bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smokers' beliefs about “Light” and “Ultra Light” cigarettes
Authors: Shiffman Saul , Pillitteri Janine L , Burton Steven L , Rohay Jeffrey M , Gitchell Joe G 
Published: May 2024

OBJECTIVETo assess beliefs about the tar and nicotine delivery characteristics and health benefits of Light and Ultra Light cigarettes among cigarette smokers.DESIGNRandom digit dialed telephone survey conducted in September 1999.SUBJECTSDaily smokers (n = 2120) of Regular (46%), Light (39%), and Ultra Light (15%) cigarettes in the USA. The sample was weighted to match the US smoker population on age, sex, and ethnicity.MAIN OUTCOME MEASURESBeliefs about Light and Ultra Light cigarettes were summarised on three dimensions: Safety (reduced health risk), Delivery (lowered tar and nicotine delivery), and Sensation (less harsh).RESULTSMost smokers believed Lights and Ultra Lights were less harsh and delivered less tar and nicotine. On average, smokers believed that Lights afforded a 25% reduction in risk, and Ultra Lights a 33% reduction in risk. Light and Ultra Light cigarette smokers evaluated the risks of their own cigarette types more favourably. Light smokers had greater interest in quitting than Ultra Light smokers. Quitting intention was modestly related to beliefs about these cigarettes. Believing that Lights and Ultra Lights delivered less tar and nicotine and that they were less harsh each independently contributed to the belief that these cigarettes were safer.CONCLUSIONSMany Light and Ultra Light smokers believe that smoking these cigarettes impart a substantial health benefit, due in part to their experience that these cigarettes are less harsh and the belief that these cigarettes deliver less tar.
Gravity-induced entanglement between two massive microscopic particles in curved spacetime: II. Friedmann–Lemaître–Robertson–Walker universe
Authors: Zhang Chi , Shu Fu-Wen 
Published: May 2024

AbstractIn our previous work (Zhang and Shu in Eur Phys J. C 84(3):256, 2024), we have explored quantum gravity induced entanglement of masses (QGEM) in curved spacetime, observing entanglement formation between particles moving along geodesics in a Schwarzschild spacetime background. We find that long interaction time induces entanglement, even for particles with microscopic mass, addressing decoherence concerns. In this work, we build upon our previous work (Zhang and Shu 2024) by extending our investigation to a time-dependent spacetime. Specifically, we explore the entanglement induced by the mutual gravitation of massive particles in the Friedmann–Lemaître–Robertson–Walker (FLRW) universe. With the help of the phase shift and the QGEM spectrum, our proposed scheme offers a potential method for observing the formation of entanglement caused by the quantum gravity of massive particles as they propagate in the FLRW universe. Consequently, it provides insights into the field of entanglement in cosmology.
Efficient and Reusable Lazy Sampling
Authors: Sanca Viktor , Chrysogelos Periklis , Ailamaki Anastasia 
Published: May 2024

Modern analytical engines rely on Approximate Query Processing (AQP) to provide faster response times than the hardware allows for exact query answering. However, existing AQP methods impose steep performance penalties as workload unpredictability increases. While offline AQP relies on predictable workloads to a priori create samples that match the queries, as soon as workload predictability diminishes, returning to existing online AQP methods that create query-specific samples with little reuse across queries results in significantly smaller gains in response times. As a result, existing approaches cannot fully exploit the benefits of sampling under increased unpredictability.
We propose LAQy, a framework for building, expanding, and merging samples to adapt to the changes in workload predicates. We propose lazy sampling to overcome the unpredictability issues that cause fast-but-specialized samples to be query-specific and design it for a scale-up analytical engine to show the adaptivity and practicality of our framework in a modern system. LAQy speeds up online sampling processing as a function of data access and computation reuse, making sampler placement after expensive operators more practical.
Anti–4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade
Authors: Jeon Seung Hyuck , You Gihoon , Park Junsik , Chung Youseung , Park Kyungjin , Kim Hyunjoo , Jeon Jaehyoung , Kim Youngkwang , Son Woo-Chan , Jeong Da Som , Shin Eui-Cheol , Lee Jung-Yun , Han Dai Hoon , Jung Jaeho , Park Su-Hyung 
Published: May 2024

Abstract

Purpose:
To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti–4-1BB×PDL1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy.

Experimental Design:
Single-cell suspensions of hepatocellular carcinoma and ovarian cancer tissues from treatment-naïve patients were used for immunophenotyping of CD8+ TILs and in vitro functional assays. Humanized hPD1/hPDL1/h4-1BB triple–knock-in mice were used to evaluate the effects of ABL503 and anti-PD1 blockade in vivo.

Results:
We observed that ABL503 successfully restored the functions of 4-1BB+ exhausted CD8+ TILs, which were enriched for tumor-specific T cells but unresponsive to anti-PD1 blockade. Importantly, compared with anti-PD1 blockade alone, the combination of ABL503 and anti-PD1 blockade further enhanced the functional restoration of human CD8+ TILs in vitro. Consistently, the combination of ABL503 with anti-PD1 in vivo significantly alleviated tumor growth and induced enhanced infiltration and activation of CD8+ TILs.

Conclusions:
ABL503, a PDL1 and 4-1BB dual-targeting bispecific antibody, elicits pronounced additive tumor growth inhibition, with increased infiltration and functionality of exhausted CD8+ T cells, which in turn enhances the anticancer effects of anti-PD1 blockade. These promising findings suggest that ABL503 (TJ-L14B) in combination with PD1 inhibitors will likely further enhance therapeutic benefit in clinical trials.
See related commentary by Molero-Glez et al., p. 3971
Project Optimus Elicits the “Holistic” Benefits of PK/PD Modeling of Immunotherapy
Authors: Gopalakrishnan Mathangi , Amaria Rodabe N. 
Published: May 2024

SummaryLeveraging a heterogeneous dataset, a recent article demonstrated the application of pharmacometric modeling to inform the dosing of nivolumab–relatlimab fixed-dose combination in special populations, including adolescents lacking clinical data. The use of model-informed approaches during clinical drug development can be cost-effective, which ensures fast access to drugs and enhances patient outcomes.See related article by Zhao et al., p. 3050
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Gornik Heather L. , Aronow Herbert D. , Goodney Philip P. , Arya Shipra , Brewster Luke Packard , Byrd Lori , Chandra Venita , Drachman Douglas E. , Eaves Jennifer M. , Ehrman Jonathan K. , Evans John N. , Getchius Thomas S.D. , Gutiérrez J. Antonio , Hawkins Beau M. , Hess Connie N. , Ho Karen J. , Jones W. Schuyler , Kim Esther S.H. , Kinlay Scott , Kirksey Lee , Kohlman-Trigoboff Debra , Long Chandler A. , Pollak Amy West , Sabri Saher S. , Sadwin Lawrence B. , Secemsky Eric A. , Serhal Maya , Shishehbor Mehdi H. , Treat-Jacobson Diane , Wilkins Luke R. 
Published: May 2024

AIM:
The “2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease” provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia).

METHODS:
A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate.

STRUCTURE:
Recommendations from the “2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease” have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.
Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes
Authors: Collet Carlos , Munhoz Daniel , Mizukami Takuya , Sonck Jeroen , Matsuo Hitoshi , Shinke Toshiro , Ando Hirohiko , Ko Brian , Biscaglia Simone , Rivero Fernando , Engstrøm Thomas , Arslani Ketina , Leone Antonio Maria , van Nunen Lokien X. , Fearon William F. , Christiansen Evald Høj , Fournier Stephane , Desta Liyew , Yong Andy , Adjedj Julien , Escaned Javier , Nakayama Masafumi , Eftekhari Ashkan , Zimmermann Frederik M. , Sakai Koshiro , Storozhenko Tatyana , da Costa Bruno R. , Campo Gianluca , West Nick E.J. , De Potter Tom , Heggermont Ward , Buytaert Dimitri , Bartunek Jozef , Berry Colin , Collison Damien , Johnson Thomas , Amano Tetsuya , Perera Divaka , Jeremias Allen , Ali Ziad , Pijls Nico H.J. , De Bruyne Bernard , Johnson Nils P. 
Published: May 2024

BACKGROUND:
Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes.

METHODS:
This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI.

RESULTS:

A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61–0.69];
P
<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79–0.84];
P
<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50–0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00–2.97]).

CONCLUSIONS:
Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04789317.
Bleeding Risk in Patients Receiving Omega‐3 Polyunsaturated Fatty Acids: A Systematic Review and Meta‐Analysis of Randomized Clinical Trials
Authors: Javaid Mustafa , Kadhim Kadhim , Bawamia Bilal , Cartlidge Timothy , Farag Mohamed , Alkhalil Mohammad 
Published: May 2024

Background
There is a potential concern about increased bleeding risk in patients receiving omega‐3 polyunsaturated fatty acids (PUFAs). The aims of this study‐level meta‐analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega‐3 PUFAs or the background use of antiplatelet treatment.

Methods and Results

Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega‐3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta‐analytic events of bleeding among patients receiving omega‐3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91–1.31];
P
=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high‐dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05–0.43];
P
=0.02) but not the background use of antiplatelet therapy (risk difference, −0.01 [95% CI, −0.02 to 0];
P
=0.056).

Conclusions
Omega‐3 PUFAs were not associated with increased bleeding risk. Patients receiving high‐dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.
Post-milking application of a Lacticaseibacillus paracasei strain impacts bovine teat microbiota while preserving the mammary gland physiology and immunity
Authors: Goetz C. , Rault L. , Cuffel J. , Poton P. , Finot L. , Boullet G. , Boutinaud M. , Even S. 
Published: May 2024

Abstract
Bovine mastitis (BM) is a major disease in dairy industry. The current approaches – mainly antibiotic treatments – are not entirely effective and may contribute to antimicrobial resistance dissemination, rising the need for alternative treatment. The present study aims to evaluate the impact of post-milking application of Lacticaseibacillus paracasei CIRM BIA 1542 (Lp1542) on the teat skin (TS) of 20 Holstein cows in mid lactation, in order to reinforce the barrier effect of the microbiota naturally present on the teat. Treatment (Lp1542, iodine or no treatment) was applied post-milking twice a day on the 4 teats of healthy animals for 15 days. Blood and milk samples, and TS swabs were collected at day (D)1, D8, D15 and D26 before morning milking and at D15 before evening milking (D15E) to evaluate Lp1542 impact at the microbial, immune and physiological levels. Lp1542 treatment resulted in a higher lactic acid bacteria and total microbial populations on TS and in foremilk (FM) at D15(E) compared with iodine treatment. Metabarcoding analysis revealed changes in the composition of TS and FM microbiota, beyond a higher Lacticaseibacillus abundance. This included a higher abundance of Actinobacteriota, including Bifidobacterium, and a lower abundance of Pseudomonadota on TS of Lp1542 compared with iodine-treated quarters. In addition, Lp1542 treatment did not trigger any major inflammatory response in the mammary gland, except interleukin 8 production and expression which tended to be slightly higher in Lp1542-treated cows compared with the others. Finally, Lp1542 treatment had no impact on the mammary epithelium functionality (milk yield and composition) and integrity (epithelial cell exfoliation into milk and milk Na+/K+ ratio). Altogether, these results indicate that a topical treatment with Lp1542 is safe with regard to mammary gland physiology and immune system, while impacting its microbiota, inviting us to further explore its effectiveness for mastitis prevention.
Exascale Computing and Data Handling: Challenges and Opportunities for Weather and Climate Prediction
Authors: Govett Mark , Bah Bubacar , Bauer Peter , Berod Dominique , Bouchet Veronique , Corti Susanna , Davis Chris , Duan Yihong , Graham Tim , Honda Yuki , Hines Adrian , Jean Michel , Ishida Junishi , Lawrence Bryan , Li Jian , Luterbacher Juerg , Muroi Chiasi , Rowe Kris , Schultz Martin , Visbeck Martin , Williams Keith 
Published: May 2024

Abstract
The emergence of exascale computing and artificial intelligence offer tremendous potential to significantly advance Earth system prediction capabilities. However, enormous challenges must be overcome to adapt models and prediction systems to use these new technologies effectively. A 2022 WMO report on exascale computing recommends “urgency in dedicating efforts and attention to disruptions associated with evolving computing technologies that will be increasingly difficult to overcome, threatening continued advancements in weather and climate prediction capabilities.” Further, the explosive growth in data from observations, model and ensemble output, and postprocessing threatens to overwhelm the ability to deliver timely, accurate, and precise information needed for decision-making. Artificial intelligence (AI) offers untapped opportunities to alter how models are developed, observations are processed, and predictions are analyzed and extracted for decision-making. Given the extraordinarily high cost of computing, growing complexity of prediction systems, and increasingly unmanageable amount of data being produced and consumed, these challenges are rapidly becoming too large for any single institution or country to handle. This paper describes key technical and budgetary challenges, identifies gaps and ways to address them, and makes a number of recommendations.
Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study
Authors: Lin Jing , Li Yue , Gui Mengcui , Bu Bitao , Li Zhijun 
Published: May 2024

Background: Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. Objectives: This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. Design: A single-center retrospective study. Methods: Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Results: Sixteen patients with MGFA class II–V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups ( p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months ( p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Conclusion: Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.
Migraine or any headaches and white matter hyperintensities and their progression in women and men
Authors: Schramm Sara Helena , Tenhagen I. , Jokisch M. , Gronewold J. , Moebus S. , Caspers S. , Katsarava Z. , Erbel R. , Stang A. , Schmidt B. 
Published: May 2024

Abstract
Background
Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders.

Methods
Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2–3 vs. 0–1) by log-binomial regression, adjusted for confounders.

Results
The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454–6880) mm3 in women and 4812 (2842–8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache.

Conclusions
Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.
Developing an SNP dataset for efficiently evaluating soybean germplasm resources using the genome sequencing data of 3,661 soybean accessions
Authors: Niu Yongchao , Yung Wai-Shing , Sze Ching-Ching , Wong Fuk-Ling , Li Man-Wah , Chung Gyuhwa , Lam Hon-Ming 
Published: May 2024

Abstract
Background
Single nucleotide polymorphism (SNP) markers play significant roles in accelerating breeding and basic crop research. Several soybean SNP panels have been developed. However, there is still a lack of SNP panels for differentiating between wild and cultivated populations, as well as for detecting polymorphisms within both wild and cultivated populations.

Results
This study utilized publicly available resequencing data from over 3,000 soybean accessions to identify differentiating and highly conserved SNP and insertion/deletion (InDel) markers between wild and cultivated soybean populations. Additionally, a naturally occurring mutant gene library was constructed by analyzing large-effect SNPs and InDels in the population.

Conclusion
The markers obtained in this study are associated with numerous genes governing agronomic traits, thus facilitating the evaluation of soybean germplasms and the efficient differentiation between wild and cultivated soybeans. The natural mutant gene library permits the quick identification of individuals with natural mutations in functional genes, providing convenience for accelerating soybean breeding using reverse genetics.