bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining factor VIII levels and thrombin/plasmin generation: A population pharmacokinetic‐pharmacodynamic model for patients with haemophilia A
Authors: Bukkems Laura H. , Valke Lars L. F. G. , Barteling Wideke , Laros‐van Gorkom Britta A. P. , Blijlevens Nicole M. A. , Cnossen Marjon H. , van Heerde Waander L. , Schols Saskia E. M. , Mathôt Ron A. A.
Published: December 2021

Aims

Prophylactic treatment of haemophilia A patients with factor VIII (FVIII) concentrate focuses on maintaining a minimal trough FVIII activity level to prevent bleeding. However, due to differences in bleeding tendency, the pharmacokinetic (PK)‐guided dosing approach may be suboptimal. An alternative approach could be the addition of haemostatic pharmacodynamic (PD) parameters, reflecting a patient's unique haemostatic balance. Our aim was to develop a population PK/PD model, based on FVIII activity levels and Nijmegen Haemostasis Assay (NHA) patterns, a global haemostatic assay that measures thrombin/plasmin generation simultaneously.

Methods

PK/PD measurements were collected from 30 patients treated with standard half‐life FVIII concentrate. The relationship between FVIII activity levels and the thrombin/plasmin generation parameters (thrombin potential, thrombin peak height and plasmin peak height), were described by sigmoidal Emax functions.

Results

The obtained EC50 value was smallest for the normalized thrombin potential (11.6 IU/dL), followed by normalized thrombin peak height (56.6 IU/dL) and normalized plasmin peak height (593 IU/dL), demonstrating that normalized thrombin potential showed 50% of the maximal effect at lower FVIII activity levels. Substantial inter‐individual variability in the PD parameters, such as EC50 of thrombin potential (86.9%) was observed, indicating that, despite similar FVIII activity levels, haemostatic capacity varies significantly between patients.

Conclusion

These data suggest that dosing based on patients' individual PK/PD parameters may be beneficial over dosing solely on individual PK parameters. This model could be used as proof‐of‐principle to examine the application of PK/PD‐guided dosing. However, the relation between the PD parameters and bleeding has to be better defined.
Influence of baseline QTc on sotalol‐induced prolongation of ventricular repolarization in men and women
Authors: Funck‐Brentano Christian , Salem Joe‐Elie
Published: December 2021

The extent of sotalol‐induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the extent of drug‐induced QTc prolongation remains unclear. This was studied around peak plasma concentration in a large cohort of 376 healthy male and 614 healthy female subjects who received 80 mg of sotalol orally. Baseline QTc was 379 ± 16 ms in men and 393 ± 15 ms in women (P < .0001). The change in QTc from baseline was highly variable among both sexes and was greater in women than in men (26.5 ± 13.2 vs.13.0 ± 10.8 ms; P < .0001). The slope of the regression line between QTc on sotalol and baseline QTc did not significantly differ from unity in men and in women, indicating that the extent of QTc prolongation with sotalol was not influenced by baseline QTc. Assessing QTc after administration of an IKr blocker may be more important than measuring a baseline QTc.
Estimating Cell Type Composition Using Isoform Expression One Gene at a Time
Authors: Heiling Hillary M. , Wilson Douglas R. , Rashid Naim U. , Sun Wei , Ibrahim Joseph G.
Published: December 2021

Human tissue samples are often mixtures of heterogeneous cell types, which can confound the analyses of gene expression data derived from such tissues. The cell type composition of a tissue sample may itself be of interest and is needed for proper analysis of differential gene expression. A variety of computational methods have been developed to estimate cell type proportions using gene-level expression data. However, RNA isoforms can also be differentially expressed across cell types, and isoform-level expression could be equally or more informative for determining cell type origin than gene-level expression. We propose a new computational method, IsoDeconvMM, which estimates cell type fractions using isoform-level gene expression data. A novel and useful feature of IsoDeconvMM is that it can estimate cell type proportions using only a single gene, though in practice we recommend aggregating estimates of a few dozen genes to obtain more accurate results. We demonstrate the performance of IsoDeconvMM using a unique data set with cell type–specific RNA-seq data across more than 135 individuals. This data set allows us to evaluate different methods given the biological variation of cell type–specific gene expression data across individuals. We further complement this analysis with additional simulations.
Is the label ‘conspiracy theory’ a cause or a consequence of disbelief in alternative narratives?
Authors: Douglas Karen M. , van Prooijen Jan‐Willem , Sutton Robbie M.
Published: December 2021

Using the label ‘conspiracy theory’ is widely perceived to be a way of discrediting wild ideas and unsubstantiated claims. However, prior research suggests that labelling statements as conspiracy theories does not reduce people's belief in them. In four studies, we probed this effect further, and tested the alternative hypothesis that the label ‘conspiracy theory’ is a consequence rather than a cause of (dis)belief in conspiracy‐related statements. Replicating prior research, Study 1 (N = 170) yielded no evidence that the label ‘conspiracy theory’ affects belief in statements. In Study 2 (N = 199), we discovered that the less people believed in statements, the more they favoured labelling them as ‘conspiracy theories’. In Studies 3 and 4 (Ns = 150 and 151), we manipulated the relative believability of statements and found that participants preferred the label ‘conspiracy theory’ for relatively less believable versus more believable statements. The current research therefore supports the hypothesis that prior (dis)agreement with a statement affects the use of the label ‘conspiracy theory’ more than the other way around.
Heterospecific infanticide among sympatric peccaries in Costa Rica
Authors: Carrillo Eduardo , Fuller Todd K.
Published: December 2021

We observed white‐lipped peccaries (Tayassu pecari) killing infant collared peccaries (Pecari tajacu) on the Osa Peninsula of Costa Rica. Camera trap data indicated high overlap of peccary activity periods, but spatio‐temporal avoidance of white‐lipped peccaries by collared peccaries. Heterospecific infanticide is unknown among ungulates, but could be an important factor in reinforcing niche partitioning.

Abstract in Spanish is available with online material.
Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes
Authors: Ueda Yasunori , Usuki Kensuke , Fujita Jiro , Matsumura Itaru , Aotsuka Nobuyuki , Sekiguchi Naohiro , Nakazato Tomonori , Iwasaki Hiromi , Takahara‐Matsubara Mariko , Sugimoto Saori , Goto Masashi , Naoe Tomoki , Kizaki Masahiro , Miyazaki Yasushi , Aakashi Koichi
Published: December 2021

DSP‐7888 is an immunotherapeutic cancer vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of DSP‐7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP‐7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2‐4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose‐limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty‐seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher‐risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8‐10.3) months. Median OS was 10.0 (90% CI, 7.6‐11.4) months in patients with a WT1‐specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3‐8.1) months in those without a WT1‐specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP‐7888 dosing emulsion.
Patient‐reported outcome measures comparing static computer‐aided implant surgery and conventional implant surgery for single‐tooth replacement: A randomized controlled trial
Authors: Kunavisarut Chatchai , Santivitoonvong Akarin , Chaikantha Sarunya , Pornprasertsuk‐Damrongsri Suchaya , Joda Tim
Published: December 2021

Objective

To compare static computer‐aided implant surgery (s‐CAIS) and conventional implant surgery (CIS) for single‐tooth replacement in posterior sites in terms of patient‐reported outcome measures (PROMs).

Methods

Forty patients were divided into two groups for treatment with s‐CAIS (Test) and CIS (Control). Patients’ anxiety level was measured using the modified dental anxiety score before implant surgery. After surgery, patients completed two questionnaires for 7 days. The first questionnaire assessed pain level using a visual analog scale (VAS) and the incident rate of pain using a 5‐point Likert scale; analgesic intake was also recorded. The second questionnaire investigated patients’ oral health‐related quality of life (OHRQoL) including postoperative symptoms, oral function, and daily activity. The difference between data was compared at significance level (α = 0.05).

Results

There was no statistically significant difference in pretreatment dental anxiety level, postoperative pain scores, and OHRQoL between treatment groups. Overall, mild or moderate dental anxiety was reported by 70% and 20% of patients, respectively. Pain score was significantly reduced by postoperative Day 3 in the test group and Day 4 in the control group, compared with baseline. Both groups significant reduced analgesic intake by postoperative Day 5. Most OHRQoL‐related complaints subsided approximately 3 days after surgery.

Conclusions

Overall, PROMs between s‐CAIS and CIS were not significantly different for the single‐tooth implant surgery in the posterior area. Postoperative symptoms after implant surgery still inevitably occurred, reflecting the normal process of oral wound healing.
Exploring the impact of climate change on the future of community‐based wildlife conservation
Authors: Carpenter Stefan
Published: December 2021

Community‐based conservation (CBC) is a wildlife governance approach popular in areas projected to experience a decline in precipitation due to climate change. A survey of residents in four Namibian CBC areas found that the overwhelming majority of respondents felt that (a) a prolonged drought coincided with an increased rate of human‐wildlife conflict (HWC), and (b) costs from HWC outweighed any CBC benefits they received. Perceptions of increased HWC frequency were negatively associated with the likelihood of respondents feeling that wildlife benefits exceeded costs. These findings raise questions about the impact of predicted climate change effects on CBC programs across much of the global south.
COVID Connections: Lessons from Adaptations to COVID‐19 as Strategies for Building Food System Resilience
Authors: O’Connell Caela , Gay Rosemary , McDonald Noreen , Tayal Sita
Published: December 2021

To identify elements of crisis response that might hold lessons for resilience beyond the current moment, we studied a central North Carolina food system during the COVID‐19 pandemic. Based on ethnographic interviews with farmers, employees and volunteers of food access organizations, and local government employees, our work found that connection, networking, innovation, and technology adoption were sources of strength and growth. Lessons: food system actors found that their social connections helped them to exchange information and resources, meet increased food needs among SNAP (Supplemental Nutrition Assistance Program) participants and Latina/os immigrants, and combine efforts to adopt technologies and learn from new labor pools. Challenges: while navigating COVID‐19, food system actors faced challenges spanning labor, safety, information, government policies, supply shortages, weather, and unreliable information. In addition to lessons and challenges, we offer a series of future research directions that we identified in our study findings. Our study shows that small‐scale production and local food organization and government responses are important and dynamic parts of a resilient food system. Regional systems’ actors were able to pivot more quickly than large‐scale systems and presented a more flexible, locally suitable model that will likely prove adaptive beyond the pandemic.
Can borderline regression method be used to standard set OSCEs in small cohorts?
Authors: Moreno‐López Rosa , Hope David
Published: December 2021

Introduction

Absolute methods of standard setting (SS) are more suitable for OSCEs. However, previous studies have theorised that borderline regression method (BRM) is not reliable for small sample sizes.

Materials and methods

OSCE results for the 2017–2019 cohorts were analysed to compare BRM versus Modified Angoff. We reported on whether the stations in multiple cohorts were sufficiently equivalent to aggregate the results together to calculate which method of SS was more reliable. We finally used the bootstrapping method to compare the accuracy of BRM for small versus simulated larger cohorts.

Results

BRM was a valid method for SS OSCEs in this dataset when station quality was sufficiently high. However, a large gap between the Angoff and BRM in some of the OSCEs was observed, which could be explained by poor use of the grading scale. Model fit statistics were generally adequate even with low sample sizes. Using the bootstrap of datasets, the error rate was much higher for low‐quality stations but was not an issue in high‐quality ones.

Discussion

This study adds to the evidence that well‐designed OSCEs can use BRM for small cohorts. However, there is a need for the institutions to properly assess their stations and their assessors, before embarking into using this method, to prevent from having to remove stations.

Conclusions

This analysis suggests that BRM is an acceptable replacement for Angoff SS in small cohorts, where there is a range of candidates undertaking the assessments and there are well‐designed OSCES with well‐trained examiners.
Effects of amniotic fluid on human keratinocyte gene expression: Implications for wound healing
Authors: Nyman Erika , Lindholm Elvira , Rakar Jonathan , Junker Johan P. E. , Kratz Gunnar
Published: December 2021

Cutaneous wounds can lead to huge suffering for patients. Early fetal wounds have the capacity to regenerate without scar formation. Amniotic fluid (AF), containing hyaluronic acid (HA), may contribute to this regenerative environment. We aimed to analyse changes in gene expression when human keratinocytes are exposed to AF or HA. Human keratinocytes were cultured to subconfluence, starved for 12 h and then randomised to be maintained in (1) Dulbecco's modified Eagle's medium (DMEM), (2) DMEM with 50% AF, or (3) DMEM with 50% fetal calf serum (FCS). Transcriptional changes were analysed using microarray and enriched with WebGestalt and Enrichr. Additionally, eight diagnostic genes were analysed using semiquantitative real‐time PCR to investigate epidermal differentiation and cellular stress after HA exposure as an alternative for AF exposure. The AF and FCS treatments resulted in enrichment of genes relating to varied aspects of epidermal and keratinocyte biology. In particular, p63‐, AP1‐ and NFE2L2‐ (Nrf2) associated genes were found significantly regulated in both treatments. More genes regulated by FCS treatment were associated with inflammatory signalling, whilst AF treatment was dominantly associated with molecular establishment of epidermis and lipid metabolic activity. HA exposure mostly resulted in gene regulation that was congruent with the AF microarray group, with increased expression of ITGA6 and LOR. We conclude that AF exposure enhances keratinocyte differentiation in vitro, which suggests that AF constituents can be beneficial for wound‐healing applications.
Adoption of Fad Diets through the Lens of the Diffusion of Innovations
Authors: Lee Heejae , Worthy Sheri
Published: December 2021

Despite unconfirmed health benefits, consumers continue to adopt fad diets. Based on Rogers' (2003) diffusion of innovations theory, we investigate which attributes are related to adoption of three popular fad diets (ketogenic, paleolithic, and intermittent fasting) relative to the expert‐recommended Mediterranean diet. Binary logistic regression results using data from an online survey of 424 US adults revealed that a diet’s complexity was negatively associated with adoption, while a diet’s relative advantage and compatibility were not related. This study adds to the literature about pro‐innovation bias by presenting evidence that Rogers’ theory may not apply to fad diet adoption behavior.
p53 in senescence – it's a marathon, not a sprint
Authors: Sheekey Eleanor , Narita Masashi
Published: December 2021

The tumour suppressor p53, a stress‐responsive transcription factor, plays a central role in cellular senescence. The role of p53 in senescence‐associated stable proliferative arrest has been extensively studied. However, increasing evidence indicates that p53 also modulates the ability of senescent cells to produce and secrete diverse bioactive factors (collectively called the senescence‐associated secretory phenotype, SASP). Senescence has been linked with both physiological and pathological conditions, the latter including ageing, cancer and other age‐related disorders, in part through the SASP. Cellular functions are generally dictated by the expression profile of lineage‐specific genes. Indeed, expression of SASP factors and their regulators are often biased by cell type. In addition, emerging evidence suggests that p53 contributes to deregulation of more stringent lineage‐specific genes during senescence. P53 itself is also tightly regulated at the protein level. In contrast to the rapid and transient activity of p53 upon stress (‘acute‐p53’), during senescence and other prolonged pathological conditions, p53 activities are sustained and fine‐tuned through a combination of different inputs and outputs (‘chronic‐p53’).
Multiple binding modes of an N‐terminal CCR5‐peptide in complex with HIV‐1 gp120
Authors: Moseri Adi , Akabayov Sabine R. , Cohen Leah S. , Naider Fred , Anglister Jacob
Published: December 2021

The N‐terminal segment of CCR5 contains four tyrosine residues, sulphation of two of which is essential for high‐affinity binding to gp120. In the present study, the interactions of gp120YU2 with a 27‐residue N‐terminal CCR5 peptide sulphated at position Y10 and Y14, i.e. Nt‐CCR5, were studied using 13C‐edited‐HMQC methyl‐NOESY [1H(13C)‐1H], combined with transferred NOE NMR spectroscopy. A large number of pairwise interactions were observed between the methyl protons of methionine, threonine, valine and isoleucine residues of gp120, and the aromatic tyrosine‐protons of Nt‐CCR5. M434, V120 and V200 of gp120 were found to interact with all four tyrosine residues, Y3, sY10, sY14 and Y15. Particularly intriguing was the observation that Y3 and Y15 interact with the same gp120 methyl protons. Such interactions cannot be explained by the single cryo‐EM structure of gp120/CD4/CCR5 complex published recently (Nature, 565, 318–323, 2019). Rather, they are consistent with the existence of a dynamic equilibrium involving two or more binding modes of Nt‐CCR5 to gp120. These different modes of binding can coexist because the surface of gp120 contains two sites that can optimally interact with a sulphated tyrosine residue and two sites that can interact favorably with a non‐sulphated tyrosine residue. Modelling of gp120YU2 complexed with the Nt‐CCR5 peptide or with the entire CCR5 receptor provides an explanation for the NMR observations and the existence of these different binding modes of the disordered N‐terminus of CCR5. The data presented extend our understanding of the two‐step model and suggest a more variable binding mode of Nt‐CCR5 with gp120.
Stepping stones towards Antarctica: Switch to southern spawning grounds explains an abrupt range shift in krill
Authors: Atkinson Angus , Hill Simeon L. , Reiss Christian S. , Pakhomov Evgeny A. , Beaugrand Gregory , Tarling Geraint A. , Yang Guang , Steinberg Deborah K. , Schmidt Katrin , Edwards Martin , Rombolá Emilce , Perry Frances A.
Published: December 2021

Poleward range shifts are a global‐scale response to warming, but these vary greatly among taxa and are hard to predict for individual species, localized regions or over shorter (years to decadal) timescales. Moving poleward might be easier in the Arctic than in the Southern Ocean, where evidence for range shifts is sparse and contradictory. Here, we compiled a database of larval Antarctic krill, Euphausia superba and, together with an adult database, it showed how their range shift is out of step with the pace of warming. During a 70‐year period of rapid warming (1920s–1990s), distribution centres of both larvae and adults in the SW Atlantic sector remained fixed, despite warming by 0.5–1.0°C and losing sea ice. This was followed by a hiatus in surface warming and ice loss, yet during this period the distributions of krill life stages shifted greatly, by ~1000 km, to the south‐west. Understanding the mechanism of such step changes is essential, since they herald system reorganizations that are hard to predict with current modelling approaches. We propose that the abrupt shift was driven by climatic controls acting on localized recruitment hotspots, superimposed on thermal niche conservatism. During the warming hiatus, the Southern Annular Mode index continued to become increasingly positive and, likely through reduced feeding success for larvae, this led to a precipitous decline in recruitment from the main reproduction hotspot along the southern Scotia Arc. This cut replenishment to the northern portion of the krill stock, as evidenced by declining density and swarm frequency. Concomitantly, a new, southern reproduction area developed after the 1990s, reinforcing the range shift despite the lack of surface warming. New spawning hotspots may provide the stepping stones needed for range shifts into polar regions, so planning of climate‐ready marine protected areas should include these key areas of future habitat.
Elite women coaches negotiating and resisting power in football
Authors: Knoppers Annelies , de Haan Donna , Norman Leanne , LaVoi Nicole
Published: December 2021

While football remains mostly a sport associated with men and national identity, it has also become a popular sport for women and girls in Western countries. Despite this success, however, the coaching of football remains a strongly male dominated occupation. In this paper, we explored how 10 elite women coaches of national football teams negotiated and resisted the entanglement of techniques of biopower, sovereign and disciplinary power within the sport. The results revealed that sovereign power as exercised by Football Associations was intertwined with forms of discursive and biopower. This power constructed men as more knowledgeable about women's football than women who have years of playing and coaching experience at the elite level in the sport. Consequently, men are more often hired to coach women. In response, elite women coaches negotiated and resisted these forms of power by engaging in problematization, public truth telling/parrhesia, self‐transformation, and by creating alternative discourses about gender and football. They constructed their fellow women coaches as being more knowledgeable and more experienced than men coaches in women's football. The findings suggest that this use of a Foucauldian analysis into the entanglement of forms of power within such male‐dominated organizations and into the technologies of the self, utilized by women coaches, provides new insights into understanding the relative lack of change in gender ratio in (sport) leadership.
Simultaneous fractionation of multiple classes of polyphenols from honeybush tea using solid‐phase extraction
Authors: Su Keran , Ee Kim Huey , Sun Jingcan , Liu Shao Quan , Lassabliere Benjamin , Feiter Ulrich , Huang Yunle , Goh Rui Min Vivian , Pua Aileen , Yu Bin
Published: December 2021

The structural diversity of polyphenols and the inherent limitations of current extraction techniques pose a challenge to extract polyphenols using a simple and green method. Hence, in this study, a method was developed to simultaneously fractionate multiple classes of polyphenols by only varying ethanol‐water solutions. Honeybush tea, which is rich in polyphenols, was selected as a model for this study. Solvent extraction followed by solid‐phase extraction (SPE) was developed to obtain a polyphenol‐rich fraction from six honeybush samples. Based on a gradient elution programme (10%, 30%, 50%, 70% and 90% (v/v) ethanol‐water solution) of SPE, the Strata X cartridge showed a better recovery of most targeted polyphenols under 0.9 mL of the drying volume and 1 mL min−1 of the dispensing speed. The elution programme for fractionating most polyphenols was as follows: single elution with 50% ethanol, followed by twice elution with 70% ethanol. The antioxidant capacity was used to analyse the differences among the polyphenol‐rich fractions from six honeybush samples. Principal component analysis (PCA) revealed that unfermented C. genistoides (GG) has the greatest antioxidant capacity among the honeybush species studied. Additionally, mangiferin, isomangiferin and vicenin‐2 were the main contributors to the antioxidant capacity in six honeybush fractions according to the correlation study.
Arid1a promotes thymocyte development through β‐selection‐dependent and β‐selection‐independent mechanisms
Authors: Yang Xiaofeng , Wang Xin , Lei Lei , Su Yanhong , Zou Yujing , Liu Haiyan , Jiao Anjun , Zhang Cangang , Liu Jun , Li Wenhua , Ding Renyi , Zhou Xiaobo , Shi Lin , Zhang Dan , Sun Chenming , Zhang Baojun
Published: December 2021

Early T‐cell development from CD4− CD8− double‐negative (DN) stage to CD4+ CD8+ double‐positive (DP) stage in the thymus is regulated through multiple steps involving a batch of sequentially expressed factors. Our preliminary data and a recent report showed that AT‐rich interaction domain 1A (Arid1a) is required for the transition from DN to DP stages, but the mechanism is not fully understood. In this study, we consolidated that conditional deletion of Arid1a in T‐cell lineage intrinsically caused developmental blocks from DN3 to DN4 stages, as well as from DN4 to DP stages using both in vivo adoptive T‐cell transfer model and in vitro culture system. The expression of intracellular TCRβ is significantly decreased in Arid1a‐deficient DN4 cells compared with WT cells. OT1 transgenic TCR can rescue the defect in the transition from DN3 to DN4 stages, but not from DN to DP stages. Furthermore, we observed a comparable or stronger proliferation capacity accompanied by a significant increase in cell death in Arid1a−/− DP cells compared with that in WT controls. RNA‐Seq analysis shows a significant enrichment of apoptotic pathway within differentially expressed genes between Arid1a−/− and WT DP cells, including the upregulation of Bim, Casp3 and Trp53 and the downregulation of Rorc, Bcl‐XL and Mcl1. Therefore, our study reveals a novel mechanism that Arid1a controls early T‐cell development by maintaining intracellular TCRβ expression‐mediated β‐selection and activating parallel cell survival pathways.
Large electrocaloric effect with ultrawide temperature span in Na1/2Bi1/2TiO3‐based lead‐free ceramics
Authors: Wei Qiumei , Fulanovic Lovro , Lalitha Kodumudi Venkataraman , Zheng Mupeng , Hou Yudong , Zhu Mankang , Liu Linjing , Chang Yunfei , Xue Rui
Published: December 2021

Innovative cooling technologies are recognized by many industries as a crucial part of their system design. A large electrocaloric effect (ECE) and extended working temperature are the key issues hindering the realization of electrocaloric refrigeration technology. In this work, large ECE (ΔT = 0.8–0.9°C @ 4 kV/mm) with an ultrawide temperature span from 30 to 120°C is noted for lead‐free (Na1/2Bi1/2)0.80Sr0.20(Zn1/3Nb2/3)xTi1‐xO3ceramics. The excellent ECE performance can be ascribed to the evolution of polar nanoregions. Our work suggests that this material is promising for applications in solid‐state refrigeration systems with a broad range of operating temperatures.
Ethanol ablation for ventricular arrhythmias: A systematic review and meta‐analysis
Authors: Creta Antonio , Earley Mark J. , Schilling Richard J. , Finlay Malcolm , Sporton Simon , Dhinoja Mehul , Hunter Ross J. , Papageorgiou Nikolaos , Ang Richard , Chow Anthony , Lowe Martin , Segal Oliver R. , Lambiase Pier D. , Providência Rui
Published: December 2021

Introduction

Ethanol ablation (EA) is an alternative option for subjects with ventricular arrhythmias (VAs) refractory to conventional medical and ablative treatment. However, data on the efficacy and safety of EA remain sparse.

Methods

A systematic literature search was conducted. The primary outcomes were 1) freedom from the targeted VA and 2) freedom from any VAs post‐EA. Additional safety outcomes were also analyzed.

Results

Ten studies were selected accounting for a population of 174 patients (62.3 ± 12.5 years, 94% male) undergoing 185 procedures. The overall acute success rate of EA was 72.4% (confidence interval [CI95%]: 65.6–78.4). After a mean follow‐up of 11.3 ± 5.5 months, the incidence of relapse of the targeted VA was 24.4% (CI95%: 17.1–32.8), while any VAs post‐EA occurred in 41.3% (CI95%: 33.7–49.1). The overall incidence of procedural complications was 14.1% (CI95%: 9.8–19.8), with pericardial complications and complete atrioventricular block being the most frequent. An anterograde transarterial approach was associated with a higher rate of VA recurrences and complications compared to a retrograde transvenous route; however, differences in the baseline population characteristics and in the targeted ventricular areas should be accounted.

Conclusion

EA is a valuable therapeutic option for VAs refractory to conventional treatment and can result in 1‐year freedom from VA recurrence in 60%–75% of the patients. However, anatomical or technical challenges preclude acute success in almost 30% of the candidates and the rate of complication is not insignificant, highlighting the importance of well‐informed patient selection. The certainty of the evidence is low, and further research is necessary.
Can crowdsourced data help to optimize atopic dermatitis treatment? Comparing web search data and environmental data in Germany
Authors: Mick A. , Tizek L. , Schielein M. , Zink A.
Published: December 2021

Background

Atopic dermatitis (AD) is one of the most common chronic skin diseases worldwide, showing various manifestations and having a severe impact on quality of life. As previous studies demonstrated, internet search analysis can help identify public interest in diseases and possible influencing factors on search behavior.

Objective

To identify AD‐related topics of interest in Germany using internet search volume.

Methods

Google Ads Keyword Planner was used to identify AD‐related search terms including their search volume in Germany on a national level as well as in 16 selected cities from January 2016 to December 2019. Identified keywords were qualitatively analyzed, and temporal trends as well as the influence of seasonal and environmental factors on search volume were assessed.

Results

Overall, 1222 AD‐related search terms with a search volume of 8 842 360 searches were identified. An increase from 2016 to 2019 and seasonal peaks from January to April of each year were observed. Nationwide, the search volume correlated with mean monthly temperature and sun duration. With increasing temperature and sun duration, a significant decrease in search queries was observed. The most populated cities showed the lowest number of searches per 100 000 inhabitants (Berlin, Hamburg, and Munich). In the eight categories formed (comorbidities, general, influential factors, localization, stage of life, symptoms/severity, therapy/information, and questions on AD), the highest proportion of search queries were assigned to the category “therapy/information” in most cities. In this category, a focus on the topics of “alternative medicine” and “home remedies“ could be observed.

Conclusion

The overall high and increasing search volume indicates a high interest in AD‐related topics, especially regarding treatment and disease education. Information provided by internet search volume analyses can optimize AD therapy and patient‐centered care by providing insight into patient needs and predicting potential climatic trigger factors.
Insights into the behavioural responses of juvenile thornback ray Raja clavata to alternating and direct current magnetic fields
Authors: Albert Luana , Olivier Frédéric , Jolivet Aurélie , Chauvaud Laurent , Chauvaud Sylvain
Published: December 2021

As part of energy transition, marine renewable energy devices (MRED) are currently expanding in developed countries inducing the deployment of dense networks of submarine power cables. Concern has thus raised about the cable magnetic emissions (direct or alternating current) because of potential interference with the sensorial environment of magneto‐sensitive species, such as sharks and rays. This study sought to assess the short‐term behavioural responses of juvenile thornback rays (Raja clavata) (n = 15) to direct and alternating (50 Hz) uniform 450‐μT artificial magnetic fields using 1 h focal‐sampling design based on a detailed ethogram. Careful control of magnetic fields' temporal and spatial scales was obtained in laboratory conditions through a custom‐made Helmholtz coil device. Overall, qualitative or quantitative behavioural responses of juvenile rays did not significantly vary between control vs. exposed individuals over the morning period. Nonetheless, rays under direct current magnetic field increased their activity over the midday period. Synchronisation patterns were also observed for individuals receiving alternating current exposure (chronologic and qualitative similarities) coupled with a high inter‐individual variance. Further studies should consider larger batches of juveniles to address the effect of long‐term exposure and explore the sensitivity range of rays with dose‐response designs.
Topography of the deep temporal arteries and implications for performing safe aesthetic injections
Authors: Nikolis Andreas , Enright Kaitlyn M. , Troupis Theodore , Koutsilieris Michael , Stratigos Alexander J. , Rigopoulos Dimitrios , Cotofana Sebastian
Published: December 2021

Background

Several studies have started investigating the safety of temporal rejuvenation using soft tissue fillers. However, as the temporal region is highly vascularized, adverse events due to intravascular injection are of primary concern. The scarcity of treatment guidelines to date have focused primarily on avoiding the superficial and middle temporal arteries. The aim of the present anatomical study was to describe the topography of the deep temporal arteries (DTAs) with reference to superficial landmarks, to aid clinicians who perform temporal injections.

Methods

The tissue layers of eight fresh‐frozen cephalic cadavers were dissected and assessed, bilaterally in the temporal region (N = 16). Distance (D) of the anterior (D1 and D3) and posterior (D2 and D4) arteries was measured from (i) the zygomaticofrontal suture line at the lateral orbital rim (D1 and D2) and (ii) the junction of the superior border of the zygomatic arch and lateral orbital rim (D3 and D4). The distance between the anterior and posterior DTAs was also recorded, at the two regions (D5).

Results

Bifurcations of the DTAs were observed in 18.75% (3/16) and 12.5% (2/16) of cases, for the anterior and posterior branches, respectively. On average [mean (standard deviation)], D1 (anterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 1.56 cm (0.59); D2 (posterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 2.98 cm (0.70); D3 (anterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 1.14 cm (0.63); D4 (posterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 2.37 cm (0.62); and D5 (distance between the anterior and posterior DTAs) = 1.54 cm (0.68).

Conclusion

To help avoid vascular adverse events while performing temporal injections, aesthetic clinicians should be conscientious of safety implications related to the anatomical location of the DTAs and their ramifications.
Treatment of superficial benign vascular tumors by high intensity focused ultrasound: Observations in two illustrative cases
Authors: Calik Jacek , Zawada Tomasz , Bove Torsten
Published: December 2021

Background

Existing therapeutic methods for reduction or removal of superficial vascular malformations and tumors have high risks of scarring and other complications that result in aesthetic appearance less favorable than the baseline. Patients are often cautioned against intervention, which can lead to psychosocial problems and low self‐esteem. Improved treatment modalities are therefore relevant from both medical and aesthetic perspectives.

Methods

Two volunteer subjects were treated with a medical 20 MHz high intensity focused ultrasound device developed for dermatological conditions. One patient was given three treatments to remove a superficial congenital hemangioma on the left middle cheek. The other patient was given a single treatment to remove seven cherry angiomas on the thighs. Handpieces with nominal focal depths of 0.8 – 1.8 mm below the skin surface were used to administer acoustic energy of 1.1 – 1.2 J/dose. An integrated dermoscope in the handpiece was used to monitor the treatment in real‐time.

Results

During treatment, blood in the capillary network of the lesions was coagulated immediately, and capillary walls were collapsed due to the thermal and mechanical effects of the high intensity focused ultrasound. During the healing phase, the areas regenerated a normal skin structure with very limited scar or dyspigmentation. At follow‐up, a clear aesthetic improvement was observed over the baseline for all treated targets with the exception of two cherry angiomas, where focal depth and/or dose coverage had not been optimal.

Conclusion

High intensity focused ultrasound is concluded to be a safe and efficient skin treatment for benign superficial vascular malformations and tumors.
Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue
Authors: Dincer Busra , Cinar Irfan , Yayla Muhammed , Toktay Erdem
Published: December 2021

Aim

Ovarian ischemia–reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury.

Methods

Thirty‐three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham‐operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion.

Results

IL‐1β, IL‐6, TNF‐α, NF‐κB, and CASP‐3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF‐κB, TNF‐α, IL‐1β, and IL‐6 expressions. GOS was also corrected by reducing the elevated expression of CASP‐3 as apoptosis‐change marker.

Conclusion

These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.
Language ideologies in a minority context: An experimental study of teachers’ responses to variation in Irish
Authors: Ó Murchadha Noel , Kavanagh Lauren
Published: December 2021

Ideologies on linguistic variation among teachers of the Irish language are the focus of this article. Participants completed an experiment in which they responded to speech samples representing traditional dialectal varieties in the Irish‐speaking communities (the Gaeltacht) and a sample representing the Irish of new speakers outside the Gaeltacht (the post‐Gaeltacht). When participants directly rate the speech varieties, the traditional Gaeltacht samples are rated significantly more positively than the post‐Gaeltacht sample. However, the post‐Gaeltacht new speaker variety is on top for standardness. When participants rate the speakers’ characteristics, a more levelled, destandardised value system is also evident. The results are related to the official regimentation of Irish today, where authority is increasingly nebulous and negotiable. The results illustrate how teacher ideologies can develop in late modernity, whether in a minority context, in a context where authority is based on authenticity and a dialect ideology is established, or where language transmission occurs largely through education and substantial numbers of new speakers use the language.
SEVERE BIODEGRADATION OF CRUDE OILS FROM THE QUIRIQUIRE FIELD, EASTERN VENEZUELAN BASIN
Authors: López Liliana , Romero Jesús A. , Lo Mónaco Salvador
Published: December 2021

Five crude oil samples from the Quiriquire field (Maturin sub‐basin, Eastern Venezuelan Basin) were analysed to evaluate their levels of biodegradation. The oils were obtained from coarse sandstones and conglomerates of the Pliocene Quiriquire Formation at depths <1000 m. Analyses of the samples’ bulk physicochemical parameters indicate variations in API gravity and in the content of saturated hydrocarbons and NSO+asphaltenes, and also in the saturate/aromatic ratio which increases in more biodegraded oils. n‐Alkane distributions are characterized by a dominant unresolved complex mixture (UCM) or hump under an envelope of peaks which lack the acyclic isoprenoids pristane and phytane. The alteration of steranes and terpanes together with the presence of 25‐norhopanes and 17‐nor‐tricyclic terpanes, and the alteration of low molecular‐weight (C20‐C21) triaromatic steroids, phenanthrene, methyl‐phenanthrene, dibenzothiophene and methyl‐dibenzothiophene, indicate that the oils have undergone severe biodegradation.

The oils contain compounds with different susceptibilities to biodegradation which is probably a consequence of the mixing of different oil charges in the Quiriquire Formation reservoir. The oils were derived from underlying source rocks in the Upper Cretaceous Guayuta Group (Querecual and San Antonio Formations), and migration into the shallow reservoir at Quiriquire field likely occurred continuously through time. Although the oils have undergone severe biodegradation, it was possible to make some inferences about their origin. Thus, the analyzed oils are interpreted to have originated from marine shale or marl source rocks containing mixed organic matter deposited under anoxic‐suboxic conditions and were generated at near peak oil window maturities.
Understanding relations between rheology, tribology, and sensory perception of modified texture foods
Authors: Sharma Madhu , Pondicherry Kartik S. , Duizer Lisa
Published: December 2021

The aim of this work was to examine relations between instrumental and sensory parameters in a texture modified food matrix, with and without saliva. Nine pureed carrot samples (eight thickened and a control) were developed with starch (0.4 and 0.8% wt/wt), xanthan (0.2 and 0.4% wt/wt) or starch–xanthan blends that met International Dysphagia Diet Standardisation Initiative (IDDSI) Level 4 guidelines using fork and spoon tests. Rheological and tribological tests were conducted on the food and simulated bolus prepared by adding fresh stimulated saliva to the food (1:5, saliva:food) to mimic oral processing. Perceived sensory properties were identified using a temporal dominance of sensations (TDS) test (n = 16) where panelists were given a list of nine attributes. The area under the curve was extracted from TDS curves for each attribute/sample and this was correlated with rheological (viscosity at 10 s−1, G′, G″, and tan δ at 1 Hz) and tribological (friction coefficient in three regimes) data. The viscosity of the control sample decreased after adding hydrocolloids (except Starch_0.8%) and with saliva incorporation. G′ and G″ either increased or were similar for xanthan and blends and decreased for starch‐thickened samples. Hydrocolloid addition increased friction for all samples and was higher with saliva addition. Sensory results showed that samples with starch were perceived as thick and grainy while xanthan was perceived as smooth and slippery. A greater number of sensory attributes correlated with viscoelastic parameters compared to friction coefficients. Correlations were highest with the saliva added samples, further highlighting the importance of including saliva during instrumental testing.
Comfort over safety: thermoregulation overshadows predation risk effects in the activity of a keystone prey
Authors: Rocha M. , Serronha A. , Rodrigues M. , Alves P. C. , Monterroso P.
Published: December 2021

The activity level is a fundamental metric of animal behavior, related to the avoidance of predators, food acquisition, and thermoregulation. Animals need to weigh their activity budget to fulfill their energetic, social and reproductive requirements over the energetic costs of these activities. This task becomes further challenging for prey species, which also need to account for predation risk. To investigate the factors shaping proactive behavioral decisions leading prey species engagement in their diel activities, we implemented a multisite year‐round monitoring study on the Iberian rabbit (Oryctolagus cuniculus algirus), a key prey species in Mediterranean ecosystems. We deployed remotely triggered cameras over 15 sites to continuously monitor Iberian rabbits' activity. We estimated activity levels from time‐of‐detection data from camera traps, and modeled it as a function of climatic, intraspecific, predation, and resource‐related covariates. We found that Iberian rabbits exhibit a bimodal activity pattern peaking at sunrise and sunset, with a more pronounced peak occurring at sunrise during the nonbreeding season, and spend 9.15 ± 3.00 h/day (mean ± sd) active. Diel activity levels were negatively affected by extreme environmental temperatures and density dependence, demonstrating the privileged importance of social interactions and normothermia maintenance. We found mammalian predator activity and abundance to have near‐negligible effects on the activity levels of this key prey, suggesting decreased antipredator behavior when risk is perceived as prolonged. Moreover, we argue that perceived risk may be more important than realized risk in shaping Iberian rabbits' activity level. These results provide valuable insights toward a comprehensive understanding of the factors underlying behavioral decisions made by prey species, relevant for maintaining their energetic and homeostatic balance.