bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic inversion of circular phase spectra: application to two-station phase-velocity dispersion estimation in western Canada
Authors: Gosselin Jeremy M , Audet Pascal , Estève Clément , Schaeffer Andrew J
Published: December 2022

Periodic directional and temporal measurements are common in seismology, and necessitate specific statistical analyses that are appropriate for circular quantities. In this work, we explore the use of a von Mises distribution as a representation of errors on circular seismological observations. Specifically, we automate the estimation of surface-wave phase-velocity dispersion for the teleseismic two-station method, which generally suffers from a 2π phase ambiguity. The use of Bayesian inverse techniques, which aim to rigorously quantify model parameter uncertainty, have become widespread throughout seismology over the last decade. Here, we apply Bayesian inversion to measurements of surface-wave phase spectra in order to estimate 1-D, path-averaged Earth structure between station pairs. The dispersion curve and associated uncertainties are additional results of the inversion, which can then be used as input for subsequent analyses (e.g. tomography). We demonstrate this technique through application to surface-wave recordings from long-running seismic stations throughout western Canada. Our results for over 10 000 station pairs reveal first-order tectonic features consistent with previous studies, which provides confidence in our approach as well as an initial step towards resolving a full 3-D seismic velocity model for the region. This work also presents a foundation for the inversion of surface-wave phase spectra to estimate 3-D Earth structure directly. Finally, the ideas presented in this work are not limited to the inversion of surface-wave phase spectra, but can also be considered for Bayesian geophysical inversion of any circular quantities.
Semilocal Milnor K-Theory
Authors: Garkusha Grigory
Published: December 2022

In this paper, semilocal Milnor $K$-theory of fields is introduced and studied. A strongly convergent spectral sequence relating semilocal Milnor $K$-theory to semilocal motivic cohomology is constructed. In weight 2, the motivic cohomology groups $H^p_{{\operatorname {Zar}}}(k,\mathbb Z(2))$, $p\leqslant 1$, are computed as semilocal Milnor $K$-theory groups $\widehat {K}^M_{2,3-p}(k)$. The following applications are given: (i) several criteria for the Beilinson–Soulé Vanishing Conjecture; (ii) computation of $K_4$ of a field; (iii) the Beilinson conjecture for rational $K$-theory of fields of prime characteristic is shown to be equivalent to vanishing of rational semilocal Milnor $K$-theory.
Influenza A and Respiratory Syncytial Virus Trigger a Cellular Response That Blocks Severe Acute Respiratory Syndrome Virus 2 Infection in the Respiratory Tract
Authors: Dee Kieran , Schultz Verena , Haney Joanne , Bissett Laura A , Magill Callum , Murcia Pablo R
Published: December 2022

Background

Multiple viruses cocirculate and contribute to the burden of respiratory disease. Virus-virus interactions can decrease susceptibility to infection and this interference can have an epidemiological impact. As humans are normally exposed to a community of cocirculating respiratory viruses, experimental coinfection studies are necessary to understand the disease mechanisms of multipathogen systems. We aimed to characterize interactions within the respiratory tract between severe acute respiratory syndrome virus 2 (SARS-CoV-2) and 2 major respiratory viruses: influenza A virus (IAV), and respiratory syncytial virus (RSV).

Methods

We performed single infections and coinfections with SARS-CoV-2 combined with IAV or RSV in cultures of human bronchial epithelial cells. We combined microscopy with quantification of viral replication in the presence or absence of an innate immune inhibitor to determine changes in virus-induced pathology, virus spread, and virus replication.

Results

SARS-CoV-2 replication is inhibited by both IAV and RSV. This inhibition is dependent on a functional antiviral response and the level of inhibition is proportional to the timing of secondary viral infection.

Conclusions

Infections with other respiratory viruses might provide transient resistance to SARS-CoV-2. It would therefore be expected that the incidence of coronavirus disease 2019 (COVID-19) may decrease during periods of high circulation of IAV and RSV.
Indole-derived compound SIS3 targets a subset of activated Smad complexes
Authors: Itoh Yuka , Sawaguchi Tomoe , Fu Hao , Omata Chiho , Saitoh Masao , Miyazawa Keiji
Published: December 2022

Smad2 and Smad3 are receptor-regulated Smad proteins that transmit signals from cytokines belonging to the transforming growth factor (TGF)-β family, which are vital for adult tissue homeostasis. The overactivation of such proteins often engenders the development of pathological conditions. Smad3 reportedly mediates TGF-β–induced fibrosis. Although various potential Smad3-specific inhibitors are being developed, their specificity and action mechanisms remain largely unknown. This study aimed to establish a biochemical platform to monitor Smad2- or Smad3-dependent TGF-β signaling using SMAD2, SMAD3 and SMAD2/3 knockout cell lines alongside TGF-β–dependent luciferase reporters and Smad mutant proteins. Using this platform, SIS3, an indole-derived compound widely used as a specific Smad3 inhibitor, was observed to preferentially suppress a subset of activated Smad complexes. However, its inhibition did not favor Smad3 signaling over Smad2 signaling. These findings indicate that SIS3 can be employed as a probe to examine the heterogeneous nature of Smad signaling that induces gene expression. However, its use as a Smad3-specific inhibitor should be avoided.
The use of a metaphyseal sleeve total knee replacement as primary treatment for Schaztker VI tibial plateau fracture
Authors: McSorley Matthew , Jabbal Monu , Walmsley Phil
Published: December 2022

Traditional treatment of tibial plateau fractures is with open reduction and internal fixation, or external fixation in severely displaced and comminuted fractures. Total joint arthroplasty for unreconstructable hip fractures is a successful and widely accepted treatment; however, such surgery for tibial plateau fractures is not a common practice. We present two cases of highly comminuted schaztker VI tibial plateau fractures in patients over the age of 65. Both patients had a metaphyseal sleeve revision knee arthroplasty as delayed primary treatment. Both patients have had excellent clinical and radiographical results at 6 months and 5 years follow-up, respectively. We present the first description in the literature of this implants use for bone loss as a result of trauma. There is growing evidence that total joint arthroplasty is an effective treatment in tibial plateau fractures, in particular for elderly patients who may be at high risk of failure from internal fixation.
Investigating dynamical properties of globular clusters through a family of lowered isothermal models
Authors: Cheng Chia-Hsuan , Jiang Ing-Guey
Published: December 2022

To investigate the dynamical properties of globular clusters, surface brightness and kinematic data were collected and fitted to a family of lowered isothermal models called limepy models. For the 18 globular clusters studied, the amounts of concentration, truncation, and anisotropy were determined. In addition, the cluster mass, half-mass radius, distance, and mass-to-light ratio were also obtained. In general, limepy models can describe these clusters well. Among these 18 clusters, NGC 5139, 6388, and 7078 have been claimed to be candidates for hosting intermediate-mass black holes in the literature. The models could not appropriately fit the central proper-motion velocity dispersion of NGC 5139, nor the slope of the proper-motion velocity dispersion profile of NGC 6388. Thus, more dedicated models with intermediate-mass black holes or a group of stellar-mass black holes at cluster centres may need to be considered. Regarding NGC 7078, our model with some degree of anisotropy can fit the data. Finally, a strong concentration–truncation anticorrelation and a truncation–semimajor-axis correlation were revealed, which could be the observational imprint of the dynamical evolution of globular clusters.
Forming blue compact dwarf galaxy through mergers
Authors: Chhatkuli Daya Nidhi , Paudel Sanjaya , Bachchan Rajesh Kumar , Aryal Binil , Yoo Jaewon
Published: December 2022

It has long been speculated that blue compact dwarf galaxies (BCDs) are formed through the interaction between low-mass gas-rich galaxies, but a few candidates of such systems have been studied in detail. We study a sample of compact star-forming dwarf galaxies that are selected from a merging dwarf galaxy catalog. We present a detailed study of their spectroscopic and structural properties. We find that these BCDs looking galaxies host extended stellar shells and thus are confirmed to be a dwarf--dwarf merger. Their stellar masses range between 8 × 107 M ⊙ and 2 × 109 M ⊙. Although the extended tail and shell are prominent in the deep optical images, the overall major axis light profile is well modeled with a two-component Sérsic function of inner compact and extended outer radii. We calculate the inner and outer component stellar-mass ratio using the two-component modeling. We find an average ratio of 4:1 (with a range of 10:1 to 2:1) for our sample, indicating that the central component dominates the stellar mass with an ongoing burst of star formation. From the measurement of Hα equivalent width, we derived the star-formation ages of these galaxies. The derived star-formation ages of these galaxies turn out to be in the order of a few 10 Myr, suggesting the recent ignition of star formation due to events of satellite interaction.
NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics
Authors: Abayazeed Aly H , Abbassy Ahmed , Müeller Michael , Hill Michael , Qayati Mohamed , Mohamed Shady , Mekhaimar Mahmoud , Raymond Catalina , Dubey Prachi , Nael Kambiz , Rohatgi Saurabh , Kapare Vaishali , Kulkarni Ashwini , Shiang Tina , Kumar Atul , Andratschke Nicolaus , Willmann Jonas , Brawanski Alexander , De Jesus Reordan , Tuna Ibrahim , Fung Steve H , Landolfi Joseph C , Ellingson Benjamin M , Reyes Mauricio
Published: December 2022

Background

Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable.

Methods

A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed.

Results

IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed.

Conclusion

NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.
Tilt-induced polar order and topological defects in growing bacterial populations
Authors: Shimaya Takuro , Takeuchi Kazumasa A
Published: December 2022

Rod-shaped bacteria, such as Escherichia coli, commonly live forming mounded colonies. They initially grow two-dimensionally on a surface and finally achieve three-dimensional growth. While it was recently reported that three-dimensional growth is promoted by topological defects of winding number +1/2 in populations of motile bacteria, how cellular alignment plays a role in nonmotile cases is largely unknown. Here, we investigate the relevance of topological defects in colony formation processes of nonmotile E. coli populations, and found that both ±1/2 topological defects contribute to the three-dimensional growth. Analyzing the cell flow in the bottom layer of the colony, we observe that +1/2 defects attract cells and −1/2 defects repel cells, in agreement with previous studies on motile cells, in the initial stage of the colony growth. However, later, cells gradually flow toward −1/2 defects as well, exhibiting a sharp contrast to the existing knowledge. By investigating three-dimensional cell orientations by confocal microscopy, we find that vertical tilting of cells is promoted near the defects. Crucially, this leads to the emergence of a polar order in the otherwise nematic two-dimensional cell orientation. We extend the theory of active nematics by incorporating this polar order and the vertical tilting, which successfully explains the influx toward −1/2 defects in terms of a polarity-induced force. Our work reveals that three-dimensional cell orientations may result in qualitative changes in properties of active nematics, especially those of topological defects, which may be generically relevant in active matter systems driven by cellular growth instead of self-propulsion.
Metaverse as a new place for online mental health services in the post-COVID-19 era: Is it a challenge or an opportunity?
Authors: Situmorang Dominikus David Biondi
Published: December 2022

In this article, the author describes the challenges and opportunities of metaverse’s presence in the world for online mental health services. Aside from that, the author provides insight that metaverse can become a new place that is more comfortable and enjoyable for everyone who can relish the online mental health meetings with a new atmosphere and sensation, especially in the post-COVID-19 era.
Clinically meaningful changes in efficacy outcomes in chronic rhinosinusitis with nasal polyposis
Authors: Mitchell Margaret B. , Workman Alan D. , Lee Stella E.
Published: December 2022

Purpose of review

Chronic rhinosinusitis with nasal polyps (CRSwNP) carries a high disease burden, and many studies have been done investigating the efficacy of various medical and surgical therapies. However, outcome metrics have varied across these studies, making it difficult to compare therapeutic efficacy on a large scale. In this article, we discuss various outcome metrics used across prior studies as well as the relationship between these measures.

Recent findings

Outcome metrics in CRSwNP studies include both clinically assessed and patient-reported outcome measures (PROMs). The former includes olfaction testing, scoring systems based on imaging and endoscopic evaluation, and histopathological and immunohistochemical evaluation of sinus tissue, and the latter includes quality-of-life instruments, symptom severity scales, and disease-control instruments. Recent studies evaluating the efficacy of new biologics have used a combination of both types of metrics.

Both clinical metrics and patient-reported outcomes provide utility in evaluating disease severity and control in patients with CRSwNP, although there are nuances when comparing therapies in this population as patients with CRSwNP are heterogeneous and may have symptoms across several domains. However, PROMs in conjunction with clinical metrics provide useful information to assess patient symptoms and response to interventions.
Gene therapy for inborn error of immunity – current status and future perspectives
Authors: Mudde Anne , Booth Claire
Published: December 2022

Purpose of review

Development of hematopoietic stem cell (HSC) gene therapy (GT) for inborn errors of immunity (IEIs) continues to progress rapidly. Although more patients are being treated with HSC GT based on viral vector mediated gene addition, gene editing techniques provide a promising new approach, in which transgene expression remains under the control of endogenous regulatory elements.

Recent findings

Many gene therapy clinical trials are being conducted and evidence showing that HSC GT through viral vector mediated gene addition is a successful and safe curative treatment option for various IEIs is accumulating. Gene editing techniques for gene correction are, on the other hand, not in clinical use yet, despite rapid developments during the past decade. Current studies are focussing on improving rates of targeted integration, while preserving the primitive HSC population, which is essential for future clinical translation.

As HSC GT is becoming available for more diseases, novel developments should focus on improving availability while reducing costs of the treatment. Continued follow up of treated patients is essential for providing information about long-term safety and efficacy. Editing techniques have great potential but need to be improved further before the translation to clinical studies can happen.
Exhaled nitric oxide in asthma: from diagnosis to management
Authors: Guida Giuseppe , Carriero Vitina , Bertolini Francesca , Pizzimenti Stefano , Heffler Enrico , Paoletti Giovanni , Ricciardolo Fabio L.M.
Published: December 2022

Purpose of review

Exhaled nitric oxide (FENO) is a noninvasive marker of eosinophilic airway inflammation, therefore, highly informative in asthma. Although FENO measurement is a potentially accessible tool to many physicians, recommendations regarding its clinical utility in diagnosing or tailoring treatment have not reached the expected diffusion. More recently FENO emerged as a biomarker for type-2 asthma phenotyping and a predictor of response to biologics.

Recent findings

The physiological discoveries and relevant acquisitions in clinical practice regarding FENO in asthma are presented. The FENO story draw a wavy path, characterized by promising findings, exciting confirmations and periods of low visibility. FENO emerged as a tool to increase the probability of asthma diagnosis. FENO predicts response to inhaled glucocorticoids (ICS), favoring the development of tailored treatment strategies and unrevealing nonadherence to ICS in difficult-to-treat or uncontrolled asthma. Finally, FENO was associated with a more severe phenotype and became a consolidated biomarker of type-2 inflammation.

FENO demonstrated to be a noninvasive and very reproducible test, encompassing many applications in the field of asthma management. Its routinely use, according to international guidelines, may improve the quality of patient assistance, from difficult-to-treat cases to biologic monitoring.
Long noncoding RNA TUG1 decreases bladder cancer chemo-sensitivity toward doxorubicin through elevating KPNA2 expression and activating the PI3K/AKT pathway via adsorbing miR-582-5p
Authors: Lu Peng , Jiang Yingchun , Xia Zongyu
Published: December 2022

Long noncoding RNA taurine-upregulated gene1 (TUG1) has been reported to be implicated in the chemo-resistance of bladder cancer. Hence, this study aimed to survey regulatory mechanism by which TUG1 regulates the chemo-resistance of bladder cancer cells to doxorubicin (DOX). Relative expression of TUG1, miR-582-5p, and karyopherin alpha 2 (KPNA2) was detected by qRT-PCR. The viability and proliferation of DOX-resistant bladder cancer cells were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Protein levels were measured by western blot analysis. The apoptosis, migration, and invasion of DOX-resistant bladder cancer cells were determined by flow cytometry or transwell assays. The relationship between TUG1 or KPNA2 and miR-582-5p was verified by dual-luciferase reporter assay. TUG1 and KPNA2 were upregulated while miR-582-5p was downregulated in resistant bladder cancer tissues and cells. TUG1 inhibition elevated cell chemo-sensitivity, facilitated cell apoptosis, and curbed proliferation, migration, invasion, and autophagy of DOX-resistant bladder cancer cells. Also, TUG1 acted as a sponge for miR-582-5p, and miR-582-5p inhibitor reversed TUG1 knockdown-mediated influence on DOX chemo-sensitivity and malignant behaviors in DOX-resistant bladder cancer cells. Furthermore, miR-582-5p targeted KPNA2, and KPNA2 overexpression counteracted the inhibitory impact of miR-582-5p mimic on DOX chemo-resistance and malignant behaviors in DOX-resistant bladder cancer cells. Additionally, TUG1 silencing inactivated the PI3K/AKT pathway through sponging miR-582-5p. TUG1 sponged miR-582-5p to increase KPNA2 expression and activated the KPNA2/PI3K/AKT pathway, thereby elevating DOX chemo-resistance and malignant behaviors in bladder cancer cells.
Identification of Subtypes of Dry Eye Disease, Including a Candidate Corneal Neuropathic Pain Subtype Through the Use of a Latent Class Analysis
Authors: Liu Zijun , Lietman Tom , Gonzales John A.
Published: December 2022

Purpose:

In the absence of a gold-standard diagnostic test for different subtypes of dry eye disease (DED), we aimed to identify latent subtypes of DED within a well-characterized cohort.

Design:

This is a cross-sectional study of participants enrolled in the Sjögren International Collaborative Clinical Alliance (SICCA).

Methods:

A latent class analysis was applied to different dry eye–related signs/tests and symptoms of ocular pain (particularly those that aligned with corneal neuropathic pain) giving relative specificities and sensitivities of each diagnostic test or symptom in the SICCA population.

Results:

Four subtypes of DED were identified with putative designations including normal, asymptomatic dry eye, symptomatic dry eye, and corneal neuropathic pain.

Conclusions:

More specific classification criteria are needed for DED. Latent class analysis applied to the signs and symptoms captured in the SICCA cohort may allow for the development and refinement of classification criteria for specific subtypes of dry eye.
Home oxygen monitoring and therapy: learning from the pandemic
Authors: Beaney Thomas , Clarke Jonathan
Published: December 2022

Purpose of review

Home oxygen monitoring and therapy have been increasingly used in the management of patients with chronic diseases. The COVID-19 pandemic has prompted the rapid uptake of remote monitoring programmes to support people with COVID-19 at home. This review discusses the recent evidence and learning in home oxygen monitoring and therapy from the pandemic.

Recent findings

Many home oxygen monitoring programmes were established around the world during the pandemic, mostly in high-income countries to support early detection of hypoxaemia and/or early hospital discharge. The characteristics of these programmes vary widely in the type of monitoring (self-monitoring or clinician-monitoring) and the patient risk groups targeted. There is a lack of evidence for benefits on clinical outcomes, including mortality, and on reductions in healthcare utilisation or cost-effectiveness, but programmes are viewed positively by patients. Recent studies have highlighted the potential bias in pulse oximetry in people with darker skin.

Recent evidence indicates that home oxygen monitoring therapy programmes are feasible in acute disease, but further research is needed to establish whether they improve patient outcomes, are cost-effective and to understand their equity impact.
Cell quiescence in planarian stem cells, interplay between p53 and nutritional stimuli
Authors: Gambino Gaetana , Iacopetti Paola , Guidi Patrizia , Ippolito Chiara , Linsalata Stefania , Salvetti Alessandra , Rossi Leonardo
Published: December 2022

Cell quiescence appeared early in evolution as an adaptive response to adverse conditions (i.e. nutrient depletion). In metazoans, quiescence has been involved in additional processes like tissue homeostasis, which is made possible by the presence of adult stem cells (ASCs). Cell cycle control machinery is a common hub for quiescence entrance, and evidence indicates a role for p53 in establishing the quiescent state of undamaged cells. Mechanisms responsible for waking up quiescent cells remain elusive, and nutritional stimulus, as a legacy of its original role, still appears to be a player in quiescence exit. Planarians, rich in ASCs, represent a suitable system in which we characterized a quiescent population of ASCs, the dorsal midline cord (DMC) cells, exhibiting unique transcriptional features and maintained quiescent by p53 and awakened upon feeding. The function of DMC cells is puzzling and we speculate that DMC cells, despite retaining ancient properties, might represent a functional drift in which quiescence has been recruited to provide evolutionary advantages.
Experience does not change the importance of wind support for migratory route selection by a soaring bird
Authors: Brønnvik Hester , Safi Kamran , Vansteelant Wouter M. G. , Byholm Patrik , Nourani Elham
Published: December 2022

Migration is a complex behaviour that is costly in terms of time, energy and risk of mortality. Thermal soaring birds rely on airflow, specifically wind support and uplift, to offset their energetic costs of flight. Their migratory routes are a record of movement decisions to negotiate the atmospheric environment and achieve efficiency. We expected that, regardless of age, birds use wind support to select their routes. Because thermal soaring is a complex flight behaviour that young birds need to learn, we expected that, as individuals gain more experience, their movement decisions will also increasingly favour the best thermal uplift conditions. We quantified how route choice during autumn migration of young European honey buzzards (
Pernis apivorus
) was adjusted to wind support and uplift over up to 4 years of migration and compared this with the choices of adult birds. We found that wind support was important in all migrations. However, we did not find an increase in the use of thermal uplifts. This could be due to the species-specific learning period and/or an artefact of the spatio-temporal scale of our uplift proxies.
Shifts in predator behaviour following climate induced disturbance on coral reefs
Authors: Rotjan Randi D. , Ray Nicholas E. , Cole Ingrid , Castro Kurt G. , Kennedy Brian R. C. , Barbasch Tina , Lesneski Kathryn C. , Lord Karina Scavo , Bhardwaj Anjali , Edens Madeleine , Karageorge Ioanna , Klawon Caitlynn , Kruh-Needleman Hallie , McCarthy Gretchen , Perez Raziel , Roberts Christopher , Trumble Isabela F. , Volk Aryanna , Torres Javon , Morey Joshua
Published: December 2022

Coral reefs are increasingly ecologically destabilized across the globe due to climate change. Behavioural plasticity in corallivore behaviour and short-term trophic ecology in response to bleaching events may influence the extent and severity of coral bleaching and subsequent recovery potential, yet our understanding of these interactions
in situ
remains unclear. Here, we investigated interactions between corallivory and coral bleaching during a severe high thermal event (10.3-degree heating weeks) in Belize. We found that parrotfish changed their grazing behaviour in response to bleaching by selectively avoiding bleached
Orbicella
spp. colonies regardless of bleaching severity or coral size. For bleached corals, we hypothesize that this short-term respite from corallivory may temporarily buffer coral energy budgets by not redirecting energetic resources to wound healing, and may therefore enable compensatory nutrient acquisition. However, colonies that had previously been heavily grazed were also more susceptible to bleaching, which is likely to increase mortality risk. Thus, short-term respite from corallivory during bleaching may not be sufficient to functionally rescue corals during prolonged bleaching. Such pairwise interactions and behavioural shifts in response to disturbance may appear small scale and short term, but have the potential to fundamentally alter ecological outcomes, especially in already-degraded ecosystems that are vulnerable and sensitive to change.
The organization of double-stranded RNA in the chikungunya virus replication organelle
Authors: Laurent Timothée , Carlson Lars-Anders
Published: December 2022

Alphaviruses are mosquito-borne, positive-sense single-stranded RNA viruses. Amongst the alphaviruses, chikungunya virus is notable as a large source of human illness, especially in tropical and subtropical regions. When they invade a cell, alphaviruses generate dedicated organelles for viral genome replication, so-called spherules. Spherules form as outward-facing buds at the plasma membrane, and it has recently been shown that the thin membrane neck that connects this membrane bud with the cytoplasm is guarded by a two-megadalton protein complex that contains all the enzymatic functions necessary for RNA replication. The lumen of the spherules contains a single copy of the negative-strand template RNA, present in a duplex with newly synthesized positive-sense RNA. Less is known about the organization of this double-stranded RNA as compared to the protein components of the spherule. Here, we analyzed cryo-electron tomograms of chikungunya virus spherules in terms of the organization of the double-stranded RNA replication intermediate. We find that the double-stranded RNA has a shortened apparent persistence length as compared to unconstrained double-stranded RNA. Around half of the genome is present in either of five conformations identified by subtomogram classification, each representing a relatively straight segment of ~25-32 nm. Finally, the RNA occupies the spherule lumen at a homogeneous density, but has a preferred orientation to be perpendicular to a vector pointing from the membrane neck towards the spherule center. Taken together, this analysis lays another piece of the puzzle of the highly coordinated alphavirus genome replication.
ATM-Mediated Translocation of RanBPM Regulates DNA Damage Response by Stabilizing p21 in Non-Small Cell Lung Cancer Cells
Authors: Deng Tanggang , Xie Lin , Xiao Yugang , Zhang Zhenbin , Peng Yuchong , Yin Linglong , Fu Yongming , Li Xiong
Published: December 2022

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is negatively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We for the first time revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.
pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity
Authors: Seidenthal Marius , Jánosi Barbara , Rosenkranz Nils , Schuh Noah , Elvers Nora , Willoughby Miles , Zhao Xinda , Gottschalk Alexander
Published: December 2022

pH-sensitive fluorescent proteins are widely used to study synaptic vesicle (SV) fusion and recycling. When targeted to the lumen of SVs, fluorescence of these proteins is quenched by the acidic pH. Following SV fusion, they are exposed to extracellular neutral pH, resulting in a fluorescence increase. SV fusion, recycling and acidification can thus be tracked by tagging integral SV proteins with pH-sensitive proteins. Neurotransmission is generally stimulated by electrophysiology, which is not feasible in small, intact animals, thus limiting the approach to cell culture regimes. Previousin vivoapproaches depended on distinct (sensory) stimuli, thus limiting the addressable neuron types. To overcome these limitations, we established an all-optical approach to stimulate and visualize SV fusion and recycling. We combined distinct pH-sensitive fluorescent proteins (inserted into the SV protein synaptogyrin) and light-gated channelrhodopsins (ChRs) for optical stimulation, overcoming optical crosstalk and thus enabling an all-optical approach. We generated two different variants of thepH-sensitiveoptogenetic reporter of vesiclerecycling (pOpsicle) and tested them in cholinergic neurons of intactCaenorhabditis elegansnematodes. First, we combined the red fluorescent protein pHuji with the blue-light gated ChR2(H134R), and second, the green fluorescent pHluorin combined with the novel red-shifted ChR ChrimsonSA. In both cases, fluorescence increases were observed after optical stimulation. Increase and subsequent decline of fluorescence was affected by mutations of proteins involved in SV fusion and endocytosis. These results establish pOpsicle as a non-invasive, all-optical approach to investigate different steps of the SV cycle.
In vivo measurement of the Young’s modulus of the cell wall of single root hairs
Authors: Pereira David , Alline Thomas , Asnacios Atef
Published: December 2022

Root hairs are cells from the root epidermis that grow as long tubular bulges perpendicular to the root. They can grow in a variety of mechanical or chemical environments. Their mechanical properties are mainly due to their stiff cell wall which also constitutes a physical barrier between the cell and its environment. Thus, it is essential to be able to quantify the cell wall mechanical properties and their adaptation to environmental cues. Here, we present a technique we developed to measure the Young’s (elastic) modulus of the root hair cell wall. In essence, using custom-made glass microplates as cantilevers of calibrated stiffness, we are able to measure the force necessary to bend a single living root hair. From these experiments one can determine the stiffness and Young’s modulus of the root hair cell wall.
Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated inT. gondiiinfection-induced cachexia
Authors: Feng Tzu-Yu , Melchor Stephanie J. , Ghumman Haider , Kester Mark , Fox Todd E. , Ewald Sarah E.
Published: December 2022

Cachexia is a life-threatening disease characterized by chronic, inflammatory muscle wasting and systemic metabolic impairment. Despite its high prevalence, there are no efficacious therapies for cachexia. Mice chronically infected with the protozoan parasiteToxoplasma gondiirepresent a novel animal model recapitulating the chronic kinetics of cachexia. To understand how perturbations to metabolic tissue homeostasis influence circulating metabolite availability we used mass spectrometry analysis. Despite the significant reduction in circulating triacylglycerides, non-esterified fatty acids, and glycerol, sphingolipid long-chain bases and a subset of phosphatidylcholines (PCs) were significantly increased in the sera of mice withT. gondiiinfection-induced cachexia. In addition, the TCA cycle intermediates α-ketoglutarate, 2-hydroxyglutarate, succinate, fumarate, and malate were highly depleted in cachectic mouse sera. Sphingolipids and their de novo synthesis precursors PCs are the major components of the mitochondrial membrane and regulate mitochondrial function consistent with a causal relationship in the energy imbalance drivingT. gondii-induced chronic cachexia.
Is intuition better than rationality? The effect of pre-decisional strategy on occupational interest forecasting in Chinese college students
Authors: Lu Di , Jiao Run Kai , Li Fei-Fei , Yin Hang , Lin Xiaoqing
Published: December 2022

Purpose

Previous studies showed that the unconscious-intuitive strategy resulted in a better choice for it is more predictive of actual interest. This benefit may be influenced by occupational engagement, for the dual process of career decisions takes it as a tool for multidevelopment and optimal adjustment. Thus, we replicated (and extended) the study of Motl et al. (2018) through two experiments to identify the role of three pre-decisional strategies and then explore the combined effects of occupational engagement and these strategies. The purpose of this paper is to address these issues.

Design/methodology/approach

The authors replicated (and extended) the study of Motl et al. (2018) through two experiments. First, both studies adopted generalized linear mixed-effects models for statistical analyses to distinguish random and fixed effects. Second, Study 2 used a computer-based process-tracing program called “Mouselab” to explore the effect of the pre-decisional strategy self-generated on participants' interest appraisals over time.

Findings

Study 1 found that engagement helped promote participants' interest experience when decisions as usual and the intuitive strategy did not produce optimal choices. Further, people with more prior knowledge about situations no longer achieved as many benefits from their allocated strategy (i.e. rational strategy) as those with less. Study 2 failed to find adequate advantages of the intuitive strategy. Specifically, people with less search depth (the heuristic-intuitive strategy) were more interested in their choices. Nevertheless, when the strategy was manipulated as variability of search (VS), it only found the promotion of engagement, but it neither found the interaction between engagement and strategy nor did strategy itself.

Originality/value

The present paper provides mixed support for adaptive career decision-making. Career counselors can use occupational engagement levels as a reference for pre-decisional strategy selection and coach clients to adopt a proper decision-making process/method to make interest forecasts.
Application of fluorescence in situ hybridization in distinguishing acral melanoma in situ from acral junctional melanocytic nevus on the volar skin in Japanese patients
Authors: Takai Sayaka , Arai Eiichi , Shojiguchi Naoko , Nakamura Yasuhiro , Momose Shuji , Fukuda Tomoo , Ishizawa Keisuke , Ogata Dai , Tsunemi Yuichiro , Nakamura Koichiro , Tsuchida Tetsuya
Published: December 2022

Four‐colored fluorescence in situ hybridization (FISH) is an ancillary diagnostic tool for melanoma. However, most studies that have investigated the usefulness of FISH primarily focused on advanced melanomas. The aim of the current study was to evaluate the effectiveness of FISH in distinguishing acral melanoma (AM) in situ from benign acral junctional nevus (AJN), two types of lesions that are difficult to differentiate via traditional clinical means. The authors investigated the usefulness of FISH in 91 acral melanocytic lesions, including 50 lesions with diagnostic discrepancies between dermoscopic and pathologic approaches or difficulty diagnosing between AM in situ and AJN, on the volar skin of Japanese patients. The authors classified the lesions based on the diagnosis of dermatologists and pathologists into four groups: (I) lesions with a unanimous diagnosis by dermatologists and pathologists as AM in situ or AJN (n = 41); (II) lesions with a unanimous diagnosis by dermatologists only as AM in situ or AJN (n = 21); (III) lesions with a unanimous diagnosis by pathologists only as AM in situ or AJN (n = 15); and (IV) all other lesions (n = 14). The dermatologists diagnosed the lesions by clinical and dermoscopic photographs alone, while the pathologists diagnosed the lesions by microscopy of hematoxylin and eosin–stained slides alone. In group I (AM in situ [n = 20] and AJN [n = 21]), four‐colored FISH demonstrated 90% sensitivity and 81% specificity in distinguishing AM in situ from AJN. There was a significant correlation between the FISH results and the unanimous diagnoses by pathologists alone (p = 0.03) in group III. However, FISH results were not significantly correlated with the unanimous diagnoses by dermatologists alone (p = 0.33) in group II. In conclusion, the four‐colored FISH probe kit was useful in distinguishing between AM in situ and AJN and may be an ancillary method when pathologists who are not experts of dermatopathology diagnose melanocytic lesions.
Application of novel technologies to reach net‐zero greenhouse gas emissions in the fresh pasteurised milk supply chain: A review
Authors: Grandsir Capucine , Falagán Natalia , Alamar M. Carmen
Published: December 2022

This review assesses the potential of three novel technologies (3‐nitrooxypropanol, ultraviolet C light cold pasteurisation and biochar) to reduce the carbon footprint produced by the fresh milk supply chain at global level. In addition to the adoption of these technologies: (i) new policies should enhance the development and implementation of international standards to optimise the quality and safety of such technologies whilst facilitating their traceability; (ii) dairy firms and technology start‐ups should benefit from worldwide emissions trading systems to limit technology implementation costs; and (iii) consumers could participate in the net‐zero challenge by adopting easy‐to‐apply sustainable practices, thus reducing their milk carbon footprint.
Risk factors and management outcomes in epistaxis: a tertiary centre experience
Authors: Hughes Jed M. , Teh Bing Mei , Hart Cameron J. , Gibbs Harry H. , Aung Ar Kar
Published: December 2022

Background

Risk factors and outcomes associated with severe epistaxis are not well understood. This study explores the associations between epistaxis severity, comorbidities, use of antiplatelets or anticoagulants and management outcomes.

Methods

This is a retrospective cross‐sectional study of all epistaxis cases presenting to the emergency department at a tertiary academic hospital from January 2016 to December 2019. Epistaxis severity was defined as mild (no intervention), moderate (required cautery and/or packing) and severe (clinical instability with reversal products, surgical or radiological intervention). Univariable and multivariable regression analyses were undertaken, with risk factors and management outcomes analysed according to severity.

Results

A total of 543 patients with epistaxis (54.2% male, mean age 74.4 ± 15.7 years) were included in this study, with 14.7% (80) having severe epistaxis. Of these presentations 216 (39.8%) were on antiplatelets, while 207 (38.1%) were on anticoagulants. In univariate analyses, clopidogrel use, hereditary haemorrhagic telangiectasia (HHT), haematological malignancy, bleeding disorders and chronic liver disease (CLD) were associated with moderate to severe epistaxis (P < 0.05), while the use of rivaroxaban was inversely associated severity (P = 0.002). Only HHT, haematological malignancy and CLD remained significant in multivariate models. Cautery as first‐line management was infrequently utilized while anticoagulation was frequently withheld. A longer length of stay (1.1 days vs. 4.3 days; P < 0.001) and higher 2‐week readmission rates (2.2% vs. 12.5%; P < 0.001) were noted with severe epistaxis compared with mild presentations.

Conclusion

Epistaxis severity is associated with certain clinical conditions and poor outcomes. Despite recommended guidelines, variations in first‐line management were evident.
Induction to neonatal resuscitation: A UK‐wide survey on practice
Authors: Hodgson Joshua , Hurley Aoife , Fawke Joe
Published: December 2022

Aim

To assess the perceived quality, and variation in quality, of Neonatal Induction Programmes in preparing medical staff to attend deliveries and deliver neonatal resuscitation if required. To delineate the components of an induction programme and the systems processes that would optimise medical staff training in delivering neonatal resuscitation.

Methods

We conducted a nationwide (United Kingdom [UK]) survey of all junior doctors working within paediatric/neonatal posts as well as the persons responsible for organising their local Neonatal Induction Programme.

Results

We received 237 respondents from diverse roles. Practitioners feel only somewhat effectively prepared to attend deliveries and deliver neonatal resuscitation. More concerningly, they report moderate‐to‐high levels of variation across different centres. Practical training is considered more important than theoretical; and basic topics more useful than advanced. The preferred approach to neonatal resuscitation training is a locally determined programme within a framework of national standards/recommendations.

Conclusion

Practitioners feel that the quality, and particularly variation in quality, of neonatal resuscitation training at induction across the United Kingdom is suboptimal. Staff indicated the utility of a framework of national standards, and indeed this survey has been instrumental in the publication of such standards by the Royal College of Paediatrics and Child Health.
Army ant males lose seasonality at a site on the equator
Authors: Tozetto Leonardo , Forrister Dale L. , Duval Megan , Hays Tobias , Garwood Nancy C. , Castro Ronald Vargas , Lattke John E. , Sendoya Sebastian , Longino John T.
Published: December 2022

Army ants are keystone predators in the tropics and subtropics. During reproduction, males fly between colonies to mate with unmated, wingless queens. The males of most species are attracted to lights, and thus their presence and the timing of reproduction can be monitored using light traps. Previous studies examined the seasonality of army ant male reproduction and its relationship to climate factors at individual sites, but less is known about variation among sites. We examined army ant male flight seasonality at three sites: (1) La Selva Biological Station in Costa Rica, a site with weak temperature seasonality and moderate rainfall and day length seasonality, (2) Yasuní National Park, Ecuador, a site with no temperature or day length seasonality and very weak rainfall seasonality, and (3) the state of Paraná in southern Brazil, a site with very strong temperature, rainfall, and day length seasonality. Army ants showed strong seasonality at the La Selva and Paraná sites, and very weak to no seasonality at the Yasuní site. At La Selva and Paraná, flight times varied among species, but were very predictable from year to year, which suggests day length or temperature as predictable cues rather than rainfall. Lack of seasonal cues near the equator may be a challenge for army ant species that need to synchronize colony reproduction, and thus may have conservation implications for minimum population sizes needed to ensure stable populations.

Abstract in Spanish is available with online material.