results show that implanted DBBM and DBBM + Gel significantly enhanced immature bone formation compared with the empty and Gel groups; the latter treatment improved soft tissue formation and impeded immature bone formation but yielded no significant effect on mature bone formation. Implantation of DBBM not only effectively reconstructed 188.83 ± 25.25% of the tissue volume of the original defect, but it also regenerated bone tissue with similar tissue composition and biomechanical properties as the original autogenous bone. We also show that implanting different biomaterials can control the composition of soft and hard tissue in reconstructed tissue constructs in calvarial bone defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 529–544, 2019.
Systematic evaluation and refinement of existing all‐atom force fields for the simulation of liquid acetonitrile
Authors: Kowsari Mohammad H. , Tohidifar Leila
Published: May 2018

The reliability of a molecular dynamics (MD) simulation study mainly depends on the accuracy of the applied force field. Unlike the ability of some potential models for reasonably predicting the thermodynamic properties of acetonitrile (ACN), simulated dynamical properties such as self‐diffusion are generally underestimated compared to experimental values. The present work focuses on the evaluation and refinement of several available all‐atom force fields for ACN and proposes a refined flexible six‐site potential model. The main modification is related to the reduction of intermolecular LJ parameters (σ and ɛ) for hydrogen atoms, especially ɛ, significantly affecting the dynamical behavior. Besides, the adjustment of σ and ɛ for nitrile carbon and nitrogen atoms helps reach optimum results. Our refined model shows an excellent agreement with the experiment for self‐diffusion coefficient and thermodynamic quantities as well as providing a qualitative description of the microscopic structure of liquid ACN. © 2018 Wiley Periodicals, Inc.
Multiple Doses of Rifabutin Reduce Exposure of Doravirine in Healthy Subjects
Authors: Khalilieh Sauzanne G. , Yee Ka Lai , Sanchez Rosa I. , Liu Rachel , Fan Li , Martell Maureen , Jordan Heather , Iwamoto Marian
Published: May 2018

Doravirine is a nonnucleoside reverse transcriptase inhibitor in clinical development for the treatment of human immunodeficiency virus‐1 infection in combination with other antiretroviral therapies. The cytochrome P450 (CYP)3A‐dependent metabolism of doravirine makes it susceptible to interactions with modulators of this pathway, including the antituberculosis treatment rifampin. Rifabutin, an alternative antibiotic used to treat tuberculosis, may have a lower‐magnitude effect on CYP3A. The aim of this trial was to determine the effect of steady‐state rifabutin on doravirine single‐dose pharmacokinetics and tolerability. In this open‐label, 2‐period, fixed‐sequence, drug‐drug interaction study, healthy subjects received a single dose of doravirine 100 mg alone and coadministered on day 14 of once‐daily administration of rifabutin 300 mg for 16 days. Plasma samples were taken to determine doravirine pharmacokinetics, and safety was monitored throughout. Dose adjustment of doravirine in the presence of coadministered rifabutin was explored through nonparametric superposition analysis. Rifabutin reduced doravirine area under the concentration‐time curve from time zero to infinite and plasma drug concentration 24 hours postdose with geometric mean ratios ([rifabutin+doravirine]/[doravirine alone]) (90%CIs) of 0.50 (0.45‐0.55) and 0.32 (0.28‐0.35), respectively. Doravirine apparent clearance increased from 5.9 L/h without rifabutin to 12.2 L/h when coadministered. Doravirine pharmacokinetics with and without coadministered rifabutin were not equivalent. Nonparametric superposition analysis projected that administration of doravirine 100 mg twice daily with rifabutin will restore steady‐state trough concentration values to efficacious levels associated with doravirine 100 mg once daily in the absence of CYP3A inducers. Doravirine may be coadministered with rifabutin when the doravirine dose frequency is increased from 100 mg once daily to 100 mg twice daily.
CYP2C19 or CYP3A5 Genotyping Does Not Predict Clinical Response to Clopidogrel
Authors: Rodríguez‐González Fayna , Martínez‐Quintana Efren , Saavedra Pedro , Medina‐Gil José M. , Riaño Marta , Garay‐Sánchez Paloma , Tugores Antonio
Published: May 2018

Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events. This clinical relapse was considered a surrogate end point to measure therapeutic response under the influence of the CYP2C19*2, *3, and *17 and CYP3A5*3 alleles, as well as the effects of concomitant medication and the presence of known cardiovascular risk factors and comorbidity. We show that either single CYP2C19 or CYP3A5 genotyping or combined were not useful to predict clinical efficacy in this cohort. Rather than genetic testing, we have found that clinical observations such as suffering type 2 diabetes mellitus requiring insulin, having several vessels affected, and concurrent medication with calcium channel blockers, regardless of CYP3A5 genotype or drug class were, in that order, the strongest independent predictors of disease relapse.