bluuebunny/crossref_metadata_2025 huggingface dataset:
Translatable plasma and CSF biomarkers for use in mouse models of Huntington’s disease
Authors: Bondulich Marie K , Phillips Jemima , Cañibano-Pico María , Nita Iulia M , Byrne Lauren M , Wild Edward J , Bates Gillian P
Published: February 2024

Huntington’s disease is an inherited neurodegenerative disorder for which a wide range of disease-modifying therapies are in development and the availability of biomarkers to monitor treatment response is essential for the success of clinical trials. Baseline levels of neurofilament light chain in CSF and plasma have been shown to be effective in predicting clinical disease status, subsequent clinical progression and brain atrophy. The identification of further sensitive prognostic fluid biomarkers is an active research area, and total-Tau and YKL-40 levels have been shown to be increased in CSF from Huntington’s disease mutation carriers. The use of readouts with clinical utility in the preclinical assessment of potential therapeutics should aid in the translation of new treatments. Here, we set out to determine how the concentrations of these three proteins change in plasma and CSF with disease progression in representative, well-established mouse models of Huntington’s disease. Plasma and CSF were collected throughout disease progression from R6/2 transgenic mice with CAG repeats of 200 or 90 codons (R6/2:Q200 and R6/2:Q90), zQ175 knock-in mice and YAC128 transgenic mice, along with their respective wild-type littermates. Neurofilament light chain and total-Tau concentrations were quantified in CSF and plasma using ultrasensitive single-molecule array (Quanterix) assays, and a novel Quanterix assay was developed for breast regression protein 39 (mouse homologue of YKL-40) and used to quantify breast regression protein 39 levels in plasma. CSF levels of neurofilament light chain and plasma levels of neurofilament light chain and breast regression protein 39 increased in wild-type biofluids with age, whereas total-Tau remained constant. Neurofilament light chain and breast regression protein 39 were elevated in the plasma and CSF from Huntington’s disease mouse models, as compared with wild-type littermates, at presymptomatic stages, whereas total-Tau was only increased at the latest disease stages analysed. Levels of biomarkers that had been measured in the same CSF or plasma samples taken at the latest stages of disease were correlated. The demonstration that breast regression protein 39 constitutes a robust plasma biomarker in Huntington’s disease mouse models supports the further investigation of YKL-40 as a CSF biomarker for Huntington’s disease mutation carriers. Neurofilament light chain and Tau are considered markers of neuronal damage, and breast regression protein 39 is a marker of inflammation; the similarities and differences in the levels of these proteins between mouse models may provide future insights into their underlying pathology. These data will facilitate the use of fluid biomarkers in the preclinical assessment of therapeutic agents for Huntington’s disease, providing readouts with direct relevance to clinical trials.
Impact of preoperative left pulmonary artery stenting on the Fontan procedure: a retrospective multicentre study
Authors: Comentale Giuseppe , Cucchi Marta , Serrao Andrea , Careddu Lucio , Napoleone Carlo Pace , Gargiulo Gaetano , Oppido Guido
Published: February 2024

OBJECTIVES

Left pulmonary artery (LPA) or bifurcation stenoses at Fontan palliation can be very challenging to treat and may also require cardioplegia and aortic transection. Moreover, the low pressure of Fontan circulation and the bulkiness of the aorta increase the risk of a patch angioplasty collapse. Pre-Fontan LPA stenting of stenotic LPAs overcomes those drawbacks therefore the present study aimed to evaluate its advantageous impact on Fontan surgery.

METHODS

A multicentre retrospective analysis was performed on 304 consecutive Fontan patients. The study population was divided into 2 groups (LPA stented, n = 62 vs not stented, n = 242); pre-and postoperative data were compared.

RESULTS

LPA-stented patients had a higher prevalence of systemic right ventricle (P = 0.01), hypoplastic left heart syndrome (P = 0.042), complex neonatal palliations (Norwood/Damus–Kaye–Stansel) and surgical LPA patch repair at Glenn (P < 0.001). No differences were found in cross-clamp rates, early (P = 0.29) and late survival (94.6% vs 98.4, P = 0.2) or complications (P = 0.14). Complex palliations on ascending aorta/aortic arch (P = 0.013) and surgical LPA repair at Glenn (P < 0.001) proved to be risk factors for LPA stenting before Fontan at multivariable analysis.

CONCLUSIONS

The LPA-stented group showed similar outcomes in terms of survival and complications rate compared to patients without LPA stenosis; however, they significantly differ in their higher preoperative risk profile and in their more complex anatomy. Complex neonatal palliations involving ascending aorta or aortic arch may increase the risk of pulmonary branches stenosis requiring stenting; therefore, preoperative stenting of LPA stenoses could help to reduce the surgical risk of complex Fontan procedure by avoiding the need for cross-clamp or complex mediastinal dissections to perform a high-risk surgical repair.
Ischaemic heart disease in patients with cancer
Authors: Ameri Pietro , Bertero Edoardo , Lombardi Marco , Porto Italo , Canepa Marco , Nohria Anju , Vergallo Rocco , Lyon Alexander R , López-Fernández Teresa
Published: February 2024

Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared to patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case by case basis. Randomized controlled trial evidence in cancer patients is very limited and there is urgent need for more data to inform clinical practice. Therefore, coexistence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.
Long read genome assembly of Automeris io (Lepidoptera: Saturniidae) an emerging model for the evolution of deimatic displays
Authors: Skojec Chelsea , Godfrey R Keating , Kawahara Akito Y
Published: February 2024

Automeris moths are a morphologically diverse group with 145 described species that have a geographic range that spans from the New World temperate zone to the Neotropics. Many Automeris have elaborate hindwing eyespots that are thought to deter or disrupt the attack of potential predators, allowing the moth time to escape. The Io moth (Automeris io), known for its striking eyespots, is a well-studied species within the genus and is an emerging model system to study the evolution of deimatism. Existing research on the eyespot pattern development will be augmented by genomic resources that allow experimental manipulation of this emerging model. Here, we present a high-quality, PacBio HiFi genome assembly for Io moth to aid existing research on the molecular development of eyespots and future research on other deimatic traits. This 490 Mb assembly is highly contiguous (N50 = 15.78 mbs) and complete (benchmarking universal single-copy orthologs = 98.4%). Additionally, we were able to recover orthologs of genes previously identified as being involved in wing pattern formation and movement.
Seismic moment tensor classification using elliptical distribution functions on the hypersphere
Authors: Hoggard Mark J , Scealy Janice L , Delbridge Brent G
Published: February 2024

Discrimination of underground explosions from naturally occurring earthquakes and other anthropogenic sources is one of the fundamental challenges of nuclear explosion monitoring. In an operational setting, the number of events that can be thoroughly investigated by analysts is limited by available resources. The capability to rapidly screen out events that can be robustly identified as not being explosions is, therefore, of great potential benefit. Nevertheless, possible mis-classification of explosions as earthquakes currently limits the use of screening methods for verification of test-ban treaties. Moment tensors provide a physics-based classification tool for the characterization of different seismic sources and have enabled the advent of new techniques for discriminating between earthquakes and explosions. Following normalization and projection of their six-degree vectors onto the hypersphere, existing screening approaches use spherically symmetric metrics to determine whether any new moment tensor may have been an explosion. Here, we show that populations of moment tensors for both earthquakes and explosions are anisotropically distributed on the hypersphere. Distributions possessing elliptical symmetry, such as the scaled von Mises–Fisher distribution, therefore provide a better description of these populations than the existing spherically symmetric models. We describe a method that uses these elliptical distributions in combination with a Bayesian classifier to achieve successful classification rates of 99 per cent for explosions and 98 per cent for earthquakes using existing catalogues of events from the western United States. The 1983 May 5 Crowdie underground nuclear test and 2018 July 20 DAG-1 deep-borehole chemical explosion are the only two explosions out of 140 that are incorrectly classified. Application of the method to the 2006–2017 nuclear tests in the Democratic People’s Republic of Korea yields 100 per cent identification rates and we provide a simple routine MTid for general usage. The approach provides a means to rapidly assess the likelihood of an event being an explosion and can be built into monitoring workflows that rely on simultaneously assessing multiple different discrimination metrics.
Statistical inference with regularized optimal transport
Authors: Goldfeld Ziv , Kato Kengo , Rioux Gabriel , Sadhu Ritwik
Published: February 2024

Optimal transport (OT) is a versatile framework for comparing probability measures, with many applications to statistics, machine learning and applied mathematics. However, OT distances suffer from computational and statistical scalability issues to high dimensions, which motivated the study of regularized OT methods like slicing, smoothing and entropic penalty. This work establishes a unified framework for deriving limit distributions of empirical regularized OT distances, semiparametric efficiency of the plug-in empirical estimator and bootstrap consistency. We apply the unified framework to provide a comprehensive statistical treatment of (i) average- and max-sliced $p$-Wasserstein distances, for which several gaps in existing literature are closed; (ii) smooth distances with compactly supported kernels, the analysis of which is motivated by computational considerations; and (iii) entropic OT, for which our method generalizes existing limit distribution results and establishes, for the first time, efficiency and bootstrap consistency. While our focus is on these three regularized OT distances as applications, the flexibility of the proposed framework renders it applicable to broad classes of functionals beyond these examples.
Maximal Polarization for Periodic Configurations on the Real Line
Authors: Faulhuber Markus , Steinerberger Stefan
Published: February 2024

We prove that among all 1-periodic configurations $\Gamma $ of points on the real line $\mathbb{R}$ the quantities $\min _{x \in \mathbb{R}} \sum _{\gamma \in \Gamma } e^{- \pi \alpha (x - \gamma )^{2}}$ and $\max _{x \in \mathbb{R}} \sum _{\gamma \in \Gamma } e^{- \pi \alpha (x - \gamma )^{2}}$ are maximized and minimized, respectively, if and only if the points are equispaced and whenever the number of points $n$ per period is sufficiently large (depending on $\alpha $). This solves the polarization problem for periodic configurations with a Gaussian weight on $\mathbb{R}$ for large $n$. The first result is shown using Fourier series. The second result follows from the work of Cohn and Kumar on universal optimality and holds for all $n$ (independent of $\alpha $).
A Call to Action: Urgently Strengthening the Future Physician-Scientist Workforce in Infectious Diseases
Authors: Swartz Talia H , Apewokin Senu , Carpenter Stephen M , Chakraborty Rana , Dennis Ann M , Houpt Eric , Surana Neeraj K , Zerr Danielle M , Pirofski Liise-anne
Published: February 2024

Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health. The importance of ID research in understanding diseases, leading to treatments and vaccines, is emphasized, along with the need to address persistent and new infections, antimicrobial resistance, and threats like HIV and influenza. The paper analyzes the physician-scientist workforce's struggles, including funding, training, and research-practice integration gaps. We suggest increased funding, better training, and mentorship, more collaborative and interdisciplinary research, and improved recognition systems. The article stresses the urgency of supporting physician-scientists in ID, advocating for proactive prevention and preparedness, and calls for immediate action to enhance ID research and care.
Effect of Vaginal Microecological Disorders on the Increased Risk of Abnormal Cervical Cytology Among Women With Human Immunodeficiency Virus in China
Authors: Wang Xiaolei , Zhang Yuanyuan , Xiao Jiang , Song Chuan , Liu Tingting , Liu Jun , Zhao Hongxin
Published: February 2024

Background

Abnormal cervical cytology is commonly observed in women with human immunodeficiency virus (WWH).

Methods

A cross-sectional study was conducted with 130 WWH and 147 age-matched healthy controls, who underwent gynecological examinations at Beijing Ditan Hospital. The presence of abnormal cervical cytology in WWH was predicted after performing a logistic regression analysis.

Results

Multivariate logistic regression revealed 3 independent factors, among which CD4 cell count ≥350 cells/μL was the protective factor, while human papillomavirus infection and abnormal vaginal pH were the risk factors.

Conclusions

Vaginal microecological disorders can increase the risk of abnormal cervical cytology in WWH.
Regulatory T and CXCR3+ Circulating Tfh Cells Concordantly Shape the Neutralizing Antibody Responses in Individuals Who Have Recovered from Mild COVID-19
Authors: Zheng Xingyu , Lu Rui , Pan Dong , Peng Liting , He Rongzhang , Hu Yabin , Chen Jun , Tang Jinyong , Rong Xiaohan , Teng Shishan , Wang You , Liu Fen , Xie Tianyi , Wu Chanfeng , Tang Yinggen , Liu Wenpei , Qu Xiaowang
Published: February 2024

Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.
Crisis and Transformative Learning in Communities of Practice: Semi-Formal Learning in CSDP during COVID-19
Authors: Bremberg Niklas , Hedling Elsa
Published: February 2024

This article analyzes learning in the EU’s Common Security and Defence Policy (CSDP) by way of drawing on recent theoretical advancements on the concept of communities of practice (CoP) in international relations (IR). The article presents an analytical framework that distinguishes between reproductive and transformative learning in relation to levels of contestation in CoPs. To illustrate the framework’s analytical usefulness, the article analyzes the case of CSDP lessons learning during the COVID-19 pandemic. The analysis draws on data from a survey as well as interviews with EU officials, and it suggests that the combination of an external crisis and an institutional momentum to facilitate collective learning produced a context where CSDP practitioners demonstrated more willingness to engage in the formal process of recording lessons. A shared sense of urgency in collecting lessons from the pandemic and the unprecedented absence of informal sites for learning practices due to restrictions of physical meetings, meant that semi-formal learning practices could fill the void of informal interactions. This provided for a unique context for transformative learning in the CSDP that is highly relevant for IR scholars interested in the political effects of learning and contestation in international organizations and in CoPs more generally.
Global Ordering and the Interaction of Communities of Practice: A Framework for Analysis
Authors: Bueger Christian , Hofius Maren , Edwards Scott
Published: February 2024

Several new frameworks for the study of the differentiation of and relations between global orders have recently been introduced to International Relations. This article demonstrates how the communities of practice (COP) framework provides complementary as well as novel answers to processes of global ordering. COP theory has become a thriving research framework and has led to substantial innovative work on the internal logics of international institutions, including the North Atlantic Treaty Organization and the European Union, and various professions, such as diplomats. Surprisingly, researchers have so far not appreciated the potential of the approach as a more general theory of global order. We argue that lifting this potential implies focusing on the interaction of and spaces between communities as well as going beyond the study of the internal logics of a discrete community. We propose a framework for the study of this interaction with a focus on its spatial and agential dimensions. We then show how this leads to an innovative research framework, drawing on an illustration from the case of global ocean governance.
Unraveling the diversity and dissemination dynamics of antimicrobial resistance genes in Enterobacteriaceae plasmids across diverse ecosystems
Authors: Sabino Yasmin Neves Vieira , de Melo Mariana Dias , da Silva Giarlã Cunha , Mantovani Hilario Cuquetto
Published: February 2024

Aim

The objective of this study was to investigate the antimicrobial resistance genes (ARGs) in plasmids of Enterobacteriaceae from soil, sewage, and feces of food-producing animals and humans.

Methods and results

The plasmid sequences were obtained from the NCBI database. For the identification of ARG, comprehensive antibiotic resistance database (CARD), and ResFinder were used. Gene conservation and evolution were investigated using DnaSP v.6. The transfer potential of the plasmids was evaluated using oriTfinder and a MOB-based phylogenetic tree was reconstructed using Fastree. We identified a total of 1064 ARGs in all plasmids analyzed, conferring resistance to 15 groups of antibiotics, mostly aminoglycosides, beta-lactams, and sulfonamides. The greatest number of ARGs per plasmid was found in enterobacteria from chicken feces. Plasmids from Escherichia coli carrying multiple ARGs were found in all ecosystems. Some of the most abundant genes were shared among all ecosystems, including aph(6)-Id, aph(3′’)-Ib, tet(A), and sul2. A high level of sequence conservation was found among these genes, and tet(A) and sul2 are under positive selective pressure. Approximately 62% of the plasmids carrying at least one ARG were potentially transferable. Phylogenetic analysis indicated a potential co-evolution of Enterobacteriaceae plasmids in nature.

Conclusion

The high abundance of Enterobacteriaceae plasmids from diverse ecosystems carrying ARGs reveals their widespread distribution and importance.
Differences in bone histomorphometry between White postmenopausal women with and without atypical femoral fracture after long-term bisphosphonate therapy
Authors: Qiu Shijing , Dhaliwal Ruban , Divine George , Warner Elizabeth , Rao Sudhaker D
Published: February 2024

Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BPs). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time-matched patients who either had AFF or did not have AFF. In this study, we performed transiliac bone biopsies in 52 White postmenopausal women with (n = 20) and without (n = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4–17 yr. Despite the matched range of treatment duration (4–17 yr), AFF patients received alendronate for significantly longer time (10.7 yr) than non-AFF patients (8.0 yr) (P = .014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical, and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3–6 mo after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have a similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration.
Enhanced osteoporotic fracture prediction in postmenopausal women using Bayesian optimization of machine learning models with genetic risk score
Authors: Wu Qing , Dai Jingyuan
Published: February 2024

This study aimed to enhance the fracture risk prediction accuracy in major osteoporotic fractures (MOFs) and hip fractures (HFs) by integrating genetic profiles, machine learning (ML) techniques, and Bayesian optimization. The genetic risk score (GRS), derived from 1,103 risk single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS), was formulated for 25,772 postmenopausal women from the Women's Health Initiative dataset. We developed four ML models: Support Vector Machine (SVM), Random Forest, XGBoost, and Artificial Neural Network (ANN) for binary fracture outcome and 10-year fracture risk prediction. GRS and FRAX clinical risk factors (CRFs) were used as predictors. Death as a competing risk was accounted for in ML models for time-to-fracture data. ML models were subsequently fine-tuned through Bayesian optimization, which displayed marked superiority over traditional grid search. Evaluation of the models' performance considered an array of metrics such as accuracy, weighted F1 Score, the area under the precision-recall curve (PRAUC), and the area under the receiver operating characteristic curve (AUC) for binary fracture predictions, and the C-index, Brier score, and dynamic mean AUC over a 10-year follow-up period for fracture risk predictions. We found that GRS-integrated XGBoost with Bayesian optimization is the most effective model, with an accuracy of 91.2% (95% CI: 90.4–92.0%) and an AUC of 0.739 (95% CI: 0.731–0.746) in MOF binary predictions. For 10-year fracture risk modeling, the XGBoost model attained a C-index of 0.795 (95% CI: 0.783–0.806) and a mean dynamic AUC of 0.799 (95% CI: 0.788–0.809). Compared to FRAX, the XGBoost model exhibited a categorical net reclassification improvement (NRI) of 22.6% (P = .004). A sensitivity analysis, which included BMD but lacked GRS, reaffirmed these findings. Furthermore, portability tests in diverse non-European groups, including Asians and African Americans, underscored the model's robustness and adaptability. This study accentuates the potential of combining genetic insights and optimized ML in strengthening fracture predictions, heralding new preventive strategies for postmenopausal women.
Familial multiple lipomatosis associated with multiple cherry hemangiomas and moles: a rare case report
Authors: Guntupalli Gopalaswamy , Ramadugu Rithika , Suvvari Tarun K , Ravipati Shivani , Thomas Vimal
Published: February 2024

Lipomas are common benign mesenchymal tumours, whereas lipomatoses are uncommon. Familial multiple lipomatosis (FML) is a rare syndrome characterized by multiple usually painless lipomas which may be associated with other conditions. FML is considered to be genetic, with various patterns of inheritance suggested. In this case report, we described a case of multiple familial lipomatosis that was misdiagnosed as dercum’s disease.
Extreme dislocation of the cervical spine—case report
Authors: Zagorac Slavisa , Vasic Milos , Novakovic Uros , Mladenovic Milos , Tulic Ivan , Teodosic Valerija , Vracevic Dragana
Published: February 2024

We present the case of rare extreme dislocation of subaxial cervical spine, which was challenging regarding type and time of surgery. A 22-year-old patient was injured in a traffic accident, from very beginning with signs of spinal shock. Severe traumatic C6/C7 dislocation with resulting transection of the spinal cord was diagnosed with MDCT imaging. The main dilemmas regarding the surgical treatment of this injury referred to the timing of surgery and the choice of surgical approach. We decided to perform posterior surgery at first stage. Postoperative her condition get worsening and on the 16th postoperative day came to the fatal outcome. Despite all the available protocols, in our case, the decision had to be made on the basis of individual multidisciplinary assessment, bearing in mind the mechanism of the injury and the clinical presentation of the injured patient.
Transverse oscillations of two parallel magnetic tubes with slowly changing density
Authors: Ruderman M S , Petrukhin N S
Published: February 2024

We study kink oscillations of the system of two parallel magnetic tubes in the presence of plasma cooling. We assume that the characteristic cooling time is much larger than the characteristic time of kink oscillations. Using the ratio of two characteristic times as a small parameter, we derive the expression for the adiabatic invariant, which is a quantity that remains constant during the cooling process. Then, we study in detail a particular case where the plasma densities in the two tubes are the same, the plasma temperature outside of the tube does not change, and the plasma temperature inside the tubes decreases exponentially. We found that cooling causes the increase of the oscillation frequencies and amplitudes. These results are the generalization of similar results previously obtained for a single magnetic tube. We compared the efficiency of amplification of kink oscillations caused by cooling in counteracting the damping of oscillations due to resonant absorption in two models of coronal magnetic loops: monolithic and consisting of two parallel filaments.
Detecting non-thermal emission in a solar microflare using nested sampling
Authors: Cooper Kristopher , Hannah Iain G , Glesener Lindsay , Grefenstette Brian W
Published: February 2024

Microflares are energetically smaller versions of solar flares, demonstrating the same processes of plasma heating and particle acceleration. However, it remains unclear down to what energy scales this impulsive energy release continues, which has implications for how the solar atmosphere is heated. The heating and particle acceleration in microflares can be studied through their X-ray emission, finding predominantly thermal emission at lower energies; however, at higher energies it can be difficult to distinguish whether the emission is due to hotter plasma and/or accelerated electrons. We present the first application of nested sampling to solar flare X-ray spectra, an approach that provides a quantitative degree of confidence for one model over another. We analyse Nuclear Spectroscopic Telescope Array X-ray observations of a small active region microflare (A0.02 GOES/XRS class equivalent) that occurred on 2021 November 17, with a new python package for spectral fitting, sunkit-spex, to compute the parameter posterior distributions and the evidence of different models representing the higher energy emission as due to thermal or non-thermal sources. Calculating the Bayes factor, we show that there is significantly stronger evidence for the higher energy microflare emission to be produced by non-thermal emission from flare-accelerated electrons than by an additional hot thermal source. Qualitative confirmation of this non-thermal source is provided by the lack of hotter (10 MK) emission in Solar Dynamic Observatory’s Atmospheric Imaging Assembly’s extreme ultraviolet data. The nested sampling approach used in this paper has provided clear support for non-thermal emission at the level of 3 × 1024 erg s−1 in this tiny microflare.
The ALMaQUEST Survey XIV: do radial molecular gas flows affect the star-forming ability of barred galaxies?
Authors: Hogarth L M , Saintonge A , Davis T A , Ellison S L , Lin L , López-Cobá C , Pan H -A , Thorp M D
Published: February 2024

We investigate whether barred galaxies are statistically more likely to harbour radial molecular gas flows and what effect those flows have on their global properties. Using 46 galaxies from the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we identify galaxies hosting optical bars using a combination of the morphological classifications in Galaxy Zoo 2 and HyperLEDA. In order to detect radial molecular gas flows, we employ full 3D kinematic modelling of the ALMaQUEST 12CO(1–0) data cubes. By combining our bar classifications with our radial bar-driven flow detections, we find that galaxies classed as barred are statistically more likely to host large-scale radial gas motions compared to their un-barred and edge-on galaxy counterparts. Moreover, the majority of barred galaxies require multicomponent surface brightness profiles in their best-fitting models, indicative of the presence of resonance systems. We find that galaxies classed as barred with radial bar-driven flows (‘barred + radial flow’ subset) have significantly suppressed global star-formation efficiencies compared to barred galaxies without radial bar-driven flows and galaxies in the other morphological sub-samples. Our ‘barred + radial flow’ subset galaxies also possess consistently centrally concentrated molecular gas distributions, with no indication of depleted gas mass fractions, suggesting that gas exhaustion is not the cause of their suppressed star formation. Furthermore, these objects have higher median gas mass surface densities in their central 1 kpc, implying that central gas enhancements do not fuel central starbursts in these objects. We propose that dynamical effects, such as shear caused by large-scale inflows of gas, act to gravitationally stabilize the inner gas reservoirs.
Accretion and magnetism on young eccentric binaries: DQ Tau and AK Sco
Authors: Pouilly Kim , Hahlin Axel , Kochukhov Oleg , Morin Julien , Kóspál Ágnes
Published: February 2024

The accretion and ejection of mass in pre-main-sequence (PMS) stars are key processes in stellar evolution as they shape the stellar angular momentum transport necessary for the stars’ stability. Magnetospheric accretion on to classical T Tauri stars and low-mass PMS stars has been widely studied in the single-star case. This process cannot be directly transferred to PMS binary systems, as tidal and gravitation effects, and/or accretion from a circumbinary disc (with variable separation of the components in the case of eccentric orbits) are in place. This work examines the accretion process of two PMS eccentric binaries, DQ Tau and AK Sco, using high-resolution spectropolarimetric time series. We investigate how magnetospheric accretion can be applied to these systems by studying the accretion-related emission lines and the magnetic field of each system. We discover that both systems are showing signs of magnetospheric accretion, despite their slightly different configurations, and the weak magnetic field of AK Sco. Furthermore, the magnetic topology of DQ Tau A shows a change relative to the previous orbital cycle studied: previously dominated by the poloidal component, it is now dominated by the toroidal component. We also report an increase of the component’s accretion and the absence of an accretion burst at the apastron, suggesting that the component’s magnetic variation might be the cause of the inter-cycle variations of the system’s accretion. We conclude on the presence of magnetospheric accretion for both systems, together with gravitational effects, especially for AK Sco, composed of more massive components.
Emergence of the temperature–density relation in the low-density intergalactic medium
Authors: Wells Alexandra , Robinson David , Avestruz Camille , Gnedin Nickolay Y
Published: February 2024

We examine the evolution of the phase diagram of the low-density intergalactic medium during the Epoch of Reionization in simulation boxes with varying reionization histories from the Cosmic Reionization on Computers project. The probability density function (PDF) of gas temperature at fixed density exhibits two clear modes: a warm and a cold temperature mode, corresponding to the gas inside and outside of ionized bubbles. We find that the transition between the two modes is ‘universal’ in the sense that its timing is accurately parametrized by the value of the volume-weighted neutral fraction for any reionization history. This ‘universality’ is more complex than just a reflection of the fact that ionized gas is warm and neutral gas is cold: it holds for the transition at a fixed value of gas density, and gas at different densities transitions from the cold to the warm mode at different values of the neutral fraction, reflecting a non-trivial relationship between the ionization history and the evolving gas density PDF. Furthermore, the ‘emergence’ of the tight temperature–density relation in the warm mode is also approximately ‘universally’ controlled by the volume-weighted neutral fraction for any reionization history. In particular, the ‘emergence’ of the temperature–density relation (as quantified by the rapid decrease in its width) occurs when the neutral fraction is 10−4 ≲ XH i ≲ 10−3 for any reionization history. Our results indicate that the neutral fraction is a primary quantity controlling the various properties of the temperature–density relation, regardless of reionization history.
Balancing Faith and Equality: Examining the Adequacy of the Doctrine of Essential Religious Practices from Gender Perspectives in India
Authors: Sonkar Sumit
Published: February 2024

The Supreme Court of India formulated the doctrine of essential religious practices as a legal framework to protect the right to religious practice while enabling the State to implement social reforms, as provided under Article 25 of the Constitution. This article contends that although this doctrine was created to reconcile competing legal frameworks, its inconsistent and incoherent application cannot meaningfully resolve religious disputes – leaving many normative gaps. Consequently, this doctrine needs to be re-evaluated to balance religious freedom with other fundamental rights. Thus, this article assesses the doctrine of essential religious practices, its nature, scope, concerns, and criticism from gender equality perspectives.
The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review
Authors: Guven Deniz Can , Kavgaci Gozde , Erul Enes , Syed Masood Pasha , Magge Tara , Saeed Anwaar , Yalcin Suayib , Sahin Ibrahim Halil
Published: February 2024

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.
Perceived experts are prevalent and influential within an antivaccine community on Twitter
Authors: Harris Mallory J , Murtfeldt Ryan , Wang Shufan , Mordecai Erin A , West Jevin D
Published: February 2024

Perceived experts (i.e. medical professionals and biomedical scientists) are trusted sources of medical information who are especially effective at encouraging vaccine uptake. The role of perceived experts acting as potential antivaccine influencers has not been characterized systematically. We describe the prevalence and importance of antivaccine perceived experts by constructing a coengagement network of 7,720 accounts based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the antivaccine community. Perceived experts had a sizable presence across the coengagement network, including within the antivaccine community where they were 9.8% of individual, English-language users. Perceived experts within the antivaccine community shared low-quality (misinformation) sources at similar rates and academic sources at higher rates compared to perceived nonexperts in that community. Perceived experts occupied important network positions as central antivaccine users and bridges between the antivaccine and provaccine communities. Using propensity score matching, we found that perceived expertise brought an influence boost, as perceived experts were significantly more likely to receive likes and retweets in both the antivaccine and provaccine communities. There was no significant difference in the magnitude of the influence boost for perceived experts between the two communities. Social media platforms, scientific communications, and biomedical organizations may focus on more systemic interventions to reduce the impact of perceived experts in spreading antivaccine misinformation.
Eigenphase distributions of unimodular circular ensembles
Authors: Nishigaki Shinsuke
Published: February 2024

Motivated by the study of Polyakov lines in gauge theories, Hanada and Watanabe recently presented a conjectured formula for the distribution of eigenphases of Haar-distributed random SU(N) matrices (β = 2), supported by explicit examples at small N and by numerical samplings at larger N. In this letter, I spell out a concise proof of their formula, and present its orthogonal and symplectic counterparts, i.e. the eigenphase distributions of Haar-random unimodular symmetric (β = 1) and selfdual (β = 4) unitary matrices parametrizing SU(N)/SO(N) and SU(2N)/Sp(2N), respectively.
A real-world pilot study assessing treatment satisfaction with avanafil in patients with erectile dysfunction
Authors: Tsai Ping-Ju , Hung Shih-Ya , Lee Tsung-Hsi , Jiann Bang-Ping
Published: February 2024

Background

Avanafil is a second-generation phosphodiesterase type 5 (PDE5) inhibitor, and offers a rapid onset of action (15 minutes). Its real-world data, including treatment satisfaction, are still lacking.

Aim

The study sought to investigate the treatment outcomes of avanafil and the factors impacting treatment satisfaction in a real-world setting.

Methods

Between November 2021 and February 2023, erectile dysfunction (ED) patients prescribed avanafil were consecutively enrolled in this phase 4, open-label, cross-sectional, observational study. At each follow-up visit (4-week intervals), participants completed a questionnaire for assessing the use and treatment-emergent adverse events of avanafil, ED severity, and treatment satisfaction.

Outcomes

The outcome measures included the Sexual Health Inventory for Men (SHIM), and Erectile Dysfunction Inventory of Treatment Satisfaction.

Results

Among 234 patients enrolled, 112 (47.9%) patients had follow-up visits and answered the questionnaire. Treatment with avanafil significantly improved the mean SHIM total score from 10.2 ± 5.6 at baseline to 17.5 ± 6.2 (P < .001). Of the patients treated with avanafil, 71.4% (n = 80 of 112) reported a >4-point improvement in the SHIM total score, and 33.1% (n = 37 of 112) reported normal erectile function. The proportion of patients satisfied with avanafil treatment (defined as Erectile Dysfunction Inventory of Treatment Satisfaction index score ≥60) was 87.5%. Several physical factors (younger age, lower waist circumference, and lower level of low-density lipoprotein), and sexual function factors (shorter duration of ED, higher SHIM total score at baseline, PDE5 inhibitor treatment naive, and acquired premature ejaculation) tended to contribute to satisfaction with avanafil treatment. Treatment-emergent adverse events occurred in 41.1% of patients, and all were mild in severity.

Clinical Implications

This study identifies the factors associated with treatment satisfaction of avanafil, which may ultimately lead to better treatment outcomes.

Strengths and Limitations

This is the first study to provide real-world evidence of avanafil for ED treatment, and validated questionnaires were used to assess erectile function and treatment satisfaction. However, the limitations of this study include single-center observational study design, small sample size, and short-term follow-up.

Conclusion

Avanafil is an effective treatment for ED, and satisfaction rate is high in an outpatient setting. The awareness of identified factors related to patient satisfaction may improve treatment outcomes.
Inhalation of particulate matter containing environmentally persistent free radicals induces endothelial dysfunction mediated via AhR activation at the air-blood interface
Authors: Aryal Ankit , Harmon Ashlyn C , Varner Kurt J , Noël Alexandra , Cormier Stephania A , Nde Divine B , Mottram Peter , Maxie Jemiah , Dugas Tammy R
Published: February 2024

Particulate matter (PM) containing environmentally persistent free radicals (EPFR) is formed by the incomplete combustion of organic wastes, resulting in the chemisorption of pollutants to the surface of PM containing redox-active transition metals. In prior studies in mice, EPFR inhalation impaired endothelium-dependent vasodilation. These findings were associated with aryl hydrocarbon receptor (AhR) activation in the alveolar type-II (AT-II) cells that form the air-blood interface in the lung. We thus hypothesized that AhR activation in AT-II cells promotes the systemic release of mediators that promote endothelium dysfunction peripheral to the lung. To test our hypothesis, we knocked down AhR in AT-II cells of male and female mice and exposed them to 280 µg/m3 EPFR lo (2.7e + 16 radicals/g) or EPFR (5.5e + 17 radicals/g) compared with filtered air for 4 h/day for 1 day or 5 days. AT-II-AhR activation-induced EPFR-mediated endothelial dysfunction, reducing endothelium-dependent vasorelaxation by 59%, and eNOS expression by 50%. It also increased endothelin-1 mRNA levels in the lungs and peptide levels in the plasma in a paracrine fashion, along with soluble vascular cell adhesion molecule-1 and iNOS mRNA expression, possibly via NF-kB activation. Finally, AhR-dependent increases in antioxidant response signaling, coupled to increased levels of 3-nitrotyrosine in the lungs of EPFR-exposed littermate control but not AT-II AhR KO mice suggested that ATII-specific AhR activation promotes oxidative and nitrative stress. Thus, AhR activation at the air-blood interface mediates endothelial dysfunction observed peripheral to the lung, potentially via release of systemic mediators.