bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypersensitivity reactions to biologicals: An EAACI position paper
Authors: Bavbek Sevim , Pagani Mauro , Alvarez‐Cuesta Emilio , Castells Mariana , Dursun Adile Berna , Hamadi Sahar , Madrigal‐Burgaleta Ricardo , Sanchez‐Sanchez Soledad , Vultaggio Alessandra
Published: June 2021

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first‐lifetime exposure or after repeated exposure, and these HSRs can be potentially life‐threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence‐based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.
Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy
Authors: Fan Rong , Niu Junqi , Ma Hong , Xie Qing , Cheng Jun , Rao Huiying , Dou Xiaoguang , Xie Jianping , Zhao Wei , Peng Jie , Gao Zhiliang , Gao Hongbo , Chen Xinyue , Chen Jinjun , Li Qiang , Tang Hong , Zhang Zhengang , Ren Hong , Cheng Mingliang , Liang Xieer , Zhu Chaonan , Wei Lai , Jia Jidong , Sun Jian , Hou Jinlin ,   Chronic Hepatitis B Study Consortium
Published: June 2021

Background

Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim

To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods

We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body‐mass index (BMI). Central obesity was evaluated by waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio.

Results

A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5‐year cumulative incidence of HCC was 2.9%. Waist‐to‐height ratio performed better in predicting HCC development than BMI, waist circumference or waist‐to‐hip ratio. Patients with central obesity (defined as waist‐to‐height ratio >0.5) had significantly higher 5‐year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist‐to‐height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12‐3.13, P = 0.017).

Conclusions

Central obesity, evaluated by the waist‐to‐height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease
Authors: Mattoo Vandita Y. , Basnayake Chamara , Connell William R. , Ding Nik , Kamm Michael A. , Lust Mark , Niewiadomski Ola , Thompson Alexander , Wright Emily K.
Published: June 2021

Background

Loss of response to anti‐TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD).

Aims

To perform a systematic review assessing the efficacy of escalated maintenance anti‐TNF therapy in CD.

Methods

EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full‐text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included.

Results

A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%‐100%) and remission (15%‐83%) after empiric dose escalation for loss of response to standard anti‐TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose‐escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure‐response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end‐points. Strategies including Bayesian dashboard‐dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long‐term outcomes.

Conclusions

Empiric escalation of maintenance anti‐TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.
Health literacy for children and families
Authors: Vaillancourt Régis , Cameron Jameason D.
Published: June 2021

The relationship between reading ability and health, known as health literacy, broadly reflects the skills and competencies required to operate within the healthcare environment. It is only recently that we have seen attempts to conceptualize health literacy in the context of medication use by using terms such as medication literacy. Health literacy changes over one's lifetime and is dependent on factors such as numeracy, education, income, gender and country. Low health literacy and low medication literacy have been identified as significant risk factors for poor health outcomes of adults and children. With an evaluation of common tools used to assess health literacy and medication literacy, the aim of this review is to describe the shared responsibility between patients and healthcare providers for the communication of health and medication information. Key strategies and interventions to improve two‐way communication between patients and healthcare providers are highlighted, with a focus on how health literacy can impact child health outcomes.
Pharmacokinetics and brain σ1 receptor occupancy of MR309, a selective σ1 receptor antagonist
Authors: Rabiner Eugenii A. , Smith Kevin , Bennett Carla , Rizzo Gaia , Lewis Yvonne , Mundin Gill , Dooner Helen , Oksche Alexander
Published: June 2021

Aims

Preclinical studies of MR309, a selective sigma‐1 receptor (σ1R) antagonist, support a potential role in treating neuropathic pain. We report 2 studies that provide insight into the pharmacokinetics (PK) and brain σ1R binding of MR309.

Methods

Steady‐state PK of MR309 (400 mg once daily and 200 mg twice‐daily [BID] for 10 days; EudraCT 2015–001818‐99 [PK study]) and the relationship between MR309 plasma exposure and brain σ1R occupancy (EudraCT 2017–000670‐11 [positron emission tomography study]) were investigated in healthy volunteers. Positron emission tomography using the σ1R ligand [11C]SA4503 was conducted at baseline, and 2 and 8 hours after a single dose of MR309 (200–800 mg). The relationship between brain σ1R occupancy and MR309 exposure was explored using data‐driven model fitting.

Results

MR309 was well tolerated, brain σ1R occupancy ranged between 30.5 and 74.9% following single‐dose MR309 (n = 7). MR309 BID provided a plasma PK profile with less fluctuation than once daily dosing (n = 16). MR309 200 mg BID yielded average steady state plasma concentrations between 2000 and 4000 ng/mL in the PK study, which corresponded to an estimated brain σ1R occupancy of 59–74%.

Conclusion

MR309 200 mg BID dose was below the 75% σ1R occupancy threshold expected to elicit maximal antinociceptive effect as observed in neuropathic pain models. Further investigations of MR309 for neuropathic pain will require higher brain σ1R occupancy, and establish the optimal dose by elucidating the clinical impact of a broad range of brain σ1R occupancy across different neuropathic pain indications.
Trade without “scale effects”
Authors: Bento Pedro
Published: June 2021

Across countries, average incomes are related to population density, but not population per se. At the same time, the number of firms in both manufacturing and services are essentially proportional to population but unrelated to density (controlling for population). Why are these distinctions important? Moving from autarky to free trade is much more like increasing population while keeping density fixed. In this paper, I extend a simple variety model by considering an economy made up of a large number of geographical markets of fixed area. Firms must incur a cost to access each market, and this cost is convex in the number of markets entered. Assuming no firm chooses to access all markets within an economy, increasing both population and the number of markets proportionately has no effect on firms’ market access decision and so the number of firms per capita and average incomes remain unchanged. The implications of the model for trade are stark. If two identical countries open up to trade, there are no gains from trade. If two different countries open up to trade but no comparative advantage exists, there are no gains from trade. Countries trade (and gains from trade exist) only if comparative advantage exists. If comparative advantage exists, the gains from trade are lower than in a standard variety model. But if comparative advantage is ignored, the true gains from trade can be much higher than the gains calculated using a standard sufficient‐statistic formula.
In‐person victimization, cyber victimization, and polyvictimization in relation to internalizing symptoms and self‐esteem in adolescents with attention‐deficit/hyperactivity disorder
Authors: Fogleman Nicholas D. , McQuade Julia D. , Mehari Krista R. , Becker Stephen P.
Published: June 2021

Background

There is mixed evidence for whether in‐person victimization and cyber victimization are differentially linked to internalizing symptoms and self‐esteem among adolescents with attention‐deficit/hyperactivity disorder (ADHD). The goals of the present study were to (1) evaluate in‐person victimization and cyber victimization in relation to internalizing symptoms (i.e., anxiety and depression) and self‐esteem and (2) examine differences in internalizing symptoms and self‐esteem between in‐person victimization, cyber victimization, and polyvictimization (i.e., both in‐person victimization and cyber victimization).

Methods

Participants were 78 adolescents (ages 13–17 years) diagnosed with ADHD who completed ratings of in‐person victimization, cyber victimization, anxiety, depression, and self‐esteem. Parents completed ratings of their adolescent's anxiety and depression.

Results

Adolescents with ADHD reported experiencing higher rates of in‐person victimization (64%) than cyber victimization (23%) in the last 30 days. In addition, 22% reported that they experienced polyvictimization. In‐person victimization was associated with higher adolescent‐reported anxiety symptoms, whereas cyber victimization was associated with higher parent‐reported depressive symptoms; both were associated with lower adolescent‐reported self‐esteem. Adolescents who reported polyvictimization reported the highest anxiety and depressive symptoms and the lowest self‐esteem.

Conclusions

Approximately one quarter of adolescents with ADHD report experiencing polyvictimization in the past month. Findings indicate that in‐person victimization and cyber victimization are each uniquely associated with lower self‐esteem and differentially associated with co‐occurring internalizing symptoms among adolescents with ADHD. Polyvictimization is especially linked to higher internalizing symptoms and lower self‐esteem. Longitudinal studies are needed to better understand the directionality of these associations.
Historical biogeography of Tetrastigma (Vitaceae): Insights into floristic exchange patterns between Asia and Australia
Authors: Peng Dan‐Xiao , Dang Viet‐Cuong , Habib Sadaf , Barrett Russell L. , Trias‐Blasi Anna , Wen Jun , Chen Zhi‐Duan , Lu Li‐Min
Published: June 2021

Biodiversity exchanges across the Malesian region, linking the distinct biotas of Asia and Australia, have long attracted the curiosity of biologists. Tetrastigma (Vitaceae) has a wide distribution in Asia through the Sunda archipelago to Australia and provides a good case to elucidate floristic exchange between Asia and Australia. Tetrastigma species have fleshy fruits that are consumed by birds, representing a lineage with a predictable dispersal across island chains. We herein estimate the divergence times and reconstruct the biogeographic history of Tetrastigma with intensive taxon sampling (96 of approximately 120 species; >80%) using 10 chloroplast loci. The biogeographic history of Tetrastigma was reconstructed with 4‐area and 6‐area divisions by delineating the Sunda region into one or three areas of endemism based on a phylogenetic bioregionalization analysis and the geological history of Malesia. The 4‐area division shows that Tetrastigma originated in continental Asia and diverged from the recently segregated genus Pseudocayratia in the early Eocene (49.43 Ma). Dispersal from continental Asia might have started in the late Eocene but mainly occurred in the last 10 Myr. Continental Asia is indicated to be the most important source area while Sunda is the biggest sink, with 16 of the 27 dispersal events inferred from continental Asia to Sunda. Only seven dispersal events are inferred arriving in the Sahul plate and one reverse dispersal from Sahul back to Asia. The 6‐area division suggests that the Philippines have been an active junction between Asia and Australia. The biogeographic history of Tetrastigma illustrates an asymmetric floristic exchange between Asia and Australia in this genus, which has been facilitated by the formation of terrestrial connections in the late Miocene and the expansion of wet tropical forests across Wallace's Line and beyond.
Colonic disease recurrence following proctectomy with end colostomy for anorectal Crohn’s disease
Authors: Lightner Amy L. , Steele Scott R. , Delaney Conor P. , Lavryk Olga , Vaidya Prashansha , McMichael John , Jia Xue , de Buck van Overstraeten Anthony , Brar Mantaj S.
Published: June 2021

Aim

In patients with anorectal Crohn's disease, it remains uncertain whether a total proctocolectomy with end ileostomy or proctectomy with end colostomy should be recommended due to the unknown rate of disease recurrence in the remaining colon.

Methods

A retrospective review of all patients with a known diagnosis of Crohn's disease who underwent a proctectomy with end colostomy for distal Crohn's disease between January 1, 2010 and January 1, 2019 at two IBD referral centres was conducted. Data collected included patient demographics, surgical variables at the time of proctectomy, and postoperative clinical, endoscopic and surgical recurrence rates.

Results

A total of 63 patients were included; mean age was 47 years (SD 15 years) and 32 (50.8%) were female. The majority of patients underwent a proctectomy with end colostomy (n = 56; 88.9%) while the remaining seven patients (11.1%) underwent a proctectomy with end colostomy and concurrent ileocectomy. A total of 55 patients (87.3%) had proctitis, 51 (81%) had perianal fistulating disease, and 34 (54%) had anal canal stenosis or ulceration. Most patients had medically refractory disease (n = 54; 85.7%) versus neoplasia (n = 9; 14.3%). The median length of long‐term follow‐up was 17.7 months (IQR: 4.72, 38.7 months). During that time, 14 (22.2%) experienced clinical recurrence, 10 of 34 evaluated (29.4%) had endoscopic recurrence, and 3 (4.76%) required a completion total abdominal colectomy for recurrent medically refractory disease in the colon.

Conclusion

Colonic recurrence remains low following proctectomy and descending colostomy suggesting this operative management strategy is reasonable in Crohn's patients with distal disease.
Solar Power and its Discontents: Critiquing Off‐grid Infrastructures of Inclusion in East Africa
Authors: Cross Jamie , Neumark Tom
Published: June 2021

Since 2010, solar energy companies in North America and Europe have played a pivotal role in delivering clean, reliable and sustainable electricity to millions of people living off the grid across sub‐Saharan Africa. However, today, off‐grid solar energy in Africa is no longer seen as an unmitigated social and economic good. Inflows of private equity investment have led the employees and customers of off‐grid solar companies to question the industry's commercial dynamics. Their critiques address the mis‐selling of solar home systems and the technical limits of off‐grid infrastructures for domestic production, framed both by dominant market paradigms and by relationships to nation, community and family. Drawing on ethnographic fieldwork in East Africa's off‐grid solar industry, this study assembles these critical perspectives into a wider analysis of off‐grid solar power as an adverse ‘infrastructure of inclusion’.
Impact of traumatic dental injury treatment on the Oral Health‐Related Quality of Life of children, adolescents, and their family: Systematic review and meta‐analysis
Authors: Milani Ana Júlia , Castilho Thuanny , Assaf Andrea Videira , Antunes Leonardo Santos , Antunes Lívia Azeredo Alves
Published: June 2021

Background/Aim

Measures of oral health‐related quality of life (OHRQoL) are useful in clinical trials to evaluate treatment outcomes. To detect the treatment impact of traumatic dental injuries (TDI) on OHRQoL is extremely relevant. The aim of this study was to assess whether there is scientific evidence of the impact of TDI treatment on OHRQoL of children, adolescents, and their families.

Material and Methods

A systematic review and meta‐analysis were conducted selecting articles from PubMed, Web of Science, Scopus, Cochrane Library, and Virtual Health Library until May 22nd, 2020. The gray literature, clinical trial registers, and a manual search were performed. Two independent reviewers selected the studies, extracted the data, and assessed the ROBINS‐I risk of bias. A meta‐analysis was performed using RevMan 5.4 program. The certainty of the evidence was evaluated using the GRADE system.

Results

In the electronic search, 413 abstracts and one registered study were found. After removing the duplicates and eligibility application, six studies were included. Individually, the studies presented low to moderate risk of bias and they found that TDI treatment reduces the negative impact on OHRQoL. In the meta‐analysis, TDI treatment improved OHRQoL for 8‐ to 10‐year‐old children (p = .03; CI 5.19 [0.62, 9.75]) (detected by CPQ 8–10 questionnaire). In the perception of parents, the children, and adolescents who had suffered TDI also had their OHRQoL improved (p = .04; CI 14.77 [0.95, 28.60]) (detected by PPQ and P‐CPQ questionnaire) but both evaluations had very low certainty of evidence.

Conclusion

Treatment of traumatic dental injuries reduces the impact on the OHRQoL of children and adolescents. However, more studies are necessary to detect the TDI treatment influence on OHRQoL of preschoolers and in the family as well to estimate the effects due to outcomes that had a very low certainty of evidence (#CRD42018091210).
Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms
Authors: Hallikainen Joona , Pyysalo Mikko , Keränen Sara , Kellokoski Jari , Koivisto Timo , Suominen Anna Liisa , Pussinen Pirkko , Pessi Tanja , Frösen Juhana
Published: June 2021

Background and purpose

Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.

Methods

Immunoglobulin A (IgA) and IgG antibodies against P. gingivalis and A. actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross‐sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria‐derived epitopes in the IA wall.

Results

Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P. gingivalis and A. actinomycetemcomitans were 1.5× and 3–3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p ≤ 0.003). IgG antibodies against P. gingivalis were 1.8× lower in unruptured IA patients (p < 0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P. gingivalis (odds ratio [OR] = 1.4, 95% confidence interval [Cl] = 1.1–1.8 and OR = 1.5, 95% Cl = 1.1–1.9; OR = 0.6, 95% Cl = 0.4–0.7 and OR = 0.5, 95% Cl = 0.4–0.7) and against A. actinomycetemcomitans (OR = 2.3, 95% Cl = 1.7–3.1 and OR = 2.1, 95% Cl = 1.5–2.9; OR = 0.6, 95% Cl = 0.4–0.8 and OR = 0.6, 95% Cl = 0.5–0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P. gingivalis epitopes in the IA wall.

Conclusions

Exposure to the periodontal pathogens P. gingivalis and A. actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.
Spike and wave discharges and fast ripples during posttraumatic epileptogenesis
Authors: Kumar Udaya , Li Lin , Bragin Anatol , Engel Jerome
Published: June 2021

Objective

The goal of the present study was to determine whether spike and wave discharges (SWDs) and SWDs with superimposed fast ripples (SWDFRs) could be biomarkers of posttraumatic epileptogenesis.

Methods

Fluid percussion injury was conducted on 13–14‐week old male Sprague Dawley rats. Immediately after traumatic brain injury (TBI), they were implanted with microelectrodes in the neocortex, hippocampus, and striatum bilaterally. Age‐matched sham rats with the same electrode implantation montage acted as controls. Wideband brain electrical activity was recorded intermittently from Day 1 of TBI, and continued from 2 to 21 weeks after TBI. SWD and SWDFR analysis was performed during the first 2 weeks to investigate whether the occurrence of this pattern predicted development of epilepsy. The remaining 3–21 weeks were used for identifying which rats became epileptic (E+ group) and which did not (E‐ group).

Results

The E+ group (n = 9) showed a significant increase in SWD rate in prefrontal cortex during Weeks 1 and 2 after TBI. The E‐ group showed a significant increase in SWD rate only in the second week. One hundred percent of rats in the E+ group displayed SWDFRs beginning from the first week after TBI. The SWDFR pattern was observed in all recorded brain areas: prefrontal and perilesional cortices, hippocampus, and striatum. None of rats in the E‐ group showed coexistence of fast ripples with SWDs.

Significance

Occurrence of SWDFRs after TBI, but not an increase in the rate of SWDs, could be a noninvasive electroencephalographic biomarker of posttraumatic epileptogenesis.
Smoothed peridynamics for the extremely large deformation and cracking problems: Unification of peridynamics and smoothed particle hydrodynamics
Authors: Zhou Xiaoping , Yao Wu‐Wen , Berto Filippo
Published: June 2021

Peridynamics (PD) and smoothed particle hydrodynamics (SPH) are definitely attractive theories in amounts of numerical mechanical methods these years, and numerous researchers have studied the similarities of these two methods. In this paper, the smoothed peridynamics (SPD) is proposed to unify these two theories in the meshless view. The SPD employs an update‐Lagrangian (UL) method, which is useful for the extremely large deformation and cracking problem. The SPD governing equation, nonlocal interaction, micro‐bond modules for elastic material are derived. In addition, the choice of the nonlocal kernel and logarithmic stretch is investigated. Finally, numerical experiments are studied to confirm the ability of SPD. The numerical results show that SPD has an excellent performance and application prospect in computational solid mechanics. Since the SPD model formulations are derived for general 3D conditions, it can be straight forwardly extended for large‐scale practical applications across disciplines.
The value of introducing customer‐to‐manufacturer model by the online retailer
Authors: Fan Xiaojun , Wang Shanshan , Wang Junbin
Published: June 2021

An increasing number of online retailers are introducing customer‐to‐manufacturer (C2M) models to offer consumers customized products in addition to standard products. Customized products can satisfy consumers’ aesthetic preferences that are unmet by current products. Thus, companies can minimize their misfit costs. Given the trend of this emerging online retail model, this study analytically explores whether and how the introduction of the C2M model affects firms’ profits, consumer surplus, and social welfare. Our analyses reveal that the introduction of the C2M model always benefits the retailer; moreover, under certain conditions, a win‐win situation occurs among the retailer, the incumbent manufacturer, and the new manufacturer. Further, the introduction of the C2M model can increase or decrease consumer surplus and foster or hinder social welfare growth, depending on the customization cost and consumers’ misfit costs.
Wound healing with “spray‐on” autologous skin grafting (ReCell) compared with standard care in patients with large diabetes‐related foot wounds: an open‐label randomised controlled trial
Authors: Manning Laurens , Ferreira Ivana Bastos , Gittings Paul , Hiew Jonathan , Ryan Erica , Baba Mendel , Raby Edward , Carville Keryln , Norman Paul E. , Davis Wendy Angela , Wood Fiona , Hamilton Emma Jane , Ritter Jens Carsten
Published: June 2021

There is an urgent need for interventions that improve healing time, prevent amputations and recurrent ulceration in patients with diabetes‐related foot wounds. In this randomised, open‐label trial, participants were randomised to receive an application of non‐cultured autologous skin cells (“spray‐on” skin; ReCell) or standard care interventions for large (>6 cm2), adequately vascularised wounds. The primary outcome was complete healing at 6 months, determined by assessors blinded to the intervention. Forty‐nine eligible foot wounds in 45 participants were randomised. An evaluable primary outcome was available for all wounds. The median (interquartile range) wound area at baseline was 11.4 (8.8‐17.6) cm2. A total of 32 (65.3%) index wounds were completely healed at 6 months, including 16 of 24 (66.7%) in the spray‐on skin group and 16 of 25 (64.0%) in the standard care group (unadjusted OR [95% CI]: 1.13 (0.35‐3.65),P = .845). Lower body mass index (P = .002) and non‐plantar wounds (P = .009) were the only patient‐ or wound‐related factors associated with complete healing at 6 months. Spray‐on skin resulted in high rates of complete healing at 6 months in patients with large diabetes‐related foot wounds, but was not significantly better than standard care (Australian New Zealand Clinical Trials Registry: ACTRN12618000511235).
Na2SO4 deposit‐induced hot corrosion of SiC fibers relevant for SiC CMCs
Authors: Herweyer Lucas A. , Opila Elizabeth J.
Published: June 2021

Hi Nicalon, Hi Nicalon S, Sylramic, and Sylramic iBN SiC fibers were exposed to ~60 μg/cm2 of Na2SO4 in a 0.1% SO2/O2 gaseous environment for times between 0.75 and 24 h at 1000°C. After exposure, the corrosion products were characterized using SEM, EDS, ICP‐OES, TEM, and EFTEM to determine their high‐temperature resistance to Na2SO4 and key reaction mechanisms. All SiC fiber types tested in this work exhibited little resistance to Na2SO4 deposit‐induced attack relative to their behavior in dry O2 environments. It was found that Hi‐Nicalon displayed the least resistance to Na2SO4 deposit‐induced attack due to excess carbon content resulting in the formation of a highly porous crystalline oxide and promotion of basic corrosion conditions. All fiber types formed a crystalline SiO2 reaction product, either cristobalite or tridymite. Sylramic and Sylramic iBN formed a crystalline SiO2 reaction layer containing TiO2 needles due oxidation of TiB2 particles. Additionally, Na2SO4 deposits resulted in pitting of all fiber surfaces.
Osmoregulation of the transcriptome of the hypothalamic supraoptic nucleus: A resource for the community
Authors: Pauža Audrys G. , Mecawi André Souza , Paterson Alex , Hindmarch Charles C. T. , Greenwood Mingkwan , Murphy David , Greenwood Michael P.
Published: June 2021

The hypothalamic supraoptic nucleus (SON) is a core osmoregulatory control centre that deciphers information about the metabolic state of the organism and orchestrates appropriate homeostatic (endocrine) and allostatic (behavioural) responses. We have used RNA sequencing to describe the polyadenylated transcriptome of the SON of the male Wistar Han rat. These data have been mined to generate comprehensive catalogues of functional classes of genes (enzymes, transcription factors, endogenous peptides, G protein coupled receptors, transporters, catalytic receptors, channels and other pharmacological targets) expressed in this nucleus in the euhydrated state, and that together form the basal substrate for its physiological interactions. We have gone on to show that fluid deprivation for 3 days (dehydration) results in changes in the expression levels of 2247 RNA transcripts, which have similarly been functionally catalogued, and further mined to describe enriched gene categories and putative regulatory networks (Regulons) that may have physiological importance in SON function related plasticity. We hope that the revelation of these genes, pathways and networks, most of which have no characterised roles in the SON, will encourage the neuroendocrine community to pursue new investigations into the new ‘known‐unknowns’ reported in the present study.
Prenatally diagnosed lower urinary tract obstruction: A 15‐year experience at two tertiary centers in Japan
Authors: Sugibayashi Rika , Wada Seiji , Ozawa Katsusuke , Muromoto Jin , Oi Rie , Yamamoto Ryo , Ishii Keisuke , Sago Haruhiko
Published: June 2021

Aim

To examine the outcomes of prenatally diagnosed lower urinary tract obstruction (LUTO) with current management using vesicoamniotic shunting (VAS).

Methods

A retrospective study of prenatally diagnosed LUTO before 26 weeks of gestation at two tertiary centers in Japan between March 2002 and September 2017. LUTO was diagnosed by ultrasound demonstration of an enlarged fetal bladder associated with hydronephrosis and/or hydroureters. VAS was offered for fetuses with LUTO at ≤26 weeks of gestational age, in the presence of oligohydramnios or decreasing amniotic fluid and a favorable fetal urinary analysis.

Results

Among 87 fetuses with LUTO, 46 (53%) were terminated before 22 weeks of gestation. Eight cases (9%) underwent VAS and one underwent fetoscopic urethrotomy. The live birth rates in the VAS and expectant groups were 100% (8/8) and 56% (18/32), respectively (p = 0.034), and the survival rates at 6 months old with a normal renal function were 38% (3/8) and 16% (5/32), respectively (p = 0.608). The etiology varied with six cases of associated anomalies among 23 diagnosed cases. Among the nine cases of posterior urethral valve (PUV), only one fetus underwent VAS at 25 weeks of gestation, ultimately surviving with mild renal dysfunction. Among the other eight cases of PUV that were managed expectantly, two died, and only one of the six survivors showed a normal renal function.

Conclusions

More than half of the prenatally diagnosed LUTO cases were terminated. VAS seemed effective for achieving a perinatal survival, regardless of etiology. The outcomes were poor in cases of expectantly managed PUV.
Association of a unicornuate uterus with adverse obstetric outcomes: A retrospective cohort study
Authors: Lü Yan , Ji Mingliang , Deng Shan , Gao Jinsong , Zhou Xiya
Published: June 2021

Objective

To estimate the association of unicornuate uterus (UU) with adverse obstetric outcomes.

Methods

Using data from 26 737 singleton childbirths from a tertiary hospital from 1999 to 2019, we identified 44 births from women with a UU. A total of 367 births from women with a normal uterus were randomly selected as controls. The outcome measures were preterm birth (PTB), breech presentation, and cesarean delivery. The subdivisions of PTB and indications for cesarean delivery were described.

Results

The presence of UU was associated with an increased risk of PTB (adjusted risk ratio [aRR], 2.3; 95% confidence interval [CI], 1.1–4.9), breech presentation (aRR, 6.2; 95% CI, 2.9–13.2), and cesarean delivery (aRR, 2.1; 95% CI, 1.8–2.7). For women with a UU, most PTBs (7/9) were moderate to late PTBs, and approximately half of the PTBs (4/9) were iatrogenic due to preeclampsia (PE). Breech presentation, PE, and prior surgery for rudimentary horn resection were UU‐related indications for cesarean delivery.

Conclusions

Women with a UU have a higher risk of PTB, breech presentation, and cesarean delivery. Understanding of the subdivisions of PTBs and indications for cesarean delivery might help clinicians when counseling women with pregnancy complicated by a UU.
Review of cadmium exposure and smoking‐independent effects on atherosclerotic cardiovascular disease in the general population
Authors: Fagerberg Björn , Barregard Lars
Published: June 2021

Background

Exposure to cadmium (Cd) via food and smoking is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood and urine levels of Cd are established biomarkers of exposure.

Objectives

To review (1) the smoking‐independent associations between Cd exposure and ASCVD, including the possible presence of a nonlinear dose–response relationship with Cd exposure and (2) the causal effects of Cd exposure on different stages of atherosclerosis.

Methods

Narrative review.

Results

Cd confers increased risk of ASCVD and asymptomatic atherosclerosis in the carotid and coronary arteries above B‐Cd >0.5 μg/L or U‐Cd >0.5 μg/g creatinine, but it has not been shown below a threshold of these exposure levels. Adjustment for smoking does not exclude the possibility of residual confounding, but several studies in never‐smoking cohorts have shown associations between Cd and ASCVD, and experimental studies have demonstrated pro‐atherosclerotic effects of Cd.

Cd accumulates in arterial walls and atherosclerotic plaques, reaching levels shown to have proatherosclerotic effects. Suggested early effects are increased subendothelial retention of atherogenic lipoproteins, which become oxidized, and endothelial dysfunction and damage with increased permeability for monocytes, which in the intima turn to macrophages and then to foam cells. Later, Cd may contribute to plaque rupture and erosion by endothelial apoptosis and degradation of the fibrous cap. Finally, by having prothrombotic and antifibrinolytic effects, the CVD risk may be further increased.

Conclusions

There is strong evidence that Cd causes ASCVD above a suggested exposure level via mechanisms in early as well as the late stages of atherosclerotic disease.
New drugs for NASH
Authors: Albhaisi Somaya A. M. , Sanyal Arun J.
Published: June 2021

Non‐alcoholic steatohepatitis (NASH) is a result of inflammation and hepatocyte injury in the presence of hepatic steatosis which can progress to cirrhosis. NASH is the most rapidly growing aetiology for liver failure and indication for liver transplantation in the United States. Non‐alcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Because of the absence of approved pharmacotherapy, weight loss and lifestyle modifications remain the safest and most effective first‐line treatment. However, this may not be effective in patients with advanced fibrosis or cirrhosis and long‐term adherence is difficult to achieve. Therefore, effective drugs are urgently needed for the treatment of NASH. Drug development targeting pathological pathways in NASH have exploded in the past decade, with numerous new drugs under investigation. This review summarizes the results of pivotal finalized phase 2 studies and provides an outline of key active studies with trial data of drugs under development.
HCC advances in diagnosis and prognosis: Digital and Imaging
Authors: Sartoris Riccardo , Gregory Jules , Dioguardi Burgio Marco , Ronot Maxime , Vilgrain Valérie
Published: June 2021

Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death worldwide. Understanding of the pathogenesis of HCC has significantly improved in the past few years due to advances in genetics, molecular biology and pathology. Several subtypes have been identified with different backgrounds and outcomes, leading to possible changes in disease management and challenging the role of imaging. Indeed, despite its pivotal role in the diagnostic workup, prognosis, and the decision‐making process in patients with HCC, these recent developments are progressively redefining the role of imaging. First and most important, liver imaging is shifting from a purely qualitative to a quantitative paradigm, integrating quantitative imaging and radiomics in a digital era. Second, to improve patient management, imaging has gradually moved beyond tumor‐centered assessment to include a broader evaluation of the liver and its function. This review describes and discusses these advances in the imaging for the diagnosis and prognosis of HCC.
Trajectory control in roundabouts with a mixed fleet of automated and human‐driven vehicles
Authors: Mohebifard Rasool , Hajbabaie Ali
Published: June 2021

This paper presents a methodology to control the trajectory of cooperative connected automated vehicles (CAVs) at roundabouts with a mixed fleet of CAVs and human‐driven vehicles (HVs). We formulate an optimization program in a two‐dimensional space for this purpose. A model predictive control‐based solution technique is developed to optimize the trajectories of CAVs at discretized time steps based on the estimated driving behavior of HVs, while the actual behavior of HVs is controlled by a microscopic traffic simulator. At each time step, the location and speed of vehicles are collected, and a decomposition‐based methodology optimizes CAV trajectories for a few time steps ahead of the system time. The optimization methodology has convexification, alternating direction method of multipliers, and cutting plane decomposition components to tackle the complexities of the problem. We tested the solution technique in a case study roundabout with different traffic demand flow rates and CAV market penetration rates. The results showed that increasing the CAV market penetration rate from 20% to 100% reduced total travel times by 2.8% to 35.8%. The analyses indicate that the presence of cooperative CAVs in roundabouts can lead to considerable improvements.
An integrative literature review and critical reflection of intersectionality theory
Authors: Ruiz Ashley M. , Luebke Jeneile , Klein Katie , Moore Kaylen , Gonzalez Michael , Dressel Anne , Mkandawire‐Valhmu Lucy
Published: June 2021

Intersectionality theory has been used by nursing scholars to offer insight into how multiple systems of oppression mutually interact to impact health and to examine how multiple social modes of existence shape individual and group experiences of health inequality. The application of intersectionality theory, however, requires a reflexive critical lens to more effectively inform nursing science and practice. We draw on a comprehensive integrative literature review to offer a critical reflection by considering the semantic and structural consistency, generalizability, simplicity and complexity, and the utility and value of intersectionality theory to nursing science and practice. If nurses are to effectively utilize intersectionality theory, it is essential that we are able to analyze and speak to the multiple modes of existence based on historical, social, economic, and political processes that impact the health of those we serve. Critical examination of intersectionality enables nurses to further consider its value and usefulness when applied to nursing science and practice, particularly when addressing health and social inequalities.
The effects of allelochemical transfer on the dynamics of hosts, parasitoids, and competing hyperparasitoids
Authors: Zimmerman Mark P. , Chan David M. , Kester Karen M. , Rael Rosalyn C. , Robertson Suzanne L.
Published: June 2021

Allelochemicals produced by plants may be ingested by herbivorous insects and transferred to higher trophic levels with potentially deleterious effects. We develop a system of differential equations to investigate the effect of the transfer of allelochemicals, such as nicotine, on the population dynamics of a system of hosts, parasitoids, and two competing hyperparasitoids that attack different life stages of the parasitoids. We find both somewhat deleterious effects of nicotine on the larvae‐attacking hyperparasitoids and increased attack rates for the pupae‐attacking hyperparasitoids can promote coexistence. We also use an evolutionary game‐theoretic approach to determine the optimal distribution of hyperparasitoid attacks among nicotine‐producing and nicotine‐free plants. With strong deleterious effects of nicotine and increased attack rates for the pupae‐attacking hyperparasitoid, we find both species attack parasitoids on the nicotine‐free plant but only pupae‐attacking hyperparasitoids attack parasitoids on the nicotine‐producing plant.

Recommendations for Resource Managers:

In the absence of nicotine and with equal attack rates, the larvae‐attacking hyperparasitoids will exclude pupae‐attacking hyperparasitoids due to the advantage of attacking an earlier life‐stage of the parasitoid.

Coexistence of larvae‐ and pupae‐attacking hyperparasitoid species can occur when the pupae‐attacking species has the advantage of a higher oviposition rate and/or when the larvae‐attacking species suffers increased mortality due to nicotine.

If mortality rates of larvae‐attacking hyperparasitoids due to nicotine become too large, they are unable to persist.

The population dynamics of systems incorporating multiple trophic levels are complex and intertwined. The presence of allelochemicals such as nicotine in the first trophic level may impact the observed diversity of hyperparasitoid species in the fourth trophic level.
Premature cardiac beats in children with structurally normal heart: autonomic dysregulation
Authors: Azak Emine , Cetin Ibrahim Ilker
Published: June 2021

Background

Premature ventricular contractions and supraventricular contractions are common rhythm disorders requiring comprehensive investigation in children. The aim of the study was to evaluate the heart rate variability (HRV) in premature ventricular contractions (PVCs) and supraventricular contractions (PSVCs) in children.

Methods

The study compared the characteristics of HRV in 175 children with PVCs and 160 children with PSVCs who underwent 24‐h Holter monitoring, with 101 healthy children.

Results

Significant differences were found between standard deviation of all normal RR intervals (SDNN), standard deviation of average RR intervals in all 5 min segments of registration (SDANN), root mean square of the successive differences (rMSSD), and the proportion of NN50 divided by total number of NNs (pNN50) values of the patient and control groups. The PVCs group had a significantly lower high frequency (HF) and higher low frequency (LF)/HF ratio and the PSVCs group had a significantly higher LF and higher LF/HF ratio compared to the control group. No significant correlation existed between frequency and the SDNN index, rMSSD, and pNN50 values of the PVCs group. The receiver operating characteristics analysis showed a significantly changed LF/HF ratio when premature contractions exceeded 60 beats per hour in children with PVCs.

Conclusions

This study indicated an increased sympathetic tone and a significantly decreased vagal tone in children with PVCs and PSVCs. HRV can be used increasingly as a non‐invasive method in the follow‐up of children with premature cardiac contractions.
Ready to change? Predicting adolescents'help‐seekingfor relationship concerns
Authors: Kanter Jeremy B. , Lannin Daniel G. , Russell Luke T. , Yazedjian Ani
Published: June 2021

Although therapy, relationship education, and online relationship resources may help alleviate relational distress, many adolescents and adults eschew help. Deciding to seek help for relationship concerns involves mental processes that reflect behavioral intentions and information‐seeking behaviors. The present paper examines the prevalence of adolescents' (N = 183) intentions and behaviors to seek relationship help, and investigates determinants of such decisions. Results indicate that only readiness to change was consistently associated with help‐seeking decisions. In contrast, other factors varied, with relationship status associated only with future intentions, and family difficulties associated only with behaviors to seek relational assistance. Programs may benefit from considering methods of disseminating information and encouraging adolescents to reflect upon reasons for considering making changes.
Ocean‐depth measurement using shallow‐water wave models
Authors: Vasan V. , Manisha  , Auroux D.
Published: June 2021

In this paper, we consider a problem inspired by the real‐world need to identify the topographical features of ocean basins. Specifically, we consider the problem of estimating the bottom impermeable boundary to an inviscid, incompressible, irrotational fluid from measurements of the free‐surface deviation alone, within the context of dispersive shallow‐water wave models. The need to consider the shallow‐water regime arises from the ill‐posed nature of the problem and is motivated by prior work. Assuming only a relatively inaccurate initial guess for the bottom‐boundary, we design an algorithm to accurately deduce the fluid velocities and the true bottom‐boundary profile. We achieve this by considering two separate inverse problems: one to deduce the bottom‐boundary from velocities and the surface deviation, and another to recover the velocities from the surface deviation and an approximate bottom‐boundary. The former is a classic inverse problem that requires the inversion of an ill‐conditioned matrix, whereas the latter employs the observer framework. Combining the two inverse problems leads to our reconstruction algorithm. We emphasize the role played by model selection and its impact on algorithm design and the accuracy of the reconstruction.