bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting
Authors: Tu Wen Juan , Melino Michelle , Dunn Jenny , McCuaig Robert D. , Bielefeldt-Ohmann Helle , Tsimbalyuk Sofiya , Forwood Jade K. , Ahuja Taniya , Vandermeide John , Tan Xiao , Tran Minh , Nguyen Quan , Zhang Liang , Nam Andy , Pan Liuliu , Liang Yan , Smith Corey , Lineburg Katie , Nguyen Tam H. , Sng Julian D. J. , Tong Zhen Wei Marcus , Chew Keng Yih , Short Kirsty R. , Le Grand Roger , Seddiki Nabila , Rao Sudha
Published: June 2023

In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection. This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.
Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
Authors: Köhler Thilo , Luscher Alexandre , Falconnet Léna , Resch Grégory , McBride Robert , Mai Quynh-Anh , Simonin Juliette L. , Chanson Marc , Maco Bohumil , Galiotto Raphaël , Riat Arnaud , Civic Natacha , Docquier Mylène , McCallin Shawna , Chan Benjamin , van Delden Christian
Published: June 2023

Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient’s isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples indicate in patient phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates reveals a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates is multifactorial and mainly due to spontaneous chromosomal mutations. All isolates recovered after phage treatment remain phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of P. aeruginosa lung colonization.
In-orbit demonstration of a re-trainable machine learning payload for processing optical imagery
Authors: Mateo-Garcia Gonzalo , Veitch-Michaelis Josh , Purcell Cormac , Longepe Nicolas , Reid Simon , Anlind Alice , Bruhn Fredrik , Parr James , Mathieu Pierre Philippe
Published: June 2023

Cognitive cloud computing in space (3CS) describes a new frontier of space innovation powered by Artificial Intelligence, enabling an explosion of new applications in observing our planet and enabling deep space exploration. In this framework, machine learning (ML) payloads—isolated software capable of extracting high level information from onboard sensors—are key to accomplish this vision. In this work we demonstrate, in a satellite deployed in orbit, a ML payload called ‘WorldFloods’ that is able to send compressed flood maps from sensed images. In particular, we perform a set of experiments to: (1) compare different segmentation models on different processing variables critical for onboard deployment, (2) show that we can produce, onboard, vectorised polygons delineating the detected flood water from a full Sentinel-2 tile, (3) retrain the model with few images of the onboard sensor downlinked to Earth and (4) demonstrate that this new model can be uplinked to the satellite and run on new images acquired by its camera. Overall our work demonstrates that ML-based models deployed in orbit can be updated if new information is available, paving the way for agile integration of onboard and onground processing and “on the fly” continuous learning.
Parabolic gratings enhance the X-ray sensitivity of Talbot interferograms
Authors: Zangi Pouria , Ikematsu Katsumasa , Meyer Pascal , Takano Hidekazu , Wu Yanlin , Gutekunst Josephine , Börner Martin , Last Arndt , Korvink Jan G. , Momose Atsushi
Published: June 2023

In grating-based X-ray Talbot interferometry, the wave nature of X-ray radiation is exploited to generate phase contrast images of objects that do not generate sufficient contrast in conventional X-ray imaging relying on X-ray absorption. The phase sensitivity of this interferometric technique is proportional to the interferometer length and inversely proportional to the period of gratings. However, the limited spatial coherency of X-rays limits the maximum interferometer length, and the ability to obtain smaller-period gratings is limited by the manufacturing process. Here, we propose a new optical configuration that employs a combination of a converging parabolic micro-lens array and a diverging micro-lens array, instead of a binary phase grating. Without changing the grating period or the interferometer length, the phase signal is enhanced because the beam deflection by a sample is amplified through the array of converging-diverging micro-lens pairs. We demonstrate that the differential phase signal detected by our proposed set-up is twice that of a Talbot interferometer, using the same binary absorption grating, and with the same overall inter-grating distance.
Distributed MPC of vehicle platoons with guaranteed consensus and string stability
Authors: Feng Yangyang , Yu Shuyou , Chen Hao , Li Yongfu , Shi Shuming , Yu Jianhua , Chen Hong
Published: June 2023

Control of vehicle platoon can effectively reduce the traffic accidents caused by fatigue driving and misoperation, reduce air resistance by eliminating the inter-vehicle gap which will effectively reduce fuel consumption and exhaust emissions. A hierarchical control scheme for vehicle platoons is proposed in this paper. Considering safety, consistency, and passengers’ comfort, a synchronous distributed model predictive controller is designed as an upper-level controller, in which a constraint guaranteeing string stability is introduced into the involved local optimization problem so as to guarantee that the inter-vehicle gap error gradually attenuates as it propagates downstream. A terminal equality constraint is added to guarantee asymptotic consensus of vehicle platoons. By constructing the vehicle inverse longitudinal dynamics model, a lower-level control scheme with feedforward and feedback controllers is designed to adjust the throttle angle and brake pressure of vehicles. A PID is used as the feedback controller to eliminate the influence of unmodeled dynamics and uncertainties. Finally, the performance of longitudinal tracking with the proposed control scheme is validated by joint simulations with PreScan, CarSim, and Simulink.
Shotgun proteomics identification of proteins expressed in the Descemet’s membrane of patients with Fuchs endothelial corneal dystrophy
Authors: Nakagawa Tatsuya , Okumura Naoki , Ikegawa Masaya , Toyama Yumiko , Nirasawa Takashi , Mascarelli Frederic , Vaitinadapoule Hanielle , Aouimeur Ines , He Zhiguo , Gain Philippe , Thuret Gilles , Koizumi Noriko
Published: June 2023

Fuchs endothelial corneal dystrophy (FECD) is a slowly evolving, bilateral disease of the corneal endothelium, characterized by an abnormal accumulation of extracellular matrix (ECM) in the basement membrane (Descemet’s membrane, DM). This results in the formation of small round excrescences, called guttae, and a progressive disappearance of endothelial cells. In the intermediate stage, the numerous guttae create significant optical aberrations, and in the late stage, the loss of endothelial function leads to permanent corneal edema. The molecular components of guttae have not been fully elucidated. In the current study, we conducted shotgun proteomics of the DMs, including guttae, obtained from patients with FECD and revealed that 32 proteins were expressed only in the FECD-DMs but not in the DMs of control subjects. Subsequent enrichment analyses identified associations with multiple ECM-related pathways. Immunostaining of flat-mounted DMs confirmed that 4 of the top 5 identified proteins (hemoglobin α, SRPX2, tenascin-C, and hemoglobin γδεβ) were expressed in FECD-DMs but not in non-FECD-DMs. Fibrinogen α was strongly expressed in FECD-DMs, but weakly expressed in non-FECD-DMs. We also demonstrated that matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) can display the in situ spatial distribution of biomolecules expressed in the DM, including the guttae.
Fusion of visible and thermal images improves automated detection and classification of animals for drone surveys
Authors: Krishnan B. Santhana , Jones Landon R. , Elmore Jared A. , Samiappan Sathishkumar , Evans Kristine O. , Pfeiffer Morgan B. , Blackwell Bradley F. , Iglay Raymond B.
Published: June 2023

Visible and thermal images acquired from drones (unoccupied aircraft systems) have substantially improved animal monitoring. Combining complementary information from both image types provides a powerful approach for automating detection and classification of multiple animal species to augment drone surveys. We compared eight image fusion methods using thermal and visible drone images combined with two supervised deep learning models, to evaluate the detection and classification of white-tailed deer (Odocoileus virginianus), domestic cow (Bos taurus), and domestic horse (Equus caballus). We classified visible and thermal images separately and compared them with the results of image fusion. Fused images provided minimal improvement for cows and horses compared to visible images alone, likely because the size, shape, and color of these species made them conspicuous against the background. For white-tailed deer, which were typically cryptic against their backgrounds and often in shadows in visible images, the added information from thermal images improved detection and classification in fusion methods from 15 to 85%. Our results suggest that image fusion is ideal for surveying animals inconspicuous from their backgrounds, and our approach uses few image pairs to train compared to typical machine-learning methods. We discuss computational and field considerations to improve drone surveys using our fusion approach.
New library of phase-change materials with their selection by the Rényi entropy method
Authors: Kulish Vladimir , Aslfattahi Navid , Schmirler Michal , Sláma Pavel
Published: June 2023

The secret to the successful and widespread deployment of solar energy for thermal applications is effective and affordable heat storage. The ability to provide a high energy storage density and the capacity to store heat at a constant temperature corresponding to the phase transition temperature of the heat storage material (phase-change material or PCM) make latent heat storage one of the most alluring methods of heat storage. Today, it can be challenging to obtain all the published data on PCM qualities, including relevant non-thermodynamic properties in addition to thermodynamic ones. The developed new PCM library contains various types of PCMs which possess broad range of operation temperatures. This new library consists of 500 substances along with nine associated properties such as phase change temperature, solidification temperature, maximum operation temperature, density, latent heat and specific heat capacity, thermal conductivity, cycleability and ignition temperature. Furthermore, a new PCM selection method, based on calculating the Rényi entropy for a given set of selection criteria, has been proposed. The newly developed selection method requires no subjective judgements. The idea of the method is inspired by earlier applications of fractal analysis methods in many areas of research.
A borate-based peroxynitrite fluorescent probe and its application in fluorescence imaging of living cells
Authors: Xie Fulan , Zhou Rui , Jian Chi , Zhang Lizhu , He Yonghui
Published: June 2023

The paper showed that 3b had high selectivity and sensitivity for ONOO−. The recognition was not disturbed by other active oxygen groups. Moreover, the probe 3b had low cytotoxicity and was successfully used to detect intracellular ONOO−.
Optical temperature-sensing phosphors with high sensitivities in a wide temperature range based on different strategies
Authors: An Songsong , Zhang Jia , Hua Zhenghe , Chen Jiajun
Published: June 2023

Rare earth ion doped luminescent materials are considered potential candidates with a wide range of applications because of their unique optical characteristics.
Conformational preference in difluoroacetamide oligomers: probing the potential for foldamers with C–H⋯O hydrogen bonds
Authors: Žabka Matej , Clayden Jonathan
Published: June 2023

The conformation of bisdifluoroacetamides is governed by dipole effects, rather than CH⋯O hydrogen bonds.
Pd-catalyzed oxidative amination of 2-alkenylquinazolin-4(3H)-ones: synthesis of methylene and vinyl derivatives of pyrrolo(pyrido)[2,1-b]quinazolinones
Authors: Vaskevych Alla I. , Savinchuk Nataliia O. , Vaskevych Ruslan I. , Shishkina Svitlana V. , Vovk Mykhailo V.
Published: June 2023

Under Pd(ii) catalysis, 2-alkenylquinazolinones undergo aza-Wacker cyclization to methylenepyrrolo(pyrido)[2,1-b]quinazolinones and/or allylic C(sp3)–H bond activation with formation of vinylpyrido[2,1-b]quinazolinones.
Simplifying asteroseismic analysis of solar-like oscillators
Authors: Nielsen M. B. , Davies G. R. , Chaplin W. J. , Ball W. H. , Ong J. M. J. , Hatt E. , Jones B. P. , Logue M.
Published: June 2023

Context.The asteroseismic analysis of stellar power density spectra is often computationally expensive. The models used in the analysis may require several dozen parameters to accurately describe features in the spectra caused by the oscillation modes and surface granulation. Many of these parameters are often highly correlated, making the parameter space difficult to quickly and accurately sample. They are, however, all dependent on a much smaller set of parameters, namely the fundamental stellar properties.

Aims.We aim to leverage this to develop a method for simplifying the process of sampling the model parameter space for the asteroseismic analysis of solar-like oscillators, with an emphasis on mode identification.

Methods.Using a large set of previous observations, we applied principal component analysis to the sample covariance matrix to select a new basis on which to sample the model parameters. Selecting the subset of basis vectors that explains the majority of the sample variance, we then redefined the model parameter prior probability density distributions in terms of a smaller set of latent parameters.

Results.We are able to reduce the dimensionality of the sampled parameter space by a factor of two to three. The number of latent parameters needed to accurately model the stellar oscillation spectra cannot be determined exactly but is likely only between four and six. Using two latent parameters, the method is able to produce models that describe the bulk features of the oscillation spectrum, while including more latent parameters allows for a frequency precision better than ≈10% of the small frequency separation for a given target.

Conclusions.We find that sampling a lower-rank latent parameter space still allows for accurate mode identification and parameter estimation on solar-like oscillators over a wide range of evolutionary stages. This allows for the potential to increase the complexity of spectrum models without a corresponding increase in computational expense.
Gravitational collapse and accretion flows in the hub filament system G323.46-0.08
Authors: Ma Yingxiu , Zhou Jianjun , Esimbek Jarken , Baan Willem , Li Dalei , Tang Xindi , He Yuxin , Ji Weiguang , Zhou Dongdong , Wu Gang , Tursun Kadirya , Komesh Toktarkhan
Published: June 2023

We studied the hub-filament system G323.46-0.08 based on archival molecular line data from the SEDIGISM 13CO survey and infrared data from the GLIMPSE, MIPS, and Hi-GAL surveys. G323.46-0.08 consists of three filaments, F-north, F-west, and F-south, that converge toward the central high-mass clump AGAL 323.459-0.079. F-west and Part1 of the F-south show clear large-scale velocity gradients 0.28 and 0.44 km s−1 pc−1, respectively. They seem to be channeling materials into AGAL 323.459-0.079. The minimum accretion rate was estimated to be 1216 M⊙ Myr−1. A characteristic V-shape appears around AGAL323.459-0.079 in the PV diagram, which traces the accelerated gas motions under gravitational collapse. This has also been supported by model fitting results. All three filaments are supercritical and they have fragmented into many dense clumps. The seesaw patterns near most dense clumps in the PV diagram suggests that mass accretion also occurs along the filament toward the clumps. Our results show that filamentary accretion flows appear to be an important mechanism for supplying the materials necessary to form the central high-mass clump AGAL 323.459-0.079 and to propel the star forming activity taking place therein.
The nanoscale pore characteristics of coking coals. Part 4: The relationship between nanoscale pore characteristics and Gieseler fluidity
Authors: Zhang Song , Cheng Huan , Shi Chunlei , Wang Qi , Wang Yiming , Xiao Luying , Hou Yunlong
Published: June 2023

The nanoscale pore characteristics of six coal samples was determined using low-temperature N2 physisorption method in Part 3 of this series of articles [Cheng et al., Metall. Res. Technol. 114, 117 (2017)], and the possibility of nanoscale pore structure parameters to supplement and improve the existing coking coal property evaluation system is preliminarily demonstrated. The study focused on the relationship between nanoscale pore characteristics and Gieseler fluidity. The results show that external specific surface areas Sext-SAST and Gieseler fluidity thermoplastic parameters (plastic range ΔT and maximum fluidity MF expressed in logarithmic form) exhibit a primary linear relationship. External pore volume VBJH-ext and average pore size d̄DB display a quadratic parabolic relationship to thermoplastic parameters ΔT and LogMF. The correlations of the prediction models constructed for ΔT and LogMF with Sext-SAST, VBJH-ext and d̄DB as independent variables reached 0.97 and 0.96, respectively, indicating that the nanoscale pore characteristics are closely related to the Gieseler fluidity, and can play an important role in predicting the thermoplasticity of coking coals.
Die Split-Turnover-Pectoralislappenplastik: eine einfache und sichere
Methode zur Deckung sternaler Defekte
Authors: Spengler Claas , Masberg Frank , Mett Roland
Published: June 2023

Die Pectoralis-Muskellappenplastik ist zur Deckung sternaler Defekte nach tiefer
sternaler Wundinfektion weit verbreitet. Sie kann entweder als klassischer
Advancement-Flap, gestielt an der A. thoracoacromialis, oder als Turnover-Flap,
gestielt an den interkostalen Perforatoren der A. thoracica interna, gehoben
werden. Der Advancement-Flap hat den Nachteil, dass eine Bedeckung des
inferioren Sternumdrittels oft nicht erzielt werden kann, während der
Turnover-Flap zwar das inferiore und mediale Drittel bedeckt, oft aber im
kranialen Drittel nicht ausreicht. Die Autoren beschreiben eine neuartige
Methode zum Breitengewinn der Turnover-Pectoralis-Lappenplastik durch
Aufsplitten dieser entlang der Muskelfasern.Bei allen zwölf Patienten,
die zwischen 2017 und 2022 mit dieser Methode behandelt wurden, konnte eine
vollständige Abheilung sowie ein Wundverschluss erzielt werden. Die
Split-Pectoralis-Lappenplastik stellt damit eine sichere und effektive Methode
zur Defektdeckung sternaler Defekte dar.
The Impact of Polypharmacy on the Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation
Authors: Grymonprez Maxim , Petrovic Mirko , De Backer Tine L. , Steurbaut Stephane , Lahousse Lies
Published: June 2023

Background Polypharmacy may affect outcomes in patients with atrial fibrillation (AF) using non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) due to interactions or reduced adherence, but comparative data are lacking. Therefore, the impact of polypharmacy on AF-related outcomes and benefit–risk profiles of NOACs in patients with polypharmacy were investigated.

Methods AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate outcomes.

Results Among 254,478 AF patients, 167,847 (66.0%) used ≥5 drugs. Polypharmacy was associated with higher stroke or systemic embolism (stroke/SE) (adjusted hazard ratio [aHR]: 1.08, 95% confidence interval [CI]: 1.02–1.15), all-cause mortality (aHR: 1.45, 95% CI: 1.40–1.50), and major bleeding risks (aHR: 1.29, 95% CI: 1.23–1.35). Among patients with polypharmacy, NOACs were associated with lower stroke/SE (aHR: 0.68, 95% CI: 0.63–0.73), all-cause mortality (aHR: 0.80, 95% CI: 0.77–0.84), major bleeding (aHR: 0.92, 95% CI: 0.87–0.97), and intracranial bleeding risks (aHR: 0.77, 95% CI: 0.69–0.85), but higher gastrointestinal bleeding risks (aHR: 1.10, 95% CI: 1.01–1.19) compared to VKAs. Major bleeding risks were lower with apixaban (aHR: 0.79, 95% CI: 0.74–0.85), but nonsignificantly different with other NOACs compared to VKAs. Lower major bleeding risks were observed with dabigatran (aHR: 0.91, 95% CI: 0.85–0.97) and apixaban (aHR: 0.77, 95% CI: 0.73–0.81) compared to rivaroxaban, and with apixaban compared to dabigatran (HR: 0.83, 95% CI: 0.77–0.90) and edoxaban (HR: 0.77, 95% CI: 0.70–0.85).

Conclusion Polypharmacy was associated with increased thromboembolic, bleeding, and mortality risks in AF patients. NOACs had better benefit–risk profiles than VKAs in patients with polypharmacy.
Inverse design of ultra-wideband transparent frequency selective surface absorbers based on evolutionary deep learning
Authors: Pan Yaxi , Dong Jian , Wang Meng , Luo Heng , Abdulkarim Yadgar I
Published: June 2023

Conventional frequency selective surface (FSS) absorbers design is time-consuming, involving multiple electromagnetic (EM) simulations for parameter scanning. A novel reverse design method is proposed utilizing evolutionary deep learning (EDL) based on an improved bacterial foraging optimization (IBFO) algorithm and a deep belief network. It establishes the relationship between the geometric structure and EM response. The combination of IBFO and EDL facilitates an efficient optimization for structural parameters, mitigating the ‘one-to-many’ problem and accelerating the design process. An optically transparent FSS absorber with an ultra-bandwidth of 8–18 GHz is designed to verify the proposed method’s capability. The simulation and experimental results demonstrate that the absorber displays exceptional characteristics such as polarization insensitivity and robustness under a 45° oblique incidence angle, making it a suitable candidate for radar stealth and photovoltaic solar energy applications. The proposed method can be applied to the design and optimization of various absorbers and complex EM devices.
Anisotropic transport properties and high-mobility of charge carriers of antiferromagnetic GdAgSb2
Authors: Roy Shubhankar , Singha Ratnadwip , Alam Rafiqul , Mandal Prabhat
Published: June 2023

We report detailed magnetic and magnetotransport properties of single-crystalline GdAgSb2 antiferromagnet. The electronic transport properties show metallic behavior along with large, anisotropic, and non-saturating magnetoresistance (MR) in transverse experimental configuration. At 2 K and 9 T, the value of MR reaches as high as ∼1.8×103%. The anisotropic MR along with additional features for applied magnetic field along some specific crystallographic directions reveal the quasi-two-dimensional nature of the Fermi surface of GdAgSb2. Hall resistivity confirms the presence of two types of charge carriers. The high carrier mobilities (∼1.2×104 cm2 V−1 s−1) and nearly-compensated electron and hole-density (∼1019 cm−3) could be responsible for the large transverse MR in GdAgSb2. We have also observed the de Haas–van Alphen oscillations in the magnetization measurements below 7 K. Furthermore, the robust planar Hall effect, which persists up to high temperatures, could indicate the nontrivial nature of the electronic band structure for GdAgSb2.
A stable r-adaptive mesh technique to analyze the advection-diffusion equation
Authors: Sultan Saad , Zhengce Zhang , Usman Muhammad
Published: June 2023

This paper offers a study of the moving mesh method employed in one-dimensional linear and nonlinear advection-diïffusion equations with different boundary and initial conditions. Advection and diffusion appear in the crux of the physical processes, where the transport of heat or other physical variables evolves. The aim is to present an accurate, stable moving finite-difference meshing scheme with its convergence. The velocity-profile of the considered cases is non-linear; therefore, the difference scheme needs mesh refinement. The moving mesh method analyzes the problem physics and adjusts the mesh according to the problem as it moves nodes in the region of more fluctuations. The approximate numerical results are estimated using four moving mesh partial differential equations with varying numbers of nodes. The moving mesh method is an r-adaptive technique that uses a fixed number of mesh nodes and moves the grids where error reduction is needed. The numerical solutions obtained are compared with the analytical solutions cited from the literature. The study presents five cases dealing with linear and non-linear examples in detail to understand the physics of the problem. The presented difference scheme is considerably more efficient than the numerical methods given in the literature.
Family of 𝒟-modules and representations with a boundedness property
Authors: Kitagawa Masatoshi
Published: June 2023

In the representation theory of real reductive Lie groups, many objects have finiteness properties. For example, the lengths of Verma modules and principal series representations are finite, and more precisely, they are bounded. In this paper, we introduce a notion of uniformly bounded families of holonomic

D

{\mathscr {D}}

-modules to explain and find such boundedness properties.

A uniform bounded family has good properties. For instance, the lengths of modules in the family are bounded and the uniform boundedness is preserved by direct images and inverse images. By the Beilinson–Bernstein correspondence, we deduce several boundedness results about the representation theory of complex reductive Lie algebras from corresponding results of uniformly bounded families of

D

{\mathscr {D}}

-modules. In this paper, we concentrate on proving fundamental properties of uniformly bounded families, and preparing abstract results for applications to the branching problem and harmonic analysis.
The role of lifestyle in the association between frailty and all-cause mortality amongst older adults: a mediation analysis in the UK Biobank
Authors: Delgado-Velandia Mario , Maroto-Rodríguez Javier , Ortolá Rosario , Rodríguez-Artalejo Fernando , Sotos-Prieto Mercedes
Published: June 2023

Objective

frailty is a syndrome characterised by increased vulnerability to stressors, which manifests as higher death risk. Whilst guidelines for frailty management usually entails lifestyle modifications (e.g. physical exercise, diet), the mediating role of lifestyle on the excess mortality associated with frailty is unclear. This study estimates the death risk due to frailty that could be avoided with a healthy lifestyle in older adults.

Subjects and Methods

we analysed data from 91,906 British individuals aged ≥60 years recruited between 2006 and 2010. At baseline, frailty was identified according to Fried’s phenotype, and a four-item Healthy Lifestyle Index (HLS) was calculated based on physical activity, diet, smoking and alcohol consumption. Mortality was ascertained from baseline through 2021. A mediation analysis under the counterfactual framework was performed adjusting for the main confounders.

Results

during a median follow-up of 12.5 years, 9,383 deaths occurred. Frailty was directly associated with all-cause mortality (hazard ratio: 2.30 [95% confidence interval {CI} 2.07, 2.54]), and inversely associated with the HLS (ß: −0.45 points [−0.49, −0.40]). The hazard ratio [95%CI] for the direct effect of frailty on mortality was 2.12 [1.91, 2.34], whilst for the indirect effect (mediated by HLS) was 1.08 [1.07, 1.10]. The mediated proportion of HLS on mortality was 13.55% [11.26, 16.20], with physical activity having the highest proportion amongst the four HLS items (7.69% [5.00, 10.40]).

Conclusions

a healthy lifestyle partly mediates the association between frailty and mortality in British older adults. Since this was an exploratory mediation analysis, these results should be specifically tested in future research.
‘Frailty as an adjective rather than a diagnosis’—identification of frailty in primary care: a qualitative interview study
Authors: Seeley Anna , Glogowska Margaret , Hayward Gail
Published: June 2023

Introduction

In 2017, NHS England introduced proactive identification of frailty into the General Practitioners (GP) contract. There is currently little information as to how this policy has been operationalised by front-line clinicians, their working understanding of frailty and impact of recognition on patient care. We aimed to explore the conceptualisation and identification of frailty by multidisciplinary primary care clinicians in England.

Methods

Qualitative semi-structured interviews were conducted with primary care staff across England including GPs, physician associates, nurse practitioners, paramedics and pharmacists. Thematic analysis was facilitated through NVivo (Version 12).

Results

Totally, 31 clinicians participated. Frailty was seen as difficult to define, with uncertainty about its value as a medical diagnosis. Clinicians conceptualised frailty differently, dependant on job-role, experience and training. Identification of frailty was most commonly informal and opportunistic, through pattern recognition of a frailty phenotype. Some practices had embedded population screening and structured reviews. Visual assessment and continuity of care were important factors in recognition. Most clinicians were familiar with the electronic frailty index, but described poor accuracy and uncertainty as to how to interpret and use this tool. There were different perspectives amongst professional groups as to whether frailty should be more routinely identified, with concerns of capacity and feasibility in the current climate of primary care workload.

Conclusions

Concepts of frailty in primary care differ. Identification is predominantly ad hoc and opportunistic. A more cohesive approach to frailty, relevant to primary care, together with better diagnostic tools and resource allocation, may encourage wider recognition.
Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease
Authors: Li Hao , Jacob Mina A , Cai Mengfei , Duering Marco , Chamberland Maxime , Norris David G , Kessels Roy P C , de Leeuw Frank-Erik , Marques José P , Tuladhar Anil M
Published: June 2023

The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions.

In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts.

We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = −0.30, Pcorrected < 0.001), lower R1 (β = −0.26, Pcorrected = 0.001), lower R2* (β = −0.32, Pcorrected < 0.001) and lower susceptibility values (β = −0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions.

Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.
Juvenile and adult expression of polyglutamine expanded huntingtin produce distinct aggregate distributions inDrosophilamuscle
Authors: Barwell Taylor , Raina Sehaj , Page Austin , MacCharles Hayley , Seroude Laurent
Published: June 2023

While Huntington’s disease (HD) is widely recognized as a disease affecting the nervous system, much evidence has accumulated to suggest peripheral or non-neuronal tissues are affected as well. Here, we utilize the UAS/GAL4 system to express a pathogenic HD construct in the muscle of the fly and characterize the effects. We observe detrimental phenotypes such as a reduced lifespan, decreased locomotion and accumulation of protein aggregates. Strikingly, depending on the GAL4 driver used to express the construct, we saw different aggregate distributions and severity of phenotypes. These different aggregate distributions were found to be dependent on the expression level and the timing of expression. Hsp70, a well-documented suppressor of polyglutamine aggregates, was found to strongly reduce the accumulation of aggregates in the eye, but in the muscle, it did not prevent the reduction of the lifespan. Therefore, the molecular mechanisms underlying the detrimental effects of aggregates in the muscle are distinct from the nervous system.
HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV
Authors: Benner Sarah E , Zhu Xianming , Hussain Sarah , Florman Sander , Eby Yolanda , Fernandez Reinaldo E , Ostrander Darin , Rana Meenakshi , Ottmann Shane , Hand Jonathan , Price Jennifer C , Pereira Marcus R , Wojciechowski David , Simkins Jacques , Stosor Valentina , Mehta Sapna A , Aslam Saima , Malinis Maricar , Haidar Ghady , Massie Allan , Smith Melissa L , Odim Jonah , Morsheimer Megan , Quinn Thomas C , Laird Gregory M , Siliciano Robert , Balagopal Ashwin , Segev Dorry L , Durand Christine M , Redd Andrew D , Tobian Aaron A R
Published: June 2023

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV.

Clinical Trials Registration. NCT02602262 and NCT03734393.
Supporting the helpers: what do peer deliverers of HIV interventions need to sustain their implementation efforts?
Authors: Jaramillo Jahn , Harkness Audrey
Published: June 2023

Peer-led HIV interventions are an increasingly common and low-cost strategy to address shortages of professionally trained health workers for implementing evidence-based HIV prevention and treatment interventions to populations who experience health disparities. There is a need to understand the experiences and unmet needs of this essential workforce responsible for implementing and delivering HIV interventions to ensure their implementation efforts are sustainable. This commentary provides a brief overview of barriers to peer deliverers’ sustained engagement in the HIV workforce and potential implementation strategies to promote the sustainment of peer deliverers’ implementation efforts.
Physicians’ Clinical Behavior During Fluid Evaluation Encounters
Authors: Syed Muhammad K. Hayat , Pendleton Kathryn , Park John , Weinert Craig
Published: June 2023

OBJECTIVES:

We sought to identify factors affecting physicians’ cognition and clinical behavior when evaluating patients that may need fluid therapy.

BACKGROUND:

Proponents of dynamic fluid responsiveness testing advocate measuring cardiac output or stroke volume after a maneuver to prove that further fluids will increase cardiac output. However, surveys suggest that fluid therapy in clinical practice is often given without prior responsiveness testing.

DESIGN:

Thematic analysis of face-to-face structured interviews.

SETTING:

ICUs and medical-surgical wards in acute care hospitals.

SUBJECTS:

Intensivists and hospitalist physicians.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We conducted 43 interviews with experienced physicians in 19 hospitals. Hospitalized patients with hypotension, tachycardia, oliguria, or elevated serum lactate are commonly seen by physicians who weigh the risks and benefits of more fluid therapy. Encounters are often with unfamiliar patients and evaluation and decisions are completed quickly without involving other physicians. Dynamic testing for fluid responsiveness is used much less often than static methods and fluid boluses are often ordered with no testing at all. This approach is rationalized by factors that discourage dynamic testing: unavailability of equipment, time to obtain test results, or lack of expertise in obtaining valid data. Two mental calculations are particularly influential: physicians’ estimate of the base rate of fluid responsiveness (determined by physical examination, chart review, and previous responses to fluid boluses) and physicians’ perception of patient harm if 500 or 1,000 mL fluid boluses are ordered. When the perception of harm is low, physicians use heuristics that rationalize skipping dynamic testing.

LIMITATIONS:

Geographic limitation to hospitals in Minnesota, United States.

CONCLUSIONS:

If dynamic responsiveness testing is to be used more often in routine clinical practice, physicians must be more convinced of the benefits of dynamic testing, that they can obtain valid results quickly and believe that even small fluid boluses harm their patients.
Diagnostic Accuracy of Group A Streptococcus Rapid Antigen Detection Test on Middle Ear Fluid in Children With Acute Otitis Media With Spontaneous Perforation: A Prospective Multicenter Evaluation
Authors: Cohen Robert , Varon Emmanuelle , Bidet Philippe , Cohen Jérémie F. , Béchet Stéphane , Couloigner Vincent , Michot Anne Sylvestre , Guiheneuf Cécile , Bonacorsi Stéphane , Levy Corinne
Published: June 2023

Group A Streptococcus is one of the leading causes of otorrhea. The performance of rapid antigen tests in 256 children with otorrhea showed excellent sensitivity, 97.3% (95% confidence interval: 90.7%–99.7%), and specificity, 100% (95% confidence interval: 98.0%–100%). In a period of increasing invasive and noninvasive group A Streptococcus infections, an early diagnosis could be useful.
Atypical Erythema Multiforme, a Clinical Mimicker of Monkeypox
Authors: Njoroge Alexander , Maramara Bennadette , Saldivar Miguel
Published: June 2023

Erythema multiforme (EM) is a skin eruption caused by a variety of triggers and may be misdiagnosed. Infection, most commonly with herpes simplex virus, has been linked to the development of EM. Mycoplasma pneumoniae is a rare but known cause in adults. Classically described as target lesions, atypical EM lacks the concentric areas of circular erythema bordered by clear zones. We present a case of atypical EM in a 71-year-old man with acute Mycoplasma pneumoniae to highlight the natural alterations of EM in a nonimmunocompromised host.
Fibroblast Activation Protein-α (FAP) Identifies Stromal Invasion in Colorectal Neoplasia
Authors: Tarín-Nieto Alexandre , Solano-Iturri Jon D. , Arrieta-Aguirre Inés , Valdivia Asier , Etxezarraga María C. , Loizate Alberto , López José I. , Larrinaga Gorka
Published: June 2023

The increasing detection of colorectal adenomas and early adenocarcinomas (ADCs) in the context of nationwide screening programs has led to a significant increase in the incidence of inconclusive diagnoses in which histopathologic analysis of endoscopic biopsies does not allow pathologists to provide a reliable diagnosis of stromal invasion. The objective of this study was to analyze the discriminative capacity of the immunohistochemical expression of fibroblast activation protein-α (FAP) in distinguishing colorectal adenomas with low-grade dysplasia (LGD) and high-grade dysplasia (HGD) from invasive intestinal-type ADCs. The study analyzed the first endoscopic biopsies from a series of patients classified as inconclusive or conclusive for stromal invasion based on the pathologic report. In total, 30 ADCs, 52 HGDs, and 15 LGDs were included in the study. FAP expression was detected in 23/30 ADCs and was negative in all adenomas with either LGD or HGD features (100% specificity and 76.7% sensitivity, area under the curve=0.883, CI=0.79-0.98). Considering these findings, we conclude that FAP is a potentially useful tool for helping pathologists identify invasive lesions in colorectal endoscopic biopsies, avoiding unnecessary biopsy repetitions.
Clinical guidelines recommending prosthetics and orthotics in Sweden: Agreement between national and regional guidelines
Authors: Hellstrand Tang Ulla , Jarl Gustav , Eriksson Marie , Johannesson G. Anton , Rusaw David F.
Published: June 2023

Background:

Despite the presence of both national and regional clinical practical guidelines (CPGs) in Sweden, no previous studies have investigated the quality of CPGs or the level of agreement between national and regional CPGs.

Objective(s):

This study aimed to assess the quality of national CPGs recommending prosthetics and orthotics (P&O) and quantify the agreement between national and regional CPGs in Sweden.

Study design:

Literature Review.

Methods:

National and regional CPGs were identified in public databases and by surveyed local nurse practitioners. Quality of the national guidelines was assessed by using AGREE II. Agreement between recommendations in the national and regional CPGs was quantified on a 4-grade rating scale (“similar,” “partially similar,” “not similar/not present,” and “different”).

Results:

Of 18 national CPGs, 3 CPGs (CPGs of Diabetes, Musculoskeletal disorders, and Stroke) had 9 recommendations related to P&O. The Musculoskeletal disorders and Stroke CPGs had quality scores .60% in all domains, and the Diabetes CPG had scores .60% in 5 of 6 domains according to AGREE II. Seven regional CPGs for P&O treatment were identified. Three national recommendations (in Diabetes CPGs) showed “similar” content for all regions, and 2 national recommendations (in Diabetes CPGs) showed “not similar” content for all regions. The remaining recommendations (Diabetes, Musculoskeletal disorders, and Stroke CPGs) had varying agreement with regional CPGs.

Conclusions:

There is a limited number of national recommendations for treatment within P&O. There was variation in the agreement of P&O–related recommendations in national and regional CPGs, which might lead to unequal care throughout the national healthcare system.
Redhead, Paroissien, Parish & Co.: British Field Science in early Independent RÍo de la Plata
Authors: de Asúa Miguel
Published: June 2023

This article explores the activities of those British travellers and settlers who carried out open field research in the Andean northwest of Río de la Plata during the 1820s. The focus is set upon Doctor Joseph Redhead, who became a regional expert on questions of mountain altitudes and natural portents such as giant fossil bones and large masses of native iron. Redhead was at the centre of a network of British doctors, entrepreneurs, adventurers and civil servants who crisscrossed the territory attracted by new mining ventures and the opening of trade, and driven by the need for geographical surveys implicit in the logic of empire. James Paroissien, Woodbine Parish, Joseph Pentland and others managed to combine research on the natural environment while engaged in their commercial, diplomatic or military missions. Particular attention is paid to the interactions of Redhead and his fellow countrymen with Humboldt and the kind of science cultivated by him, as well as to issues of scientific authority at the time of deciding on the cause of unexplained natural phenomena.
Making science for the Portuguese Empire: The Royal Maritime, Military and Geographic Society (1798–1809)
Authors: Martins Carlos Moura , Figueiredo Fernando B.
Published: June 2023

The Sociedade Real Marítima, Militar e Geográfica (Royal Maritime, Military and Geographic Society) was a scientific institution founded in Portugal by the Minister of the Navy, Rodrigo de Sousa Coutinho, in the late eighteenth century. Its advent was contemporary with the rise of hydrographic institutes in several European maritime powers. However, the Royal Maritime, Military and Geographic Society differed from the specialization of those institutions, being deeply involved in determining longitudes and producing good precision hydrographic cartography. Conceived as a multidisciplinary institute gathering scientific and technical knowledge and focusing on overseas and metropolitan territories, it had an intense activity, resulting in a scientific production (unfortunately largely lost) in tune with its foreign counterparts. However, and unlike other European hydrographic institutes, this Portuguese institute had an ephemeral existence.