bluuebunny/crossref_metadata_2025 huggingface dataset:
Coxiella
co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress–induced cell death
Authors: Loterio Robson K. , Thomas David R. , Andrade Warrison , Lee Yi Wei , Santos Leonardo L. , Mascarenhas Danielle P. A. , Steiner Thiago M. , Chiaratto Jéssica , Fielden Laura F. , Lopes Leticia , Bird Lauren E. , Goldman Gustavo H. , Stojanovski Diana , Scott Nichollas E. , Zamboni Dario S. , Newton Hayley J.
Published: August 2023

The causative agent of human Q fever,
Coxiella burnetii,
is highly adapted to infect alveolar macrophages by inhibiting a range of host responses to infection. Despite the clinical and biological importance of this pathogen, the challenges related to genetic manipulation of both
C. burnetii
and macrophages have limited our knowledge of the mechanisms by which
C. burnetii
subverts macrophages functions. Here, we used the related bacterium
Legionella pneumophila
to perform a comprehensive screen of
C. burnetii
effectors that interfere with innate immune responses and host death using the greater wax moth
Galleria mellonella
and mouse bone marrow–derived macrophages. We identified MceF (Mitochondrial Coxiella effector protein F), a
C. burnetii
effector protein that localizes to mitochondria and contributes to host cell survival. MceF was shown to enhance mitochondrial function, delay membrane damage, and decrease mitochondrial ROS production induced by rotenone. Mechanistically, MceF recruits the host antioxidant protein Glutathione Peroxidase 4 (GPX4) to the mitochondria. The protective functions of MceF were absent in primary macrophages lacking GPX4, while overexpression of MceF in human cells protected against oxidative stress–induced cell death.
C. burnetii
lacking MceF was replication competent in mammalian cells but induced higher mortality in
G. mellonella,
indicating that MceF modulates the host response to infection. This study reveals an important
C. burnetii
strategy to subvert macrophage cell death and host immunity and demonstrates that modulation of the host antioxidant system is a viable strategy to promote the success of intracellular bacteria.
Heritage speakers’ processing of the Spanish subjunctive
Authors: López-Beltrán Priscila , Dussias Paola E.
Published: August 2023

We investigated linguistic knowledge of subjunctive mood in heritage speakers of Spanish who live in a
long-standing English-Spanish bilingual community in Albuquerque, New Mexico. Three experiments examine the constraints on
subjunctive selection. Experiment 1 and Experiment 2 employed pupillometry to investigate heritage speakers’ online sensitivity to
the presence of the subjunctive with non-variable governors (Lexical conditioning) and with negated governors (Structural
conditioning). Experiment 3 employed an elicited production task to examine production of subjunctive in the same contexts. The
findings of the heritage group were compared to those of a group of Spanish-dominant Mexican bilinguals. Results showed that in
comprehension and production, heritage speakers were as sensitive as the Spanish-dominant bilinguals to the lexical and structural
factors that condition mood selection. In comprehension, the two groups experienced an increased pupillary dilation in conditions
where the indicative was used but the subjunctive was expected. In addition, high-frequency governors and irregular subordinate
verbs boosted participants’ sensitivity to the presence of the subjunctive. In production, there were no significant differences
between heritage speakers and Spanish-dominant bilinguals when producing the subjunctive with non-variable and negated
governors.
Rie1 and Sgn1 form an RNA-binding complex that enforces the meiotic entry cell fate decision
Authors: Gaspary Alec , Laureau Raphaelle , Dyatel Annie , Dursuk Gizem , Simon Yael , Berchowitz Luke E.
Published: August 2023

Budding yeast cells have the capacity to adopt few but distinct physiological states depending on environmental conditions. Vegetative cells proliferate rapidly by budding while spores can survive prolonged periods of nutrient deprivation and/or desiccation. Whether or not a yeast cell will enter meiosis and sporulate represents a critical decision that could be lethal if made in error. Most cell fate decisions, including those of yeast, are understood as being triggered by the activation of master transcription factors. However, mechanisms that enforce cell fates posttranscriptionally have been more difficult to attain. Here, we perform a forward genetic screen to determine RNA-binding proteins that affect meiotic entry at the posttranscriptional level. Our screen revealed several candidates with meiotic entry phenotypes, the most significant being RIE1, which encodes an RRM-containing protein. We demonstrate that Rie1 binds RNA, is associated with the translational machinery, and acts posttranscriptionally to enhance protein levels of the master transcription factor Ime1 in sporulation conditions. We also identified a physical binding partner of Rie1, Sgn1, which is another RRM-containing protein that plays a role in timely Ime1 expression. We demonstrate that these proteins act independently of cell size regulation pathways to promote meiotic entry. We propose a model explaining how constitutively expressed RNA-binding proteins, such as Rie1 and Sgn1, can act in cell fate decisions both as switch-like enforcers and as repressors of spurious cell fate activation.
Inhomogeneous spatial distribution of non radiative recombination centers in GaN/InGaN nanowire heterostructures studied by cathodoluminescence
Authors: Concordel Alexandre , Rochat Névine , Quach Anh My Naht , Rouvière Jean-Luc , Jacopin Gwénolé , Napierala Jérôme , Daudin Bruno
Published: August 2023

In order to elucidate the mechanisms responsible for cathodoluminescence intensity variations at the scale of single InGaN/GaN nanowire heterostructures, a methodology is proposed based on a statistical analysis on ensembles of several hundreds of nanowires exhibiting a diameter of 180, 240 and 280 nm. For 180 nm diameter, we find that intensitiy variations are consistent with incorporation of point defects obeying Poisson’s statistics. For wider diameters, intensity variations at the scale of single NWs are observed and assigned to local growth conditions fluctuations. Finally, for the less luminescent nanowires, a departure from Poisson’s statistics is observed suggesting the possible clustering of non independent point defects.
Analysis of an aligned magnetic nano-Casson fluid flow along with bio-convection based on Stefan's blowing
Authors: Saleem Musharafa , Tufail Muhammad Nazim
Published: August 2023

This theoretical study illustrates the effect of an inclined stretching sheet with bio-mixed convection, aligned magnetohydrodynamics (MHD), porous medium, Joule heating, viscous dissipation, the Buongiorno nanofluid model, and chemical reaction effects. Stefan blowing (SB) and partial slips, as well as our presumptions and laws, like the conservation of mass, momentum, and energy, must all be taken into consideration when solving our partial differential equations (PDEs). Similarity transformations are used in the context of a gyro-tactic motile microorganism flowing through an inclined stretched surface to produce ordinary differential equations (ODEs). The BVP4C method generates numerical results for different parameters through MATLAB programming. Additionally, a numerical and graphical exploration of the effects of numerous developing variables on the velocity, temperature, concentration, and density of motile bacteria is done. To verify the accuracy of the numerical model, the findings of the numerical research are compared to experimental data. Microbial distribution decreases with both negative and positive SB (suction and injection) attitudes, as indicated by the Peclet number and microbe movement coefficient. The mobility of microorganisms increases with higher values of the Lewis number, which governs their motility. The Lewis number and chemical reaction parameters affect the volume fraction transfer during the flow of the nano-Casson fluid in both the suction and injection cases of the SB effect, leading to increased concentration transfer.
Elevated nocturnal respiratory rates in the mitochondria of CAM plants: current knowledge and unanswered questions
Authors: Leverett Alistair , Borland Anne M
Published: August 2023

Crassulacean acid metabolism (CAM) is a metabolic adaptation that has evolved convergently in 38 plant families to aid survival in water-limited niches. Whilst primarily considered a photosynthetic adaptation, CAM also has substantial consequences for nocturnal respiratory metabolism. Here, we outline the history, current state and future of nocturnal respiration research in CAM plants, with a particular focus on the energetics of nocturnal respiratory oxygen consumption. Throughout the 20th century, research interest in nocturnal respiration occurred alongside initial discoveries of CAM, although the energetic and mechanistic implications of nocturnal oxygen consumption and links to the operation of the CAM cycle were not fully understood. Recent flux balance analysis (FBA) models have provided new insights into the role that mitochondria play in the CAM cycle. Several FBA models have predicted that CAM requires elevated nocturnal respiratory rates, compared to C3 species, to power vacuolar malic acid accumulation. We provide physiological data, from the genus Clusia, to corroborate these modelling predictions, thereby reinforcing the importance of elevated nocturnal respiratory rates for CAM. Finally, we outline five unanswered questions pertaining to nocturnal respiration which must be addressed if we are to fully understand and utilize CAM plants in a hotter, drier world.
A new approach to an old problem: how to categorize the habit of ferns and lycophytes
Authors: Zotz Gerhard , Armenia Lisa , Einzmann Helena J R
Published: August 2023

Background and Aims

Substrate preferences are often treated as species traits and are used to distinguish different habits, i.e. an epiphytic, lithophytic or terrestrial habit. Such a categorization, however, ignores substantial intraspecific variation. An approach that takes biological variability within a species into account is needed.

Methods

We focused on four large genera of ferns and lycophytes and found relevant information in >500 sources, such as online databases, checklists, floras and species descriptions. Translating textual information into a quantitative index, we quantified the propensity to grow on either substrate as a continuous trait for 1475 species.

Key Results

Only a minority of species exhibited strict substrate fidelity, but a majority of them showed clear habitat preferences. The relative frequencies of intermediates between strict lithophytes, epiphytes and terrestrials does not support the frequent notion of ecological similarity of the lithophytic and epiphytic habitat.

Conclusions

The compiled data are useful immediately for ecological and evolutionary studies with the focal taxa. More importantly, we propose the replacement of the concept of distinct habits with one of gradual differences. This should have a profound impact on any such study with plants in general.
The Role of Calcium Hydroxylapatite (Radiesse) as a Regenerative Aesthetic Treatment: A Narrative Review
Authors: Aguilera Shino Bay , McCarthy Alec , Khalifian Saami , Lorenc Z Paul , Goldie Kate , Chernoff W Gregory
Published: August 2023

For decades, a wide variety of natural and synthetic materials have been used to augment human tissue to improve aesthetic outcomes. Dermal fillers are some of the most widely used aesthetic treatments throughout the body. Initially, the primary function of dermal fillers was to restore depleted volume. As biomaterial research has advanced, however, a variety of biostimulatory fillers have become staples in aesthetic medicine. Such fillers often contain a carrying vehicle and a biostimulatory material that induces de novo synthesis of major structural components of the extracellular matrix. One such filler, Radiesse (Merz Aesthetics, Raleigh, NC), is composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel. In addition to immediate volumization, Radiesse treatment results in increases of collagen, elastin, vasculature, proteoglycans, and fibroblast populations via a cell-biomaterial–mediated interaction. When injected, Radiesse acts as a cell scaffold and clinically manifests as immediate restoration of depleted volume, improvements in skin quality and appearance, and regeneration of endogenous extracellular matrices. This narrative review contextualizes Radiesse as a regenerative aesthetic treatment, summarizes its unique use cases, reviews its rheological, material, and regenerative properties, and hypothesizes future combination treatments in the age of regenerative aesthetics.

Level of Evidence: 5
Expansion of clinico-genetic spectrum of PRDX3 disease: a literature review with two additional cases
Authors: Cho Jaeso , Yoon Jihoon G , Lee Seungbok , Kim Sheehyun , Kim Soo Yeon , Kim Man Jin , Moon Jangsup , Chae Jong-Hee
Published: August 2023

Cho et al. identified two Korean ataxia patients with novel variants, thereby broadening the clinico-genomic findings of PRDX3 disease. The novel variants (Asp171Gly and Arg207Ter) were found in compound heterozygotes with the previously reported variant (Arg170Ter). Identification of these pathogenic PRDX3 variants in East Asians highlights the need for increased awareness of PRDX3 disease.
Type A aortic dissection: optimal annual case volume for surgery
Authors: Kawczynski Michal J , van Kuijk Sander M J , Olsthoorn Jules R , Maessen Jos G , Kats Suzanne , Bidar Elham , Heuts Samuel
Published: August 2023

Background and Aims

The current study proposes a novel volume–outcome (V–O) meta-analytical approach to determine the optimal annual hospital case volume threshold for cardiovascular interventions in need of centralization. This novel method is applied to surgery for acute type A aortic dissection (ATAAD) as an illustrative example.

Methods

A systematic search was applied to three electronic databases (1 January 2012 to 29 March 2023). The primary outcome was early mortality in relation to annual hospital case volume. Data were presented by volume quartiles (Qs). Restricted cubic splines were used to demonstrate the V–O relation, and the elbow method was applied to determine the optimal case volume. For clinical interpretation, numbers needed to treat (NNTs) were calculated.

Results

One hundred and forty studies were included, comprising 38 276 patients. A significant non-linear V–O effect was observed (P < .001), with a notable between-quartile difference in early mortality rate [10.3% (Q4) vs. 16.2% (Q1)]. The optimal annual case volume was determined at 38 cases/year [95% confidence interval (CI) 37–40 cases/year, NNT to save a life in a centre with the optimal volume vs. 10 cases/year = 21]. More pronounced between-quartile survival differences were observed for long-term survival [10-year survival (Q4) 69% vs. (Q1) 51%, P < .01, adjusted hazard ratio 0.83, 95% CI 0.75–0.91 per quartile, NNT to save a life in a high-volume (Q4) vs. low-volume centre (Q1) = 6].

Conclusions

Using this novel approach, the optimal hospital case volume threshold was statistically determined. Centralization of ATAAD care to high-volume centres may lead to improved outcomes. This method can be applied to various other cardiovascular procedures requiring centralization.
Ordinary Weimar: Global Press Photography, ‘Distant Seeing’ and the Normalcy of Crisis in the 1920s
Authors: Zierenberg Malte
Published: August 2023

Press photography was an important medium of public communication in Germany in the 1920s. Scholarship on the topic has had two distinct foci. First, research on the ‘golden age’ of visual news has mainly concentrated on the visual coverage and political implications of singular events or certain topics. Secondly, the history of photography tends to concentrate on the period’s most prominent photographers, highlighting exceptional and high-quality examples of the genre. This article argues for a change of perspective, emphasizing press photography as an industry that disseminated thousands of pictures to a wide public. Focusing on its production side and a form of ‘distant seeing’ gives a better understanding of the transnational iconography of the present as it was manufactured within this professional field. Examining portfolios distributed by important actors, such as Georg Pahl’s Berlin-based photo agency, helps chart the visual media landscape through which people became acquainted with local events and national and international politics. This iconography contributed to an image of ‘Weimar’ as a society which appeared much more ‘normal’ and more comparable to the developments in other countries than ex post interpretations of Weimar as a society in crisis suggest. Global press photography fostered homogenization of the ‘mattering maps’ of a transnational public. This concentration on the global embedding of press photography and its products balances interpretations which use photographic sources to stress either the glamorous or the dramatic aspects of life in the 1920s. The transnational collation of visual news created an image of Weimar as only one among several societies challenged by modern crisis.
AAV-Vectored Expression of Marburg Virus–Neutralizing Antibody MR191 Provides Complete Protection From Challenge in a Guinea Pig Model
Authors: Rghei Amira D , Cao Wenguang , He Shihua , Lopes Jordyn A , Zielinska Nicole , Pei Yanlong , Thompson Brad , Banadyga Logan , Wootton Sarah K
Published: August 2023

Although there are no approved countermeasures available to prevent or treat disease caused by Marburg virus (MARV), potently neutralizing monoclonal antibodies (mAbs) derived from B cells of human survivors have been identified. One such mAb, MR191, has been shown to provide complete protection against MARV in nonhuman primates. We previously demonstrated that prophylactic administration of an adeno-associated virus (AAV) expressing MR191 protected mice from MARV. Here, we modified the AAV-MR191 coding sequence to enhance efficacy and reevaluated protection in a guinea pig model. Remarkably, 4 different variants of AAV-MR191 provided complete protection against MARV, despite administration 90 days prior to challenge. Based on superior expression kinetics, AAV-MR191-io2, was selected for evaluation in a dose-reduction experiment. The highest dose provided 100% protection, while a lower dose provided ∼88% protection. These data confirm the efficacy of AAV-mediated expression of MR191 and support the further development of this promising MARV countermeasure.
Prevalence of erythromycin-resistant emm92-type invasive group A streptococcal infections among injection drug users in West Virginia, United States, 2021–23
Authors: Powell Lillie M , Choi Soo Jeon , Haught Breanna L , Demkowicz Ryan , LaSala P Rocco , Lukomski Slawomir
Published: August 2023

Background

Increasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and the USA over the past several years. Coupled with this are observations of higher rates of resistance to erythromycin and clindamycin.

Objectives

To characterize iGAS and pharyngitis isolates from West Virginia (WV), a US state outside of the national Active Bacteria Core surveillance purview, where risk factors associated with iGAS infections are prevalent.

Methods

Seventy-seven invasive group A Streptococcus isolates were collected from 67 unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021 to 2023. Invasive isolates and 20 unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibility in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm subtype and detection of MLSB resistance determinants.

Results

Twenty-six (39%) isolates were of a single emm92 type. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported IV drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, 51 (76%) of the 67 iGAS isolates were determined to carry MLSB resistance.

Conclusions

Isolates of emm92 type (clonal subtype emm92.0) were associated with iGAS infections in adult IV drug users, but not with paediatric pharyngitis, and were uniformly resistant to erythromycin and clindamycin.
ClientEarth v Shell plc and the (Un)Suitability of UK Company Law and Litigation to Pursue Climate-Related Goals
Authors: Iglesias-Rodríguez Pablo
Published: August 2023

In February 2023, ClientEarth filed a derivative claim in the High Court of England and Wales against the Board of Directors of Shell plc for alleged breaches of their duties under the Companies Act 2006. According to ClientEarth, Shell’s Board of Directors has failed to put in place an energy transition strategy consistent with the Paris Agreement, increasing the exposure of Shell plc to climate risks and hindering its long-term commercial viability. This analysis assesses the legal grounds of ClientEarth’s claim in light of the UK’s company law framework, and the High Court’s judgements of May and July 2023 dismissing ClientEarth’s application. It argues that, despite the lack of solid legal grounds for ClientEarth’s derivative claim, this case may serve to advance climate-related goals. More generally, the analysis reflects on how this dispute evidences the growing gap between the objectives of environmental law on the one side and those of company law on the other side.
A Tale of Two Tails: A New Unique Information Share Measure Based on Copulas
Authors: Shi Yanlin
Published: August 2023

I propose a novel measure of information share, termed tail information share (TIS), which focuses on modeling the tail dependence of price innovations using copulas. I discuss its detailed technical properties, including unique identifiability, estimation procedures, and statistical properties. The proposed TIS improves over two commonly used measures by providing meaningful economic rationale and unique identifiability. My simulation studies indicate that TIS can yield more accurate estimates of market-specific contributions to price discovery when tail dependence is present. Additionally, I demonstrate the asymptotic consistency and efficiency of TIS estimators. An empirical illustration is provided using a new dataset of high-frequency crude oil futures.
Autonomous Electron Tomography Reconstruction with Machine Learning
Authors: Millsaps William , Schwartz Jonathan , Di Zichao Wendy , Jiang Yi , Hovden Robert
Published: August 2023

Modern electron tomography has progressed to higher resolution at lower doses by leveraging compressed sensing (CS) methods that minimize total variation (TV). However, these sparsity-emphasized reconstruction algorithms introduce tunable parameters that greatly influence the reconstruction quality. Here, Pareto front analysis shows that high-quality tomograms are reproducibly achieved when TV minimization is heavily weighted. However, in excess, CS tomography creates overly smoothed three-dimensional (3D) reconstructions. Adding momentum to the gradient descent during reconstruction reduces the risk of over-smoothing and better ensures that CS is well behaved. For simulated data, the tedious process of tomography parameter selection is efficiently solved using Bayesian optimization with Gaussian processes. In combination, Bayesian optimization with momentum-based CS greatly reduces the required compute time—an 80% reduction was observed for the 3D reconstruction of SrTiO3 nanocubes. Automated parameter selection is necessary for large-scale tomographic simulations that enable the 3D characterization of a wider range of inorganic and biological materials.
Periodic changes in the morphology of the Galactic resonance rings
Authors: Melnik A M , Podzolkova E N , Dambis A K
Published: August 2023

We study the periodic enhancement of either trailing or leading segments of the resonance elliptical rings in the dynamical model of the Galaxy which reproduces distributions of observed velocities derived from Gaia DR3 (EDR3) data along the Galactocentric distance. The model disc forms a nuclear ring, an inner combined ring, and outer resonance rings R1 and R2. The backbone of the inner combined ring is banana-type orbits around the Lagrange equilibrium points L4 and L5. Orbits associated with the unstable equilibrium points L1 and L2 also support the inner ring. We have found the changes of the morphology of the inner ring with a period of P = 0.57 ± 0.02 Gyr, which is close to the period of revolution along the long-period orbits around the points L4 and L5. A possible explanation of these morphological changes is the formation of an overdensity which then begins circulating along the closed contour. In the region of the Outer Lindblad Resonance (OLR), we have found the changes of the morphology of the outer rings with a period of P = 2.0 ± 0.1 Gyr. Probably, the morphological changes of the outer rings are due to the orbits trapped by the OLR. These orbits exhibit librations of the direction of orbital elongation with respect to the minor axis of the bar as well as the long-term variations in the stellar angular momentum, energy, average radius of the orbit, and eccentricity. Among many librating orbits, we discovered orbits with the libration period of P = 1.91 ± 0.01 Gyr, which may cause the morphological changes of the outer rings.
Milliarcsecond core size dependence of the radio variability of blazars
Authors: Hsu Po-Chih , Koay Jun Yi , Matsushita Satoki , Hwang Chorng-Yuan , Hovatta Talvikki , Kiehlmann Sebastian , Readhead Anthony , Max-Moerbeck Walter , Reeves Rodrigo
Published: August 2023

Studying the long-term radio variability (time-scales of months to years) of blazars enables us to gain a better understanding of the physical structure of these objects on subparsec scales, and the physics of supermassive black holes. In this study, we focus on the radio variability of 1157 blazars observed at 15 GHz through the Owens Valley Radio Observatory Blazar Monitoring Program. We investigate the dependence of the variability amplitudes and time-scales, characterized based on model fitting to the structure functions, on the milliarcsecond core sizes measured by Very Long Baseline Interferometry. We find that the most compact sources at milliarcsecond scales exhibit larger variability amplitudes and shorter variability time-scales than more extended sources. Additionally, for sources with measured redshifts and Doppler boosting factors, the correlation between linear core sizes against variability amplitudes and intrinsic time-scales is also significant. The observed relationship between variability time-scales and core sizes is expected, based on light travel-time arguments. This variability versus core size relation extends beyond the core sizes measured at 15 GHz; we see significant correlation between the 15 GHz variability amplitudes (as well as time-scales) and core sizes measured at other frequencies, which can be attributed to a frequency–source size relationship arising from the intrinsic jet structure. At low frequencies of 1 GHz where the core sizes are dominated by interstellar scattering, we find that the variability amplitudes have significant correlation with the 1 GHz intrinsic core angular sizes, once the scatter broadening effects are deconvoluted from the intrinsic core sizes.
The hologenome ofDaphnia magnareveals possible DNA methylation and microbiome-mediated evolution of the host genome
Authors: Chaturvedi Anurag , Li Xiaojing , Dhandapani Vignesh , Marshall Hollie , Kissane Stephen , Cuenca-Cambronero Maria , Asole Giovanni , Calvet Ferriol , Ruiz-Romero Marina , Marangio Paolo , Guigó Roderic , Rago Daria , Mirbahai Leda , Eastwood Niamh , Colbourne John K , Zhou Jiarui , Mallon Eamonn , Orsini Luisa
Published: August 2023

Properties that make organisms ideal laboratory models in developmental and medical research are often the ones that also make them less representative of wild relatives. The waterflea Daphnia magna is an exception, by both sharing many properties with established laboratory models and being a keystone species, a sentinel species for assessing water quality, an indicator of environmental change and an established ecotoxicology model. Yet, Daphnia’s full potential has not been fully exploited because of the challenges associated with assembling and annotating its gene-rich genome. Here, we present the first hologenome of Daphnia magna, consisting of a chromosomal-level assembly of the D. magna genome and the draft assembly of its metagenome. By sequencing and mapping transcriptomes from exposures to environmental conditions and from developmental morphological landmarks, we expand the previously annotates gene set for this species. We also provide evidence for the potential role of gene-body DNA-methylation as a mutagen mediating genome evolution. For the first time, our study shows that the gut microbes provide resistance to commonly used antibiotics and virulence factors, potentially mediating Daphnia's environmental-driven rapid evolution. Key findings in this study improve our understanding of the contribution of DNA methylation and gut microbiota to genome evolution in response to rapidly changing environments.
SFyNCS detects oncogenic fusions involving non-coding sequences in cancer
Authors: Zhong Xiaoming , Luan Jingyun , Yu Anqi , Lee-Hassett Anna , Miao Yuxuan , Yang Lixing
Published: August 2023

Fusion genes are well-known cancer drivers. However, most known oncogenic fusions are protein-coding, and very few involve non-coding sequences due to lack of suitable detection tools. We develop SFyNCS to detect fusions of both protein-coding genes and non-coding sequences from transcriptomic sequencing data. The main advantage of this study is that we use somatic structural variations detected from genomic data to validate fusions detected from transcriptomic data. This allows us to comprehensively evaluate various fusion detection and filtering strategies and parameters. We show that SFyNCS has superior sensitivity and specificity over existing algorithms through extensive benchmarking in cancer cell lines and patient samples. We then apply SFyNCS to 9565 tumor samples across 33 tumor types in The Cancer Genome Atlas cohort and detect a total of 165,139 fusions. Among them, 72% of the fusions involve non-coding sequences. We find a long non-coding RNA to recurrently fuse with various oncogenes in 3% of prostate cancers. In addition, we discover fusions involving two non-coding RNAs in 32% of dedifferentiated liposarcomas and experimentally validated the oncogenic functions in mouse model.
The Politics of Babbling in Mum and the Sothsegger
Authors: Outhwaite Patrick
Published: August 2023

This article contends that the alliterative long-line poem Mum and the Sothsegger redefines and develops the meanings of the Middle English verb babelen (to babble). I argue that the Mum-poet shifted the meaning of the word from denoting idle prattle and nonsensical, infantile vocalizations into a simple and transparent form of communication that was ideal for telling truths. Those who babble are directly opposed to those who keep mum or communicate in a subtle and complex manner, obscuring and manipulating the truth through their confusing rhetoric and glosses. The Mum-poet pits simplicity against complexity in his political commentary, advocating for the most straightforward, utilitarian manner of speech in statecraft.
Comparison of Standard Calendar GA4+7 Plant Growth Regulator Programs to Applications Timed to Rainfall Events for Management of Scarf Skin, a Fruit Finish Disorder of Apple
Authors: Strickland David A. , Londo Jason P. , Cox Kerik D.
Published: August 2023

Scarf skin is a fruit finish disorder of apple that leads to reduced grade quality and rejected crop loads. Although not established as a disorder specific to certain cultivars, the manifestation of the disorder is more apparent on red-skinned cultivars such as Gala and Stayman at harvest, where its whiteish cast is held in clear contrast with the redness of the mature fruit. The disorder afflicts fruit during the first 40 days after petal fall as the fruitlet is developing, although symptoms of the disorder may not be clearly visible until many months after. The exact causes of apple scarf skin are not well defined, although it is known that the presence of the disorder can be influenced by environment, fruit size, and some pesticides. Management currently relies on four applications of the plant hormones gibberellins A4 and A7 (GA4+7) during the first 40 days after bloom. Here, we describe our attempts to use a commercialized GA4+7 product (ProVide 10SG) starting at petal fall, with applications made after or before rainfall events, to ease rainfall's putative influence on scarf skin development. We compared our programs to the standard program over 4 years in research orchards and a commercial orchard but observed no consistent reduction in scarf skin severity or incidence of out-of-grade fruit, in part due to the year-to-year variability in the manifestation of scarf skin. Rainfall, at the thresholds defined, does not appear to be a sufficiently significant factor influencing scarf skin development such that a GA4+7 management program can be designed.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Stressed and Depressed: Prevalence of Anxiety and/or Depression in Physician Assistant Students
Authors: Davis Erin M. , Kauffman Mackenzie R. , Welborn Kelsey E. , Bachor Sarah , Miller Paul M.
Published: August 2023

Introduction

This research highlights the prevalence of anxiety and/or depression among physician assistant (PA) students compared with the general population. It is believed that the results of this study will encourage graduate programs to place a stronger emphasis on the mental health of students and create a more positive learning environment.

Methods

An original survey was created using questions from Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and several original questions. The survey was distributed using a SurveyMonkey link to directors of all accredited US PA programs. Program directors were asked to distribute the survey to their students. The survey remained open for 6 weeks, after which a cross-sectional statistical analysis was performed to compare the results with national anxiety and depression data in the United States.

Results

There is a statistically significant increase in the rate of occurrence of anxiety and/or depression among PA students compared with the general population. According to survey results, 84.4% of respondents experienced feelings of anxiety and 80.9% experienced feelings of depression while enrolled in PA school. Physician assistant students found the greatest need for anxiety and depression treatment during the didactic portion of their program.

Discussion

When compared with the national population, the level of anxiety in PA students was found to be 65.3% higher and the levels of depression in PA students to be 72.5% higher. These results should encourage PA programs and health care providers to take action regarding the mental health of future providers.
Effect of Light Intensity on the Relative Afferent Pupillary Defect in Unilateral Neuro-ophthalmic Pathology
Authors: Negi Rahul , Raviselvan Munispriyan , Yarravarapu Divyank , Chillakala Koteswararao , Durai C. V. Reena , Baskar Juhi , Jain Ashish , Bisht Karan , Bhate Manjushree , Bharadwaj Shrikant R.
Published: August 2023

SIGNIFICANCE

Objective pupillometry with standardized light intensities allows a comprehensive assessment of the relative afferent pupillary defect in patients with unilateral neuro-ophthalmic pathology.

PURPOSE

This study aimed to determine the impact of varying light intensities on the grade of relative afferent pupillary defect in unilateral neuro-ophthalmic pathology vis-à-vis healthy controls.

METHODS

Monocular pupillary light reflexes of 20 controls (14 to 50 years) and 31 cases (12 to 72 years) with clinically diagnosed relative afferent pupillary defect were measured thrice using 1-second-long light pulses, followed by 3 seconds of darkness, at eight light intensities (6.4 to 1200 lux) using objective pupillometry. The relative afferent pupillary defect was quantified as the ratio of the percentage change in the direct light reflexes of the left and right eyes. Its change with light intensity was described using standard exponential fits.

RESULTS

The median (25th to 75th interquartile range) defect score of 54.8% cases decreased from baseline values of 1.58 (1.25 to 1.87) for right eye pathology and 0.45 (0.39 to 0.55) for left eye pathology to saturation values of 1.18 (1.05 to 1.31) and 0.98 (0.95 to 1.06), respectively, at light intensities between 56.9 and 300.5 lux. Like controls (1.01 [1.00 to 1.06]), the defect scores of the remaining 45.2% cases were constant with light intensity at 1.23 (1.18 to 1.46) and 0.87 (0.86 to 0.89) for right and left eye pathologies, respectively.

CONCLUSIONS

Relative afferent pupillary defects may decrease with test light intensity in a significant proportion of patients with unilateral neuro-ophthalmic pathology. This highlights the importance of objective pupillometry with standardization light intensities for clinical assessment of afferent pupillary defects.
A systematic review on cross-cultural validations and psychometric solidity of the orthotics and prosthetics user survey
Authors: Valero Julián M. , Satústegui Pedro J. , Salavera Carlos E. , Sanz López Vanessa , Laborda Ana A. , Hidalgo César
Published: August 2023

Research is essential to reflect patients' satisfaction with their devices in the field of Prosthetics and Orthotics, record their performance and health-related quality of life. This requires culturally adapted questionnaires for each country. Periodic assessment of validity and test fit are essential elements for the long-term utility and effectiveness of psychometric tests. This article reviews the psychometric properties of the Orthotics and Prosthetics Users Survey (OPUS). The purpose, in addition to its adaptation to the Spanish-speaking population, involves a review/update of content, statistical analyses, and validity studies, until a larger number of studies are conducted. Study design: a Systematic review. A systematic literature search was carried out in specialized search engines: Alcorze (University of Zaragoza), MEDLINE (PubMed), and EMBASE of original articles published since 2000. Eleven items belonging to the OPUS were obtained, according to the language of the country where they were validated, and promising psychometric properties were confirmed (reflecting reliability values between 0.62 and 0.95; Cronbach's α scores between 0.73 and 0.98) with sample sizes between 10 and 321. The study concluded by stating that the OPUS was validated in different languages, reporting good psychometric robustness so far. Further deployment, refinement, and validation of this survey by country is warranted in view of its promising use.
Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part I: Evolution and Optimization of 3D-Printed Scaffolds for Repair of Defects
Authors: Nayak Vasudev V. , Slavin Blaire , Bergamo Edmara T.P. , Boczar Daniel , Slavin Benjamin R. , Runyan Christopher M. , Tovar Nick , Witek Lukasz , Coelho Paulo G.
Published: August 2023

Bone tissue regeneration is a complex process that proceeds along the well-established wound healing pathway of hemostasis, inflammation, proliferation, and remodeling. Recently, tissue engineering efforts have focused on the application of biological and technological principles for the development of soft and hard tissue substitutes. Aim is directed towards boosting pathways of the healing process to restore form and function of tissue deficits. Continued development of synthetic scaffolds, cell therapies, and signaling biomolecules seeks to minimize the need for autografting. Despite being the current gold standard treatment, it is limited by donor sites’ size and shape, as well as donor site morbidity. Since the advent of computer-aided design/computer-aided manufacturing (CAD/CAM) and additive manufacturing (AM) techniques (3D printing), bioengineering has expanded markedly while continuing to present innovative approaches to oral and craniofacial skeletal reconstruction. Prime examples include customizable, high-strength, load bearing, bioactive ceramic scaffolds. Porous macro- and micro-architecture along with the surface topography of 3D printed scaffolds favors osteoconduction and vascular in-growth, as well as the incorporation of stem and/or other osteoprogenitor cells and growth factors. This includes platelet concentrates (PCs), bone morphogenetic proteins (BMPs), and some pharmacological agents, such as dipyridamole (DIPY), an adenosine A2A receptor indirect agonist that enhances osteogenic and osteoinductive capacity, thus improving bone formation. This two-part review commences by presenting current biological and engineering principles of bone regeneration utilized to produce 3D-printed ceramic scaffolds with the goal to create a viable alternative to autografts for craniofacial skeleton reconstruction. Part II comprehensively examines recent preclinical data to elucidate the potential clinical translation of such 3D-printed ceramic scaffolds.
The Accuracy of Classification Systems in Nonsyndromic Sagittal Craniosynostosis
Authors: Skadorwa Tymon , Skadorwa Joanna , Wierzbieniec Olga
Published: August 2023

Numerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects. The aim of the study was to assess the accuracy of 4 classifications of NSC discussed in the literature by defining the associations among the classifications, individual features (sex, age, cranial index), and objective morphologic criteria (frontal bossing, retrocoronal constriction, sagittal ridge, and occipital bulleting). The study was conducted on anonymized thin-cut CT scans of 133 children with NSC 1 to 12 months old (mean age 5.42 mo). The type of cranial dysmorphology was assessed using 4 classification systems, focusing on skull shape, pattern of sagittal suture closure (Heuzé classification), deformation of skull vault (Sakamoto classification), and a single-dominant feature (David classification). Each patient was also independently investigated for the presence of morphologic criteria. A multivariate analysis was performed to explore the relations among the classifications and assess their accuracy. In the analyzed cohort sphenocephaly (38.3%), CFF type by Heuzé (30.8%), type I by Sakamoto (72.9%), and a central type by David (42.9%) were dominant findings. Regarding the morphologic criteria, frontal bossing was observed the most frequently (91.7%). The age of patients and cranial index differed significantly among the shapes of skull and David classifications (P<0.001). The shape-based system showed the strongest correlation with other classifications and with measurable variables. Other classifications have much in common and some overlap, but none of them constitutes a standalone system to define all aspects of cranial dysmorphology in NSC.
Using Virtual Patients to Support Empathy Training in Health Care Education
Authors: Gilbert Alan , Carnell Stephanie , Lok Benjamin , Miles Anna
Published: August 2023

Introduction

Empathy is essential for effective patient care. Yet, research shows suboptimal empathy in patient-practitioner interactions. Intelligent virtual patient simulations may offer an effective educational tool for empathy training. This observational study explored the quality of speech pathology of students' empathy responses in virtual patient simulations.

Methods

Using the 7-point Empathic Communication Coding System (ECCS), we examined 72 students' empathic communication during a 12-week virtual patient interview series as part of their standard curriculum across 4 cohorts (a total of 388 empathic responses). The ECCS data were tallied and graphically displayed. We compared year groups (cohorts from 2015 to 2018), changes over semester, and differences between virtual patients.

Results

Median ECCS scores were 4 of a maximum of 6 (interquartile range, 3) across all interviews. Most students (89%) scored between a level 2 (implicit recognition) and level 5 (confirmation) with only a few responses scoring at the lowest 2 levels of empathy (0: denial, 0.5%; 1: automatic recognition, 2%) or the highest level of empathy (6: shared feeling or experience, 9%). Students consistently acknowledged patients' feelings and often offered an action, solution, or reassurance. However, shared feelings or experiences were infrequent.

Conclusions

Although virtual patient simulations do not replace experiential learning such as simulation, standardized patients, and clinical practicum, they offer a safe environment to practice skills. This article provides support for designing larger controlled clinical trials and provides insights for educators on how to design virtual patient empathic opportunities of varying complexity for students.
Vitamins in neuropathy: pathophysiological and therapeutic roles
Authors: Chen Peng , Song Xue-Jun
Published: August 2023

Purpose of review

Vitamin deficiency is a risk factor in the development of peripheral neuropathy, which leads to complex and severe diseases. This review provides an update overview of the literature on the roles of vitamins in peripheral neuropathy, highlighting their pathophysiological and therapeutic roles.

Recent findings

The importance and clinical manifestations and implications of the vitamins and vitamin deficiencies are further demonstrated in peripheral neuropathy and the associated diseases. Vitamin deficiency is common in various severe and complex diseases such as diabetes, chemotherapy, acute nutritional axonal neuropathy, dermatitis, complex regional pain syndrome, postherpetic neuralgia, carpal tunnel syndrome, and so forth and some rare clinical case reports. There is evidence that deficiencies of almost all vitamins are associated with diabetic neuropathy. Vitamin supplementation may serve as an effective therapeutic strategy.

The vitamins play critical roles in maintaining physiological functions, and vitamin deficiencies cause peripheral neuropathy with various severe and complex diseases. The therapeutic benefits of vitamins and further understanding of the mechanisms for vitamin treatment effects should be emphasized and highlighted. More clinical trials are needed to establish optimal treatment strategies for vitamins in the various neuropathies. A large range of people/patients screening for vitamin deficiencies may be considered in order to provide early diagnosis and timely medical assistance.