bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tocilizumab suppresses NF-kappa B activation via toll-like receptor 9 signaling by reducing cell-free DNA in rheumatoid arthritis
Authors: Hashimoto Teppei , Yoshida Kohsuke , Yokoyama Yuichi , Hashimoto Naonori , Kaneshiro Kenta , Yoshikawa Takahiro , Tateishi Koji , Terashima Yasuhiro , Matsui Kiyoshi , Hashiramoto Akira 
Published: June 2023

Abstract
Endogenous DNA is released into the bloodstream as cell-free DNA (cfDNA) following cell death and is associated with various pathological conditions. However, their association with therapeutic drugs against rheumatoid arthritis (RA) remains unknown. Therefore, we investigated the significance of cfDNA in RA treated with tocilizumab and tumour necrosis factor inhibitor (TNF-I). Biological DMARDs (bDMARDs), including tocilizumab and TNF-I, were administered to 77 and 59 RA patients, respectively. Plasma cfDNA levels were measured at weeks 0, 4, and 12 by quantitative polymerase chain reaction. Disease activity was evaluated at the same time point using DAS28ESR. cfDNA levels from RA synovial cells treated with tocilizumab or etanercept for 24 h were measured. Human toll-like receptor 9 (hTLR9)-expressing HEK293 cells, which release secreted embryonic alkaline phosphatase (SEAP) upon NF-κB activation, were stimulated by cfDNA from RA patients, and subsequently, SEAP levels were determined. NF-κB translocation was evaluated by immunofluorescence staining with or without tocilizumab. The DAS28ESR significantly improved in both bDMARD groups at week 12. However, plasma cfDNA levels significantly decreased in the tocilizumab group at week 12 compared to that in week 0. cfDNA levels correlated with DAS28ESR in biological treatment-naïve patients administered tocilizumab. cfDNA levels in synovial cells were significantly suppressed by tocilizumab treatment and unaltered with etanercept. HEK293 cells released SEAP upon cfDNA stimulation, and the observed NF-κB nuclear translocation was suppressed by tocilizumab. Tocilizumab suppressed inflammation via the TLR9 pathway by decreasing cfDNA levels. Regulation of cfDNA may be a therapeutic target for RA.
One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial
Authors: Jilg Nikolaus , Chew Kara W , Giganti Mark J , Daar Eric S , Wohl David A , Javan Arzhang Cyrus , Kantor Amy , Moser Carlee , Coombs Robert W , Neytman Gene , Hoover Keila , Jana Atasi , Hart Phil A , Greninger Alexander L , Szurgot Bob , Eron Joseph J , Currier Judith S , Hughes Michael D , Smith Davey M , Li Jonathan Z ,   for the ACTIV-2/A5401 Study Team, Chew Kara , Smith David , Daar Eric , Wohl David , Currier Judith , Eron Joseph , Javan Arzhang Cyrus , Hughes Michael , Moser Carlee , Giganti Mark , Ritz Justin , Hosey Lara , Roa Jhoanna , Patel Nilam , Colsh Kelly , Rwakazina Irene , Beck Justine , Sieg Scott , Li Jonathan , Fletcher Courtney , Fischer William , Evering Teresa , Coombs Robert , Ignacio Rachel Bender , Cardoso Sandra , Corado Katya , Jagannathan Prasanna , Jilg Nikolaus , Perelson Alan , Pillay Sandy , Riviere Cynthia , Singh Upinder , Taiwo Babafemi , Gottesman Joan , Newell Matthew , Pedersen Susan , Dragavon Joan , Jennings Cheryl , Greenfelder Brian , Murtaugh William , Kosmyna Jan , Gapara Morgan , Shahkolahi Akbar , Szurgot Bob 
Published: June 2023

Abstract

Background
Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults.

Methods
We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28.

Results
Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA &lt;LLoQ on days 3, 7, and 14. Through day 28, 6 (5.6%) participants in the camostat arm and 5 (4.7%) in the placebo arm were hospitalized; 1 participant in the camostat arm subsequently died. Grade ≥3 TEAEs occurred in 10.1% of camostat versus 6.5% of placebo participants (P = .35).

Conclusions
In a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths.
Clinical Trials Registration. ClinicalTrials.gov identifier: NCT 04518410.
Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States
Authors: Lewnard Joseph A , Hong Vennis , Bruxvoort Katia J , Grant Lindsay R , Jódar Luis , Cané Alejandro , Arguedas Adriano , Pomichowski Magdalena E , Gessner Bradford D , Tartof Sara Y 
Published: June 2023

Abstract

Background
Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged &lt;65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults.

Methods
We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status.

Results
Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3–131.8) and 108.6 (50.4–159.1) medically attended LRTI cases; 21.9 (10.1–32.0) and 26.6 (12.4–38.7) hospitalized LRTI cases; and 7.1 (3.3–10.5) and 8.7 (4.0–12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged &lt;65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6–131.5) and 102.7 (47.8–156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4–8.6) and 6.2 (2.8–10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4–1.4) and 1.1 (0.5–1.7) excess LRTI-associated deaths per 10 000 person-years.

Conclusions
Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.
Stealth Address Schemes With Fast Retrievability Based On Subgroup Membership Assumptions Related To Factoring
Authors: Wang Xin , Lin Li , Wang Yao 
Published: June 2023

Abstract
Stealth address is a known technique to ensure the privacy (anonymity) of a recipient participating in a certain transaction in a distributed blockchain scenario. However, most existing stealth address schemes require linear judge time and search time $\mathcal{O}(n)$, where $n$ is the number of transactions of a certain block, so the only way to claim transactions for a recipient is to traverse the transaction list to find out whether an ever-arrived transaction belongs to him. To overcome this drawback, we proposed the notion of Fast Stealth Address (FSA), a novel approach that simultaneously preserves privacy and improves search efficiency of recipients. We give a generic construction of FSA scheme under subgroup membership assumption related to factoring and instantiate concrete schemes based on specific number-theoretic assumptions. Our framework mainly improves on two aspects: (i) allowing constant recognize time $\mathcal{O}(1)$ to judge whether a certain block contains recipient’s transactions and (ii) allowing logarithmic search time $\mathcal{O}(\log{n})$ to find out the precise transactions intended for a recipient. We formalize the security model of an FSA scheme and provide provable security analysis to ensure the security of our constructions. Besides, we implement our schemes to measure their real-world performance on several metrics and give comparison results to stealth address scheme utilized by Monero.
A Genetic Algorithm Based Scheduling Method With Carrier Aggregation In 5G Networks
Authors: Hsu Ching-Kuo 
Published: June 2023

Abstract
Recently, 5G has become an important mechanism to serve a growing amount of users in the network, which provides enhanced mobile broadband (eMBB) and ultra-reliable low latency communications (URLLC) services. Meanwhile, Carrier Aggregation (CA) is a promising 5G technology which lets users aggregate fragmented carrier components (CCs) to enhance transmission efficiency. This paper addresses 5G scheduling problem in the CA-enabled eMBB–URLLC coexistence network using genetic algorithm (GA). The key idea is first treating the serving time slot of each user equipment (UE) as a gene and combining all genes to form a chromosome, then generating a set of chromosomes as the initial population and letting the population evolve to iteratively select the fittest one as the resource scheduling decision. Up to now, this is the first work using GA for solving the scheduling problem in the CA-enabled 5G network. Simulation results show that our proposed method can serve the most UEs ($4\%$) with the highest throughput ($7.1\%$) and lower delay.
Hybrid Optimal Ensemble SVM Forest Classifier for Task Offloading in Mobile Cloud Computing
Authors: Subramaniam Erana Veerappa Dinesh , Krishnasamy Valarmathi 
Published: June 2023

AbstractMobile devices (MDs) are becoming more prevalent and their battery life is optimised by offloading tasks to cloud servers. However, communication costs must be considered when offloading tasks. To make task offloading worthwhile, it is important to measure the energy consumed during communication activities. Thus, a heterogeneous framework is developed to enhance the energy efficiency of smartphones by analysing parameters such as task and non-task offloading, local cloudlets, radio access networks and remote cloud servers. This paper proposes a task offloading framework that uses a novel algorithm, the Hybrid Red Fox Flow Direction-based Ensemble SVM Forest Classifier, to enhance the system parameters and schedule tasks in offloading cloud computing conditions. The multi-objective function aims to improve user satisfaction by maximising resource utilisation and minimising function. The framework was tested in the Cloudsim simulation tool and compared with different techniques, with the results demonstrating its superiority in terms of energy efficiency and system performance. The proposed framework can optimise the energy efficiency of MDs and improve battery life.
Efficacy and safety of modified endoscopic submucosal tunnel dissection for superficial esophageal circumferential lesions
Authors: Tian Ye , Xue Chengjun , Li Xiaomin , Bai Jianan , Xiao Zequan , He Qibin , Kan Jingbao , Zhu Guoqin , Tang Qiyun 
Published: June 2023

SUMMARY
To evaluate the efficacy and safety of intra-tunnel dissection using hemostatic forceps and needle-type device for patients with esophageal circumferential lesions (ECLs). Patients with ECLs were enrolled in the study and underwent endoscopic submucosal tunnel dissection (ESTD) or hemostatic forceps-based ESTD (ESFTD). All patients were divided into three subgroups according to longitudinal length of the lesions (LLLs): &gt;8 cm, 4–8 cm and &lt; 4 cm. The clinical data such as gender, age, length of lesions and operating time were collected. A total of 152 patients were included in this study and comprised 80 cases of ESFTD and 72 cases of ESTD. The procedure time was markedly shorter in the ESFTD group than in the ESTD group (P &lt; 0.001). Moreover, ESFTD significantly increased the rate of complete resection and reduced specimen injury in LLLs &gt;8 cm and 4–8 cm subgroup compared with ESTD (P &lt; 0.001), but not in &lt;4 cm subgroup (P &gt; 0.05). The perforation and infection rate were similar in ESFTD and ESTD group (P &gt; 0.05). However, ESFTD effectively decreased the muscular injury rate’ the duration of chest pain and the time from endoscopic surgery to first occurrence of esophageal stenosis compared with ESTD group (P &lt; 0.01). ESFTD has better efficacy and safety than ESTD in the treatment of ECLs, especially for large lesions. ESFTD could be recommended for patients with ECLs.
Systematic review of quality of life after esophagectomy and total gastrectomy in patients with gastro-esophageal junction cancer
Authors: Walmsley James , Ariyarathenam Arun , Berrisford Richard , Humphreys Lee , Sanders Grant , Tham Ji Chung , Wheatley Tim , Chan David S Y 
Published: June 2023

SUMMARY
The optimal management of cancer of the gastro-esophageal junction (GEJ) is an area of contention. GEJ tumors are typically resected via total gastrectomy or esophagectomy. Despite many studies aiming to determine the superiority of either procedure based on surgical or oncological outcomes, the evidence is equivocal. Data focusing specifically on quality of life (QoL), however, is limited. This systematic review was performed to determine if there is any difference in patient’s QoL after total gastrectomy or esophagectomy. A systematic search of PubMed, Medline and Cochrane libraries was conducted for literature published between 1986 and 2023. Studies that used the internationally validated questionnaires EORTC QLQ-C30 and EORTC-QLQ-OG25, to compare QoL after esophagectomy to gastrectomy for the management of GEJ cancer were included. Five studies involving 575 patients undergoing either esophagectomy (n = 365) or total gastrectomy (n = 210) for GEJ tumors were included. QoL was predominantly assessed at 6, 12 and 24 months postoperatively. Although individual studies demonstrated significant differences in certain domains, these differences were not consistently demonstrated in more than one study. There is no evidence to suggest any significant differences in QoL after total gastrectomy compared to esophagectomy for management of gastro-esophageal junction cancer.
Phenotyping heart failure by genetics and associated conditions
Authors: Wong Joshua , Peters Stacey , Marwick Thomas H 
Published: June 2023

Abstract
Heart failure is a highly heterogeneous disease, and genetic testing may allow phenotypic distinctions that are incremental to those obtainable from imaging. Advances in genetic testing have allowed for the identification of deleterious variants in patients with specific heart failure phenotypes (dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and hypertrophic cardiomyopathy), and many of these have specific treatment implications. The diagnostic yield of genetic testing in heart failure is modest, and many rare variants are associated with incomplete penetrance and variable expressivity. Environmental factors and co-morbidities have a large role in the heterogeneity of the heart failure phenotype. Future endeavours should concentrate on the cumulative impact of genetic polymorphisms in the development of heart failure.
Foreign Investors of the World, Unite! The International Association for the Promotion and Protection of Private Foreign Investments (APPI) 1958–1968
Authors: Batselé Filip 
Published: June 2023

Abstract
This article studies lobbying efforts by the actors that investment treaties protect – namely, foreign investors. It uses a legal-historical approach to analyse the activities of the International Association for the Promotion and Protection of Private Foreign Investments (Association internationale pour la promotion et la protection des investissements privés en territoires étrangers or APPI), a transnational business interest association that lobbied for better protection of private foreign investment under international law. The article considers the role of this group in lobbying for three multilateral investment treaties (an investment code, investor-state arbitration and investment insurance) during the 1950s and 1960s, using unexplored archival sources. The article makes three substantive contributions to the literature. First, it shows that the key actors involved in APPI were a transnational advocacy network of businessmen and lawyers at multinational companies, mainly in the oil and banking sector. Second, it shows how these two types of actors (businessmen and lawyers) acted symbiotically. The businessmen provided access to policy-makers and introduced company lawyers into the policy-making cycle. The company lawyers provided expertise and specific legal texts with which civil servants could work. Third, it argues that, despite the group members’ common goal to improve foreign investment security, competing individual initiatives and institutional competition, next to state preferences, often impeded more effective lobbying.
The Future in the Past? The Replication of Existing Treaty Language in the Making of the ILC’s Draft Articles on Crimes against Humanity
Authors: Biazatti Bruno 
Published: June 2023

Abstract
Treaty-making often occurs through the reuse of existing legal solutions. Instead of creating new language, drafters often replicate past treaty wording in the instrument under negotiation. The Draft Articles on Prevention and Punishment of Crimes against Humanity (DACaH), formulated by the International Law Commission (ILC or the Commission), were an example. This article evaluates the ILC’s reliance on past treaty language to produce the DACaH. In addition to assessing some contextual reasons why, and the manner in which, the Commission used such a drafting approach, this article notes that, given its mandate as an expert body subsidiary to the United Nations General Assembly, the ILC may face specific challenges while using this technique. Taking the DACaH as a case study, the article also explores some pragmatic and normative considerations that may motivate or impact the replication of past treaty language in international law-making. In conclusion, the ILC’s reliance on existing treaty wording to craft the DACaH was deeply consequential as it was part of the Commission’s broader goal of placating states via the adoption of an effective, but minimalist and conformist, set of draft articles with greater chances of becoming a widely adhered to treaty.
Wars of Recovery
Authors: Lieblich Eliav 
Published: June 2023

Abstract
Aggressor state A occupies territory belonging to victim state V. After decades, V decides to go to war to recover its territory, although hostilities have long subsided. Are such ‘wars of recovery’ lawful under international law? Should they be? Recent conflicts have generated a heated scholarly debate on this question, which has ended in stark disagreement. A permissive approach argues that wars of recovery are lawful instances of self-defence, while a restrictive view claims that situations of prolonged occupation are territorial disputes that should be settled peacefully. This article uncovers the theoretical premises that underlie both approaches. As it shows, the dilemma reflects a larger tension within the contemporary international law on the use of force – mainly, between its traditional focus on state rights such as territory and sovereignty and a competing view that seeks to place individual rights at the core of the legal regime. As the article shows, deciding on the question of wars of recovery requires making commitments in four normative spheres: instrumentally, it requires considering questions of international stability, and, non-instrumentally, it requires considering questions of justice as well as possible justifications for killing and sacrifice. These considerations, however, result in instability owing, among other factors, to the fluctuating effects of the passage of time, which follow our normative assumptions about the legal order. Ultimately, the article suggests that those engaging in debate on wars of recovery make explicit their normative assumptions on the ends of jus ad bellum and that, in any case, even if wars of recovery would be deemed legal, they would still remain heavily contestable owing to strong competing reasons against them.
Towards an extended resource theory of marital power: parental education and household decision-making in rural China
Authors: Cheng Cheng , Xie Yu 
Published: June 2023

Abstract
Existing literature on the resource theory of marital power has focused on the relative resources of spouses and overlooked the resource contributions of spouses’ extended families. We propose an extended resource theory that considers how the comparative resources of a couple’s natal families are directly associated with marital power, net of the comparative resources of the couple. Using data from the China Panel Family Studies, we examine how the relative education of a couple’s respective parents affects the wife’s decision-making power, net of the relative education of the couple. Results suggest that the higher the wife’s parental education relative to her husband’s parental education, the more likely she is to have the final say over household financial decisions. Our study underscores the importance of situating the study of marital power in the extended family context and highlights the significance of social origins and intergenerational exchanges for marital power.
Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis
Authors: Meng Zhaojie , Zhang Shuya , Li Wei , Wang Yunzhe , Wang Minjie , Liu Xin , Liu Cong-Lin , Liao Sha , Liu Tianxiao , Yang Chongzhe , Lindholt Jes S , Rasmussen Lars M , Obel Lasse M , Stubbe Jane , Diederichsen Axel C , Sun Yong , Chen Yabing , Yu Paul B , Libby Peter , Shi Guo-Ping , Guo Junli 
Published: June 2023

Abstract

Aims
Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis.

Methods and results
Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4−/−, and Il13−/− mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries.

Conclusion
Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.