bluuebunny/crossref_metadata_2025 huggingface dataset:
Door Locks, Wall Stickers, Fireplaces: Assemblage Theory and Home (Un)Making in Lewisham’s Temporary Accommodation
Authors: Harris Ella , Brickell Katherine , Nowicki Mel
Published: June 2020

This paper explores resident experiences of life in PLACE/Ladywell, a “pop‐up” social housing scheme in London providing temporary accommodation for homeless families. Specifically, we consider barriers to, and assertions of, homemaking in this temporary setting through fixtures and fittings—a door lock, wall stickers, and a fireplace. The paper utilises assemblage thinking to understand homemaking within these time‐limited and constrained circumstances. Despite their seeming banality, fixtures and fittings offer a material, politicised, and lively means of studying the attempted and thwarted production of home by residents living in PLACE/Ladywell. The absence of door locks reduces parents’ ability to maintain privacy and intimate relations; restrictions on hanging pictures and other decorative measures are circumvented by the use of wall stickers; and a defiant decorative fireplace establishes a sense of home in a temporary setting. Together, these objects constitute vital elements in negotiations between fixity and impermanence in temporary accommodation.
Thyroid cancer metastasis is associated with an overabundance of defective follicular helper T cells
Authors: Qian Guangfang , Wu Min , Zhao Yuanyuan , Li Qing , Zhang Mimi , Cai Chen , Tong Danian
Published: June 2020

Metastatic thyroid cancers are more difficult to treat and have a significantly worse prognosis than localized thyroid cancers. Previous studies have shown that follicular helper T cells (Tfh) may participate in antitumor immune responses. Here, we investigated the characteristics of Tfh cells in patients with differentiated thyroid cancer (DTC) at various severities, including patients with localized disease, cervical metastasis, and distant metastasis. In circulating CD4 T cells, the proportion of CD4+CXCR5+ Tfh‐like cells was significantly higher in patients with distant metastasis than in healthy controls, patients with local disease, and patients with cervical metastasis. Also, the expression of Tfh cell‐associated surface molecules, such as PD‐1, ICOS, and BTLA, tended to be higher in patients with cervical and distant metastasis than in healthy controls. However, the expression of secreted molecules, such as IL‐10, IL‐21, and CXCL13, was significantly lower in patients with distant metastasis than in healthy controls and patients with local disease. Additionally, circulating Tfh‐like cells from patients with distant metastasis were less capable of supporting B‐cell growth and IgM secretion. We also examined the CD4+CXCR5+ Tfh‐like cells in tumor samples. Tumor‐infiltrating Tfh‐like cells were highly enriched in the pulmonary metastasis compared to the local tumor and the cervical metastasis. However, tumor‐infiltrating Tfh‐like cells from pulmonary metastasis displayed higher PD‐1, TIM‐3, and lower IL‐21 expression than those from the local tumor. Together, this study identified that the metastasis of DTC patients was associated with an overabundance of defective Tfh cells.
Performance analysis of high‐throughput HPV testing on three automated workflows
Authors: Loonen Anne J. M. , Huijsmans Cornelis J. J. , Geurts‐Giele Willemina R. R. , Leeijen Cindy , van der Linden Johannes C. , van den Brule Adriaan J. C.
Published: June 2020

Primary high‐risk human papillomavirus (hrHPV) DNA testing has been introduced in several countries worldwide, including The Netherlands. The objective of this study was to compare three automated workflow procedures for hrHPV testing of which the hrHPV detection assays meet the international guidelines for HPV testing. To mimic a realistic screening situation, we aimed to process 15 000 residual PreservCyt cervical samples in a period of 3 months. During a 3 months period, four technicians were involved in processing 5000 specimens per month on three automated platforms, (1) Qiagen Digene® HC2 HPV DNA test (HC2, signal amplification); (2) Roche Cobas® HPV test (DNA amplification), and (3) Hologic Aptima® HPV test (RNA amplification). We measured and scored general aspects (time‐to‐results, hands‐on‐time (HOT)), maintenance, pre‐run, run and post‐run aspects, inventory (orders, storage), and number of errors on a scale from 1 to 10. As determined for one complete workflow each, maximum processing capacity and HOT were 296 samples and 2 h:55 m, 282 samples and 3 h:20 m, and 264 samples and 4 h:15 m for Aptima, Cobas, and HC2, respectively. The mean throughput time per run was 5 h:51 m for Cobas in which 94 samples could be processed. For Aptima, the mean throughput time per run was 6 h:30 m for 60 samples. Mean throughput time for HC2 is longer since results were provided on day 2. In this study, the fully automated Aptima workflow scores best with a 7.2, followed by Cobas with a score of 7.1 and HC2 with a score of 5.8. Although all HPV tests used in this comparison meet the international test guidelines, the performance (workflow) characteristics of the assays vary widely. A specific choice of a laboratory for high‐throughput testing can be different based on the laboratory's demands, but also hands‐on‐time, time‐to‐results/ # samples, maintenance, pre‐run, run and post‐run parameters, consumables, technical support, and number of errors are important operational factors for the selection of a fully automated workflow for hrHPV testing.
Review article: FODMAPS, prebiotics and gut health‐the FODMAP hypothesis revisited
Authors: Gibson Peter R. , Halmos Emma P. , Muir Jane G.
Published: June 2020

Background

Restriction of dietary FODMAP intake can alleviate symptoms in patients with irritable bowel syndrome. Because many FODMAPs have prebiotic actions, there is concern that their dietary restriction leads to dysbiosis with health consequences, and their intake is being encouraged by addition to foods and via supplements.

Aims

To examine the hazards and benefits of high and low FODMAP intake.

Methods

Current literature was reviewed and alternative hypotheses formulated.

Results

Low FODMAP intake reduces abundance of faecal Bifidobacteria without known adverse outcomes and has no effect on diversity, but the reduction in bacterial density may potentially be beneficial to gut health. Supplementary prebiotics can markedly elevate the intake of FODMAPs over levels consumed in the background diet. While this increases the abundance of Bifidobacteria, it adversely affects gut health in animal studies by inducing colonic mucosal barrier dysfunction, mucosal inflammation and visceral hypersensitivity. Rapid colonic fermentation is central to the identified mechanisms that include injury from high luminal concentrations of short‐chain fatty acids and low pH, and inflammatory effects of increased endotoxin load and glycation of macromolecules. Whether these observations translate into humans requires further study. Opposing hypotheses are presented whereby excessive intake of FODMAPs might have health benefits via prebiotic effects, but might also be injurious and contribute to the apparent increase in functional intestinal disorders.

Conclusions

Reduced FODMAP intake has few deleterious effects on gut microbiota. Consequences (both positive and negative) of excessive carbohydrate fermentation in the human intestines from elevated FODMAP intake require more attention.
Involvement of H2S, NO and BDNF‐TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole‐induced kindling and cognitive impairments in mice
Authors: Ahmed Marwa A. , Kamel Esam O.
Published: June 2020

Cognitive dysfunction was observed in pentylenetetrazole (PTZ)‐kindled mice. The potential effectiveness of simvastatin (SIM) on PTZ‐induced kindling and cognitive impairments in mice was evaluated. The influence of SIM on hydrogen sulphide (H2S), nitric oxide (NO), reactive aldehydes and brain‐derived neurotrophic factor/tyrosine receptor kinase B (BDNF‐TrkB) signalling was also investigated. Kindling and cognitive impairments in mice were induced by 12 ip injections of PTZ (35 mg/kg) once every alternate day. The levels of reactive aldehydes and nitrite were increased while H2S was decreased in PTZ‐treated mice. These results were accompanied by a reduction in the gene expression of aldehyde dehydrogenase 2, cystathionine β‐synthase, BDNF and TrkB. In PTZ‐kindled mice, a rise in brain inducible nitric oxide synthase protein expression associated with histopathological changes was observed. SIM administration (1, 5 and 10 mg/kg, daily orally) along with alternate day of PTZ (35 mg/kg) resulted in a decrease in PTZ‐induced kindling with a dose‐dependent improvement in cognitive function. SIM (10 mg/kg) prevented, to variable extent, the disturbances associated with PTZ‐kindled mice with cortical, cerebellar and hippocampal structural improvement. These results suggested that SIM triggers multiple mechanisms that improve cognitive function in PTZ‐kindled mice through modulation of oxidative stress, H2S, NO and BDNF‐TrkB signalling pathway.
Practical wisdom as an adaptive algorithm for leadership: Integrating Eastern and Western perspectives to navigate complexity and uncertainty
Authors: Trinh Mai P. , Castillo Elizabeth A.
Published: June 2020

In this paper, we integrate Eastern and Western perspectives of practical wisdom to answer the question,how can practical wisdom transfer across cultural boundaries in a world of increasing interconnection?We describe key properties of practical wisdom in early Western and Eastern schools of thoughts and explain how the concept of practical wisdom in ancient philosophy aligns with modern‐day complex system science. We identify seven qualities of complex adaptive systems as a universal pattern that underlies both Eastern and Western perspectives. From these qualities, we develop an integrated conceptual framework of practical wisdom as factors both internal and external to the self that promote continuous coupling with the broader operating environment. We propose that practical wisdom functions as an adaptive algorithm capable of continuously evaluating its processing rules to maintain fit with the operating environment while generating ongoing novelty. This generativity expands developmental potential across multiple levels and fosters open‐endedness, evolvability, and antifragility. With this functional understanding, ethics can no longer be marginalized—it must be recognized as the foundation for sustainable organizing because it reliably creates a network topology that makes innovation and long‐term success possible. We close with actions leaders can take to foster practical wisdom.
The calling of the virtuous manager: Politics shepherded by practical wisdom
Authors: Potts Garrett
Published: June 2020

This paper extends an ongoing discussion about establishing a sharper way to conduct ethical investigations into managerial virtue. It does so by relying on Alasdair MacIntyre's moral philosophy in place of those more dominant approaches taken by scholars who make up the field of positive social science. A connection is drawn herein between a MacIntyrean “narrative approach” to investigating managerial virtue and the idea of “work as a calling.” Specifically, it will be argued that the MacIntyrean‐influenced idea of “work as a calling” provides a substantive moral vision that supports an understanding of how virtuous managers ought to narrate their primary workplace motivations. Ultimately, virtuous managers fulfill a “political calling” to support and sustain (a) good work, (b) the good of individual lives, and (c) the common good of communities that their organization reaches. To do this, they must rely on the “shepherd virtue” of practical wisdom (phronesis). Practical wisdom aids virtuous managers’ thinking about achieving the ends of their “calling” as well as any necessary course‐corrections that ought to be made toward the better achievement of those good and worthy ends.
Conceptions of dignity in the Charlie Gard, Alfie Evans and Isaiah Haastrup cases
Authors: Jonas Monique , Evans Amanda
Published: June 2020

In 2017 and 2018, the English courts were asked to decide whether continued life‐sustaining treatment was in the best interests of three infants: Charlie Gard, Alfie Evans and Isaiah Haastrup. Each infant had sustained catastrophic, irrecoverable brain damage. Dignity played an important role in the best interests assessments reached by the Family division of the High Court in each case. Multiple conceptions of dignity circulate, with potentially conflicting implications for infants such as Charlie, Alfie and Isaiah. The judgements do not explicate the conceptions of dignity upon which they rely. This article reconstructs the conceptions of dignity invoked in these judgements, finding that a broadly Kantian, agential conception dominates, under which human dignity requires the prospect of agency. This conception is situated within the broader body of thought on dignity, and the potentially adverse implications of applying the reconstructed conception in best interests assessments for infants with severely restricted consciousness are discussed.
Are urologists in trouble with SARS‐CoV‐2? Reflections and recommendations for specific interventions
Authors: Kunz Yannic , Horninger Wolfgang , Pinggera Germar‐M
Published: June 2020

Objective

To assess the risk of viral infection during urological surgeries due to the possible hazards in tissue, blood, urine and aerosolised particles generated during surgery, and thus to understand the risks and make recommendations for clinical practice.

Patients and Methods

We reviewed the available literature on urological and other surgical procedures in patients with virus infections, such as human papillomavirus, human immunodeficiency virus and hepatitis B, and current publications on coronavirus disease 2019 (COVID‐19).

Results

Several possible pathways for viral transmission appear in the literature. Recently, groups have detected severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in the urine and faeces, even after negative pharyngeal swabs. In addition, viral RNA can be detected in the blood and several tissues. During surgery, viral particles are released, aerosol‐borne and present a certain risk of transmission and infection. However, there is currently no evidence on the exact risk of infection from the agents mentioned above. It remains unclear whether or not viral particles in the urine, blood or faeces are infectious.

Conclusions

Whether SARS‐CoV‐2 can be transmitted by aerosols remains controversial. Irrespective of this, standard surgical masks offer inadequate protection from SARS‐CoV‐2. Full personal protective equipment, including at least filtering facepiece‐2 masks and safety goggles should be used. Aerosolised particles might remain for a long time in the operating theatre and contaminate other surfaces, e.g. floors or computer input devices. Therefore, scrupulous hygiene and disinfection of surfaces must be carried out. To prevent aerosolisation during laparoscopic interventions, the pneumoperitoneum should be evacuated with suction devices. The use of virus‐proof high‐efficiency particulate air filters is recommended. Local separation of anaesthesia/intubation and the operating theatre can reduce the danger of viral transmission. Lumbar anaesthesia should be considered especially in endourology. Based on current knowledge, COVID‐19 is not a contraindication for acute urological surgery. However, if possible, as European guideline committees recommend, non‐emergency urological interventions should be postponed until negative SARS‐CoV‐2 tests become available.
Multifunctional opioid receptor agonism and antagonism by a novel macrocyclic tetrapeptide prevents reinstatement of morphine‐seeking behaviour
Authors: Brice‐Tutt Ariana C. , Wilson Lisa L. , Eans Shainnel O. , Stacy Heather M. , Simons Chloe A. , Simpson Grant G. , Coleman Jeremy S. , Ferracane Michael J. , Aldrich Jane V. , McLaughlin Jay P.
Published: June 2020

Background and Purpose

The macrocyclic tetrapeptide natural product CJ‐15,208 (cyclo[Phe‐d‐Pro‐Phe‐Trp]) is a multifunctional μ‐opioid receptor and κ‐opioid receptor agonist and κ‐opioid receptor antagonist that produces antinociception and prevents stress‐induced reinstatement of extinguished cocaine‐conditioned place preference (CPP). We hypothesized that an analogue of CJ‐15,208, cyclo[Pro‐Sar‐Phe‐d‐Phe], would demonstrate multifunctional μ‐opioid receptor and κ‐opioid receptor ligand activity, producing potent antinociception with fewer liabilities than selective μ‐opioid receptor agonists, while preventing both drug‐ and stress‐induced reinstatement of morphine‐induced CPP.

Experimental Approach

The opioid receptor agonist and antagonist activity of cyclo[Pro‐Sar‐Phe‐d‐Phe] was characterized after i.c.v. and i.p. administration to C57BL/6J or transgenic opioid receptor “knockout” mice using the 55°C warm‐water tail‐withdrawal assay. Liabilities of locomotor coordination, respiration and spontaneous ambulation, and direct rewarding or aversive properties were assessed. Finally, the ability of cyclo[Pro‐Sar‐Phe‐d‐Phe] to block morphine‐ and stress‐induced reinstatement of extinguished CPP was determined.

Key Results

cyclo[Pro‐Sar‐Phe‐d‐Phe] demonstrated dose‐dependent, short‐lasting antinociception, with an ED50 (and 95% confidence interval) of 0.15 (0.05–0.21) nmol i.c.v. and 1.91 (0.40–3.54) mg·kg−1 i.p., mediated by μ‐ and κ‐opioid receptors. The macrocyclic tetrapeptide also demonstrated potent dose‐dependent κ‐opioid receptor antagonist‐like activity at 2.5, but not at 4.5, h after administration. cyclo[Pro‐Sar‐Phe‐d‐Phe] displayed reduced liabiities compared with morphine, attributed to its additional activity at κ‐receptors. Pretreatment with cyclo[Pro‐Sar‐Phe‐d‐Phe] prevented stress‐ and drug‐induced reinstatement of extinguished morphine‐place preference responses in a time‐dependent manner.

Conclusions and Implications

These data suggest that cyclo[Pro‐Sar‐Phe‐d‐Phe] is a promising lead compound for both the treatment of pain with reduced sideeffects and preventing both drug‐ and stress‐induced relapse in morphine‐abstinent subjects.
Statins: Could an old friend help in the fight against COVID‐19?
Authors: Rodrigues‐Diez Raul R. , Tejera‐Muñoz Antonio , Marquez‐Exposito Laura , Rayego‐Mateos Sandra , Santos Sanchez Laura , Marchant Vanessa , Tejedor Santamaria Lucía , Ramos Adrian M. , Ortiz Alberto , Egido Jesus , Ruiz‐Ortega Marta
Published: June 2020

The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID‐19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID‐19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS‐CoV‐2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well‐known anti‐inflammatory properties of statins, by blocking several molecular mechanisms, including NF‐κB and NLRP3 inflammasomes, could limit the “cytokine storm” in severe COVID‐19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID‐19 outcomes.

Linked Articles

This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Spatial and temporal variations in minibasin geometry and evolution in salt tectonic provinces: Lower Congo Basin, offshore Angola
Authors: Ge Zhiyuan , Gawthorpe Rob L. , Zijerveld Leo , Oluboyo Ayodeji P.
Published: June 2020

In passive margin salt basins, the distinct kinematic domains of thin‐skinned extension, translation and contraction exert important controls on minibasin evolution. However, the relationship between various salt minibasin geometries and kinematic domain evolution is not clear. In this study, we use a semi‐regional 3D seismic reflection dataset from the Lower Congo Basin, offshore Angola, to investigate the evolution of a network of minibasins and intervening salt walls during thin‐skinned, gravity‐driven salt flow. Widespread thin‐skinned extension occurred during the Cenomanian to Coniacian, accommodated by numerous distributed normal faults that are typically 5–10 km long and spaced 1–4 km across strike within the supra‐salt cover. Subsequently, during the Santonian–Paleocene, multiple, 10–25 km long, 5–7 km wide depocentres progressively grew and linked along strike to form elongate minibasins separated by salt walls of comparable lengths. Simultaneous with the development of the minibasins, thin‐skinned contractional deformation occurred in the southwestern downslope part of the study area, forming folds and thrusts that are up to 20 km long and have a wavelength of 2–4 km. The elongate minibasins evolved into turtle structures during the Eocene to Oligocene. From the Miocene onwards, contraction of the supra‐salt cover caused squeezing and uplift of the salt walls, further confining the minibasin depocentres. We find kinematic domains of extension, translation and contraction control the minibasin initiation and subsequent evolution. However, we also observe variations in minibasin geometries associated with along‐strike growth and linkage of depocentres. Neighbouring minibasins may have different subsidence rates and maturity leading to marked variations in their geometry. Additionally, migration of the contractional domain upslope and multiple phases of thin‐skinned salt tectonics further complicates the spatial variations in minibasin geometry and evolution. This study suggests that minibasin growth is more variable and complex than existing domain‐controlled models would suggest.
Leonurus sibiricus root extracts decrease airway remodeling markers expression in fibroblasts
Authors: Wieczfinska J , Sitarek P , Kowalczyk T , Pawliczak R
Published: June 2020

Bronchial asthma is believed to be provoked by the interaction between airway inflammation and remodeling. Airway remodeling is a complex and poorly understood process, and controlling it appears key for halting the progression of asthma and other obstructive lung diseases. Plants synthesize a number of valuable compounds as constitutive products and as secondary metabolites, many of which have curative properties. The aim of this study was to evaluate the anti-remodeling properties of extracts from transformed and transgenic Leonurus sibiricus roots with transformed L. sibiricus roots extract with transcriptional factor AtPAP1 overexpression (AtPAP1). Two fibroblast cell lines, Wistar Institute-38 (WI-38) and human fetal lung fibroblast (HFL1), were incubated with extracts from transformed L. sibiricus roots (TR) and roots with transcriptional factor AtPAP1 over-expression (AtPAP1 TR). Additionally, remodeling conditions were induced in the cultures with rhinovirus 16 (HRV16). The expressions of metalloproteinase 9 (MMP)-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), arginase I and transforming growth factor (TGF)-β were determined by quantitative polymerase chain reaction (qPCR) and immunoblotting methods. AtPAP1 TR decreased arginase I and MMP-9 expression with no effect on TIMP-1 or TGF-β mRNA expression. This extract also inhibited HRV16-induced expression of arginase I, MMP-9 and TGF-β in both cell lines (P < 0·05) Our study shows for the first time to our knowledge, that transformed AtPAP1 TR extract from L. sibiricus root may affect the remodeling process. Its effect can be attributed an increased amount of phenolic acids such as: chlorogenic acid, caffeic acid or ferulic acid and demonstrates the value of biotechnology in medicinal research.
Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina
Authors: Wu Lei , Zhang Kan , Sun Liping , Bai Jie , Zhang Mazhong , Zheng Jijian
Published: June 2020

Aims

During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine‐induced apoptosis.

Methods

We performed terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non‐integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine‐induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+. Experiments were performed using whole‐mount retinas dissected from Sprague Dawley rats.

Results

The TUNEL and immunohistochemical assays indicated that ketamine‐induced neuronal apoptosis in early developing rat retina. Blockade of non‐integrin laminin receptor promoted ketamine‐induced apoptosis, while non‐integrin laminin receptor activation attenuated ketamine‐induced apoptosis. Ketamine‐induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine‐induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine‐induced neuronal apoptosis.

Conclusion

Laminin degradation by MMP9 promoted ketamine‐induced neuronal apoptosis in early developing rat retina. The non‐integrin laminin receptor may be a pathway involved in ketamine‐induced apoptosis. Zn2+ downregulation may play a protective role against ketamine‐induced neuronal apoptosis through inhibiting MMP9 activity.
Efficacy of cannabinoids for treating paediatric spasticity in cerebral palsy or traumatic brain injury: what is the evidence?
Authors: Nielsen Suzanne , Hall Wayne
Published: June 2020

This commentary is on the original article by Fairhurst et al. on pages 1031–1039 of this issue.
Quantification of tricuspid regurgitation area by 3‐dimensional color Doppler echocardiography considering different clinical settings
Authors: Chouchani Mehrez , Michaelsen Jochen , Langenbrink Lukas , Piatkowski Michal , Altiok Ertunc , Hoffmann Rainer
Published: June 2020

Purpose

The precise assessment of tricuspid regurgitation (TR) using 2D imaging techniques may be associated with significant difficulties due to the nonround regurgitation area. Direct analysis of the regurgitation area by 3D color Doppler echocardiography at the vena contracta (3D VCA) has the potential to adequately quantify even complex TR. This study compared 3D VCA for quantification of the TR with the regurgitant area determined by proximal isovolumetric convergence method (PISA‐EROA) considering different clinical settings.

Methods

In 95 patients with TR of different severity, the regurgitant orifice area was determined by 3D color Doppler echocardiography and by PISA‐EROA. Using 3D color Doppler echocardiography, the regurgitant orifice area was determined three times in each patient considering 3 datasets.

Results

Mean 3D VCA was 0.27 ± 0.14, 0.27 ± 0.13, and 0.29 ± 0.14 cm2, respectively, as determined by three separate measurements in each of the 95 patients. There was a mean relative deviation between the three measurements in each patient of 12.4 ± 14.9%. The regurgitant orifice area using the PISA method was 0.28 ± 0.14 cm2. There was a mean difference of 0.07 cm2 (95% CI −0.124 to 0.138 cm2) between 3D VCA and PISA‐EROA. The correlation between 3D VCA and PISA‐EROA was r = .88 (P < .001). Considering a grading of TR severity in grade I (regurgitant area < 0.2 cm2), grade II (area 0.2–0.4 cm2), and grade III (area > 0.4 cm2), there was a good agreement between severity grade determined by 3D VCA and severity grade determined by PISA‐EROA (kappa 0.71).

Conclusion

The analysis of the VCA of a TR using 3D color Doppler echocardiography is an alternative method to determine the regurgitant severity with good agreement to the PISA method.
Pathophysiology of the aortic regurgitation Doppler signal end‐diastolic notching: “A‐dip insight”
Authors: Giannakopoulos Georgios , Rey Florian , Müller Hajo
Published: June 2020

A 76‐year‐old man was admitted to the hospital with symptoms of severe decompensated heart failure. Initial echocardiogram showed normal left ventricular (LV) ejection fraction, grade II diastolic dysfunction, and mild‐to‐moderate aortic regurgitation. The aortic regurgitant Doppler signal exhibited an end‐diastolic notching, called an A‐dip. After intravenous diuretic therapy and 3 kg weight loss, a new echocardiogram was performed showing a grade I diastolic dysfunction and complete abolishment of the A‐dip. Aortic A‐dip is a rare finding denoting increased LV filling pressures. Conditions that favor its occurrence are increased LV stiffness, low diastolic blood pressure, and preserved left atrial contractility.
Partial bivoltinism in a gregarious endoparasitoid: larval diapause as influenced by season and sharing a host
Authors: Evans Edward W.
Published: June 2020

The yearly timing of the life cycle of a parasitoid is a key element of its life‐history strategy. I examine here factors influencing the expression of partial bivoltinism in Tetrastichus julis Walker (Hymenoptera: Eulophidae), a specialist parasitoid introduced to North America to attack its univoltine host, the cereal leaf beetle, Oulema melanopus (L.) (Coleoptera: Chrysomelidae). The varying tendency was assessed of individuals of this gregarious larval parasitoid to either emerge as adults in the same summer they mature, or to enter diapause to emerge the following year. Parasitized hosts were obtained by rearing cereal leaf beetles collected as mature larvae from grain fields in northern Utah (western USA) throughout the growing seasons in 2013 and 2014. Cocoons spun by these beetles were held to determine patterns over the spring and summer in the tendency of the parasitoid to forgo larval diapause. A high percentage (nearly 90% in 2013) of parasitoid individuals were found to forgo diapause and emerge in the same summer from earliest maturing hosts. This percentage rapidly declined to 20% or less of individuals forgoing diapause and emerging from cocoons as the summer advanced. The percentage of parasitoid individuals forgoing diapause increased significantly at a given time of season (early or late) as the number of conspecifics with which an individual shared a host larva increased. These results may reflect a trade‐off for individual parasitoids in which greater success in finding – and ovipositing in – host larvae the following spring vs. in summer, is countered by reduced survivorship in diapausing over the winter vs. emerging in the same summer in which the parasitoid matures. Expression of partial bivoltinism of T. julis, as affected strongly by both season and within‐host density, results in high rates of parasitism of cereal leaf beetles both early and late in the season.
Altered resting‐state functional connectivity between subregions in the thalamus and cortex in migraine without aura
Authors: Qin Z. X. , Su J. J. , He X. W. , Zhu Q. , Cui Y. Y. , Zhang J. L. , Wang M. X. , Gao T. T. , Tang W. , Hu Y. , Liu Y. S. , Qiao Y. , Liu J. R. , Li J. Q. , Du X. X.
Published: June 2020

Background and purpose

Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes.

Methods

A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age‐ and sex‐matched healthy controls underwent resting‐state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed‐based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions.

Results

The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R‐IPL) and right middle frontal gyrus. Furthermore, the FC Z‐scores between the VPN and R‐IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z‐scores between the VPN and R‐IPL.

Conclusion

These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R‐IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.
Relationship between saliva and plasma rufinamide concentrations in patients with epilepsy
Authors: Franco Valentina , Gatti Giuliana , Mazzucchelli Iolanda , Marchiselli Roberto , Fattore Cinzia , Rota Paola , Galimberti Carlo Andrea , Capovilla Giuseppe , Beccaria Francesca , De Giorgis Valentina , Johannessen Landmark Cecilie , Perucca Emilio
Published: June 2020

The assay of saliva samples provides a valuable alternative to the use of blood samples for therapeutic drug monitoring (TDM), at least for certain categories of patients. To determine the feasibility of using saliva sampling for the TDM of rufinamide, we compared rufinamide concentrations in paired samples of saliva and plasma collected from 26 patients with epilepsy at steady state. Within‐patient relationships between plasma rufinamide concentrations and dose, and the influence of comedication were also investigated. Assay results in the two tested fluids showed a good correlation (r2 = .78, P < .0001), but concentrations in saliva were moderately lower than those in plasma (mean saliva to plasma ratio = 0.7 ± 0.2). In eight patients evaluated at three different dose levels, plasma rufinamide concentrations increased linearly with increasing dose. Patients receiving valproic acid comedication had higher dose‐normalized plasma rufinamide levels than patients comedicated with drugs devoid of strong enzyme‐inducing or enzyme‐inhibiting activity. Overall, these findings indicate that use of saliva represents a feasible option for the application of TDM in patients treated with rufinamide. Because rufinamide concentrations are lower in saliva than in plasma, a correction factor is needed if measurements made in saliva are used as a surrogate for plasma concentrations.
Natural history collections are critical resources for contemporary and future studies of urban evolution
Authors: Shultz Allison J. , Adams Benjamin J. , Bell Kayce C. , Ludt William B. , Pauly Gregory B. , Vendetti Jann E.
Published: June 2020

Urban environments are among the fastest changing habitats on the planet, and this change has evolutionary implications for the organisms inhabiting them. Herein, we demonstrate that natural history collections are critical resources for urban evolution studies. The specimens housed in these collections provide great potential for diverse types of urban evolution research, and strategic deposition of specimens and other materials from contemporary studies will determine the resources and research questions available to future urban evolutionary biologists. As natural history collections are windows into the past, they provide a crucial historical timescale for urban evolution research. While the importance of museum collections for research is generally appreciated, their utility in the study of urban evolution has not been explicitly evaluated. Here, we: (a) demonstrate that museum collections can greatly enhance urban evolution studies, (b) review patterns of specimen use and deposition in the urban evolution literature, (c) analyze how urban versus rural and native versus nonnative vertebrate species are being deposited in museum collections, and (d) make recommendations to researchers, museum professionals, scientific journal editors, funding agencies, permitting agencies, and professional societies to improve archiving policies. Our analyses of recent urban evolution studies reveal that museum specimens can be used for diverse research questions, but they are used infrequently. Further, although nearly all studies we analyzed generated resources that could be deposited in natural history collections (e.g., collected specimens), a minority (12%) of studies actually did so. Depositing such resources in collections is crucial to allow the scientific community to verify, replicate, and/or re‐visit prior research. Therefore, to ensure that adequate museum resources are available for future urban evolutionary biology research, the research community—from practicing biologists to funding agencies and professional societies—must make adjustments that prioritize the collection and deposition of urban specimens.
Peritoneal fluid accumulation in the femoral canal as a result of a post‐traumatic femoral hydrocele in a mature Warmblood stallion
Authors: Baldwin C. M. , Priestnall S. L. , McMaster M.
Published: June 2020

The following case report documents the clinical presentation, ultrasonographic appearance, surgical management and outcome of a horse with a traumatic tear extending from the superficial and deep inguinal rings, across the aponeurosis of the external abdominal oblique muscle and inguinal ligament, disrupting the femoral ring, vascular lacuna and peritoneum. This subsequently resulted in fluid accumulation within the femoral canal. This unusual injury and presentation gives rise to discussion of the aetiology and nomenclature that should be used to properly describe this injury.
Equine focal mucopurulent placentitis associated withStenotrophomonas maltophilia
Authors: Gomes V. C. L. , Del Piero F. , Langohr I. M. , de Aguiar L. H. , Anderson A. , Sones J. L. , Pinto C. R.
Published: June 2020

Two cases of focal mucopurulent placentitis (FMP) associated withStenotrophomonas maltophiliaare reported herein. The first patient, a 12‐year‐old Quarter Horse mare, aborted at 287 days of gestation and the fetus and placenta were submitted for post‐mortem examination. Histopathological findings included chronic exudative allantochorionitis and fetal multifocal suppurative hepatitis. The second patient, a 10‐year‐old Thoroughbred mare, prematurely delivered a live foal at 293 days of gestation. Chronic exudative allantochorionitis and perifunisitis were diagnosed. The foal was severely compromised and was euthanised. On post‐mortem examination, pneumonia, myocardial and hepatic necrosis, and sepsis were diagnosed. The fetal membranes of both mares had a thick adherent mass of exudate overlaying the chorionic surface. The lesions were well demarcated, and the underlining chorion was avillous, pale and thickened.Stenotrophomonas maltophiliawas isolated from the exudate of both mares and from the lungs and stomach of the fetus from the first patient. To the authors’ knowledge, this is the first clinical description of FMP associated withS. maltophiliain the USA. The aetiopathogenesis of placentitis induced by this micro‐organism and its relevance as an emerging pathogen in equine reproduction remains to be further elucidated.
HDAC11 is a novel regulator of fatty acid oxidative metabolism in skeletal muscle
Authors: Hurtado Erica , Núñez‐Álvarez Yaiza , Muñoz Mar , Gutiérrez‐Caballero Cristina , Casas Josefina , Pendás Alberto M. , Peinado Miguel A. , Suelves Mònica
Published: June 2020

Skeletal muscle is the largest tissue in mammalian organisms and is a key determinant of basal metabolic rate and whole‐body energy metabolism. Histone deacetylase 11 (HDAC11) is the only member of the class IV subfamily of HDACs, and it is highly expressed in skeletal muscle, but its role in skeletal muscle physiology has never been investigated. Here, we describe for the first time the consequences of HDAC11 genetic deficiency in skeletal muscle, which results in the improvement of muscle function enhancing fatigue resistance and muscle strength. Loss of HDAC11 had no obvious impact on skeletal muscle structure but increased the number of oxidative myofibers by promoting a glycolytic‐to‐oxidative muscle fiber switch. Unexpectedly, HDAC11 was localized in muscle mitochondria and its deficiency enhanced mitochondrial content. In particular, we showed that HDAC11 depletion increased mitochondrial fatty acid β‐oxidation through activating the AMP‐activated protein kinase‐acetyl‐CoA carboxylase pathway and reducing acylcarnitine levels in vivo, thus providing a mechanistic explanation for the improved muscle strength and fatigue resistance. Overall, our data reveal a unique role of HDAC11 in the maintenance of muscle fiber‐type balance and the mitochondrial lipid oxidation. These findings shed light on the mechanisms governing muscle metabolism and may have implications for chronic muscle metabolic disease management.
Protein regulator of cytokinesis 1 regulates chromosome dynamics and cytoplasmic division during mouse oocyte meiotic maturation and early embryonic development
Authors: Zhou Cheng‐Jie , Wang Dong‐Hui , Kong Xiang‐Wei , Han Zhe , Hao Xin , Wang Xing‐Yue , Wen Xin , Liang Cheng‐Guang
Published: June 2020

In contrast to the homeokinesis of mitosis, asymmetric division of cytoplasm is the conspicuous feature of meiosis in mammalian oocytes. Protein regulator of cytokinesis 1 (PRC1) is an important regulator during mitotic spindle assembly and cytoplasmic division, but its functions in oocyte meiosis and early embryo development have not been fully elucidated. In this study, we detected PRC1 expression and localization and revealed a nuclear, spindle midzone‐related dynamic pattern throughout meiotic and mitotic progressions. Treatment of oocytes with the reagents taxol or nocodazole disturbed the distribution of PRC1 in metaphase II oocytes. Further, PRC1 depletion led to failure of first polar body (PB1) extrusion and spindle migration, aneuploidy and defective kinetochore–microtubule attachment and spindle assembly. Overexpression of PRC1 resulted in PB1 extrusion failure, aneuploidy and serious defects of spindle assembly. To investigate PRC1 function in early embryos, we injected Prc1 morpholino into zygotes and 2‐cell stage embryos. Depletion of PRC1 in zygotes impaired 4‐cell, morula and blastocyst formation. Loss of PRC1 in single or double blastomeres in 2‐cell stage embryos significantly impaired cell division, indicating its indispensable role in early embryo development. Co‐immunoprecipitation showed that PRC1 interacts with polo‐like kinase 1 (PLK1), and functional knockdown and rescue experiments demonstrated that PRC1 recruits PLK1 to the spindle midzone to regulate cytoplasmic division during meiosis. Finally, kinesin family member 4 knockdown downregulates PRC1 expression and leads to PRC1 localization failure. Taken together, our data suggest PRC1 plays an important role during oocyte maturation and early embryonic development by regulating chromosome dynamics and cytoplasmic division.
Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria
Authors: Sho Takuya , Suda Goki , Ogawa Koji , Shigesawa Taku , Suzuki Kazuharu , Nakamura Akihisa , Ohara Masatsugu , Umemura Machiko , Kawagishi Naoki , Natsuizaka Mitsuteru , Nakai Masato , Morikawa Kenichi , Furuya Ken , Baba Masaru , Ito Jun , Yamamoto Yoshiya , Kobayashi Tomoe , Meguro Takashi , Saga Akiyoshi , Miyagishima Takuto , Terasita Katsumi , Takagi Tomofumi , Kamiyama Toshiya , Taketomi Akinobu , Sakamoto Naoya
Published: June 2020

Aim

This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial).

Methods

In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression‐free‐survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial.

Results

Of the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child–Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child–Pugh‐score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS.

Conclusion

Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.
Reappraisal of the papillary urothelial neoplasm of low malignant potential (PUNLMP)
Authors: Jones Timothy D , Cheng Liang
Published: June 2020

Although the papillary urothelial neoplasm of low malignant potential (PUNLMP) diagnostic category was retained in the updated 2016 World Health Organisation (WHO) classification of tumours of the urinary system, there still exists a great deal of controversy regarding the biological behaviour of these tumours. We review PUNLMP tumours and histological grading with an emphasis on the histomorphological, genetic and clinical similarities between PUNLMP and low‐grade non‐invasive papillary urothelial carcinoma. A literature search using PubMed was performed. All relevant literature concerning PUNLMP and the grading of urothelial tumours was reviewed. PUNLMPs cannot be reliably distinguished from low‐grade non‐invasive papillary urothelial carcinomas based on the histomorphological criteria outlined in the WHO 2004/2016 classification system. PUNLMPs and low‐grade non‐invasive papillary urothelial carcinomas are not only morphologically similar, but also share similar molecular genetic alterations and a similar risk of recurrence and progression. In addition, there are no consensus recommendations for a different method of treatment and follow‐up for these two tumour types. Attempting to distinguish PUNLMP from low‐grade papillary urothelial carcinoma adds an unnecessary level of complexity to the grading and classification of urothelial tumours. We feel that PUNLMP terminology should be abandoned and that all such tumours should be classified as low‐grade carcinomas until more objective determinants of clinical outcome can be established.