bluuebunny/crossref_metadata_2025 huggingface dataset:
Virus diversity in metagenomes of a lichen symbiosis (Umbilicaria phaea): complete viral genomes, putative hosts and elevational distributions
Authors: Merges Dominik , Dal Grande Francesco , Greve Carola , Otte Jürgen , Schmitt Imke
Published: October 2021

Viruses can play critical roles in symbioses by initiating horizontal gene transfer, affecting host phenotypes, or expanding their host's ecological niche. However, knowledge of viral diversity and distribution in symbiotic organisms remains elusive. Here we use deep‐sequenced metagenomic DNA (PacBio Sequel II; two individuals), paired with a population genomics approach (Pool‐seq; 11 populations, 550 individuals) to understand viral distributions in the lichen Umbilicaria phaea. We assess (i) viral diversity in lichen thalli, (ii) putative viral hosts (fungi, algae, bacteria) and (iii) viral distributions along two replicated elevation gradients. We identified five novel viruses, showing 28%–40% amino acid identity to known viruses. They tentatively belong to the families Caulimoviridae, Myoviridae, Podoviridae and Siphoviridae. Our analysis suggests that the Caulimovirus is associated with green algal photobionts (Trebouxia) of the lichen, and the remaining viruses with bacterial hosts. We did not detect viral sequences in the mycobiont. Caulimovirus abundance decreased with increasing elevation, a pattern reflected by a specific algal lineage hosting this virus. Bacteriophages showed population‐specific patterns. Our work provides the first comprehensive insights into viruses associated with a lichen holobiont and suggests an interplay of viral hosts and environment in structuring viral distributions.
Edible coatings as osmotic dehydration pretreatment in nutrient‐enhanced fruit or vegetable snacks development: A review
Authors: Kowalska Hanna , Marzec Agata , Domian Ewa , Kowalska Jolanta , Ciurzyńska Agnieszka , Galus Sabina
Published: October 2021

Edible coatings (ECs) are thin layers applied on food to protect it and improve quality. They are made from bio‐based materials such as polysaccharides, proteins, lipids, or their composites. The incorporation of functional agents, such as bioactive compounds, vitamins, or antimicrobials into the EC, has been investigated to control the shelf life of many food products from horticulture ones to processed food. Osmotic dehydration (OD) as a mild technology may also positively impact the availability of innovative fruit snacks and consequently influence consumer health. Combination of the EC with the OD aims to remove water through the semipermeable membrane while limiting the transfer of solutes from the dehydrated tissue and in the opposite direction from the osmotic solution to the food. The development trend of the snack market is expanding, especially with health‐promoting properties. Consumers pay increasing attention to quality of food and its beneficial effects on health. This review attempts to provide the advancement of recent studies on the application of the EC before the OD of different fresh or fresh‐cut fruit and vegetables. A fundamental theory related to the methodology of creating the EC, their composition, and the influence on the physicochemical properties of products that are osmo‐dehydrated to a medium water content or additionally dried to a low water content have been described. Efforts have been exerted to introduce hydrocolloids used in the production of the EC, including new sources of biopolymers such as agricultural waste and by‐products. The perspectives of using ECs in the technology of producing pro‐healthy snacks are emphasized.
Is extended release naltrexone superior to buprenorphine‐naloxone to reduce drinking among outpatients receiving treatment for opioid use disorder? A secondary analysis of the CTN X:BOT trial
Authors: Roache John D. , Pavlicova Martina , Campbell Aimee , Choo Tse‐Hwei , Peavy Michelle , Kermack Andrea S. , Nunes Edward V. , Rotrosen John
Published: October 2021

Background

The comparative effectiveness of extended‐release naltrexone versus buprenorphine‐naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine‐naloxone, BUP‐NX) or injected antagonist (extended release naltrexone, XR‐NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR‐NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR‐NTX (n = 204) was superior to BUP‐NX (n = 270) in reducing drinking or heavy drinking in patients with OUD.

Methods

Standard drink units consumed were measured using the Timeline Follow‐back method. Mixed‐models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink.

Results

Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as “heavy.” Within this subsample, at baseline, the BUP‐NX group reported more mean drinks per drinking day than the XR‐NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment.

Conclusions

There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR‐NTX would be superior to BUP‐NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD.
Neurobeachin, a promising target for use in the treatment of alcohol use disorder
Authors: Cuzon Carlson Verginia C. , Aylwin Carlos F. , Carlson Timothy L. , Ford Matthew , Mesnaoui Houda , Lomniczi Alejandro , Ferguson Betsy , Cervera‐Juanes Rita P.
Published: October 2021

Hazardous, heavy drinking increases risk for developing alcohol use disorder (AUD), which affects ~7% of adult Americans. Thus, understanding the molecular mechanisms promoting risk for heavy drinking is essential to developing more effective AUD pharmacotherapies than those currently approved by the FDA. Using genome‐wide bisulfate sequencing, we identified DNA methylation (DNAm) signals within the nucleus accumbens core (NAcC) that differentiate nonheavy and heavy ethanol‐drinking rhesus macaques. One differentially DNAm region (D‐DMR) located within the gene neurobeachin (NBEA), which promotes synaptic membrane protein trafficking, was hypermethylated in heavy drinking macaques. A parallel study identified a similar NBEA D‐DMR in human NAcC that distinguished alcoholic and nonalcoholic individuals. To investigate the role of NBEA in heavy ethanol drinking, we engineered a viral vector carrying a short hairpin RNA (shRNA) to reduce the expression of NBEA. Using two murine models of ethanol consumption: 4 days of drinking‐in‐the‐dark and 4 weeks of chronic intermittent access, the knockdown of NBEA expression did not alter average ethanol consumption in either model. However, it did lead to a significant increase in the ethanol preference ratio. Following withdrawal, whole‐cell patch clamp electrophysiological experiments revealed that Nbea knockdown led to an increase in spontaneous excitatory postsynaptic current amplitude with no alteration in spontaneous inhibitory postsynaptic currents, suggesting a specific role of NBEA in trafficking of glutamatergic receptors. Together, our findings suggest that NBEA could be targeted to modulate the preference for alcohol use.
Evaluation of the outcome of apexogenesis in traumatised anterior and carious posterior teeth using mineral trioxide aggregate: a 5‐year retrospective study
Authors: Mousivand Shima , Sheikhnezami Mahshid , Moradi Saeed , Koohestanian Niloufar , Jafarzadeh Hamid
Published: October 2021

The purpose of this study was to evaluate the outcome of apexogenesis with mineral trioxide aggregate (MTA) in traumatised anterior and carious posterior teeth over 5 years. A comprehensive chart review was performed to obtain a retrospective of sequential previously completed cases with recalls. Clinical and radiographic data were collected for 97 vital immature teeth (40 traumatised anterior and 57 carious posterior teeth) pulpotomised (partial or full pulpotomy) using MTA with an average follow‐up time of 5 years. Chi‐squared test and Fisher’s exact test were implemented to analyse data. The success rate in anterior teeth and posterior teeth was 82.5% and 96.4% respectively. Crown discolouration was observed in 25 (62.5%) anterior teeth. There was a significant difference between the number of successful and unsuccessful cases (P < 0.05) and there was no correlation between type of treatment and success/failure (P > 0.05). The success rate of apexogenesis using MTA in immature teeth was relatively high.
Quantitative evaluation of aerosol generation during manual facemask ventilation
Authors: Shrimpton A. J. , Brown J. M. , Gregson F. K. A. , Cook T. M. , Scott D. A. , McGain F. , Humphries R. S. , Dhillon R. S. , Reid J. P. , Hamilton F. , Bzdek B. R. , Pickering A. E. ,   the AERATOR study group
Published: October 2021

Manual facemask ventilation, a core component of elective and emergency airway management, is classified as an aerosol‐generating procedure. This designation is based on one epidemiological study suggesting an association between facemask ventilation and transmission during the SARS‐CoV‐1 outbreak in 2003. There is no direct evidence to indicate whether facemask ventilation is a high‐risk procedure for aerosol generation. We conducted aerosol monitoring during routine facemask ventilation and facemask ventilation with an intentionally generated leak in anaesthetised patients. Recordings were made in ultraclean operating theatres and compared against the aerosol generated by tidal breathing and cough manoeuvres. Respiratory aerosol from tidal breathing in 11 patients was reliably detected above the very low background particle concentrations with median [IQR (range)] particle counts of 191 (77–486 [4–1313]) and 2 (1–5 [0–13]) particles.l‐1, respectively, p = 0.002. The median (IQR [range]) aerosol concentration detected during facemask ventilation without a leak (3 (0–9 [0–43]) particles.l‐1) and with an intentional leak (11 (7–26 [1–62]) particles.l‐1) was 64‐fold (p = 0.001) and 17‐fold (p = 0.002) lower than that of tidal breathing, respectively. Median (IQR [range]) peak particle concentration during facemask ventilation both without a leak (60 (0–60 [0–120]) particles.l‐1) and with a leak (120 (60–180 [60–480]) particles.l‐1) were 20‐fold (p = 0.002) and 10‐fold (0.001) lower than a cough (1260 (800–3242 [100–3682]) particles.l‐1), respectively. This study demonstrates that facemask ventilation, even when performed with an intentional leak, does not generate high levels of bioaerosol. On the basis of this evidence, we argue facemask ventilation should not be considered an aerosol‐generating procedure.
Scales of Justice: “International Standards” and “Local Ownership” at a Hybrid Tribunal
Authors: Hughes Rachel , Elander Maria
Published: October 2021

This paper argues that a politics of scale plays a fundamental but uninterrogated role in internationalised criminal justice processes such as hybrid tribunals. Scale discourses—producing specific notions of “the international” and “the local”—are so naturalised in these endeavours that their regressive effects remain unacknowledged. Following Annelise Riles’ ground‐breaking analysis of the politics of scale in colonial law, and feminist critiques of scale discourse in accounts of globalisation and conflict, we think critically about “the international” and “the local” in a postcolonial and post‐conflict justice context. Using the case of the Extraordinary Chambers in the Courts of Cambodia (ECCC), we specifically examine the operation and effects of discourses of “international standards” and “local ownership”. We argue that denaturalising scale in international criminal justice would serve a wider project to decolonise international law and address the specific forms of disenfranchisement currently enacted by dominant “scales of justice”.
Contemporary outcomes of durable ventricular assist devices in adults with congenital heart disease as a bridge to heart transplantation
Authors: Das Bibhuti B. , Kogon Brian , Deshpande Shriprasad R. , Slaughter Mark S. , Trivedi Jaimin R.
Published: October 2021

Objectives

This study aimed to compare the clinical characteristics, risk factors, and overall survival outcomes in adults with congenital heart disease (ACHD) bridged to transplantation with a ventricular assist device (VAD) versus no‐VAD.

Methods

The study included 894 ACHD patients aged ≥18 years listed for primary heart transplantation between 2010 and 2019 from the United Network for Organ Sharing database. Primary outcomes were waitlist and 1‐year post‐transplant mortality between VAD and no‐VAD ACHD patients.

Results

Of 894 ACHD patients included in the study, 91(10.1%) had VAD support at the time of listing. Patients who needed VAD support were mostly males, heavier, and had higher pulmonary artery pressure than the no‐VAD group at the listing. The overall waitlist mortality was 38% in the VAD group than 17% in the no‐VAD group (p < 0.01). ECMO use was associated with significantly higher mortality than either group. There was no significant difference in 1‐year post‐transplant mortality between VAD versus no‐VAD at the time of transplant (15% vs. 17%; p = 0.66). Multivariate regression analysis found that BMI <20 kg/m2 (hazard ratio (HR) 1.1; p = 0.01), bilirubin >2 mg/dl (HR 1.1; p = 0.03), creatinine >2 mg/dl (HR 1.3; p = 0.04) and ECMO at transplant (HR 1.4; p = 0.03) increased early post‐transplant mortality.

Conclusions

The one‐year post‐transplant mortality rate was no different for ACHD patients that received VAD versus no‐VAD. These findings suggest that a VAD should be considered an option to support ACHD patients as a bridge to heart transplantation.
Epithelial–mesenchymal transition‐related serum markers ET‐1, IL‐8 and TGF‐β2 are elevated in a Finnish wet age‐related macular degeneration cohort
Authors: Liukkonen Mikko P. K. , Paterno Jussi J. , Kivinen Niko , Siintamo Leea , Koskela Ali K. J. , Kaarniranta Kai
Published: October 2021

Purpose

It has been hypothesized that epithelial–mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age‐related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT‐associated markers were altered in the serum of wet AMD patients. Serum biomarkers associated with the various pathological processes of AMD may present an avenue towards identifying and characterizing the birth mechanisms of wet AMD, its progression and severity, paving the way towards the application of precision medicine.

Methods

We chose to measure the serum levels of known biomarkers of EMT – EGF (epidermal growth factor), ET‐1 (endothelin 1), IL‐8 (interleukin 8), TGF‐β1 and TGF‐β2 (transforming growth factor‐beta 1 and 2) and VEGF‐A (vascular endothelial growth factor A) – using enzyme‐linked immunosorbent assays. We measured them from 71 Finnish wet AMD patients who were receiving intravitreal anti‐VEGF‐A injection treatments, as well as 64 age‐adjusted controls.

Results

We found significantly elevated levels of ET‐1, IL‐8 and TGF‐β2 in the serums of wet AMD patients.

Conclusions

ET‐1, IL‐8 and TGF‐β2 appear to be useful serum biomarkers in understanding active wet AMD. However, we cannot conclude that local retinal EMT‐processes could be observed from the corresponding systemic serum biomarkers in patients undergoing anti‐VEGF‐A treatments.
Editorial: autoimmune diseases in microscopic colitis—how does this information help clinicians?
Authors: Pardi Darrell
Published: October 2021

LINKED CONTENT

This article is linked to Wildt et al paper. To view this article, visit https://doi.org/10.1111/apt.16614
Theorising from the Belt and Road Initiative (一带一路)
Authors: Lin Shaun , Shimazu Naoko , Sidaway James D.
Published: October 2021

As frame for the set that follows, this article first considers the range of theoretical interpretations of China's Belt and Road Initiative (BRI). Our focus, however, is on a related yet distinct set of questions. Rather than theorising BRI per se, we approach BRI as a source of theoretical implications and reflection – asking what it signals and implies for wider cultural, economic, political, social and urban theories, and for histories of and afterlives of imperial geopolitics.
Approaches towards tissue‐selective pharmacology of the mineralocorticoid receptor
Authors: Clarisse Dorien , Deng Lisa , de Bosscher Karolien , Lother Achim
Published: October 2021

Mineralocorticoid receptor antagonists (MRAs) are highly effective therapies for cardiovascular and renal disease. However, the widespread clinical use of currently available MRAs in cardiorenal medicine is hampered by an increased risk of hyperkalaemia. The mineralocorticoid receptor (MR) is a nuclear receptor responsible for fluid and electrolyte homeostasis in epithelial tissues, whereas pathophysiological MR activation in nonepithelial tissues leads to undesirable pro‐inflammatory and profibrotic effects. Therefore, new strategies that selectively target the deleterious effects of the MR but spare its physiological function are needed. In this review, we discuss recent pharmacological developments starting from novel non‐steroidal MRAs, such as finerenone or esaxerenone, that are now entering clinical use, to concepts arising from the current knowledge of the MR signalling pathway, aiming at receptor–coregulator interaction, epigenetics or downstream effectors of the MR.

LINKED ARTICLES

This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone‐Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc
Sedimentary architecture of a Late Cretaceous under‐filled rift basin, Canterbury Basin, New Zealand
Authors: Barrier Andrea , Browne G. H. , Nicol A. , Bassett Kari
Published: October 2021

The Canterbury Basin in southeastern Zealandia was initiated during the late Albian (ca. 105 Ma) as a rift system, prior to the onset of seafloor spreading between Zealandia and eastern Gondwana at ca. 85 Ma. Basin‐fill architecture and sediment types have been determined from interpretation of 2D and 3D seismic‐reflection lines tied to five wells and compared to outcrop data from the literature. These data show that Cretaceous syn‐rift basin‐fill architecture was controlled by normal faulting, which produced basin and range topography that persisted for more that ca. 30 Myr after the cessation of faulting. Initial sedimentation was dominated by short drainage systems sourced from within the basin to produce alluvial fans along fault scarps, which inter‐fingered with axial‐flowing braided river conglomerates, coal measures and mudstone‐rich lake deposits in more central portions of the basins. Marine incursion of the basin from the east commenced during rifting and onset of Gondwana breakup, with maximum water depths achieved in the Oligocene. Post‐rifting, detrital sediments were mainly sourced locally from structural highs and augmented by pelagic sedimentation, which collectively draped and eventually buried most of the earlier‐formed horsts by the Early Eocene. The temporal persistence of basin and range topography reflected the low rates of erosion of horst blocks compared to the rates of fault displacement. The lack of substantial sediment input from outside of the rift basin was a key factor in the under‐filling of the Canterbury Basin. This research emphasises the key role played by sediment supply in rift basin filling. Despite an abundance of active faulting at initiation, some rift basins may fill slowly over tens of million years after rift cessation.
Body mass index is inversely associated with capillary ketones at the time of colonoscopy: Implications for SGLT2i use
Authors: Hamblin Peter S. , Wong Rosemary , Ekinci Elif I. , Sztal‐Mazer Shoshana , Balachandran Shananthan , Frydman Aviva , Hanrahan Timothy P. , Hu Raymond , Ket Shara N. , Moss Alan , Ng Mark , Ragunathan Sashikala , Bach Leon A.
Published: October 2021

Objective

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i‐treated type 2 diabetes compared with non‐SGLT2i‐treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia.

Design

Cross‐sectional, multicentre, observational study June–December 2020 in four Australian tertiary hospitals.

Participants

Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i‐treated and 105 non‐SGLT2i‐treated type 2 diabetes, 65 IFG and 151 normoglycaemia.

Measurements

Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose.

Results

In SGLT2i‐treated diabetes, BMI (ρ = −0.43 [95% confidence interval: −0.67, −0.11]) and duration since last SGLT2i dose (ρ = −0.33 [−0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non‐SGLT2i‐treated diabetes, BMI correlated negatively (ρ = −0.24 [−0.42, −0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = −0.20 [−0.35, −0.04]) and fasting glucose (ρ = −0.31 [−0.45, −0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i‐treated participants only BMI remained independently associated.

Conclusions

In SGLT2i‐treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.
Phylogenomics and loci dropout patterns of deeply diverged Zodarion ant‐eating spiders suggest a high potential of RAD‐seq for genus‐level spider phylogenetics
Authors: Ortiz David , Pekár Stano , Dianat Malahat
Published: October 2021

RAD sequencing yields large amounts of genome‐wide data at a relatively low cost and without requiring previous taxon‐specific information, making it ideal for evolutionary studies of highly diversified and neglected organisms. However, concerns about information decay with phylogenetic distance have discouraged its use for assessing supraspecific relationships. Here, using Double Digest Restriction Associated DNA (ddRAD) data, we perform the first deep‐level approach to the phylogeny of Zodarion, a highly diversified spider genus. We explore the impact of loci and taxon filtering across concatenated and multispecies coalescent reconstruction methods and investigate the patterns of information dropout in reference to both the time of divergence and the mitochondrial divergence between taxa. We found that relaxed loci‐filtering and nested taxon‐filtering strategies maximized the amount of molecular information and improved phylogenetic inference. As expected, there was a clear pattern of allele dropout towards deeper time and mitochondrial divergences, but the phylogenetic signal remained strong throughout the phylogeny. Therefore, we inferred topologies that were almost fully resolved, highly supported, and noticeably congruent between setups and inference methods, which highlights overall inconsistency in the taxonomy of Zodarion. Because Zodarion appears to be among the oldest and most mitochondrially diversified spider genera, our results suggest that ddRAD data show high potential for inferring intra‐generic relationships across spiders and probably also in other taxonomic groups.
Adapting regulatory drug‐drug interaction guidance to design clinical pharmacokinetic natural product‐drug interaction studies: A NaPDI Center recommended approach
Authors: Cox Emily J. , Rettie Allan E. , Unadkat Jashvant D. , Thummel Kenneth E. , McCune Jeannine S. , Paine Mary F.
Published: October 2021

Pharmacokinetic drug interactions precipitated by botanical and other natural products (NPs) remain critically understudied. Investigating these complex interactions is fraught with difficulties due to the methodologic and technical challenges associated with the inherently complex chemistries and product variability of NPs. This knowledge gap is perpetuated by a continuing absence of a harmonized framework regarding the design of clinical pharmacokinetic studies of NPs and NP‐drug interactions. Accordingly, this Recommended Approach, the fourth in a series of Recommended Approaches released by the Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center), provides recommendations for the design of clinical pharmacokinetic studies involving NPs. Building on prior Recommended Approaches and data generated from the NaPDI Center, such a framework is presented for the design of (1) phase 0 studies to assess the pharmacokinetics of an NP and (2) clinical pharmacokinetic NP‐drug interaction studies. Suggestions for NP sourcing, dosing, study design, participant selection, sampling periods, and data analysis are presented. With the intent to begin addressing the gap between regulatory agencies’ guidance documents about drug‐drug interactions and contemporary NPDI research, the objective of this Recommended Approach is to propose methods for the design of clinical pharmacokinetic studies of NPs and NP‐drug interactions.
Patch/plaque mycosis‐fungoides‐like presentations of DUSP22‐translocated T‐cell lymphomas
Authors: Runge John S. , Novice Madison L. , Briones Naomi , Williams Kiyanna , Lowe Lori , Boyer Daniel F. , Wilcox Ryan A. , Tejasvi Trilokraj , Hristov Alexandra C.
Published: October 2021

The DUSP22‐IRF4 gene rearrangement results in downregulation of DUSP22, a presumed tumor suppressor in T‐cell lymphomagenesis. It has been described in some cases of primary cutaneous and systemic anaplastic large‐cell lymphoma, lymphomatoid papulosis, and transformed mycosis fungoides. Here we describe two patients with clinical lesions resembling patch/plaque mycosis fungoides that did not meet WHO criteria for large‐cell transformation on histopathology yet showed a DUSP22 translocation. One patient who had a history of systemic anaplastic large‐cell lymphoma with DUSP22 translocation presented with cutaneous involvement by his systemic lymphoma along with lymphomatoid papulosis and mycosis‐fungoides‐like lesions, all showing an identical immunophenotype and T‐cell clone. These cases expand the spectrum of DUSP22‐rearranged lymphomas to include mycosis‐fungoides‐like presentations without large‐cell transformation.
Bayesian causal inference in visuotactile integration in children and adults
Authors: Verhaar Erik , Medendorp Wijbrand Pieter , Hunnius Sabine , Stapel Janny C.
Published: October 2021

If cues from different sensory modalities share the same cause, their information can be integrated to improve perceptual precision. While it is well established that adults exploit sensory redundancy by integrating cues in a Bayes optimal fashion, whether children under 8 years of age combine sensory information in a similar fashion is still under debate. If children differ from adults in the way they infer causality between cues, this may explain mixed findings on the development of cue integration in earlier studies. Here we investigated the role of causal inference in the development of cue integration, by means of a visuotactile localization task. Young children (6–8 years), older children (9.5–12.5 years) and adults had to localize a tactile stimulus, which was presented to the forearm simultaneously with a visual stimulus at either the same or a different location. In all age groups, responses were systematically biased toward the position of the visual stimulus, but relatively more so when the distance between the visual and tactile stimulus was small rather than large. This pattern of results was better captured by a Bayesian causal inference model than by alternative models of forced fusion or full segregation of the two stimuli. Our results suggest that already from a young age the brain implicitly infers the probability that a tactile and a visual cue share the same cause and uses this probability as a weighting factor in visuotactile localization.
The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections
Authors: Rombouts Karlijn B. , van Merrienboer Tara A. R. , Ket Johannes C. F. , Bogunovic Natalija , van der Velden Jolanda , Yeung Kak Khee
Published: October 2021

Background

Aortic aneurysms (AA) are pathological dilations of the aorta, associated with an overall mortality rate up to 90% in case of rupture. In addition to dilation, the aortic layers can separate by a tear within the layers, defined as aortic dissections (AD). Vascular smooth muscle cells (vSMC) are the predominant cell type within the aortic wall and dysregulation of vSMC functions contributes to AA and AD development and progression. However, since the exact underlying mechanism is poorly understood, finding potential therapeutic targets for AA and AD is challenging and surgery remains the only treatment option.

Methods

In this review, we summarize current knowledge about vSMC functions within the aortic wall and give an overview of how vSMC functions are altered in AA and AD pathogenesis, organized per anatomical location (abdominal or thoracic aorta).

Results

Important functions of vSMC in healthy or diseased conditions are apoptosis, phenotypic switch, extracellular matrix regeneration and degradation, proliferation and contractility. Stressors within the aortic wall, including inflammatory cell infiltration and (epi)genetic changes, modulate vSMC functions and cause disturbance of processes within vSMC, such as changes in TGF‐β signalling and regulatory RNA expression.

Conclusion

This review underscores a central role of vSMC dysfunction in abdominal and thoracic AA and AD development and progression. Further research focused on vSMC dysfunction in the aortic wall is necessary to find potential targets for noninvasive AA and AD treatment options.
Critical appraisal of the information available on traumatic dental injuries found in applications
Authors: Loureiro Jéssica Muniz , Jural Lucas Alves , Soares Thais Rodrigues Campos , Risso Patrícia A. , Fonseca‐Gonçalves Andréa , Magno Marcela Baraúna , Maia Lucianne Cople
Published: October 2021

Background/Aims

Traumatic dental injuries (TDI) are a public health problem and the search for information becomes essential to help in their management. The aim of this study was to search existing TDI applications (Apps) to critically describe the characteristics and main information found in them regarding TDI.

Methodology

Searches were performed in the Play Store (Android) and App Store (iOS), using MeSH terms, synonyms and terms related to dental emergencies and TDI, in English, Spanish and Portuguese. Apps with information on the management of post‐TDI emergencies or TDI prevention were included. The type of operating system (Android/iOS), cost (free/paid), target audience (dentist/patient), age of classification (free/>17 years old), language, star rating (1★ to 5★), number of downloads and post‐download ratings, type of dentition (primary/permanent), reference used for classification according to TDI type and management (International Association for Dental Traumatology/Andreasen/others/not reported), and available content (prevention/emergency management/preservation/illustrations) were evaluated.

Results

Among 486 apps, 13 were eligible: 11 for Android and 2 for iOS. Most were free (92.3%), for patients (38.4%) and had a free age classification (90.9%). The main language was English (53.8%), and most of the Apps either had no information on star ratings (46.1%) or received 4★ (23.1%). The number of downloads was not reported (23.1%) or was fewer than 100 (23.1%). Most of the Apps were for permanent teeth (61.5%) and had explanations about dental management for TDI emergencies (92.3%) and multiple TDIs (61.5%). Most Apps addressed the importance of monitoring TDIs (76.9%) and contained illustrative images (76.9%). However, many did not report the TDI classification (46.1%), and 38.5% reported TDI prevention.

Conclusions

Information on dental trauma management according to dental injury, inclusion of images, target audience, type of TDI and their prevention varied in the available Apps. However, most were focused on permanent teeth and addressed several TDI in English language only.
Complex introgression among three diverged largemouth bass lineages
Authors: Silliman Katherine , Zhao Honggang , Justice Megan , Thongda Wilawan , Bowen Bryant , Peatman Eric
Published: October 2021

Hybrid zones between diverged lineages offer a unique opportunity to study evolutionary processes related to speciation. Natural and anthropogenic hybridization in the black basses (Micropterus spp.) is well documented, including an extensive intergrade zone between the widespread northern Largemouth Bass (M. salmoides) and the Florida Bass (M. floridanus). Phenotypic surveys have identified an estuarine population of Largemouth Bass (M. salmoides) in the Mobile‐Tensaw Delta, with larger relative weight and smaller adult size compared to inland populations, suggesting a potential third lineage of largemouth bass. To determine the evolutionary relationships among these Mobile Delta bass populations, M. salmoides and M. floridanus, putative pure and intergrade populations of all three groups were sampled across the eastern United States. Phylogenetic analyses of 8582 nuclear SNPs derived from genotype‐by‐sequencing and the ND2 mitochondrial gene determined that Delta bass populations stem from a recently diverged lineage of Largemouth Bass. Using a novel quantitative pipeline, a panel of 73 diagnostic SNPs was developed for the three lineages, evaluated for accuracy, and then used to screen 881 samples from 52 sites for genetic integrity and hybridization on the Agena MassARRAY platform. These results strongly support a redrawing of native ranges for both the intergrade zone and M. floridanus, which has significant implications for current fisheries management. Furthermore, Delta bass ancestry was shown to contribute significantly to the previously described intergrade zone between northern Largemouth Bass and Florida Bass, suggesting a more complex pattern of secondary contact and introgression among these diverged Micropterus lineages.
Topical 5‐fluorouracil as an adjunct treatment in equine corneolimbal squamous cell carcinoma
Authors: Offer K. S. , Marchesi F. , Sutton D. G. M.
Published: October 2021

An 11‐year‐old crossbreed mare was presented with a nodular, pink mass at the temporal corneolimbal junction of the right eye. Histopathology confirmed the diagnosis of invasive squamous cell carcinoma. The mare underwent lamellar keratectomy and conjunctivectomy under general anaesthesia, followed by adjunctive topical chemotherapy with 1% 5‐fluorouracil solution for 10 days post‐operatively. Adverse effects included moderate conjunctival inflammation and exuberant granulation tissue formation at the surgical site, responding to surgical debulking and topical corticosteroid application. No mass regrowth was present at 12 months following discharge. This report describes the successful use of topical 1% 5‐FU as an adjunctive treatment for equine ocular squamous cell carcinoma.
Multi‐view rank‐based random forest: A new algorithm for prediction in eSports
Authors: Birant Kokten Ulas
Published: October 2021

The main problem associated with the random forest (RF) algorithm is its application of random feature subset selection technique over a single vector. In this technique, the irrelevant or redundant features in a single‐view data have equal chances with the important features to be selected for training a classifier, leading to misclassification. To overcome this problem, this article proposes a novel algorithm, called multi‐view rank‐based random forest (MVRRF). The proposed algorithm builds a set of decision trees from multi‐view data by using a rank‐based feature selection strategy. The main advantages of our method are that (i) it extends the RF algorithm for multi‐view learning, and (ii) it reduces the chances of irrelevant and redundant feature selection, and thus it usually improves the accuracy, generalizability and robustness of the classification models. The aim of our study is to predict the match result of the game League of Legends in electronic sports (eSports). Thus, the eSports teams can define trustworthy strategies through important features. The proposed method can be successfully used in other fields as well as eSports. The experiments that were conducted on a publicly available eSports dataset show that the proposed MVRRF algorithm (93.32%) outperforms the standard RF algorithm (86.38%) on multi‐view data in terms of accuracy. Furthermore, the experimental results also show that our method achieved higher performance than the methods tested in the state of the art studies on the same dataset.
Timeless in animal circadian clocks and beyond
Authors: Cai Yao D. , Chiu Joanna C.
Published: October 2021

TIMELESS (TIM) was first identified as a molecular cog in the Drosophila circadian clock. Almost three decades of investigations have resulted in an insightful model describing the critical role of Drosophila TIM (dTIM) in circadian timekeeping in insects, including its function in mediating light entrainment and temperature compensation of the molecular clock. Furthermore, exciting discoveries on its sequence polymorphism and thermosensitive alternative RNA splicing have also established its role in regulating seasonal biology. Although mammalian TIM (mTIM), its mammalian paralog, was first identified as a potential circadian clock component in 1990s due to sequence similarity to dTIM, its role in clock regulation has been more controversial. Mammalian TIM has now been characterized as a DNA replication fork component and has been shown to promote fork progression and participate in cell cycle checkpoint signaling in response to DNA damage. Despite defective circadian rhythms displayed by mtim mutants, it remains controversial whether the regulation of circadian clocks by mTIM is direct, especially given the interconnection between the cell cycle and circadian clocks. In this review, we provide a historical perspective on the identification of animal tim genes, summarize the roles of TIM proteins in biological timing and genomic stability, and draw parallels between dTIM and mTIM despite apparent functional divergence.
Experimental evidence shows minor contribution of nitrogen deposition to global forest carbon sequestration
Authors: Schulte‐Uebbing Lena F. , Ros Gerard H. , de Vries Wim
Published: October 2021

Human activities have drastically increased nitrogen (N) deposition onto forests globally. This may have alleviated N limitation and thus stimulated productivity and carbon (C) sequestration in aboveground woody biomass (AGWB), a stable C pool with long turnover times. This ‘carbon bonus’ of human N use partly offsets the climate impact of human‐induced N2O emissions, but its magnitude and spatial variation are uncertain. Here we used a meta‐regression approach to identify sources of heterogeneity in tree biomass C‐N response (additional C stored per unit of N) based on data from fertilization experiments in global forests. We identified important drivers of spatial variation in forest biomass C‐N response related to climate (potential evapotranspiration), soil fertility (N content) and tree characteristics (stand age), and used these relationships to quantify global spatial variation in N‐induced forest biomass C sequestration. Results show that N deposition enhances biomass C sequestration in only one‐third of global forests, mainly in the boreal region, while N reduces C sequestration in 5% of forests, mainly in the tropics. In the remaining 59% of global forests, N addition has no impact on biomass C sequestration. Average C‐N responses were 11 (4–21) kg C per kg N for boreal forests, 4 (0–8) kg C per kg N for temperate forests and 0 (−4 to 5) kg C per kg N for tropical forests. Our global estimate of the N‐induced forest biomass C sink of 41 (−53 to 159) Tg C yr−1 is substantially lower than previous estimates, mainly due to the absence of any response in most tropical forests (accounting for 58% of the global forest area). Overall, the N‐induced C sink in AGWB only offsets ~5% of the climate impact of N2O emissions (in terms of 100‐year global warming potential), and contributes ~1% to the gross forest C sink.
Ethyl caffeate ameliorated amyloid‐beta42 protein‐associated toxicity inPC12cells andDrosophila melanogaster
Authors: Tan Florence Hui Ping , Hadri Nurulhuda Athirah Binti , Najimudin Nazalan , Watanabe Nobumoto , Azzam Ghows
Published: October 2021

Aim

Alzheimer's disease (AD) is the most pervasive neurodegenerative disorder in societies globally. Till now, the mechanism behind this disease is still equivocal. Amyloid‐beta42 protein (Aβ42), the most toxic and aggressive Aβ species, is the main focus of this study. The naturally occurring ethyl caffeate (EC) is associated with various medicinal properties. Here, EC was tested for its protective properties against Aβ42's toxic effects.

Methods

As treatment of Aβ42 has been shown to cause neuronal cell death, EC was first screened with Aβ42‐incubated PC12 neuronal cells. Next, the compound was tested on theDrosophila melanogasterAD model using the rough eye phenotype assay, lifespan assay and negative geotaxis assay.

Results

EC ameliorated PC12 cells from cell death linked to Aβ42 exposure. UsingDrosophilaexpressing human Aβ42, feeding of EC was able to partially rescue the rough eye phenotype, lengthen the lifespan of ADDrosophilaand enhanced the mobility of middle‐aged ADDrosophila.

Conclusion

Overall, the results of this study showed that EC might possess therapeutic properties for AD.Geriatr Gerontol Int 2021; 21: 1125–1130.
Virtual learning experiences in population health nursing course during the COVID‐19 pandemic
Authors: Manakatt Bushra M. , Carson Zachary W. , Penton Rebekah L. , Demello Annalyn S.
Published: October 2021

Aim

To discuss the virtual learning strategies used in population health nursing course during the coronavirus disease 2019 (COVID‐19) pandemic.

Background

The School of Nursing faculty in a South Central University in the United States quickly combined innovation with digital resources and transitioned a course in population health during the COVID‐19 pandemic. Nursing faculty were challenged to develop student nursing objectives in assessment, planning, intervention and evaluation of vulnerable populations in the community through a virtual environment.

Reflections of population health nursing clinical education

The experiences of five clinical groups are described, covering adults with disabilities, older people, patients with COVID‐19 and youth populations.

Discussion

The course objectives were met through use of a digital environment. Collaborative interventions were designed and implemented with community stakeholders while maintaining social distancing policies. Successes included increased frequency of communication and learning opportunities for students and the community, and student satisfaction. Barriers to student learning were not related to the digital learning environment, although the older adults required modifications to use electronic devices.

Conclusion

Virtual classrooms are a viable platform to teach population health nursing and to benefit vulnerable populations.

Implications for nursing practice

Virtual learning offers benefits within academia and the community. Technology offers the possibility to improve mental health among older people and enhance knowledge among the general population. Students are better able to connect with clinical faculty and stakeholders through digital platforms.

Implications for nursing policy

Nurses play a vital role in improving population health and can collaborate with community stakeholders to implement innovative and sustainable solutions to nursing education, practices and policy. Digital platforms can enhance the involvement of students through these collaborations during and after the pandemic.
Fusion of apoptosis‐related protein Cytochrome c with anti‐HER‐2 single‐chain antibody targets the suppression of HER‐2+ breast cancer
Authors: Lu DanDan , Guo YiChen , Hu YunFeng , Wang Min , Li Chen , Gangrade Abhishek , Chen JiaHui , Zheng ZiHui , Guo Jun
Published: October 2021

Cancer treatment has gradually developed from toxic chemotherapy to targeted therapy with fewer side effects. Approximately 30% of breast cancer patients overexpress human epidermal growth factor receptor 2 (HER‐2). Previous studies have successfully produced single‐chain antibodies (scFv) targeting HER‐2+ breast cancer; however, scFv have poor stability, easy aggregation and a shorter half‐life, which have no significant effect on targeting therapy. Moreover, scFv has been considered as a drug delivery platform that can kill target cells by effector molecules. However, the functional killing domains of immunotoxins are mainly derived from plant or bacterial toxins, which have a large molecular weight, low tissue permeability and severe side effects. To address these concerns, we designed several apoptotic immune molecules to replace exogenous toxins using endogenous apoptosis‐related protein DNA fragmentation factor 40 (DFF40) and tandem‐repeat Cytochrome c base on caspase‐3 responsive peptide (DEVD). Our results suggest that DFF40 or Cytc fusion scFv specifically targets HER‐2 overexpressing breast cancer cells (SK‐BR‐3 and BT‐474) rather than HER‐2 negative cells (MDA‐MB‐231 and MCF‐7). Following cellular internalization, apoptosis‐related proteins inhibited tumour activity by initiating endogenous apoptosis pathways, which significantly reduced immunogenicity and toxic side effects. Therefore, we suggest that immunoapoptotic molecules may become potential drugs for targeted immunotherapy of breast cancer.