bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in epitope‐specific antibodies to pertussis toxin after infection and acellular vaccinations
Authors: Knuutila Aapo , Dalby Tine , Barkoff Alex‐Mikael , Jørgensen Charlotte Sværke , Fuursted Kurt , Mertsola Jussi , Markey Kevin , He Qiushui
Published: August 2020

Objectives

Pertussis toxin (PT) is a component of all acellular pertussis vaccines. PT must be detoxified to be included in acellular vaccines, which results in conformational changes in the functional epitopes of PTs. Therefore, induced epitope‐specific antibodies to PT may vary after vaccinations or natural infections, and this information could reveal biomarkers implicated for protection and successful immunisation.

Methods

Pertussis toxin epitope‐specific antibodies in sera from 152 vaccinated children and 72 serologically confirmed patients were tested with a blocking ELISA, based on monoclonal antibodies that target protective PT epitopes.

Results

All study groups induced considerable antibody titres to subunit 1 (S1). Of interest, S3 7E10‐specific antibodies were present in patients, but not after vaccinations (P < 0.001). The impact of glutaraldehyde treatment of PT was visible on epitope 1D7 (S1), whereas epitopes 1B7 (S1) and 10D (S1) were more preserved. Antibodies to these epitopes were higher after three primary vaccine doses than after a single booster dose.

Conclusion

The high amount of 7E10‐specific antibodies in patients suggests this epitope might be functionally relevant in protection. The overall characteristics of epitope‐specific antibodies are influenced by infection or vaccination background, by the used detoxification method of PT and by the amount of the toxin used in immunisation.
OMIP‐068: High‐Dimensional Characterization of Global and Antigen‐Specific B Cells in Chronic Infection
Authors: Cascino Katherine , Roederer Mario , Liechti Thomas
Published: August 2020

This 24‐color flow cytometry panel focuses on characterizing antigen‐specific B cells and precise delineation of B‐cell subsets in chronic infections and is applicable to other chronic diseases such as autoimmunity. The panel was optimized for human cryopreserved peripheral blood mononuclear cells (PBMCs). Markers were chosen to extensively distinguish B‐cell lineages (CD19, CD20, CD10, CD38, CD24, IgM, IgD, CD27, CD21, CD43, CD5). Inclusion of antigen‐specific probes was of high priority in order to assess hepatitis B virus (HBV) antigen‐specific B cells for our purposes. These probes can be readily exchanged for other pathogen‐specific probes or additional markers for the panel to be tailored to desired research questions beyond HBV. In addition, we included a comprehensive and unique set of functional markers such as chemokine receptors (CXCR3, CXCR5), co‐stimulatory molecule (CD86), Fc receptor (CD32), regulatory molecules (BTLA, CD39), and inhibitory markers associated with chronic infections (PD‐1, FcRL5, CD11c, CD22) to enable in‐depth analysis of global and antigen‐specific B cells during chronic infection. © 2020 International Society for Advancement of Cytometry
Performance analysis of handover delay and buffer capacity in mobile OpenFlow‐based networks
Authors: Panev Strahil , Latkoski Pero
Published: August 2020

Software‐defined networking (SDN) is a network concept that brings significant benefits for the mobile cellular operators. In an SDN‐based core network, the average service time of an OpenFlow switch is highly influenced by the total capacity and type of the output buffer, which is used for temporary storage of the incoming packets. In this work, the main goal is to model the handover delay due to the exchange of OpenFlow‐related messages in mobile SDN networks. The handover delay is defined as the overall delay experienced by the mobile node within the handover procedure, when reestablishing an ongoing session from the switch in the source eNodeB to the switch in the destination eNodeB. We propose a new analytical model, and we compare two systems with different SDN switch designs that model a continuous time Markov process by using quasi‐birth–death processes: (1) single shared buffer without priority (model SFB), used for all output ports for both control and user traffic, and (2) two isolated buffers with priority (model priority finite buffering [PFB]), one for control and the other for user plane traffic, where the control traffic is always prioritized. The two proposed systems are compared in terms of total handover delay and minimal buffer capacity needed to satisfy a certain packet error ratio imposed by the link. The mathematical modeling is verified via extensive simulations. In terms of handover delay, the results show that the model PFB outperforms the model SFB, especially for networks with high number of users and high probability of packet‐in messages. As for the buffer dimensioning analysis, for lower arrival rates, low number of users, and low probability of packet‐in messages, the model SFB has the advantage of requiring a smaller buffer size.
Genetic algorithm for biobjective optimization of indoor LTE femtocell deployment
Authors: Figueras‐Benítez George E. , Badra Renny E.
Published: August 2020

The optimization of indoor femtocell base stations (FBS) placement is a highly complex problem in which multiple performance figures can be considered. In this paper, we propose a biobjective optimization approach based on non‐dominated sorting genetic algorithm II (NSGA‐II) to solve the indoor FBS deployment problem in residential scenarios where a single cell is deployed within the coverage of a single dominant interfering external macro base station (MBS). The optimization problem is formulated with the objective of jointly minimizing outage probability and maximizing normalized downlink average throughput. Several conditions are simultaneously considered under the framework of Monte Carlo simulations, such as the effect of co‐channel interference in uplink and downlink, buildings with arbitrary layouts, realistic transmission schemes and antenna radiation patterns, random user distributions, and a well‐established empirical path loss model. The proposed algorithm, which determines the location and orientation of the FBS's antenna that provides a suitable compromise between the two objective functions, is evaluated in this paper. First, two different experiments are proposed to investigate the algorithm convergence; then, statistical analyses are formulated to characterize the relation between the values achieved for both objective functions; finally, the computational load is evaluated. Results indicate the convergence of the proposed method towards the real Pareto front and a significant reduction of the computational time with respect to a reference method based on exhaustive search, while pointing at new criteria for the selection of the objective functions.
Two new genetically modified mouse alleles labeling distinct phases of retinal ganglion cell development by fluorescent proteins
Authors: Ge Yichen , Wu Fuguo , Cheng Mobin , Bard Jonathan , Mu Xiuqian
Published: August 2020

Background

During development, all retinal cell types arise from retinal progenitor cells (RPCs) in a step‐wise fashion. Atoh7 and Pou4f2 mark, and function in, two phases of retinal ganglion cell (RGC) genesis; Atoh7 functions in a subpopulation of RPCs to render them competent for the RGC fate, whereas Pou4f2 participates in RGC fate specification and RGC differentiation. Despite extensive research on their roles, the properties of the two phases represented by these two factors have not been well studied, likely due to the retinal cellular heterogeneity.

Results

In this report, we describe two novel knock‐in mouse alleles, Atoh7zsGreenCreERT2 and Pou4f2FlagtdTomato, which labeled retinal cells in the two phases of RGC development by fluorescent proteins. Also, the Atoh7zsGreenCreERT2 allele allowed for indirect labeling of RGCs and other cell types upon tamoxifen induction in a dose‐dependent manner. Further, these alleles could be used to purify retinal cells in the different phases by fluorescence assisted cell sorting (FACS). Single cell RNA‐seq analysis of purified cells from Atoh7zsGreenCreERT2 retinas further validated that this allele labeled both transitional/competent RPCs and their progenies including RGCs.

Conclusions

Thus, these two alleles are very useful tools for studying the molecular and genetic mechanisms underlying RGC formation.
On chip synthesis of Au nanoparticles by microwave heating
Authors: Takeuchi Masaya , Kishihara Mitsuyoshi , Fukuoka Takao , Yamaguchi Akinobu , Utsumi Yuichi
Published: August 2020

We demonstrated the on‐chip synthesis of Au nanoparticles achieved by a microwave‐induced reaction in a microfluidic channel. The chip structure consists of a waveguide and a microchannel through the inside of the waveguide. A postwall waveguide, in which metallic posts are continuously arranged on the side wall, is utilized to confine microwave fields. This configuration allows a solution to be inserted inside the waveguide by the microchannel passing between the metallic posts. In order to realize the miniaturization of the chip, the 24.125 GHz industrial, scientific, and medical (ISM) band is utilized instead of the commonly used 2.45 GHz ISM band. When pure water is heated in the microchannel under microwave input power of 3.0 W, temperature increases to 70°C were confirmed. In this paper, this chip is adapted to synthesize Au nanoparticles via a microwave‐induced reaction. After irradiating at a microwave power of 3.0 W and an irradiation time of 5 min, we observed absorbance and dynamic light scattering of the reactant, and the results indicated the generation of Au nanoparticles. This microwave synthesis system allows us to achieve automatic and rapid selective synthesis of nanoparticles in a solution.
Diverging responses to threats across generations in zooplankton
Authors: Sha Yongcui , Tesson Sylvie V. M. , Hansson Lars‐Anders
Published: August 2020

Our understanding on how organisms evolutionarily cope with simultaneously occurring, multiple threats over generations is still elusive. In a long‐term experimental study, we therefore exposed clones of a freshwater cladoceran, Daphnia magna, to threats from predation and ultraviolet radiation (UVR) during three consecutive parthenogenetic generations. We show that Daphnia can adapt to different sets of threats within three generations through modifying morphology, swimming behavior, or life‐history traits. When faced with predator cues, D. magna responded with reduced body size, whereas exposure to UVR induced behavioral tolerance when again exposed to this threat. Such UVR‐tolerant behavior was initially associated with a reduced clutch size, but Daphnia restored the reproductive output gradually through generations. The findings advance our understanding on how those common invertebrates, with a global distribution, are able to persist and rapidly become successful in a changing environment.
Predicted alteration of surface activity as a consequence of climate change
Authors: Gade Meaghan R. , Connette Grant M. , Crawford John A. , Hocking Daniel J. , Maerz John C. , Milanovich Joseph R. , Peterman William E.
Published: August 2020

Wildlife are faced with numerous threats to survival, none more pressing than that of climate change. Understanding how species will respond behaviorally, physiologically, and demographically to a changing climate is a cornerstone of many contemporary ecological studies, especially for organisms, such as amphibians, whose persistence is closely tied to abiotic conditions. Activity is a useful parameter for understanding the effects of climate change because activity is directly linked to fitness as it dictates foraging times, energy budgets, and mating opportunities. However, activity can be challenging to measure directly, especially for secretive organisms like plethodontid salamanders, which only become surface active when conditions are cool and moist because of their anatomical and physiological restrictions. We estimated abiotic predictors of surface activity for the seven species of the Plethodon jordani complex. Five independent data sets collected from 2004 to 2017 were used to determine the parameters driving salamander surface activity in the present day, which were then used to predict potential activity changes over the next 80 yrs. Average active seasonal temperature and vapor pressure deficit were the strongest predictors of salamander surface activity and, without physiological or behavioral modifications, salamanders were predicted to exhibit a higher probability of surface activity during peak active season under future climate conditions. Temperatures during the active season likely do not exceed salamander thermal maxima to cause activity suppression and, until physiological limits are reached, future conditions may continue to increase activity. Our model is the first comprehensive field‐based study to assess current and future surface activity probability. Our study provides insights into how a key behavior driving fitness may be affected by climate change.
Warm temperatures increase population growth of a nonnative defoliator and inhibit demographic responses by parasitoids
Authors: Ward Samuel F. , Aukema Brian H. , Fei Songlin , Liebhold Andrew M.
Published: August 2020

Changes in thermal regimes that disparately affect hosts and parasitoids could release hosts from biological control. When multiple natural enemy species share a host, shifts in host–parasitoid dynamics could depend on whether natural enemies interact antagonistically vs. synergistically. We investigated how biotic and abiotic factors influence the population ecology of larch casebearer (Coleophora laricella), a nonnative pest, and two imported parasitoids,Agathis pumilaandChrysocharis laricinellae, by analyzing (1) temporal dynamics in defoliation from 1962 to 2018, and (2) historical, branch‐level data on densities of larch casebearer and parasitism rates by the two imported natural enemies from 1972 to 1995. Analyses of defoliation indicated that, prior to the widespread establishment of parasitoids (1962 to ~1980), larch casebearer outbreaks occurred in 2–6 yr cycles. This pattern was followed by a >15‐yr period during which populations were at low, apparently stable densities undetectable via aerial surveys, presumably under control from parasitoids. However, since the late 1990s and despite the persistence of both parasitoids, outbreaks exhibiting unstable dynamics have occurred. Analyses of branch‐level data indicated that growth of casebearer populations,A. pumilapopulations, and within‐casebearer densities ofC. laricinellae—a generalist whose population dynamics are likely also influenced by use of alternative hosts—were inhibited by density dependence, with high intraspecific densities in one year slowing growth into the next. Casebearer population growth was also inhibited by parasitism fromA. pumila, but notC. laricinellae, and increased with warmer autumnal temperatures. Growth ofA. pumilapopulations and within‐casebearer densities ofC. laricinellaeincreased with casebearer densities but decreased with warmer annual maximum temperatures. Moreover, parasitism byA. pumilawas associated with increased growth of within‐casebearer densities ofC. laricinellaewithout adverse effects on its own demographics, indicating a synergistic interaction between these parasitoids. Our results indicate that warming can be associated with opposing effects between trophic levels, with deleterious effects of warming on one natural enemy species potentially being exacerbated by similar impacts on another. Coupling of such parasitoid responses with positive responses of hosts to warming might have contributed to the return of casebearer outbreaks to North America.
Transcatheter tricuspid valve repair in the setting of heart failure with preserved or reduced left ventricular ejection fraction
Authors: Kresoja Karl‐Patrik , Lauten Alexander , Orban Mathias , Rommel Karl‐Philipp , Alushi Brunilda , Besler Christian , Braun Daniel , Unterhuber Matthias , Stangl Karl , Landmesser Ulf , Massberg Steffen , Thiele Holger , Hausleiter Jörg , Lurz Philipp
Published: August 2020

Aims

Severe tricuspid regurgitation (TR) impairs prognosis in patients with left‐sided heart failure (HF) with preserved (≥50%, HFpEF) and reduced ejection fraction (<50%, HFrEF). Transcatheter tricuspid valve edge‐to‐edge repair (TTVR) potentially improves prognosis among patients with severe TR. We sought to assess the impact of left‐sided HF types on outcomes of TTVR.

Methods and results

In this retrospective study, 71 HFpEF and 40 HFrEF patients, defined according to the European Society of Cardiology criteria, with isolated TR treated by TTVR in two tertiary care centres between 2016 and 2019 were analysed. The primary outcome was a composite outcome of all‐cause mortality and HF hospitalization at 12 months [median follow‐up 238 (interquartile range 175–365) days]. Additionally, a propensity score matching with a conservatively treated cohort of 914 patients with severe TR was performed. Procedural success did not differ between HFpEF (mean age 75.9 ± 9.3 years) or HFrEF (mean age 74.7 ± 9.1 years) patients (86% vs. 78%, P = 0.299). The primary endpoint occurred more frequently in patients with HFrEF as compared to HFpEF (50% vs. 30%, P = 0.016). Procedural success was associated with a reduced occurrence of the primary endpoint among patients with HFpEF (P < 0.001) but not HFrEF (P = 0.813), while both groups showed improvement in New York Heart Association functional class (both P < 0.001). After matching for age, EuroSCORE II, presence of a right ventricular lead and systolic pulmonary artery pressure, successful TTVR was associated with lower mortality as compared to conservative therapy in HFpEF patients (P = 0.020), but not in HFrEF patients (P = 0.274).

Conclusion

Transcatheter tricuspid valve edge‐to‐edge repair might be a treatment option in patients with severe TR and HFpEF compared to conservative therapy.
Mothers’ appraisals of injustice in the context of their child’s chronic pain: An interpretative phenomenological analysis
Authors: Baert Fleur , McParland Joanna , Miller Megan Marie , Hirsh Adam Todd , Wallace Ewan , Dickson Adele , Trost Zina , Vervoort Tine
Published: August 2020

Background

In line with research highlighting the role of observer appraisals in understanding individuals’ pain experience, recent work has demonstrated the effects of parental child‐ and self‐oriented injustice appraisals on child pain‐related outcomes. However, research on parental injustice appraisals is in its infancy and lacks a valid and context‐specific operationalization of what parental injustice appraisals of child pain precisely entail. The current study presents an in‐depth qualitative analysis of parental child‐ and self‐oriented appraisals of injustice in the context of their child's chronic pain.

Methods

Twenty‐one mothers of children living with chronic pain participated in one of five focus group interviews conducted in Ghent (Belgium), Glasgow (Scotland) and Indianapolis (USA).

Results

The interviews were subjected to interpretative phenomenological analysis, which revealed three key justice‐related themes, labelled ‘You shouldn't be in this much pain’, ‘The problem's probably with the mother’ and ‘At least it's not cancer’. Maternal injustice appraisals focused mainly on the child rather than the self and reflected various perceived barriers to their efforts to provide quality of life for their child. A fourth theme labelled ‘Not everybody gets a healthy child’ reflected maternal strategies to effectively cope with the child's condition and the associated appraisals of injustice.

Conclusions

The current findings attest to the relevance of (child‐ and self‐oriented) injustice in the parental experience of caring for a child with chronic pain and provides insight into the specific content and scope of these appraisals. As such, this study provides valuable insights to further research in this area.

Significance

The current study presents an in‐depth qualitative analysis of parental appraisals of injustice in the context of their child's chronic pain condition. The findings provide valuable insights into the phenomenology of this construct and may inform future research and assessment methods. Furthermore, the themes reported in this study may contribute to clinical practice, as they may raise awareness of parental concerns regarding their child's pain management.
An insight into charge/discharge behaviors of lithium/sodium‐sulfur conversion batteries and their similarity to the lithium/sodium‐ion intercalation batteries: Relation of delivered capacity vs current rate
Authors: Kalantarian Mohammad Mahdi , TaherTalari Maryam , Yousefi‐Mashhour Hatef
Published: August 2020

This paper proposes a mathematic relationship between obtained capacity and the corresponding current rate for the Li‐S and Na‐S conversion batteries. Using experimental data on different conditions of the Li/Na‐S batteries, taken from literature, it is established that the inverse value of obtained capacity is changing linearly with respect to square root of the corresponding applied current rate. The theoretical‐based relationship has been established for the Li‐ion and Na‐ion batteries. Therefore, this paper proposes similar behavior for the conversion and intercalation batteries. The proposed relationship and its beyond approach proffer estimations of: alteration of capacity by rate, optimal cathode mass, corresponding reaction components, and fraction of (in)active particles. Also, they offer a quantitative criterion for performance and rate‐capability, the capability to justify observed phenomena, and also qualification of the powder, preparation, and assembling of the cell.
Chances and challenges of machine learning‐based disease classification in genetic association studies illustrated on age‐related macular degeneration
Authors: Guenther Felix , Brandl Caroline , Winkler Thomas W. , Wanner Veronika , Stark Klaus , Kuechenhoff Helmut , Heid Iris M.
Published: August 2020

Imaging technology and machine learning algorithms for disease classification set the stage for high‐throughput phenotyping and promising new avenues for genome‐wide association studies (GWAS). Despite emerging algorithms, there has been no successful application in GWAS so far. We establish machine learning‐based phenotyping in genetic association analysis as misclassification problem. To evaluate chances and challenges, we performed a GWAS based on automatically classified age‐related macular degeneration (AMD) in UK Biobank (images from 135,500 eyes; 68,400 persons). We quantified misclassification of automatically derived AMD in internal validation data (4,001 eyes; 2,013 persons) and developed a maximum likelihood approach (MLA) to account for it when estimating genetic association. We demonstrate that our MLA guards against bias and artifacts in simulation studies. By combining a GWAS on automatically derived AMD and our MLA in UK Biobank data, we were able to dissect true association (ARMS2/HTRA1, CFH) from artifacts (near HERC2) and identified eye color as associated with the misclassification. On this example, we provide a proof‐of‐concept that a GWAS using machine learning‐derived disease classification yields relevant results and that misclassification needs to be considered in analysis. These findings generalize to other phenotypes and emphasize the utility of genetic data for understanding misclassification structure of machine learning algorithms.
The Power of Single‐Cell Analysis for the Study of Liver Pathobiology
Authors: Chu Angela L. , Schilling Joel D. , King Kevin R. , Feldstein Ariel E.
Published: August 2020

Single cell transcriptomics has emerged as a powerful lens through which to study the molecular diversity of complex tissues such as the liver, during health and disease, both in animal models and in humans. The earliest gene expression methods measured bulk tissue RNA, but the results were often confusing because they derived from the combined transcriptomes of many different cell types in unknown proportions. To better delineate cell‐type‐specific expression, investigators developed cell isolation, purification, and sorting protocols, yet still, the RNA derived from ensembles of cells obscured recognition of cellular heterogeneity. Profiling transcriptomes at the single‐cell level has opened the door to analyses that were not possible in the past. In this review, we discuss the evolution of single cell transcriptomics and how it has been applied for the study of liver physiology and pathobiology to date.
Ten‐Eleven Translocation 1 Promotes Malignant Progression of Cholangiocarcinoma With Wild‐Type Isocitrate Dehydrogenase 1
Authors: Bai Xuewei , Zhang Hongyu , Zhou Yamei , Nagaoka Katsuya , Meng Jialin , Ji Chengcheng , Liu Dan , Dong Xianghui , Cao Kevin , Mulla Joud , Cheng Zhixiang , Mueller William , Bay Amalia , Hildebrand Grace , Lu Shaolei , Wallace Joselynn , Wands Jack R. , Sun Bei , Huang Chiung‐Kuei
Published: August 2020

Background and Aims

Cholangiocarcinoma (CCA) is a highly lethal disease without effective therapeutic approaches. The whole‐genome sequencing data indicate that about 20% of patients with CCA have isocitrate dehydrogenase 1 (IDH1) mutations, which have been suggested to target 2‐oxoglutarate (OG)–dependent dioxygenases in promoting CCA carcinogenesis. However, the clinical study indicates that patients with CCA and mutant IDH1 have better prognosis than those with wild‐type IDH1, further complicating the roles of 2‐OG‐dependent enzymes.

Approach and Results

This study aimed to clarify if ten‐eleven translocation 1 (TET1), which is one of the 2‐OG‐dependent enzymes functioning in regulating 5‐hydroxymethylcytosine (5hmC) formation, is involved in CCA progression. By analyzing The Cancer Genome Atlas (TCGA) data set, TET1 mRNA was found to be substantially up‐regulated in patients with CCA when compared with noncancerous bile ducts. Additionally, TET1 protein expression was significantly elevated in human CCA tumors. CCA cells were challenged with α‐ketoglutarate (α‐KG) and dimethyl‐α‐KG (DM‐α‐KG), which are cosubstrates for TET1 dioxygenase. The treatments with α‐KG and DM‐α‐KG promoted 5hmC formation and malignancy of CCA cells. Molecular and pharmacological approaches were used to inhibit TET1 activity, and these treatments substantially suppressed 5hmC and CCA carcinogenesis. Mechanistically, it was found that knockdown of TET1 may suppress CCA progression by targeting cell growth and apoptosis through epigenetic regulation. Consistently, targeting TET1 significantly inhibited CCA malignant progression in a liver orthotopic xenograft model by targeting cell growth and apoptosis.

Conclusions

Our data suggest that expression of TET1 is highly associated with CCA carcinogenesis. It will be important to evaluate TET1 expression in CCA tumors before application of the IDH1 mutation inhibitor because the inhibitor suppresses 2‐hydroxyglutarate expression, which may result in activation of TET, potentially leading to CCA malignancy.
Clinical Research in Hepatology in the COVID‐19 Pandemic and Post‐Pandemic Era: Challenges and the Need for Innovation
Authors: Verna Elizabeth C. , Serper Marina , Chu Jaime , Corey Kathleen , Fix Oren K. , Hoyt Karen , Page Kimberly A. , Loomba Rohit , Li Ming , Everson Gregory T. , Fried Michael W. , Garcia‐Tsao Guadalupe , Terrault Norah , Lok Anna S. , Chung Raymond T. , Reddy K. Rajender
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C and studying the natural history of many forms of chronic liver disease. National Institutes of Health, foundation, and industry funding have provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field. Instantaneously, however, all nonessential research activities were halted when the pandemic started, forcing those involved in clinical research to rethink their research strategy, including a shift to coronavirus disease 2019 research while endeavoring to maintain their preexisting agenda. Strategies to maintain the integrity of ongoing studies, including patient follow‐up, safety assessments, and continuation of investigational products, have included a shift to telemedicine, remote safety laboratory monitoring, and shipping of investigational products to study subjects. As a revamp of research is being planned, unique issues that face the research community include maintenance of infrastructure, funding, completion of studies in the predetermined time frame, and the need to reprogram career path timelines. Real‐world databases, biomarker and long‐term follow up studies, and research involving special groups (children, the homeless, and other marginalized populations) are likely to face unique challenges. The implementation of telemedicine has been dramatically accelerated and will serve as a backbone for the future of clinical research. As we move forward, innovation in clinical trial design will be essential for conducting optimized clinical research.
LPCN 1144 Resolves NAFLD in Hypogonadal Males
Authors: Albhaisi Somaya , Kim Kilyoung , Baker Jonathan , Chidambaram Nachiappan , Patel Mahesh V. , Charlton Michael , Sanyal Arun J.
Published: August 2020

Hypogonadism affects hepatic lipid metabolism and is expected to promote nonalcoholic fatty liver disease (NAFLD). The aims of this study were to determine (1) the prevalence of NAFLD in hypogonadal males and (2) the impact of correction of hypogonadism by LPCN 1144 (Lipocine, Inc., Salt Lake City, UT), an oral testosterone prodrug, on NAFLD in this population. Data were derived from a multicenter open‐label single‐arm trial of LPCN 1144 for hypogonadal males, in which a subset (n = 36) had serial magnetic resonance imaging–proton density fat fraction measurements (National Clinical Trial 03868059). NAFLD prevalence, defined by magnetic resonance imaging–proton density fat fraction ≥5%, was 66%. Eighty‐one percent of those with baseline liver fat (BL) ≥5% had improvement in liver fat content, and NAFLD resolved in 33% of subjects at 8 weeks (mean relative reduction: 45%) and 48% (mean relative reduction: 55%) after 16 weeks of LPCN 1144 therapy. The reduction in liver fat was greater in those with higher BL (BL ≥5%: 71%; BL ≥8%: 80%; and BL ≥10%: 75%). Normalization rate of alanine aminotransferase and gamma‐glutamyltransferase greater than the upper limit of normal range were 100% and 50% of treated patients, respectively. LPCN 1144 was not associated with major adverse events. Conclusion: Treatment with LPCN 1144 (oral T prodrug) in hypogonadal males with NAFLD resolved NAFLD in approximately half of the affected patients without any safety signals. Further studies are needed to validate its use in hypogonadal males with nonalcoholic steatohepatitis.
Health Care Resource Use and Cost Burden of Chronic Kidney Disease in Patients With Chronic Liver Disease: A Real‐World Claims Analysis
Authors: Rustgi Vinod K. , Li You , John Tina , Catalano Carolyn , Elsaid Mohamed I.
Published: August 2020

Chronic Liver Disease (CLD) is associated with an increased risk of chronic kidney disease (CKD). However, the health care burden of CKD in the CLD spectrum is unknown. We aimed to evaluate the health care use and cost burdens associated with CKD in patients with CLD in the United States by using real‐world claims data. We analyzed data from the Truven Health MarketScan Commercial Claims database from 2010 to 2015. A total of 19,664 patients with CLD with or without comorbid CKD were identified using International Classification of Diseases, Ninth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service‐specific unadjusted and adjusted health care parameters were analyzed for the 12 months following an index date selected at random to capture whole disease burdens. In CLD, comorbid CKD was associated with a higher annual number of claims per person (CKD vs. no CKD, 69 vs. 55) and higher total annual median health care costs (CKD vs. no CKD, $21,397 vs. $16,995). A subanalysis stratified by CKD category showed that health care use and cost burden in CLD increased with disease stage, with a peak 12‐month median cost difference of $77,859 in patients on dialysis. The adjusted per person annual health care cost was higher for CKD cases compared to controls ($35,793 vs. $24,048, respectively; P < 0.0001). Stratified by the type of CLD, the highest between‐group adjusted cost differences were for cirrhosis, viral hepatitis, hemochromatosis, and nonalcoholic fatty liver disease. Conclusion: CKD is a cost multiplier in CLD. The CKD health care burden in liver disease differs by the type of CLD. Improved CKD screening and proactive treatment interventions for at‐risk patients can limit the excess burden associated with CKD in patients with CLD.
A parametric study of a photovoltaic panel with cylindrical fins under still and moving air conditions in Iraq
Authors: Farhan Ammar A. , Alaskari Mustafa , Alhamadani Ahmed
Published: August 2020

Photovoltaic (PV) panel temperature plays a vital role in the performance of PV panels. When PV temperature increases, the electrical power and efficiency decrease. In the present study, a simple simulated model is derived and implemented for a 70‐W finned PV panel and the results are compared with those for a reference (unfinned) PV panel. The effect of various parameters including fin diameter, fin height, ambient temperature, fin coverage‐to‐area ratio, and solar irradiance level on PV performance are examined. It is concluded that more electrical power is generated under moving air than under still air conditions as solar irradiance increases. The optimum values for fin diameter, fin height, and fin coverage‐to‐area ratio are 0.005 m, 0.25 m, and 50%, respectively. The maximum simulated power difference between the finned and unfinned PV panels is 5 W under realistic weather conditions. The amount of power generated during the summer season would be about 3.32 kW·h greater than that by the reference PV panel over the same period. The root square percent deviation values between the results of the proposed model and previously published experimental data for panel temperature, electrical power, and electrical efficiency are 3.36%, 5.26%, and 5.48%, respectively.
Constraining water age dynamics in a south‐eastern Australian catchment using an age‐ranked storage and stable isotope approach
Authors: Buzacott Alexander J.V. , van der Velde Ype , Keitel Claudia , Vervoort R. Willem
Published: August 2020

Improving our knowledge of the travel times of water through catchments is critical for the management and protection of water resources and to improve our understanding of fundamental catchment behaviour. In this study we use the age‐ranked storage framework StorAge Selection (SAS) to investigate travel times in the Corin catchment, a headwater catchment in the south‐east of Australia covered by native Eucalyptus species. Few studies have applied the SAS framework globally and in energy‐intensive areas where catchment losses are heavily in favour of evapotranspiration relative to streamflow. A combination of observed and modelled values of oxygen‐18 (δ18O), the stable isotope in water, are used to constrain storage selection preferences of streamflow and evapotranspiration and the size of the catchment active storage. The highest performing parameter combinations that could reproduce δ18O in streamflow were dependent on a strong preference for young water in evapotranspiration, and a mixture of weak young and old water preference in streamflow. The mean travel time of streamflow over the study period 2007–2019, weighted by the flow rate, is limited to within a probable range of 2.81–9.77 years. The size of the active storage, a key parameter in the SAS framework, was poorly identified, and in combination with the isotopic inputs into the model, contributed to the uncertainty of the results. We discuss the implications of the results with respect to the study area, as well as within the context of SAS research globally and identify ways to improve the modelling process.
Hyaluronic acid optimises therapeutic effects of hydrogen peroxide‐induced oxidative stress on breast cancer
Authors: Abbasi Ardeshir , Pakravan Nafiseh , Hassan Zuhair Mohammad
Published: August 2020

Distinguishing the multiple effects of reactive oxygen species (ROS) on cancer cells is important to understand their role in tumour biology. On one side, ROS can be oncogenic by promoting hypoxic conditions, genomic instability and tumorigenesis. Conversely, elevated levels of ROS‐induced oxidative stress can induce cancer cell death. This is evidenced by the conflicting results of research using antioxidant therapy, which in some cases promoted tumour growth and metastasis. However, some antioxidative or ROS‐mediated oxidative therapies have also yielded beneficial effects. To better define the effects of oxidative stress, in vitro experiments were conducted on 4T1 and splenic mononuclear cells (MNCs) under hypoxic and normoxic conditions. Furthermore, hydrogen peroxide (H2O2; 10–1,000 μM) was used as an ROS source alone or in combination with hyaluronic acid (HA), which is frequently used as drug delivery vehicle. Our result indicated that the treatment of cancer cells with H2O2 + HA was significantly more effective than H2O2 alone. In addition, treatment with H2O2 + HA led to increased apoptosis, decreased proliferation, and multiphase cell cycle arrest in 4T1 cells in a dose‐dependent manner under normoxic or hypoxic conditions. As a result, migratory tendency and the messenger RNA levels of vascular endothelial growth factor, matrix metalloproteinase‐2 (MMP‐2), and MMP‐9 were significantly decreased in 4T1 cells. Of note, HA treatment combined with 100–1,000 μM H2O2 caused more damage to MNCs as compared to treatment with lower concentrations (10–50 μM). Based on these results, we propose to administer high‐dose H2O2 + HA (100–1000 μM) for intratumoural injection and low doses for systemic administration. Intratumoural route could have toxic and inhibitory effects not only on the tumour but also on residential myeloid cells defending it, whereas systemic treatment could stimulate peripheral immune responses against the tumour. More in vivo research is required to confirm this hypothesis.
HomeoboxC6 affects the apoptosis of human vascular endothelial cells and is involved in atherosclerosis
Authors: Long Xiangshu , You Ganhua , Wu Qiang , Zhou Yu , Xiao Yan , Yu Fuxun , Deng Shiyan , Mo Rui , Song Fang , Huang Jing , Tian Maobo
Published: August 2020

Apoptosis of vascular endothelial cells (VECs) is highly important in the occurrence and development of atherosclerosis (AS). HomeboxC6 (HOXC6) is expressed in higher levels in multiple malignant tissues, and it influences the malignant biological behavior of the cancer cells. However, the effects of HOXC6 on AS and the apoptosis of VECs have not been fully elucidated. In this study, we demonstrated that HOXC6 expression was increased in aortic wall of AS rats and peripheral blood monocytes of patients with coronary heart disease. Furthermore, it was uncovered that BAX expression was upregulated, while BCL‐2 expression was downregulated in the aortic wall of AS rats. The apoptosis of human VECs (HVECs) cultured normally or treated with oxidized low‐density lipoprotein in vitro was decreased after transfection with HOXC6‐siRNA. Moreover, the results of Western blot analysis unveiled that the expressions of proapoptotic proteins, such as BAX, caspase‐3, cleaved‐caspase‐3, and caspase‐9 were reduced, while the expression of antiapoptotic protein, BCL‐2, was elevated. Meanwhile, mRNA and protein expressions of phospholipase C beta (PLCβ) were decreased, the phosphorylation levels of protein kinase C zeta (PKCζ) and nuclear transcription factor‐κB‐p65 (NF‐κBp65) and the membrane translocation of PKCζ were reduced as well. Besides, the expression of interleukin‐18 (IL‐18) protein was downregulated. However, after overexpression of HOXC6, the opposite trends of the abovementioned indices were observed. Furthermore, the inhibition of apoptosis induced by HOXC6‐siRNA was reversed by lysophosphatidylcholine, an activator of PKCζ. Taken together, our results indicated that HOXC6 can promote the apoptosis of HVECs and may be involved in the occurrence and development of AS, which may be partially associated with the activation of PLCβ/PKCζ/NF‐κBp65/IL‐18 signaling pathway.
Intermittent parathyroid hormone promotes cementogenesis via ephrinB2‐EPHB4 forward signaling
Authors: Li Tiancheng , Wang Han , Lv Chunxiao , Huang Li , Zhang Cheng , Zhou Chenchen , Zou Shujuan , Duan Peipei
Published: August 2020

Intermittent parathyroid hormone (PTH) promotes periodontal repair, but the underlying mechanisms remained unclear. Recent studies found that ephrinB2‐EPHB4 forward signaling mediated the anabolic effect of PTH in bone homeostasis. Considering the similarities between cementum and bone, we aimed to examine the therapeutic effect of PTH on resorbed roots and explore the role of forward signaling in this process. In vivo experiments showed that intermittent PTH significantly accelerated the regeneration of root resorption and promoted expression of EPHB4 and ephrinB2. When the signaling was blocked, the resorption repair was also delayed. In vitro studies showed that intermittent PTH promoted the expression of EPHB4 and ephrinB2 in OCCM‐30 cells. The effects of PTH on the mineralization capacity of OCCM‐30 cells was mediated through the ephrinB2‐EPHB4 forward signaling. These results support the premise that the anabolic effects of intermittent PTH on the regeneration of root resorption is via the ephrinB2‐EPHB4 forward signaling pathway.
Interference of gadolinium dechelated from MR contrast agents by calcium signaling in neuronal cells of GnRH
Authors: Baykara Murat , Ozcan Mete , Bilgen Mehmet , Kelestimur Haluk
Published: August 2020

Contrast agents (CAs) used in magnetic resonance imaging (MRI) are produced by chelating the metal gadolinium (Gd) with organic ligand molecules to form stable complexes. But, Gd3+ may dissociate from the CAs and subsequently might become toxic to its environment. Besides toxicity, it might inhibit calcium channels on cell membranes and this action could be detrimental to the cells governing biological development. The aim of this study was to investigate the interference of Gd3+ dechelated from the CAs by calcium signaling in the neuronal cells of gonadotropin‐releasing hormone (GnRH), regulating puberty, and sexual development. The study used the mouse GT1‐7 cell line as a model system, and Fura‐2 based calcium imaging for detecting the interruption of intracellular calcium transport by the extracellular presence of Gd3+ as released from the CAs; gadodiamide and gadoterate meglumine, when the cells were stimulated in vitro culture by exposure to melatonin.The CA gadoterate meglumine interfered minimally with the calcium signaling, and thus its use is preferable in standard MRI exams. The release of Gd3+ from gadodiamide was significant and becomes of great concern as it may impact the neurophysiology of the neuronal cells in general, and gonadotropin production in particular, even in normal patients without nephrogenic systemic fibrosis. The toxicity induced by the influx of dechelated Gd3+ in the neurons of GnRH would have significant implications for puberty and reproductive functions.
Sieving process selects sugarcane bagasse with lower recalcitrance to xylan solubilization
Authors: Alves Rosângela C , Melati Ranieri B , Casagrande Giovanna MS , Contiero Jonas , Pagnocca Fernando C , Brienzo Michel
Published: August 2020

BACKGROUND

Sugarcane bagasse is a heterogeneous and organized material that needs a pretreatment to access the polysaccharides (cellulose and xylan). The particle size of a non‐milled bagasse can influence the xylan and xylose solubilization, as well as the enzymatic hydrolysis of the pretreated material. Using bagasse selected on 16‐, 30‐, 40‐ and 50‐mesh sieves: xylan solubilization was performed with hydrogen peroxide; xylose was solubilized with diluted sulfuric acid; and enzymatic hydrolysis was conducted for glucose yield evaluation.

RESULTS

The xylose solubilized by acid pretreatment resulted in a maximum of 6.59 g L−1 with no influence of particle size. The solubilized xylan showed linear correlation with a variation of 36.18% (16‐mesh bagasse) to 71.43% (<50‐mesh bagasse). Pretreated material submitted to enzymatic hydrolysis revealed that particle size influenced the pretreatment, increasing the glucose yield.

CONCLUSIONS

The results showed that non‐milled sugarcane bagasse particle size selection positively influenced the solubilization of xylan, improving the enzymatic hydrolysis of the pretreated material. © 2020 Society of Chemical Industry (SCI)
Electrochemical dehalogenation of dibromomethane and 1,2‐dibromoethane to non‐toxic products using a carbon fiber brush electrode
Authors: Fernández‐Verdejo David , Sulonen Mira LK , Pérez‐Trujillo Míriam , Marco‐Urrea Ernest , Guisasola Albert , Blánquez Paqui
Published: August 2020

BACKGROUND

Dibromomethane (DBM) and 1,2‐dibromoethane (DBA) are two brominated volatile contaminants used in several industrial applications which are often detected in groundwater. The electrochemical degradation of DBM and DBA was studied at different cathode potentials (−0.8, −1 and −1.2 V versus Standard Hydrogen Electrode) in aqueous solution using an inexpensive graphite fiber brush electrode.

RESULTS

The degradation followed first‐order kinetics with respect to the nominal concentration of the brominated compounds, and the kinetic constant increased concomitantly with the decrease of the cathode potential. During the electrochemical dehalogenation 96.8% and 99.8% of the bromide in DBM and DBA was released as bromine ions, respectively. The main non‐brominated compounds detected during the degradation of DBM and DBA were methane and ethene, respectively. In addition, traces of formic acid for DBM and acetic acid for DBA degradation were detected. The non‐toxicity of the effluent was confirmed by a Microtox test.

CONCLUSION

The efficient electrochemical degradation of DBM and DBA and the lack of toxic products open the door for a simple and non‐toxic electrochemical approach for removing aliphatic brominated compounds from aquifers and other water sources. © 2020 Society of Chemical Industry (SCI)