bluuebunny/crossref_metadata_2025 huggingface dataset:
Jordan decomposition of non-Hermitian fermionic quadratic forms
Authors: Kitahama Shunta , Yoshida Hironobu , Toyota Ryo , Katsura Hosho
Published: January 2024

We give a rigorous proof of conjecture 3.1 by Prosen (2010 J. Stat. Mech. 2010 P07020) on the nilpotent part of the Jordan decomposition of a quadratic fermionic Liouvillian. We also show that the number of Jordan blocks of each size can be expressed in terms of the coefficients of a polynomial called the q-binomial coefficient, and describe the procedure for obtaining the Jordan canonical form of the nilpotent part.
Two-stage robust programming model for active distribution network with a high proportion of renewable energy
Authors: Liu Chao , Zhang Peng , Huang Zongjun , Yang Liu
Published: January 2024

To reduce operating costs and obtain the optimal location and capacity of renewable energy access, a two-stage robust planning model is studied for active distribution networks with a high proportion of renewable energy access. To build a function to minimize annual comprehensive costs, the constraints of power flow, branch power, and node voltage of the active distribution network are studied. Considering the characteristics and properties of power flow safety constraints, the mixed integer second-order cone transformation is used to construct a mixed integer convex programming model, which is convenient for efficiently obtaining the global optimal solution. To avoid the influence of uncertainty, a two-stage robust model is constructed. The explicit maximum value method is used to obtain the solution results that satisfy the planning model of all uncertain problems. Experiments show that the model can obtain the optimal access position and capacity of renewable energy. After application, it can reduce the annual comprehensive cost of the distribution network and ensure the stable and safe operation of the active distribution network.
Active alarm method for switchgear status based on K-means clustering and multi-dimensional feature quantities
Authors: Zhou Jinglong , Zhi Ruifeng , Shang Yanyun , Li Zhenlin , Shang Shulei
Published: January 2024

Switchgear is the critical equipment of the distribution network, and its status evaluation is of great significance to improve the reliability of the distribution network. Addressing the issues of high subjectivity and low accuracy in current methods of status evaluation, we propose an active alarm method for switchgear status based on K-means clustering and multi-dimensional feature quantities. We configure multiple sensors at different locations inside the switchgear to monitor and obtain multi-source data based on IoT sensing technology. We establish a multi-dimensional status dataset of the switchgear and analyze its fluctuation. We acquire the relationship between the number of clusters K and the sum of squares of errors by clustering the obtained multi-dimensional dataset of switchgear through the K-means clustering status evaluation algorithm. We also calculate the sum of squares of errors under different clusters and the optimal number of clustering levels. Finally, we combine a set of switchgear operation data to obtain the switchgear health status by cluster analysis, which verifies the effectiveness of the evaluation method.
Numerical simulation of flow and heat transfer of n-decane in composite tube under supercritical pressure
Authors: Ma Hailong , Gao Hui , Zhao Jiajun , Zhang Chen , Wen Dongsheng
Published: January 2024

As scramjet propulsion systems face big challenges in thermal protection performance, regenerative cooling techniques have been proposed to improve heat transfer behavior. This study introduced a novel design of composite cooling channel with bends and conducted computational fluid dynamics (CFD) simulations to analyze the flow characteristics, heat transfer behavior, and pyrolysis of hydrocarbon fuel within the tube. Results show that the presence of bends significantly enhances heat transfer, leading to an increased temperature and conversion. The composite tube with 15 bends demonstrated a 19.9% increase in conversion rate compared to the straight tube. Hence, proper structure design can improve the regenerative cooling performance which may promote the development of scramjet propulsion systems.
Research on the additional drag of turboshaft engine inlet under complex aerodynamic interference
Authors: Cheng Benlin , Huang Xing , Shan Hang , Cui Jiahang , Cai Feichao
Published: January 2024

In response to the complex aerodynamic interference in the inlet flow field of a turboshaft engine and the difficulty in calculating additional drag, a study was conducted based on numerical algorithms to calculate additional drag. Through the numerical calculation of the internal and external interference flow field model of the helicopter rotor and body, the inlet, the integral component of the exit section parameter, and the inner channel drag are extracted, and the calculation model of additional drag based on the momentum balance of the inlet channel and the control body of the pre-inlet tube is established. The calculation and analysis are carried out according to different operating conditions such as flight speed and inlet flow change. The results show that the calculation model of additional drag based on the three-dimensional numerical value of the interference flow field, considering the aerodynamic interference of incoming flow conditions, rotor, and body on the flow field, can realize the additional drag analysis under complex conditions. The downwash flow generated by the rotor affects the inlet front streamlines and additional drag, and the additional drag of the left and right inlets will also be different.
A stability-enhanced approach for aerodynamic heating computation in high-speed flows
Authors: Zhang Ye , Yu Hang , Ren Weijie , Li Hua
Published: January 2024

Near-space vehicles face severe aerothermal environments due to hypersonic speeds. Accurately predicting hypersonic aerodynamic heating is crucial for the design of spacecraft’s thermal protection systems, aerodynamic shapes, and propulsion systems. Numerical simulations have become an important tool for computing aerothermal environments under extreme conditions. However, there is a contradiction between the robustness and low dissipation characteristics of existing numerical methods for hypersonic flow fields. This paper proposes an effective dimension hybrid approach that enhances the robustness of AUSM-family schemes while maintaining their low dissipation characteristics. Numerical experiments demonstrate the proposed approach’s effectiveness and potential for practical engineering applications.
Numerical simulation analysis of anchor pullout under radial pressurization of anchor solid
Authors: Ren Chenfeng , Shi Xin
Published: January 2024

The rock structure of weak rock formation is loose with low strength, which is easy to deform. Due to insufficient elongation and bearing capacity, anchor anchorage system damage is frequent and serious. Given the above problems, this paper researches the radial increase in compressive stress anchoring mechanism and uses finite element software ABAQUS simulation algorithms to obtain different radial pressurization conditions under the deformation of the surrounding rock law and the anchor pulling the anchor and the surrounding rock displacement stress change rule. The results show that when applying the radial pressure of 1.5 MPa, the surrounding rock and the anchor stress reach their maximum value, and the displacement reaches its minimum value. Field testing and monitoring results show that radial pressurized anchors can effectively control the deformation of the roadway perimeter rock and improve the anchoring effect.
Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles
Authors: Yenurkar Devyani , Ruocco Maria , Pragya  , Liang Lily , Mukherjee Sudip
Published: January 2024

Nanomedicine often failed clinically to show therapeutic efficacy due to reduced particle circulation and enhanced capture by the reticuloendothelial system, including the liver. Developing novel immunomodulatory surface coating can prevent macrophage capture and increase the particle circulation of the nanomedicine, resulting in higher therapeutic efficiency. Herein, we demonstrate the development of immunomodulatory small molecule (RZA15) with triazole functionality using copper-catalyzed click chemistry to conjugate onto spherical polystyrene nanoparticles (NPs) using amide coupling reactions, achieving higher blood circulation and lesser macrophage uptake of the nanoconjugates (NCs). In this work, we evaluated the effectiveness of RZA15 coating for the enhanced circulation of polystyrene NPs of 100 nm size, which is commonly utilized for various drug delivery applications, and compared with poly(ethylene)glycol coatings. Several polystyrene NC formulations were analyzed in vitro in normal and macrophage cells for cell viability and cellular uptake studies. In vitro studies demonstrated lesser macrophage uptake of the NCs following RZA15 coating. Finally, in vivo, blood-circulation, pharmacokinetics, and biodistribution studies were performed in the C57BL/6J mouse model that endorsed the substantial role of RZA15 in reducing liver and spleen capture and results in extended circulation in blood. Coating immunomodulatory small molecules to nanoparticles can severely enhance the potential therapeutic effects of nanomedicine at lower doses in near future.
Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings
Authors: Ding Peng , Ding Xiaoyue , Li Jingyu , Guo Wei , Okoro Oseweuba Valentine , Mirzaei Mahta , Sun Yanfang , Jiang Guohua , Shavandi Amin , Nie Lei
Published: January 2024

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.
A heparin-based nanogel system for redox and pH dual-responsive delivery of cisplatin
Authors: Thi Huong Nguyen , Ngoc Son Nguyen , Minh Thanh Vu , Van Quan Le , Bui Vu Thuy Duong , Nguyen Ngoc Hoi
Published: January 2024

Heparin recently has been discovered as a novel anti-cancer agent. The combinations of heparin with other agents was reported not only to reduce the undesired effects of free heparin and increase the cellular uptake of the delivered molecules, but also is the basis for the design and development of multi-stimulation response systems to improve their killing cancer cell efficiency at the target positions. This study aimed to design a redox and pH dual-responsive anticancer system based on heparin for cisplatin (CPT) therapy. Heparin was first cross-linked with Poloxamer 407 chains via disulfide bridges to form a redox-sensitive system Hep-P407. CPT was then encapsulated into the Hep-P407 system via the complex of Platin and carboxyl groups to form the redox/pH-responsive system CPT@Hep-P407. The obtained Hep-P407 systems were proved and characterized using specific techniques including 1H-NMR, zeta potential, Dynamic Light Scattering (DLS) and Fourier-transform infrared spectroscopy. The dual-responsive behavior to redox and pH of CPT@Hep-P407 was proved through DLS, zeta and in vitro release analysis meanwhile its cytotoxicity was investigated using Resazurin assay. The CPT@Hep-P407 system is expected to be a promising redox/pH-responsive anticancer system based on heparin for CPT therapy.
Not even 6 dB: Gaussian quantum illumination in thermal background
Authors: Volkoff T J
Published: January 2024

In analyses of target detection with Gaussian state transmitters in a thermal background, the thermal occupation is taken to depend on the target reflectivity in a way which simplifies the analysis of the symmetric quantum hypothesis testing problem. However, this assumption precludes comparison of target detection performance between an arbitrary transmitter and a vacuum state transmitter, i.e. ‘detection without illumination’, which is relevant in a bright thermal background because a target can be detected by its optical shadow or some other perturbation of the background. Using a target-agnostic thermal environment leads to the result that the oft-claimed 6 dB possible reduction in the quantum Chernoff exponent for a two-mode squeezed vacuum transmitter over a coherent state transmitter in high-occupation thermal background is an unachievable limiting value, only occurring in a limit in which the target detection problem is ill-posed. Further analyzing quantum illumination in a target-agnostic thermal environment shows that a weak single-mode squeezed transmitter performs worse than ‘no illumination’, which is explained by the noise-increasing property of reflected low-intensity squeezed light.
A comparative study on the spectral characteristics of nanosecond pulsed discharges in atmospheric He and a He+2.3%H2O mixture
Authors: CHEN 陈 Chuanjie 传杰 , PENG 彭 Dongyu 东宇 , LIU 刘 Botong 博通 , ZHANG 张 Tinglin 婷琳 , QIAN 钱 Muyang 沐杨 , ZHOU 周 Feng 锋 , WANG 王 Rugang 如刚
Published: January 2024

Nanosecond pulsed discharges at atmospheric pressure in a pin-to-pin electrode configuration are well reproducible in time and space, which is beneficial to the fundamentals and applications of low-temperature plasmas. In this experiment, the discharges in helium (He) and He with 2.3% water vapor (H2O) are driven by a series of 10 ns overvoltage pulses (~13 kV). Special attention is paid to the spectral characteristics obtained in the center of discharges by time-resolved optical emission spectroscopy. It is found that in helium, the emission of atomic and molecular helium during the afterglow is more intense than that in the active discharge, while in the He+2.3%H2O mixture, helium emission is only observed during the discharge pulse and the molecular helium emission disappears. In addition, the emissions of OH(A-X) and Hα present similar behavior that increases sharply during the falling edge of the voltage pulse as the electrons cool down rapidly. The gas temperature is set to remain low at 540 K by fitting the OH(A-X) band. A comparative study on the emission of radiative species (He, He2, OH and H) is performed between these two discharge cases to derive their main production mechanisms. In both cases, the dominant primary ion is He+ at the onset of discharges, but their He+ charge transfer processes are quite different. Based on these experimental data and a qualitative discussion on the discharge kinetics, with regard to the present discharge conditions, it is shown that the electron-assisted three-body recombination processes appear to be the significant sources of radiative OH and H species in high-density plasmas.
Blood Pressure Measurements Obtained by Community-Dwelling Adults Are Similar to Nurse-Obtained Measurements: The SMART-BP Validate Study
Authors: Liu Xiaoyue , Slone Sarah E , Chen Yuling , Yeboah-Kordieh Yvette , Alharthi Abeer , Amihere Johnitta , Moyo-Songonuga Sharon , Lane Tynetta , Ostchega Yechiam , Brady Tammy M , Himmelfarb Cheryl R , Commodore-Mensah Yvonne
Published: January 2024

BACKGROUND

Self-measured blood pressure (SMBP) is an effective strategy for managing and controlling hypertension. However, uncertainty regarding patients’ ability to accurately measure their blood pressure (BP) contributes to treatment inertia. Therefore, we compared BP measurements with the Omron HEM-9210T device obtained by nurses and community-dwelling adults after training.

METHODS

This cross-sectional study was conducted in a simulated home environment at an academic institution. After a 5-min rest, a trained nurse measured a participant’s BP twice at a 1-min interval. The participants then ambulated at their usual pace for 2 min. Next, they were asked to rest for 5 min, during which each individual watched a 3-min video on SMBP. Following the rest, the participants obtained two readings at a 1-min interval.

RESULTS

We recruited 102 community-dwelling adults with a mean age of 54 (±14) years; 59% female, 88% Black race, and 63% with a hypertension diagnosis. Half (n = 51) had a home BP monitor. Overall, there were no significant differences between nurse- and participant-obtained systolic BP (mean difference [MD]: −1.1; standard deviation [SD]: 8.0; P = 0.178) or diastolic BP (MD: −0.9; SD: 5.5; P = 0.111). Participants who used an extra-large cuff had higher self-measured diastolic BP (MD: −2.9; SD: 4.5; P = 0.010). All participants demonstrated satisfactory SMBP skills after the training.

CONCLUSIONS

Community-dwelling adults can accurately measure BP after a 3-min video training. Integrating SMBP training into patient encounters may result in reliable home BP measurements, improving hypertension management and clinical decision making.
Goals and benefits in topical treatment for psoriasis: development and pilot validation of a patient-reported outcomes tool, the Patient Benefit Index for Topical Treatment (PBI-TOP)
Authors: Blome Christine , Hülswitt Lennart , Meineke Anna , Augustin Matthias , Ohm Frenz , Rusch Judith , Janke Toni Maria
Published: January 2024

Background

Topical agents are an essential component of psoriasis therapy.

Objectives

To develop a new version of the patient-reported Patient Benefit Index assessing the importance and achievement of treatment goals in topical psoriasis therapy in adult patients (PBI-TOP).

Methods

Through semi-structured interviews, focus groups and free-text questionnaires, patients reported their needs in topical treatment. Based on qualitative content analysis, items were developed by a consensus group and were refined in cognitive debriefing interviews. A pilot validation assessed the PBI-TOP and convergent criteria [Dermatology Life Quality Index (DLQI); Psoriasis Area and Severity Index (PASI); affected Body Surface Area (BSA)].

Results

Thirty patients (26–72 years, mean 47; 60% male) reported various treatment goals relating to the themes ‘effectiveness’ and ‘characteristics of the preparation’. Twenty patients took part in cognitive debriefings (22–84 years, mean 50.6, 50% male). There were 154 patients who participated in the pilot validation (18–85 years, mean 46.9, 63.6% male). An importance-weighted total score on overall effectiveness and three subscales based on exploratory factor analysis were defined: effectiveness on symptoms, effectiveness on quality of life (QoL), and characteristics of the preparation. All scores showed excellent internal consistency (α > 0.9). The global effectiveness score correlated significantly with DLQI (r = –0.41), PASI (r = –0.32) and BSA (r = –0.22). The effectiveness subscales (symptoms; QoL) correlated significantly with DLQI (r = –0.41; –0.32) and PASI (r = –0.27; –0.33). The score on characteristics of the preparation correlated significantly with the DLQI (r = –0.34).

Conclusions

The PBI-TOP showed good feasibility and favourable psychometric characteristics in this pilot validation.
Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials
Authors: Lebwohl Mark , Warren Richard B , Sofen Howard , Imafuku Shinichi , Paul Carle , Szepietowski Jacek C , Spelman Lynda , Passeron Thierry , Vritzali Eleni , Napoli Andrew , Kisa Renata M , Buck Alex , Banerjee Subhashis , Thaçi Diamant , Blauvelt Andrew
Published: January 2024

Background

In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis.

Objective

To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials.

Methods

In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician’s Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy).

Results

At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu­cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders.

Conclusions

Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years.
Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning
Authors: Lötsch Jörn , Brosig Oskar , Slobodova Jana , Kringel Dario , Haehner Antje , Hummel Thomas
Published: January 2024

Loss of olfactory function is a typical acute coronavirus disease 2019 (COVID-19) symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows for assessing the long-term prognosis of its olfactory impact.

Participants (n = 722) of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days were approached in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on an 11-point numerical scale [0,…10]. Neither the frequency of olfactory diagnostic categories nor olfactory test scores showed any COVID-19-related effects. Olfactory diagnostic categories (anosmia, hyposmia, or normosmia) were similarly distributed among former patients and controls (0.86%, 18.97%, and 80.17% for former patients and 1.17%, 17.51%, and 81.32% for controls). Former COVID-19 patients, however, showed differences in their subjective perception of their own olfactory function. The impact of this effect was substantial enough that supervised machine learning algorithms detected past COVID-19 infections in new subjects, based on reduced self-awareness of olfactory performance and parosmia, while the diagnosed olfactory function did not contribute any relevant information in this context.

Based on diagnosed olfactory function, results suggest a positive prognosis for COVID-19-related olfactory loss in the long term. Traces of former infection are found in self-perceptions of olfaction, highlighting the importance of investigating the long-term effects of COVID-19 using reliable and validated diagnostic measures in olfactory testing.
High compositional and functional similarity in the microbiome of deep-sea sponges
Authors: Díez-Vives Cristina , Riesgo Ana
Published: January 2024

Sponges largely depend on their symbiotic microbes for their nutrition, health, and survival. This is especially true in high microbial abundance (HMA) sponges, where filtration is usually deprecated in favor of a larger association with prokaryotic symbionts. Sponge-microbiome association is substantially less understood for deep-sea sponges than for shallow water species. This is most unfortunate, since HMA sponges can form massive sponge grounds in the deep sea, where they dominate the ecosystems, driving their biogeochemical cycles. Here, we assess the microbial transcriptional profile of three different deep-sea HMA sponges in four locations of the Cantabrian Sea and compared them to shallow water HMA and LMA (low microbial abundance) sponge species. Our results reveal that the sponge microbiome has converged in a fundamental metabolic role for deep-sea sponges, independent of taxonomic relationships or geographic location, which is shared in broad terms with shallow HMA species. We also observed a large number of redundant microbial members performing the same functions, likely providing stability to the sponge inner ecosystem. A comparison between the community composition of our deep-sea sponges and another 39 species of HMA sponges from deep-sea and shallow habitats, belonging to the same taxonomic orders, suggested strong homogeneity in microbial composition (i.e. weak species-specificity) in deep sea species, which contrasts with that observed in shallow water counterparts. This convergence in microbiome composition and functionality underscores the adaptation to an extremely restrictive environment with the aim of exploiting the available resources.
Cryo-electron microscopy reveals the impact of the nucleosome dynamics on transcription activity
Authors: Arita Kyohei
Published: January 2024

The structural biology of nucleosomes and their complexes with chromatin-associated factors contributes to our understanding of fundamental biological processes in the genome. With the advent of cryo-electron microscopy (cryo-EM), several structures are emerging with histone variants, various species and chromatin-associated proteins that bind to nucleosomes. Cryo-EM enables visualization of the dynamic states of nucleosomes, leading to the accumulation of knowledge on chromatin-templated biology. The cryo-EM structure of nucleosome in Komagataella pastoris, as studied by Fukushima et al., provided the insights into transcription ability of RNAPII with nucleosome dynamics. In this commentary, we review the recent advances in the structural biology of nucleosomes and their related biomolecules.
Femoral neck width genetic risk score is a novel independent risk factor for hip fractures
Authors: Tobias Jonathan H , Nethander Maria , Faber Benjamin G , Heppenstall Sophie V , Ebsim Raja , Cootes Tim , Lindner Claudia , Saunders Fiona R , Gregory Jenny S , Aspden Richard M , Harvey Nicholas C , Kemp John P , Frysz Monika , Ohlsson Claes
Published: January 2024

Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29–1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30–1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05–1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06–1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction.
The European Climate Law: Strengthening EU Procedural Climate Governance?
Authors: Kulovesi Kati , Oberthür Sebastian , van Asselt Harro , Savaresi Annalisa
Published: January 2024

In 2021, the European Union (EU) adopted the so-called European Climate Law (ECL), enshrining in law the 2050 climate-neutrality objective and upgraded 2030 emission reduction target. The ECL bears the hallmarks of what we term ‘procedural climate governance’, which comprises the regulatory frameworks, instruments, institutions and processes that shape substantive climate policies and their implementation. This article identifies seven key functions of procedural climate governance—target-setting; planning; monitoring and evaluation; climate policy integration; scientific expert advice; access to justice; and public participation—and uses these for critically assessing the ECL. We argue that while the ECL has significantly strengthened important aspects of EU procedural climate governance, further reforms are needed for the EU to develop and implement the substantive policies towards a climate-neutral and climate-resilient economy and society and to bolster public support and ownership of the transition. The upcoming reviews of the ECL and the Governance Regulation provide a critical opportunity for strengthening procedural climate governance in the EU.
Rights-based Climate Litigation in Colombia: An Assessment of Claims, Remedies, and Implementation
Authors: de la Rosa Calderón María Daniela
Published: January 2024

Climate litigation in Colombia is increasingly centred on fundamental and/or constitutional human rights. This note evaluates rights-based climate litigation in Colombia through the lens of five cases that protect ecosystems: the Atrato River, the Combeima River, and the Bruno River; the Amazon rainforest; and the Páramos ecosystem. First, the framing of cases is analysed. Second, the judges’ interpretations of the link between constitutional rights and climate change (if any), their reasoning, the scope of the remedies granted, and their intended impact are analysed. Relatedly, the note explores whether decisions that do not explicitly mention climate change can be considered climate cases as their remedies directly or indirectly affect climate change mitigation or adaptation. Finally, the note examines the status of compliance with or implementation of judicial remedies in climate cases.
Children, Religion and the Ethics of Influence: introduction to the symposium
Authors: Tillson John
Published: January 2024

It is morally impermissible for parents, educators, and others to initiate children into religious belief systems. That is the provocative conclusion of John Tillson’s Children, Religion and the Ethics of Influence—the book which is the focus of the present symposium. This introduction briefly summarizes the book’s arguments together with the criticisms levelled against them. The symposium includes critiques by Matthew Clayton, Anca Gheaus, Michael Hand, David Lewin, and Ruth Wareham. Clayton and Wareham propose alternative bases for prohibiting religious initiation, whilst Hand, Lewin, and Gheaus propose conditions under which religious initiation may be permissible. The symposium concludes with a rejoinder by Tillson.
TIC 184 743 498: the first tri-axial stellar pulsator
Authors: Zhang Valencia , Rappaport Saul , Jayaraman Rahul , Kurtz Donald W , Handler Gerald , Fuller James , Borkovits Tamas
Published: January 2024

We have discovered a δ Scuti pulsator in a tight binary (P = 1.053 d) with nine pulsation modes whose frequencies are between 38 and 56 d−1. Each of these modes exhibits amplitude modulations and π-rad phase shifts twice per orbital cycle. Five of these modes exhibit amplitude and phase shifts that are readily explained by dipole pulsations along an axis that is aligned with the binary’s tidal axis. The novelty of the system lies in the remaining four pulsation modes, which we show are dipole pulsations along an axis that is perpendicular to both the tidal axis and the binary’s orbital angular momentum axis. There are additionally two pulsation modes whose amplitudes and phases do not change significantly with orbital phase; they are explained as dipole modes along an axis aligned with the orbital/rotation axis. Hence, we propose that TIC 184 743 498 is a tri-axial pulsator, the first of its kind.
Galaxies decomposition with spiral arms – II. A multiwavelength case study of M 51
Authors: Marchuk Alexander A , Chugunov Ilia V , Gontcharov George A , Mosenkov Aleksandr V , Il’in Vladimir B , Savchenko Sergey S , Smirnov Anton A , Poliakov Denis M , Seguine Jonah , Chazov Maxim I
Published: January 2024

Spiral structure can contribute significantly to a galaxy’s luminosity. However, only rarely are proper photometric models of spiral arms used in decompositions. As we show in the previous work, including the spirals as a separate component in a photometric model of a galaxy would both allow to obtain their structural parameters, and reduce the systematic errors in estimating the parameters of other components. Doing so in different wavebands, one can explore how their properties vary with the wavelength. In this paper, second in this series, we perform decomposition of M 51 in 17 bands, from the far-ultraviolet (UV) to far-infrared, using imaging from the DustPedia project. We use the same 2D photometric model of spiral structure where each arm is modelled independently. The complex and asymmetric spiral structure in M 51 is reproduced relatively well with our model. We analyse the differences between models with and without spiral arms, and investigate how the fit parameters change with wavelength. In particular, we find that the spiral arms demonstrate the largest width in the optical, whereas their contribution to the galaxy luminosity is most significant in the UV. The disc central intensity drops by a factor of 1.25–3 and its exponential scale changes by 5–10 per cent when spiral arms are included, depending on wavelength. Taking into account the full light distribution across the arms, we do not observe the signs of a long-lived density wave in the spiral pattern of M 51 as a whole.
Identification of promoter activity in gene-less cassettes from Vibrionaceae superintegrons
Authors: Blanco Paula , Hipólito Alberto , García-Pastor Lucía , Trigo da Roza Filipa , Toribio-Celestino Laura , Ortega Alba Cristina , Vergara Ester , San Millán Álvaro , Escudero José Antonio
Published: January 2024

Integrons are genetic platforms that acquire new genes encoded in integron cassettes (ICs), building arrays of adaptive functions. ICs generally encode promoterless genes, whose expression relies on the platform-associated Pc promoter, with the cassette array functioning as an operon-like structure regulated by the distance to the Pc. This is relevant in large sedentary chromosomal integrons (SCIs) carrying hundreds of ICs, like those in Vibrio species. We selected 29 gene-less cassettes in four Vibrio SCIs, and explored whether their function could be related to the transcription regulation of adjacent ICs. We show that most gene-less cassettes have promoter activity on the sense strand, enhancing the expression of downstream cassettes. Additionally, we identified the transcription start sites of gene-less ICs through 5′-RACE. Accordingly, we found that most of the superintegron in Vibrio cholerae is not silent. These promoter cassettes can trigger the expression of a silent dfrB9 cassette downstream, increasing trimethoprim resistance >512-fold in V. cholerae and Escherichia coli. Furthermore, one cassette with an antisense promoter can reduce trimethoprim resistance when cloned downstream. Our findings highlight the regulatory role of gene-less cassettes in the expression of adjacent cassettes, emphasizing their significance in SCIs and their clinical importance if captured by mobile integrons.
Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors
Authors: Giacomini Giulia , Piquet Sandra , Chevallier Odile , Dabin Juliette , Bai Siau-Kun , Kim Byungjin , Siddaway Robert , Raught Brian , Coyaud Etienne , Shan Chun-Min , Reid Robert J D , Toda Takenori , Rothstein Rodney , Barra Viviana , Wilhelm Therese , Hamadat Sabah , Bertin Chloé , Crane Alexander , Dubois Frank , Forne Ignasi , Imhof Axel , Bandopadhayay Pratiti , Beroukhim Rameen , Naim Valeria , Jia Songtao , Hawkins Cynthia , Rondinelli Beatrice , Polo Sophie E
Published: January 2024

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3′-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.
An Introduction and Practical Guide to Strategies for Analyzing Longitudinal Data in Clinical Trials of Smoking Cessation Treatment: Beyond Dichotomous Point-Prevalence Outcomes
Authors: Kypriotakis George , Bernstein Steven L , Bold Krysten W , Dziura James D , Hedeker Donald , Mermelstein Robin J , Weinberger Andrea H
Published: January 2024

Conceptualizing tobacco dependence as a chronic relapsing condition suggests the need to use analytic strategies that reflect that premise. However, clinical trials for smoking cessation typically define the primary endpoint as a measure of abstinence at a single timepoint distal to the intervention, typically 3–12 months. This reinforces the concept of tobacco outcomes as a dichotomous state—one is, or is not, abstinent. Fortunately, there are several approaches available to handle longitudinal data that reflect the relapsing and remitting nature of tobacco use during treatment studies. In this paper, sponsored by the Society for Research on Nicotine and Tobacco’s Treatment Research Network, we present an introductory overview of these techniques and their application in smoking cessation clinical trials. Topics discussed include models to examine abstinence outcomes (eg, trajectory models of abstinence, models for transitions in smoking behavior, models for time to event), models that examine reductions in tobacco use, and models to examine joint outcomes (eg, examining changes in the use of more than one tobacco product). Finally, we discuss three additional relevant topics (ie, heterogeneity of effects, handling missing data, and power and sample size) and provide summary information about the type of model that can be used based on the type of data collected and the focus of the study. We encourage investigators to familiarize themselves with these techniques and use them in the analysis of data from clinical trials of smoking cessation treatment.

Implications Clinical trials of tobacco dependence treatment typically measure abstinence 3–12 months after participant enrollment. However, because smoking is a chronic relapsing condition, these measures of intervention success may not accurately reflect the common trajectories of tobacco abstinence and relapse. Several analytical techniques facilitate this type of outcome modeling. This paper is meant to be an introduction to these concepts and techniques to the global nicotine and tobacco research community including which techniques can be used for different research questions with visual summaries of which types of models can be used for different types of data and research questions.
Associations of Prevalence of E-cigarette Use With Quit Attempts, Quit Success, Use of Smoking Cessation Medication, and the Overall Quit Rate Among Smokers in England: A Time-Series Analysis of Population Trends 2007–2022
Authors: Jackson Sarah E , Brown Jamie , Beard Emma
Published: January 2024

Introduction

This study aimed to (1) provide up-to-date estimates of how changes in the prevalence of e-cigarette use have been associated with changes in smoking cessation activities and use of licensed treatments among smokers in England and (2) explore any changes in these associations over time.

Methods

Data were aggregated quarterly on 67 548 past-year smokers between Q1-2007 and Q4-2022. Explanatory variables were the prevalence of (1) current e-cigarette use among smokers and (2) e-cigarette use during a quit attempt. Outcomes were rates of quit attempts and overall quits among past-year smokers, and the quit success rate and use of licensed treatments among those who made a quit attempt.

Results

The success rate of quit attempts increased by 0.040% (95% CI 0.019; 0.062) for every 1% increase in the prevalence of e-cigarette use during a quit attempt. No clear evidence was found for an association between current e-cigarette use and the quit attempt rate (Badj = 0.008 [95% CI −0.045; 0.061]) or overall quit rate (Badj = 0.063 [−0.031; 0.158]); or between use of e-cigarettes during a quit attempt and the overall quit rate (Badj = 0.030 [−0.054; 0.114]), use of prescription medication (varenicline/bupropion/nicotine replacement therapy [NRT]: Badj = −0.036 [−0.175; 0.102]), or use of over-the-counter NRT (Badj = −0.052 [−0.120; 0.015]). There was no clear evidence this pattern of associations has changed substantially over time.

Conclusions

Changes in the prevalence of e-cigarette use in England through 2022 have been positively associated with the success rate of quit attempts but not clearly associated with the quit attempt rate, overall quit rate, or use of licensed smoking cessation treatments.

Implications

If the association between the increase in e-cigarette use and the quit success rate is causal, then the use of e-cigarettes in quit attempts has helped in the region of 30 000 to 50 000 additional smokers in England to successfully quit each year since they became popular in 2013, over and above the number who were quitting before the advent of e-cigarettes.
Enhancing accountability for police use of lethal force: Global monitoring and comparative benchmarking
Authors: Skinner Stephen
Published: January 2024

Policing and law enforcement bodies and the public authorities that govern them should be accountable for all deaths connected with a use of force. Accountability is a requirement of international human rights law and related provisions on the use of force, and foundational to legitimate, constrained, and consensual policing in liberal democracies. However, divergence in normative compliance and types of state system means that accountability for lethal force is inconsistent around the world. This paper discusses how a global system for monitoring lethal force could enhance accountability by making effective use of comparative benchmarking.
Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies
Authors: Han Yan-Jie , Shao Chi-Yun , Yao Ying , Zhang Zhe , Fang Ming-Zhi , Gong Tao , Zhang Ya-Jie , Li Min
Published: January 2024

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.
Fiscal Decentralization and Health Care Access and Quality: Evidence from Local Governments around the World
Authors: Kyriacou Andreas P , Roca-Sagalés Oriol
Published: January 2024

In this article, we consider how decentralizing health spending to local governments affects health care access and quality. Based on data from forty-nine countries around the world from 1996 to 2015, we find that decentralizing health spending is inimical to timely and effective health care. We also explore the role of two specific channels through which fiscal decentralization can undermine health outcomes: externalities and foregone economies of scale. We find that decentralizing health expenditure to the local level may generate externalities to the detriment of health outcomes when it is accompanied by locally elected municipal politicians who are not subject to national parties. Our results further suggest that fiscal decentralization can improve health access and quality when approximately two-thirds or more of the people in a country live in localities with more than 300,000 inhabitants, implying that below this threshold economies of scale may be foregone.