bluuebunny/crossref_metadata_2025 huggingface dataset:
Infectious mononucleosis is associated with an increased incidence of NAFLD
Authors: Loosen Sven H. , Kostev Karel , Luedde Tom , Roderburg Christoph
Published: November 2022

Background

Non‐alcoholic fatty liver disease (NAFLD) has become the leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although various genetic and lifestyle‐related risk factors have been identified, its pathophysiology has not yet been fully unravelled. While acute EBV infection in the setting of infectious mononucleosis can lead to acute hepatitis, the long‐term hepatic sequelae of infectious mononucleosis are still poorly understood.

Methods

This retrospective cohort study included 13,859 patients with and 13,859 matched individuals without infectious mononucleosis from the Disease Analyzer database (IQVIA). Multivariable Cox regression analyses were used to evaluate the association between infectious mononucleosis and NAFLD.

Results

Within 10 years of the index date, 2.64% of patients with infectious mononucleosis and 1.78% of individuals without infectious mononucleosis had been diagnosed with NAFLD (p < .001). The incidence of NAFLD was 263.9 cases per 100,000 person‐years among individuals with infectious mononucleosis and 164.5 cases per 100,000 person‐years among those without. Multivariable regression analyses indicated that infectious mononucleosis was significantly associated with the incidence of NAFLD (HR: 1.73) both among women (HR: 1.73) and among men (HR: 1.70). In age‐stratified analyses, the association between infectious mononucleosis and NAFLD was most pronounced for the groups aged between 41 and 50 years (HR: 2.94) and >50 years (HR: 2.68).

Conclusion

Infectious mononucleosis is significantly associated with the incidence of NAFLD in a large cohort from Germany. These findings suggest a pathophysiological involvement of EBV in the development of NAFLD and could stimulate research efforts to better understand the pathophysiology of this emerging global medical burden.
Effectiveness of progressive moderate‐vigorous intensity elastic resistance training on quality of life and perceived functional abilities in people with hemophilia: Secondary analysis of a randomized controlled trial
Authors: Cruz‐Montecinos Carlos , Pérez‐Alenda Sofía , Casaña José , Carrasco Juan J. , Andersen Lars L. , López‐Bueno Rubén , Nuñez‐Cortés Rodrigo , Bonanad Santiago , Querol Felipe , Calatayud Joaquín
Published: November 2022

Introduction and Aim

Strength exercise training is advised for people with hemophilia (PWH); however, few studies have been published and have methodological limitations. The purpose of this study was to evaluate the effectiveness of progressive elastic resistance training on quality of life and perceived functional abilities in PWH.

Methods

Participants were randomly allocated to the intervention (n = 10) or control (n = 10) group. The intervention group performed progressive moderate‐vigorous elastic resistance training (2 days/week, a total of 8 weeks), focusing on the muscles of the knee, elbow, and ankle joints. The control group continued its usual daily activities for 8 weeks. Quality of life (A36 Hemofilia‐QoL®) and perceived functional abilities (Haemophilia Activities List) were assessed at baseline and an 8‐week follow‐up.

Results

The intervention group improved the quality‐of‐life dimension of joint damage perception in comparison to the control group (p = .015, large effect size). Regarding perceived functional abilities, the intervention group improved lying, sitting, kneeling, and standing (p = .006, small effect size), and complex lower extremities activities (i.e., walking short and long‐distance, and up‐down stairs) (p = .006, small effect size) compared to the control group. No other significant differences were observed.

Conclusions

Eight weeks of progressive moderate‐vigorous elastic resistance training in PWH improve the quality‐of‐life dimension of joint damage perception and perceived functional abilities (lying/sitting/kneeling/standing, and complex lower extremities activities). Our results suggest a limited effect of the program on the other items of quality of life measured by the questionnaire as emotional functioning, mental health, and social relationships. Importantly, no serious adverse effects occurred.
Short‐ and long‐interval intracortical inhibition in EPM1 is related to genotype
Authors: Silvennoinen Katri , Säisänen Laura , Hyppönen Jelena , Rissanen Saara M. , Karjalainen Pasi A. , D'Ambrosio Sasha , Jimenez‐Jimenez Diego , Zagaglia Sara , Rothwell John C. , Balestrini Simona , Sisodiya Sanjay M. , Julkunen Petro , Mervaala Esa , Kälviäinen Reetta
Published: November 2022

Objective

Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)–induced long‐interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short‐interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1.

Methods

TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter‐stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed.

Results

The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age‐ and sex‐matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p < .001) and SICI (rho = 0.689; p = .006).

Significance

Our results strengthen the finding of deranged γ‐aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease‐modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.
CC chemokine ligand 20 (CCL20) positively regulates collagen type I production in 3D skin equivalent tissues
Authors: Bandow Kenjiro , Smith Avi , Watkins Trishawna , Shenk Sasha , Gerami‐Naini Behzad , Garlick Jonathan A.
Published: November 2022

Chemokines are a group of small proteins that induce chemoattraction and inflammation and contribute to the differentiation and homeostasis of various cell types. Here we explored the role of chemokines, extracellular matrix production, and myofibroblast differentiation in self‐assembled skin equivalents (SASE), a three‐dimensional (3D) skin‐equivalent tissue model. We found that the expression of three chemokines, C‐C motif chemokine ligand (CCL) 20, C‐X‐C motif chemokine ligand (CXCL) 5, and CXCL8, increased with differentiation to myofibroblasts. Addition of recombinant CCL20 to human skin fibroblast induced collagen Type I alpha 2 gene expression, but did not affect the expression of alpha smooth muscle actin expression. Conversely, siRNA gene knockdown of CCL20 effectively inhibited the expression of collagen Type I gene and protein. Furthermore, when the CCL20 gene in fibroblasts was knocked down in SASE, collagen Type I synthesis and stromal thickness were decreased. Taken together, these results have indicated the utility of SASE in understanding how cytokines such as CCL20 positively regulate extracellular matrix proteins such as collagen Type I production during myofibroblast differentiation in 3D tissues that mimic human skin.
Ductile failure and damage localization in Al6061‐T6 characterized by in situ X‐ray computed tomography and neural network segmentation
Authors: Seede Raiyan , Johnson Kyle , Noell Philip J.
Published: November 2022

Damage initiation and localization in uniaxial tension tests of an Al6061‐T6 alloy are evaluated and quantified using in situ X‐ray computed tomography and a neural network segmentation strategy. This segmentation strategy offers significant advantages over traditional thresholding in quantifying microstructural and damage evolution metrics. Void nucleation was observed to occur throughout the deformation process, whereas void volume did not grow significantly until later stages of deformation. Localized analysis determined that void nucleation begins in and around the necked region during the early stages of deformation, whereas limited damage nucleation occurs outside of the neck until late stages of deformation. Lastly, inhomogeneities in void and particle spacing in the initial undeformed state of the material are observed to correlate well with the location of damage localization and necking during deformation. These results provide new insights into the ductile failure of Al alloys and how preexisting defects influence damage and rupture.
Linking multiple hypotheses to a unifying framework of range‐size variation: A case study with American oaks (Quercus spp.)
Authors: Wu Yingtong , Ricklefs Robert E.
Published: November 2022

Aim

Closely related species vary greatly in range size. To understand what drives range‐size variation, we established an integrative framework focusing on two causal pathways: the amount of currently suitable habitat (ASH) and range filling (i.e., the occupancy of ASH). Instead of testing different hypotheses in isolation, we linked four hypotheses to this unifying framework: we tested the niche breadth and niche position hypotheses, which explain range‐size variation via effects on ASH; we also tested the colonization ability and post‐glacial migration lag hypotheses, which explain range‐size variation via range filling.

Location

The Americas.

Time period

Last Glacial Maximum (LGM) to present.

Major taxa studied

One hundred and eighty‐three oak species.

Methods

We extracted locality records and measured range size as the area of occupancy (AOO) and extent of occurrence (EOO). We used Maxent models and current environmental layers to quantify ASH, niche breadth and niche position. We used seven phenotypic traits as proxies of colonization ability. We calculated post‐glacial accessibility to currently suitable habitat, in addition to the proportion of currently suitable habitat covered by LGM ice sheets. Using structural equation models and regression models, we tested the four hypotheses. Finally, we examined how ASH and range filling contributed interactively to range‐size variation by quantifying variance and covariance.

Results

Our results supported all four hypotheses. Additionally, we found that variance in ASH and range filling contributed to a similar extent to variance in AOO, with almost zero covariance between ASH and range filling. In contrast, range filling accounted for almost all the variance in EOO, and we detected a significant negative covariance between ASH and range filling.

Main conclusions

In oaks, factors associated with range filling are at least as important as niche properties in determining range size. Our framework is generalizable to other study systems for testing the contributions of two pathways, ASH and range filling, to range‐size variation.
Late diagnosis of HIV in 2022: Why so little change?
Authors: Collins Simon , Namiba Angelina , Sparrowhawk Alex , Strachan Sophie , Thompson Marc , Nakamura Hideta
Published: November 2022

Background

The proportion of people who are diagnosed late is a key metric to measure the public health response to HIV. But this percentage remains stubbornly high in nearly every country. Delays in accessing antiretroviral therapy affects both (i) individual health, due to a higher risk of mortality, and (ii) population‐based health, due to continued risk of transmission. Despite huge efforts to increase testing, late diagnosis continues to be an indication of a public health failure.

Outline

This short review includes community perspectives on why late diagnosis continues and how it may be reduced. We discuss both structural barriers that prevent people from testing earlier and personal reasons why some people still refuse testing when offered. We note that late diagnosis is reported in all countries and in all demographic groups and that sex, gender, age, and sexuality all affect these rates. However, even in groups with high HIV awareness, such as in gay and bisexual men in the UK, more than one in three people with HIV continue to be diagnosed late. Fears and prejudice about HIV based on outdated information are still common among both health workers and people using health services. For example, testing is still not offered in primary or emergency care settings, and even free testing might not be accepted if someone fears the outcome might jeopardize their resident status, employment, relationship, or health.

In addition to developing targeted projects to reach the highest‐risk groups, a positive mainstream public campaign could make testing more acceptable at a broad population level across all demographics. This could challenge and repair the media campaigns from the 1980s that still contribute to the stigma that frightens people away from testing now. We hope that an effective approach in one country might also help others.
Interleukin‐10 promoter variability is associated with the susceptibility, severity, and clinical outcomes of aplasitc anemia in Han‐Chinese population
Authors: Wang Shichong , You Yahong , Ge Meili , Shao Yingqi , Huo Jiali , Ren Xiang , Li Xingxin , Huang Jinbo , Zhang Jing , Wang Min , Nie Neng , Jin Peng , Zheng Yizhou
Published: November 2022

Introduction

Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST.

Methods

In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)‐10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA.

Results

We observed that CT genotype of IL‐10 rs1800896 was associated with a decreased risk of AA (adjusted OR = 0.541 [95% CI 0.295–0.993], p = .047). Besides, the disease severity differed considerably by IL‐10 gene promoter genotypes and alleles. Furthermore, IL‐10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR = 0.409 [95% CI 0.178–0.943, p = .036] for rs1800871 and GG + GT vs. TT, adjusted OR = 0.396 [95% CI 0.173–0.909, p = .028] for rs1800872, respectively).

Conclusion

The polymorphisms of IL‐10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.
Conflictividad laboral en contextos de fragmentación y pluralismo sindical. Análisis empírico del caso de Chile
Authors: PÉREZ AHUMADA Pablo , OCAMPO Gino
Published: November 2022

La incidencia de las huelgas en Chile ha aumentado sustancialmente desde finales de la década de 2000. En este artículo analizamos la actividad huelguista centrándonos en un aspecto clave del modelo de relaciones laborales chileno: el pluralismo sindical. A partir de una encuesta representativa de las empresas del sector privado, estimamos modelos de regresión logística que indican que el pluralismo sindical incrementa significativamente la probabilidad de huelgas en las empresas. Sin embargo, nuestro análisis no permite concluir que el efecto positivo del pluralismo sindical se explique por la competencia entre sindicatos, tal como sugiere parte de la bibliografía internacional.
Extremely enhanced thermal stability of Y2/3Cu3Ti4O12 ceramics by a Pechini method
Authors: Wei Yaxin , He Donglin , Fu Zhilong , Liu Yafei , Wu Ruifeng , Li Wenyuan , Lu Min , Xie Yahong , Chang Aimin , Zhang Bo
Published: November 2022

Y2/3Cu3Ti4O12 ceramic is a novel semiconductor with potential applications in electronic devices. However, its resistance drift and surface structure defects limit the application for negative temperature coefficient thermistor devices. A comparative study of solid‐phase and a Pechini processing of Y2/3Cu3Ti4O12 is presented in this paper, in the particular comparative study of stability. The Pechini method is found to be effective in lowering sintering temperature and improving thermal stability (ΔR/R0 < 0.3％) in comparison with solid‐phase method. The origin of the stability deterioration is related to the oxidation state of Cu ions and the migration of sublattice. The Pechini method overcomes stoichiometric ratio deviations and cation vacancy diffusion, thus reducing metal ion segregation in a continuous high‐temperature environment and thereby showing unique insensitivity to oxygen. The important role of the Pechini method in improving thermal stability is revealed, which is expected to be used in the preparation of high stability electron devices.
A randomized prospective study comparing single‐balloon‐assisted colonoscopy and cap‐assisted colonoscopy in patients with previous incomplete conventional colonoscopy
Authors: Cheng Tsz Fai , Cheng Ka Shing
Published: November 2022

Introduction

Cecal intubation may be unsuccessful by conventional colonoscopy in some patients. Single‐balloon‐assisted colonoscopy (SBC) and cap‐assisted colonoscopy (CAC) were studied to solve this problem. There was no head‐to‐head comparison between them.

Methods

We conducted a randomized study from 2018 to 2021 to compare cecal intubation rate of SBC and CAC in patients with previous incomplete conventional colonoscopy. We recruited patients with incomplete conventional colonoscopy in two hospitals in Hong Kong. Patients were randomized into SBC group and CAC group in 1:1 ratio. In the case of failure in cecal intubation by allocated method, alternative modality would be performed as rescue.

Results

Forty‐four patients were recruited. Cecal intubation rate was superior in SBC group (22/22, 100%) than CAC group (16/22, 72.7%) (P = 0.02). No difference in cecal intubation time, polyp detection rate, and diagnostic gain in area not examined previously. SBC induced less discomfort (modified Gloucester comfort score 2.14 vs 2.63, P = 0.03) with use of comparable amount of midazolam and fentanyl as CAC. For patients failed cecal intubation by CAC, all (n = 6) were rescued successfully by SBC. Body weight, body mass index (BMI), and waist circumference were greater in rescue subgroup. More patients were obese (BMI ≥ 25 kg/m) in rescue subgroup (67% vs 19%). None in rescue subgroup had history of successful cecal intubation by conventional colonoscopy (0% vs 56%, P = 0.046). However, we failed to demonstrate significant association in multivariate analysis owing to small sample size. No adverse event was noted.

Conclusion

SBC is superior to CAC in cecal intubation in patients with previous incomplete conventional colonoscopy.
Is TGR5 a therapeutic target for the treatment of spinal cord injury?
Authors: Smaling Anna , Romero‐Ramírez Lorenzo , Mey Jörg
Published: November 2022

Bile acids, which are synthesized in liver and colon, facilitate the digestion of dietary lipids. In addition to this metabolic function, they also act as molecular signals with activities in the nervous system. These are mediated primarily by a G‐protein‐coupled bile acid receptor (known as TGR5). Preceded by a long tradition in Chinese medicine, bile acids are now being investigated as therapeutic options in several neuropathologies. Specifically, one bile acid, tauroursodeoxycholic acid (TUDCA), which passes the blood–brain barrier and shows anti‐inflammatory and anti‐apoptotic effects, has been tested in animal models of spinal cord injury (SCI). In this review, we discuss the evidence for a therapeutic benefit in these preclinical experiments. At the time of writing, 12 studies with TGR5 agonists have been published that report functional outcomes with rodent models of SCI. Most investigations found cytoprotective effects and benefits regarding the recovery of sensorimotor function in the subacute phase. When TUDCA was applied in a hydrogel into the lesion site, a significant improvement was obtained at 2 weeks after SCI. However, no lasting improvements with TUDCA treatment were found, when animals were assessed in later, chronic stages. A combination of TUDCA with stem cell injection failed to improve the effect of the cellular treatment. We conclude that the evidence does not support the use of TUDCA as a treatment of SCI. Nevertheless, cytoprotective effects suggest that different modes of application or combinatorial therapies might still be explored.

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Legal mobilization and branches of law: Contesting racialized policing in French courts
Authors: Boutros Magda
Published: November 2022

When activists use the law to promote social change, how does the branch of law (criminal law, civil law, etc.) matter for movement outcomes? To examine this question, the article builds on legal mobilization scholarship, and on a qualitative study comparing three litigation strategies to contest racialized policing in France: mobilizing criminal law to hold officers accountable for police killings, mobilizing civil law to sue the state for racial profiling, and combining criminal and civil law to contest racialized police harassment. The findings suggest that three characteristics of legal branches matter for legal mobilization: (i) the branch's dominant paradigm (e.g., punitive vs. compensatory) determines how the problem gets framed and which actors are blamed for it; (ii) the legal provisions of each branch shape which aspects of the problem get highlighted, and which are obscured; (iii) the procedural and evidentiary rules determine the extent to which activists and victims can intervene in the fact-finding process and thus how much they can influence the strength of their claims in court. When they mobilize the law, social change actors strategize around the opportunities and constraints of various branches of law, to try influencing judicial decisions and the media coverage of cases.
Alfin‐like transcription factor VqAL4 regulates a stilbene synthase to enhance powdery mildew resistance in grapevine
Authors: Yan Chaohui , Yang Na , Li Ruimin , Wang Xinqi , Xu Yan , Zhang Chaohong , Wang Xiping , Wang Yuejin
Published: November 2022

Resveratrol is a phytoalexin that is synthesized by stilbene synthase (STS). Resveratrol in the human diet is known to have beneficial effects on health. We previously identified six novel STS (VqNSTS) transcripts from the transcriptome data of Vitis quinquangularis accession Danfeng‐2. However, the functions of and defensive mechanisms triggered by these VqNSTS transcripts remain unknown. In the present study, we demonstrate that the expression of five of these six novel members, VqNSTS2–VqNSTS6, can be induced by the powdery mildew‐causing fungus Uncinula necator. Additionally, overexpression of VqNSTS4 in the V. vinifera susceptible cultivar Thompson Seedless promoted accumulation of stilbenes and enhanced resistance to U. necator by activating salicylic acid (SA) signalling. Furthermore, our results indicate that the Alfin‐like (AL) transcription factor VqAL4 can directly bind to the G‐rich element (CACCTC) in the VqNSTS4 promoter and activate gene expression. Moreover, overexpression of VqAL4 in Thompson Seedless enhanced resistance to U. necator by promoting stilbene accumulation and activating SA signalling. Conversely, RNA interference‐mediated silencing of VqNSTS4 and VqAL4 resulted in increased susceptibility to U. necator. Collectively, our results reveal that VqNSTS4, regulated by VqAL4, enhances grapevine resistance to powdery mildew by activating SA signalling. Our findings may be useful to improve disease resistance in perennial fruit trees.
Passive somatosensory training enhances piano skill in adolescent and adult pianists: A preliminary study
Authors: Furuya Shinichi , Tanibuchi Ryuya , Nishioka Hayato , Kimoto Yudai , Hirano Masato , Oku Takanori
Published: November 2022

Sensory afferent information, such as auditory and somatosensory feedback while moving, plays a crucial role in both control and learning of motor performance across the lifespan. Music performance requires skillful integration of multimodal sensory information for the production of dexterous movements. However, it has not been understood what roles somatosensory afferent information plays in the acquisition and sophistication of specialized motor skills of musicians across different stages of development. In the present preliminary study, we addressed this issue by using a novel technique with a hand exoskeleton robot that can externally move the fingers of pianists. Short‐term exposure to fast and complex finger movements generated by the exoskeleton (i.e., passive movements) increased the maximum rate of repetitive piano keystrokes by the pianists. This indicates that somatosensory inputs derived from the externally generated motions enhanced the quickness of the sequential finger movements in piano performance, even though the pianists did not voluntarily move the fingers. The enhancement of motor skill through passive somatosensory training using the exoskeleton was more pronounced in adolescent pianists than adult pianists. These preliminary results implicate a sensitive period of neuroplasticity of the somatosensory‐motor system of trained pianists, which emphasizes the importance of somatosensory‐motor training in professional music education during adolescence.
Corneal tissue changes following short‐term soft contact lens wear of different materials
Authors: Consejo Alejandra , Trillo‐Moreno Irene , Remon Laura
Published: November 2022

Purpose

To study the effect of different soft contact lens (CL) materials during short‐term wear on corneal tissue.

Methods

Twenty‐two healthy participants wore both silicone hydrogel (MyDay, CooperVision) and hydrogel soft CLs (Biomedics 1 day extra, CooperVision) for 8 h per lens. In each session, Scheimpflug images were captured before and immediately after CL removal. Images were analysed using the densitometry distribution analysis, a technique from which two parameters, α (corneal transparency) and β (corneal homogeneity), were estimated. In addition, the central corneal thickness changes after CL wear and the influence of the CL material on corneal transparency were evaluated.

Results

The β parameter (homogeneity) increased by 5% after wearing both CL materials (paired t‐test, p < 0.001). However, the α parameter (transparency) only increased in half of the participants. No material was found to be more determinant in causing the corneal densitometry changes. Statistically significant but not clinically relevant changes in corneal thickness were observed.

Conclusions

Biomarkers of corneal tissue integrity (α and β) were affected by short‐term soft contact lens wear. The observed changes in corneal transparency and homogeneity were not clinically relevant but support the importance of participant‐material biocompatibility.
Justification of empiric methodology to determine dexmedetomidine dose for the TREX study
Authors: Disma Nicola , Goffredo Bianca M. , Cairoli Sara , Cirillo Ginevra , Morse James , Anderson Brian J. ,   the TREX (Trial Remifentanil DEXmedetomidine) Italian Investigators
Published: November 2022

Introduction

Dexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59–67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates.

Methods

The TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicenter, superiority trial comparing neurological outcome after standard sevoflurane anesthesia with dexmedetomidine/remifentanil, and low dose sevoflurane anesthesia in children aged less than 2 years undergoing anesthesia of 2 h or longer. In this report, dexmedetomidine pharmacokinetics were analyzed in the interventional arm of the Italian population.

Results

There were 162 blood samples from 32 infants (22 male and 10 female). The median (IQR) age was 12 (5.2–15.5) months, weight 9.9 (7.3–10.8) kg. Duration of anesthesia ranged from 2 to 6 h. None of the children were born premature (median postnatal age 39 weeks, IQR 38–40 weeks). A 3‐compartment PK model that incorporated allometric scaling and a maturation function demonstrated plasma concentration observations from the current Italian arm of the TREX study were consistent with those predicted by a “universal” model using pooled data obtained from neonates to adults.

Conclusions

This current PK analysis from the Italian arm of the TREX study confirms that plasma concentration of dexmedetomidine is predictable using known covariates such as age and size. The initial target concentration (0.6 μg.L−1) used to sedate children cared for in the intensive care after cardiac surgery was inadequate for infants in the current TREX study. A target concentration 1 mcg.L−1, corresponding to a loading dose of 1 mcg.kg−1 followed by an infusion of 1 mcg.kg−1.h−1, provided adequate sedation.
High‐frequency (10 kHz) spinal cord stimulation (SCS) as a salvage therapy for failed traditional SCS: A narrative review of the available evidence
Authors: Provenzano David Anthony , Park Nicholas , Edgar Deborah , Bovinet Chris , Tate Jordan
Published: November 2022

Introduction

Traditional spinal cord stimulation (t‐SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed ‘salvage’ or ‘rescue’). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy.

Methods

We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥ 3 months of follow‐up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t‐SCS LoE.

Results

Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥ 50% pain relief from baseline), with mean pain relief of 60%. Among repeat‐trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy‐related safety issues were reported among the included articles.

Conclusion

Preliminary data suggest that chronic back and/or leg pain patients with t‐SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method.
Evaluation of strategies to optimize training populations for genomic prediction in oat (Avena sativa)
Authors: Sørensen Espen Sannes , Jansen Constantin , Windju Susanne , Crossa Jose , Sonesson Anna Kristina , Lillemo Morten , Alsheikh Muath
Published: November 2022

Genomic selection is a promising breeding methodology that could increase selection accuracy and intensity and reduce generation interval. As the cost of genotyping decreases, it will be important to optimize training populations for costly phenotypic experiments for many complex traits. The aim of this research was to evaluate different optimization strategies, by using historical data from the Norwegian oat breeding programme at Graminor. In this paper, we focus on the optimization criteria: genetic diversity, phenotypic variance and genetic similarity between the training and testing populations. The four training population strategies—prediction core, diversity core, phenotypic selection and random selection—were applied to an oat candidate population of 1124 lines. An independent testing population was used to calculate the mean prediction abilities for the traits days to heading and plant height. Moreover, the strategies were tested in three independent wheat populations. The results showed that prediction core was the most promising strategy to select training populations with high genetic similarity to the testing set, high genetic diversity, and high phenotypic variance, which resulted in higher prediction ability across population sizes and traits.
The Resonance of Church and State: “Churchstate” Geopolitics, the 2009 Honduran Coup, and the Antidemocratic Turn in the Americas
Authors: Girard William
Published: November 2022

Throughout the Americas, in countries such as Honduras, Paraguay, Brazil, Bolivia, and the United States, right‐wing governments allied with conservative Christians have increasingly pursued violent and antidemocratic means to acquire and maintain political power. Understanding the success of these regimes requires clarity about the ways that “church” and “state” both fuse and diverge. Based on extensive ethnographic fieldwork in Honduras during the 2009 coup, this article details the right‐wing de facto government and Pentecostal churches’ conjoined efforts to bolster support for the coup by focusing on a specific mode of governance: the mapping and moralizing of space. In this case, church and state were unified in both their description of Honduras as a single, bounded entity and their division of other Latin American nations into the categories of friend or enemy. Yet, church and state did not align in their temporalities, ultimate aims, and the agents they depicted as active in the political struggles after the coup. Nevertheless, rather than fragmenting the pro‐coup movement, this combination of overlap and divergence strengthened this mode of governance and brought together a broad coalition in favor of the coup. [state, Christianity, governance, geography, secular, Honduras]
Conflict settlement and identity in territorial claims
Authors: Macaulay Christopher
Published: November 2022

Territorial claims with an ethnic or identity component have been recognized as one of the most enduring and intractable sources of international conflict. Building on previous research which recognized the role of issue indivisibility in making compromise more difficult, this article focuses on the management of territorial claims with an identity or ethnic component. Utilizing the latest Issue Correlates of War (ICOW) dataset, the frequency, success, and qualitative content of negotiations over territorial claims are analyzed. The newest version of the ICOW dataset expands the spatial domain of Hensel and Mitchell's previous work that included the Americas and Western Europe, expanding this domain to include the entire world, and more closely examines the role of concessions in the negotiations process. The results support the contention that issue indivisibility hampers compromise behavior and negotiation success in identity‐based territorial claims. Negotiations are less likely to occur, but surprisingly, more likely to succeed. Successful agreements are also more likely to see major concessions and territorial change. Identity‐based claims are also less likely to end through compromise outcomes like negotiations, and more likely to terminate through unilateral action and violence. The results suggest that identity claims are punctuated by rare bouts of significant negotiations—much of which is driven by conquest, violence, and unilateral action.

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Co‐occurring bunchgrasses are associated with different plant species in dry pine savannas
Authors: Baruzzi Carolina , Li Daijiang , Fill Jennifer M. , Crandall Raelene M.
Published: November 2022

Grass species are often included during restoration to reinstate feedbacks with fire. In biodiverse pine savannas of the southeastern United States, wiregrass (Aristida beyrichiana) is the preferred candidate for restoring low‐intensity fires through the understory. Less common but locally co‐dominant in dry pine savannas, pineywoods dropseed (Sporobolus junceus) is another bunchgrass candidate for restoration. If two bunchgrass species associate with different suites of plants in the understory, restoring both could support a twofold goal of restoring fire regimes and plant biodiversity. To guide restoration goals, we tested the hypothesis that in natural (i.e. not recently restored) dry pine savannas in North Florida where wiregrass and dropseed are co‐dominant, they are associated with different understory plant species richness, occurrence, and abundance under or adjacent to their canopies. Species richness of associated plants did not differ between bunchgrass species or with distance from bunchgrass (i.e. under vs. adjacent). Some associated plant species, however, were more likely to occur and had greater abundance with one or the other bunchgrass species irrespective of distance. Our results suggest that including more than one bunchgrass species in restoration plantings could increase dry pine savanna biodiversity while also reinstating plant‐fire feedbacks.
The suitability of investor‐State dispute settlement and host State counterclaims for implementing climate change international responsibility
Authors: Mejía‐Lemos Diego
Published: November 2022

This article examines the suitability of investor‐State dispute settlement (ISDS) for implementing international responsibility arising out of breaches of climate change obligations, based on a comprehensive review of literature, international decisions and instruments, with a particular focus on counterclaims by host States in ISDS arbitral proceedings. ISDS may prove suitable for these purposes, notably by virtue of the flexibility and hybridity of ISDS arbitral proceedings and the enforceability of ISDS arbitral awards. The flexibility of ISDS results in procedural frameworks more adaptable than other forms of international dispute settlement. The hybridity of ISDS, combining both internal and international legal rules, provides grounds for climate change claims or counterclaims not afforded by national or international law operating separately. And crucially, notwithstanding limitations inherent in the ad hoc nature of ISDS, the enforceability of ISDS arbitral awards furnishes unparalleled opportunities to effectively implement international responsibility for breaches of climate change obligations.
The novel HLA‐A*24:02:159 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Zhang Ying , Zheng Zhong‐Zheng , Du Ke‐Ming , An Lin , Lou Shi‐feng
Published: November 2022

HLA‐A*24:02:159 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 3.
Bilateral mastocytic and fibroblastic nodular proliferative dermatosis affecting ear margins in three domestic cats
Authors: Lefrançois Julie , Sauvé Frédéric , Benoit‐Biancamano Marie‐Odile , Dallaire André , Bernardi de Souza Lucilene
Published: November 2022

This case series describes the clinical appearance, histopathological findings and therapeutic trials of proliferative nodular lesions on bilateral ear margins of three domestic cats including two littermates. All therapeutic trials were unsuccessful. While the aetiology remains unclear, this report highlights different hypotheses in presenting this unusual inflammatory and fibroblastic dermatosis in cats.
Modified toggle pin technique combined with prosthetic capsular reconstruction for surgical stabilization of coxofemoral luxation in a Shetland pony
Authors: Müller Eva M. T. , Ehrle Anna , Pozzi Antonio , Lasarzik de Ascurra Juliane , Lischer Christoph J. , Kümmerle Jan M.
Published: November 2022

Objective

To describe open reduction and surgical stabilization of a coxofemoral luxation in a pony using a modified toggle pin technique and prosthetic joint capsule reconstruction without osteotomy of the greater trochanter.

Animal

A 2‐year‐old Shetland pony with a bodyweight of 167 kg.

Study design

Case report.

Methods

Radiographic examination confirmed craniodorsal luxation of the left coxofemoral joint. An open reduction with the aid of a pulley system was performed. A toggle pin was inserted through a bone tunnel extending from the level of the femoral shaft through the femoral head and the center of the acetabulum for the pin to be positioned on the medial wall of the acetabulum. FiberWire was subsequently passed through the cranial and caudal aspects of the acetabulum as well as a transverse tunnel in the femoral neck in a figure of 8 to facilitate capsular reconstruction. The pony was placed in a sling for 8 weeks and gradually returned to normal activity over 2 months.

Results

Postoperative radiographic examination confirmed the position of the femoral head in the acetabulum with the implants in place. On 2‐year follow‐up the pony was sound at walk and trot.

Conclusion

A combined intra‐ and extra‐articular stabilization technique for coxofemoral luxation in a pony resulted in successful long‐term reduction and excellent outcome.
Opioid-prescribing considerations in patients with cancer and substance misuse or substance use disorder: a scoping review protocol
Authors: Jones Katie Fitzgerald , Malinowski Jennifer , Paice Judith , Childers Julie , Bulls Hailey W. , Morrison Jeni , Ho J. Janet , Alsbrook Karen , Nugent Shannon , Broglio Kathleen , Nickels Katrina , Holbein Monika , Parajuli Jyotsana , Merlin Jessica S.
Published: November 2022

Objective:

This scoping review aims to describe factors in the existing literature that may inform opioid-prescribing decisions for patients with a past or present history of cancer and past or present substance misuse or substance use disorder.

Introduction:

Opioids and opioid-related decisions are critical components of cancer care. Most individuals with cancer will experience pain during cancer care, and over half of patients will receive an opioid prescription. Opioid-prescribing decisions require weighing the benefits and harms. The presence of substance misuse or substance use disorder may elevate the risk of opioid-related harms, but there is a lack of consensus on managing patients at this intersection.

Inclusion criteria:

This review will consider studies that include adult patients with a past or present history of cancer who also have pain and current or historical substance misuse or substance use disorder. The pain may be cancer-related or non-cancer-related. Studies of patients with all types of cancer will be eligible for inclusion, with the exception of non-melanoma skin cancers. Eligible studies will explore factors that inform opioid-prescribing decisions in this patient population.

Methods:

The review will be conducted according to JBI methodology for scoping reviews. Studies written in English since database inception will be included. The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase, APA PsycINFO, and Google Scholar. Eligible studies will undergo data extraction by 2 independent reviewers using a data extraction tool created by the authors. A narrative summary will describe study characteristics, population details, and strategies used to determine appropriate pain management in the patient population.
Proximal dendritic localization of NALCN channels underlies tonic and burst firing in nigral dopaminergic neurons
Authors: Hahn Suyun , Um Ki Bum , Kim So Woon , Kim Hyun Jin , Park Myoung Kyu
Published: November 2022

In multipolar nigral dopamine (DA) neurons, the highly excitable proximal dendritic compartments (PDCs) and two Na+‐permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. However, the causal link between them is unknown. Here we report that the proximal dendritic localization of NALCN underlies pacemaking and burst firing in DA neurons. Our morphological analysis of nigral DA neurons reveals that TRPC3 is ubiquitously expressed in the whole somatodendritic compartment, but NALCN is localized within the PDCs. Blocking either TRPC3 or NALCN channels abolished pacemaking. However, only blocking NALCN, not TRPC3, degraded burst discharges. Furthermore, local glutamate uncaging readily induced burst discharges within the PDCs, compared with other parts of the neuron, and NALCN channel inhibition dissipated burst generation, indicating the importance of NALCN to the high excitability of PDCs. Therefore, we conclude that PDCs serve as a common base for tonic and burst firing in nigral DA neurons.

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Key points

Midbrain dopamine (DA) neurons are slow pacemakers that can generate tonic and burst firings, and the highly excitable proximal dendritic compartments (PDCs) and two Na+‐permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking.

We find that slow tonic firing depends on the basal activity of both the NALCN and TRPC3 channels, but that burst firing does not require TRPC3 channels but relies only on NALCN channels.

We find that TRPC3 is ubiquitously expressed in the entire somatodendritic compartment, but that NALCN exists only within the PDCs in nigral DA neurons.

We show that NALCN channel localization confers high excitability on PDCs and is essential for burst generation in nigral DA neurons.

These results suggest that PDCs serve as a common base for tonic and burst firing in nigral DA neurons.