bluuebunny/crossref_metadata_2025 huggingface dataset:
ISO order imbalances and individual stock returns
Authors: Cox Justin
Published: December 2020

I examine the relation between intermarket sweep order (ISO) order imbalances and the daily returns of individual stocks. First, I show that ISO order imbalances are positively related to contemporaneous returns. Second, I find that price pressures emanating from ISO imbalances are persistent and predict cumulative abnormal returns up to 2 months. The predictive power of ISO order imbalances on contemporaneous and future abnormal returns is strongest for firms in the smallest firm size quintile. Finally, I analyze herding among ISO order imbalances and find strong commonality. My results indicate that ISOs contribute to both short‐ and long‐term return formation.
Microwave vacuum drying of Pereskia aculeata Miller leaves: Powder production and characterization
Authors: Monteiro Ricardo Lemos , Garcia Analiz Hüntemann , Tribuzi Giustino , Mattar Carciofi Bruno Augusto , Laurindo João Borges
Published: December 2020

Pereskia aculeata Miller (PAM) is a non‐conventional leaf vegetable that has drawn attention due to its remarkable nutritional quality, such as a high protein, carotenoids, and vitamin content. This study aimed to produce dehydrated PAM‐leaves by air‐drying (AD), freeze‐drying (FD), and microwave vacuum drying (MWVD), and evaluate the quality and physicochemical properties (moisture, aw, bulk density, particle density, bed porosity, apparent solubility, dispersion time, and β‐carotene content) of the dried powdered leaves. To produce powders with aw lower than 0.4 and moisture content below 6%, MWVD showed a drying time of 1.3 and 0.8 hr using the input power of 300 W and 500 W, respectively; besides, the final drying time for AD and FD was around 10 and 16 hr, respectively. MWVD dried powder showed bed porosity of ~67% and solubility around 30%, slightly less porous, and with a similar solubility to the FD‐powder. PAM powder dehydrated by MWVD preserved about 66% of the original content of β‐carotene equivalent for both microwave power, which is only 15% lower of the content in the FD‐powder, and twice bigger than AD‐powder. The MWVD of PAM allowed obtaining high‐quality powders comparable to the freeze‐dried PAM.

Practical Applications

As Pereskia aculeata Miller (PAM) is a leaf vegetable with high protein, carotenoids, and vitamin contents, its powders can be a suitable and stable presentation for a new proteinaceous product. This use of PAM as a powder with high protein concentration is in agreement with the global trend that seeks new plant‐based protein sources. In this way, the study of drying processes that result in PAM powders with suitable properties is of interest to researchers and food industries.
Embedding Function into Health Care
Authors: Ling Shari M. , Lipp Michael J. , Schreiber Michelle
Published: December 2020

This editorial comments on the article by Callahan et al. in this issue.
Utilization and Functional Outcomes Among Medicare Home Health Recipients Varied Across Living Situations
Authors: Wang Jinjiao , Ying Meiling , Temkin‐Greener Helena , Shang Jingjing , Caprio Thomas V. , Li Yue
Published: December 2020

BACKGROUND/OBJECTIVES

Home health (HH) is a major type of home‐based skilled care available to Medicare beneficiaries. We examined the association between living situation (home alone, home with others, and assisted living (AL) residence) and utilization and functional outcomes among Medicare HH recipients.

DESIGN

Analysis of national data from the Outcome and Assessment Information Set, HH Compare, Medicare claims, and Area Health Resource Files.

SETTING

Medicare‐certified HH agencies in the United States.

PARTICIPANTS

National population of Medicare beneficiaries ≥65 years old who received HH care in CY 2017 (N = 6,637,496).

MEASUREMENTS

Outcomes included time‐to‐event measures of hospitalization and emergency department (ED) visits, and improvement in activities of daily living (ADL) from the start to the end of the HH admission.

RESULTS

AL residents (12%) and patients living alone at home (24%) had longer survival time without hospitalization and ED visits than patients living with others at home (64%). Adjusting for covariates and HH agency‐level random effects, and compared with patients living with others, AL residents had lower risk of hospitalization (hazard ratio (HR) = 0.85, P < .001) and ED visit (HR = 0.92, P < .001); however, less ADL improvement (β = 0.29 (29% less of total independence in one ADL)); and patients living alone had lower risk of hospitalization (HR = 0.94, P < .001) and ED visit (HR = 0.93, P < .001), yet more ADL improvement (β = −0.15 (15% more of total independence in one ADL)).

CONCLUSION

In the national population of Medicare HH recipients, patients living with others at home had the highest risk of hospitalization and ED visits, whereas AL residents had the lowest risk of hospitalization and patients living alone at home had the lowest risk of ED visits, meaning that combined support from HH and AL reduces acute care admissions. Evidence‐based interventions are needed for HH patients living with others at home to avoid unnecessary acute care use.
Hippocampal hyperglutamatergic signaling matters: Early targeting glutamate neurotransmission as a preventive strategy in Alzheimer's disease
Authors: Gulyaeva Natalia V.
Published: December 2020

This Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Hascup and coworkers provide novel data showing that riluzole, an anti‐glutamatergic drug, may be a promising early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to amyloid beta (Aβ) plaque accumulation and cognitive decline. The mice APP/PS1, a model of AD, initially are cognitively normal but have elevated glutamate release in the hippocampus at 2–4 months of age. They begin showing cognitive decline and Aβ plaque accumulation at approximately 6–8 months of age, and show obvious AD neuropathology and cognitive impairment at 10–12 months. The riluzole treatment over 4 months (at 2–6 months of age) targeting early changes in glutamatergic neurotransmission prevents cognitive decline observed at 12 months of age and restores glutamatergic neurotransmission. This is one of the most convincing preclinical evidence supporting the idea of targeting glutamate neurotransmission in patients at risk for AD and to use riluzole for this purpose.

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Mutual Fund Holdings of Credit Default Swaps: Liquidity, Yield, and Risk
Authors: JIANG WEI , OU JITAO , ZHU ZHONGYAN
Published: December 2020

This study analyzes the motivations for and consequences of funds' credit default swap (CDS) investments using mutual funds' quarterly holdings from pre‐ to postfinancial crisis. Funds invest in CDS when facing unpredictable liquidity needs. Funds sell more in reference entities when the CDS is liquid relative to the underlying bonds and buy more when the CDS‐bond basis is more negative. To enhance yield, funds engage in negative basis trading and sell CDS with the highest spreads within rating categories, and with spreads higher than those of their bond portfolios. Funds with superior portfolio returns also demonstrate more skill in CDS trading.
Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review
Authors: Rimmer Michael P. , Fishwick Katherine , Henderson Ian , Chinn David , Al Wattar Bassel H. , Quenby Siobhan
Published: December 2020

Objective

To determine the value of uterine CD138+ cells, as a marker of chronic endometritis, in predicting subsequent reproductive outcome in women with history of recurrent pregnancy loss.

Design

A prospective longitudinal study.

Setting

Tertiary specialized clinic.

Patients

Women with history of recurrent pregnancy loss or implantation failure over a 12‐months follow‐up period.

Intervention

We quantified the CD138+ cells/high powered field (hpf) using immunohistochemistry and image analysis of endometrial biopsies obtained during the secretory stage post ovulation.

Main outcome measures

Live birth and subsequent pregnancy loss. We calculated the receiver operator curve for predicting subsequent pregnancy loss and reported using relative risk (RR) and 95% confidence intervals (CI).

Results

We enrolled 344 women of whom 88 became pregnant (88/344, 25.5%). Half of them had a subsequent live birth (47/88, 53%) and the rest lost their pregnancy (41/88, 46%). The median CD138+ score was significantly lower in the live birth group (P < 0.005) and women with a CD138+ score ≥ 16/hpf had a higher risk of subsequent miscarriage (RR 10.0, 95% CI 2.78–36.02). CD138+ cells count showed a good prediction for subsequent pregnancy loss in high‐risk women with an area under the curve of 0.75 (95% CI 0.59–0.82, P = 0.01). A cut‐off value of 4–6 cells/hpf offered the best predictive accuracy with higher scores predicting worse reproductive outcome. Our findings are limited by the small event rate and the sample size of our cohort.

Conclusion

Quantifying CD138+ cells by immunohistochemistry in women with a history of recurrent pregnancy loss is helpful to diagnose chronic endometritis and predict subsequent reproductive outcome.
Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis
Authors: Eldhagen P. , Berg S. , Lund L.H. , Sörensson P. , Suhr O.B. , Westermark P.
Published: December 2020

Background

Wild‐type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.

Objective

To study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.

Materials and methods

A total of 250 patients, aged 50–89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0‐4. All patients with grade 3‐4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT‐proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.

Results

Amyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3‐4; all had fibril type A (mixture of full‐length TTR and fragmented TTR). Twenty‐nine of 42 patients with grade 3‐4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome.

Conclusions

The prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.
An intersectional perspective on the intergenerational transmission of trauma and state‐perpetrated violence
Authors: Heberle Amy E. , Obus Elsia A. , Gray Sarah A. O.
Published: December 2020

We utilize intersectionality as the framework for analyzing and critiquing the literature on the intergenerational transmission of trauma in early childhood. In particular, we assess the extent to which the literature replicates the oppression of marginalized and minoritized children and families by deemphasizing traumas and traumatic processes that are attributable to interlocking systems of oppression. In addition, building on the emphasis on systems that is central to intersectionality, we assess the degree to which the literature engages with trauma perpetrated through formal social systems. We assert that an intersectional lens demands acknowledgement of state‐perpetrated violence and that this acknowledgment is absent from the extant literature. To illustrate our argument, we present three structural analyses (“cases”) of state‐perpetrated violence, leveraging life course theory and theories of historical and cultural trauma in addition to intersectionality theory to draw inferences about the intergenerational impacts of these cases. Through our analysis, we demonstrate how efforts to reduce contemporary state‐perpetrated violence and repair the effects of historical state‐perpetrated violence are well aligned with ongoing efforts in the public policy arena at promoting early childhood mental health and family thriving. We close with a proposed agenda for better integrating such efforts into research and policy.
A qualitative study of service users’ experiences of mental health nurses’ knowledge and skills in relation to medication
Authors: Pearson Mark , Sibson Tara , Carter Timothy
Published: December 2020

Introduction

The role of the mental health nurse in relation to medications remains complex. Despite an increasing focus on pharmacology within pre‐registration nurse education, there is limited research exploring how mental health service users experience mental health nurses’ knowledge and skills in relation to medication.

Aim

To explore the experiences of service users working with mental health nurses, in relation to the nurses’ knowledge and skills associated with medicines management.

Method

The research prioritized the principles of co‐production and was undertaken collaboratively with a researcher with lived experience. Data were collected via semi‐structured interviews with individuals who have accessed UK mental health services. Interviews were audio‐recorded, transcribed verbatim and subjected to thematic analysis.

Results

Three themes were generated from the data: inconsistencies in knowledge and practice, holistic therapeutic engagement and dialogical approach to medicines.

Discussion

Service users may have a sense of uncertainty around the role of the nurse, potentially resulting in frustration and anxiety. However, mental health nurses also possess unique skills in relation to medicines management.

Implications for practice

The findings emphasize that service users value not only pharmacological knowledge but also unique skills in facilitating dialogue, prioritising shared decision‐making and practical support in medicines optimization.
Phylogenomics of Perityleae (Compositae) provides new insights into morphological and chromosomal evolution of the rock daisies
Authors: Lichter‐Marck Isaac H. , Freyman William A. , Siniscalchi Carolina M. , Mandel Jennifer R. , Castro‐Castro Arturo , Johnson Gabriel , Baldwin Bruce G.
Published: December 2020

Rock daisies (Perityleae; Compositae) are a diverse clade of seven genera and ca. 84 minimum‐rank taxa that mostly occur as narrow endemics on sheer rock cliffs throughout the southwest United States and northern Mexico. Taxonomy of Perityleae has traditionally been based on morphology and cytogenetics. To test taxonomic hypotheses and utility of characters emphasized in past treatments, we present the first densely sampled molecular phylogenies of Perityleae and reconstruct trait and chromosome evolution. We inferred phylogenetic trees from whole chloroplast genomes, nuclear ribosomal cistrons, and hundreds of low‐copy nuclear genes using genome skimming and target capture. Discordance between sources of molecular data suggests an underappreciated history of hybridization in Perityleae. Phylogenies support the monophyly of subtribe Peritylinae, a distinctive group possessing a four‐lobed disc corolla; however, all of the phylogenetic trees generated in this study reject the monophyly of the most species‐rich genus, Perityle, as well as its sections: Perityle sect. Perityle, Perityle sect. Laphamia, and Perityle sect. Pappothrix. Using reversible jump MCMC, our results suggest that morphological characters traditionally used to classify members of Perityleae have evolved multiple times within the group. A base chromosome number x = 9 gave rise to higher base numbers in subtribe Peritylinae (x = 12, 13, 16, 17, 18, and 19) through polyploidization, followed by ascending or descending dysploidy. Most taxa constitute a monophyletic lineage with a base chromosome number of x = 17, with multiple neo‐polyploidization events. These results demonstrate the advantages and obstacles of next‐generation sequencing approaches in synantherology while laying the foundation for taxonomic revision and comparative study of the evolutionary ecology of Perityleae.
Dry mouth diagnosis and saliva substitutes—A review from a textural perspective
Authors: Hu Jing , Andablo‐Reyes Efren , Mighell Alan , Pavitt Sue , Sarkar Anwesha
Published: December 2020

The aim of this review is to assess the objective and subjective diagnosis, as well as symptomatic topical treatment of dry mouth conditions with a clear focus on textural perspective. We critically examine both the current practices as well as outline emerging possibilities in dry mouth diagnosis and treatment, including a patent scan for saliva substitutes. For diagnosis, salivary flow rates and patient‐completed questionnaires have proven to be useful tools in clinical practice. To date, objective measurements of changes in mechanical properties of saliva via rheological, adsorption, and tribological measurements and biochemical properties of saliva such as assessing protein, mucins (MUC5B) are seldom incorporated into clinical diagnostics; these robust diagnostic tools have been largely restricted to application in non‐clinical settings. As for symptomatic treatments of dry mouth, four key agents including lubricating, thickening, adhesive, and moisturizing agents have been identified covering the overall landscape of commercial saliva substitutes. Although thickening agents such as modified celluloses, polysaccharide gum, polyethylene glycol, and so forth are most commonly employed saliva substitutes, they offer short‐lived relief from dry mouth and generally do not provide boundary lubrication properties of real human saliva. Innovative technologies such as self‐assembly, emulsion, liposomes, and microgels are emerging as novel saliva substitutes hold promise for alternative approaches for efficient moistening and lubrication of the oral mucosa. Their adoption into clinical practice will depend on their efficacies, duration of relief, and ease of application by the practitioners and patient compliance.
A novel approach for obtaining 12‐lead electrocardiograms in horses
Authors: Hesselkilde Eva M. , Isaksen Jonas L. , Petersen Bettina V. , Carstensen Helena , Jespersen Thomas , Pehrson Steen , Kanters Jørgen K. , Buhl Rikke
Published: December 2020

Background

In equine medicine, 12‐lead electrocardiograms (ECGs) rarely are used, which may in part be a result of shortcomings in the existing guidelines for obtaining 12‐lead ECGs in horses. The guidelines recommend placing the limb leads on the extremities, which is inappropriate because the ventricular mean electrical axis is then perpendicular to the limb leads, leading to large variations in ECG configuration even among healthy horses. From an electrophysiological point of view, the leads instead should be parallel to the electrical axis to minimize variability.

Objective

Develop an improved method for obtaining 12‐lead ECGs in horses based on electrophysiology and cardiac electrical vectors relevant to horses.

Animals

Thirty‐five healthy Standardbred horses.

Methods

Two ECGs obtained at rest; 1 ECG with the electrodes placed according to the method developed in the present study, the Copenhagen method, and 1 ECG following existing guidelines.

Results

In the Copenhagen method, we repositioned the limb electrodes to the thorax to better capture the electrical activity of the heart. Variation in the mean electrical axis decreased dramatically with the Copenhagen method (SD decreased from 24.6° to 1.6°, P < .001). Consequently, this new method provided stable ECGs with repeatable configurations.

Conclusions and Clinical Importance

With this novel method, the ECG is recorded with respect to the electric axis to fully realize the potential of 12‐lead ECG in horses. The Copenhagen method delivered more consistent and reliable ECG recordings compared to existing guidelines. The Copenhagen method potentially allows for expanded use of 12‐lead ECGs in equine medicine.
Depletion of MHC supertype during domestication can compromise immunocompetence
Authors: Smallbone Willow , Ellison Amy , Poulton Simon , van Oosterhout Cock , Cable Joanne
Published: December 2020

The major histocompatibility complex (MHC) plays an important role in infectious disease resistance. The presence of certain MHC alleles and functionally similar groups of MHC alleles (i.e., supertypes) has been associated with resistance to particular parasite species. Farmed and domesticated fish stocks are often depleted in their MHC alleles and supertype diversity, possibly as a consequence of artificial selection for desirable traits, inbreeding (loss of heterozygosity), genetic drift (loss of allelic diversity) and/or reduced parasite biodiversity. Here we quantify the effects of depletion of MHC class II genotype and supertype variation on resistance to the parasite Gyrodactylus turnbulli in guppies (Poecilia reticulata). Compared to the descendants of wild‐caught guppies, ornamental fish had a significantly reduced MHC variation (i.e., the numbers of MHC alleles and supertypes per individual, and per population). In addition, ornamental fish were significantly more susceptible to G. turnbulli infections, accumulating peak intensity 10 times higher than that of their wildtype counterparts. Four out of 13 supertypes were associated with a significantly reduced parasite load, and the presence of some supertypes had a dramatic effect on the intensity of infection. Remarkably, the ornamental and wildtype fish differed in the supertypes that were associated with parasite resistance. Analysis with a genetic algorithm showed that resistance‐conferring supertypes of the wildtype and ornamental fish shared two unique amino acids in the peptide‐binding region of the MHC that were not found in any other alleles. These data show that the supertype demarcation captures some, but not all, of the variation in the immune function of the alleles. This study highlights the importance of managing functional MHC diversity in livestock, and suggests there might be some immunological redundancy among MHC supertypes.
Increased incidence of candidemia in a tertiary care hospital with the COVID‐19 pandemic
Authors: Nucci Marcio , Barreiros Gloria , Guimarães Luiz Felipe , Deriquehem Vitor A.S. , Castiñeiras Anna Carla , Nouér Simone A.
Published: December 2020

Background

The incidence of candidemia in our hospital has been stable over an 18‐year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia.

Methods

In March 2020, the hospital was prepared to receive patients with COVID‐19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID‐19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2).

Results

We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID‐19 patients). Compared with non‐COVID‐19 patients, COVID‐19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655‐836) and 523 (interquartile range 389‐574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non‐COVID‐19 patients, 2.68 if we consider only cases of candidemia in COVID‐19 patients and 14.80 considering only admissions of patients with COVID‐19.

Conclusions

The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID‐19 patients.
L‐DOPA regulates α‐synuclein accumulation in experimental parkinsonism
Authors: Deffains Marc , Canron Marie‐Hélène , Teil Margaux , Li Qin , Dehay Benjamin , Bezard Erwan , Fernagut Pierre‐Olivier
Published: December 2020

Aims

Widespread accumulation of misfolded α‐synuclein aggregates is a key feature of Parkinson's disease (PD). Although the pattern and extent of α‐synuclein accumulation through PD brains is known, the impact of chronic dopamine‐replacement therapy (the gold‐standard pharmacological treatment of PD) on the fate of α‐synuclein is still unknown. Here, we investigated the distribution and accumulation of α‐synuclein in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) non‐human primate model of PD and determined the effect of chronic L‐DOPA treatment on MPTP‐induced α‐synuclein pathology.

Methods

We measured the density of α‐synuclein and tau immuno‐positive neurons in the substantia nigra, putamen, hippocampal CA1 region, temporal cortex and dentate nucleus of control, MPTP and MPTP+L‐DOPA‐treated monkeys. Moreover, we also extracted and quantified Triton‐X (TX) soluble and insoluble α‐synuclein in putamen and hippocampus samples from a separate cohort of control, MPTP and MPTP+L‐DOPA‐treated monkeys.

Results

MPTP‐induced α‐synuclein accumulation in NHP model of PD was not limited to the substantia nigra but also occurred in the putamen, hippocampal CA1 region and temporal cortex. Tau was increased only in the temporal cortex. Moreover, increased intraneuronal TX insoluble α‐synuclein was truncated, but not in the structural form of Lewy bodies. The MPTP‐induced increase in α‐synuclein levels was abolished in animals having received L‐DOPA in all the brain regions, except in the substantia nigra.

Conclusions

Dopamine replacement therapy can dramatically ameliorate α‐synuclein pathology in the MPTP NHP model of PD. Therefore, patient's dopaminergic medication should be systematically considered when assessing α‐synuclein as a biomarker for diagnosis, monitoring disease progression and response to disease‐modifying treatments.
Development of HM Government example menus for early years’ settings in England
Authors: Mucavele P. , Wall C. , Whiting L.
Published: December 2020

Early childhood is a critical time for growth and development, but diets of young children in England are not fully in line with dietary recommendations, and childhood obesity is a national and international concern. The importance of early years’ settings in promoting healthy food choices and helping to prevent obesity has been highlighted, and the extension in entitlement to funded early education and childcare in England over recent years provides an opportunity to encourage more children to develop good eating habits. Food provision in early years’ settings is required to be ‘healthy, balanced and nutritious’, and voluntary food and drink guidelines were published in 2012 to support settings in England to meet this requirement. However, since these guidelines were developed, revised Dietary Reference Values for energy, sugars and dietary fibre have been published. As part of the government's Childhood obesity: A plan for action, Public Health England commissioned the Children's Food Trust to produce example menus for early years’ settings, to support provision of meals and snacks meeting current dietary recommendations. A multi‐sectoral external reference group was convened and advised on the protocol for developing two seasonal example menus, including revising the underpinning nutrient framework for 1‐4 year‐olds, and developing an appropriate framework for infants aged 6–12 months, as previous menus did not cater for this age group. This article describes the process of developing the example menus and associated guidance, which have since been published by HM Government, and offers recommendations for effective implementation.
European Society for Neurogastroenterology and Motility (ESNM) recommendations for the use of high‐resolution manometry of the esophagus
Authors: Tack Jan , Pauwels Ans , Roman Sabine , Savarino Edoardo , Smout André ,   the ESNM HRM consensus group
Published: December 2020

Background

Several patients in gastroenterology practice present with esophageal symptoms, and in case of normal endoscopy with biopsies, high‐resolution manometry (HRM) is often the next step. Our aim was to develop a European consensus on the clinical application of esophageal HRM, to offer the clinician guidance in selecting patients for HRM and using its results to optimize clinical outcome.

Methods

A Delphi consensus was initiated with 38 multidisciplinary experts from 16 European countries who conducted a literature summary and voting process on 71 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 statements.

Results

The process generated guidance on when to consider esophageal HRM, how to perform it, and how to generate the report. The Delphi process also identified several areas of uncertainty, such as the choice of catheters, the duration of fasting and the position in which HRM is performed, but recommended to perform at least 10 5‐ml swallows in supine position for each study. Postprandial combined HRM impedance is considered useful for diagnosing rumination. There is a large lack of consensus on treatment implications of HRM findings, which is probably the single area requiring future targeted research.

Conclusions and inferences

A multinational and multidisciplinary group of European experts summarized the current state of consensus on technical aspects, indications, performance, analysis, diagnosis, and therapeutic implications of esophageal HRM.
Genome wide natural variation of H3K27me3 selectively marks genes predicted to be important for cell differentiation in Phaeodactylum tricornutum
Authors: Zhao Xue , Rastogi Achal , Deton Cabanillas Anne Flore , Ait Mohamed Ouardia , Cantrel Catherine , Lombard Berangère , Murik Omer , Genovesio Auguste , Bowler Chris , Bouyer Daniel , Loew Damarys , Lin Xin , Veluchamy Alaguraj , Vieira Fabio Rocha Jimenez , Tirichine Leila
Published: December 2020

In multicellular organisms, Polycomb Repressive Complex2 (PRC2) is known to deposit tri‐methylation of lysine 27 of histone H3 (H3K27me3) to establish and maintain gene silencing, critical for developmentally regulated processes. The PRC2 complex is absent in both widely studied model yeasts, which initially suggested that PRC2 arose with the emergence of multicellularity. However, its discovery in several unicellular species including microalgae questions its role in unicellular eukaryotes.

Here, we use Phaeodactylum tricornutum enhancer of zeste E(z) knockouts and show that P. tricornutum E(z) is responsible for di‐ and tri‐methylation of lysine 27 of histone H3.

H3K27me3 depletion abolishes cell morphology in P. tricornutum providing evidence for its role in cell differentiation. Genome‐wide profiling of H3K27me3 in fusiform and triradiate cells further revealed genes that may specify cell identity.

These results suggest a role for PRC2 and its associated mark in cell differentiation in unicellular species, and highlight their ancestral function in a broader evolutionary context than currently is appreciated.
Histone H3 lysine4 trimethylation‐regulated GRF11 expression is essential for the iron‐deficiency response in Arabidopsis thaliana
Authors: Singh Surjit , Kailasam Sakthivel , Lo Jing‐Chi , Yeh Kuo‐Chen
Published: December 2020

Iron (Fe) homeostasis in plants is controlled by both transcription factors (TFs) and chromatin remodeling through histone modification. To date, few studies have reported the existence of histone modification in maintaining the Fe‐deficiency response. However, the reports that do exist shed light on various histone modifications, but knowledge of the activation mark in Fe‐deficiency response is lacking.

By using a forward genetics approach, we identified a crucial allele for Fe‐deficiency response, NON‐RESPONSE TO Fe‐DEFICIENCY2 (NRF2), previously described as EARLY FLOWERING8 (ELF8) associated with an activation mark on histone modification, histone H3 lysine4 trimethylation. In the nrf2‐1 mutant, a point mutation at ELF8T404I, exhibits impaired expression of GENERAL REGULATORY FACTOR11 (GRF11) and downstream genes in the Fe‐uptake pathway.

In vivo chromatin immunoprecipitation revealed that in roots, NRF2/ELF8 is essential for the expression of GRF11 for Fe‐deficiency response, whereas in shoots, NRF2/ELF8 regulates FLOWERING LOCUS C (FLC) expression for flowering time control.

In summary, a key factor, NRF2/ELF8, involved in epigenetic regulation essential for both flowering time control and Fe‐deficiency response is uncovered.
The role of transcription factor 7‐like 2 in metabolic disorders
Authors: Zhang Zhensheng , Xu Li , Xu Xiao
Published: December 2020

Transcription factor 7‐like 2 (TCF7L2), a member of the T cell factor/lymphoid enhancer factor family, generally forms a complex with β‐catenin to regulate the downstream target genes as an effector of the canonical Wnt signalling pathway. TCF7L2 plays a vital role in various biological processes and functions in many organs and tissues, including the liver, islet and adipose tissues. Further, TCF7L2 down‐regulates hepatic gluconeogenesis and promotes lipid accumulation. In islets, TCF7L2 not only affects the insulin secretion of the β‐cells but also has an impact on other cells. In addition, TCF7L2 influences adipogenesis in adipose tissues. Thus, an out‐of‐control TCF7L2 expression can result in metabolic disorders. The TCF7L2 gene is composed of 17 exons, generating 13 different transcripts, and has many single‐nucleotide polymorphisms (SNPs). The discovery that these SNPs have an impact on the risk of type 2 diabetes (T2D) has attracted thorough investigations in the study of TCF7L2. Apart from T2D, TCF7L2 SNPs are also associated with type 1, posttransplant and other types of diabetes. Furthermore, TCF7L2 variants affect the progression of other disorders, such as obesity, cancers, metabolic syndrome and heart diseases. Finally, the interaction between TCF7L2 variants and diet also needs to be investigated.
Clinical applications of miniscrews that broaden the scope of non‐surgical orthodontic treatment
Authors: Choi Sung‐Hwan , Jeon Ji Yoon , Lee Kee‐Joon , Hwang Chung‐Ju
Published: December 2020

Previously, in the case of malocclusion owing to skeletal discrepancy in adults, the amount of tooth movement was limited since there was no reliable skeletal anchorage device. The only way to treat this case was by repositioning the maxilla and mandible via orthognathic surgery, but most patients are reluctant to undergo surgery owing to the risk and expenses incurred. However, with the current introduction and use of miniscrews as temporary anchorage devices, the entire dental arch can be relocated to a target position without surgery, thus broadening the scope of non‐surgical orthodontic treatment compared to the past. For a non‐surgical approach to improve skeletal discrepancy, anteroposterior, vertical and transverse displacements of the dental arch are necessary. In this case, the localization of the centre of resistance of the whole arch must precede the appliance design with an appropriate biomechanical design. Especially, in the transverse dimension, the envelope of discrepancy is reportedly narrow, and the tooth movement must accompany the orthopaedic correction involving the midpalatal suture expansion. Recently, in adults with transverse maxillomandibular discrepancy, miniscrew‐assisted rapid palatal expansion (MARPE) can be performed. Moreover, compared to surgically assisted rapid palatal expansion, MARPE reduces the cost to the patient and achieves clinically acceptable stable maxillary expansion. In this article, we will discuss the role of total arch movement and MARPE in widening the scope of non‐surgical orthodontic treatment, despite the inherent limitations of miniscrews' mechanical aspects.
Bone Cement Implantation Syndrome in Bone Tumor Surgeries: Incidence, Risk Factors, and Clinical Experience
Authors: Yang Tsung‐han , Yang Rong‐sen , Lin Chih‐peng , Tseng Tzu‐hao
Published: December 2020

Objective

To investigate the incidence and risk factors of bone cement implantation syndrome (BCIS) in bone tumor surgeries.

Methods

This was a retrospective observational study. We investigated patients who underwent bone tumor surgeries requiring cementation as part of the surgery between March 2016 and January 2018. We reviewed medical records, including formal anesthesia records and operation notes. Patients with complete data files were included. To investigate the general incidence of BCIS in tumor surgeries, patients of all ages, genders and tumor types were included. Vital signs, including oxygen saturation, blood pressure, heart rate, and respiratory rate, were checked and recorded once every 1–2 min after cementation. Accurate time points of cementation were recorded on formal anesthesia record sheets by the anesthesiologists. The definition and severity of BCIS were based on the classification system proposed in previous studies: grade I, moderate hypoxia (SpO2 <94%) or hypotension (fall in systolic blood pressure >20%); grade II, severe hypoxia (SpO2 <88%) or hypotension (fall in systolic blood pressure >40%) or unexpected loss of consciousness; and grade III, cardiovascular collapse requiring cardiopulmonary resuscitation. We also compared the incidence of BCIS between those patients with and without possible risk factors, including intraoperative blood loss, arthroplasty, use of an intramedullary device, patient age, gender, tumor location, and preexisting lung cancer or lung metastasis.

Results

A total of 88 patients were included. BCIS occurred in 23 patients, with an incidence of 26.1%. Among them, 19 had grade I and 4 had grade II BCIS. There was no patients with grade III BCIS. The lowest blood pressure occurred within 10 min in 21 (87.5%) patients and within 20 min for all patients. A total of 9 grade I BCIS were self‐limiting. The other 10 grade I hypotension cases and all grade II hypotension cases recovered after administration of a vasoconstrictor medication. Preexisting lung cancer or lung metastasis was the risk factor for BCIS; 40.0% of patients (16 in 40 patients) with preexisting lung cancer or metastasis had BCIS, whereas only 14.6% of patients (7 in 48 patients) without lung lesions had BCIS. There was no risk difference in terms of arthroplasty, old age, and increased blood loss. Apart from grades I and II bone cement implantation syndrome, there were no other major complications, including death, cardiovascular events, or cerebrovascular events.

Conclusion

Bone cement implantation syndrome is not unusual in bone tumor surgeries, and preexisting lung cancer or lung metastasis is a risk factor.
Heck’s disease occurring after Epstein‐Barr virus‐associated smooth muscle tumors in an immunosuppressed child
Authors: Arbelo‐Ramos Natasha , Anderson Katelyn , Joshi Avni , Wieland Carilyn , Tyring Stephen , Rady Peter , Tollefson Megha
Published: December 2020

A 10‐year‐old Guatemalan girl with past medical history of Epstein‐Barr virus‐associated smooth muscle tumors (EBV‐SMT) and combined immunodeficiency presented for evaluation of painful intraoral lesions. On examination, she was noted to have multiple, white to flesh‐colored, soft, flat‐topped papules, and plaques on the buccal and labial mucosa. Human papillomavirus type 13 was detected on PCR with PGMY primers of previously biopsied buccal tissue, confirming a diagnosis of Heck's disease (multifocal epithelial hyperplasia). We present an immunosuppressed, pediatric patient with two rare, virus‐associated neoplastic disorders that have not been previously reported to occur in the same individual.
The OPR gene family in watermelon: Genome‐wide identification and expression profiling under hormone treatments and root‐knot nematode infection
Authors: Guang Y. , Luo S. , Ahammed G. J. , Xiao X. , Li J. , Zhou Y. , Yang Y.
Published: December 2020

The enzyme 12‐oxo‐phytodienoic acid reductase (OPR) is important in the jasmonic acid (JA) biosynthesis pathway and thus plays a vital role in plant defence. However, systematic and comprehensive analyses of OPR genes in watermelon and their roles in defence responses are extremely limited.

The physicochemical properties, phylogenetic tree, gene structure and cis‐acting elements of watermelon OPR genes were analysed using bioinformatics, and qRT‐PCR and RNA‐Seq were applied to assay expression of OPR genes in watermelon.

A total of five OPR family genes were identified in watermelon, which were unevenly distributed across the four chromosomes. Phylogenetic analysis assigned OPR members from different plant species to five subfamilies (OPRI–OPRV). The motif compositions of OPR members were relatively conserved. Expression analysis using qRT‐PCR revealed that ClOPR genes, except for ClOPR5, were highly expressed in the flower and fruit. RNA‐seq analysis showed that the ClOPR genes had different expression patterns during flesh and rind development. Furthermore, the ClOPR genes, particularly ClOPR2 and ClOPR4, were significantly upregulated by exogenous JA, salicylic acid (SA) and ethylene (ET) treatments. In addition, red light induced expression of ClOPR2 and ClOPR4 in leaves and roots of root‐knot nematode (RKN)‐infected watermelon plants, suggesting their involvement in red light‐induced defence against RKN.

These results provide a theoretical basis for elucidating the diverse functions of OPR family genes in watermelon.
Governing through markets: Multinational firms in the bazaar economy
Authors: Cohen Amy J. , Jackson Jason
Published: December 2020

This article highlights a counterintuitive dynamic of neoliberal globalization. India has controversially liberalized foreign investment rules in the politically sensitive food retail sector. Critics argue that India bowed to pressure from multinational corporations, consistent with a common view that under neoliberalism markets eclipse state power. We suggest by contrast that policymakers seek multinational firms to strengthen their capacity to govern food markets that for centuries have been dominated by networks of local traders. These traders use informal conventions of market governance that have long proven resistant to centralized state control. Global retailers promise to transform these opaque, “traditional” systems into transparent, “modern,” supply chains that comply with liberal rule of law principles. Thus we argue the turn to multinational capital should neither be understood simply through the logics of state capture or welfare economics, but rather also as a political governance project that illustrates how different kinds of markets produce different conceptions of the state.
Extreme Values, Means, and Inequality Measurement
Authors: Bossert Walter , D’Ambrosio Conchita , Kamaga Kohei
Published: December 2020

We examine some ordinal measures of inequality that are familiar from the literature. These measures have a quite simple structure in that their values are determined by combinations of specific summary statistics such as the extreme values and the arithmetic mean of a distribution. In spite of their common appearance, there seem to be no axiomatizations available so far, and this paper is intended to fill that gap. In particular, we consider the absolute and relative variants of the range, the max‐mean and the mean‐min orderings, and quantile‐based measures. In addition, we provide some empirical observations that are intended to illustrate that, although these orderings are straightforward to define, some of them display a surprisingly high correlation with alternative (more complex) measures.
Mast cell density in metastatic renal cell carcinoma: Association with prognosis and tumour‐infiltrating lymphocytes
Authors: Yao Jiaxi , Xi Wei , Chen Xiang , Xiong Ying , Zhu Yanjun , Wang Hang , Hu Xiaoyi , Guo Jianming
Published: December 2020

Tumour‐infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumour‐infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow‐up data were collected from 231 patients with mRCC; TIMs (mast cells density positive to tryptase), along with CD8+ and CD4+ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log‐rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression‐free survival (OS, P = .008, and PFS, P = .016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR = 0.624, 95% CI: 0.420‐0.927, P = .020) and PFS (HR = 0.658, 95% CI: 0.466‐0.930, P = .019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one‐ and two‐year OS (P = .002 and P = .004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (P = .008 and P = .001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co‐existence of CD8+ and CD4+ TILs, which have anti‐tumour effects on activation status.