bluuebunny/crossref_metadata_2025 huggingface dataset:
A network meta‐analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation
Authors: Kotsakis Georgios A. , Lian Qinshu , Ioannou Andreas L. , Michalowicz Bryan S. , John Mike T. , Chu Haitao
Published: February 2018

Background

A wide selection of Interdental Oral Hygiene (IOH) aids is available to consumers. Recommendations for selection are, however, limited by the lack of direct comparisons in available studies. We aimed to assess the comparative efficacy of IOH aids using Bayesian Network Meta‐Analysis (BNMA).

Methods

Two independent reviewers performed a systematic literature review of randomized clinical trials assessing IOH aids, based on a focused question. Gingival inflammation (Gingival Index (GI), Bleeding‐on‐probing (BOP)) was the primary outcome and plaque and probing depth were secondary outcomes A random‐effects arm‐based BNMA model was run for each outcome; posterior medians and 95% credible‐intervals (CIs) summarized marginal distributions of parameters.

Results

A two‐phase selection process identified 22 trials assessing 10 IOH aids as brushing adjuncts. Interdental brushes (IB) yielded the largest reduction in GI (0.23 [95% CI: 0.09, 0.37]) as toothbrushing adjuncts, followed by water‐jet (WJ) (0.19 [95% CI: 0.14, 0.24]). Rankings based on posterior probabilities revealed that IB and WJ had the highest probability of being “best” (64.7% and 27.4%, respectively) for GI reduction, whereas the probability for toothpick and floss being the “best” IOH aids was near zero. Notably, except for toothpicks, all IOH aids were better at reducing GI as compared with control.

Conclusions

BNMA enabled us to quantitatively evaluate IOH aids and provide a global ranking of their efficacy. Interdental brushes and water‐jets ranked high for reducing gingival bleeding, whereas toothpicks and floss ranked last. The patient‐perceived benefit of IOH aids is not clear because gingival inflammation measures are physical indicators of periodontal health.
Periodontal profile classes predict periodontal disease progression and tooth loss
Authors: Morelli Thiago , Moss Kevin L. , Preisser John S. , Beck James D. , Divaris Kimon , Wu Di , Offenbacher Steven
Published: February 2018

Background

Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person‐level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss.

Methods

The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person‐level disease pattern and severity) and seven TPCs (tooth‐level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person‐level composite risk scores (Index of Periodontal Risk [IPR]).

Results

Individuals in two PPCs (PPC‐G: Severe Disease and PPC‐D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC‐G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss.

Conclusions

These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived personalized propensity scores provide clinical periodontal definitions that reflect disease patterns in the population and offer a useful system for patient stratification that is predictive for disease progression and tooth loss.
Self‐perceived oral symptoms and periodontal status among young intravenous heroin addicts: A cross‐sectional case‐control study
Authors: Mehmood Abid , Abduljabbar Tariq , Al‐Hamoudi Nawwaf , Gholamiazizi Elham , Kellesarian Sergio Varela , Vohra Fahim , Javed Fawad
Published: February 2018

Background

It is hypothesized that (a) self‐perceived oral symptoms (OSs) are worse in intravenous heroin addicts (IHA) than controls; and (b) clinical periodontal inflammatory parameters (plaque index [PI], bleeding on probing [BOP], PD and clinical attachment loss [AL]), number of missing teeth (MT), and radiographic marginal bone loss (MBL) are higher in IHA compared with controls. The aim was to compare the self‐perceived OSs and periodontal parameters among young IHA and controls.

Methods

Sociodemographic data, self‐perceived OSs and duration and daily frequency of intravenous heroin use was gathered using a structured questionnaire. Full‐mouth PI, BOP, PD, and clinical AL were measured, and number of MT were recorded. Mesial and distal MBL on all teeth was measured on digital radiographs. Odds ratios (OR) with 95% confidence intervals (CI) were computed for self‐perceived OSs and periodontal parameters were assessed using the Mann Whitney U‐test and logistic regression analysis. Sample‐size was estimated, and level of significance was set at P < 0.05.

Results

OR (95% CI) for self‐perceived loose teeth (P < 0.001), pain in teeth (P < 0.001), dry mouth (P < 0.001), burning sensation in mouth (P < 0.001), bleeding gums (P < 0.001) and pain during chewing (P < 0.001) were significantly higher in the test than control group. Number of MT (P < 0.05), PI (P < 0.05), clinical AL (P < 0.05), and mesial (P < 0.05) and distal (P < 0.05) MBL were statistically significantly higher among individuals in the test group compared with the control group.

Conclusion

Self‐perceived OSs and periodontal inflammatory parameters were worse in IHA than controls.
Early intervention of peri‐implantitis and periodontitis using a mouse model
Authors: Wong Ryan L. , Hiyari Sarah , Yaghsezian Aline , Davar Mina , Casarin Maísa , Lin Yi‐Ling , Tetradis Sotirios , Camargo Paulo M. , Pirih Flavia Q.
Published: February 2018

Background

Peri‐implantitis is an inflammatory response to bacterial biofilm resulting in bone loss and can ultimately lead to implant failure. Because of the lack of predictable treatments available, a thorough understanding of peri‐implantitis's pathogenesis is essential. The objective of this study is to evaluate and compare the response of acute induced peri‐implantitis and periodontitis lesions after insult removal.

Methods

Implants were placed in one‐month‐old C57BL/6J male mice eight weeks post extraction of their left maxillary molars. Once osseointegrated, ligatures were placed around the implants and contralateral second molars of the experimental groups. Controls did not receive ligatures. After one week, half of the ligatures were removed, creating the ligature‐retained and ligature‐removed groups. Mice were sacrificed at two time points, 5 and 14 days, from ligature removal. The specimens were analyzed via micro‐computed tomography and histology.

Results

By 5 and 14 days after ligature removal, the periodontitis group experienced significant bone gain, whereas the peri‐implantitis group did not. Histologically, all implant groups exhibited higher levels of cellular infiltrate than any of the tooth groups. Osteoclast numbers increased in peri‐implantitis and periodontitis ligature‐retained groups and decreased following insult removal. Collagen was overall more disorganized in peri‐implantitis than periodontitis for all groups. Peri‐implantitis experimental groups revealed greater matrix metalloproteinase‐8 and NF‐kB levels than periodontitis.

Conclusions

Implants respond slower and less favorably to insult removal than teeth. Future research is needed to characterize detailed peri‐implantitis disease pathophysiology.
Preparation, aroma characteristics and volatile compounds of flavorings from enzymatic hydrolyzed rice bran protein concentrate
Authors: Arsa Supeeraya , Theerakulkait Chockchai
Published: February 2018

BACKGROUND

Rice bran is a by‐product obtained from the rice milling industry. The aims of this research were to add value to rice bran by preparation of enzymatic hydrolyzed rice bran protein concentrate (HRPC) as a flavoring agent and the flavoring which was produced by HRPC has not been investigated. Different drying methods (freeze‐drying and spray‐drying) and fructose additions were studied for improvement of rice bran protein sensorial aroma characteristics.

RESULTS

The most abundant amino acids in liquid HRPC (LH) were glutamic acid, arginine, aspartic acid and leucine. The intensity of desirable aromas, such as cereal‐like, nut‐like, milk‐powder‐like, sweet, and cocoa‐like aroma, were higher in spray‐dried HRPC powder (SHP) than in LH and freeze‐dried HRPC. Volatile compounds, such as aldehydes, pyrazines and ketones, were significantly increased in HRPC powders in which fructose was added before spray‐drying (SHP‐F). Higher amounts of 2‐methylbutanal, 3‐methylbutanal, phenylacetaldehyde, 2,5‐dimethylpyrazine, vanillin, 2‐acetylpyrrole and maltol were detected in SHP‐F. Moreover, these compounds had high odor active values, which accounted for the cocoa‐like, sweet, nut‐like, and milk‐powder‐like characteristics of SHP‐F.

CONCLUSIONS

These findings could lead to the creation of desirable aroma characteristics of rice bran protein concentrate by different preparation methods. © 2018 Society of Chemical Industry
The Current State of Ultrasound Training in Obstetrics and Gynecology Residency Programs
Authors: Alrahmani Layan , Codsi Elisabeth , Borowski Kristi S.
Published: February 2018

Objectives

We evaluated the current state of ultrasound training in obstetrics and gynecology (OB‐GYN) residency programs across the United States.

Methods

An electronic survey was sent to OB‐GYN residency program directors and OB‐GYN residents. Responses were obtained in September 2016. Program directors and residents were asked to reflect on their current ultrasound curriculum.

Results

A total of 93 program directors and 437 residents responded. Respondents were mostly from university programs located in tertiary centers. Ultrasound curricula varied: 11% of program directors and 23% of residents did not have any ultrasound‐related didactics; of those who did, 27% of program directors and 40% of residents had it yearly or less. Three‐quarters had mandatory ultrasound rotations, and few offered ultrasound electives (program directors, 52%; residents, 28%). Most residents were required to perform ultrasound examinations daily or weekly (98%). Most stated that the main focus of the rotation was OB only. Skill was evaluated mainly subjectively by direct observation. Although most program directors stated that residents were satisfactory/excellent in ultrasound, 22% would not treat patients on the basis of ultrasound examinations performed by their senior residents. Similarly, of all postgraduate year 4 respondents (n = 86), 76% stated that they will require additional training to be able to perform or read ultrasound examinations independently, and 43% would not treat a patient on the basis of their own ultrasound examinations without further confirmation. Residents believed that the biggest obstacle in ultrasound training is lack of dedicated faculty time (41%).

Conclusions

Recognizing the lack of clearly defined milestones in ultrasound training in OB‐GYN residency, this study confirms the substantial heterogeneity in curricula between programs, highlighting a need for a standardized ultrasound curriculum.
The Thermodynamic Links between Substrate, Enzyme, and Microbial Dynamics in Michaelis–Menten–Monod Kinetics
Authors: Maggi Federico , M. Tang Fiona H. , Riley William J.
Published: February 2018

Accurate prediction of the temperature response of the velocity v of a biochemical reaction has wide applications in cell biology, reaction design, and biomass yield enhancement. Here, we introduce a simple but comprehensive mechanistic approach that uses thermodynamics and biochemical kinetics to describe and link the reaction rate and Michaelis–Menten constants (kT and T) with the biomass yield and mortality rate (T and δT) as explicit functions of . The temperature control is exerted by catabolic enthalpy at low temperatures and catabolic entropy at high temperatures, whereas changes in cell and enzyme–substrate heat capacity shift the anabolic electron use efficiency eA and the maximum reaction velocity vmax. We show that cells have optimal growth when the catabolic (differential) free energy of activation decreases the cell free energy harvest required to duplicate their internal structures as long as electrons for anabolism are available. With the described approach, we accurately predicted observed glucose fermentation and ammonium nitrification dynamics across a wide temperature range with a minimal number of thermodynamics parameters, and we highlight how kinetic parameters are linked to each other using first principles.
Genome analysis of two novel Pseudomonas strains exhibiting differential hypersensitivity reactions on tobacco seedlings reveals differences in nonflagellar T3SS organization and predicted effector proteins
Authors: Tchagang Caetanie F. , Xu Renlin , Doumbou Cyr Lézin , Tambong James T.
Published: February 2018

Multilocus sequence analysis (MLSA) of two new biological control strains (S1E40 and S3E12) of Pseudomonas was performed to assess their taxonomic position relative to close lineages, and comparative genomics employed to investigate whether these strains differ in key genetic features involved in hypersensitivity responses (HRs). Strain S3E12, at high concentration, incites HRs on tobacco and corn plantlets while S1E40 does not. Phylogenies based on individual genes and 16S rRNA‐gyrB‐rpoB‐rpoD concatenated sequence data show strains S1E40 and S3E12 clustering in distinct groups. Strain S3E12 consistently clustered with Pseudomonas marginalis, a bacterium causing soft rots on plant tissues. MLSA data suggest that strains S1E40 and S3E12 are novel genotypes. This is consistent with the data of genome‐based DNA‐DNA homology values that are below the proposed cutoff species boundary. Comparative genomics analysis of the two strains revealed major differences in the type III secretion systems (T3SS) as well as the predicted T3SS secreted effector proteins (T3Es). One nonflagellar (NF‐T3SS) and two flagellar T3SSs (F‐T3SS) clusters were identified in both strains. While F‐T3SS clusters in both strains were relatively conserved, the NF‐T3SS clusters differed in the number of core components present. The predicted T3Es also differed in the type and number of CDSs with both strains having unique predicted protease‐related effectors. In addition, the T1SS organization of the S3E12 genome has protein‐coding sequences (CDSs) encoding for key factors such as T1SS secreted agglutinin repeats‐toxins (a group of cytolysins and cytotoxins), a membrane fusion protein (LapC), a T1SS ATPase of LssB family (LapB), and T1SS‐associated transglutaminase‐like cysteine proteinase (LapP). In contrast, strain S1E40 has all CDSs for the seven‐gene operon (pelA‐pelG) required for Pel biosynthesis but not S3E12, suggesting that biofilm formation in these strains is modulated differently. The data presented here provide an insight of the genome organization of these two phytobacterial strains.
Abrus agglutinin stimulates BMP‐2‐dependent differentiation through autophagic degradation of β‐catenin in colon cancer stem cells
Authors: Panda Prashanta K. , Naik Prajna P. , Praharaj Prakash P. , Meher Biswa R. , Gupta Piyush K. , Verma Rama S. , Maiti Tapas K. , Shanmugam Muthu K. , Chinnathambi Arunachalam , Alharbi Sulaiman A. , Sethi Gautam , Agarwal Rajesh , Bhutia Sujit K.
Published: February 2018

Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor‐specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP‐2) and β‐catenin during the colon cancer progression, indicating that their possible intervention through “forced differentiation” in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, and enhances sensitivity to the anticancer therapeutics. The low dose AGG (max. dose = 100 ng/mL) decreased the expression of stemness‐associated molecules such as CD44 and β‐catenin in the HT‐29 cell derived colonospheres. Further, AGG augmented colonosphere differentiation, as demonstrated by the enhanced CK20/CK7 expression ratio and induced alkaline phosphatase activity. Interestingly, the AGG‐induced expression of BMP‐2 and the AGG‐induced differentiation were demonstrated to be critically dependent on BMP‐2 in the colonospheres. Similarly, autophagy‐induction by AGG was associated with colonosphere differentiation and the gene silencing of BMP‐2 led to the reduced accumulation of LC3‐II, suggesting that AGG‐induced autophagy is dependent on BMP‐2. Furthermore, hVps34 binds strongly to BMP‐2, indicating a possible association of BMP‐2 with the process of autophagy. Moreover, the reduction in the self‐renewal capacity of the colonospheres was associated with AGG‐augmented autophagic degradation of β‐catenin through an interaction with the autophagy adaptor protein p62. In the subcutaneous HT‐29 xenograft model, AGG profoundly inhibited the growth of tumors through an increase in BMP‐2 expression and LC3‐II puncta, and a decrease in β‐catenin expression, confirming the antitumor potential of AGG through induction of differentiation in colorectal cancer.
Decreased SCIN expression, associated with promoter methylation, is a valuable predictor for prognosis in acute myeloid leukemia
Authors: Zhang Zhi‐Hui , Zhang Wei , Zhou Jing‐Dong , Zhang Ting‐Juan , Ma Ji‐Chun , Xu Zi‐Jun , Lian Xin‐Yue , Wu De‐Hong , Wen Xiang‐Mei , Deng Zhao‐Qun , Lin Jiang , Qian Jun
Published: February 2018

The present study was aimed to investigate SCIN expression as well as promoter methylation and further explore their clinical relevance in acute myeloid leukemia (AML) patients. Real‐time quantitative PCR was carried out to detect the expression level of SCIN in 119 AML patients and 37 healthy controls. Real‐time quantitative methylation‐specific PCR and bisulfite sequencing PCR were carried out to detect SCIN promoter methylation levels in 103 AML patients and 29 controls. As compared with controls, the level of SCIN transcript was significantly down‐regulated in AML patients (P = 0.001), and the level of methylated SCIN promoter was significantly higher in AML patients (P = 0.001). Moreover, the level of promoter methylation was weakly negatively correlated with SCIN expression in AML patients (R = −0.265, P = 0.027). Demethylation of SCIN promoter by 5‐aza‐2′‐deoxycytidine could restore its expression in leukemic cell line THP1. The age of SCINlow patients was significantly higher and C/EBPA mutation was significantly less than SCINhigh patients (P = 0.039 and 0.038, respectively). Moreover, the rate of complete remission (CR) of SCINlow patients was significantly lower than SCINhigh patients (P = 0.009). Kaplan‐Meier analysis showed that low SCIN expression was associated with shorter overall survival (P = 0.036). Cox regression analysis demonstrated low SCIN expression was an independent poor prognostic factor (P = 0.047). Furthermore, SCIN expression was restored in those patients who achieved CR after induction therapy (P = 0.003). These findings indicate that decreased SCIN expression associated with its promoter methylation is a valuable biomarker for predicting adverse prognosis in AML patients.
Global strong solution to the three dimensional nonhomogeneous incompressible magnetohydrodynamic equations with density‐dependent viscosity and resistivity
Authors: Li Huanyuan
Published: February 2018

In this paper, we consider an initial boundary value problem for the 3‐dimensional nonhomogeneous incompressible magnetohydrodynamic equations with density‐dependent viscosity and resistivity coefficients over a bounded smooth domain. Global in time unique strong solution is proved to exist when the L2 norms of initial vorticity and current density are both suitably small with arbitrary large initial density, and the vacuum of initial density is also allowed.

Finally, we revisit the Navier‐Stokes model without electromagnetic effect. We find that this initial boundary problem also admits a unique global strong solution under other conditions. In particular, we prove small kinetic‐energy strong solution exists globally in time, which extends the recent result of Huang and Wang.
Effects of Different Lipid Sources on Growth and Fatty Acid Composition of Juvenile Triangular Bream Megalobrama terminalis
Authors: Tian Hanlin , Wang Jiteng , Han Tao , Yang Min , Xu Hanying , Sheng Jianhai , Zheng Puqiang
Published: February 2018

Five diets containing lipids from different sources, namely fish oil (FO), soybean oil (SO), linseed oil (LO), rapeseed (canola) oil (RO), and palm oil (PO), were fed to juvenile Triangular Bream Megalobrama terminalis (initially weight, 1.20 ± 0.02 g) for 70 d. At the end of the feeding trial, weight gain (WG), specific growth rate (SGR), feed conversion ratio (FCR), and daily feed intake (DFI) were not significantly different among all treatments. The retention rates of C22:6(n-3) (docosahexaenoic acid [DHA]) in fish fed LO-based (143.8%) diets were significantly higher than in those fed FO-based (61.0%) diet. Moreover, fish fed LO-based diet showed a significantly higher C20:5(n-3) (eicosapentaenoic acid [EPA]) content (1.6%) in the liver than fish fed SO-, RO-, and PO-based (1.1, 0.9, and 0.9%, respectively) diets. The retention rates of C20:4(n-6) (arachidonic acid [ARA]) in fish fed RO-based (341.3%) diets were significantly higher than in those fed FO-, LO-, and PO-based (87.3, 176.8, and 216.3%, respectively) diets, while fish fed SO- and RO-based diets had significantly higher ARA concentrations in the liver than did fish fed FO-based diet. The fatty acid compositions of fish tissues were significantly affected by different lipid sources. Fish fed vegetable oil (VO) diets had lower n-3 long-chain polyunsaturated fatty acid (LC-PUFAs) concentrations in dorsal muscles than did fish in the FO group (18.4%), and significant differences were detected in fish fed SO (10.1%) and RO (10.9%) diets. These results showed that Triangular Bream have an ability to synthesize DHA, EPA, and ARA from alpha-linolenic acid (ALA) and linoleic acid (LA). However, fish fed VO-based diets could reduce the nutritional value of the fish flesh.
Influence of length effect on embankment slope reliability in 3D
Authors: Hicks Michael A. , Li Yajun
Published: February 2018

Embankment slopes composed of spatially variable soils have a variety of different failure modes that are affected by the correlation distances of the material properties and the geometry and total length of the slope. This paper examines the reliability of soil slopes for embankments of different length and uses parallel computing to analyse very long embankments (up to 100 times the embankment height) for a clay soil characterised by a spatially varying undrained shear strength. Based on a series of analyses using the 3D random finite element method (RFEM), it is first shown that the reliability of slopes of various length can be efficiently computed by combining simple probability theory with a detailed 3D RFEM analysis of a representative shorter slope of length 10 times the slope height. RFEM predictions of reliability indices for longer slopes are then compared with results obtained using Vanmarcke's (1977a) simplified 3D method and Calle's (1985) extended 2D approach. It is shown that these methods can give significantly different results, depending on the horizontal scale of fluctuation relative to the slope length, with RFEM predicting a lower slope reliability than the Vanmarcke and Calle solutions in all cases. The differences in the solutions are evaluated and attributed to differences in the assumed and computed failure surface geometries.
Revisiting the existence of an effective stress for wet granular soils with micromechanics
Authors: Duriez Jérôme , Wan Richard , Pouragha Mehdi , Darve Félix
Published: February 2018

A possible effective stress variable for wet granular materials is numerically investigated based on an adapted discrete element method (DEM) model for an ideal three‐phase system. The DEM simulations consider granular materials made of nearly monodisperse spherical particles, in the pendular regime with the pore fluid mixture consisting of distinct water menisci bridging particle pairs. The contact force‐related stress contribution to the total stresses is isolated and tested as the effective stress candidate for dense or loose systems. It is first recalled that this contact stress tensor is indeed an adequate effective stress that describes stress limit states of wet samples with the same Mohr‐Coulomb criterion associated with their dry counterparts. As for constitutive relationships, it is demonstrated that the contact stress tensor used in conjunction with dry constitutive relations does describe the strains of wet samples during an initial strain regime but not beyond. Outside this so‐called quasi‐static strain regime, whose extent is much greater for dense than loose materials, dramatic changes in the contact network prevent macroscale contact stress‐strain relationships to apply in the same manner to dry and unsaturated conditions. The presented numerical results also reveal unexpected constitutive bifurcations for the loose material, related to stick‐slip macrobehavior.
On uniformly most reliable two‐terminal graphs
Authors: Bertrand Hayley , Goff Owen , Graves Christina , Sun Maggie
Published: February 2018

A two‐terminal graph is an undirected graph G with vertex set V(G), edge set E(G), and two specified target vertices in V(G). If each edge of such a graph operates independently with the same fixed probability p, the two‐terminal reliability is the probability that there exists a path between the target vertices. A two‐terminal graph is uniformly most reliable if its reliability polynomial is greater than or equal to that of all other two‐terminal graphs with the same fixed number of vertices, n, and edges, m. In this article, we present specific values of n and m for which no uniformly most reliable two‐terminal simple graph exists, as well as values of n and m for which there does exist a uniformly most reliable two‐terminal simple graph.
Bifurcation analysis of nonlinear time‐periodic time‐delay systems via semidiscretization
Authors: Molnar T. G. , Dombovari Z. , Insperger T. , Stepan G.
Published: February 2018

Bifurcations of the periodic stationary solutions of nonlinear time‐periodic time‐delay dynamical systems are analyzed. The solution operator of the governing nonlinear delay‐differential equation is approximated by a sequence of nonlinear maps via semidiscretization. The subsequent nonlinear maps are combined to a single resultant nonlinear map that describes the evolution over the time period. Fold, flip, and Neimark‐Sacker bifurcations related to the fixed point of this map are analyzed via center manifold reduction and normal form theorems. The analysis unfolds the approximate stability properties and bifurcations of the stationary solution of the delay‐differential equation and, at the same time, allows the approximate computation of the arising period‐1, period‐2, and quasi‐periodic solution branches. The method is demonstrated for the delayed Mathieu‐Duffing equation, and the results are verified by numerical continuation.
Hydroxylysine deficiency, conspicuous skeletal lesions and a strange burial practice in a historical German island population
Authors: Burkhardt A. , Grupe G.
Published: February 2018

Eighty‐two complete and partial human skeletons were excavated from a burial site on the island of Borkum in the North Sea. The site covers a period of 400 years from the middle of the 14th century AD until 1720 AD. The position of the skeletons in situ suggests rapid disposal of the bodies. About 75% of the skeletons were male and of a quite robust constitution, and about 60% of all individuals died rather young between 20 and 40 years of age. All male skeletons exhibited particular pathological alterations as a result of the typical daily activities of seafaring men, including severe degenerative joint disease and pronounced osteochondropathies. In juvenile skeletons, these pathologies were accompanied by inflammatory processes without exception. Palaeodietary reconstruction by stable isotope analysis resulted in a protein rich diet, confirming fishing as an important part of the subsistence economy. The juveniles derived substantially more protein from plant food than the adults. Bone collagen amino acid profiles were short of hydroxylysine, suggesting that the conspicuous pathological lesions could also have been caused by a systemic connective tissue disease. Possible etiology of the disease is discussed and related to both the uneven sex ratio of the inhumations and the burial context.
Richter transformation driven by Epstein–Barr virus reactivation during therapy‐related immunosuppression in chronic lymphocytic leukaemia
Authors: García‐Barchino Maria J , Sarasquete Maria E , Panizo Carlos , Morscio Julie , Martinez Antonio , Alcoceba Miguel , Fresquet Vicente , Gonzalez‐Farre Blanca , Paiva Bruno , Young Ken H , Robles Eloy F , Roa Sergio , Celay Jon , Larrayoz Marta , Rossi Davide , Gaidano Gianluca , Montes‐Moreno Santiago , Piris Miguel A , Balanzategui Ana , Jimenez Cristina , Rodriguez Idoia , Calasanz Maria J , Larrayoz Maria J , Segura Victor , Garcia‐Muñoz Ricardo , Rabasa Maria P , Yi Shuhua , Li Jianyong , Zhang Mingzhi , Xu‐Monette Zijun Y , Puig‐Moron Noemi , Orfao Alberto , Böttcher Sebastian , Hernandez‐Rivas Jesus M , Miguel Jesus San , Prosper Felipe , Tousseyn Thomas , Sagaert Xavier , Gonzalez Marcos , Martinez‐Climent Jose A
Published: February 2018

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein–Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B‐cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV– tumours, EBV+ DLBCLs derived predominantly from IGVH‐hypermutated CLL, and they also showed CLL‐unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo‐immunotherapy, a non‐germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy‐related immunosuppression can transform either CLL cells or non‐tumoural B lymphocytes into EBV+ DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B‐cell lymphocytosis (MBL) was performed in Rag2–/– IL2γc–/– mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV+ B‐cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL‐unrelated but also CLL‐related), recapitulating the principal features of EBV+ DLBCL in patients. Accordingly, clonally related and unrelated EBV+ DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B‐cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV+ DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Brincidofovir as Salvage Therapy for Adenovirus Disease in Intestinal Transplant Recipients
Authors: Sulejmani Nimisha , Nagai Shunji , Safwan Mohamed , Rizzari Michael D. , Raoufi Mohammad , Abouljoud Marwan S. , Ramesh Mayur
Published: February 2018

Background

Adenoviruses are double‐stranded DNA viruses that typically cause mild self‐limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or U.S. Food and Drug Administration–approved medications exist for the treatment of adenovirus disease.

Aims

We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy.

Results

The first patient was a 44‐year‐old woman who developed adenoviral enteritis 1 month after transplantation, which resolved with ribavirin therapy. Two weeks later, the infection recurred, and brincidofovir was initiated. While receiving this therapy for 3 months, she developed severe acute rejection, which was managed with rabbit antithymocyte globulin followed by infliximab. Eventually, complete resolution of the rejection and adenoviral enteritis was achieved. At 12 months posttransplantation, the patient was healthy and tolerating enteral feeding. The second patient was a 28‐year‐old man who had undergone isolated intestinal transplantation 6 years before he presented with generalized weakness and an increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance immunosuppression was reduced, and brincidofovir was started. The infection resolved with a month of therapy. Six months after the infection, he was healthy and tolerating enteral feeding.

Conclusion

This is the first publication, to our knowledge, to describe two cases in which brincidofovir was used to successfully treat adenovirus infection in intestinal transplant recipients. Thus, these cases demonstrate that brincidofovir appears to be a safe and effective option in the management of adenoviral enteritis in these patients.
A Multi‐Omics Analysis of Glycine max Leaves Reveals Alteration in Flavonoid and Isoflavonoid Metabolism Upon Ethylene and Abscisic Acid Treatment
Authors: Gupta Ravi , Min Cheol Woo , Kramer Katharina , Agrawal Ganesh Kumar , Rakwal Randeep , Park Ki‐Hun , Wang Yiming , Finkemeier Iris , Kim Sun Tae
Published: February 2018

Phytohormones are central to plant growth and development. Despite the advancement in our knowledge of hormone signaling, downstream targets, and their interactions upon hormones action remain largely fragmented, especially at the protein and metabolite levels. With an aim to get new insight into the effects of two hormones, ethylene (ET) and abscisic acid (ABA), this study utilizes an integrated proteomics and metabolomics approach to investigate their individual and combined (ABA+ET) signaling in soybean leaves. Targeting low‐abundance proteins, our previously established protamine sulfate precipitation method was applied, followed by label‐free quantification of identified proteins. A total of 4129 unique protein groups including 1083 differentially modulated in one (individual) or other (combined) treatments were discerned. Functional annotation of the identified proteins showed an increased abundance of proteins related to the flavonoid and isoflavonoid biosynthesis and MAPK signaling pathway in response to ET treatment. HPLC analysis showed an accumulation of isoflavones (genistin, daidzein, and genistein) upon ET treatment, in agreement with the proteomics results. A metabolome analysis assigned 79 metabolites and further confirmed the accumulation of flavonoids and isoflavonoids in response to ET. A potential cross‐talk between ET and MAPK signaling, leading to the accumulation of flavonoids and isoflavonoids in soybean leaves is suggested.
Protein Network Analysis and Functional Studies of Calcium Oxalate Crystal‐Induced Cytotoxicity in Renal Tubular Epithelial Cells
Authors: Peerapen Paleerath , Chaiyarit Sakdithep , Thongboonkerd Visith
Published: February 2018

Our previous expression study has reported a set of proteins with altered levels in renal tubular cells after exposure to calcium oxalate monohydrate (COM) crystals, which are the main composition of kidney stones. However, their functional significance remained largely unknown. In this study, protein network analysis revealed that the significantly altered proteins induced by COM crystals were involved mainly in three main functional networks, including i) cell proliferation and wound healing; ii) oxidative stress and mitochondrial function; and iii) cellular junction complex and integrity. Cell proliferation and wound healing assays showed that the COM‐treated cells had defective proliferation and tissue healing capability, respectively. Oxyblot analysis demonstrated accumulation of the oxidized proteins, whereas intracellular ATP level was significantly increased in the COM‐treated cells. Additionally, level of zonula occludens‐1 (ZO‐1), a tight junction protein, was significantly decreased, consistent with the significant declines in transepithelial resistance (TER) and level of RhoA signaling molecule in the COM‐treated cells. These findings indicate significant perturbations in mitochondrial and oxidative stress axis that cause defective cell proliferation, tissue healing capability, junctional protein complex, and cellular integrity of renal tubular epithelial cells exposed to COM crystals that may play important roles in kidney stone pathogenesis.
Respiratory syncytial virus is an “opportunistic” killer
Authors: Caballero Mauricio T. , Polack Fernando P.
Published: February 2018

Respiratory syncytial virus (RSV), responsible for more than three million yearly hospitalizations and up to 118 000 deaths in children under 5 years, is the leading pulmonary cause of death for this age group that lacks a licensed vaccine. Ninety‐nine percent of deaths due to the virus occur in developing countries. In‐hospital RSV fatalities affect previously healthy term infants in association with bacterial sepsis, clinically significant pneumothoraxes and, to a lesser extent, comorbid conditions. Community deaths affect low‐income children from socially vulnerable families and appear to be as frequent as inpatient fatalities. In industrialized countries, RSV deaths occur almost exclusively in children with premorbid conditions.

In a sense, RSV is an “opportunistic” killer. It needs a synergistic premorbid, medical practice‐related, infectious, or social co‐factor to cause a fatal outcome. But while the complex problems associated with these co‐factors await solutions, candidate vaccines, long‐lived monoclonal antibodies and antivirals against RSV are under clinical evaluation. It seems reasonable to predict that the landscape of RSV infections will look different in the next decade.
Medication adherence in pediatric asthma: A systematic review of the literature
Authors: Gray Wendy N. , Netz Mallory , McConville Andrew , Fedele David , Wagoner Scott T. , Schaefer Megan R.
Published: February 2018

Objective

To provide a systematic review of correlates of adherence to inhaled corticosteroids (ICS) in pediatric asthma across the individual, family, community, and healthcare system domains.

Methods

Articles assessing medication adherence in pediatric asthma published from 1997 to 2016 were identified using PsychINFO, Medline, and CINAHL. Search terms included asthma, compliance, self‐management, adherence, child, and youth. Search results were limited to articles: 1) published in the US; 2) using a pediatric population (0‐25 years old); and 3) presenting original data related to ICS adherence. Correlates of adherence were categorized according to the domains of the Pediatric Self‐Management Model. Each article was evaluated for study quality.

Results

Seventy‐nine articles were included in the review. Family‐level correlates were most commonly reported (N = 51) and included socioeconomic status, race/ethnicity, health behaviors, and asthma knowledge. Individual‐level correlates were second‐most common (N = 37), with age being the most frequently identified negative correlate of adherence. Health care system correlates (N = 24) included enhanced asthma care and patient‐provider communication. Few studies (N = 10) examined community correlates of adherence. Overall study quality was moderate, with few quantitative articles (26.38%) and qualitative articles (21.4%) referencing a theoretical basis for their studies.

Conclusions

All Pediatric Self‐Management Model domains were correlated with youth adherence, which suggests medication adherence is influenced across multiple systems; however, most studies assessed adherence correlates within a single domain. Future research is needed that cuts across multiple domains to advance understanding of determinants of adherence.
Effects of Charge Size on Slow Cook‐Off Characteristics of AP/HTPB Composite Propellant in Base Bleed Unit
Authors: Li Wenfeng , Yu Yonggang , Ye Rui
Published: February 2018

To investigate the effects of charge size on the slow cook‐off characteristics of trilobite ammonium perchlorate (AP)/hydroxyl‐terminated polybutadiene (HTPB) composite propellant with slits, a cook‐off model of three‐dimensional base bleed unit is developed based on the two‐step decomposition reaction mechanism of AP/HTPB propellant at the external heating rates from 3.3 to 9 K/h. The charge length of AP/HTPB propellant is 72 mm with 43 mm to 53 mm in grain diameter, and the grain diameter is 43 mm with 72 mm to 90 mm in charge length, respectively. The results show that heating rate and charge size determine the ignition position of AP/HTPB propellant. The effects of charge size on the ignition position and cook‐off temperature are small at the heating rate of 3.3 K/h. As the heating rate increases to 4.6 K/h–6 K/h, with the grain diameter and charge length extending, the ignition position gradually moves from the inner wall to the surface near the slit, meanwhile the cook‐off temperature changes obviously. When the heating rate increases to 9 K/h, the ignition position of AP/HTPB propellant at different charge sizes all occurs on the outer interface between the propellant and slit, there is no obvious influence of different charge sizes on the ignition temperature of AP/HTPB propellant. Additionally, the law of ignition time of AP/HTPB propellant to charge size is the same at different heating rates.
Lifetime stayers in urban, rural, and highly rural communities in Montana
Authors: Erickson Lance D. , Sanders Scott R. , Cope Michael R.
Published: February 2018

Modernity can be characterised by a shift from a communal to an individual orientation where social mobility is one of individuals' primary goals. However, for individuals to achieve social mobility, they often must also be geographically mobile. Consequently, geographic immobility or staying in place needs to be theorised and examined directly. In this context, the life course perspective provides a useful framework to understand staying. The role transitions associated with different life stages represent different decision points where choices to stay must be deliberate. We use state‐representative data from Montana (USA) in 2010 to perform an exploratory analysis of stayers. Using a variety of community and individual predictors, we find that high community attachment, low satisfaction with one's community, and/or local services make being a stayer more likely. In separate models of being a stayer by rurality, age group, educational attainment, and having a dependent in the home, the pattern of results suggests that interpretations of high attachment and low satisfaction among stayers as being indicators of being “stuck” may be incorrect. Instead, even in the absence of being satisfied with one's community, community attachment may be indicative of deliberate decisions to stay. We discuss the limitations of addressing staying using cross‐sectional data and suggest future avenues for better understanding those who stay in place throughout their lives.
Mining the Synergistic Core Allosteric Modules Variation and Sequencing Pharmacological Module Drivers in a Preclinical Model of Ischemia
Authors: Zhang Yingying , Zhao Zide , Yu Yanan , Liu Jun , Wang Pengqian , Li Bing , Zhang Xiaoxu , Chen Yinying , Wang Zhong
Published: February 2018

Identifying the variation of core modules and hubs seems to be critical for characterizing variable pharmacological mechanisms based on topological alteration of disease networks. We first identified a total of eight core modules by using an approach of multiple modular characteristic fusing (MMCF) from different targeted networks in ischemic mice. Interestingly, the value of module disturbance intensity (MDI) increased in drug combination group. Second, we redefined a weak allosteric module and a strong allosteric module. Then, we identified 15 pharmacological module drivers (PMDs) by leave‐one‐out screening with a cutoff of two folds, which were at least, in part, validated by expression and variation of topological contribution. Finally, we revealed the fusional and emergent variation of PMD in core modules contributing to multidimensional synergistic mechanism in ischemic mice and rats. Our findings provide a new set of drivers that might promote the pharmacological modular flexibility and offer a potential avenue for disease treatment.
A GaN‐Based VCSEL with a Convex Structure for Optical Guiding
Authors: Hayashi Natsumi , Ogimoto Junichiro , Matsui Kenjo , Furuta Takashi , Akagi Takanobu , Iwayama Sho , Takeuchi Tetsuya , Kamiyama Satoshi , Iwaya Motoaki , Akasaki Isamu
Published: February 2018

In this paper, room‐temperature continuous‐wave operation of a GaN‐based vertical‐cavity surface‐emitting laser (VCSEL) with a convex structure for optical guiding is demonstrated. The GaN‐based VCSEL is designed and fabricated with the convex structure containing a 15‐nm step between the center area and the peripheral area of the VCSEL with a Nb2O5 spacer layer. In theory the convex structure with a 1.5% relative refractive index difference between the areas could provide more than 10 high‐order modes. Experimental emission spectra and near field pattern images clearly suggested a multi‐mode operation of the VCSEL with the convex structure. In addition, the VCSEL shows a lower threshold current, 2 mA, and a higher maximum light output power, 0.88 mW, which are superior to those of our standard VCSEL fabricated simultaneously without the convex structure. These results indicate that the optical guiding with the convex structure plays an important role in developments of GaN‐based VCSELs.