bluuebunny/crossref_metadata_2025 huggingface dataset:
Sheared Peridotite and Megacryst Formation Beneath the Kaapvaal Craton: a Snapshot of Tectonomagmatic Processes across the Lithosphere–Asthenosphere Transition
Authors: Tappe Sebastian , Massuyeau Malcolm , Smart Katie A , Woodland Alan B , Gussone Nikolaus , Milne Sarah , Stracke Andreas
Published: May 2021

The cratonic lithosphere–asthenosphere boundary is commonly invoked as the site of sheared peridotite and megacryst formation, a well-recognized petrological assemblage whose genetic relationships—if any—remain poorly understood. We have undertaken a comprehensive petrology and Sr–Nd–Hf–Ca isotope study of sheared peridotite xenoliths and clinopyroxene megacrysts from the c. 1150 Ma Premier kimberlite pipe on the central Kaapvaal craton in South Africa. New textural and mineral trace element evidence suggests that strong tectonic and magmatic overprinting affected the lower cratonic mantle over a vertical distance of ≥50 km from the lithosphere–asthenosphere boundary located at ∼200–225 km depth. Although modification of the central Kaapvaal cratonic mantle is commonly linked to the c. 2056 Ma Bushveld large igneous event, our thermobarometry, mantle redox, and Sr–Nd–Hf–Ca isotope data support a model in which volatile-rich low-volume melts and associated high-density fluids refertilized the lithosphere base shortly before or during asthenosphere-derived kimberlite and carbonatite magmatism at around 1150 Ma. This episode of lithospheric mantle enrichment was facilitated by exceptionally strong shear movements, as are recorded in the plastically deformed peridotites. We argue that stress-driven segregation of percolating carbonated melts contributed to megacryst formation along, or in close proximity to, shear zones within the cratonic mantle lithosphere. Integration of our results from the Kaapvaal craton and modern petrological concepts allows for the identification of a lithosphere–asthenosphere transition zone between ∼150 and 225 km depth. This horizon is defined by intersections of the ∼40–42 mW m–2 Premier paleogeotherm with (1) CO2–H2O-present solidus curves for peridotite (upper bound), and (2) typical mantle adiabats with potential temperatures between 1315 and 1420 °C (lower bound). At Premier, the most strongly deformed sheared peridotites occur mainly between ∼160 and 185 km depth, firmly within the lithosphere–asthenosphere transition zone. Contrary to many previous models, we suggest that sheared peridotite formation occurs in localized deformation zones spaced out across the entire width of the lithosphere–asthenosphere transition zone, rather than being restricted to a single thin layer at the craton base where mantle flow causes viscous drag. Hence, plate-tectonic stresses acting on the lower cratonic lithosphere may be accommodated by extensive networks of shear zones, which provide transient pathways and sinks for percolating volatile-rich melts, linking the formation of megacrysts and sheared peridotites.
The circadian-controlled PIF8–BBX28 module regulates petal senescence in rose flowers by governing mitochondrial ROS homeostasis at night
Authors: Zhang Yi , Wu Zhicheng , Feng Ming , Chen Jiwei , Qin Meizhu , Wang Wenran , Bao Ying , Xu Qian , Ye Ying , Ma Chao , Jiang Cai-Zhong , Gan Su-Sheng , Zhou Hougao , Cai Youming , Hong Bo , Gao Junping , Ma Nan
Published: May 2021

Reactive oxygen species (ROS) are unstable reactive molecules that are toxic to cells. Regulation of ROS homeostasis is crucial to protect cells from dysfunction, senescence, and death. In plant leaves, ROS are mainly generated from chloroplasts and are tightly temporally restricted by the circadian clock. However, little is known about how ROS homeostasis is regulated in nonphotosynthetic organs, such as petals. Here, we showed that hydrogen peroxide (H2O2) levels exhibit typical circadian rhythmicity in rose (Rosa hybrida) petals, consistent with the measured respiratory rate. RNA-seq and functional screening identified a B-box gene, RhBBX28, whose expression was associated with H2O2 rhythms. Silencing RhBBX28 accelerated flower senescence and promoted H2O2 accumulation at night in petals, while overexpression of RhBBX28 had the opposite effects. RhBBX28 influenced the expression of various genes related to respiratory metabolism, including the TCA cycle and glycolysis, and directly repressed the expression of SUCCINATE DEHYDROGENASE 1, which plays a central role in mitochondrial ROS (mtROS) homeostasis. We also found that PHYTOCHROME-INTERACTING FACTOR8 (RhPIF8) could activate RhBBX28 expression to control H2O2 levels in petals and thus flower senescence. Our results indicate that the circadian-controlled RhPIF8–RhBBX28 module is a critical player that controls flower senescence by governing mtROS homeostasis in rose.
The international Pediatric Oncology Exercise Guidelines (iPOEG)
Authors: Wurz Amanda , McLaughlin Emma , Lategan Conné , Chamorro Viña Carolina , Grimshaw Sarah L , Hamari Lotta , Götte Miriam , Kesting Sabine , Rossi Francesca , van der Torre Patrick , Guilcher Gregory M T , McIntyre Krista , Culos-Reed S Nicole
Published: May 2021

Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as ≥ 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.
Amniotic Band Syndrome in Adult Combined with Persistent Depressive Disorder
Authors: Kolasinski Jerzy , Kolenda Malgorzata , Kolasinska Dominika
Published: May 2021

Congenital amniotic band syndrome (ABS) is an anomaly with no proven etiology occurring in 0.7 per 10,000 live births. This defect mostly concerns the extremities and is often accompanied by other developmental anomalies. There are many methods of treatment for this type of defect, such as simple excision and suturing, local V-Y plasty, Z-plasty, multiple Z “plasties” or multiple W plasties, plasty with deepithelized or non-deepithelized rectangular lobes, and rigottomies complemented with lipofilling. The literature most often describes cases of treated children. There are no case reports of ABS treatment in adults. However, failure to undertake such treatment in childhood may result in serious mental dysfunction. We present the case of a 39-year-old woman with congenital ABS, in whom failure to provide proper treatment in childhood resulted in persistent depressive disorder development. The applied treatment, consisting of multiple Z plasties, liposuction, and fat grafting, resulted in improved appearance of her lower extremity, as well as the cessation of mental symptoms.
Prospective comparative study: metabolomics profiles of exudate and serum for patients with and without venous ulcer wound itch
Authors: Paul Julia C. , Yilmaz Ali , Pieper Barbara A. , Liu Zijuan , Graham Stewart F.
Published: May 2021

Introduction:

Itch is an unpleasant sensation that elicits the desire to scratch and can cause great distress, particularly in persons with venous ulcers. This pilot study explored the difference in metabolic profiles for wound exudate and serum in patients with or without venous ulcer wound itch.

Methods:

Patient information, wound assessment, and itch sensation ratings were recorded. Wound fluid and blood were collected for metabolomics assays. High-resolution mass spectrometry coupled with liquid chromatography and 1-dimensional proton nuclear magnetic resonance spectrometry were used to profile wound fluid and serum samples.

Results:

Patients (N=21) were included (ages: 32–91 y) with venous ulcers that itched (n=10) or did not itch (n=11). Metabolomic profiling discovered a previously unreported biochemical pathway for glycine, serine, and threonine metabolism in both serum and wound fluid significantly associated with itch. Using wound exudate, we developed diagnostic algorithms capable of discriminating between patients who itched and those who did not, with an area under the curve (95% confidence interval)=0.705 (0.461–0.948).

Discussion:

Our results demonstrate that the glycine-serine-threonine pathway is the most significantly altered metabolic pathway associated with venous ulcer itch. This pathway may serve as a biomarker for itch in patients with venous ulcers and help to identify itch before scratching further exasperates the ulcer. Studies with larger patient numbers are critically required to validate these findings. Our results may lead to novel therapeutic targets for the prophylactic treatment of itch.
Comparative analysis of 2 biometers using swept-source OCT technology
Authors: Panthier Christophe , Rouger Helene , Gozlan Yoni , Moran Sarah , Gatinel Damien
Published: May 2021

Purpose:

To report the repeatability, level of agreement, and correlation of 2 swept-source optical coherence tomography (SS-OCT) biometers, the IOLMaster 700 (biometer A) and the ANTERION (biometer B).

Setting:

Rothschild Foundation Hospital, Paris, France.

Design:

Prospective comparative case series.

Methods:

Consecutive patients who attended for cataract assessment had SS-OCT biometry performed with the reference, biometer A, and biometer B. Axial length, mean keratometry, central corneal thickness, anterior chamber depth, lens thickness, and corneal diameter measurements (white-to-white [WTW] distance) were measured. The intraoperator repeatability was calculated using analysis of variance and repeatability limits. Correlations were assessed, and the level of agreement between the biometers was represented with the Bland-Altman method.

Results:

The study comprised 63 patients (125 eyes). There was a statistically significant difference between the 2 biometers in all measurements (P < .05). All repeatability measurements were very high, as were the level of correlation and level of agreement between biometer A and biometer B for all parameters.

Conclusions:

Biometer B provided good agreement and repeatability compared with biometer A; however, all parameters were not interchangeable, particularly, the WTW measurement and the high keratometric values.
Ninety Years of Multiple Psychotic-Like and Spiritual Experiences in a Doctor Honoris Causa
Authors: Damiano Rodolfo Furlan , Machado Liliane , Loch Alexandre Andrade , Moreira-Almeida Alexander , Machado Leonardo
Published: May 2021

Psychotic experiences are common experiences shared by a considerable part of the world's population. Moreover, most of the individuals who report these experiences also report those called spiritual and dissociative phenomena. In specific culture and religious backgrounds, these experiences are frequently seen as a part of normal human experiences, usually called mediumship. We report a case of a famous Brazilian medium with 90 years of experiencing psychotic-like, dissociative and/or spiritual experiences, but coped well with the experiences and never sought psychiatric or psychological assistance. The medium received several honorific prizes, such as doctor honoris causa from different institutions, published more than 200 books, and ran a nonprofit organization that takes care of 5000 people daily. Finally, we review the literature on this topic and stress the urge for more research aiming to distinguish pathological and nonpathological psychotic experiences to avoid overmedicalization and iatrogenic treatments.
The Moderating Effect of Older Adults' Receptive Arts Engagement on the Association Between Resilience and Anxiety Symptoms During Coronavirus Breakout
Authors: Keisari Shoshi , Hoffman Yaakov , Ring Lia , Palgi Yuval
Published: May 2021

In this study, we evaluated whether levels of receptive arts engagement (visiting museums/concerts/the theater/the cinema) during the year preceding the COVID-19 outbreak may have served as a psychological resource for older adults that mitigated the association between resilience levels and COVID-19 anxiety when the pandemic broke out. Data were collected after the enactment of the first emergency regulations (between March 15 and April 1, 2020) via the Qualtrics Survey Software link that was sent out through social media platforms. In total, 205 participants aged 65 to 92 (mean age, 72.32; SD, 5.63) reported general anxiety symptom levels (GAD-7) (Spitzer et al., 2006), resilience (Connor-Davidson Resilience Scale), frequency of receptive arts engagement in the previous year, health status, exposure to risk situations, and behavioral changes due to the pandemic. Our hypothesis that receptive arts would moderate the resilience–COVID-19 anxiety link was examined by a multiple hierarchical regression analysis and with the PROCESS computational tool. Findings show that resilience was associated with COVID-19 anxiety and that this association was moderated by levels of receptive arts engagement. The findings show that high levels of prior art engagement constituted a potent buffer against subsequent COVID-19 anxiety. Policy makers may benefit older adults by encouraging their engagement in arts activities, even during social distancing.
Modifying food items valuation and weight with gamified executive control training
Authors: Najberg Hugo , Rigamonti Maurizio , Mouthon Michael , Spierer Lucas
Published: May 2021

Recent lines of research suggest that repeated executive control of motor responses to food items modifies their perceived value and in turn their consumption. Cognitive interventions involving the practice of motor control and attentional tasks have thus been advanced as potential approach to improve eating habits. Yet, their efficacy remains debated, notably due to a lack of proper control for the effects of expectations. We examined whether a one-month intervention combining the practice of Go/NoGo and Cue approach training modified the perceived palatability of food items (i.e. decrease in unhealthy and increase in healthy food items' palatability ratings), and in turn participants’ weights. We assessed our hypotheses with a parallel, double-blind, randomized controlled trial. Motivation and adherence to the intervention were maximized by a professional-level gamification of the training tasks. The control intervention differed from the experimental intervention only in the biasing of the stimulus–response mapping rules, enabling to balance expectations between the two groups and thus to conclude on the causal influence of motoric control on items valuation. We found a larger decrease of the unhealthy items' palatability ratings in the experimental (20.6%) than control group (13.1%). However, we did not find any increase of the healthy items’ ratings or weight loss. Overall, the present registered report confirms that the repeated inhibition of motor responses to food cues, together with the development of attentional biases away from these cues, reduces their perceived value.
Adsorption and release on three-dimensional graphene oxide network structures
Authors: Kim Sunnam , Moriya Sho , Maruki Sakura , Fukaminato Tuyoshi , Ogata Tomonari , Kurihara Seiji
Published: May 2021

In this study, three-dimensional network architectures are constructed using nano-sized graphene oxide (nGO) as the building block. The cross-linking reaction of nGO is conducted in sub-micrometre water droplets in an emulsion system to control the size of the networks by restricting the reaction space. Two types of three-dimensional GO networks with different cross-linking lengths were constructed, and their methyl orange adsorption and release behaviours were investigated under external stimuli, such as thermal treatment, ultrasonic wave treatment and near-infrared light irradiation.
Automatic radioisotope manipulation for small amount of nuclear medicine using an EWOD device with a dimple structure
Authors: Mogi Katsuo , Kimura Hiroyuki , Kondo Yuto , Inoue Tomoya , Adachi Shungo , Natsume Tohru
Published: May 2021

Delicate animal experiments and microdose clinical trials using short-lived radioisotopes require rapid preparation with high accuracy and careful attention to safety within a limited timeframe. We have developed an open-style electrowetting on dielectric (EWOD) device containing dimple structures for the rapid preparation of radiolabelled reagents. The device was demonstrated by automatic preparation of a technetium diethylenetriamine pentaacetate (
99m
Tc-DTPA) with high chelation efficiency (99.7 ± 0.13%). Additionally, we demonstrated the single-photon emission computed tomography/computed tomography imaging of mouse kidney using the
99m
Tc-DTPA prepared with the EWOD device. The obtained organ tomographic images were sufficient for the evaluation of mouse models for specific diseases. These results indicate that manual radiolabelling for a small amount of nuclear medicine can be replaced by a process using the proposed EWOD device as a human error reduction technique.
Full-scale pore size distribution features of uranium-bearing sandstone in the northwest of Xinjiang, China
Authors: Zeng Sheng , Li Hao , Zhang Ni , Sun Bing , Li Jinzhu , Liu Yulong
Published: May 2021

As an important nuclear fuel, uranium in sandstone uranium deposits is mainly extracted byin situleaching. The porosity of sandstone is one of the important indexes determiningin situleaching efficiency. Moreover, the microscopic pore size distribution (PSD) of the uranium-bearing layer has an important effect on porosity. It is necessary to feature the pore structure by various techniques because of the different pore types and sizes in the uranium layer. In this paper, combined with nitrogen gas adsorption, nuclear magnetic resonance techniques and scanning electron microscopy, the full-scale PSD features of uranium-bearing sandstone in the northwest of Xinjiang are effectively characterized. The results show that pores structure of uranium-bearing sandstone include dissolution pores (d≤ 50 nm), intergranular pores (50 nm <d≤ 200 µm) and microfractures. Intergranular pores of 60 nm and 1 µm are the significant contributors to pore volume. The effects of the pore volume of two pore types (dissolution pores and intergranular pores) on the porosity of uranium-bearing sandstone are analysed. The results show that intergranular pores have the greater influence on the porosity and are positively correlated to the porosity. Dissolution pores have little effect on the porosity, but it is one of the key factors for improving uranium recovery. Moreover, the greater the difference of PSD between sandstones, the stronger the interlayer heterogeneity of uranium-bearing sandstone. This kind of interlayer heterogeneity leads to the change of permeability in the horizontal direction of strata. It provides a basis for a reasonable setting of well type and well spacing parameters.
The influence of cooperation and competition on preschoolers' prosociality toward in-group and out-group members
Authors: Toppe Theo , Hardecker Susanne , Zerres Franca , Haun Daniel B. M.
Published: May 2021

Past research suggests that children favour their in-group members over out-group members as indicated by selective prosociality such as sharing or social inclusion. This preregistered study examined how playing a cooperative, competitive or solitary game influences German 4- to 6-year-olds’ in-group bias and their general willingness to act prosocially, independent of the recipient's group membership (N= 144). After playing the game, experimenters introduced minimal groups and assessed children's sharing with an in-group and an out-group member as well as their social inclusion of an out-group member into an in-group interaction. Furthermore, we assessed children's physical engagement and parents' social dominance orientation (SDO)—a scale indicating the preference for inequality among social groups—to learn more about inter-individual differences in children's prosocial behaviours. Results suggest that children showed a stronger physical engagement while playing competitively as compared with cooperatively or alone. The different gaming contexts did not impact children's subsequent in-group bias or general willingness to act prosocially. Parental SDO was not linked to children's prosocial behaviours. These results indicate that competition can immediately affect children's behaviour while playing but raise doubt on the importance of cooperative and competitive play for children's subsequent intergroup and prosocial behaviour.
Studying the suitability of hybrid micelle liquid chromatography for estimating the lipophilicity of some partial dopamine agonists used to attain the reward circuit
Authors: Wahba M. E. K. , El Wasseef D. , El Sherbiny D.
Published: May 2021

Three micellar-based mobile phases were developed and optimized for the simultaneous determination of certain partial dopamine agonists that are used to overcome the withdrawal symptoms of abused drugs, namely aripiprazole, pramipexole and piribedil. The studied drugs were separated using micellar liquid chromatography, hybrid micellar liquid chromatography (HMLC) and microemulsion liquid chromatography (MELC). The three developed mobile phases were studied to estimate their suitability for the measurement of log
p
-values of the studied drugs. Experimental determination of log

P
m/w

values using the three mobile phases demonstrates that HMLC is the mobile phase of choice since the obtained practical log

P
m/w

values were in accordance with the reported log
P
values, and calculated log
P
and log
D
values. An explanation of the obtained results was presented based on the separation retention mechanism for each chromatographic technique. Furthermore, the effect of the pH and the column temperature in HMLC on the practical log

P
m/w

values was studied. To verify its suitability for experimental measurement of log

P
m/w
 ,

HMLC was subjected to full validation according to the United States Pharmacopeia.
Genetic diversity of the Nubian ibex in Oman as revealed by mitochondrial DNA
Authors: Al-Ghafri Mataab K. , White Patrick J. C. , Briers Robert A. , Dicks Kara L. , Ball Alex , Ghazali Muhammad , Ross Steven , Al-Said Taimur , Al-Amri Haitham , Al-Umairi Mudhafar , Al-Saadi Hani , Aka'ak Ali , Hardan Ahmed , Zabanoot Nasser , Craig Mark , Senn Helen
Published: May 2021

The Nubian ibex (Capra nubiana) is patchily distributed across parts of Africa and Arabia. In Oman, it is one of the few free-ranging wild mammals found in the central and southern regions. Its population is declining due to habitat degradation, human expansion, poaching and fragmentation. Here, we investigated the population's genetic diversity using mitochondrial DNA (D-loop 186 bp and cytochromeb487 bp). We found that the Nubian ibex in the southern region of Oman was more diverse (D-loop HD; 0.838) compared with the central region (0.511) and gene flow between them was restricted. We compared the genetic profiles of wild Nubian ibex from Oman with captive ibex. A Bayesian phylogenetic tree showed that wild Nubian ibex form a distinct clade independent from captive animals. This divergence was supported by high mean distances (D-loop 0.126, cytochromeb0.0528) and highFSTstatistics (D-loop 0.725, cytochromeb0.968). These results indicate that captive ibex are highly unlikely to have originated from the wild population in Oman and the considerable divergence suggests that the wild population in Oman should be treated as a distinct taxonomic unit. Further nuclear genetic work will be required to fully elucidate the degree of global taxonomic divergence of Nubian ibex populations.
Two-dimensional adaptive dynamics of evolutionary public goods games: finite-size effects on fixation probability and branching time
Authors: Johnson Brian , Altrock Philipp M. , Kimmel Gregory J.
Published: May 2021

Public goods games (PGGs) describe situations in which individuals contribute to a good at a private cost, but others can free-ride by receiving a share of the public benefit at no cost. The game occurs within local neighbourhoods, which are subsets of the whole population. Free-riding and maximal production are two extremes of a continuous spectrum of traits. We study the adaptive dynamics of production and neighbourhood size. We allow the public good production and the neighbourhood size to coevolve and observe evolutionary branching. We explain how an initially monomorphic population undergoes evolutionary branching in two dimensions to become a dimorphic population characterized by extremes of the spectrum of trait values. We find that population size plays a crucial role in determining the final state of the population. Small populations may not branch or may be subject to extinction of a subpopulation after branching. In small populations, stochastic effects become important and we calculate the probability of subpopulation extinction. Our work elucidates the evolutionary origins of heterogeneity in local PGGs among individuals of two traits (production and neighbourhood size), and the effects of stochasticity in two-dimensional trait space, where novel effects emerge.
Two different synchronous spectrofluorimetric approaches for simultaneous determination of febuxostat and ibuprofen
Authors: Magdy Galal , Belal Fathalla , Abdel-Megied Ahmed M. , Abdel Hakiem Ahmed F.
Published: May 2021

Two green, simple and sensitive synchronous spectrofluorimetric methods were developed for the first time for the simultaneous estimation of febuxostat (FEB) and ibuprofen (IBU). Method I is constant-wavelength synchronous spectrofluorimetry where FEB and IBU were recorded at 329 and 258 nm, respectively, using Δ
λ
of 40 nm. Method II is constant-energy synchronous spectrofluorimetry using a wavenumber interval of −4000 cm
−1
. All measurements were carried out in a borate buffer of pH 7 and distilled water for dilution which increased the methods' greenness. The two methods were rectilinear over concentration ranges of 30.0–700.0 ng ml
−1
and 0.5–9.0 µg ml
−1
in the first method and 20.0–500.0 ng ml
−1
and 0.1–8.0 µg ml
−1
in the second method for FEB and IBU, respectively. High sensitivity was attained for the two drugs with limits of quantitations (LODs) down to 0.41 and 5.51 ng ml
−1
in the first method and 0.25 and 3.32 ng ml
−1
in the second method for FEB and IBU, respectively. Recovery percentages were in the range of 97.3–101.9% after extraction from spiked human plasma samples, demonstrating high bioanalytical applicability. The two methods were further applied to tablet dosage forms with good recovery results. The methods' greenness was assessed according to the analytical Eco-Scale and Green Analytical Procedure Index guidelines.
Mycoplasma affects baseline gene expression and the response to glucocorticoids in vocal fold fibroblasts
Authors: Doyle Carina , Nakamura Ryosuke , Bing Renjie , Rousseau Bernard , Branski Ryan C.
Published: May 2021

Introduction.
In vitro experimentation is intentionally contrived to isolate specific phenomena in the context of profound biological complexity. Mycoplasmas in the upper airway likely contribute to this complexity and play a largely unknown role in both health and disease. Similarly, the presence and role of mycoplasma in in vitro investigation are largely unknown.

Hypothesis. We hypothesize mycoplasma in human vocal fold fibroblasts (VFF) will affect both basal gene-expression patterns as well as the cell response to exogenous stimuli.

Aim. We sought to determine mycoplasma presence across vocal fold fibroblast cultures, basal transcriptional changes as a function of mycoplasma, and responsiveness to exogenous glucocorticoids in mycoplasma-positive and -negative VFF.

Methodology. PCR-based mycoplasma detection was performed in an immortalized human VFF line as well as rat and rabbit primary VFF cultures and extracted rat laryngeal tissue. RNA sequencing was performed in mycoplasma-positive and -negative human cells at baseline and in response to dexamethasone.

Results. Mycoplasma was identified in the human cell line as well as primary culture from rabbits. Mycoplasma was not detected in tissue or primary culture from rat vocal folds. Basal mRNA expression in human VFF differed significantly following mycoplasma treatment. In addition, differential responses to dexamethasone were observed across multiple pathways as a function of mycoplasma presence in these cells. Pathways including apoptosis, DNA damage repair, and G1 to S cell cycle signalling were significantly enriched in mycoplasma-positive cells.

Conclusion. Variability of mycoplasma presence across culture conditions and differential responses to exogenous stimuli as a function of mycoplasma presence are potentially problematic for the translation of in vitro experimentation in the upper aerodigestive tract. It remains unclear if these findings represent contamination or the baseline state of this specialized tissue.
Detection of choroidal hypoperfusion in giant cell arteritis using swept-source optical coherence tomographic angiography
Authors: Lu Edward S. , Yuan Amy , Cohen Devon A. , Katz Raviv , Miller John B. , Gaier Eric D.
Published: May 2021

Objective

To determine whether swept-source optical coherence tomographic angiography (SS-OCTA) can demonstrate choroidal perfusion abnormalities seen on fluorescein angiography (FA) in giant cell arteritis (GCA).

Design

Observational case series.

Participants

Six eyes of 3 patients with bilateral ischemic optic neuropathy secondary to GCA, and one control patient without ocular involvement from biopsy-confirmed GCA.

Methods

En face SS-OCTA (DRI OCT Triton, Topcon, Tokyo, Japan) and FA centered on the macula were obtained at presentation. SS-OCTA was segmented into superficial and deep retinal capillary plexuses and the choriocapillaris laminae. SS-OCTA images were independently analyzed for perfusion abnormalities and compared with corresponding FA images.

Main Outcome Measures

Correspondence of choroidal angiographic abnormalities on SS-OCTA and FA.

Results

SS-OCTA showed decreased angiographic signal within the choriocapillaris in 5/6 eyes and corresponded to hypoperfusion abnormalities on FA in similar geographic distributions in 5/5 eyes. SS-OCTA also showed dilation of the deep retinal capillary plexus overlying the area of choroidal hypoperfusion in one eye. In the one eye without angiographic signal abnormalities on SS-OCTA, no perfusion changes were noted on FA. One control patient without ocular involvement from biopsy-confirmed GCA did not show choroidal perfusion changes on SS-OCTA or FA.

Conclusions

This case series demonstrates comparability between SS-OCTA and FA in detection and characterization of choroidal hypoperfusion secondary to GCA. As a rapid and non-invasive tool, SS-OCTA may serve as a viable alternative to FA in the diagnostic evaluation of GCA.
Alzheimer’s Disease Classification Using 2D Convolutional Neural Networks
Authors: Liang Gongbo , Xing Xin , Liu Liangliang , Ying Qi , Lin Ai-Ling , Jacobs Nathan
Published: May 2021

Alzheimer’s disease (AD) is a non-treatable and non-reversible disease that affects about 6% of people who are 65 and older. Brain magnetic resonance imaging (MRI) is a pseudo-3D imaging modality that is widely used for AD diagnosis. Convolutional neural networks with 3D kernels (3D CNNs) are often the default choice for deep learning based MRI analysis. However, 3D CNNs are usually computationally costly and data-hungry. Such disadvantages post a barrier of using modern deep learning techniques in the medical imaging domain, in which the number of data can be used for training is usually limited. In this work, we propose three approaches that leverage 2D CNNs on 3D MRI data. We test the proposed methods on the Alzheimer’s Disease Neuroimaging Initiative dataset across two popular 2D CNN architectures. The evaluation results show that the proposed method improves the model performance on AD diagnosis by 8.33% accuracy or 10.11% auROC, while significantly reduce the training time by over 89%. We also discuss the potential causes for performance improvement and the limitation. We believe this work can serve as a strong baseline for future researchers.
Report: Evaluating the ability of the TMA Clinical Decision Support platform to identify interventions in a clinical setting
Authors: Resnikoff Joshua , Giraldo Yessica , Williamson Lina
Published: May 2021

The TMA Precision Health Clinical Decision Support system is a commercially available software platform focused on the confirmation of a precision diagnosis and generation of a personalized care plan to rapidly deliver therapeutic optionality and improve quality of life for rare and complex disease patients. For this study, we worked with our partners in Medellin, Colombia to evaluate the efficacy of the platform in identifying previously unexplored modes of care within a small sample population of adult patients suffering from a diverse set of rare diseases. Although challenges were encountered during the curation of data from multiple sources, personalized care plans and medication options were identified successfully for 94% of cases, suggesting a high level of impact for deployment at scale.
Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure
Authors: Gladding Patrick A. , Young Renee , Cooper Maxine , Loader Suzanne , Smith Kevin , Zarate Erica , Green Saras , Villas-Boas Silas G. , Shepherd Phillip , Kakadiya Purvi , Thorstensen Eric , Keven Christine , Coe Margaret , Jüllig Mia , Zhang Edmond , Schlegel Todd T.
Published: May 2021

Background

Multiomics delivers more biological insight than targeted investigations. We applied multiomics to patients with heart failure with reduced ejection fraction (HFrEF).

Methods

46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LCMS/GCMS) and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudinal strain, ejection fraction and NTproBNP. A consumer breath acetone (BrACE) sensor validated results in n=73.

Results

28 metabolites were identified by GCMS, 35 by LCMS and 4 volatiles by SPME in plasma and urine. Alanine, aspartate and glutamate, citric acid cycle, arginine biosynthesis, glyoxylate and dicarboxylate metabolism were altered in HFrEF. Plasma acetone correlated with NT-proBNP (r = 0.59, 95% CI 0.4 to 0.7), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE> 1.5 ppm discriminated HF from other cardiac pathology (AUC 0.8, 95% CI 0.61 to 0.92, P < 0.0001).

Conclusion

Breath acetone discriminated HFrEF from other cardiac pathology using a consumer sensor, but was not cardiac specific.
Cardiovascular Disease in the Peruvian Highlands: Local Perceptions, Barriers, and Paths to Preventing Chronic Diseases in Andean Adults
Authors: Samaniego Giuliana Sanchez , Peña Stella Hartinger , Tallman Paula Skye , Mäusezahl Daniel
Published: May 2021

Objectives

Public health interventions can be improved by understanding peoples’ explanatory models of disease. We explore awareness and perceptions of cardiovascular diseases (CVD) and options for preventive actions in young rural adults highlanders.

Methods

46 men and women from communities in Cajamarca, Peru were purposively selected to participate in eight focus groups, where participants discussed their understanding and perceived causes of CVD as well as barriers and pathways to healthy lifestyles.

Results

Fresh foods, physical activity, unpleasant emotions, and healthcare access were cited as important determinants of healthy lifestyles. Barriers to healthy diets included lacking nutritional knowledge, fluctuating food prices, and limited access to foodstuffs. Women felt particularly vulnerable to CVD and identified gendered barriers to manage stress and engage in leisure sports. Low health literacy, distance and poor doctor-patient relationships prevented participants from fully accessing healthcare.

Conclusions

CVD prevention should consider local knowledge of these diseases and of healthy lifestyles and harness ongoing programmes that have successfully promoted good nutrition in children and pregnant women. In concert with public-private parterships, governments should include health prevention for the entire family.
Description and clinical validation of a real-time AI diagnostic companion for fetal ultrasound examination
Authors: Stirnemann Julien J. , Besson Remi , Spaggiari Emmanuel , Rojo Sandra , Loge Frederic , Peyro-Saint-Paul Helene , Allassonniere Stephanie , Le Pennec Erwan , Ville Yves
Published: May 2021

Objective

To describe a real-time decision support system (DSS), named SONIO, to assist ultrasound-based prenatal diagnosis and to assess its performance using a clinical database of precisely phenotyped postmortem examinations.

Population and Methods

This DSS is knowledge-based and comprises a dedicated thesaurus of 294 syndromes and diseases. It operates by suggesting, at each step of the ultrasound examination, the best next symptom to check for in order to optimize the diagnostic pathway to the smallest number of possible diagnoses. This assistant was tested on a single-center database of 251 cases of postmortem phenotypes with a definite diagnosis. Adjudication of discordant diagnoses was made by a panel of external experts. The primary outcome was a target concordance rate >90% between the postmortem diagnosis and the top-7 diagnoses given by SONIO when providing the full phenotype as input. Secondary outcomes included concordance for the top-5 and top-3 diagnoses; We also assessed a “1-by-1” model, providing only the anomalies sequentially prompted by the system, mimicking the use of the software in a real-life clinical setting.

Results

The validation database covered 96 of the 294 (32.65%) syndromes and 79% of their overall prevalence in the SONIO thesaurus. The adjudicators discarded 42/251 cases as they were not amenable to ultrasound based diagnosis. SONIO failed to make the diagnosis on 7/209 cases. On average, each case displayed 6 anomalies, 3 of which were considered atypical for the condition. Using the ‘full-phenotype’ model, the success rate of the top-7 output of Sonio was 96.7% (202/209). This was 91.9% and 87.1% for the top-5 and top-3 outputs respectively. Using the “1-by-1” model, the correct diagnosis was within the top-7, top-5 and top-3 of SONIO’s output in 72.4%, 69.3% and 63.1%.

Conclusion

Sonio is a robust DSS with a success-rate >95% for top-7 ranking diagnoses when the full phenotype is provided, using a large database of noisy real data. The success rate over 70% using the ‘1-by-1’ model was understandably lower, given that SONIO’s sequential queries may not systematically cover the full phenotype.
Internal Neurolysis for the Treatment of Trigeminal Neuralgia: Systematic Review
Authors: Sabourin Victor , Lavergne Pascal , Mazza Jacob , Head Jeffrey , Al-Saiegh Fadi , Stefanelli Tony , Karsy Michael , Evans James
Published: May 2021

Introduction

Trigeminal neuralgia remains a challenging disease with significant debilitating symptoms and variable efficacy in terms of treatment options, namely microvascular decompression (MVD), stereotactic radiosurgery (SRS), and percutaneous rhizotomy. Internal neurolysis (IN) is an alternative treatment that may be provide patient benefit but has limited understanding. We performed a systematic review of IN treatment of trigeminal neuralgia.

Methods

Studies from 2000 to 2021 that assessed IN in trigeminal neuralgia were aggregated and independently reviewed. Weighted averages for demographics, outcomes and complications were generated.

Results

A total of 520 patients in 12 studies were identified with 384 who underwent IN (mean age 53.8 years, range 46-61.4 years). A mean follow-up time of 36.5 months (range 12-90 months) was seen. Preoperative symptoms were present for about 55.0 months before treatment and pain was predominantly in V2/3 (26.8%) followed by other distributions. An excellent to good outcome (Barrow Neurological Institute Pain Score [BNI-PS] I-III) was seen in 83.7% of patients (range 72-93.8%). Pain outcomes at 1 year were excellent in 58-78.4%, good or better in 77-93.75% and fair or better in 80-93.75% of patients. On average facial numbness following IN was seen in 96% of patients however at follow-up remained in only 1.75-10%. The vast majority of remaining numbness was not significantly distressing to patients. Subgroup comparisons of IN vs. recurrent MVD, IN vs. radiofrequency ablation, the impact of IN during the absence of vascular compression as well as IN with and without MVD were also evaluated.

Conclusions

IN represents a promising approach for surgical treatment of trigeminal neuralgia in the absence of vascular compression or in potential cases of recurrence. Complications were limited in general. Further study is required to evaluate the impact of IN via higher quality prospective studies.
‘Resistance is futile’: Weaker selection for resistance during larger epidemics further increases prevalence and depresses host density
Authors: Walsman Jason C. , Duffy Meghan A. , Cáceres Carla E. , Hall Spencer R.
Published: May 2021

What determines how much resistance hosts evolve? One might intuit that hosts evolve higher resistance when parasites are more abundant. However, the opposite pattern can arise due to costs of resistance. Here we illustrate with mathematical, experimental, and field approaches how ecological context can increase parasite abundance and select for lower resistance. ‘Resistance is futile’ when all host genotypes become sufficiently infected. To make this argument, we first analyzed an eco-evolutionary model of parasites, hosts, and hosts’ resources. We determined eco-evolutionary outcomes for resistance (mathematically, transmission rate) and densities along gradients that drive epidemic size. When epidemic drivers are high, hosts evolve lower resistance, amplifying epidemics and decreasing host density. Experimental mesocosms qualitatively agreed. In the experiment, higher supply of nutrients drove larger epidemics of survival-reducing fungal parasites. Evolving zooplankton hosts were less resistant at high nutrients than at low. Less resistance, in turn, was associated with higher infection prevalence and lower host density. We also analyzed the size of naturally occurring epidemics, finding a broad, bimodal distribution of epidemic sizes consistent with the eco-evolutionary model. Together, our three approaches supported predictions that high epidemic drivers lead to evolution of lower resistance which drives higher prevalence and lower host density.
An efficient protocol for chromosome isolation from sterlet (A. ruthenus) embryos and larvae
Authors: Fopp-Bayat Dorota , Kuciński Marcin
Published: May 2021

In the present study, the development of an efficient and feasible protocol for chromosome preparation from sterlet (A. ruthenus) embryos and larvae was carried out. In the established protocol, the mean efficiency of chromosome extraction ranged from 70 to 100%. The average number of recorded metaphases per slide was between 9 to 15. In general, the most satisfactory results were obtained for embryos at 6 dpf and larvae at the age of up to 7 dph. In the 24 dpf group, chromosome isolation was possible without immersion in spindle poison, however; in successive developmental stages, the minimal immersion time exceeded 1.5 hours, regardless of chorionation. Immersion for 14 hours did not compromise the efficacy of chromosome isolation. In the current study, successful chromosome isolation was determined mainly by hypotonization conditions. Younger developmental stages generally require the shortest hypotonization times, whereas older larvae require longer hypotonization times. The optimal hypotonization period is 5-15 minutes for embryos at 24 dpf, 40 minutes for embryos at 4dpf, and 50-60 minutes for fish at 6 dpf-7 dph. The only exception was the 24 hpf group where only blastula cells were used. An additional overnight fixation step significantly enhanced chromosome quality and supported chromosome counting especially in the 24 dpf group. The quality and quantity of chromosome slides were also significantly determined by tissue type, and the slides prepared from heads (gill cells) produced the best results.
Genomic Surveillance of COVID-19 Variants with Language Models and Machine Learning
Authors: Nagpal Sargun , Pal Ridam , Ashima  , Tyagi Ananya , Tripathi Sadhana , Nagori Aditya , Ahmad Saad , Mishra Hara Prasad , Malhotra Rishabh , Kutum Rintu , Sethi Tavpritesh
Published: May 2021

The global efforts to control COVID-19 are threatened by the rapid emergence of novel SARS-CoV-2 variants that may display undesirable characteristics such as immune escape, increased transmissibility or pathogenicity. Early prediction for emergence of new strains with these features is critical for pandemic preparedness. We present Strainflow, a supervised and causally predictive model using unsupervised latent space features of SARS-CoV-2 genome sequences. Strainflow was trained and validated on 0.9 million sequences for the period December, 2019 to June, 2021 and the frozen model was prospectively validated from July, 2021 to December, 2021. Strainflow captured the rise in cases two months ahead of the Delta and Omicron surges in most countries including the prediction of a surge in India as early as beginning of November, 2021. Entropy analysis of Strainflow unsupervised embeddings clearly reveals the explore-exploit cycles in genomic feature-space, thus adding interpretability to the deep learning based model. We also conducted codon-level analysis of our model for interpretability and biological validity of our unsupervised features. Strainflow application is openly available as an interactive web-application for prospective genomic surveillance of COVID-19 across the globe.
Listeria monocytogenes utilizes the ClpP1/2 proteolytic machinery for fine-tuned substrate degradation under heat stress
Authors: Balogh Dóra , Eckel Konstantin , Fetzer Christian , Sieber Stephan A.
Published: May 2021

Listeria monocytogenes exhibits two ClpP isoforms (ClpP1/ClpP2) which assemble into a heterooligomeric complex with enhanced proteolytic activity. Herein, we demonstrate that the formation of this complex depends on temperature and reaches a maximum ratio of about 1:1 at heat shock conditions, while almost no complex formation occurred below 4°C. In order to decipher the role of the two isoforms at elevated temperatures, we constructed L. monocytogenes ClpP1, ClpP2 and ClpP1/2 knockout strains and analyzed their protein regulation in comparison to the wild type (WT) strain via whole proteome mass-spectrometry (MS) at 37 °C and 42 °C. While ΔclpP1 strain only altered the expression of very few proteins, ΔclpP2 and ΔclpP1/2 strains revealed the dysregulation of many proteins at both temperatures. These effects were corroborated by crosslinking co-immunoprecipitation MS analysis. Thus, while ClpP1 serves as a mere enhancer of protein degradation in the heterocomplex, ClpP2 is essential for ClpX binding and thus functions as a gatekeeper for substrate entry. Applying an integrated proteomic approach combining whole proteome and co-immunoprecipitation datasets, several putative ClpP2 substrates were identified in the context of different temperatures and discussed with regards to their function in cellular pathways such as the SOS response.