bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and Significance of MMPs in Synovial Fluid, Serum and PBMC Culture Supernatant Stimulated by LPS in Osteoarthritis Patients With or Without Diabetes
Authors: Luo Simin , Shi Qiping , Chen Junyuan , Wang Huajun , Wu Wenrui , Zha Zhengang
Published: December 2017

Objective Patients with Type 2 Diabetes mellitus (T2DM) are prone to osteoarthritis (OA). Matrix metalloproteinases (MMPs), an essential modulator in cartilage matrix homeostasis, increase in T2DM and OA. We aimed to ascertain the expression difference of MMPs and function in mononuclear cells after stimulating by lipopolysaccharide (LPS) in OA patients with or without diabetes.

Methods 30 knee OA patients without T2DM (OA group), 20 knee OA patients with T2DM (DM-OA group) and 5 healthy volunteers recruited as control were enrolled from January 2016 to January 2017. The expression levels of MMPs in both serum and synovial fluid were initially detected in three groups by enzyme-linked immunosorbent assay (ELISA). After stimulation of peripheral blood mononuclear cell (PBMC) with LPS, the release of MMPs were determined and evaluated.

Results The expression of MMP-1, -7, -8, -9, -10 and -12 in synovial fluid in DM-OA group were significantly higher than in OA group and healthy control. The expression of MMP-1 and -7 in serum were highest in DM-OA group. LPS significantly promotes the production of MMP-1, -8, -9 and -10 in PBMC of each group after 4 h stimulation. It is worth to note that the LPS-stimulated MMP-8 and -9 elevations were more prominent in DM-OA group compared with their counterparts.

Conclusion High levels of MMP-1, -7, -8, -9, -10, and -12 in the synovial fluid might be one of important reasons that diabetes patients are more frequently suffered from OA. Inflammation-induced malfunction of mononuclear cells would stimulate MMP-8 and -9 secretion to various extents.
Unilateraler dekompensierender Strabismus sursoadductorius mit und ohne Hypotrophie des M. obliquus superior – orthoptische Unterscheidungsmerkmale im Erwachsenenalter
Authors: Gusek-Schneider Gabriele-Charlotte , Kästle Nicola , Reil Franziska , Schürhoff Sabine , Engelhorn Tobias
Published: December 2017

Einleitung Das klinische Bild des dekompensierenden Strabismus sursoadductorius (dSSA) ist keine ätiologisch homogene Entität. Eine häufige unmittelbare Ursache des dSSA ist die Hypotrophie des M. obliquus superior (HMOS). In dieser Studie werden klinische Merkmale des dSSA mit und ohne HMOS verglichen.

Patienten und Methoden Es wurden 25 konsekutive Patienten im Alter von 14 – 69 Jahren (Median 43 Jahre) in die Studie eingeschlossen, 14 mit im 3-T-MRT erwiesener HMOS (Gruppe 1), 11 ohne HMOS (Gruppe 2). Die HMOS war definiert durch eine Minderung des mediolateralen (ML) Durchmessers und der anhand des ML sowie des kraniokaudalen (CC) Durchmessers errechneten Fläche = (ML · CC/4) · π auf der koronaren Schicht der größten Ausdehnung des betroffenen M. obliquus superior auf < 80% im Vergleich zum kontralateralen M. obliquus superior. Die Gruppen wurden bez. Kopfzwangshaltung (KZH), Zyklo- und Vertikaldeviationen und des Kopfneigephänomens verglichen. Die Patienten wurden in die Knapp-Klassifikation eingeteilt.

Ergebnisse Sowohl die Inzidenz einer KZH mit 14/14 vs. 5/11 (χ2 = 0,003) als auch deren Ausmaß mit 11,1 ± 4,5° vs. 3,2 ± 4,1° (p < 0,001) war in Gruppe 1 größer als in Gruppe 2, ebenso das Bielschowsky-Kopfneigephänomen mit 9,3 ± 4,3° bzw. 3,8 ± 4,9° (p = 0,008). Die Hypertropie war in Gruppe 1 größer als in Gruppe 2 in Adduktion: 16,7 ± 5,3° vs. 9,3 ± 3,4° (p < 0,001) und bei Abblick in Adduktion des betroffenen Auges: 14,6 ± 7,1 vs. 7,2 ± 3,7° (p = 0,03). In Gruppe 1 war die Zunahme der vertikalen Deviationen nur in der Sagittalebene größer als in Gruppe 2: 2,8 ± 7,8 vs. − 2,4 ± 4,2 (p = 0,04); die Exzyklodeviation war in Gruppe 1 in allen 3 Ebenen (Sagittalebene, Abduktion, Adduktion) größer als in Gruppe 2: 1,3 ± 4,1 vs. − 2,9 ± 2,8 (p = 0,006), 2,4 ± 5,2 vs. − 2,2 ± 2,9 (p = 0,01), 0,5 ± 3,8 vs. − 2,7 ± 3,9 (p = 0,05). Die Knapp-Klassifikation II lag bei 6 von 15 Patienten der Gruppe 1 vor und nur in dieser (χ2 = 0,03).

Schlussfolgerung In beiden Gruppen fand sich eine große Streuung der Vertikaldeviationen. Bei Patienten ohne HMOS überschritt die Vertikaldeviation in Adduktion nicht 15°. Patienten mit HMOS zeigen aufgrund der früh entwickelten Ausgleichsinnervation nicht das typische Bild einer später erworbenen Trochlearisparese. Eine Vertikaldeviation über 15° in Adduktion, Zunahme der Exzyklorotation im Abblick in allen 3 Ebenen und die Einordbarkeit in Typ II nach der Knapp-Klassifikation sind relativ zuverlässige Hinweise auf das Vorliegen einer HMOS. Ein international einheitlicher Begriff für diese Patientengruppe wie z. B. M.-obliquus-superior-Schwäche oder M.-obliquus-superior-Hypotrophie wäre erstrebenswert.
Interface Si donor control to improve dynamic performance of AlGaN/GaN MIS-HEMTs
Authors: Song Liang , Fu Kai , Zhang Zhili , Sun Shichuang , Li Weiyi , Yu Guohao , Hao Ronghui , Fan Yaming , Shi Wenhua , Cai Yong , Zhang Baoshun
Published: December 2017

In this letter, we have studied the performance of AlGaN/GaN metal-insulator-semiconductor high electron mobility transistors (MIS-HEMTs) with different interface Si donor incorporation which is tuned during the deposition process of LPCVD-SiNx which is adopted as gate dielectric and passivation layer. Current collapse of the MIS-HEMTs without field plate is suppressed more effectively by increasing the SiH2Cl2/NH3 flow ratio and the normalized dynamic on-resistance (RON) is reduced two orders magnitude after off-state VDS stress of 600 V for 10 ms. Through interface characterization, we have found that the interface deep-level traps distribution with high Si donor incorporation by increasing the SiH2Cl2/NH3 flow ratio is lowered. It’s indicated that the Si donors are most likely to fill and screen the deep-level traps at the interface resulting in the suppression of slow trapping process and the virtual gate effect. Although the Si donor incorporation brings about the increase of gate leakage current (IGS), no clear degradation of breakdown voltage can be seen by choosing appropriate SiH2Cl2/NH3 flow ratio.
Characterization of strain and its effects on ferromagnetic nickel nanocubes
Authors: Manna Sohini , Kim Jong Woo , Lubarda Marko V. , Wingert James , Harder Ross , Spada Fred , Lomakin Vitaliy , Shpyrko Oleg , Fullerton Eric E.
Published: December 2017

We report on the interplay of magnetic properties and intrinsic strain in ferromagnetic nickel nanocubes with cubic anisotropy. Via coherent x-ray diffraction imaging we observed compressive stress at the bottom surface of these cubes. The nanocubes with {100} facets described and imaged in this study were synthesized using a single-step CVD process. Micromagnetic simulations predict the presence of vortices at remanence in the absence of strain. The effects of strain resulting from the compressive stress on the magnetic response of the ferromagnetic cubes is investigated. We observe that measured intrinsic strain is too low to change the magnetic anisotropy of ferromagnetic cubes but topological behavior of magnetic vortices is sensitive to even this low range of strain.
Efficient multiscale magnetic-domain analysis of iron-core material under mechanical stress
Authors: Nishikubo Atsushi , Ito Shumpei , Mifune Takeshi , Matsuo Tetsuji , Kaido Chikara , Takahashi Yasuhito , Fujiwara Koji
Published: December 2017

For an efficient analysis of magnetization, a partial-implicit solution method is improved using an assembled domain structure model with six-domain mesoscopic particles exhibiting pinning-type hysteresis. The quantitative analysis of non-oriented silicon steel succeeds in predicting the stress dependence of hysteresis loss with computation times greatly reduced by using the improved partial-implicit method. The effect of cell division along the thickness direction is also evaluated.
Transportation of cold plasma jet in multiple-mirror magnetic field
Authors: Ivanov I. A. , Batkin V. I. , Burdakov A. V. , Burmasov V. S. , Kuklin K. N. , Mekler K. I. , Polosatkin S. V. , Postupaev V. V. , Sidorov E. N. , Rovenskikh A. F.
Published: December 2017

New experimental results on magnetic compression and transport of low-temperature arc plasma are presented. In the experiments, the transport efficiency of the plasma stream in a multiple-mirror configuration was compared with the same in a uniform solenoidal field. The magnetic compression ratio of the plasma stream varied from 5 to 60 at the initial diameter of 5 cm. As the result, the plasma with (1 – 4)×1020 m-3 density at the axis was obtained at ∼3 m distance from the plasma source. Theory predicted that a multiple-mirror magnetic field should not significantly decelerate and weaken collisional plasma. The experiment confirmed this prediction. In the presented work, we simulated the baseline scenario of GOL-NB filling by cold start plasma.
Gaussian basis sets for use in correlated molecular calculations. XI. Pseudopotential-based and all-electron relativistic basis sets for alkali metal (K–Fr) and alkaline earth (Ca–Ra) elements
Authors: Hill J. Grant , Peterson Kirk A.
Published: December 2017

New correlation consistent basis sets based on pseudopotential (PP) Hamiltonians have been developed from double- to quintuple-zeta quality for the late alkali (K–Fr) and alkaline earth (Ca–Ra) metals. These are accompanied by new all-electron basis sets of double- to quadruple-zeta quality that have been contracted for use with both Douglas-Kroll-Hess (DKH) and eXact 2-Component (X2C) scalar relativistic Hamiltonians. Sets for valence correlation (ms), cc-pVnZ-PP and cc-pVnZ-(DK,DK3/X2C), in addition to outer-core correlation [valence + (m−1)sp], cc-p(w)CVnZ-PP and cc-pwCVnZ-(DK,DK3/X2C), are reported. The –PP sets have been developed for use with small-core PPs [I. S. Lim et al., J. Chem. Phys. 122, 104103 (2005) and I. S. Lim et al., J. Chem. Phys. 124, 034107 (2006)], while the all-electron sets utilized second-order DKH Hamiltonians for 4s and 5s elements and third-order DKH for 6s and 7s. The accuracy of the basis sets is assessed through benchmark calculations at the coupled-cluster level of theory for both atomic and molecular properties. Not surprisingly, it is found that outer-core correlation is vital for accurate calculation of the thermodynamic and spectroscopic properties of diatomic molecules containing these elements.
A Wong-Zakai approximation for random invariant manifolds
Authors: Jiang Tao , Liu Xianming , Duan Jinqiao
Published: December 2017

Random invariant manifolds are geometric objects useful for understanding complex dynamics under stochastic influences. But these random objects are difficult to be visualized geometrically or computed numerically. The current work provides a perturbation approach to approximate these random invariant manifolds. We first discuss the existence of a random invariant manifold for a class of stochastic evolutionary equations. Then, we approximate the random invariant manifold by the invariant manifold of a new system with smooth colored noise (i.e., integrated Ornstein-Uhlenbeck processes). The convergence in a pathwise Wong-Zakai sense is shown.
DyNetViewer: a Cytoscape app for dynamic network construction, analysis and visualization
Authors: Li Min , Yang Jie , Wu Fang-Xiang , Pan Yi , Wang Jianxin
Published: December 2017

The molecular interactions in a cell are varying with time and surrounded environmental cues. The construction and analysis of dynamic molecular networks can elucidate dynamic cellular mechanisms of different biological functions and provide a chance to understand complex diseases at the systems level. Here, we develop DyNetViewer, a Cytoscape application that provides a range of functionalities for the construction, analysis and visualization of dynamic protein–protein interaction networks. The current version of DyNetViewer consists of four different dynamic network construction methods, twelve topological variation analysis methods and four clustering algorithms. Moreover, visualization of different topological variation of nodes and clusters over time enables users to quickly identify the most variations across many network states.

Availability and implementation

DyNetViewer is freely available with tutorials at the Cytoscape (3.4+) App Store (http://apps.cytoscape.org/apps/dynetviewer).

Supplementary information

Supplementary data are available at Bioinformatics online.
Mustguseal: a server for multiple structure-guided sequence alignment of protein families
Authors: Suplatov Dmitry A , Kopylov Kirill E , Popova Nina N , Voevodin Vladimir V , Švedas Vytas K
Published: December 2017

Motivation

Comparative analysis of homologous proteins in a functionally diverse superfamily is a valuable tool at studying structure-function relationship, but represents a methodological challenge.

Results

The Mustguseal web-server can automatically build large structure-guided sequence alignments of functionally diverse protein families that include thousands of proteins basing on all available information about their structures and sequences in public databases. Superimposition of protein structures is implemented to compare evolutionarily distant relatives, whereas alignment of sequences is used to compare close homologues. The final alignment can be downloaded for a local use or operated on-line with the built-in interactive tools and further submitted to the integrated sister web-servers of Mustguseal to analyze conserved, subfamily-specific and co-evolving residues at studying a protein function and regulation, designing improved enzyme variants for practical applications and selective ligands to modulate functional properties of proteins.

Availability and implementation

Freely available on the web at https://biokinet.belozersky.msu.ru/mustguseal.

Supplementary information

Supplementary data are available at Bioinformatics online.
Analytic Continuation of Equivariant Distributions
Authors: Gourevitch Dmitry , Sahi Siddhartha , Sayag Eitan
Published: December 2017

We establish a method for constructing equivariant distributions on smooth real algebraic varieties from equivariant distributions on Zariski open subsets. This is based on Bernstein’s theory of analytic continuation of holonomic distributions. We use this to construct H-equivariant functionals on principal series representations of G, where G is a real reductive group and H is an algebraic subgroup. We also deduce the existence of generalized Whittaker models for degenerate principal series representations. As a special case, this gives short proofs of existence of Whittaker models on principal series representations and of analytic continuation of standard intertwining operators. Finally, we extend our constructions to the p-adic case using a recent result of Hong and Sun.
Managing Challenging Behavior in Adolescents with Autism Spectrum Disorder
Authors: Matheis Maya , Estabillo Jasper A. , Matson Johnny L.
Published: December 2017

The term “challenging behavior” describes a wide range of behaviors that may be harmful to an individual and that pose significant risks related to health, emotional distress, or exclusion from community settings. Challenging behaviors occur at high rates among individuals with autism spectrum disorder (ASD). Some forms of challenging behavior include: aggression, self-injurious behavior (SIB), stereotypical behavior, pica, and vomiting/rumination. Functional behavioral assessment (FBA) is the process of gathering and interpreting data related to the underlying function of a behavior. Interventions that target the function of a behavior are more effective and efficient. Behavioral treatment methods for challenging behavior are based on operant principles of reinforcement and punishment. Several common treatment methods are described. Suggestions for the assessment and treatment of challenging behaviors are outlined.
Two Novel Fungal Symbionts Fusarium kuroshium sp. nov. and Graphium kuroshium sp. nov. of Kuroshio Shot Hole Borer (Euwallacea sp. nr. fornicatus) Cause Fusarium Dieback on Woody Host Species in California
Authors: Na Francis , Carrillo Joseph D. , Mayorquin Joey S. , Ndinga-Muniania Cedric , Stajich Jason E. , Stouthamer Richard , Huang Yin-Tse , Lin Yu-Ting , Chen Chi-Yu , Eskalen Akif
Published: December 2017

Shot hole borer (SHB)-Fusarium dieback (FD) is a new pest-disease complex affecting numerous tree species in California and is vectored by two distinct, but related ambrosia beetles (Euwallacea sp. nr. fornicatus) called polyphagous shot hole borer (PSHB) and Kuroshio shot hole borer (KSHB). These pest-disease complexes cause branch dieback and tree mortality on numerous wildland and landscape tree species, as well as agricultural tree species, primarily avocado. The recent discovery of KSHB in California initiated an investigation of fungal symbionts associated with the KSHB vector. Ten isolates of Fusarium sp. and Graphium sp., respectively, were recovered from the mycangia of adult KSHB females captured in three different locations within San Diego County and compared with the known symbiotic fungi of PSHB. Multigene phylogenetic analyses of the internal transcribed spacer region (ITS), translation elongation factor-1 alpha (TEF1-α), and RNA polymerase II subunit (RPB1, RPB2) regions as well as morphological comparisons revealed that two novel fungal associates Fusarium kuroshium sp. nov. and Graphium kuroshium sp. nov. obtained from KSHB were related to, but distinct from the fungal symbionts F. euwallaceae and G. euwallaceae associated with PSHB in California. Pathogenicity tests on healthy, young avocado plants revealed F. kuroshium and G. kuroshium to be pathogenic. Lesion lengths from inoculation of F. kuroshium were found to be significantly shorter compared with those caused by F. euwallaceae, while no difference in symptom severity was detected between Graphium spp. associated with KSHB and PSHB. These findings highlight the pest disease complexes of KSHB-FD and PSHB-FD as distinct, but collective threats adversely impacting woody hosts throughout California.
Transcriptional Changes in Dorsal Spinal Cord Persist after Surgical Incision Despite Preemptive Analgesia with Peripheral Resiniferatoxin
Authors: Raithel Stephen J. , Sapio Matthew R. , LaPaglia Danielle M. , Iadarola Michael J. , Mannes Andrew J.
Published: December 2017

Background

Peripheral nociceptors expressing the ion channel transient receptor potential cation channel, subfamily V, member 1, play an important role in mediating postoperative pain. Signaling from these nociceptors in the peri- and postoperative period can lead to plastic changes in the spinal cord and, when controlled, can yield analgesia. The transcriptomic changes in the dorsal spinal cord after surgery, and potential coupling to transient receptor potential cation channel, subfamily V, member 1–positive nociceptor signaling, remain poorly studied.

Methods

Resiniferatoxin was injected subcutaneously into rat hind paw several minutes before surgical incision to inactivate transient receptor potential cation channel, subfamily V, member 1–positive nerve terminals. The effects of resiniferatoxin on postincisional measures of pain were assessed through postoperative day 10 (n = 51). Transcriptomic changes in the dorsal spinal cord, with and without peripheral transient receptor potential cation channel, subfamily V, member 1–positive nerve terminal inactivation, were assessed by RNA sequencing (n = 22).

Results

Peripherally administered resiniferatoxin increased thermal withdrawal latency by at least twofold through postoperative day 4, increased mechanical withdrawal threshold by at least sevenfold through postoperative day 2, and decreased guarding score by 90% relative to vehicle control (P < 0.05). Surgical incision induced 70 genes in the dorsal horn, and these changes were specific to the ipsilateral dorsal horn. Gene induction with surgical incision persisted despite robust analgesia from resiniferatoxin pretreatment. Many of the genes induced were related to microglial activation, such as Cd11b and Iba1.

Conclusions

A single subcutaneous injection of resiniferatoxin before incision attenuated both evoked and nonevoked measures of postoperative pain. Surgical incision induced transcriptomic changes in the dorsal horn that persisted despite analgesia with resiniferatoxin, suggesting that postsurgical pain signals can be blocked without preventing transcription changes in the dorsal horn.
RETINAL ARTERY OCCLUSION AFTER INTRAVASCULAR PROCEDURES
Authors: Cho Soo Chang , Jung Cheolkyu , Lee Joo Yong , Kim Sang Jin , Park Kyu Hyung , Woo Se Joon
Published: December 2017

Purpose:

To evaluate clinical characteristics and possible mechanisms of retinal artery occlusion (RAO) after intravascular procedures.

Methods:

This study is retrospective case series and literature review. Twenty-seven patients with intravascular procedure–associated RAO (10 new patients and 17 from previous reports) were divided into Groups 1 and 2 according to assumed etiology—dislodged and new emboli, respectively. Clinical features and etiology of RAO were analyzed.

Results:

Branch and central RAO were observed in 17 (63%) and 10 (37%) patients, respectively, and 61.1% of patients exhibited final BCVA ≥20/40. Intravascular procedures were performed at the carotid artery (48.1%), heart (25.9%), carotid artery or heart (3.7%), brain (11.1%), scalp/glabella (7.4%), and thyroid (3.7%). Ratio of patients with immediate and delayed (≥24 hours after procedure) onset of RAO was 17 (63.0%):10 (37.0%). In Group 1 (n = 16), RAO was associated with dislodged plaques in the carotid artery (9; 56.3%), heart (6; 37.5%), or carotid artery/heart (1; 6.3%), and one patient each experienced acute brain infarction and contralateral branch retinal artery occlusion. In group 2 (n = 11), RAO was associated with new thrombi (6; 54.5%) or emboli (5; 45.5%), and one patient experienced ocular pain, ophthalmoplegia, and blepharoptosis.

Conclusion:

Intravascular procedures might result in RAO because of embolic plaques dislodged from the carotid artery or heart, or new thrombi or embolic materials migrating through collateral channels. Branch retinal artery occlusion was more frequent than central retinal artery occlusion after intravascular procedures, which resulted in relatively good visual outcomes. Patients should be informed about immediate or delayed presentation of RAO after intravascular procedures.
Insurance Type and Access to Health Care Providers and Appointments Under the Affordable Care Act
Authors: Alcalá Héctor E. , Roby Dylan H. , Grande David T. , McKenna Ryan M. , Ortega Alexander N.
Published: December 2017

Background:

Millions of adults have gained insurance through the Affordable Care Act (ACA). However, disparities in access to care persist.

Objective:

This study examined differences in access to primary and specialty care among patients insured by private individual market insurance plans (both on-exchange and off-exchange) and Medicaid compared with those with employer-sponsored insurance.

Research Design:

Using data from the 2014 and 2015 California Health Interview Survey, logistic regression analyses were used to calculate the odds of being unable to access primary care providers, access specialty care providers and receive a needed doctor’s appointment in a timely manner, with insurance type serving as the independent variable. Interaction terms examined if the expiration of the ACA’s optional Medicaid primary care fee increase in 2014 modified any of these associations.

Results:

Findings showed poorer access to providers among those insured through Medicaid and the individual market (whether purchased through the state’s health insurance exchange or off-exchange) relative to employer-based insurance. Poor access to primary care providers was seen among private coverage purchased via exchanges, relative to private coverage purchased on the individual market. In addition, findings showed that reduction of Medicaid fees coincided with reduced ability to see primary care providers. However, a similar trend was seen among those with employer-based coverage, which suggests that this change may not be attributable to reductions in Medicaid fees.

Conclusion:

Despite ACA-related gains in insurance coverage, those with on-exchange and off-exchange individual private insurance plans and Medicaid encounter more barriers to care than those with employer-based insurance.
Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes
Authors: Montalban-Bravo Guillermo , Garcia-Manero Guillermo , Jabbour Elias
Published: December 2017

Purpose of review

Hypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.

Recent findings

Recent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.

Despite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care.
PD-L1 Immunohistochemistry Highlights Bone Marrow Involvement by Classic Hodgkin Lymphoma in Staging Biopsies: Implications for Diagnosis and Tumor Microenvironment Alterations
Authors: Xing Wei , Mai Nicholas , Dresser Karen , Chen Benjamin J.
Published: December 2017

Programmed cell death ligand 1 (PD-L1) is cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. Previous studies have demonstrated consistent expression of PD-L1 by Reed-Sternberg (RS) cells, as well as nonmalignant tumor-infiltrating macrophages in classic Hodgkin lymphoma (CHL). Bone marrow involvement by CHL is uncommon, being present in 5% to 10% of cases, but indicates Ann Arbor stage IV disease. Given the mixed inflammatory infiltrate that characterizes CHL, detection of RS cells in small bone marrow biopsies may be difficult. We sought to investigate the diagnostic utility of PD-L1 expression in staging bone marrow biopsies from patients with newly diagnosed CHL. Forty-four staging bone marrow biopsies from patients with newly diagnosed CHL were examined for PD-L1 expression by immunohistochemistry. Eight bone marrow biopsies were positive for involvement by CHL (8/44, 18%) and all were positive for PD-L1 (8/8, 100%), including a case that was originally nondiagnostic. Membranous PD-L1 expression was restricted to RS cells and the adjacent nontumor inflammatory cells admixed within areas of fibrosis. Uninvolved bone marrow biopsies and normal-appearing marrow in cases positive for CHL were negative for PD-L1. In comparison, bone marrow biopsies with myelofibrosis caused by myeloproliferative or myelodysplastic disorders were negative for significant PD-L1 staining. PD-L1 expression in RS cells and surrounding inflammatory cells is a sensitive marker for bone marrow involvement by CHL. In cases where RS cells are infrequent, PD-L1 staining in regions of fibrosis may serve as a useful diagnostic clue to involvement by CHL.
Soft-Tissue Reconstruction of the Complicated Knee Arthroplasty: Principles and Predictors of Salvage
Authors: Colen David L. , Carney Martin J. , Shubinets Valeriy , Lanni Michael A. , Liu Tiffany , Levin L. Scott , Lee Gwo-Chin , Kovach Stephen J.
Published: December 2017

Background:

Total knee arthroplasty is a common orthopedic procedure in the United States and complications can be devastating. Soft-tissue compromise or joint infection may cause failure of prosthesis requiring knee fusion or amputation. The role of a plastic surgeon in total knee arthroplasty is critical for cases requiring optimization of the soft-tissue envelope. The purpose of this study was to elucidate factors associated with total knee arthroplasty salvage following complications and clarify principles of reconstruction to optimize outcomes.

Methods:

A retrospective review of patients requiring soft-tissue reconstruction performed by the senior author after total knee arthroplasty over 8 years was completed. Logistic regression and Fisher’s exact tests determined factors associated with the primary outcome, prosthesis salvage versus knee fusion or amputation.

Results:

Seventy-three knees in 71 patients required soft-tissue reconstruction (mean follow-up, 1.8 years), with a salvage rate of 61.1 percent, mostly using medial gastrocnemius flaps. Patients referred to our institution with complicated periprosthetic wounds were significantly more likely to lose their knee prosthesis than patients treated only within our system. Patients with multiple prior knee operations before definitive soft-tissue reconstruction had significantly decreased rates of prosthesis salvage and an increased risk of amputation. Knee salvage significantly decreased with positive joint cultures (Gram-negative greater than Gram-positive organisms) and particularly at the time of definitive reconstruction, which also trended toward an increased risk of amputation.

Conclusions:

In revision total knee arthroplasty, prompt soft-tissue reconstruction improves the likelihood of success, and protracted surgical courses and contamination increase failure and amputations. The authors show a benefit to involving plastic surgeons early in the course of total knee arthroplasty complications to optimize genicular soft tissues.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Herpes Zoster Optic Neuropathy
Authors: Kaufman Aaron R. , Myers Eileen M. , Moster Mark L. , Stanley Jordan , Kline Lanning B. , Golnik Karl C.
Published: December 2017

Background:

Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON.

Methods:

A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes.

Results:

Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5–4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6–30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity.

Conclusion:

Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.
Peripheral infrastructure vectors and an extended set of plant parts for the modular cloning system
Authors: Gantner Johannes , Ilse Theresa , Ordon Jana , Kretschmer Carola , Gruetzner Ramona , Löfke Christian , Dagdas Yasin , Bürstenbinder Katharina , Marillonnet Sylvestre , Stuttmann Johannes
Published: December 2017

Standardized DNA assembly strategies facilitate the generation of multigene constructs from collections of building blocks in plant synthetic biology. A common syntax for hierarchical DNA assembly following the Golden Gate principle employing Type IIs restriction endonucleases was recently developed, and underlies the Modular Cloning and GoldenBraid systems. In these systems, transcriptional units and/or multigene constructs are assembled from libraries of standardized building blocks, also referred to as phytobricks, in several hierarchical levels and by iterative Golden Gate reactions. This combinatorial assembly strategy meets the increasingly complex demands in biotechnology and bioengineering, and also represents a cost-efficient and versatile alternative to previous molecular cloning techniques. For Modular Cloning, a collection of commonly used Plant Parts was previously released together with the Modular Cloning toolkit itself, which largely facilitated the adoption of this cloning system in the research community. Here, a collection of approximately 80 additional phytobricks is provided. These phytobricks comprise e.g. modules for inducible expression systems, different promoters or epitope tags, which will increase the versatility of Modular Cloning-based DNA assemblies. Furthermore, first instances of a “peripheral infrastructure” around Modular Cloning are presented: While available toolkits are designed for the assembly of plant transformation constructs, vectors were created to also use coding sequence-containing phytobricks directly in yeast two hybrid interaction or bacterial infection assays. Additionally, DNA modules and assembly strategies for connecting Modular Cloning with Gateway Cloning are presented, which may serve as an interface between available resources and newly adopted hierarchical assembly strategies. The presented material will be provided as a toolkit to the plant research community and will further enhance the usefulness and versatility of Modular Cloning.
The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes
Authors: Rodríguez-Carballo Eddie , Lopez-Delisle Lucille , Zhan Ye , Fabre Pierre J. , Beccari Leonardo , El-Idrissi Imane , Huynh Thi Hanh Nguyen , Ozadam Hakan , Dekker Job , Duboule Denis
Published: December 2017

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed. The resulting progressive release in boundary effect triggered inter-TAD contacts, favored by the activity of the newly accessed enhancers. However, the boundary was highly resilient, and only a 400-kb deletion, including the whole-gene cluster, was eventually able to merge the neighboring TADs into a single structure. In this unified TAD, both proximal and distal limb enhancers nevertheless continued to work independently over a targeted transgenic reporter construct. We propose that the whole HoxD cluster is a dynamic TAD border and that the exact boundary position varies depending on both the transcriptional status and the developmental context.
The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes
Authors: Fan Hui , Lv Pin , Huo Xiangru , Wu Jicheng , Wang Qianfeng , Cheng Lu , Liu Yun , Tang Qi-Qun , Zhang Ling , Zhang Feng , Zheng Xiaoqi , Wu Hao , Wen Bo
Published: December 2017

Eukaryotic chromosomes are folded into higher-order conformations to coordinate genome functions. In addition to long-range chromatin loops, recent chromosome conformation capture (3C)-based studies have indicated higher levels of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood. Via high-throughput assays, including in situ Hi-C, DamID, ChIP-seq, and RNA-seq, we investigated roles of the Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), a nuclear matrix (NM)-associated protein, in 3D genome organization. Upon the depletion of HNRNPU in mouse hepatocytes, the coverage of lamina-associated domains (LADs) in the genome increases from 53.1% to 68.6%, and a global condensation of chromatin was observed. Furthermore, disruption of HNRNPU leads to compartment switching on 7.5% of the genome, decreases TAD boundary strengths at borders between A (active) and B (inactive) compartments, and reduces chromatin loop intensities. Long-range chromatin interactions between and within compartments or TADs are also significantly remodeled upon HNRNPU depletion. Intriguingly, HNRNPU mainly associates with active chromatin, and 80% of HNRNPU peaks coincide with the binding of CTCF or RAD21. Collectively, we demonstrated that HNRNPU functions as a major factor maintaining 3D chromatin architecture, suggesting important roles of NM-associated proteins in genome organization.
An interpretive structural modeling approach to advertisement effectiveness in the Indian mobile phone industry
Authors: Maheshwari Prateek , Seth Nitin , Gupta Anoop Kumar
Published: December 2017

Purpose

The mobile phone industry in India is highly competitive, fast paced and technology-driven. In such a hyper competitive era, effective advertising is considered a key success driver for a mobile phone brand. The purpose of this paper is to identify advertisement effectiveness dimensions for Indian mobile phone industry and to develop hierarchical interrelationships among these dimensions in the Indian print context.

Design/methodology/approach

Structured Delphi approach is used to derive the set of dimensions for advertisement effectiveness. Further, techniques such as interpretive structural modeling and MICMAC analysis are used to establish hierarchical linkages among identified dimensions.

Findings

On the basis of experts’ opinion, refinement through structured Delphi resulted in the identification of 14 advertisement effectiveness dimensions specific to Indian mobile phone industry. Interpretive structural modeling assisted in the development of linkages among these identified dimensions based on their interrelations. Further, attention, relevance, excitability, liking and consumer preference, etc., turned out to be the dimensions of utmost importance for measuring advertisement effectiveness for the Indian mobile phone industry.

Research limitations/implications

The present research work is limited to the recognition and development of hierarchical interrelationships among advertisement effectiveness dimensions specific to mobile phone business in the Indian print context only. Further studies may be carried out for other product or service category in some different media context.

Practical implications

The present research has several significant implications for academics and advertising practitioners involved in designing and developing promotional campaigns for mobile phone brands in India. The identified 14 dimensions and developed hierarchical model provide valuable insights for improving advertisement effectiveness.

Originality/value

This paper demonstrated successful implementation of Delphi and interpretive structural modeling technique to explore the research area of advertisement effectiveness.
How Can the CAP Promote Rural Jobs?
Authors: Matthews Alan
Published: December 2017

Promoting rural jobs goes well beyond agricultural policy, but targeted agricultural policies can play a role. The key lesson is to invest in increasing the sector's supply of both market and non‐market goods and services, recognising that the jobs created will often be in related non‐farm sectors of the rural economy. Subsidising employment in low‐productivity agriculture is neither a sensible nor sustainable job‐creation strategy. It makes far more sense to focus on ‘smart’ agricultural support and investments which help farmers and local communities to overcome specific barriers and constraints to improve their productivity. Many investment‐promoting support measures can already be provided under CAP rules today although they are often constrained by funding limitations, for example, in Member States’ Rural Development Programmes. If policymakers want the CAP to do more to maximise its contribution to jobs and growth, these productive supports should be prioritised in the coming CAP negotiations. At the same time, there should be a greater focus on the training and skill needs for the existing agricultural workforce, including paid workers who are often forgotten in farm policy discussions.
Examining caries aetiology in adolescence with structural equation modelling
Authors: Curtis A.M. , Cavanaugh J.E. , Levy S.M. , VanBuren J. , Marshall T.A. , Warren J.J.
Published: December 2017

Objectives

This analysis examines the aetiology of caries development in adolescents using structural equation modelling to identify behavioural mediators of the relationship between socioeconomic status (SES) and caries incidence, and to investigate the role of sex on caries‐preventive behaviour and caries.

Methods

This analysis was based on data from the Iowa Fluoride Study, a longitudinal study of a birth cohort. We hypothesized that socioeconomic status earlier in life has a direct effect on caries development and an indirect effect from improved behavioural variables—dental visit attendance, toothbrushing frequency and percentage of beverage intake consisting of sugar‐sweetened beverages—and that sex also plays a role in behavioural variables, as well as caries. A structural equation model was developed based on these hypotheses, and direct and indirect standardized path coefficients were calculated, as well as their standard errors.

Results

Based on our proposed model, SES at birth significantly influences SES during adolescence, but not adolescent behaviours. The effect of SES during adolescence on caries in the permanent dentition is mediated by adolescent behaviours. Female participants have worse caries than male participants, despite lower self‐reported percentages of sugar‐sweetened beverage intake and more frequent brushing and dental attendance.

Conclusions

This analysis models the relationships among known causal factors for caries and suggests that the role of SES in caries may not be as important as previously thought and different behaviours that affect oral health between males and females as well as differences in caries between the sexes could begin during adolescence. These findings could help improve caries prevention programmes for adolescents.
Visit‐to‐visit HbA1c variability and systolic blood pressure (SBP) variability are significantly and additively associated with mortality in individuals with type 1 diabetes: An observational study
Authors: Wightman Stuart S. , Sainsbury Christopher A. R. , Jones Gregory C.
Published: December 2017

Aim

To investigate the relationship between variability in both visit‐to‐visit HbA1c and SBP and mortality in individuals with type 1 diabetes.

Methods

The Scottish Care Information (SCI) Diabetes dataset was used to identify 5952 individuals with type 1 diabetes for inclusion in this observational study. The SCI‐Diabetes dataset allowed access to blood pressure values, HbA1c readings, demographic information and mortality rates for all study participants. Participants were dichotomized to above and below median values for both HbA1c coefficient of variation (CV) and SBP CV, thus dividing participants into 4 cohorts for survival analysis. Survival analysis was carried out over 1430 days. A Cox proportional hazard model was used to allow comparison of mortality between the 4 cohorts.

Results

Of the 5952 patients, death occurred in 416. CV for both HbA1c and SBP were significantly associated with mortality. The median values for HbA1c CV and SBP CV were 8.0 and 8.1, respectively. The hazard ratio for high HbA1c CV only (P = .0015) was 1.78 ± 0.36. The hazard ratio for high SBP CV only (P = .0018) was 1.69 ± 0.33. The hazard ratio for both high HbA1c CV and high SBP CV (P < .00001) was 2.37 ± 0.32.

Conclusions

Our findings demonstrate that variability of both HbA1c and SBP is significantly and additively associated with mortality in individuals with type 1 diabetes. The variability of these parameters might be useful for risk stratification and is a potential target for future interventional studies.
Use of linear and convex ultrasound transducers for evaluation of retrosternal area in patients after cardiac surgery
Authors: Cantinotti Massimiliano , Giordano Raffaele , Corana Giulia , Franchi Eliana , Koestenberger Martin , Kutty Shelby
Published: December 2017

The use of linear and convex transducers is usually reserved for ultrasound imaging of vessels, abdominal organs, and lungs. However, the use of these transducers may be extended for the evaluation of thoracic structures. We describe our experience with the use of linear and convex transducers in the evaluation of the retrosternal area, which is usually difficult to visualize by conventional echocardiography and so could provide improved diagnostic information in patients after cardiac surgery.
Metacommunities in river networks: The importance of network structure and connectivity on patterns and processes
Authors: Tonkin Jonathan D. , Heino Jani , Altermatt Florian
Published: December 2017

Rivers are spatially organised into hierarchic dendritic networks. This unique physical structure and the associated directionality of physical flows set them apart from most other environments by regulating the dispersal of resident biota and therefore the distribution of biodiversity.

The aim of this special issue is to highlight the importance of the river network on structuring biodiversity, particularly through metacommunity dynamics and associated dispersal processes.

The issue covers a wide range of topics, including disease spread, nutrient uptake, trophic dynamics, effects of anthropogenic stressors and the joint roles of dispersal and environmental filtering. Contributions employ a broad range of approaches, including field and laboratory experiments, modelling, population genetics and conceptual synthesis.

Although these studies represent just a sample of the research that is being performed on biodiversity and metacommunity dynamics in river networks, several important findings have emerged; a common theme being that the structure of the network and spatial dynamics clearly influence the dynamics of populations and communities, and their functions. By taking a broad taxonomic focus (from diatoms and protists to fish), and spanning a large geographic gradient (from the tropics to the subarctic), this special issue provides a broad look at the dynamics that occur in river networks relating to their unique makeup. We hope that this selection of studies spurs additional research on these interesting, globally important, yet severely threatened ecological systems.