bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of differences in whey composition on the physicochemical properties of whey butter
Authors: Kasapcopur Eren , Mohammed Aram M , Colakoglu Abdullah S
Published: April 2021

The objective of this work was to determine the effects of whey composition on the physicochemical properties of whey butter and compare with milk butter based on these properties. Whey samples were obtained from the whey processing plants located in different regions of Turkey. Whey composition influenced the major and minor components of whey butters. Differences among the whey butters were observed on titratable acidy (TA, 0.43–0.55%), acid value (AV, 0.75–0.90 mg KOH/g), moisture (17.33–19.05%), fat (80.23–81.47%), nonfat solid (0.66–1.20%), NaCl (0.10–0.23%), peroxide value (PV, 1.08–1.50 meq O2/kg), total carotenoids (1.78–2.21 mg/kg), γ‐ and total tocopherols (1.06–1.41 and 27.02–27.33 mg/kg, respectively), Ca (73.12–94.72 mg/kg), P (56.03–72.20 mg/kg), K (73.36–140.10 mg/kg), Mg (12.83–18.12 mg/kg), Na (63.95–165.85 mg/kg), total minerals (283.32–485.53 mg/kg), colour (L*, 86.46–89.52 and b*, 12.21–15.52) and certain fatty acids. The milk butters were one‐ to threefold lower in TA, AV, moisture, NaCl and PV and one‐ to 3.4‐fold higher in fat, nonfat solids, protein, total carotenoids, α‐, γ‐ and total tocopherols, Ca, P, K, Mg and total minerals. Whey butters were distinctly brighter and less yellower. Butter source had no effect on iodine value (35.39 ± 0.15 g I2/100 g), saponification value (225.22 ± 0.17 mg KOH/g), β‐tocopherol (0.41 ± 0.02 mg/kg), certain fatty acids, melting characteristic and thermo‐oxidative stability. The cluster analysis enabled the division of whey and milk butters into two separate groups. These results highlighted that partial transfer of certain compounds from milk to whey during cheese manufacturing and biochemical and chemical changes such as lipolysis, hydrolysis and oxidation that occur in the period from the whey production to butter processing were largely responsible for the differences in the whey and milk butter properties.
The Role of Moral Devaluation in Phasing Out Fossil Fuels: Limits for a Socioecological Fix
Authors: Furnaro Andrea
Published: April 2021

By putting into conversation theories of capital devaluation, the scholarship on the socioecological fix, and critical energy studies, this paper offers a conceptual framework to study the phase‐out of fossil fuel energy infrastructure. The concept of moral devaluation is presented, which emphasises the interaction of economic, political, and socioecological dimensions shaping the main forces, constraints, and regulatory mechanisms to devalue emission‐intensive fixed capital. This notion of moral devaluation is useful to inform empirical research on the institutional arrangements through which the devaluation of fixed fossil fuel capital is resisted and organised. Moreover, this notion complements current studies about the possibility of a capital switch to renewable energies as a socioecological fix to the climate and other entangled crises of capitalism, by emphasising that the devaluation of fixed capital represents a constraining condition for the rapid emergence of a socioecological fix based on fixed capital formation in the low‐carbon energy sector.
Pharmacological HIF‐PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation
Authors: Burmakin Mikhail , Fasching Angelica , Kobayashi Hanako , Urrutia Andrés A. , Damdimopoulos Anastasios , Palm Fredrik , Haase Volker H.
Published: April 2021

Aim

Hypoxia‐inducible factors (HIFs) are O2‐sensitive transcription factors that regulate multiple biological processes which are essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF‐prolyl hydroxylase domain (PHD) dioxygenases (HIF‐PHIs) activate HIF‐dependent transcriptional programs and have broad clinical potential. HIF‐PHIs are currently in global late‐stage clinical development for the treatment of anaemia associated with chronic kidney disease. Although the effects of hypoxia on renal haemodynamics and function have been studied in animal models and in humans living at high altitude, the effects of pharmacological HIF activation on renal haemodynamics, O2 metabolism and metabolic efficiency are not well understood.

Methods

Using a cross‐sectional study design, we investigated renal haemodynamics, O2 metabolism, gene expression and NO production in healthy rats treated with different doses of HIF‐PHIs roxadustat or molidustat compared to vehicle control.

Results

Systemic administration of roxadustat or molidustat resulted in a dose‐dependent reduction in renovascular resistance (RVR). This was associated with increased glomerular filtration rate (GFR), urine flow and tubular sodium transport rate (TNa). Although both total O2 delivery and TNa were increased, more O2 was extracted per transported sodium in rats treated with high‐doses of HIF‐PHIs, suggesting a reduction in metabolic efficiency. Changes in RVR and GFR were associated with increased nitric oxide (NO) generation and substantially suppressed by pharmacological inhibition of NO synthesis.

Conclusions

Our data provide mechanistic insights into dose‐dependent effects of short‐term pharmacological HIF activation on renal haemodynamics, glomerular filtration and O2 metabolism and identify NO as a major mediator of these effects.
Promoting children's inquiry performances in alternate reality games: A mobile concept mapping‐based questioning approach
Authors: Liang Hsin‐Yi , Hsu Tien‐Yu , Hwang Gwo‐Jen
Published: April 2021

Active inquiry plays a key role in science education. To facilitate children's motivation, alternate reality games are applied to engage children actively in inquiry in authentic learning contexts. However, the complexity of real‐world contexts and the ambiguity of game puzzles increase the difficulty for children to conduct effective inquiries. To achieve successful inquiry‐based learning, concept mapping is an effective learning strategy to guide children to organise related information as well as to brainstorm for possible solutions. Accordingly, this study proposes a mobile concept mapping‐based questioning approach for environmental education. A quasi‐experimental study was conducted to evaluate the effectiveness of the proposed approach and the conventional questioning approach in game‐based inquiry‐based learning. The results showed that the proposed approach had a more significant effect on learning achievement, critical thinking, and learning attitude than the conventional questioning approach. However, cognitive overload negatively affected the children's learning. Besides, it was found that improper use of concept maps could limit their creative problem‐solving performances.

Practitioner notes

What is already known about this topic

Alternate reality game (ARG) significantly promotes children’s learning motivation and engagement of game‐based inquiry learning activities.

Most children have difficulties in learning with ARGs due to the complexity of real‐world contexts and the ambiguity of the puzzles.

Children cannot construct knowledge effectively without proper learning supports in their cognitive process; however, it is challenge to provide proper learning supports without distracting children from gaming.

What this paper adds

An ARG with a mobile concept mapping‐based questioning approach (ARG‐CMQ) was applied to facilitate meaningful inquiry‐based learning for children in different real environments (school campuses and in science museums).

Both quantitative and qualitative analyses were examined to identify the effect of different learning strategies to support children learning with ARGs.

ARG‐CMQ improved children’s learning achievement, critical thinking and learning attitude better than conventional ARGs.

ARG‐CMQ might limit children’s divergent thinking and influences their creative problem‐solving performance.

Implications for practice and/or policy

ARG‐CMQ is a potential approach for inquiry‐based learning in real environments, especially in improving learning perceptions and higher‐order cognitive abilities.

ARG‐CMQ can be used to support competency‐based education.
Efficacy and safety of intravitreal methotrexate for vitreo‐retinal lymphoma – 20 years of experience
Authors: Habot‐Wilner Zohar , Frenkel Shahar , Pe’er Jacob
Published: April 2021

Vitreo‐retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients’ characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo‐retina (49%), solely the CNS (37%) or solely the vitreo‐retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate–severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side‐effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side‐effects.
Protective properties of GLP‐1 and associated peptide hormones in neurodegenerative disorders
Authors: Hölscher Christian
Published: April 2021

Type 2 diabetes mellitus and the associated desensitisation of insulin signalling has been identified as a risk factor for progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and others. Glucagon‐like peptide 1 (GLP‐1) is a hormone that has growth factor‐like and neuroprotective properties. Several clinical trials have been conducted, testing GLP‐1 receptor agonists in patients with Alzheimer's disease, Parkinson's disease or diabetes‐induced memory impairments. The trials showed clear improvements in Alzheimer's disease, Parkinson's disease and diabetic patients. Glucose‐dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) is the ‘sister’ incretin hormone of GLP‐1. GIP analogues have shown neuroprotective effects in animal models of disease and can improve on the effects of GLP‐1. Novel dual GLP‐1/GIP receptor agonists have been developed that can enter the brain at an enhanced rate. The improved neuroprotective effects of these drugs suggest that they are superior to single GLP‐1 receptor agonists and could provide disease‐modifying care for Alzheimer's disease and Parkinson's disease patients.

LINKED ARTICLES

This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Habitat alteration modifies the structure and function of mixed‐species flocks in an Andean landscape
Authors: Vásquez‐Ávila Bernarda , Knowlton Jessie L. , Espinosa Carlos I. , Tinoco Boris A.
Published: April 2021

Understanding the responses of species interactions to land‐use change is a key challenge in ecology and conservation. In the tropical Andes, a large proportion of birds interact with other bird species and create networks of mixed‐species flocks; however, the widespread effects of land‐use change in the region raise concerns about the alteration of these interactions. Here we explored how structural (i.e., species richness and size) and functional (i.e., network connectivity indices) parameters of mixed flocks change along a gradient from open vegetation to native forest habitats. This study was conducted in the southern Andes of Ecuador, where we sampled mixed‐species flocks in 12 areas for five consecutive months, and applied network analysis tools to characterize structural parameters (observed richness, flock size, flock encounter rate, composition) and functional parameters (degree, weighted degree, cluster, and skewness) of flocks. We found that the network indices, degree and weighted degree of species, were positively associated with areas of dense vegetation and native trees. These two network indices indicated that mixed flocks occupying native forest have higher connectivity, a factor that can promote the stability of flocks. The structural parameters of flocks, species richness, and abundance, were not associated with the vegetation structure. Overall, our results show that functional parameters of flocks can be more sensitive than structural parameters to the effects of land‐use change in our study area. We demonstrate the importance of combining the analysis of structure and functionality of flocks to reveal the effects of land‐use change. Lastly, our results highlight the importance of mature native forest for the conservation of species and the maintenance of non‐trophic interactions.

Abstract in Spanish is available with online material.
Prognostic significance of carcinoembryonic antigen combined with carbohydrate antigen 19‐9 following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer
Authors: Zheng Zhifang , Wang Xiaojie , Lu Xingrong , Huang Ying , Chi Pan
Published: April 2021

Aim

The clinical significance of carcinoembryonic antigen (CEA) combined with carbohydrate antigen 19‐9 (CA19‐9) in patients with rectal cancer is not well established. The aim of this study was to determine the prognostic value of these combined tumour markers in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT).

Method

A total of 687 consecutive patients with LARC who underwent nCRT and radical surgery were analysed. Tumour characteristics, recurrence‐free survival (RFS) and overall survival (OS) were compared according to the number of elevated tumour markers measured before and after nCRT. In addition, the prognostic significance of perioperative changes in the combined tumour markers was further evaluated.

Result

The RFS and OS rates decreased in a stepwise manner in association with the number of elevated pre‐ and post‐nCRT tumour markers (all p < 0.05). Multivariate analysis showed that only the number of elevated post‐nCRT tumour markers was an independent prognostic factor (both p < 0.05). For 311 patients with elevated pre‐nCRT tumour markers, normalization of the tumour markers after nCRT was an independent prognostic protective factor (both p < 0.05), and patients with both markers elevated post‐nCRT had a 2.5‐ and 3.7‐fold increased risk of recurrence and death, respectively (p < 0.05). Furthermore, normalization of post‐nCRT tumour markers after surgery was also closely related to an improved prognosis.

Conclusion

This combination of post‐nCRT tumour markers can accurately predict the long‐term survival of patients with LARC treated with nCRT and curative resection, and normalization of the combined tumour markers after either nCRT or surgery was associated with better survival.
A retrospective analysis of the safety and efficacy of apixaban use after lung transplant
Authors: Reininger Kevin A. , Sam Teena , Patel Raksha S. , Grazia Todd J. , Naik Chetan A. , Ausloos Kenneth A. , Rosenblatt Randall L. , Lam In Lok L.
Published: April 2021

Direct acting oral anticoagulants (DOACs) have become the mainstay of treatment for patients requiring anticoagulation for atrial arrhythmias and venous thromboembolism (VTE) but safety and efficacy has not been established in lung transplantation. This is a retrospective review of 28 adult lung transplant patients who were prescribed apixaban for stroke prevention in atrial arrhythmias or treatment of VTE between October 15, 2015 and December 31, 2018. The primary outcome was a composite of efficacy and safety measured by recurrence or breakthrough of stroke or thromboembolism and bleeding events. Seven patients were treated for atrial arrhythmias and 21 treated for VTE. Fifteen patients received CYP3A4 or P‐gp inhibitors at initiation of anticoagulation, and 4 of these patients received strong CYP3A4 inhibitors. During the follow‐up period, one breakthrough DVT and one clinically relevant non‐major bleed were observed. These data suggest that apixaban may be safe to use for lung transplant patients, and larger studies are warranted to assess long‐term outcomes as well as safety and efficacy of alternative DOACs.
Synaptic NMDA receptor signalling controls R‐type calcium channel recruitment
Authors: Feng Zhendong , Glebov Oleg O.
Published: April 2021

Regulation of extracellular Ca2+ influx by neuronal activity is a key mechanism underlying synaptic plasticity. At the neuronal synapse, activity‐dependent Ca2+ entry involves N‐methyl‐D‐aspartate receptors (NMDARs) and voltage‐gated calcium channels (VGCCs); the relationship between NMDARs and VGCCs, however, is poorly understood. Here, we report that neuronal activity rapidly (1h) regulates recruitment of R‐type VGCCs in hippocampal neurons through synaptic NMDAR signalling. This finding reveals a link between two key neuronal signalling pathways, suggesting a feedback mode for regulation of synaptic Ca2+ signalling.
Physical and cognitive profiles in motoric cognitive risk syndrome in an older population from Southern Italy
Authors: Bortone Ilaria , Griseta Chiara , Battista Petronilla , Castellana Fabio , Lampignano Luisa , Zupo Roberta , Sborgia Giancarlo , Lozupone Madia , Moretti Biagio , Giannelli Gianluigi , Sardone Rodolfo , Panza Francesco
Published: April 2021

Background and purpose

In older age, physical and cognitive declines have been shown to occur simultaneously or consequent to one another, and several operational definitions have been proposed to consider the co‐presence of the two declines; for example, “Motoric cognitive risk syndrome” (MCR) has been proposed as a definition for the coexistence of slow gait plus subjective cognitive complaints. Given the increasing interest in MCR and its potential role as both biomarker and therapeutic target, we aimed to estimate its prevalence in a large cohort of non‐demented older subjects, and to examine the associations between physical status, global cognitive dysfunction, and impairment in various cognitive domains in MCR.

Methods

A population‐based sample of 1041 older people in Southern Italy (mean age 75.15 years) was enrolled. We defined MCR using slowness and a single question for subjective cognitive complaints. We also administered a comprehensive neuropsychological test battery, together with tests assessing physical function.

Results

The prevalence of MCR was 9.9% (95% confidence interval 8.2–11.9). MCR was associated with decreased processing speed and executive function after adjusting for all relevant confounders. However, we found no significant association of MCR with decreased global cognition and immediate/delayed free recall of verbal memory. MCR was also associated with increased exhaustion, low muscle strength, and low physical activity, and increased levels of C‐reactive protein and interleukin‐6.

Conclusions

The present findings on MCR prevalence and associated cognitive and physical domains and inflammatory biomarkers may help to uncover altered pathways and therapeutic targets for intervention during the long preclinical phase of neurodegenerative dementia.
Hay versus haylage: Forage type influences the equine urinary metabonome and faecal microbiota
Authors: Leng Joy , McNally Susan , Walton Gemma , Swann Jonathan , Proudman Chris , Argo Caroline , Emery Sue , La Ragione Roberto , Eustace Robert
Published: April 2021

Background

Gut microbial communities are increasingly being linked to diseases in animals and humans. Obesity and its associated diseases are a concern for horse owners and veterinarians, and there is a growing interest in the link among diet, the intestinal microbiota and metabolic disease.

Objectives

Assess the influence of long‐term hay or haylage feeding on the microbiota and metabolomes of 20 Welsh mountain ponies.

Study design

Longitudinal study.

Methods

Urine, faeces and blood were collected from 20 ponies on a monthly basis over a 13‐month period. Urine and faeces were analysed using proton magnetic resonance (1H NMR) spectroscopy and faecal bacterial DNA underwent 16S rRNA gene sequencing.

Results

Faecal bacterial community profiles were observed to be different for the two groups, with discriminant analysis identifying 102 bacterial groups (or operational taxonomic units, OTUs) that differed in relative abundance in accordance with forage type. Urinary metabolic profiles of the hay‐ and haylage‐fed ponies were significantly different during 12 of the 13 mo of the study. Notably, the urinary excretion of hippurate was greater in the hay‐fed ponies for the duration of the study, while ethyl‐glucoside excretion was higher in the haylage‐fed ponies.

Main limitations

The study was undertaken over a 13‐month period and both groups of ponies had access to pasture during the summer months.

Conclusions

The data generated from this study suggest that the choice of forage may have implications for the intestinal microbiota and metabolism of ponies and, therefore, potentially their health status. Understanding the potential implication of feeding a particular type of forage will enable horse owners to make more informed choices with regard to feed, especially if their horse or pony is prone to weight gain.
Revisiting sardine recruitment hypotheses: Egg‐production‐based survival index improves understanding of recruitment mechanisms of fish under climate variability
Authors: Takasuka Akinori , Nishikawa Haruka , Furuichi Sho , Yukami Ryuji
Published: April 2021

Proportionality between spawning stock biomass (SSB) and annual total egg production (TEP) has been an inherent assumption in spawner–recruitment models for fisheries management and studies on recruitment mechanisms in fish. However, recent evidence of density dependence in egg production has led to a need to reconsider the validity of recruitment per spawning stock biomass (RPS), which is a SSB‐based survival index from hatching to recruitment, in recruitment studies. Here we revisit sardine recruitment hypotheses based on recruitment per egg production (RPE), which is a TEP‐based survival index, by reanalyzing published data for the Pacific stock of Japanese sardine (Sardinops melanostictus) in the Kuroshio Current system at a multidecadal scale. By adopting RPE, we detected statistically significant relationships of the survival from hatching to recruitment to large‐scale ocean climate anomaly, ambient temperature in the nursery grounds and growth rate during the early life stages. None of these relationships were detected by RPS. We propose the adoption of TEP‐based survival indices rather than SSB‐based ones in future studies on recruitment mechanisms of fish in relation to environmental and biological factors. Developing egg‐production‐based survival indices has the potential to improve understanding of recruitment mechanisms of fish under climate variability.
A GRASP/Path‐Relinking algorithm for the traveling purchaser problem
Authors: Cuellar‐Usaquén Daniel , Gomez Camilo , Álvarez‐Martínez David
Published: April 2021

The Traveling Purchaser Problem (TPP) is a generalization of the TSP that consists in choosing which nodes (markets) to visit to create a tour that allows to buy a set of products at minimum transportation and purchasing cost. The TPP has gained attention due to the computational challenges it poses and the potential applications it can support in today's technology‐driven industry. This paper presents a GRASP‐based methodology for the TPP based on three constructive procedures (route‐first, purchase‐first, and purchase‐and‐route) and two local search operators (insert and remove). The methodology is strengthened with a Path Relinking strategy to improve the GRASP performance by re‐combining a set of elite solutions and with a Filtering strategy to improve the algorithm's efficiency by avoiding local search operations on the least promising solutions. The algorithm is tested with 855 instances of the asymmetric TPP and 190 instances of the symmetric TPP. Computational results prove the benefit of including the Path Relinking and Filtering strategies and suggest that the purchase‐first constructive procedure is the most competitive in terms of objective function value with little extra effort in execution time with respect to the other constructive procedures. Our results outperform published results for the asymmetric TPP in a statistically significant way and show competitive performance for the symmetric TPP.
What does it mean to be Black and White? A meta‐ethnographic review of racial socialization in Multiracial families
Authors: Green McKenzie N. , Charity‐Parker Bianka M. , Hope Elan C.
Published: April 2021

Racial socialization—parent–child communication about race—may promote cohesion and relational satisfaction in Multiracial Black–White families, where parents and children have unique racial experiences. However, little is known about how racial socialization is actually practiced in Multiracial families. The current paper addresses this gap by synthesizing the existing qualitative literature on racial socialization in Multiracial Black–White families. Seventeen articles were identified using three electronic databases and appraised based on a critical review form for qualitative investigations. We then used meta‐ethnographic methods and two theoretical frameworks to explore patterns of racial socialization, which included messages about (1) Monoracial Black experiences, (2) the irrelevance of race (e.g., color‐evasiveness), and (3) Multiracial experiences. The findings illuminate the intricacies of parental racial socialization in Multiracial Black–White families. The implications for family theory and practice are discussed.
Restricted mean survival time versus conventional measures for treatment decision‐making
Authors: Kim Dae Hyun , Shi Sandra M. , Carroll Danette , Najafzadeh Mehdi , Wei Lee‐Jen
Published: April 2021

Background/objectives

Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in the event‐free days. It remains uncertain whether communicating treatment benefit and harm using RMST‐based summary is more effective than conventional summary based on absolute and relative risk reduction. We compared the effect of RMST‐based approach and conventional approach on decisional conflict using an example of intensive versus standard blood pressure‐lowering strategies.

Design

On‐line survey.

Setting

A convenience sample of patients in the United States.

Participants

Two hundred adults aged 65 and older with hypertension requiring anti‐hypertensive treatment (response rate 85.5%).

Interventions

Participants were randomly assigned to either RMST‐based summary or conventional summary about the benefit and harm of blood pressure‐lowering strategies.

Measurements

Decisional Conflict Scale (DCS), ranging from 0 (no conflict) to 100 (high conflict), and preference for intensive blood pressure‐lowering strategy.

Results

Participants assigned to RMST‐based approach (n = 100) and conventional approach (n = 100) had similar age (mean [standard deviation, SD]: 72.3 [5.6] vs 72.8 [5.5] years) and proportions of female (50 [50.0%] vs 61 [61.0%]) and white race (92 [92.0%] vs 92 [92.0%]). The mean (SD) DCS score was 25.2 (15.0) for RMST‐based approach and 25.6 (14.1) for conventional approach (p = 0.84). The number (%) of participants who preferred intensive strategy was 10 (10.0%) for RMST‐based approach and 14 (14.0%) for conventional approach (p = 0.52). The results were consistent in subgroups defined by age, sex, education level, cardiovascular disease status, and predicted mortality risk categories.

Conclusion

In a sample of relatively healthy older adults with hypertension, RMST‐based approach was as effective as conventional approach on decisional conflict about choosing a blood pressure‐lowering strategy. This study provides proof‐of‐concept evidence that RMST‐based approach can be used in conjunction with absolute and relative risk reduction for communicating treatment benefit and harm in a decision aid.
Single intracerebroventricular progranulin injection adversely affects the blood–brain barrier in experimental traumatic brain injury
Authors: Hummel Regina , Lang Manuel , Walderbach Simona , Wang Yong , Tegeder Irmgard , Gölz Christina , Schäfer Michael K. E.
Published: April 2021

Progranulin (PGRN) is a neurotrophic and anti‐inflammatory factor with protective effects in animal models of ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury (TBI). Administration of recombinant (r) PGRN prevents exaggerated brain pathology after TBI in Grn‐deficient mice, suggesting that local injection of recombinant progranulin (rPGRN) provides therapeutic benefit in the acute phase of TBI. To test this hypothesis, we subjected adult male C57Bl/6N mice to the controlled cortical impact model of TBI, administered a single dose of rPGRN intracerebroventricularly (ICV) shortly before the injury, and examined behavioral and biological effects up to 5 days post injury (dpi). The anti‐inflammatory bioactivity of rPGRN was confirmed by its capability to inhibit the inflammation‐induced hypertrophy of murine primary microglia and astrocytes in vitro. In C57Bl/6N mice, however, ICV administration of rPGRN failed to attenuate behavioral deficits over the 5‐day observation period. (Immuno)histological gene and protein expression analyses at 5 dpi did not reveal a therapeutic benefit in terms of brain injury size, brain inflammation, glia activation, cell numbers in neurogenic niches, and neuronal damage. Instead, we observed a failure of TBI‐induced mRNA upregulation of the tight junction protein occludin and increased extravasation of serum immunoglobulin G into the brain parenchyma at 5 dpi. In conclusion, single ICV administration of rPGRN had not the expected protective effects in the acute phase of murine TBI, but appeared to cause an aggravation of blood–brain barrier disruption. The data raise questions about putative PGRN‐boosting approaches in other types of brain injuries and disease.

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Predictors of health service use by family caregivers of persons with multimorbidity
Authors: Canca‐Sánchez José C. , García‐Mayor Silvia , Morales‐Asencio José Miguel , Gómez‐Gónzalez Alberto José , Kaknani‐Uttumchandani Shakira , Cuevas Fernández‐Gallego Magdalena , Lupiáñez‐Pérez Inmaculada , Caro‐Bautista Jorge , León‐Campos Álvaro
Published: April 2021

Background

Informal caregivers of patients with multiple chronic conditions are socially good, promoting the sustainability of a large part of home care provision. However, this very demanding activity causes health problems that increase their own need for health services. This study analyses the use of health services by informal carers, comparing it with the use made by the general population with similar characteristics.

Methodology

Cross‐sectional analytical study carried out in the Malaga‐Valle Guadalhorce Primary Health Care District (Spain). Healthcare demand and perceived health were measured in the family caregivers, compared to the general population. Strobe Statement for observational studies has been used to strength the report of the results.

Results

Final sample consisted of 314 family caregivers together with a subsample of 2.290 non‐caregivers taken from data of the National Health Survey. This subsample was paired by gender with our sample. Formal caregivers make fewer annual visits to the health services, with respect to the general population, regardless of the perceived level of health. The difference of the means between those who perceive their health as very poor was 0.11 (95% CI: 0.01 to 0.20) consultations with the family doctor, 0.21 (95% CI: 0.15 to 0.26) consultations with medical specialists and 1.70 (95% CI: 1.52 to 1.87) emergency room attention. Three independent factors were identified that predispose to the increased use of health services: background of greater education achievement (OR 8.13, 95% CI: 1.30 to 50.68), non‐cohabitation with the care recipient (OR 3.57, 95% CI: 1.16 to 11.11) and a more positive physical quality of life component (OR 1.06; 95% CI: 1.03 to 1.09).

Discussion and Implications

Intrinsic components of the caregiver reveal their independent relationship with the provision of informal care and the use of health services. A broader vision is needed for the factors that influence the health of these caregivers to develop multipurpose interventions and improve the consistency and effectiveness of the health services offered to the caregiver.
Influence of contextual factors on death by suicide in rural and urban settings
Authors: Shiner Brian , Peltzman Talya , Cornelius Sarah L. , Gui Jiang , Jiang Tammy , Riblet Natalie , Gottlieb Daniel J. , Watts Bradley V.
Published: April 2021

Purpose

To examine the association between contextual factors, represented by geographic and community health variables, and suicide among rural and urban Department of Veterans Affairs health care users (VA users).

Methods

We performed a retrospective cohort study of 12,700,847 VA users between 2003 and 2017. We assigned contextual factors based on individuals’ home address at the ZIP Code (area deprivation), county (sunlight exposure, altitude, and community health), and state level (firearm ownership), using publicly available data sources. We grouped contextual factors by quintiles or prespecified thresholds, depending on the nature of each variable. We obtained mortality data from the National Death Index. We measured the effect of living in a place with the highest versus lowest level of each contextual factor on odds of suicide using logistic regression, adjusting for individual compositional factors abstracted from VA electronic medical records data. We used random forest modeling to build prediction models for suicide based on contextual factors among rural and urban veterans.

Findings

Almost all contextual factors we examined were significantly associated with suicide among rural and urban VA users, even after adjusting for individual compositional factors. However, no contextual variables were strong protective or risk factors (0.52.0), and prediction models leveraging these contextual factors had poor accuracy among both rural (0.51, 95% CI: 0.48‐0.54) and urban (0.53, 95% CI: 0.51‐0.55) VA users.

Conclusions

A wide variety of contextual factors is significantly associated with suicide among rural and urban VA users. However, the factors we measured contributed very little to individual‐level suicide risk.
Allopurinol hepatotoxicity is associated with human leukocyte antigen Class I alleles
Authors: Fontana Robert J. , Li Yi‐Ju , Phillips Elizabeth , Saeed Naba , Barnhart Huiman , Kleiner David , Hoofnagle Jay ,   the Drug Induced Liver Injury Network
Published: April 2021

Background/Aims

Allopurinol can cause HLA class I‐associated life‐threatening severe skin reactions. However, HLA risk and association with clinical features in allopurinol hepatotoxicity are unknown.

Methods

Eleven of 17 patients with suspected allopurinol hepatotoxicity enrolled into the Drug‐Induced Liver Injury Network were adjudicated as definite, highly likely, or probable. High‐resolution HLA sequencing was undertaken in cases and compared with population and other DILI controls.

Result

Median age was 60 years, 54% were male, and 63% African‐ American, 27% Caucasian, and 9% Hispanic. Patients presented at a median of 52 days after starting allopurinol, all were hospitalized and six were jaundiced. The median peak ALT, alkaline phosphatase, and total bilirubin were 525 U/L, 521 U/L, and 7.8 mg/dl, respectively, with a median R ratio of 2.7 at onset. During follow‐up, nine patients were treated with corticosteroids including five of the six with suspected DRESS. Three patients died including two from liver failure at 38 and 45 days after onset, and the remaining eight recovered. Three HLA alleles were found to be overrepresented in allopurinol cases, particularly in African Americans: HLA‐B*58:01, which has been previously linked to severe skin reactions, and HLA‐B*53:01 and HLA‐A*34:02, all of which are more frequently found in African Americans than European Americans or Latinos.

Conclusions

Allopurinol hepatotoxicity is associated with systemic hypersensitivity, a short latency to onset, African‐American race and three HLA risk alleles, HLA‐B*58:01, HLA‐B*53:01, and HLA‐A*34:02‐58:01 testing may help confirm a diagnosis of hepatotoxicity in allopurinol‐treated patients.
DNA methylation status of MutS genes in ameloblastoma
Authors: do Amaral‐Silva Gleyson Kleber , Pereira Thaís dos Santos Fontes , Rocha André Caroli , Mariz Bruno Augusto Linhares Almeida , Prado‐Ribeiro Ana Carolina , Fonseca Felipe Paiva , Gomez Ricardo Santiago , Vargas Pablo Agustin
Published: April 2021

Objectives

Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas.

Materials and Methods

The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin‐embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at −196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real‐time PCR (qPCR) assay. The ameloblastoma paraffin‐embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage.

Results

There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry.

Conclusion

Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.
Assessing public value failure in government adoption of artificial intelligence
Authors: Schiff Daniel S. , Schiff Kaylyn Jackson , Pierson Patrick
Published: April 2021

In the context of rising delegation of administrative discretion to advanced technologies, this study aims to quantitatively assess key public values that may be at risk when governments employ automated decision systems (ADS). Drawing on the public value failure framework coupled with experimental methodology, we address the need to measure and compare the salience of three such values—fairness, transparency, and human responsiveness. Based on a preregistered design, we administer a survey experiment to 1460 American adults inspired by prominent ADS applications in child welfare and criminal justice. The results provide clear causal evidence that certain public value failures associated with artificial intelligence have significant negative impacts on citizens' evaluations of government. We find substantial negative citizen reactions when fairness and transparency are not realized in the implementation of ADS. These results transcend both policy context and political ideology and persist even when respondents are not themselves personally impacted.
Expression of cancer testis antigens in thymic epithelial tumors
Authors: Sakane Tadashi , Murase Takayuki , Okuda Katsuhiro , Masaki Ayako , Nakanishi Ryoichi , Inagaki Hiroshi
Published: April 2021

Cancer testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. However, to our knowledge, expression of the antigens in thymic epithelial tumors has not been examined yet. We examined the immunohistochemical expression of five CTAs (MAGE‐A, NY‐ESO‐1, MAGE‐C1, SAGE and GAGE7) in 192 cases of thymic epithelial tumor. The CTAs were variably expressed in the thymic epithelial tumors. Type B component of type AB thymomas, type B1/B2/B3 thymomas, and thymic carcinomas showed a generally positive correlation between the malignancy grades and positive expression rates in four CTAs other than MAGE‐C1. In thymic squamous cell carcinomas (SqCCs), four antigens except for MAGE‐C1 showed high expression rates ranging from 23.1% to 43.6%. In the prognostic analysis, a positive expression of SAGE (P = 0.0485) and GAGE7 (P = 0.0289) were associated with a shorter overall survival in type B2/B3 thymomas, respectively. In thymic SqCC, a positive MAGE‐A expression was significantly associated with an increased level of programmed death ligand in tumor‐infiltrating lymphocytes (P = 0.0181). We showed (i) a frequent CTA expression, (ii) a general correlation of CTA expression with tumor malignancy grades and (iii) a prognostic impact in some of the CTAs.
Effect of low temperature and high humidity stress on physiology of cucumber at different leaf stages
Authors: Amin B. , Atif M. J. , Wang X. , Meng H. , Ghani M. I. , Ali M. , Ding Y. , Li X. , Cheng Z.
Published: April 2021

Low temperature (LT) and high humidity (HH) are important environmental factors in greenhouses and plastic tunnels during the cold season, as they hamper plant growth and development.

Here, we studied the effect of LT (day/night: 9/5 °C, 25/18 °C as control) and HH (95%, 80% as control) on young cucumber plants at the 2, 4 or 6 leaf stages.

LT+HH stress resulted in a decline in shoot, root and total fresh and dry weights, and decreased Pn, gs, Tr, Fv/Fm, qP, ETR and chlorophyll, and increased MDA, H2O2, O2‐, NPQ and Ci as compared to the control at the 2 leaf stage. SOD, POD, CAT, APX and GR were upregulated under LT+HH stress as compared to the control at the 6 leaf stage. ABA and JA increased under LT+HH stress as compared to the control at the 6 leaf stage, while IAA and GA decreased under LT+HH stress as compared to the control at the 2 leaf stage.

Our results show that LT+HH stress affects young cucumber plant photosynthetic efficiency, PSII activity, antioxidant defence system, ROS and hormone profile. Plants at the 6 leaf stage were more tolerant than at the 2 and 4 leaf stages under stress conditions.
Jama'at‐e‐Islami and Trust Building in Bangladesh
Authors: Mostofa Shafi Md
Published: April 2021

Bangladesh is the third‐largest Muslim country in the world where Islamic ideals inherently influence people's thought and actions. One of the Islamist political parties that has been trying to influence the Bangladeshi population is the Jama'at‐e‐Islami (JeI). The JeI is one of the oldest and largest Islamist political parties in the country and has continuously exerted its influence on the social ethos and state policy. JeI's unconditional support for Islamization and a society based on Sharia law undoubtedly attracts some sections of the Bangladeshi population. Apart from promoting an Islamist totalitarian ideology, it also maintains a requirement of religious purification for choosing its party members; a strategy that has earned a reputation as a party with robust intraparty discipline. To enhance its trust‐based relationships with its members (at both the horizontal and vertical levels), JeI helps its members through various means, including the provision of financial support, social welfare programs, and charity activities. Although the targeted population are their members, these schemes have had an impact, however minimal, on the Bangladeshi population to redress its anti‐independence stance in 1971, on the failure to send an apology message for what JeI did in 1971, and on the worldwide failure of political Islam.

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Authors: Farouk Abubakar Umar , Jibril Rabiu Saminu , Maigoshi Zaharaddeen Salisu , Ahamad Tijjani Habibu , Bako Muktar Musa
Published: April 2021

The study explores appropriate mechanism for diversifying Nigeria’s revenue to tap from the opportunities offered by the blue economy. The study conceptually reviewed extant literature as a basis for acquiring an in depth understanding of the phenomenon with a view to offer practical recommendations on the issue. The study discovered that blue economy has the potential of augmenting government revenue if the financial and environmental issues bedeviling the development of the sector are properly addressed. Thus, the study recommends political will and strong institutions for effective running and implementation of blue economy strategies in the nation based on the existing international standards. It also suggested that, to boost revenue from blue economy, Area-based Management needs to be established.
Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp.
Authors: Kornelsen Vanessa , Kumar Ayush
Published: April 2021

Acinetobacter
spp. have become of increased clinical importance as studies have shown the antimicrobial resistant potential of these species. Efflux pumps can lead to reduced susceptibility to a variety of antibiotics and are present in large number across
Acinetobacter
spp.
ToxR Mediates the Antivirulence Activity of Phenyl-Arginine-β-Naphthylamide To Attenuate Vibrio cholerae Virulence
Authors: Weng Yuding , Bina Thomas F. , Bina X. Renee , Bina James E.
Published: April 2021

Multidrug efflux systems belonging to the resistance-nodulation-cell division (RND) family are ubiquitous in Gram-negative bacteria and are critical for antimicrobial resistance. This realization has led to efforts to develop efflux pump inhibitors (EPI) for use as adjuvants for antibiotic treatment of resistant organisms.
A Dynamic, Ring-Forming Bactofilin Critical for Maintaining Cell Size in the Obligate Intracellular Bacterium Chlamydia trachomatis
Authors: Brockett Mary R. , Lee Junghoon , Cox John V. , Liechti George W. , Ouellette Scot P.
Published: April 2021

Bactofilins are polymer-forming cytoskeletal proteins that are widely conserved in bacteria. Members of this protein family have diverse functional roles such as orienting subcellular molecular processes, establishing cell polarity, and aiding in cell shape maintenance.