bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and acute exacerbation for patients with idiopathic pulmonary fibrosis (IPF) or non-IPF idiopathic interstitial pneumonias: 5-year follow-up analysis of a prospective multi-institutional patient registry
Authors: Tsubouchi Kazuya , Hamada Naoki , Tokunaga Shoji , Ichiki Katsuyuki , Takata Shohei , Ishii Hiroshi , Kitasato Yasuhiko , Okamoto Masaki , Kawakami Satoru , Yatera Kazuhiro , Kawasaki Masayuki , Fujita Masaki , Yoshida Makoto , Maeyama Takashige , Harada Taishi , Wataya Hiroshi , Torii Ryo , Komori Masashi , Mizuta Yuichi , Tobino Kazunori , Harada Eiji , Yabuuchi Hidetake , Nakanishi Yoichi , Okamoto Isamu 
Published: November 2023

ObjectiveFew prospective cohort studies with relatively large numbers of patients with non-idiopathic pulmonary fibrosis (non-IPF) of idiopathic interstitial pneumonia (IIP) have been described. We aimed to assess disease progression and cause of death for patients with non-IPF IIPs or IPF under real-life conditions.MethodsData were analysed for a prospective multi-institutional cohort of 528 IIP patients enrolled in Japan between September 2013 and April 2016. Diagnosis of IPF versus non-IPF IIPs was based on central multidisciplinary discussion, and follow-up surveillance was performed for up to 5 years after patient registration. Survival and acute exacerbation (AE) were assessed.ResultsIPF was the most common diagnosis (58.0%), followed by unclassifiable IIPs (35.8%) and others (6.2%). The 5-year survival rate for non-IPF IIP and IPF groups was 72.8% and 53.7%, respectively, with chronic respiratory failure being the primary cause of death in both groups. AE was the second most common cause of death for both non-IPF IIP (24.1%) and IPF (23.5%) patients. The cumulative incidence of AE did not differ significantly between the two groups (p=0.36), with a 1-year incidence rate of 7.4% and 9.0% in non-IPF IIP and IPF patients, respectively. We found that 30.2% and 39.4% of non-IPF IIP and IPF patients, respectively, who experienced AE died within 3 months after an AE event, whereas 55.8% and 66.7% of such patients, respectively, died within 5 years after registration.ConclusionCloser monitoring of disease progression and palliative care interventions after AE are important for non-IPF IIP patients as well as for IPF patients.
Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS)
Authors: Toorop Alyssa A , van Lierop Zoë YGJ , Gelissen Liza MY , Hoitsma Elske , Zeinstra Esther MPE , van Rooij Luuk C , van Munster Caspar EP , Vennegoor Anke , Mostert Jop P , Wokke Beatrijs HA , Kalkers Nynke F , Hoogervorst Erwin LJ , van Eijk Jeroen JJ , Roosendaal Christiaan M , Kragt Jolijn J , Eurelings Marijke , van Genugten Jessie , Nielsen Jessica , Sinnige LGF , Kloosterziel Mark E , Arnoldus Edo PJ , van Dijk Gert W , Bouvy Willem H , Wessels Mark HJ , Boonkamp Lynn , Strijbis Eva MM , van Oosten Bob W , De Jong Brigit A , Lissenberg-Witte Birgit I , Barkhof Frederik , Moraal Bastiaan , Teunissen Charlotte E , Rispens Theo , Uitdehaag Bernard MJ , Killestein Joep , van Kempen Zoé LE 
Published: November 2023

BackgroundExtended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.MethodsThe NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID).ResultsResults of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI −4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy.ConclusionsMS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks.Trial registration numberNCT04225312.
Comorbidities prior to out-of-hospital cardiac arrest and diagnoses at discharge among survivors
Authors: Hjärtstam Nellie , Rawshani Araz , Hellsén Gustaf , Råmunddal Truls 
Published: November 2023

BackgroundOut-of-hospital cardiac arrest (OHCA) has a dismal prognosis with overall survival around 10%. Previous studies have shown conflicting results regarding the prevalence and significance of comorbidities in OHCA, as well as the underlying causes. Previously, 80% of sudden cardiac arrest have been attributed to coronary artery disease. We studied comorbidities and discharge diagnoses in OHCA in all of Sweden.MethodsWe used the Swedish Registry of Cardiopulmonary Resuscitation, merged with the Inpatient Registry and Outpatient Registry to identify patients with OHCA from 2010 to 2020 and to collect all their comorbidities as well as discharge diagnoses (among those admitted to hospital). Patient characteristics were described using means, medians and SD. Survival curves were performed among hospitalised patients with acute myocardial infarction (AMI) as well as heart failure.ResultsA total of 54 484 patients with OHCA were included, of whom 35 894 (66%) were men. The most common comorbidities prior to OHCA were hypertension (43.6%), heart failure (23.6%), chronic ischaemic heart disease (23.6%) and atrial fibrillation (22.0%). Previous AMI was prevalent in 14.8% of men and 10.9% of women. Among women, 18.0% had type 2 diabetes, compared with 19.6% of the men. Among hospitalised patients, 30% were diagnosed with AMI, 27% with hypertension, 20% with ischaemic heart disease and 18% with heart failure as discharge diagnoses.ConclusionIn summary, we find evidence that nowadays a minority of cardiac arrests are due to coronary artery disease and AMIs and its complications. Only 30% of all cases of OHCA admitted to hospital were diagnosed with AMI. Coronary artery disease is now likely in the minority with regard to causes of OHCA.
Smoking history and all-cause, ischaemic heart disease and lung cancer mortality: follow-up study of 358 551 men and women aged 40–43 years
Authors: Tverdal Aage , Selmer Randi , Thelle Dag S 
Published: November 2023

AimsWe studied the health consequences of quitting smoking before age 43 by time since quitting, number of years smoked and cigarettes smoked per day. The outcomes were all-cause, ischaemic heart disease and lung cancer mortality.DesignProspective study.SettingNorwegian counties.ParticipantsMen and women aged 40–43 years who participated in a national cardiovascular screening programme and who were followed from 1985 to 2018.MeasurementsSelf-reports from questionnaire on time since quitting smoking, years smoked and number of cigarettes per day, and measurements of height, weight and blood pressure, and a blood sample where serum was analysed for total serum cholesterol and triglycerides.FindingsThe all-cause mortality rate was 30% higher among quitters less than 1 year ago compared with never smokers (adjusted HR=1.30, 95% CI 1.18–1.43 in men and HR=1.31, 95% CI 1.16 to 1.50 in women). Quitters who had smoked longer than 20 years had 23% higher mortality in men (HR=1.23, 95% CI 1.14 to 1.34) and 32% higher mortality in women (HR=1.32, 95% CI 1.18 to 1.49). Past smoking of more than 20 cigarettes/day was associated with HR=1.14 (1.05–1.23) in men and HR=1.16 (1.01–1.32) in women. The HR for lung cancer was 6.77 (95% CI 4.86 to 9.45) for quitting men who had smoked for more than 20 years compared with never smokers. The corresponding figure for women was 5.75 (95% CI 4.08 to 8.09).ConclusionsThe mortality among quitters was close to that of never smokers, except for a higher mortality for lung cancer, which on the other hand was much lower than the lung cancer mortality in current smokers.
Integrating enhanced efficiency fertilizers and nitrogen rates to improve Canada Western Red Spring wheat
Authors: Fast Adam , Strydhorst Sheri , Wang Zhijie , Hernandez-Ramirez Guillermo , Hao Xiying , Semach Greg , Thompson Laurel , Holzapfel Chris , Enns Jessica , Spaner Dean , Beres Brian L. 
Published: November 2023

Granular urea fertilizer applied at planting is prone to nitrogen (N) losses in certain environments. Enhanced efficiency fertilizers (EEFs) are developed to mitigate losses and optimize plant uptake. To determine the benefits of EEFs in grain yield and quality enhancement in Canada Western Red Spring (CWRS) wheat, an experiment was conducted from 2019 to 2022 at eight sites in Alberta and Saskatchewan, Canada. The effects of five N sources [urea; urea + urease inhibitor, N-( n-butyl)thiophosphoric triamide (NBPT); urea + nitrification inhibitor, nitrapyrin; urea + dual-inhibitor, NBPT + dicyandiamide; and polymer-coated urea, ESN® (Environmentally Smart Nitrogen®)] and four N rates (60, 120, 180, and 240 kg N ha−1) on CWRS wheat production were examined. Results indicated that N source affected grain yield in Dark Brown Chernozem soils but not in Black Chernozem or Dark Grey Luvisol soils. In Dark Brown Chernozem soils, a dual inhibitor increased grain yield by 3.1% and 3.9% relative to urea and polymer-coated urea, respectively, while all other EEFs attained similar results. The use of a dual inhibitor EEF led to greater net returns compared to urea and polymer-coated urea in the Dark Brown Chernozem soils. Grain protein concentration increased linearly with increasing N rate from 60 to 240 kg N ha−1. Generally, a rate of 120 kg N ha−1 was optimal for CWRS wheat grown in Canadian prairie conditions when coupled with EEFs, particularly a dual inhibitor, and grain yield and protein were often responsive.
Gravitational decoupling of anisotropic stars in the Brans–Dicke theory
Authors: Bamba Kazuharu , Bhatti M. Z. , Yousaf Z. , Shoukat Z. 
Published: November 2023

AbstractAnisotropic spherically symmetric solutions within the framework of the Brans–Dicke theory are uncovered through a unique gravitational decoupling approach involving a minimal geometric transformation. This transformation effectively divides the Einstein field equations into two separate systems, resulting in the alteration of the radial metric component. The first system encompasses the influence of the seed source, derived from the metric functions of the isotropic Tolman IV solution. Meanwhile, the anisotropic source is subjected to two specific constraints in order to address the second system. By employing matching conditions to determine the unknown constants at the boundary of the stellar object, a comprehensive examination of the internal structure of stellar systems ensues. This investigation delves into the impact of the decoupling parameter, the Brans–Dicke parameters, and a scalar field on the structural characteristics of anisotropic spherically symmetric spacetimes, all while considering the strong energy conditions.
Lévy-Leblond equation and Eisenhart–Duval lift in Koopman–von Neumann mechanics
Authors: Parida Bikram Keshari , Sen Abhijit , Dhasmana Shailesh , Silagadze Zurab K. 
Published: November 2023

The Koopman–von Neumann (KvN) mechanics is an approach that was formulated long ago to answer the question regarding the existence of a Hilbert space representation of classical mechanics. KvN mechanics is a non-relativistic theory, and it is not clear how spin can be included in it, since spin is widely regarded as a relativistic property. Cabrera et al., in Eur. Phys. J. Spec. Top. 227, 2195 (2019) argued that the Spohn equation [Spohn, Ann. Phys. 282, 420 (2000)] is the correct classical framework for the Koopman–von Neumann theory corresponding to the Dirac equation. However, after Lévy-Leblond’s seminal work on this topic, it became clear that spin naturally arises also from the Galilean invariant wave equations, without any need of relativistic considerations. Inspired by this, we propose another possibility of including spin in the KvN formalism: the Lévy-Leblond equation in the Koopman–von Neumann formalism can be obtained as a null reduction of the massless Dirac equation in the Eisenhart–Duval lift metric. To illustrate the idea, we implement it for a one-dimensional classical system without magnetic interactions.
Fine-grain Quantitative Analysis of Demand Paging in Unified Virtual Memory
Authors: Allen Tyler , Cooper Bennett , Ge Rong 
Published: November 2023

The abstraction of a shared memory space over separate CPU and GPU memory domains has eased the burden of portability for many HPC codebases. However, users pay for ease of use provided by system-managed memory with a moderate-to-high performance overhead. NVIDIA Unified Virtual Memory (UVM) is currently the primary real-world implementation of such abstraction and offers a functionally equivalent testbed for in-depth performance study for both UVM and future Linux Heterogeneous Memory Management (HMM) compatible systems. The continued advocacy for UVM and HMM motivates improvement of the underlying system. We focus on UVM-based systems and investigate the root causes of UVM overhead, a non-trivial task due to complex interactions of multiple hardware and software constituents and the desired cost granularity.
In our prior work, we delved deeply into UVM system architecture and showed internal behaviors of page fault servicing in batches. We provided quantitative evaluation of batch handling for various applications under different scenarios, including prefetching and oversubscription. We revealed that the driver workload depends on the interactions among application access patterns, GPU hardware constraints, and host OS components. Host OS components have significant overhead present across implementations, warranting close attention.
This extension furthers our prior study in three aspects: fine-grain cost analysis and breakdown, extension to multiple GPUs, and investigation of platforms with different GPU-GPU interconnects. We take a top-down approach to quantitative batch analysis and uncover how constituent component costs accumulate and overlap, governed by synchronous and asynchronous operations. Our multi-GPU analysis shows reduced cost of GPU-GPU batch workloads compared to CPU-GPU workloads. We further demonstrate that while specialized interconnects, NVLink, can improve batch cost, their benefits are limited by host OS software overhead and GPU oversubscription. This study serves as a proxy for future shared memory systems, such as those that interface with HMM, and the development of interconnects.
Small Cell Lung Cancer Plasticity Enables NFIB-Independent Metastasis
Authors: Ko Julie H. , Lambert Kyle E. , Bhattacharya Debadrita , Lee Myung Chang , Colón Caterina I. , Hauser Haley , Sage Julien 
Published: November 2023

Abstract

Metastasis is a major cause of morbidity and mortality in patients with cancer, highlighting the need to identify improved treatment and prevention strategies. Previous observations in preclinical models and tumors from patients with small cell lung cancer (SCLC), a fatal form of lung cancer with high metastatic potential, identified the transcription factor NFIB as a driver of tumor growth and metastasis. However, investigation into the requirement for NFIB activity for tumor growth and metastasis in relevant in vivo models is needed to establish NFIB as a therapeutic target. Here, using conditional gene knockout strategies in genetically engineered mouse models of SCLC, we found that upregulation of NFIB contributes to tumor progression, but NFIB is not required for metastasis. Molecular studies in NFIB wild-type and knockout tumors identified the pioneer transcription factors FOXA1/2 as candidate drivers of metastatic progression. Thus, while NFIB upregulation is a frequent event in SCLC during tumor progression, SCLC tumors can employ NFIB-independent mechanisms for metastasis, further highlighting the plasticity of these tumors.

Significance:
Small cell lung cancer cells overcome deficiency of the prometastatic oncogene NFIB to gain metastatic potential through various molecular mechanisms, which may represent targets to block progression of this fatal cancer type.
Hybrid chaotic map with L-shaped fractal Tromino for image encryption and decryption
Authors: Victor Juvvanapudi Sharon Rose , Rajesh Kumar Pullakura , Satyanarayana Reddy Konala Veera Venkata 
Published: November 2023

Insecure communication in digital image security and image storing are considered as important challenges. Moreover, the existing approaches face problems related to improper security at the time of image encryption and decryption. In this research work, a wavelet environment is obtained by transforming the cover image utilizing integer wavelet transform (IWT) and hybrid discrete cosine transform (DCT) to completely prevent false errors. Then the proposed hybrid chaotic map with L-shaped fractal Tromino offers better security to maintain image secrecy by means of encryption and decryption. The proposed work uses fractal encryption with the combination of L-shaped Tromino theorem for enhancement of information hiding. The regions of L-shaped fractal Tromino are sensitive to variations, thus are embedded in the watermark based on a visual watermarking technique known as reversible watermarking. The experimental results showed that the proposed method obtained peak signal-to-noise ratio (PSNR) value of 56.82dB which is comparatively higher than the existing methods that are, Beddington, free, and Lawton (BFL) map with PSNR value of 8.10 dB, permutation substitution, and Boolean operation with PSNR value of 21.19 dB and deoxyribonucleic acid (DNA) level permutation-based logistic map with PSNR value of 21.27 dB.
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function
Authors: Xu Weiyi , Billon Cyrielle , Li Hui , Wilderman Andrea , Qi Lei , Graves Andrea , Rideb Jernie Rae Dela Cruz , Zhao Yuanbiao , Hayes Matthew , Yu Keyang , Losby McKenna , Hampton Carissa S. , Adeyemi Christiana M. , Hong Seok Jae , Nasiotis Eleni , Fu Chen , Oh Tae Gyu , Fan Weiwei , Downes Michael , Welch Ryan D. , Evans Ronald M. , Milosavljevic Aleksandar , Walker John K. , Jensen Brian C. , Pei Liming , Burris Thomas , Zhang Lilei 
Published: November 2023

BACKGROUND:
Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.

METHODS:
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload–induced HF model in vivo. We conducted comprehensive functional, multi-omics (RNA sequencing and metabolomics studies), and genetic dependency studies both in vivo and in vitro to dissect the molecular mechanism, ERR isoform dependency, and target specificity.

RESULTS:
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload–induced HF without affecting cardiac hypertrophy. A broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particularly genes involved in fatty acid metabolism and mitochondrial function. Metabolomics analysis showed substantial normalization of metabolic profiles in fatty acid/lipid and tricarboxylic acid/oxidative phosphorylation metabolites in the mouse heart with 6-week pressure overload. ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo. Using both in vitro and in vivo genetic dependency experiments, we show that ERRγ is the main mediator of ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity. ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocytes.

CONCLUSIONS:
ERR agonists maintain oxidative metabolism, which confers cardiac protection against pressure overload–induced HF in vivo. Our results provide direct pharmacologic evidence supporting the further development of ERR agonists as novel HF therapeutics.
Colloquium 4 Commentary on Sanday
Authors: Ionescu Cristina 
Published: November 2023

Abstract
Sanday reads the Statesman as intertwining images with dialectical thinking. On the one hand, we advance from opinions to knowledge by gradually turning away from images and embracing rational arguments instead; on the other, dialectical knowledge must rely on images in order to be effective for the political community. My present comments come not to challenge, but rather to complement, and perhaps refine, Sanday’s account. I begin by highlighting the distinction that the Stranger draws between types of images, namely as perceptible likenesses and as likenesses in account respectively, and then reflect on how this distinction helps in leading the interlocutor’s search for the nature of statesmanship as well as in implementing insights in the practical life of the city. All of this supports the view that Plato has never had a problem with imitation or images as such, but only with our ignorance vis-à-vis our engagement with imitation and usage of images, and with our ignorance as to what are the objects that we imitate, in other words, figuring out whether they are images of Forms or of sensible things.
Colloquium 5 Commentary on Katz
Authors: McCready-Flora Ian C. 
Published: November 2023

Abstract
In this response to Emily Katz’s “Aristotle’s Rejection of Mathematized Metaphysics,” I raise questions about her central interpretive claim that mathematical forms cannot, for Aristotle, appear among first principles of nature. Topics addressed include the notion of priority, especially in the sciences; the relationship between natural change and material realization; and the general nature and scope of mathematical explanations for physical phenomena.
The 3Rs Alone Will Not Reduce Total Animal Experimentation Numbers: A Fundamental Misunderstanding in Need of Correction
Authors: Müller Nico D. 
Published: November 2023

Abstract
Government authorities often view the 3Rs of “replace, reduce, refine” popularized by Russell and Burch as both a regulatory principle and a governance principle aimed at reducing the total amount of animal distress in science. They thus expect that the 3Rs should, in time, result in changes in total animal experimentation numbers. Communications by Swiss authorities provide stark examples of this expectation. But the 3Rs do not aim at affecting animal experimentation at the level of total numbers; rather, they focus on study design in the individual case. While the underlying philosophy of the 3Rs indeed included a principle of seeking feasible overall reforms, this notion is completely absent in the 3Rs framework itself. Authorities need to stop treating the 3Rs as a means to reduce total distress and should instead invest resources into developing feasible and effective strategies for transformative governance in animal research.