bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhododendron maximumimpacts seed bank composition and richness followingTsuga canadensisloss in riparian forests
Authors: Cofer Tristan M. , Elliott Katherine J. , Bush Janis K. , Miniat Chelcy F.
Published: April 2018

Southern Appalachian riparian forests have undergone changes in composition and function from invasive pathogens and pests.Castanea dentatamortality in the 1930s from chestnut blight (Cryphonectria parasitica) andTsuga canadensismortality in the 2000s from the hemlock woolly adelgid (Adelges tsugae) have led to the expansion and increased growth ofRhododendron maximum, an evergreen subcanopy shrub. A better understanding of seed bank characteristics and the various abiotic and biotic factors that affect the seed bank may be useful in determining the restoration potential of forest communities following invasion‐related disturbances. We compared the seed bank of two deciduous forest types: hardwood forests with a denseR. maximumsubcanopy (hereafter,RR) and hardwood forests withoutR. maximum(hereafter,HWD). We evaluated numerous microenvironmental variables through principal component analysis (PCA) and correlated the derivedPCAaxes scores to seed bank density and richness across forest types. We found that seed bank density was comparable between the forests types; however, seed bank richness was much lower inRRthanHWDand the species composition was dissimilar between forest types. Twenty‐eight of 64 (44%) species in the seed bank ofHWDwere not found in the seed bank ofRR. Species that were represented in both forest types were often found in contrasting densities. Most notably, seed bank densities of several woody species were considerably higher inRR(85%) thanHWD(45%), while herbaceous seed bank density was lower inRR(11%) thanHWD(50%). Mineral soilpH, soil nutrient availability, and soil moisture were lower, and organic soil (Oi + Oe + Oa) depth and mass were greater in theRRthanHWDforest type.PCAcorrelations revealed thatPCA4 (represented by understory density and Oe + Oa phosphorus and carbon/nitrogen ratio) was negatively correlated with total seed bank density.PCA1 (represented by Oe + Oa cations and phosphorus, understory richness, ground‐layer cover, and mineral soilpH) andPCA4 were positively correlated with total seed bank richness. These results suggest that the soil seed bank will not be the primary mode of recruitment to establish a diverse and herbaceous‐rich community if a RR is present.
Microbial decomposers not constrained by climate history along a Mediterranean climate gradient in southern California
Authors: Baker Nameer R. , Khalili Banafshe , Martiny Jennifer B. H. , Allison Steven D.
Published: April 2018

Microbial decomposers mediate the return of CO2 to the atmosphere by producing extracellular enzymes to degrade complex plant polymers, making plant carbon available for metabolism. Determining if and how these decomposer communities are constrained in their ability to degrade plant litter is necessary for predicting how carbon cycling will be affected by future climate change. We analyzed mass loss, litter chemistry, microbial biomass, extracellular enzyme activities, and enzyme temperature sensitivities in grassland litter transplanted along a Mediterranean climate gradient in southern California. Microbial community composition was manipulated by caging litter within bags made of nylon membrane that prevent microbial immigration. To test whether grassland microbes were constrained by climate history, half of the bags were inoculated with local microbial communities native to each gradient site. We determined that temperature and precipitation likely interact to limit microbial decomposition in the extreme sites along our gradient. Despite their unique climate history, grassland microbial communities were not restricted in their ability to decompose litter under different climate conditions across the gradient, although microbial communities across our gradient may be restricted in their ability to degrade different types of litter. We did find some evidence that local microbial communities were optimized based on climate, but local microbial taxa that proliferated after inoculation into litterbags did not enhance litter decomposition. Our results suggest that microbial community composition does not constrain C‐cycling rates under climate change in our system, but optimization to particular resource environments may act as more general constraints on microbial communities.
Effects of intraspecific phenotypic variation on species coexistence
Authors: Hausch Stephen , Vamosi Steven M. , Fox Jeremy W.
Published: April 2018

Intraspecific variation can promote or inhibit species coexistence, both by increasing species’ competitive abilities, and by altering the relative strengths of intraspecific and interspecific competition. Effects of intraspecific variation on coexistence can occur via complementarity of different variants, and via a selection effect: initially‐variable populations are more likely to contain highly competitive variants that might determine the ability of the population as a whole to both invade and resist invasion. We tested the effects of intraspecific variation and composition on coexistence by assaying the mutual invasibility of populations of two competing bean weevil species (Callosobruchus maculatusandC. chinensis) when each was initiated with one, three, or five genetically‐ and phenotypically‐distinct lineages. Our results reveal that intraspecific variation is a double‐edged sword for species coexistence. Increasing intraspecific variation increased species’ abilities to invade, and to resist invasion, via selection effects and intraspecific niche complementarity among conspecific lineages, thereby creating the potential for exclusion among mismatched competitors. But intraspecific variation also increased the scope for resource partitioning, creating the potential for stable coexistence. Stable coexistence occurred only when intraspecific variation caused species to exhibit both relatively evenly‐matched competitive abilities and sufficiently‐strong resource partitioning. Our work explains the conflicting results of previous studies.
Homozygous missense MYBPC3 Pro873His mutation associated with increased risk for heart failure development in hypertrophic cardiomyopathy
Authors: Kissopoulou Antheia , Trinks Cecilia , Green Anna , Karlsson Jan‐Erik , Jonasson Jon , Gunnarsson Cecilia
Published: April 2018

Hypertrophic cardiomyopathy (HCM) is a primary autosomal‐dominant disorder of the myocardium with variable expressivity and penetrance. Occasionally, homozygous sarcomere genetic variants emerge while genotyping HCM patients. In these cases, a more severe HCM phenotype is generally seen. Here, we report a case of HCM that was diagnosed clinically at 39 years of age. Initial symptoms were shortness of breath during exertion. Successively, he developed a wide array of severe clinical manifestations, which progressed to an ominous end‐stage heart failure that resulted in heart transplantation. Genotype analysis revealed a missense MYBPC3 variant NM_000256.3:c.2618C>A,p.(Pro873His) that presented in the homozygous form. Conflicting interpretations of pathogenicity have been reported for the Pro873His MYBPC3 variant described here. Our patient, presenting with two copies of the variant and devoid of a normal allele, progressed to end‐stage heart failure, which supports the notion of a deleterious effect of this variant in the homozygous form.
Dynamic Metal–Ligand Bonds as Scaffolds for Autonomously Healing Multi‐Responsive Materials
Authors: Mauro Matteo
Published: April 2018

Supramolecular functional materials featuring self‐healing properties are a fascinating class of materials that are currently attracting great interest. In this respect, use of dynamic metal–ligand bonds has received much less attention than other reversible interactions – either covalent bonds or noncovalent interactions. Nonetheless, systems and materials with enhanced and special functionalities might arise from the synergic combination of labile coordination bonds and the physicochemical properties – optical, magnetic, electrical, catalytic, and so on – associated with the presence of judiciously chosen metal ions or organic ligands. Here, advances in the field of healing and multi‐functional materials based on the reversible formation of metal‐ligand bonds are highlighted through a selection of key examples, including bioinspired ones.
Bayesian hierarchical model for variations in earthquake peak ground acceleration within small‐aperture arrays
Authors: Rahpeyma Sahar , Halldorsson Benedikt , Hrafnkelsson Birgir , Jónsson Sigurjón
Published: April 2018

Knowledge of the characteristics of earthquake ground motion is fundamental for earthquake hazard assessments. Over small distances, relative to the source–site distance, where uniform site conditions are expected, the ground motion variability is also expected to be insignificant. However, despite being located on what has been characterized as a uniform lava‐rock site condition, considerable peak ground acceleration (PGA) variations were observed on stations of a small‐aperture array (covering approximately 1 km2) of accelerographs in Southwest Iceland during the Ölfus earthquake of magnitude 6.3 on May 29, 2008 and its sequence of aftershocks. We propose a novel Bayesian hierarchical model for the PGA variations accounting separately for earthquake event effects, station effects, and event‐station effects. An efficient posterior inference scheme based on Markov chain Monte Carlo (MCMC) simulations is proposed for the new model. The variance of the station effect is certainly different from zero according to the posterior density, indicating that individual station effects are different from one another. The Bayesian hierarchical model thus captures the observed PGA variations and quantifies to what extent the source and recording sites contribute to the overall variation in ground motions over relatively small distances on the lava‐rock site condition.
Hazard‐compatible modification of stochastic ground motion models
Authors: Tsioulou Alexandra , Taflanidis Alexandros A. , Galasso Carmine
Published: April 2018

A computationally efficient framework is presented for modification of stochastic ground motion models to establish compatibility with the seismic hazard for specific seismicity scenarios and a given structure/site. The modification pertains to the probabilistic predictive models that relate the parameters of the ground motion model to seismicity/site characteristics. These predictive models are defined through a mean prediction and an associated variance, and both these properties are modified in the proposed framework. For a given seismicity scenario, defined for example by the moment magnitude and source‐to‐site distance, the conditional hazard is described through the mean and the dispersion of some structure‐specific intensity measure(s). Therefore, for both the predictive models and the seismic hazard, a probabilistic description is considered, extending previous work of the authors that had examined description only through mean value characteristics. The proposed modification is defined as a bi‐objective optimization. The first objective corresponds to comparison for a chosen seismicity scenario between the target hazard and the predictions established through the stochastic ground motion model. The second objective corresponds to comparison of the modified predictive relationships to the pre‐existing ones that were developed considering regional data, and guarantees that the resultant ground motions will have features compatible with observed trends. The relative entropy is adopted to quantify both objectives, and a computational framework relying on kriging surrogate modeling is established for an efficient optimization. Computational discussions focus on the estimation of the various statistics of the stochastic ground motion model output needed for the entropy calculation.
The emergence, maintenance, and demise of diversity in a spatially variable antibiotic regime
Authors: Leale Alanna M. , Kassen Rees
Published: April 2018

Antimicrobial resistance (AMR) is a growing global threat that, in the absence of new antibiotics, requires effective management of existing drugs. Here, we use experimental evolution of the opportunistic human pathogen Pseudomonas aeruginosa to explore how changing patterns of drug delivery modulates the spread of resistance in a population. Resistance evolves readily under both temporal and spatial variation in drug delivery and fixes rapidly under temporal, but not spatial, variation. Resistant and sensitive genotypes coexist in spatially varying conditions due to a resistance-growth rate trade-off which, when coupled to dispersal, generates negative frequency-dependent selection and a quasi-protected polymorphism. Coexistence is ultimately lost, however, because resistant types with improved growth rates in the absence of drug spread through the population. These results suggest that spatially variable drug prescriptions can delay but not prevent the spread of resistance and provide a striking example of how the emergence and eventual demise of biodiversity is underpinned by evolving fitness trade-offs.
Superior stimulation of female fecundity by subordinate males provides a mechanism for telegony
Authors: Pascoal Sonia , Jarrett Benjamin J. M. , Evans Emma , Kilner Rebecca M.
Published: April 2018

When females mate promiscuously, rival males compete to fertilise the ova. In theory, a male can increase his success at siring offspring by inducing the female to lay more eggs, as well as by producing more competitive sperm. Here we report that the evolutionary consequences of fecundity stimulation extend beyond rival males, by experimentally uncovering effects on offspring. With experiments on the burying beetle Nicrophorus vespilloides, we show that smaller subordinate males are better able to stimulate female fecundity than larger, dominant males. Furthermore dominant males also benefit from the greater fecundity induced by smaller males, and so gain from the female's earlier promiscuity - just as predicted by theory. By inducing females to produce more offspring on a limited resource, smaller males cause each larva to be smaller, even those they do not sire themselves. Fecundity stimulation thus promotes the non-genetic inheritance of offspring body size, and provides a mechanism for telegony.
Experimental Investigation of Heat Loss from a Passive DMFC using Differential Interferometer
Authors: Vasanth P. , Kolar Ajit K.
Published: April 2018

The knowledge of heat loss from the fuel cell will be helpful to decide on material components and fixture design. In the present study, a new methodology is proposed to estimate heat loss from passive DMFC using interferometry technique. Printed circuit board (PCB) fixture is adapted in our study that replaces end plate and current collector. The accurate cell temperature distribution is useful to estimate the heat from the cell fixture. The cell temperature distribution is measured based on infra‐red (IR) thermography and this temperature distribution is used to estimate the heat transfer coefficient of the fuel cell. Differential interferometer (DI) technique is used to estimate the heat transfer under different operating conditions of the fuel cell. The cell surface temperature measured on the cathode gas diffusion layer (GDL) is 42 °C for 5M methanol concentration whereas for 1M, it is 32 °C. Based on the analysis , the average heat transfer coefficient of the cell at vertical PCB rib orientation using 5M methanol concentration is estimated to be 2.7 Wm−2 K−1. A two‐dimensional non‐isothermal single‐phase half‐cell (cathode) model is developed and compared with experiments. The cell temperature distribution obtained from model is in good agreement with experiments. The model is extended to study the effect of PCB orientation and thermal conductivity of PCB material on heat loss. The cell at vertical PCB rib orientation retains 15 ‐ 20% more heat than horizontal rib. Therefore, the cell temperature showed 42 °C and performed 10% better compared to horizontal PCB rib.
Petrography and geochemistry of Oligocene to Lower Miocene sandstones in the Baiyun Sag, Pearl River Mouth Basin, South China Sea: Provenance, source area weathering, and tectonic setting
Authors: Ma Ming , Chen Guojun , Li Chao , Zhang Gongcheng , Lv Chengfu , Xue Lianhua , Shen Huailei , Zhao Zhao
Published: April 2018

There is a controversy regarding the source area and weathering intensity of Oligocene to Lower Miocene sediments in the Baiyun Sag of the Pearl River Mouth Basin. Detrital modes, geochemistry, heavy mineral data, and detrital zircon U–Pb ages were analysed to understand the provenance, source area weathering, and tectonic setting of Oligocene to Lower Miocene sandstones in the Baiyun Sag. Petrographic data reveal that the sandstones were derived from a recycled orogen. With increasing transport distance, sediment maturity increased correspondingly. The Oligocene to Lower Miocene sandstones in the Baiyun Sag have low compositional maturity and have experienced low to moderate weathering. The sediments of the Zhuhai Formation have experienced relatively strong weathering intensity compared with those of the Enping and lower Zhujiang formations. Due to low degree of illitization and differences in the geochemical compositions of the sediments, the continental island arc data from different boreholes in the Baiyun Sag are more irregularly distributed in the A‐CN‐K plot. The modal composition (e.g., quartz, feldspar, and lithic fragments) and geochemical indices (Al2O3/TiO2 ratio; Al2O3‐TiO2 diagram; discriminant F1‐F2 diagram; Eu/Eu*, La/Sc, La/Co, Th/Sc, and Th/Co ratios; Hf‐La/Th and La/Sc‐Co/Th diagrams; and rare earth element patterns) indicate that the sediments in the Baiyun Sag are mainly derived from felsic source rocks. Although the uplift around the Baiyun Sag includes multistage magmatism and basic rocks, it has little influence on the sediment in the depression, and no sediments were transported by the Han River to the Baiyun Sag. Geochemical data and detrital zircon U–Pb ages suggest that the Pearl River was formed in the Early Oligocene and became the main source for the sediments in this area. The river carried felsic material from the South China Coast forming a large delta on the northern slope of the Baiyun Sag. The ratios of Eu/Eu*, La/Sc, La/Co, Th/Sc and Th/Co, and heavy mineral data indicate that the sediments transported by the Pearl River to the Baiyun Sag were changed from the arc‐dominated coastal zone to the interior of the South China Block during the Late Oligocene to Early Miocene and even reached the south‐eastern margin of the Tibetan Plateau (West Yunnan Plateau). The La‐Th‐Sc and Th‐Sc‐Zr/10 diagrams suggest that the provenance of these sandstones is evolved continental island arc or an active continental margin setting.
An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia
Authors: Wilson Stephen M. , Yen Melodie , Eriksson Dana K.
Published: April 2018

Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test–retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post‐stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test‐retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia.
Locoregionally advanced oral cavity cancer: A propensity‐score matched analysis on overall survival with emphasis on the impact of adjuvant radiotherapy
Authors: Shin Jacob Y. , Yoon Ja Kyoung , Shin Aaron K. , Diaz Aidnag Z.
Published: April 2018

Abstrac

Background

The purpose of this study was to determine the impact of adjuvant radiotherapy (RT) in locoregionally advanced oral cavity cancer.

Methods

Data were extracted from the National Cancer Data Base, of which overall survival (OS) is the only outcome variable available. The chi‐square test and Cox regression models were used.

Results

A total of 6654 patients were identified. The utilization of adjuvant RT has increased over time. A propensity matched cohort included 3946 patients, exactly one‐half of whom received adjuvant RT. Independent predictors associated with receipt of adjuvant RT included age, Charlson/Deyo comorbidity score, extracapsular extension, surgical margins, and T and N classifications. On multivariable analysis, adjuvant RT remained an independent prognosticator for OS.

Conclusion

Receipt of adjuvant RT is a prognostic factor associated with improved OS, its utilization has increased over time, and it should be considered for clinically suitable patients who have undergone resection for the disease.
Greater caregiving risk, better infant memory performance?
Authors: Rifkin‐Graboi Anne , Quan Jeffry , Richmond Jenny , Goh Shaun Kok Yew , Sim Lit Wee , Chong Yap Seng , Bureau Jean‐Francois , Chen Helen , Qiu Anqi
Published: April 2018

Poor early life care often relates to cognitive difficulties. However, newer work suggests that in early‐life, adversity may associate with enhanced or accelerated neurodevelopment. We examine associations between postnatal caregiving risks (i.e., higher self‐reported postnatal‐anxiety and lower observed maternal sensitivity) and infant relational memory (i.e., via deferred imitation and relational binding). Using subsamples of 67–181 infants (aged 433–477 post‐conceptual days, or roughly five to seven months since birth) taking part in the GUSTO study, we found such postnatal caregiving risk significantly predictive of “better” performance on a relational binding task following a brief delay, after Bonferroni adjustments. Subsequent analyses suggest that the association between memory and these risks may specifically be apparent among infants spending at least 50% of their waking hours in the presence of their mothers. Our findings echo neuroimaging research concerning similar risk exposure and larger infant hippocampal volume, and likewise underscore the importance of considering developmental context in understanding early life experience. With this in mind, these findings caution against the use of cognitive outcomes as indices of experienced risk.
Facile Synthesis of Internal and C‐Terminal Peptide α‐Ketoamides with Fmoc‐Solid Phase Peptide Synthesis
Authors: Rohrbacher Florian , Zwicky André , Bode Jeffrey W.
Published: April 2018

We report a general and operationally simple method for the solid phase synthesis of α‐ketoamide peptides using standard Fmoc solid phase peptide synthesis. The method delivers deprotected peptide α‐ketoamides directly upon resin cleavage without any additional steps, and tolerates all side chain functional groups. A small collection of C‐terminal and internal α‐ketoamide peptides – including two reported protease inhibitors (HCV and SUB1) – were prepared in good yields. In addition, we demonstrate that our method serves as versatile platform for the convenient preparation of cyclic α‐ketoamide peptides, photocagged peptide α‐ketoamides, and fluorescently labeled peptides.
Phase Ib/II study of safety and efficacy of low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory alimentary tract cancer
Authors: Chen Meixia , Nie Jing , Liu Yang , Li Xiang , Zhang Yan , Brock Malcolm V. , Feng Kaichao , Wu Zhiqiang , Li Xiaolei , Shi Lu , Li Suxia , Guo Mingzhou , Mei Qian , Han Weidong
Published: April 2018

The pressing need for improved therapeutic outcomes provides a good rationale for identifying effective strategies for alimentary tract (AT) cancer treatment. The potential re‐sensitivity property to chemo‐ and immunotherapy of low‐dose decitabine has been evident both preclinically and in previous phase I trials. We conducted a phase Ib/II trial evaluating low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory (R/R) esophageal, gastric or colorectal cancers. Forty‐five patients received either the 5‐day decitabine treatment with subsequent readministration of the previously resistant chemotherapy (decitabine‐primed chemotherapy, D‐C cohort) or the aforementioned regimen followed by cytokine‐induced killer cells therapy (D‐C and cytokine‐induced killer [CIK] cell treatment, D‐C + CIK cohort) based on their treatment history. Grade 3 to 4 adverse events (AEs) were reported in 11 (24.4%) of 45 patients. All AEs were controllable, and no patient experienced a treatment‐related death. The objective response rate (ORR) and disease control rate (DCR) were 24.44% and 82.22%, respectively, including two patients who achieved durable complete responses. Clinical response could be associated with treatment‐free interval and initial surgical resection history. ORR and DCR reached 28% and 92%, respectively, in the D‐C + CIK cohort. Consistently, the progression‐free survival (PFS) of the D‐C + CIK cohort compared favorably to the best PFS of the pre‐resistant unprimed therapy (p = 0.0001). The toxicity and ORRs exhibited were non‐significantly different between cancer types and treatment cohort. The safety and efficacy of decitabine‐primed re‐sensitization to chemoimmunotherapy is attractive and promising. These data warrant further large‐scale evaluation of drug‐resistant R/R AT cancer patients with advanced stage disease.
A genomic copy number signature predicts radiation exposure in post‐Chernobyl breast cancer
Authors: Wilke Christina M. , Braselmann Herbert , Hess Julia , Klymenko Sergiy V. , Chumak Vadim V. , Zakhartseva Liubov M. , Bakhanova Elena V. , Walch Axel K. , Selmansberger Martin , Samaga Daniel , Weber Peter , Schneider Ludmila , Fend Falko , Bösmüller Hans C. , Zitzelsberger Horst , Unger Kristian
Published: April 2018

Breast cancer is the second leading cause of cancer death among women worldwide and besides life style, age and genetic risk factors, exposure to ionizing radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation‐induced double‐strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation‐exposed and non‐exposed female patients. We analyzed resected breast cancer tissues from 68 exposed female Chernobyl clean‐up workers and evacuees and 68 matched non‐exposed control patients for CNAs by array comparative genomic hybridization analysis (aCGH). Using a stepwise forward–backward selection approach a non‐complex CNA signature, that is, less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set (p value < 0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22‐11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23‐11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA signature that has the potential to allow identification of radiation‐associated breast cancer at the individual level.
A case–control study of HIV infection and cancer in the era of antiretroviral therapy in Rwanda
Authors: Mpunga Tharcisse , Znaor Ariana , Uwizeye F. Regis , Uwase Aline , Munyanshongore Cyprien , Franceschi Silvia , Clifford Gary M.
Published: April 2018

The aim of this study was to assess the association between HIV infection and cancer risk in Rwanda approximately a decade after the introduction of antiretroviral therapy (cART). All persons seeking cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda from 2012 to 2016 were routinely screened for HIV, prior to being confirmed with or without cancer (cases and controls, respectively). Cases were coded according to ICD‐O‐3 and converted to ICD10. Associations between individual cancer types and HIV were estimated using adjusted unconditional logistic regression. 2,656 cases and 1,196 controls differed by gender (80.3% vs. 70.8% female), age (mean 45.5 vs. 37.7 years), place of residence and proportion of diagnoses made by histopathology (87.5% vs. 67.4%). After adjustment for these variables, HIV was significantly associated with Kaposi Sarcoma (n = 60; OR = 110.3, 95%CI 46.8–259.6), non‐Hodgkin lymphoma (NHL) (n = 265; OR = 2.5, 1.4–4.6), Hodgkin lymphoma (HL) (n = 76; OR = 5.2, 2.3–11.6) and cancers of the cervix (n = 560; OR = 5.9, 3.8–9.2), vulva (n = 23; OR = 17.8, 6.3–50.1), penis (n = 29; OR = 8.3, 2.5–27.4) and eye (n = 17; OR = 4.7, 1.0–25.0). Associations varied by NHL/HL subtype, with that for NHL being limited to DLBCL (n = 56; OR = 6.6, 3.1–14.1), particularly plasmablastic lymphoma (n = 6, OR = 106, 12.1–921). No significant associations were seen with other commonly diagnosed cancers, including female breast cancer (n = 559), head and neck (n = 116) and colorectal cancer (n = 106). In conclusion, in the era of cART in Rwanda, HIV is associated with increased risk of a range of infection‐related cancers, and accounts for an important fraction of cancers presenting to a referral hospital.
Front Cover: Spectrally encoded coherence tomography and reflectometry: Simultaneous en face and cross‐sectional imaging at 2 gigapixels per second (J. Biophotonics 4/2018)
Authors: El‐Haddad Mohamed T. , Bozic Ivan , Tao Yuankai K.
Published: April 2018

SECTR is a novel multimodal imaging platform for combined volumetric optical coherence tomography (OCT) and en face spectrally encoded reflectometry (SER). The authors demonstrate three‐dimensional motion‐tracking with millisecond temporal and micron spatial resolution using complementary data from OCT and SER, and preliminary algorithms and results showing real‐time image aiming and multi‐volumetric mosaicking for reconstruction of wide‐field composites. The image shows a noninvasively imaged nine‐field mosaic of in vivo human retina and depth‐resolved visualization of tissue microstructures.

Further details can be found in the article by Mohamed T. El‐Haddad, Ivan Bozic, and Yuankai K. Tao (e201700268)

image
Biomimetic sulfated polyethylene glycol hydrogel inhibits proteoglycan loss and tumor necrosis factor‐α‐induced expression pattern in an osteoarthritis in vitro model
Authors: Hemmati‐Sadeghi Shabnam , Dey Pradip , Ringe Jochen , Haag Rainer , Sittinger Michael , Dehne Tilo
Published: April 2018

This study aimed to evaluate the potential of an anti‐inflammatory polyethylene glycol (PEG) hydrogel for osteoarthritis (OA) management in an OA in vitro model. Freshly isolated porcine chondrocytes were maintained in high‐density cultures to form cartilage‐like three‐dimensional micromasses. Recombinant porcine tumor necrosis factor‐alpha (TNF‐α) was used to induce OA‐like changes. Normal and OA‐like micromasses were treated with dendritic polyglycerol sulfate‐based PEG hydrogel. Live/dead staining showed that all micromasses remained vital and presented similar morphological characteristics. Safranin‐O staining demonstrated a typical depletion of glycosaminoglycans in TNF‐α‐treated micromasses but not in the presence of the hydrogel. There was no distinct difference in immunohistochemical detection of type II collagen. Microarray data showed that rheumatoid arthritis and TNF signaling pathways were down regulated in hydrogel‐treated OA‐like micromasses compared to nontreated OA‐like micromasses. The hydrogel alone did not affect genes related to OA such as ANPEP, COMP, CXCL12, PTGS2, and TNFSF10, but it prevented their regulation caused by TNF‐α. This study provides valuable insights toward a fully synthetic hydrogel for the intra‐articular treatment of OA. The findings proved the potential of this hydrogel to prevent the development of TNF‐α‐induced OA with regard to proteoglycan loss and TNF‐α‐induced expression pattern without additional signs of differentiation and inflammation. © 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: 490–500, 2019.
Osteoporosis and Hip Fracture Risk From Routine Computed Tomography Scans: The Fracture, Osteoporosis, and CT Utilization Study (FOCUS)
Authors: Adams Annette L , Fischer Heidi , Kopperdahl David L , Lee David C , Black Dennis M , Bouxsein Mary L , Fatemi Shireen , Khosla Sundeep , Orwoll Eric S , Siris Ethel S , Keaveny Tony M
Published: April 2018

Methods now exist for analyzing previously taken clinical computed tomography (CT) scans to measure a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) at the hip and a finite element analysis–derived femoral strength. We assessed the efficacy of this “biomechanical CT” (BCT) approach for identifying patients at high risk of incident hip fracture in a large clinical setting. Using a case-cohort design sampled from 111,694 women and men aged 65 or older who had a prior hip CT scan, a DXA within 3 years of the CT, and no prior hip fracture, we compared those with subsequent hip fracture (n = 1959) with randomly selected sex-stratified controls (n = 1979) and analyzed their CT scans blinded to all other data. We found that the age-, race-, and body mass index (BMI)-adjusted hazard ratio (HR; per standard deviation) for femoral strength was significant before (women: HR = 2.8, 95% confidence interval [CI] 2.2–3.5; men: 2.8, 2.1–3.7) and after adjusting also for the (lowest) hip BMD T-score by BCT (women: 2.1, 1.4–3.2; men: 2.7, 1.6–4.6). The hazard ratio for the hip BMD T-score was similar between BCT and DXA for both sexes (women: 2.1, 1.8–2.5 BCT versus 2.1, 1.7–2.5 DXA; men: 2.8, 2.1–3.8 BCT versus 2.5, 2.0–3.2 DXA) and was higher than for the (lowest) spine/hip BMD T-score by DXA (women: 1.6, 1.4–1.9; men: 2.1, 1.6–2.7). Compared with the latter as a clinical-practice reference and using both femoral strength and the hip BMD T-score from BCT, sensitivity for predicting hip fracture was higher for BCT (women: 0.66 versus 0.59; men: 0.56 versus 0.48), with comparable respective specificity (women: 0.66 versus 0.67; men: 0.76 versus 0.78). We conclude that BCT analysis of previously acquired routine abdominal or pelvic CT scans is at least as effective as DXA testing for identifying patients at high risk of hip fracture. © 2018 American Society for Bone and Mineral Research.
The Role of Bmp2 in the Maturation and Maintenance of the Murine Knee Joint
Authors: Gamer Laura W , Pregizer Steven , Gamer Jackson , Feigenson Marina , Ionescu Andreia , Li Qing , Han Lin , Rosen Vicki
Published: April 2018

Bone morphogenetic proteins (BMPs) are key regulators of skeletal development, growth, and repair. Although BMP signaling is required for synovial joint formation and is also involved in preserving joint function after birth, the role of specific BMP ligands in adult joint homeostasis remains unclear. The purpose of this study was to define the role of Bmp2 in the morphogenesis and maintenance of the knee joint. To do this, we first created Bmp2-LacZ and Gdf5-LacZ knock-in mice and compared their expression patterns in the developing and postnatal murine knee joint. We then generated a knockout mouse model using the Gdf5-cre transgene to specifically delete Bmp2 within synovial joint-forming cells. Joint formation, maturation, and homeostasis were analyzed using histology, immunohistochemistry, qRT-PCR, and atomic force microscopy (AFM)-based nanoindentation to assess the cellular, molecular, and biomechanical changes in meniscus and articular cartilage. Bmp2 is expressed in the articular cartilage and meniscus of the embryonic and adult mouse knee in a pattern distinct from Gdf5. The knee joints of the Bmp2 knockout mice form normally but fail to mature properly. In the absence of Bmp2, the extracellular matrix and shape of the meniscus are altered, resulting in functional deficits in the meniscus and articular cartilage that lead to a progressive osteoarthritis (OA) like knee pathology as the animals age. These findings demonstrate that BMP activity provided by Bmp2 is required for the maturation and maintenance of the murine knee joint and reveal a unique role for Bmp2 that is distinct from Gdf5 in knee joint biology. © 2018 American Society for Bone and Mineral Research.
Resveratrol inhibits the proliferation and induces the apoptosis in ovarian cancer cells via inhibiting glycolysis and targeting AMPK/mTOR signaling pathway
Authors: Liu Yu , Tong Lin , Luo Yan , Li Xin , Chen Gaowen , Wang Yifeng
Published: April 2018

Aerobic glycolysis is an important metabolic rewiring in cancer cells to promote glucose uptake and lactate production, and targeting aerobic glycolysis becomes a promising therapeutic approach for cancer. Here we reported that a small polyphenol resveratrol exhibited profound anti‐tumor efficacy on human ovarian cancer. Resveratrol markedly inhibited the proliferation, migration, and invasion of A2780 and SKOV3 ovarian cancer cells, while impaired glycolysis, and induced apoptosis in these cells. Exposure to resveratrol increased the expression and activation of AMPK and Caspase 3, and decreased the expression and activation of AMPK downstream kinase mTOR. Moreover, AMPK inhibitor Compound C significantly abolished the effects of resveratrol on the activation of AMPK and Caspase 3 and the inhibition of mTOR. In addition, in vivo data indicated that resveratrol suppressed ovarian cancer growth and liver metastasis in xenograft mouse model. In conclusion, our findings provide new insight into the mechanism underlying anticancer efficacy of resveratrol and help the utilization of resveratrol as a novel agent for the treatment of ovarian cancer.
Calmodulin antagonist enhances DR5‐mediated apoptotic signaling in TRA‐8 resistant triple negative breast cancer cells
Authors: Fancy Romone M. , Kim Harrison , Napier Tiara , Buchsbaum Donald J. , Zinn Kurt R. , Song Yuhua
Published: April 2018

Patients with triple negative breast cancer (TNBC) have no successful “targeted” treatment modality, which represents a priority for novel therapy strategies. Upregulated death receptor 5 (DR5) expression levels in breast cancer cells compared to normal cells enable TRA‐8, a DR5 specific agonistic antibody, to specifically target malignant cells for apoptosis without inducing normal hepatocyte apoptosis. Drug resistance is a common obstacle in TRAIL‐based therapy for TNBC. Calmodulin (CaM) is overexpressed in breast cancer. In this study, we characterized the novel function of CaM antagonist in enhancing TRA‐8 induced cytotoxicity in TRA‐8 resistant TNBC cells and its underlying molecular mechanisms. Results demonstrated that CaM antagonist(s) enhanced TRA‐8 induced cytotoxicity in a concentration and time‐dependent manner for TRA‐8 resistant TNBC cells. CaM directly bound to DR5 in a Ca2+ dependent manner, and CaM siRNA promoted DR5 recruitment of FADD and caspase‐8 for DISC formation and TRA‐8 activated caspase cleavage for apoptosis in TRA‐8 resistant TNBC cells. CaM antagonist, trifluoperazine, enhanced TRA‐8 activated DR5 oligomerization, DR5‐mediated DISC formation, and TRA‐8 activated caspase cleavage for apoptosis, and decreased anti‐apoptotic pERK, pAKT, XIAP, and cIAP‐1 expression in TRA‐8 resistant TNBC cells. These results suggest that CaM could be a key regulator to mediate DR5‐mediated apoptotic signaling, and suggests a potential strategy for using CaM antagonists to overcome drug resistance of TRAIL‐based therapy for TRA‐8 resistant TNBC.
Hypothyroidism and hyperthyroidism change ectoenzyme activity in rat platelets
Authors: Baldissarelli Jucimara , Santi Adriana , Schmatz Roberta , Martins Caroline C. , Zanini Daniela , Reichert Karine P. , Thomé Gustavo R. , Palma Taís V. , da Costa Pauline , Morsch Vera M. , Schetinger Maria R.C.
Published: April 2018

The purinergic system has an important role in the regulation of vascular functions. The interference of thyroid hormones in this system and in cardiovascular events has been studied in recent years. However, the mechanisms involved in vascular, purinergic, and oxidative changes in thyroid disorders are not completely understood. Therefore, the present study aimed to assess purinergic enzyme activity in platelets from rats with hypothyroidism and hyperthyroidism induced, respectively, by continuous exposure to methimazole (MMI) at 20 mg/100 mL or L‐thyroxine at 1.2 mg/100 mL in drinking water for 1 month. Results showed that rats exposed to L‐thyroxine had a significant decrease in NTPDase activity, wherein ATP hydrolysis was 53% lower and ADP hydrolysis was 40% lower. Moreover, ecto‐5′‐nucleotidase activity was decreased in both groups, by 39% in the hypothyroidism group and by 52% in the hyperthyroidism group. On the other hand, adenosine deaminase (ADA) activity was increased in hyperthyroidism (75%), and nucleotide pyrophosphatase/phosphodiesterase (NPP) activity was increased in animals with hypothyroidism (127%) and those with hyperthyroidism (128%). Our findings suggest that changes in purinergic enzyme and purine levels could contribute to the undesirable effects of thyroid disturbances. Moreover, oxidative stress and, in particular, a high level of ROS production, showed a causal relation with changes in ectonucleotidase activity and nucleotide and nucleoside levels.
Impact of replacement of the central benzene ring in anthracene by a heterocyclic ring on electronic excitations and reorganization energies in anthratetrathiophene molecules
Authors: Tripathi Anuj , Prabhakar Chetti
Published: April 2018

The impact of changing the central benzene ring on the electronic excitations and reorganization energies (λ) of the anthratetrathiophene (ATT) molecules is studied by density functional theory (DFT) and time‐dependent DFT (TD‐DFT) quantum chemical calculations. The effect of changing the position of the sulfur atom at the periphery of anthracene on the optical and charge transfer properties is also studied. The calculated results suggest that the HOMO, LUMO, HOMO–LUMO energy gap, ionization potential (IP), electron affinity (EA), hole extraction potential (HEP), electron extraction potential (EEP), and reorganization energies (λ) are affected by replacing the central ring with different heterocyclic rings and the position of the sulfur atom. In addition, all molecules show good hole‐ and electron‐transport properties. This work may be helpful for future design and preparation of high‐performance charge‐transport materials.
Long noncoding RNA H19 mediates LCoR to impact the osteogenic and adipogenic differentiation of mBMSCs in mice through sponging miR‐188
Authors: Wang Yijun , Liu Wentao , Liu Yadong , Cui Jianli , Zhao Zhiwei , Cao Hui , Fu Zhuo , Liu Bin
Published: April 2018

The research aimed to examine the expression of lncRNA H19, miR‐188, and LCoR in mouse bone marrow stromal stem cells (mBMSCs), and to investigate the regulatory mechanism of lncRNA H19/miR‐188/LCoR in osteogenic and adipogenic differentiation of mBMSCs. The expression of miR‐188 in mBMSCs and osteogenesis induced mBMSCs was detected by stem‐loop RT‐PCR, while the expression of H19 and LCoR in mBMSCs and adipogenesis induced mBMSCs was examined by qRT‐PCR. Luciferase reporter assay verified the targeted relationship between miR‐188 and H19 or LCoR. Cell proliferation ability was determined by MTT assay, while cell surface markers of mBMSCs were analyzed via flow cytometry. Alkaline phosphatase staining and Alizarin red staining was utilized to detect the osteogenic differentiation capability of mBMSCs, whereas Oil red O staining was applied to examine the ability of adipogenic differentiation of mBMSCs. The expression of miR‐188 was lower in osteogenesis induced mBMSCs compared with normal mBMSCs, while H19 and LCoR were downregulated in adipogenic induced mBMSCs. Si‐H19 could significantly increase the mRNA level of miR‐188. Meanwhile, miR‐188 directly regulated LCoR in mBMSCs. Overexpression of miR‐188 and knockdown of LCoR suppressed osteogenic differentiation and induced adipogenic differentiation in mBMSCs. Long noncoding RNA H19 mediates LCoR to regulate the balance between osteogenic and adipogenic differentiation of mBMSCs in mice through sponging miR‐188.
Regulatory T and T helper 17 cells: Their roles in preeclampsia
Authors: Hosseini Arezoo , Dolati Sanam , Hashemi Vida , Abdollahpour‐Alitappeh Meghdad , Yousefi Mehdi
Published: April 2018

Regulatory T (Treg) cells have been identified as key immune regulators and are important to fetal survival within the maternal uterus. T helper 17 (Th17) cells have also emerged as a new subset of effector helper T cells and play significant roles in host defense against extracellular pathogens, autoimmune conditions, and inflammatory chronic diseases. Recent findings have provided strong support for the contribution of Th17 and Treg cells to successful pregnancy. Disorders of pregnancy such as preeclampsia (PE) and recurrent spontaneous abortion (RSA) are associated with low frequencies of Treg cells and high levels of Th17 cells. Here, we review current knowledge on Tregs and Th17 cells and shed light on their roles in both normal pregnancy and PE. We also discuss the imbalance between Th17 cells and Treg cells which is known as a major contributory factor in the pathophysiology of PE.
Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients
Authors: Kawazoe Atsuko , Funaki Tomoo , Kim Seongryul
Published: April 2018

Busulfan is the most common chemotherapy agent used in allogeneic hematopoietic cell transplant (HCT) conditioning regimens. As narrow therapeutic index and interpatient variability exists in the effectiveness and toxicity of conditioning regimens, personalizing intravenous busulfan therapy is desirable. Population pharmacokinetic‐based approaches have been applied to therapeutic drug monitoring for the purpose of personalizing therapy. A population pharmacokinetic analysis with the objective of personalizing therapy in Japanese patients was conducted by integrating pediatric patient data with adult patient data. McCune's model, a 2‐compartment model that includes maturation of clearance and allometric scaling of clearance and volume of distribution, was used for the analysis. McCune's model could precisely describe the Japanese data, and the estimated parameters were similar to McCune's results for non‐Japanese, indicating that there are no racial differences in busulfan pharmacokinetics. Using this model, the plasma concentrations for once‐daily dosing were simulated to adapt new dosage regimens for the benefit and convenience of both patients and medical staff. The predicted busulfan concentrations were within the therapeutic range.