bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in cardiogenic shock: characteristics and prognosis
Authors: Parraga Gutierrez R , Ferrera C , Jimenez B , Cerrillo L , Noriega F J , Fernandez-Jimenez R , Nogales T , Nombela L , Fernandez-Ortiz A , Viana-Tejedor A
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): Hospital Clinico San Carlos.

Background

Cardiogenic shock (CS) is a life-threatening condition caused by severe heart dysfunction. While significant advances have been made in the management and treatment of cardiogenic shock, there is growing recognition of the importance of considering gender-specific differences in the presentation and outcomes of this condition. Recent research highlights gender-related variations in how the condition is presented, managed, and its outcomes. Understanding these differences is crucial for tailored and effective treatment. Our goal is to identify potential gender differences in terms of the characteristics and prognosis of CS.

Methods

From 2013 to 2023, 142 consecutive patients diagnosed with CS in and admitted to an Acute Cardiac Care Unit in a tertiary care hospital were recruited. Demographic, clinical, and analytical variables were retrospectively collected. Patient were followed-up to November-2023 and clinical events were also recorded. For purposes of analysis, patients were classified in woman (N=95) and men (N=47). Success, in terms of IABP use, was defined as patient’s survival to the index event. Failure of IABP was defined as in-hospital death. A multivariate logistic regression analysis was performed to identify potential predictors of success. A descriptive analysis of clinical, analytical, and demographic parameters was performed in both groups, followed by a survival curve analysis to assess differences in prognosis between both sexes.

Results

Mean age was 67.3±12.2 years and 67.0% were females. There were no significant differences in cardiovascular risk factor and comorbidities between groups: hypertension (61.2% vs 38.8%, p 0.077), diabetes (65.9% vs 34.1%, p 0.866), chronic kidney disease (75% vs 25%, p 0.465), previous stroke (61.5% vs 38.5%, p 0.666) in woman vs men group respectively. STEMI was the most frequent cause of CS requiring an IABP in men (33.7%) but NSTEMI was in women (67.7%). Regarding the CS classification, both groups had a similar distribution of the severity and complexity of the shock (Figure 1). There were also no differences in hemodynamic parameters, analytical results, complete revascularization, and left ventricular ejection fraction (LVEF) between men and women (Figure 1). There were also no differences in hemodynamic parameters, analytical results, complete revascularization, and left ventricular ejection fraction (LVEF) between men and women (Figure 1). The complications, mortality (Figure 2), and long-term mortality were also similar in both groups.

Conclusions

In our observational study, there were no differences between genders in terms of characteristics, shock complexity, and prognosis.
Lipid profile in patients with acute coronary syndrome undergoing cardiac rehabilitation. Characteristics and effects of the program. The importance of small and dense LDL (LDLpd)
Authors: Lucas Garcia M , Paez Munoz R , Padilla Rodriguez G , Pelaz Sanchez M , Hidalgo Urbano R J , Martinez Quesada M M
Published: May 2024

Funding Acknowledgements

None.

Introduction

Recently it has been shown that not all lipid risk for atherosclerosis is due to LDL cholesterol. Both remnant particles and small and dense LDL (LDLpd) have been associated with a higer risk of the first cardiovascular events and recurrences.

Methods

We analyzed the lipid profile at admission of patients undergoing a cardiac rehabilitation (CR) program in a tertiary referral hospital, in association with other analytical parameters, clinical characteristics and outcomes of CR in these patients. We collected data from patients who completed the programme between January 2022 and March 2023 on admission and at the end of the programme. Clinical and anthropometric data and the results of the stress tests were collected. We defined a TG/HDL ratio greater than 2 as being associated with the presence of small and dense LDL.

Results

170 patients who had complete analytical profiles at hospital admission were included, 80.5% were male with a mean age 57.9+/-9 years, 92.5% were referred after an acute coronary syndrome, 25.6% were diabetic, 56.6% were smokers and 37.7% were obese.

LDLpd at hospital admission was present in 73.4% of the patients. Male gender was more likely (86.3 vs. 68.9%, p=0.01, p=0.01) as well as being obese (83.9 vs 68.8%, p=0.04). No differences were found in terms of age, presence of DM, smoking or peripheral arterial disease. Nor did functional capacity or baseline quality of life. Less improvement was found in the SF 36 questionnaire (-6 vs +20, p=0.011), but similar in ergometry.

Basal lipid profile was associated with higher total Ch values (173 vs 149, p=0.002), Ch LDL (104 vs 79, p=0.000), remnants (32 vs 14, p=0.000). As for baseline LDL, 51.6% with LDLpd,had it high LDL Ch>100 mg/dl, compared to 22.2% of those without LDLpd (P=0.002).

As for the profile at discharge, we found that 63.5% still had LDLpd at discharge from the CR program ( vs. 15.9% of those without elevated LDLpd, P=0.000) and 22% had elevated remnants (P=0.002).

After CR, these patients still had higher TG values (128 vs 81, p=0.000), lower HDL-C (44 vs 56, p=0.003) and higher remnants (24 vs 17, p=0.000) despite the fact that a greater decrease in remnants and TG/HDL in this group.

Conclusions

More than one third of the patients who undergo a Cardiac Rehabilitation Program in our centre have LDLpd. Initially, male and obese patients have higher LDL and remnants. A weaker effect of the CR program in improving the lipidic profile has been observed in those patients. Consideration should be given to enhance lipid-lowering and intensive weight-loss treatments to decrease cardiovascular risk in this population.
Evaluation of deep learning estimation of whole heart anatomy from automated cardiovascular magnetic resonance short- and long-axis analyses in UK Biobank
Authors: Muffoletto Marica , Xu Hao , Burns Richard , Suinesiaputra Avan , Nasopoulou Anastasia , Kunze Karl P , Neji Radhouene , Petersen Steffen E , Niederer Steven A , Rueckert Daniel , Young Alistair A
Published: May 2024

Aims

Standard methods of heart chamber volume estimation in cardiovascular magnetic resonance (CMR) typically utilize simple geometric formulae based on a limited number of slices. We aimed to evaluate whether an automated deep learning neural network prediction of 3D anatomy of all four chambers would show stronger associations with cardiovascular risk factors and disease than standard volume estimation methods in the UK Biobank.

Methods and results

A deep learning network was adapted to predict 3D segmentations of left and right ventricles (LV, RV) and atria (LA, RA) at ∼1 mm isotropic resolution from CMR short- and long-axis 2D segmentations obtained from a fully automated machine learning pipeline in 4723 individuals with cardiovascular disease (CVD) and 5733 without in the UK Biobank. Relationships between volumes at end-diastole (ED) and end-systole (ES) and risk/disease factors were quantified using univariate, multivariate, and logistic regression analyses. Strength of association between deep learning volumes and standard volumes was compared using the area under the receiving operator characteristic curve (AUC). Univariate and multivariate associations between deep learning volumes and most risk and disease factors were stronger than for standard volumes (higher R2 and more significant P-values), particularly for sex, age, and body mass index. AUCs for all logistic regressions were higher for deep learning volumes than standard volumes (P < 0.001 for all four chambers at ED and ES).

Conclusion

Neural network reconstructions of whole heart volumes had significantly stronger associations with CVD and risk factors than standard volume estimation methods in an automatic processing pipeline.
Rescue retrograde coronary venous ethanol ablation of ventricular tachycardia storm in a patient with Lamin A/C cardiomyopathy: a case report
Authors: De Smet Maarten A J , Tavernier Rene , Duytschaever Mattias , Knecht Sébastien , le Polain de Waroux Jean-Benoît
Published: May 2024

Background

Left ventricular (LV) summit arrhythmias account for up to 14% of LV arrhythmias. The ablation of LV summit arrhythmias is challenging, as testified by the fact that radiofrequency (RF) catheter ablation failure is frequent. Retrograde coronary venous ethanol infusion has been proposed as an alternative approach for the ablation of LV summit arrhythmias.

Case summary

A 47-year-old man with Lamin A/C cardiomyopathy was referred for the ablation of a pleiomorphic ventricular tachycardia (VT) storm, with dominant morphology compatible with LV summit origin. He first received a combined endo- and epicardial RF ablation with the elimination of three clinically relevant VTs. However, the dominant VT could not be ablated due to the proximity of the coronary vasculature and phrenic nerve and remained inducible. Accordingly, an urgent rescue redo procedure consisting of retrograde coronary venous ethanol ablation was performed. Based on the best pace-match and precocity, the first septal, retro-pulmonary branch and the first diagonal branch were infused with ethanol with immediate cessation of the tachycardia and non-inducibility. Anti-arrhythmic drugs were withdrawn, while guideline-directed medical therapy for heart failure was continued. No complications occurred. After 3 months, the patient remained free from any arrythmias.

Discussion

Ablation of LV summit arrythmias is challenging, especially in the context of an electrical storm or in patients with structural heart disease. In such a situation, rescue ablation with retrograde coronary venous ethanol infusion represents an attractive alternative ablation modality.
Genomic resources of aquatic Lepidoptera, Elophila obliteralis and Hyposmocoma kahamanoa, reveal similarities with Trichoptera in amino acid composition of major silk genes
Authors: Heckenhauer Jacqueline , Plotkin David , Martinez Jose I , Bethin Jacob , Pauls Steffen U , Frandsen Paul B , Kawahara Akito Y
Published: May 2024

While most species of butterflies and moths (Lepidoptera) have entirely terrestrial life histories, ∼0.5% of the described species are known to have an aquatic larval stage. Larvae of aquatic Lepidoptera are similar to caddisflies (Trichoptera) in that they use silk to anchor themselves to underwater substrates or to build protective cases. However, the physical properties and genetic elements of silks in aquatic Lepidoptera remain unstudied, as most research on lepidopteran silk has focused on the commercially important silkworm, Bombyx mori. Here, we provide high-quality PacBio HiFi genome assemblies of 2 distantly-related aquatic Lepidoptera species [Elophila obliteralis (Pyraloidea: Crambidae) and Hyposmocoma kahamanoa (Gelechioidea: Cosmopterigidae)]. As a step toward understanding the evolution of underwater silk in aquatic Lepidoptera, we used the genome assemblies and compared them to published genetic data of aquatic and terrestrial Lepidoptera. Sequences of the primary silk protein, h-fibroin, in aquatic moths have conserved termini and share a basic motif structure with terrestrial Lepidoptera. However, these sequences were similar to aquatic Trichoptera in that the percentage of positively and negatively charged amino acids was much higher than in terrestrial Lepidoptera, indicating a possible adaptation of silks to aquatic environments.
FlourishCare Model of Integrated Care: The Validation of the Flourish Index—Revised
Authors: Faul Anna C , D’Ambrosio Joseph G , Cotton Samantha G , Dobson Molly M , Furman Christian D , Gordon Barbara A , Linzy Katherine E , Yankeelov Pamela A
Published: May 2024

Background and Objectives

This study validates the Flourish Index–Revised (FI-R), a tool evaluating integrated healthcare models. The original Flourish Index (FI) was developed in 2018 and has been refined to align with the FlourishCare (FC) Model (Model) for geriatric primary care.

Research Design and Methods

The Model provides integrated biopsychosocial healthcare to older adults. The FI-R uses 25 quality-of-care indicators and 7 contextual community indicators. The FI-R was validated with Categorial Principal Components Analysis (CATPCA) using a sample of 949 patients 50+ who were mostly female (73%), non-Hispanic White (70%), living in urban areas (90%), and married (29%), single (22%), or divorced (19%). The mean age was 73.46 (standard deviation [SD] = 10.86) and mean years of education was 14.30 (SD = 2.14).

Results

CATPCA showed a 4-dimensional structure of biological, psychological, and 2 social determinants of health (SDOH) subdomains: health behaviors and community. Final selection of indicators was based on total variance accounted for >0.30, absolute values of item loadings >0.45, and not having cross-loadings >0.45 on 2 factors. Internal consistency (Cronbach’s alpha) for the determinants were biological = 0.75, psychological = 0.76, SDOH:community = 0.70, SDOH:health behaviors = 0.50, and total FI-R = 0.95. Sensitivity to change was shown for the total FI-R, psychological determinants, and SDOH:health behaviors, but not for biological determinants.

Discussion and Implications

The validation of the FI-R shows promise for its usability to evaluate integrated healthcare models using existing measures in electronic health systems. More work is needed to improve the incorporation of SDOH:sociodemographics into the FI-R.
The expression of mantle seismic anisotropy in the global seismic wavefield
Authors: Wolf Jonathan , Long Maureen D , Frost Daniel A , Nissen-Meyer Tarje
Published: May 2024

The dependence of seismic wave speeds on propagation or polarization direction, called seismic anisotropy, is a relatively direct indicator of mantle deformation and flow. Mantle seismic anisotropy is often inferred from measurements of shear-wave splitting. A number of standard techniques to measure shear-wave splitting have been applied globally; for example, *KS splitting is often used to measure upper mantle anisotropy. In order to obtain robust constraints on anisotropic geometry, it is necessary to sample seismic anisotropy from different directions, ideally using different seismic phases with different incidence angles. However, many standard analysis techniques can only be applied for certain epicentral distances and source–receiver geometries. To search for new ways to detect mantle anisotropy, instead of focusing on the sensitivity of individual phases, we investigate the wavefield as a whole: we apply a ‘wavefield differencing’ approach to (systematically) understand what parts of the seismic wavefield are most affected by splitting due to seismic anisotropy in the mantle. We analyze differences between synthetic global wavefields calculated for isotropic and anisotropic input models, incorporating seismic anisotropy at different depths. Our results confirm that the seismic phases that are commonly used in splitting techniques are indeed strongly influenced by mantle anisotropy. However, we also identify less commonly used phases whose waveforms reflect the effects of anisotropy. For example, PS is strongly affected by splitting due to seismic anisotropy in the upper mantle. We show that PS can be used to fill in gaps in global coverage in shear-wave splitting data sets (for example, beneath ocean basins). We find that PcS is also a promising phase, and present a proof-of-concept example of PcS splitting analysis across the contiguous United States using an array processing approach. Because PcS is recorded at much shorter distances than *KS phases, PcS splitting can therefore fill in gaps in backazimuthal coverage. Our wavefield differencing results further hint at additional potential novel methods to detect and characterize splitting due to mantle seismic anisotropy.
The Duty of Arbitrators to Raise Suspected Corruption or to Investigate Poorly Particularized Allegations of Corruption
Authors: Trein Margrit
Published: May 2024

A question that continues to trouble and divide arbitral tribunals concerns the way in which they should or must conduct themselves in circumstances where they either suspect that the dispute before them is tainted by corruption, but neither party has raised allegations of corruption, or where a party simply asserts corruption, but does not attempt to particularize its allegations properly, let alone seek to substantiate them. These issues are not purely academic, they do arise in practice. The approaches that arbitral tribunals take in such situations vary greatly, with passive approaches eroding trust in the integrity and legitimacy of arbitration. This article seeks to contribute to the existing literature by providing an analytical framework by reference to applicable laws and rules to ascertain in what circumstances the duty of arbitral tribunals to raise or investigate their suspicions of corruption is triggered and explores the contours and content of the duty.
Redox Biomarkers in Asymptomatic Latent Human Tuberculosis: A Comparison With Active Disease
Authors: Petrillo Sara , Di Prinzio Reparata Rosa , Quatrana Andrea , Santoro Annapaola , Torda Caterina , Mastroianni Claudio Maria , Raponi Massimiliano , Zaffina Salvatore , Piemonte Fiorella
Published: May 2024

Background

Latent tuberculosis infection is an asymptomatic infection caused by Mycobacterium tuberculosis. Previous studies have shown a host-protective role for heme oxygenase-1 (HO-1) during M. tuberculosis infection and an important involvement of glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggesting a crucial role for glutathione (GSH) in the granulomatous response to M. tuberculosis infection, with altered GSH levels associated with decreased host resistance. The aim of this study was to provide additional tools for discriminating between the pathologic tuberculosis state and asymptomatic infection.

Methods

We analyzed the expression of genes coding for HO-1 and GPX4 enzymes in blood of subjects with latent tuberculosis infection, active tuberculosis, and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with evaluation of GCL coding gene expression, responsible for GSH de novo synthesis.

Results

Our findings highlight a shift in glutathione homeostasis towards a more reducing conditions in latent tuberculosis infection, and a different modulation of GSH-dependent genes and HO-1 expression compared to active tuberculosis.

Conclusions

This study provides useful tools to understand the redox background that directs the infection toward the asymptomatic or active disease.
Gender Washing War: Arms Manufacturers and the Hijacking of #InternationalWomensDay
Authors: Jester Natalie , Walters Rosie
Published: May 2024

If asked what “arms manufacturer” first brings to mind, few people would likely answer “women’s rights.” And yet, each International Women’s Day (IWD), leading global arms manufacturers present themselves as working to help bring about gender equality. “Gender washing” refers to corporate social responsibility communications aimed at presenting a corporation as empowering to women and girls, even while their own products, supply chains, or employment practices harm them. In this article, we show how arms manufacturers use social media communications about IWD to gender wash their images, positioning themselves as progressive and caring. Bringing into conversation feminist work in Security Studies and International Political Economy, we identify new varieties of gender washing specific to war and martial violence: client military and government partnerships, and constructive silence. We also expand the global hierarchy of publics targeted by gender washing communications, reflecting the fact that unlike other transnational corporations, arms manufacturers are not concerned with garnering “brand loyalty” amongst the general public. Rather, they communicate both to and with Global North governments and militaries. Thus, what is at stake in these representations, we argue, is not simply the reputation of the individual corporations concerned, but a broader process of gender washing war.
Automating literature screening and curation with applications to computational neuroscience
Authors: Ji Ziqing , Guo Siyan , Qiao Yujie , McDougal Robert A
Published: May 2024

Objective

ModelDB (https://modeldb.science) is a discovery platform for computational neuroscience, containing over 1850 published model codes with standardized metadata. These codes were mainly supplied from unsolicited model author submissions, but this approach is inherently limited. For example, we estimate we have captured only around one-third of NEURON models, the most common type of models in ModelDB. To more completely characterize the state of computational neuroscience modeling work, we aim to identify works containing results derived from computational neuroscience approaches and their standardized associated metadata (eg, cell types, research topics).

Materials and Methods

Known computational neuroscience work from ModelDB and identified neuroscience work queried from PubMed were included in our study. After pre-screening with SPECTER2 (a free document embedding method), GPT-3.5, and GPT-4 were used to identify likely computational neuroscience work and relevant metadata.

Results

SPECTER2, GPT-4, and GPT-3.5 demonstrated varied but high abilities in identification of computational neuroscience work. GPT-4 achieved 96.9% accuracy and GPT-3.5 improved from 54.2% to 85.5% through instruction-tuning and Chain of Thought. GPT-4 also showed high potential in identifying relevant metadata annotations.

Discussion

Accuracy in identification and extraction might further be improved by dealing with ambiguity of what are computational elements, including more information from papers (eg, Methods section), improving prompts, etc.

Conclusion

Natural language processing and large language model techniques can be added to ModelDB to facilitate further model discovery, and will contribute to a more standardized and comprehensive framework for establishing domain-specific resources.
The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review
Authors: Gilbert Alexandra , Samuel Robert , Cagney Daniel , Sebag-Montefiore David , Brown Julia , Brown Sarah R
Published: May 2024

The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex setup pathways (including quality assurance, user training, and integrating multiple modalities of treatment) may hinder clinical advances.

We carried out a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, reviewing the findings using a landscape analysis. Results were summarized descriptively, reporting on trial characteristics highlighting the benefits, limitations, and challenges of developing and implementing radiotherapy master protocols, with three case studies selected to explore these issues in more detail.

Twelve studies were suitable for inclusion (4 platform trials, 3 umbrella trials, and 5 basket trials), evaluating a mix of solid tumor sites in both curative and palliative settings. The interventions were categorized into 1) novel agent and radiotherapy combinations; 2) radiotherapy dose personalization; and 3) device evaluation, with a case study provided for each intervention. Benefits of master protocol trials for radiotherapy intervention include protocol efficiency for implementation of novel radiotherapy techniques; accelerating the evaluation of novel agent drug and radiotherapy combinations; and more efficient translational research opportunities, leading to cost savings and research efficiency to improve patient outcomes.

Master protocols offer an innovative platform under which multiple clinical questions can be addressed within a single trial. Due to the complexity of radiotherapy trial setup, cost and research efficiency savings may be more apparent than in systemic treatment trials. Use of this research approach may be the change needed to push forward oncological innovation within radiation oncology.
Personal genital satisfaction is associated with differences in perception of male and female sexual anatomy and function
Authors: Choi Una E , Nicholson Ryan C , Grutman Aurora J , Cohen Andrew J
Published: May 2024

Background

Prior studies primarily of men correlated low personal genital satisfaction (PGS) with decreased sexual activity; however, the association between PGS and genital anatomy perceptions is unknown, and there is a paucity of studies examining women.

Aim

We assessed the relationship between genital satisfaction, survey respondent sexual activity, and perceptions of anatomy and function.

Methods

A 54-item REDCap survey was distributed to any-gendered volunteers ≥18 years of age through ResearchMatch from January to March 2023. Responses were split into (1) high PGS and (2) low PGS. Analysis was performed using chi-square tests on survey responses and a Mann Whitney U test on median satisfaction level.

Outcomes

Outcomes were genital anatomy perceptions, sexual activity, and respondents’ PGS.

Results

Of the 649 respondents who started the survey, 560 (86.3%) completed it. Median PGS was 7 of 10, forming subgroups of high (≥7 of 10) satisfaction (n = 317 of 560 [56.6%]) and low (<7 of 10) satisfaction (n = 243 of 560 [43.4%]). The mean age was 45.8 ± 16.8 years, and demographics were notable for 72.1% women (n = 404 of 560), 83.2% White (n = 466 of 560), 47.9% married (n = 268 of 560), and 75.5% bachelor’s degree holders (n = 423 of 560). Comparing high- and low-PGS groups, more low-PGS respondents felt normal flaccid penis length to be <2 inches (11.1% vs 5.1%; P = .008). High-PGS respondents more often responded that it is normal for women to have orgasms over half the time (20.8% vs 13.2%; P = .0002) or to identify as being sexually active (81.1% vs 71.6%; P = .008). Women were more likely than men to report larger normal testicle sizes as 60.1 to 90 mL (24.5% vs 10.3%; P < .0001), whereas more men felt that normal testicle size was 7 to 15 mL (26.3% vs 11.4%; P < .0001). Orgasm length perceptions also differed: more women felt female orgasm length was 2.6 to 5 seconds (36.6% vs 16.7%; P < .0001), and more men believed female orgasms to be longer, at 7.6 to 10 seconds (29.5% vs 17.3%; P = .002), 10.1 to 12.5 seconds (11.5% vs 5.2%; P = .0008), and >12.5 seconds (12.2% vs 5.7%; P = .009). Respondents’ views on their genitalia differed by gender, with women more likely to feel that their genitals are normal compared with men (89.4% vs 75.0%; P < .0001).

Clinical Implications

PGS may be a useful screening tool given its association with sexual activity.

Strengths and Limitations

Our large-scale survey assesses public perceptions of genital anatomy and function. Limitations include a lack of gender nonbinary perceptions.

Conclusion

Gender and PGS interact with perceptions of male anatomy and female sexual activity, and the frequency of sexual activity was higher among high-PGS respondents; however, the direction of these interactions remains unclear and requires future causal analysis.
The density of virialized clusters as a probe of dark energy
Authors: Paraskevas Evangelos A , Perivolaropoulos Leandros
Published: May 2024

We use the spherical collapse model to demonstrate that the observable average density of virialized clusters depends on the properties of dark energy along with the properties of gravity on cluster scales and can therefore be used as a probe of these properties. As an application of this approach, we derive the predicted virialized densities and radii of cluster mass structures for a wide range of values of the cosmological constant (including negative values) as a function of the turnaround redshift. For the value of ΩΛ,0 = −0.7 (with Ωm,0 = 0.3), we find an amplification of the density of virialized clusters which can be as large as 80 per cent compared to Planck18/lambda Cold Dark Matter (ΛCDM) for a turnaround redshift zmax ≳ 2. Such an amplification may lead to more efficient early galaxy formation in this class of models, in accordance with the recent findings of JWST, which may be partially pertinent to the Λ sign switching models (ΛsCDM), which have been suggested as potential solutions to the observed Hubble and S8 discrepancies.
Estimating major merger rates and spin parameters ab initio via the clustering of critical events
Authors: Cadiou Corentin , Pichon-Pharabod Eric , Pichon Christophe , Pogosyan Dmitri
Published: May 2024

We build a model to predict from first principles the properties of major mergers. We predict these from the coalescence of peaks and saddle points in the vicinity of a given larger peak, as one increases the smoothing scale in the initial linear density field as a proxy for cosmic time. To refine our results, we also ensure, using a suite of ∼400 power-law Gaussian random fields smoothed at ∼30 different scales, that the relevant peaks and saddles are topologically connected: they should belong to a persistent pair before coalescence. Our model allows us to (a) compute the probability distribution function of the satellite-merger separation in Lagrangian space: they peak at three times the smoothing scale; (b) predict the distribution of the number of mergers as a function of peak rarity: haloes typically undergo two major mergers (>1:10) per decade of mass growth; (c) recover that the typical spin brought by mergers: it is of the order of a few tens of per cent.
EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells
Authors: García-Rodríguez Néstor , Domínguez-García Iria , Domínguez-Pérez María del Carmen , Huertas Pablo
Published: May 2024

DNA replication faces challenges from DNA lesions originated from endogenous or exogenous sources of stress, leading to the accumulation of single-stranded DNA (ssDNA) that triggers the activation of the ATR checkpoint response. To complete genome replication in the presence of damaged DNA, cells employ DNA damage tolerance mechanisms that operate not only at stalled replication forks but also at ssDNA gaps originated by repriming of DNA synthesis downstream of lesions. Here, we demonstrate that human cells accumulate post-replicative ssDNA gaps following replicative stress induction. These gaps, initiated by PrimPol repriming and expanded by the long-range resection factors EXO1 and DNA2, constitute the principal origin of the ssDNA signal responsible for ATR activation upon replication stress, in contrast to stalled forks. Strikingly, the loss of EXO1 or DNA2 results in synthetic lethality when combined with BRCA1 deficiency, but not BRCA2. This phenomenon aligns with the observation that BRCA1 alone contributes to the expansion of ssDNA gaps. Remarkably, BRCA1-deficient cells become addicted to the overexpression of EXO1, DNA2 or BLM. This dependence on long-range resection unveils a new vulnerability of BRCA1-mutant tumors, shedding light on potential therapeutic targets for these cancers.
Genome-wide analysis of mRNA decay in Arabidopsis shoot and root reveals the importance of co-translational mRNA decay in the general mRNA turnover
Authors: Carpentier Marie-Christine , Receveur Anne-Elodie , Boubegtitene Alexandre , Cadoudal Adrien , Bousquet-Antonelli Cécile , Merret Rémy
Published: May 2024

Until recently, the general 5′-3′ mRNA decay was placed in the cytosol after the mRNA was released from ribosomes. However, the discovery of an additional 5′ to 3′ pathway, the Co-Translational mRNA Decay (CTRD), changed this paradigm. Up to date, defining the real contribution of CTRD in the general mRNA turnover has been hardly possible as the enzyme involved in this pathway is also involved in cytosolic decay. Here we overcame this obstacle and created an Arabidopsis line specifically impaired for CTRD called XRN4ΔCTRD. Through a genome-wide analysis of mRNA decay rate in shoot and root, we tested the importance of CTRD in mRNA turnover. First, we observed that mRNAs tend to be more stable in root than in shoot. Next, using XRN4ΔCTRD line, we demonstrated that CTRD is a major determinant in mRNA turnover. In shoot, the absence of CTRD leads to the stabilization of thousands of transcripts while in root its absence is highly compensated resulting in faster decay rates. We demonstrated that this faster decay rate is partially due to the XRN4-dependent cytosolic decay. Finally, we correlated this organ-specific effect with XRN4ΔCTRD line phenotypes revealing a crucial role of CTRD in mRNA homeostasis and proper organ development.
Cerebral clues: serum neurofilament light chain (sNfL) as a novel biomarker for immune check point inhibitor (ICI) mediated seronegative encephalitis
Authors: Zahid Anza , Tummala Sudhakar
Published: May 2024

Immune checkpoint inhibitor (ICI) mediated encephalitides are increasingly being recognized in the literature, but atypical cases may be missed or misdiagnosed. Recent efforts are directed to identify biomarkers to help elucidate early diagnosis and treatment. Herein, we describe two cases of antibody negative ICI-mediated encephalitis with elevated serum Neurofilament light chain (sNfL) levels. Practical Implication: Baseline and longitudinal measurements of serum neurofilament light chains can help determine treatment strategies and prognosis in patients with suspected immune checkpoint inhibitor encephalitis.
Depletion of squalene epoxidase in synergy with glutathione peroxidase 4 inhibitor RSL3 overcomes oxidative stress resistance in lung squamous cell carcinoma
Authors: Li Guo , Chen Lu , Bai Hua , Zhang Li , Wang Jie , Li Weimin
Published: May 2024

Background

Lung squamous cell carcinoma (LUSC) lacks effective targeted therapies and has a poor prognosis. Disruption of squalene epoxidase (SQLE) has been implicated in metabolic disorders and cancer. However, the role of SQLE as a monooxygenase involved in oxidative stress remains unclear.

Methods

We analyzed the expression and prognosis of lung adenocarcinoma (LUAD) and LUSC samples from GEO and TCGA databases. The proliferative activity of the tumors after intervention of SQLE was verified by cell and animal experiments. JC-1 assay, flow cytometry, and Western blot were used to show changes in apoptosis after intervention of SQLE. Flow cytometry and fluorescence assay of ROS levels were used to indicate oxidative stress status.

Results

We investigated the unique role of SQLE expression in the diagnosis and prognosis prediction of LUSC. Knockdown of SQLE or treatment with the SQLE inhibitor terbinafine can suppress the proliferation of LUSC cells by inducing apoptosis and reactive oxygen species accumulation. However, depletion of SQLE also results in the impairment of lipid peroxidation and ferroptosis resistance such as upregulation of glutathione peroxidase 4. Therefore, prevention of SQLE in synergy with glutathione peroxidase 4 inhibitor RSL3 effectively mitigates the proliferation and growth of LUSC.

Conclusion

Our study indicates that the low expression of SQLE employs adaptive survival through regulating the balance of apoptosis and ferroptosis resistance. In future, the combinational therapy of targeting SQLE and ferroptosis could be a promising approach in treating LUSC.
Substantial unrealised global biodiversity of continental microcrustaceans
Authors: Macêdo Rafael L , Toutain Mathieu , Reid Janet , Soto Ismael , Haubrock Phillip J , Cuthbert Ross N , Rocha Odete
Published: May 2024

Freshwater ecosystems provide essential services for human well-being, with their conservation success reliant on the precise quantification of biodiversity. Diplostraca (= Cladocera) and Copepoda are diverse groups of microcrustaceans in aquatic ecosystems, important for a multitude of these services. We examined biodiversity trends of these groups, utilizing a comprehensive dataset, approximately 2341 studies, spanning from the early 19th Century to the present day, aiming at predicting the total number of microcrustacean species that will have been described by 2100. Descriptions increased until the 1900s, surged, and then declined after 1975. The predictive models indicate that by the year 2100, an additional 16–68% of cladoceran species and 37–126% of copepod species are likely to be identified, representing a significant portion of currently unrealised biodiversity. Eighteen prolific authors contributed to a quarter of these descriptions, with the rest spread among numerous authorities. Based on our extrapolation, the total number of microcrustacean species could potentially exceed 6114 by 2050 and 9046 by 2100, notwithstanding extinctions. These findings, which point to a significant amount of unrealised biodiversity, underscore the need to refine biodiversity estimates beyond conventional expert opinion. Such accuracy is crucial for addressing the underappreciated scale of the current biodiversity crisis.
UVC (254 nm) and Far UVC (222 nm) Irradiation Affects In Vitro Growth of Colletotrichum sp. Isolates and Their Infection of Detached Strawberry Leaves
Authors: Smith Barbara J. , Sampson Blair J. , Copes Warren E. , Takeda Fumiomi , Janisiewicz Wojciech J. , Stafne Eric T. , Sakhanokho Hamidou F. , Carroll Jennifer B.
Published: May 2024

Conventional ultraviolet C at 254 nm (UVC) and Far UVC at 222 nm (Far UVC) were evaluated as alternatives to fungicides for disease control. Conidia of 13 isolates of strawberry anthracnose pathogens (five Colletotrichum species in two complexes: C. acutatum and C. gloeosporioides) were uniformly dispersed onto agar and irradiated with UVC and Far UVC doses ranging from 52 to 1,248 J·m−2. After 48 h of incubation, a UVC dose of 1,248 J·m−2 and Far UVC doses from 234 to 935 J·m−2 reduced Colletotrichum colony counts to <10 colonies/Petri dish. Cultures exposed to UVC light followed by 4 h of darkness had lower colony counts than cultures incubated under continuous light. This dark incubation period was not required for Far UVC to obtain optimal lethality, indicating Far UVC irradiation can be applied during the day or night and achieve similar fungal lethality. Inoculation of detached leaves of three anthracnose-susceptible strawberry cultivars with conidial suspensions of Colletotrichum spp. revealed that UV irradiation can affect development of anthracnose symptoms. Leaves receiving UVC doses of 312 and 624 J·m−2 or a Far UVC dose of 467 J·m−2 reduced anthracnose infection with little or no plant injury. A UVC dose of 1,248 J·m−2 and Far UVC doses ≥ 467 J·m−2 inflicted varying degrees of plant injury. Disease control intended to reduce the number of fungicidal applications could be developed with moderate doses of UVC and Far UVC irradiation while slowing the evolution of pesticide-resistant strains.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Host and Shelter Plants for the Beet Leafhopper, Which Vectors Curly Top Viruses and Phytoplasmas in Southern Idaho
Authors: Strausbaugh Carl A. , Wenninger Erik J. , Jackson Laurie K. , Vincill Eric
Published: May 2024

Weeds and crop plants not only serve as reproductive hosts and transitory or shelter plants for the beet leafhopper (BLH; Circulifer tenellus) but also as sources of plant pathogens that can then be vectored by the BLH. Thus, the plants that the BLHs are feeding on and infecting are of interest and may be changing over time. Therefore, BLH samples from a recent survey were investigated through DNA barcoding via the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit ( rbcL) and maturase K ( matK) chloroplast gene regions to determine what the BLHs had been feeding on prior to capture on yellow sticky cards in southern Idaho during 2020 and 2021. In June of both years, the first generation of BLHs predominately fed on Pinus spp. (59 to 76% of samples), which were likely in mountainous areas, and dispersed approximately 48 to 80 km to crop and sagebrush steppe locations. During July to September, the BLHs predominantly fed on Salsola spp. (Russian thistle; 61 to 66% of samples) and Bassia scoparia (kochia; 15% of samples). In both years, the BLHs that fed on pine had the highest percentage (55 and 75%, respectively) of samples with beet curly top virus based on primers that can detect both the Worland and Colorado strains. In both years, BLHs that had fed on Russian thistle and alfalfa had the highest percentage of samples with Spinach curly top Arizona virus. These data will be utilized in the development of future curly top management plans.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Whole-Genome Sequence Resources for Pseudomonas amygdali pv. sesami and Xanthomonas arboricola Isolated from Sesame (Sesamum indicum) in North Carolina in 2022
Authors: D'Amico-Willman Katherine M. , Montalban Kimberly M. , Joglekar Prasanna , Duin Izabela Moura , Ritchie David F. , Fagen Jennie , Huerta Alejandra I.
Published: May 2024

Sesame ( Sesamum indicum) is a specialty crop with increasing interest as an alternative, rotational crop for U.S. agricultural systems. This crop is susceptible to several pathogens, including Pseudomonas and Xanthomonas species. Two bacterial isolates were recently cultured from sesame in North Carolina symptomatic of bacterial spot and identified as Pseudomonas amygdali pv. sesami (Pas) and Xanthomonas sp. These isolates were used for hybrid whole-genome sequencing and assembly using Illumina and PacBio to develop robust genomic resources for these disease-causing strains. The results provide the most complete Pas genome available and placed the Xanthomonas sp. isolate into the X. arboricola species designation. Improved genomic resources for pathogens of sesame are needed to accurately detect, characterize, and employ timely management of the disease.

[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 .
Randomized Controlled Trial of Telementoring During Resource-Limited Patient Care Simulation Improves Caregiver Performance and Patient Survival
Authors: Pamplin Jeremy C. , Veazey Sena R. , Barczak Stacie , Fonda Stephanie J. , Serio-Melvin Maria L. , Ross Kevin S. , Colombo Christopher J.
Published: May 2024

OBJECTIVES:

To determine the impact of telementoring on caregiver performance during a high-fidelity medical simulation model (HFMSM) of a critically ill patient in a resource-limited setting.

DESIGN:

A two-center, randomized, controlled study using a HFMSM of a patient with community-acquired pneumonia complicated by acute respiratory distress syndrome.

SETTING:

A notional clinic in a remote location staffed by a single clinician and nonmedical assistant.

PARTICIPANTS:

Clinicians with limited experience managing critically ill patients.

INTERVENTIONS:

Telemedicine (TM) support.

MEASUREMENTS:

The primary outcome was clinical performance as measured by accuracy, reliability, and efficiency of care. Secondary outcomes were patient survival, procedural quality, subjective assessment of the HFMSM, and perceived workload.

MAIN RESULTS:

TM participants (N = 11) performed better than non-TM (NTM, N = 12) in providing expected care (accuracy), delivering care more consistently (reliability), and without consistent differences in efficiency (timeliness of care). Accuracy: TM completed 91% and NTM 42% of expected tasks and procedures. Efficiency: groups did not differ in the mean (± sd) minutes it took to obtain an advanced airway successfully (TM 15.2 ± 10.5 vs. NTM 22.8 ± 8.4, p = 0.10) or decompress a tension pneumothorax with a needle (TM 0.7 ± 0.5 vs. NTM 0.6 ± 0.9, p = 0.65). TM was slower than NTM in completing thoracostomy (22.3 ± 10.2 vs. 12.3 ± 4.8, p = 0.03). Reliability: TM performed 13 of 17 (76%) tasks with more consistent timing than NTM. TM completed 68% and NTM 29% of procedural quality metrics. Eighty-two percent of the TM participants versus 17% of the NTM participants simulated patients survived (p = 0.003). The groups similarly perceived the HFMSM as realistic, managed their patients with personal ownership, and experienced comparable workload and stress.

CONCLUSIONS:

Remote expertise provided with TM to caregivers in resource-limited settings improves caregiver performance, quality of care, and potentially real patient survival. HFMSM can be used to study interventions in ways not possible with real patients.
Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference—A Case Study
Authors: Cattaneo Dario , Caloni Beatrice , Caronni Stefania , Calvagna Nunziata , Bonini Igor , Giacomelli Andrea , Gervasoni Cristina
Published: May 2024

Background:

Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations.

Methods:

A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia.

Results:

A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses.

Conclusions:

The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug–drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.
Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study
Authors: Lien Thuy N. T. , Mohamed Sherin M. M. , van den Bogaard Bas , Touw Daan J. , Franssen Eric J. F.
Published: May 2024

This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.