bluuebunny/crossref_metadata_2025 huggingface dataset:
Change in Bone Density and Reduction in Fracture Risk: A Meta-Regression of Published Trials
Authors: Bouxsein Mary L , Eastell Richard , Lui Li-Yung , Wu Lucy A , de Papp Anne E , Grauer Andreas , Marin Fernando , Cauley Jane A , Bauer Douglas C , Black Dennis M ,   for the FNIH Bone Quality Project
Published: January 2019

Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.
The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report
Authors: Ebeling Peter R , Akesson Kristina , Bauer Douglas C , Buchbinder Rachelle , Eastell Richard , Fink Howard A , Giangregorio Lora , Guanabens Nuria , Kado Deborah , Kallmes David , Katzman Wendy , Rodriguez Alexander , Wermers Robert , Wilson H Alexander , Bouxsein Mary L
Published: January 2019

Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40–70%. © 2018 American Society for Bone and Mineral Research.
Hepatic effects of long‐term tamoxifen administration to cycling female rats
Authors: Resende Albina Dolores , Leal Sandra , Batista‐Pinto Carla , Garcez Fernanda , Sá Susana Isabel
Published: January 2019

The metabolic implications of tamoxifen (TAM) used as preventive therapy of young premenopausal women with high risk of breast cancer is unknown. To unravel this problem, an animal model of long‐term TAM administration to cycling young adult female rats was used to evaluate its effects in the liver. Body weight and food consumption were monitored, and at the end of the study, both parameters were lower in TAM‐treated rats. Biochemical measurements showed that the TAM administration induced alterations in serum levels of liver enzymes when compared with control rats at different stages of the estrous cycle. In TAM‐treated rats, lower glycogen storage was observed in hepatocytes close to the portal areas and pericentrolobular cells had a higher concentration of glycogen. Liver sections of TAM‐treated rats presented mild steatosis—a high percentage of area occupied by lipid droplets in the hepatocytes. These results point to metabolic changes upon long‐term TAM therapy.
Exploring adverse effects of puerarin on catalase by multiple spectroscopic investigations and docking studies in vitro
Authors: Zhang Bai , Li Ming , Wang Qi , Zhai Aihua
Published: January 2019

Puerarin belongs to one of the most familiar tradition medicines of China, but adverse effects of puerarin during the clinical treatment have been found for years, the mechanisms of which remain unclear. In this study, toxic mechanisms of puerarin on the structure and function of catalase were studied by multiple spectroscopic techniques, isothermal titration calorimetric measurement, and molecular docking methods in vitro. Results showed puerarin could inhibit the activity of catalase due to direct interactions between puerarin and catalase, resulting in conformational and functional changes of the enzyme. To be specific, puerarin statically quenched catalase fluorescence, bound into the active site channel of catalase, hindered the path of the catalytic substrate (H2O2), affected its skeleton conformation and secondary structure, and interacted with the enzymatically related residues through hydrophobic interactions (ΔH > 0 and ΔS > 0) spontaneously (ΔG < 0). This study illustrates potential adverse effects of puerarin, which should catch more attentions during the clinical diagnosis.
Solving the calcium gluconate shortage in real‐time: Mistakes made and lessons learned
Authors: Williams Lance A. , Sikora James , Richardson Carole , Rigi Mohammed , Boshell Nick , Palmer Lakeyra , Dunn Sondra , Slover Terry , Peavey Daniel , Guillory Bryan , Marques Marisa B.
Published: January 2019

Purpose

During a national shortage of calcium gluconate, we switched to calcium chloride for routine supplementation for peripheral blood stem cell (PBSC) collections. Subsequently, we analyzed the postprocedure ionized calcium level, as we aimed for an equivalent result compared to before the shortage.

Methods

Pharmacy representatives helped us to find an “equivalent” substitute for calcium gluconate at 46.5 mEq in 500 mL normal saline, infused at 100 mL/hour. After instituting a presumably comparable protocol using calcium chloride (40.8 mEq in 250 mL normal saline at a rate of 100 mL/hour), we reviewed ionized calcium results post‐PBSC procedures to compare with those obtained with calcium gluconate. Having noticed a difference in the mean values, we adjusted the rate of calcium chloride to reach our desired outcome.

Results

Twenty‐seven procedures were analyzed on 15 unique patients. We used the Spectra OPTIA with a whole blood: anticoagulant ratio of 13:1. Ionized calcium levels post‐PBSC collection with the first calcium chloride protocol were significantly higher (P = 0.003) in nine patients treated. Subsequently, we decreased the calcium chloride infusion rate to 75 mL/hour and achieved similar mean levels to calcium gluconate (P = 0.382).

Conclusion

Changes in replacement fluids for apheresis procedures can be complex, particularly when dealing with electrolytes that could be clinically significant at critically high or low levels. Once we recognized the need to take into account the amount of elemental calcium infused, we achieved the desired postprocedure ionized calcium results. This study can serve as a lesson for future shortages of infusions used during apheresis procedures.
Structural insights into the aggregation mechanism of huntingtin exon 1 protein fragment with different polyQ‐lengths
Authors: Priya S. Binny , Gromiha M. Michael
Published: January 2019

Huntington disease is a neurodegenerative disorder caused by the expansion of polyglutamine (polyQ) at the N‐terminal of the huntingtin exon 1 protein. The detailed structure and the mechanism behind this aggregation remain unclear and it is assumed that the polyQ undergoes a conformational transition to the β‐sheet structure when it aggregates. Investigating the misfolding of polyQ facilitates the determination of the molecular mechanism of aggregation and can potentially help in developing a novel approach to inhibit polyQ aggregation. Moreover, the flanking sequences of the polyQ region play a vital role in structural changes and the aggregation mechanism. We performed all‐atom molecular dynamics simulations to gain structural insights into the aggregation mechanism using eight different models with glutamine repeat lengths Q27, Q27P11, Q34, Q35, Q36, Q40, Q50, and Q50P11. In the models without flanking polyPs, we noticed that the transformation of a random coil to β‐sheet occurs when the number of Q increases. We also found that the flanking polyPs prevent aggregation by decreasing the probability of forming a β‐sheet structure. When polyQ length increases, the 17 N‐terminal flanking residues are more likely to adopt a β‐sheet conformation from α‐helix and coil. From our simulations, we suggest that at least 34 glutamines are required for initiating aggregation and 40 residues length is critical for the aggregation of huntingtin exon 1 protein for disease onset. This study provides structural insights into misfolding and the role of flanking sequences in huntingtin aggregation which will further help in developing therapeutic strategies for Huntington's disease.
Clarifying pathways to poor psychological health: The mediating role of psychosocial factors in the relationship between general psychopathology and quality of life impairment in patients diagnosed with schizophrenia
Authors: Liu Jianlin , Abdin Edimansyah , Verma Swapna , Sim Kang , Chong Siow Ann , Subramaniam Mythily
Published: January 2019

Objectives

The present study examines the latent factor structure of general psychopathology and investigates the mediating role of unmet psychosocial concerns, motivation, and medication side effects in the relationship between general psychopathology and quality of life (QOL) impairment in patients with schizophrenia.

Methods

A total of 251 patients completed self‐report measures of unmet psychosocial concerns, motivation, medication side effects, and physical/mental QOL impairment. The severity of schizophrenia was assessed on the Positive and Negative Syndrome Scale.

Results

Exploratory factor analysis revealed one latent factor (emotional distress) of general psychopathology. Mediation path analyses controlling for confounding variables revealed significant indirect effects of unmet psychosocial concerns, motivation, and medication side effects on emotional distress and physical/mental QOL impairment.

Conclusions

Our findings suggest that identifying optimal methods of managing co‐occurring emotional distress as well as secondary psychosocial factors on psychological health may improve QOL among patients diagnosed with schizophrenia.
I won't obey!: Psychologically Controlling Parenting and (Non)‐Clinical Adolescents' Responses to Rule‐setting
Authors: Brenning Katrijn M. , Antrop Inge , Van Petegem Stijn , Soenens Bart , De Meulenaere Jan , Rodríguez‐Meirinhos Ana , Vansteenkiste Maarten
Published: January 2019

Objectives

This study examined associations between maternal psychologically controlling parenting and adolescents’ responses to rule‐setting as well as the link between both study variables and adolescents’ internalizing and externalizing problems.

Method

Both clinical and nonclinical adolescents reported upon maternal psychological control, responses to rule‐setting (i.e., oppositional defiance, submissive compliance, negotiation, and accommodation) and both adolescents and mothers reported upon adolescents’ problems.

Results

Perceived psychological control related positively to adolescents’ oppositional defiance and submissive compliance and negatively to negotiation and accommodation. Further, an integrated path model indicated that psychological control related to externalizing problems via oppositional defiance and internalizing problems via submissive compliance.

Conclusions

Psychological control relates to different types of problem behaviors via diverse responses to maternal rule‐setting. The discussion emphasizes the importance of future prevention and intervention programs to focus on both parenting and on adolescents’ active contribution to their socialization process.
Investigation of indolamine 2, 3 dioxygenase (IDO‐1) gene expression by real‐time PCR among patients with lung cancer
Authors: Haji Mazdarani Mojtaba , Jafarikia Milad , Nemati Fahimeh
Published: January 2019

Introduction

The aim of this study was to evaluate the expression of IDO‐1 gene and cancerous grades of non‐small cell lung cancer (NSCLC) and its subclasses among patients with lung cancer using real‐time polymerase chain reaction (PCR).

Materials and Methods

A total of 35 clinical samples were collected from patients with NSCLC. To evaluate the IDO‐1 gene after the extraction of RNA and complementary DNA (cDNA) synthesis using real‐time PCR, the expression of the gene was investigated. The western blot analysis method was used for protein expression.

Results

The highest grade, IIIa grade included six patients (17.1%). Approximately 74% of adenocarcinoma cases were in T‐categories of lung cancer and 25% of patients in IIIa grade. Patients in the IIA and IIB categories belong to the SCC subclass. Results showed that the expression of INDO 5.22 fold gene was more common in patients with lung cancer than NSCLC. Protein expression in western blot analysis in patients compared with normal 3.22 fold change increased.

Conclusion

The evidence shows that IDO‐1 is a key parameter that inhibits antitumor immune responses in humans. This study has added interesting data to the
IDO community for analyzing the expression of cancerous human cancer cells and cancer tissue in humans. The results showed that
IDO‐1 not only participates in the process of escape from tumor immunity but can also contribute to the safety of the pretumor area. A wide variety of observed
IDO‐1 expression values ​​among patients may present serious barriers to the clinical performance of anti‐
IDO strategies at present.
Mycobacterium avium paratuberculosis and Mycobacterium avium complex and related subspecies as causative agents of zoonotic and occupational diseases
Authors: Eslami Majid , Shafiei Morvarid , Ghasemian Abdolmajid , Valizadeh Saeid , Al‐Marzoqi Ali Hussein , Shokouhi Mostafavi Seyyed Khalil , Nojoomi Farshad , Mirforughi Seyede Amene
Published: January 2019

Mycobacterium avium complex (MAC) and
Mycobacterium avium paratuberculosis (MAP) cause zoonotic infections transmitted by birds and livestock herds. These pathogens have remained as serious economic and health threats in most areas of the world. As zoonotic diseases, the risk of development of occupational disease and even death outcome necessitate implementation of control strategies to prevent its spread. Zoonotic MAP infections include Crohn’s disease, inflammatory bowel disease, ulcerative colitis, sarcoidosis, diabetes mellitus, and immune‐related diseases (such as Hashimoto’s thyroiditis). Paratuberculosis has classified as type B epidemic zoonotic disease according to world health organization which is transmitted to human through consumption of dairy and meat products. In addition, MAC causes pulmonary manifestations and lymphadenitis in normal hosts and human immunodeficiency virus (HIV) progression (by serotypes 1, 4, and 8). Furthermore, other subspecies have caused respiratory abscesses, neck lymph nodes, and disseminated osteomyelitis in children and ulcers. However, the data over the occupational relatedness of these subspecies is rare. These agents can cause occupational infections in susceptible herd breeders. Several molecular methods have been recognized as proper strategies for tracking the infection. In this study, some zoonotic aspects, worldwide prevalence and control strategies regarding infections due to MAP and MAC and related subspecies has been reviewed.
Dexamethasone interferes with osteoblasts formation during osteogenesis through altering IGF‐1‐mediated angiogenesis
Authors: Xu Shengsong , Guo Rui , Li Pei‐Zhi , Li Ke , Yan Yu , Chen Jianlong , Wang Guang , Brand‐Saberi Beate , Yang Xuesong , Cheng Xin
Published: January 2019

Dexamethasone (Dex), a synthetic glucocorticoid (GC) with long‐lasting treatment effects, has been proved to exert a modulatory effect on osteoblast proliferation and differentiation during embryonic osteogenesis. However, it is still controversial if Dex exposure influences endochondral ossification and the underlying mechanism. In this study, chick embryos in vivo and preosteoblast cell cultures in vitro were utilized to investigate the effects of Dex on osteoblast formation and differentiation during the skeletal development. We first demonstrated that Dex exposure could shorten the long bones of 17‐day chick embryos in vivo, and also downregulated the expressions of osteogenesis‐related genes. Next, we established that Dex exposure inhibited the proliferation and viability of preosteoblasts‐MC3TC‐E1 cells, and the addition of insulin‐like growth factor 1 (IGF‐1) could dramatically rescue these negative effects. On the basis of remarkable changes in the rescue experiments, we next verified the important role of angiogenesis in osteogenesis by culturing isolated embryonic phalanges in Dulbecco's modified Eagle's medium culture or on the chick chorioallantoic membrane (CAM). Then, we transplanted MC3T3‐E1 cell masses onto the CAM. The data showed that Dex exposure reduced the vessel density within the developed cell mass, concomitantly with the downregulation of IGF‐1 pathway. We verified that the inhibition of blood vessel formation caused by Dex could be rescued by IGF‐1 treatment using the CAM angiogenesis model. Eventually, we demonstrated that the shortened length of the phalanges in the presence of Dex could be reversed by IGF‐1 addition. In summary, these findings suggested that the inhibition of Igf‐1 signal caused by Dex exposure exerts a detrimental impact on the formation of osteoblasts and angiogenesis, which consequently shortens long bones during osteogenesis.
Dihydrotestosterone synthesis in the sheep corpus luteum and its potential mechanism in luteal regression
Authors: Xiao Longfei , Song Liangli , Hu Junjie , Zhang Quanwei , Jiang Yuting , Duan Hongwei , Zhang Yong , Zhao Xingxu , Hua Yongli
Published: January 2019

Corpus luteum (CL) regression is a complex physiological process. Previous studies have shown that dihydrotestosterone (DHT) may be involved in regulating CL regression, but the mechanism is still unclear. In this study, we evaluated the localization of the two isoforms of DHT synthetase 5α‐reductase (5α‐red1 and 5α‐red2) and androgen receptor (AR) in sheep CL, and investigated 5α‐red1, 5α‐red2, AR, and DHT levels at different luteal stages of CL (early, middle, and late phase) by immunohistochemistry, quantitative real‐time polymerase chain reaction, and western blot analysis. Moreover, we cultured luteal cells from middle phase CL and treated them with different concentrations of DHT (10−10–10
−6 M) and the AR antagonist flutamide (10
−5 M), to evaluate whether DHT is involved in the regulation of progesterone (P4) secretion and progesterone nuclear receptor (PGR) expression and whether these effects are regulated by the AR pathway. We also investigated the effects of DHT and flutamide on prostaglandin F2α (PGF2α) secretion and apoptotic gene and protein expression. Our results showed that 5α‐red1, 5α‐red2, and AR were expressed in the CL, and their expression and DHT levels were changed during the luteal phase. DHT was involved in mediating P4 and PGF2α secretion and PGR and apoptotic gene and protein expression. The effects of DHT on CL were at least partially regulated by the AR pathway. This study reveals the mechanism of action of DHT on sheep CL regression and lays the foundation for further exploration of androgen regulation of CL function.
Impairment of cognitive function in ornithine transcarbamylase deficiency is global rather than domain‐specific and is associated with disease onset, sex, maximum ammonium, and number of hyperammonemic events
Authors: Buerger Corinna , Garbade Sven F. , Dietrich Alber Fabienne , Waisbren Susan E. , McCarter Robert , Kölker Stefan , Burgard Peter ,   on behalf of the Urea Cycle Disorders Consortium
Published: January 2019

Beginning in 2006, the Urea Cycle Disorders Consortium (UCDC) has conducted a longitudinal study of eight inherited deficiencies of enzymes and transporters of the urea cycle, including 444 individuals with ornithine transcarbamylase deficiency (OTCD), of whom 300 (67 males, 233 females) received psychological evaluation. In a cross‐sectional study (age range, 3‐71 years), analysis of covariance (ANCOVA) determined the association between outcomes in five cognitive domains (global intelligence, executive functions, memory, visuomotor integration, visual perception) and sex, age at testing and timing of disease onset defined as early onset (≤28 days; EO), late onset (LO), or asymptomatic (AS). The dataset of 183 subjects with complete datasets (31 males, 152 females) revealed underrepresentation of EO subjects (2 males, 4 females), who were excluded from the ANCOVA. Although mean scores of LO and AS individuals were within 1 SD of the population norm, AS subjects attained significantly higher scores than LO subjects and males higher scores than females. Correlations between cognitive domains were high, particularly intelligence proved to be a distinguished indicator for cognitive functioning. Maximum plasma ammonium concentration and intelligence correlated significantly higher in EO (r = −0.47) than in LO subjects (r = 0.04). Correlation between the number of hyperammonemic events and intelligence scores were similar for EO (r = −0.30) and LO (r = −0.26) individuals. The number of clinical symptoms was significantly associated with intelligence (r = −0.28) but not with scores in other domains. Results suggest that OTCD has a global impact on cognitive functioning rather than a specific effect on distinct cognitive domains.
Automated production of [68Ga]Ga‐DOTANOC and [68Ga]Ga‐PSMA‐11 using a TRACERlab FXFN synthesis module
Authors: Garcia‐Arguello Segundo Francisco , Lopez‐Lorenzo Beatriz , Ruiz‐Cruces Rafael
Published: January 2019

The interest in gallium‐68 labelled positron‐emission tomography probes continues to increase around the world. However, one of the barriers for routine clinical use is the cost of the automated synthesis units for relatively simple labelling procedures. Herein, we describe the adaptation of a TRACERlab FXFN synthesis module for the automated production of gallium‐68 radiopharmaceuticals using a cation‐exchange cartridge for postprocessing of the 68Ge/68Ga generator eluate. The recovery of activity from the cartridge was 95.6% to 98.9% using solutions of acidified sodium chloride (5 M with pH = 1‐3). The radiosyntheses of [68Ga]Ga‐DOTANOC and [68Ga]Ga‐PSMA‐11 were performed using acetate sodium buffer or 4‐(2‐hydroxyethyl)piperazine‐1‐ethanesulfonic acid, with a total duration of 21 and 23 minutes, respectively, including generator elution and radiopharmaceutical dispensing. Activity yields were 77% ± 2% for [68Ga]Ga‐PSMA‐11 and 68% ± 3% for [68Ga]Ga‐DOTANOC (n > 100). The labelled peptides had a radiochemical purity exceeding 97%, and all quality control parameters were in conformity with the limits prescribed by the European Pharmacopoeia.
Ontogeny of the catfish pectoral‐fin spine (Teleostei: Siluriformes)
Authors: Kubicek Kole M. , Britz Ralf , Conway Kevin W.
Published: January 2019

The characteristic and morphologically variable pectoral‐fin spine of catfishes (order Siluriformes) has been well‐investigated based on later developmental stages (juveniles and adults) but information on the earliest life stages are lacking. Here, we document the ontogeny of pectoral‐fin spines in four siluroid (Ictalurus punctatus, Noturus gyrinus, Silurus glanis and Akysis vespa) and two loricarioid catfishes (Corydoras panda and Ancistrus sp.). To further our understanding of pectoral‐fin spine development, we also examined adult and juvenile specimens representing 41 of the currently 43 recognized families of catfishes. Development of the pectoral‐fin spine is similar in all catfishes and resembles the development of a typical soft fin ray. Fusion between hemitrichia of the anteriormost lepidotrichium occurs proximally first, forming the spine proper, with growth of the spine occurring through the subsequent fusion of developing distal hemitrichial segments that comprise the spurious ray. The variation of pectoral‐fin spine morphology observed is largely attributed to the presence/absence of five traits, which either develop as part of the hemitrichial segments that are added to the distal tip of the spine during growth (distal rami, anterior/posterior serrae) or develop independent of these segments (denticuli and odontodes).
Modeling and simulation of dual‐material‐gate AlGaN/GaN high‐electron‐mobility transistor using finite difference method
Authors: Kandasamy Sowmya , N.B. Balamurugan
Published: January 2019

A model for a dual‐material‐gate AlGaN/GaN high‐electron‐mobility transistor has been developed by a finite difference method. The method permits the modeling of dual material as two individual single materials by splitting the 2‐D Poisson equation into two separate 1‐D equations. The unified model of two separate 1‐D equations is formed by applying the boundary conditions. The proposed model estimates the surface potential, electric field, threshold voltage, and drain current by considering the work functions of two metal gates, their length difference, and applied drain voltage. The accuracy of the model can be verified using Technology Computer‐Aided Design (TCAD) simulations.
Effects of growth conditions on siderophore producing bacteria and siderophore production from Indian Ocean sector of Southern Ocean
Authors: Sinha Alok K. , Parli Venkateswaran Bhaskar , Tripathy Sarat C. , Sarkar Amit , Prabhakaran Sabu
Published: January 2019

Iron is an important element for growth and metabolism of all marine organisms, including bacteria. Most (99.9%) of iron in oceans are bound to organic ligands like siderophores and siderophore‐like compounds. Distribution of bioavailable iron mainly depends on pH and temperature of the ocean. Due to global warming and ocean acidification, bioavailability of iron may alter and in turn effect the response of marine bacteria. In this study, we investigated the effect of growth conditions like pH, temperature, and iron (III) concentrations on growth and siderophore production in selected heterotrophic bacteria isolated from waters around Kerguelen Islands (KW) and Prydz Bay (PB). Microcosm experiments were carried out on two KW‐isolates (Enterococcus casseliflavus and Psychrobacter piscatorii) and five PB‐isolates (Pseudoalteromonas tetraodonis, Bacillus cereus, Psychrobacter pocilloporae, Micrococcus aloeverae, and Pseudomonas weihenstephanensis) which produced either hydroxamate‐type or catecholate‐type siderophores. Increasing iron concentrations (10 nM to 50 μM) increased the growth rate of all isolates while siderophore production (% siderophore) generally reduced at higher iron concentration. Siderophore production peaked at early log phase, probably in response to higher iron‐demand. Temperature and pH experiments showed that most isolates produced more siderophore at 15 and 25 °C temperature and pH 8.5. These results reveal that in future ocean conditions (warmer and acidified waters), bacterial growth and siderophore production may get affected and thereby influencing iron uptake and associated biogeochemical processes.
Characterization of the chondrogenic and osteogenic potential of male and female human muscle‐derived stem cells: Implication for stem cell therapy
Authors: Scibetta Alex C. , Morris Elizabeth R. , Liebowitz Andrea B. , Gao Xueqin , Lu Aiping , Philippon Marc J. , Huard Johnny
Published: January 2019

People of all backgrounds are susceptible to bone and cartilage damage, and these injuries can be debilitating. Current treatments for bone and cartilage injuries are less than optimal, and we are interested in developing new approaches to treat these diseases, specifically using human muscle‐derived stem cells (hMDSCs). Our lab previously demonstrated that sex differences exist between male and female murine MDSCs; thus, this paper sought to investigate whether sex differences also exist in hMDSCs. In the present study, we characterized the chondrogenic and osteogenic sex differences of hMDSCs in vitro and in vivo. We performed in vitro osteogenic and chondrogenic differentiation using hMDSC pellet cultures. As demonstrated by microCT, histology, and immunohistochemistry, male hMDSCs were more chondrogenic and osteogenic than their female counterparts in vitro. No differences were observed based on the sex of hMDSCs in osteogenic and chondrogenic gene expression and cell surface markers. For our in vivo study, we transduced hMDSCs with lenti‐BMP2/GFP and transplanted these cells into critical‐sized calvarial defects in mice. MicroCT results revealed that male hMDSCs regenerated more bone at 2 weeks and demonstrated higher bone density at 4 and 6 weeks than female hMDSCs. Histology demonstrated that both male and female hMDSCs regenerated functional bone. Clinical relevance: These studies reinforce that stem cells isolated from male and female patients differ in function, and we should disclose the sex of cells used in future studies. Considering sex differences of hMDSCs may help to improve cell‐based therapies for autologous cell treatment of bone and cartilage damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1339–1349, 2019.
Tissue sealants for the prevention of lymphoceles after radical inguinal lymph node dissection in patients with melanoma: A systematic review and individual patient data meta‐analysis
Authors: Gerken Andreas L. H. , Dobroschke Jakob , Reißfelder Christoph , Hetjens Svetlana , Braun Volker , Di Monta Gianlica , Jakob Jens , Hohenberger Peter , Nowak Kai , Herrle Florian
Published: January 2019

Background and Objectives

Postoperative lymphoceles and further wound complications occur frequently after radical inguinal lymph node dissection (ILND). In various studies, tissue sealants have shown to reduce the incidence of postoperative morbidity.

Methods

A systematic review and meta‐analysis of randomized controlled trials (RCTs) investigating the effectiveness of tissue sealants in reducing the incidence of postoperative lymphoceles following ILND in patients with melanoma was conducted. Individual patient data was requested to pool the data for meta‐analysis appropriately.

Results

Thousand seven hundred twenty‐nine manuscripts were screened for eligibility. Six RCTs published between 1986 and 2012 were identified including 194 patients for ILND. Only four RCTs were included in the meta‐analysis. No study properly defined the term “lymphocele.” Tissue sealants failed to influence the duration of drain placement (mean difference [MD] = −3.05 days; z = 1.18;
P = 0.24), total drainage volume (MD = 598.39 mL;
z = 1.49;
P = 0.14), the incidence of postoperative seroma, wound infection and skin necrosis.

Conclusions

No improvement was identified with the use of tissue sealants, however, a valid comparison of the results of included trials was difficult owing to the lack of a definition of the term “lymphocele.” Other surgical techniques and trials using validated endpoint definitions are required to reevaluate these findings.
Number of positive lymph nodes better predicts survival for oral cavity cancer
Authors: Lee Hojun , Roh Jong‐Lyel , Cho Kyung‐Ja , Choi Seung‐Ho , Nam Soon Yuhl , Kim Sang Yoon
Published: January 2019

Background

We compared the predictive ability of our proposed N classification with that of the American Joint Committee on Cancer (AJCC) nodal (N) classification for oral cavity squamous cell carcinoma (OCC).

Methods

We assessed 345 OCC patients who underwent primary tumor extirpation and neck lymph node (LN) dissection. N classification was analyzed by recursive partitioning analysis and compared with the AJCC N classification by c‐index. Cox proportional hazards regression analyses were used to determine associations between tumor or nodal factors and disease‐free survival (DFS) or overall survival (OS).

Results

Positive LNs were found in 149 patients (43.2%). In multivariate models, the number of positive LNs and LN ratio strongly associated with DFS and OS (P < 0.001). Our new N classification was proposed with four categories of N0, N1 (1 positive LN), N2 (2‐4 positive LNs or extranodal extension > 2 mm), and N3 (≥5 positive LNs). The c‐index for the proposed N classification showed improvement in survival predictions (0.735; 95% CI, 0.703‐0.767) compared with the AJCC N classification (0.701; 0.667‐0.735).

Conclusions

The number of positive LNs and LN ratios strongly associated with posttreatment recurrence and survival for OCC. Using positive LN numbers with the N classification improves OCC survival predictions.
Design, construction, and application of a regional ocean database: A case study in Jiaozhou Bay, China
Authors: Yuan Yuan , Jalón‐Rojas Isabel , Wang Xiao Hua , Song Dehai
Published: January 2019

Access to geophysical data poses a challenge in Oceanography and Marine Sciences. Ocean databases are an efficient solution to storing, standardizing, validating, and sharing marine and environmental data. However, ocean databases of regional seas and coastal systems are still rare. In this article, we describe a regional ocean database for Jiaozhou Bay, a coastal system affected by increasing anthropogenic activities, such as land reclamation, a cross‐bay bridge construction, and land‐based pollutant discharges. Understanding the impact of human activities on Jiaozhou Bay requires a comprehensive range of research on biogeochemical and physical changes, and on the current environmental state of the bay. The Jiaozhou Bay database described here aims to inform this key research and also to serve as a reference for the future development of regional ocean databases. It includes three kinds of variables: on‐site, satellite, and modeling data. The database structure is unified and incorporates file names, header information (including metadata), measured values and data‐quality flags, which facilitate data exchange and use. We propose a system of data‐quality flags, based on 13 checks that encompass quality control of the different kinds of variables (e.g., satellite 2D data and on‐site profile data). Three examples, one for each type of data, illustrate the use and value of the Jiaozhou Bay database in better understanding the oceanographic characteristics of this bay and the impact of intensive anthropogenic activities on its marine environment.
Oxidation behavior of austenitic steel Sanicro25 and TP347HFG in supercritical water
Authors: Zhu Zhongliang , Jiang Dongfang , Cao Qi , Xu Hong , Khan Hasan Izhar , Zhang Naiqiang
Published: January 2019

Oxidation tests of austenitic steel Sanicro25 and TP347HFG were implemented at 600–700 °C in supercritical water under 25 MPa without dissolved oxygen. With an increase in temperature, the weight change of TP347HFG steel increases significantly while the weight change of Sanicro25 increases relatively slow. A double layer oxide scale formed on TP347HFG and Sanicro25 steel, which was composed of Fe‐rich oxide layer and a Cr‐rich inner oxide layer. Small amount of Cr2O3 was observed for TP347HFG but a continuous Cr2O3 formed at interface of oxide and matrix for Sanicro25 at 600 and 700 °C. Furthermore, Fe2O3 is detected at 600–700 °C for Sanicro25. The effect mechanism of temperature and the Cr content on oxidation rate and oxide composition were discussed.
Highly Thermally Conductive Polyimide Composites via Constructing 3D Networks
Authors: Ding Dongliang , Wang Haitao , Wu Zhiqiang , Chen Yanhui , Zhang Qiuyu
Published: January 2019

Easy and high efficient methods are in great demand to obtain polyimide (PI) composites with high thermal conductivity in the electronic packaging field. In this work, PI/boron nitride (BN) composites with high thermal conductivity are easily fabricated. Tightly connected and well‐arranged BN platelets construct effective 3D thermally conductive networks in the PI matrix upon hot pressing, after BN platelets are coated on the surface of PI granules by the help of a kind of PI adhesive. The thermal conductivity of the PI/BN composites reaches as high as 4.47 W mK–1at a low BN loading of 20 vol%, showing an enhancement of 2099%, compared to pure PI. Such enhancement of the thermal conductivity is the highest compared with the results in the open literature. Our work is a good example that utilized the sufficient physical connection (aggregates) of thermally conductive fillers to significantly promote the thermal conductivity of polymer composites.
Venous bypass grafts versus arteriovenous loops as recipient vessels for microvascular anastomosis in lower extremity reconstructions: A matched‐pair analysis
Authors: Henn Dominic , Bigdeli Amir K. , Horsch Miriam , Weiß Christel , Kühner Clemens , Hirche Christoph , Schmidt Volker J. , Kneser Ulrich
Published: January 2019

Background

Limb salvage in patients with peripheral vascular disease (PVD) and soft tissue defects often requires both a restoration of blood flow to the lower extremity and soft tissue coverage. Outcomes of free tissue transfer may be affected by vein grafts, which can be used for the placement of an autologous venous bypass or an arteriovenous (AV) loop leading to different hemodynamic situations. The purpose of this study was to investigate whether free flap anastomosis to a bypass or an AV loop can be performed with comparable results.

Methods

We performed a matched‐pair analysis of 22 patients with PVD undergoing free flap reconstructions of the lower extremity with end‐to‐side anastomosis to an autologous venous bypass (n = 11, 1 female and 10 male patients) or an AV loop (n = 11, 2 female and 9 male patients). Defects caused by trauma, infection, ulcer, or fasciotomy were reconstructed in each group with 5 muscle‐based flaps, 3 parascapular flaps, 2 anterolateral thigh (ALT) flaps, and 1 conjoined latissimus dorsi and parascapular flap. Postoperative complications including thromboses, flap failures, wound complications, and hematomas were compared.

Results

Postoperative complication rates including 1 venous pedicle thrombosis (9%vs. 0%, P = 1.0), minor (18% vs. 9%, P = 1.0) and major wound complications (45% vs. 27%, P = .69) as well as hematomas (27% vs. 36%, P = 1.0) did not show relevant differences between the groups. Flap failures were absent in both groups.

Conclusion

In patients with PVD, autologous venous bypass grafts may be used for end‐to‐side anastomoses of free flaps, with postoperative outcomes being comparable to AV loop reconstructions.
Relative energy approach to a diffuse interface model of a compressible two‐phase flow
Authors: Feireisl Eduard , Petcu Madalina , Pražák Dalibor
Published: January 2019

We propose a simple model for a two‐phase flow with a diffuse interface. The model couples the compressible Navier‐Stokes system governing the evolution of the fluid density and the velocity field with the Allen‐Cahn equation for the order parameter. We show that the model is thermodynamically consistent, in particular, a variant of the relative energy inequality holds. As a corollary, we show the weak‐strong uniqueness principle, meaning any weak solution coincides with the strong solution emanating from the same initial data on the life span of the latter. Such a result plays a crucial role in the analysis of the associated numerical schemes. Finally, we perform the low Mach number limit obtaining the standard incompressible model.
Multistrain edge‐based compartmental model on networks
Authors: Lv JianPing , Jin Zhen
Published: January 2019

Multistrain diseases, which are infected through individual contacts, pose severe public health threat nowadays. In this paper, we build competitive and mutative two‐strain edge‐based compartmental models using probability generation function (PGF) and pair approximation (PA). Both of them are ordinary differential equations. Their basic reproduction numbers and final size formulas are explicitly derived. We show that the formula gives a unique positive final epidemic size when the reproduction number is larger than unity. We further consider competitive and mutative multistrain diseases spreading models and compute their basic reproduction numbers. We perform numerical simulations that show some dynamical properties of the competitive and mutative two‐strain models.
Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders
Authors: Hou Chen , Zhang Weimin , Li Jianke , Du Lin , Lv Ou , Zhao Shengjuan , Li Jia
Published: January 2019

Pomegranate (Punica granatum Linn) is used in the prevention and treatment of metabolic syndrome in recent decades. Imbalances in lipid metabolism are profound features of metabolic disorders. In vivo and in vitro studies have shown that extracts of different pomegranate fractions (peels, flowers, juice, and seeds) regulate lipid metabolism in metabolic‐disorder‐associated diseases such as atherosclerosis, nonalcoholic fatty liver disease, and type 2 diabetes, helping to alleviate the development of diseases. Amelioration of oxidative stress and the inflammatory response is considered an important reason underlying the regulation of lipid metabolism by pomegranate extracts. Mitochondria, the major cellular site for lipid oxidation, are strongly associated with cellular oxidative and inflammatory status and are likely to be a target for pomegranate extract action. This review summarizes the main findings about the effects of different pomegranate fraction extracts on lipid metabolism in metabolic‐disorder‐associated diseases and analyses how pomegranate extracts achieve their effects. Furthermore, it also provides an important basis for the research and development of pomegranate‐related nutrients or drugs.
Antihypertensive Potential of Coenzyme Q10 via Free Radical Scavenging and Enhanced Akt‐nNOS Signaling in the Nucleus Tractus Solitarii in Rats
Authors: Chen Hsin‐Hung , Yeh Tung‐Chen , Cheng Pei‐Wen , Ho Wen‐Yu , Ho Chiu‐Yi , Lai Chi‐Cheng , Sun Gwo‐Ching , Tseng Ching‐Jiunn
Published: January 2019

Scope

In the Natural Medicines database, coenzyme Q10 (CoQ10) is classified as possibly effective for the treatment of hypertension. Patients with hypertension frequently have a significant deficiency of the antioxidant CoQ10. Furthermore, reactive oxygen species are overproduced in the nucleus tractus solitarii (NTS) during the cardiovascular regulation of hypertension in vivo. However, the molecular mechanisms by which CoQ10 modulates cardiovascular functions in the NTS are unclear. In this study, the effects of CoQ10 on superoxide generation, downstream NO signaling in the NTS, and blood pressure were evaluated in rats with fructose‐induced hypertension.

Methods and Results

Treatment with oral CoQ10 for 4 weeks abolished nicotinamide adenine dinucleotide phosphate‐oxidase (NADPH oxidase) activation, decreased p38 phosphorylation, and increased superoxide dismutase 2 production in the NTS of fructose‐fed rats. The serum levels of uric acid decrease in response to CoQ10 treatment in fructose‐fed rats. Oral CoQ10 reduced blood pressure by inducing Akt and nNOS phosphorylation in NTS of fructose‐induced hypertensive rats.

Conclusion

Oral CoQ10 decreases blood pressure by negatively regulating fructose‐induced NADPH oxidase levels, abolishing ROS generation, reducing p38 phosphorylation, and enhancing the Akt‐nNOS pathway in the NTS. These results support the beneficial effects of CoQ10 in oxidative stressassociated hypertension.
The myotonic dystrophy experience: a North American cross‐sectional study
Authors: Hagerman Katharine A. , Howe Sarah J. , Heatwole Chad R. ,   the Christopher Project Reference Group
Published: January 2019

Introduction: Myotonic dystrophy (DM) is a chronic, multisystemic, neurological condition. Patients and caregivers are uniquely suited to identify what symptoms are most important and highlight the unmet needs that are most relevant to DM. Methods: We conducted a North American, cross‐sectional study of people with DM type‐1, congenital DM, and DM type‐2 and their family members. We sent patients and caregivers separate surveys to identify and quantitate the issues of greatest importance, examine the differences between groups, and identify the most important challenges experienced by this population. Results: 1,180 people with DM and 402 family members/caregivers responded to the surveys. They reported considerable physical and cognitive symptoms, extensive diagnostic delays, and varying clinical phenotypes on the basis of DM type. Discussion: Marked disease burden and numerous unmet needs exist in DM. These needs vary based on DM type and highlight the complex clinical phenotypes of these neurological disorders. Muscle Nerve 59:457–464, 2019