bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensity of statin therapy after ischaemic stroke and long-term outcomes: a nationwide cohort study
Authors: Kytö Ville , Åivo Julia , Ruuskanen Jori O 
Published: June 2024

BackgroundStatins are essential for secondary prevention after ischaemic stroke (IS). However, statin intensity recommendations differ, and there is a concern about intracerebral haemorrhage (ICH). We studied the long-term impacts of initial statin intensity following IS.MethodsConsecutive patients using high-intensity, moderate-intensity or low-intensity statin early after IS (n=45 512) were retrospectively studied using national registries in Finland. Differences were adjusted using multivariable regression. The primary outcome was all-cause death within 12-year follow-up (median 5.9 years). Secondary outcomes were recurrent IS, cardiovascular death and ICH studied using competing risk analyses.ResultsHigh-intensity therapy was initially used by 16.0%, moderate-intensity by 73.8% and low-intensity by 10.2%. Risk of death was lower with high-intensity versus moderate-intensity (adjusted HR (adj.HR) 0.92; 95% CI 0.87 to 0.97; number needed to treat (NNT) 32.0), with moderate-intensity versus low-intensity (adj.HR 0.91; 95% CI 0.87 to 0.95; NNT 27.5) and with high-intensity versus low-intensity (adj.HR 0.83; 95% CI 0.78 to 0.89; NNT 14.6) statin. There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS (p<0.0001) and cardiovascular death (p<0.0001). The occurrence of ICH was not associated with initial statin intensity (p=0.646).ConclusionsFollowing IS, more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH. These findings emphasise the importance of high statin intensity shortly after IS.
Exploring causality with biliary atresia at different levels: two-sample Mendelian randomization study
Authors: Liu Shaowen , Musha Jiayinaxi , Wang Zhiru , Wang Xueting , Li Tengfei , Zhan Jianghua 
Published: June 2024

BackgroundIn recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA).MethodsGenome-wide association studies (GWAS) data of 41 inflammatory cytokines, 731 immune cell traits, and 1400 metabolites were obtained from public databases as exposure factors. The outcome information was obtained from a GWAS meta-analysis of 499 children with BA and 1928 normal controls. Inverse variance weighting was the primary causality analysis. Cochran Q-test, MR-Egger intercept, MR pleiotropy residual sum and outlier, and ‘leave-one-out’ analyses were used for sensitivity analysis. Reverse MR, MR-Steiger, and Linkage Disequilibrium Score were used to exclude the effects of reverse causality, genetic association, and linkage disequilibrium.ResultsMR results showed that a total of seven traits had potential causal relationships with BA, including three inflammatory cytokines: eotaxin (odds ratio (OR)=1.45, 95% confidence interval (CI): 1.08 to 1.95,pFDR=0.18), G-CSF (OR=4.21, 95% CI: 1.75 to 10.13,pFDR=0.05) and MCP-1/MCAF (OR=1.53, 95% CI: 1.12 to 2.10,pFDR=0.14); three immune cell traits: CD8dim NKT/T cells ratio (OR=0.59, 95% CI: 0.45 to 0.77,pFDR=0.06), CD8dim NKT counts (OR=0.58, 95% CI: 0.43 to 0.78,pFDR=0.06), CD8dim NKT/lymphocyte ratio (OR=0.63, 95% CI: 0.49 to 0.81,pFDR=0.06); one metabolite: X-12261 levels (OR=2.86, 95% CI: 1.73 to 4.74,pFDR=0.06).ConclusionsIn this study, eotaxin, G-CSF, MCP-1/MCAF, and X-12261 levels were shown to be risk factors for BA. However, CD8dim NKT/T cells ratio, CD8dim NKT counts, and CD8dim NKT/lymphocyte ratio were protective factors for BA. These findings provided a promising genetic basis for the etiology, diagnosis, and treatment of BA.
Seasonal changes in hydration in free-living Japanese children and adolescents
Authors: Amano Tatsuro , Sato Kotaro , Otsuka Junto , Okamoto Yumi , Takada Shota , Kato Hanano , Yokoyama Shotaro , Oshima Shoma , Hosokawa Yuri , Fujii Naoto , Mündel Toby , Kenny Glen P. , Hiwa Takako , Inoue Yoshimitsu 
Published: June 2024

Changes in hydration status occur throughout the day affecting physiological and behavioural functions. However, little is known about the hydration status of free-living Japanese children and the seasonality of this response. We evaluated hydration status estimated by urine osmolality (Uosm) in 349 children (189 boys and 160 girls, 9.5 ± 2.6 years, range: 6–15 years) upon waking at home and during a single school day in spring (April) and summer (July). Further, we assessed the efficacy of employing self-assessment of urine colour (UC; based on an 8-point scale) by children to monitor their hydration status. Early morning Uosm was greater in the spring (903 ± 220 mOsm L−1; n = 326) as compared to summer (800 ± 244 mOsm L−1; n = 125) ( P = 0.003, paired t test, n = 104). No differences, however, were observed in Uosm during the school day ( P = 0.417, paired t test, n = 32). While 66% and 50% of children were considered underhydrated (Uosm ≥ 800 mOsm L−1) upon waking in the spring and summer periods, respectively, more children were underhydrated (∼12%) during the school day. Self-reported UC was similar between seasons as assessed in the morning and school day ( P ≥ 0.101, paired t test), which differed from the pattern of responses observed with Uosm. We showed that a significant number of Japanese children are likely underhydrated especially in the spring period. Children do not detect seasonal changes in hydration from self-assessed UC, limiting its utility to manage hydration status in children.
A Closer Look into IPFS: Accessibility, Content, and Performance
Authors: Shi Ruizhe , Cheng Ruizhi , Han Bo , Cheng Yue , Chen Songqing 
Published: June 2024

The InterPlanetary File System (IPFS) has recently gained considerable attention. While prior research has focused on understanding its performance characterization and application support, it remains unclear: (1) what kind of files/content are stored in IPFS, (2) who are providing these files, (3) are these files always accessible, and (4) what affects the file access performance.
To answer these questions, in this paper, we perform measurement and analysis on over 4 million files associated with CIDs (content IDs) that appeared in publicly available IPFS datasets. Our results reveal the following key findings: (1) Mixed file accessibility: while IPFS is not designed for a permanent storage, accessing a non-trivial portion of files, such as those of NFTs and video streams, often requires multiple retrieval attempts, potentially blocking NFT transactions and negatively affecting the user experience. (2) Dominance of NFT (non-fungible token) and video files: about 50% of stored files are NFT-related, followed by a large portion of video files, among which about half are pirated movies and adult content. (3) Centralization of content providers: a small number of peers (top-50), mostly cloud nodes hosted by tech companies, serve a large portion (95%) of files, deviating from IPFS's intended design goal. (4) High variation of downloading throughput and lookup time: large file retrievals experience lower average throughput due to more overhead for resolving file chunk CIDs, and looking up files hosted by non-cloud nodes takes longer. We hope that our findings can offer valuable insights for (1) IPFS application developers to take into consideration these characteristics when building applications on top of IPFS, and (2) IPFS system developers to improve IPFS and similar systems to be developed for Web3.
Who's Got My Back? Measuring the Adoption of an Internet-wide BGP RTBH Service
Authors: Anghel Radu , Zhauniarovich Yury , Gañán Carlos 
Published: June 2024

Distributed Denial-of-Service (DDoS) attacks continue to threaten the availability of Internet-based services. While countermeasures exist to decrease the impact of these attacks, not all operators have the resources or knowledge to deploy them. Unwanted Traffic Removal Service (UTRS), being one of the oldest community-based anti-DDoS services aims at mitigating major DDoS attacks through the Border Gateway Protocol (BGP).
In this paper we develop and evaluate a methodology to automatically detect UTRS participation in the wild. To this end, we deploy a measurement infrastructure and devise a methodology to detect UTRS-based traffic blocking. Using this methodology, we conducted a longitudinal analysis of UTRS participants over ten weeks. Our results show that at any point in time, there were 562 participants, including multihomed, stub, transit, and IXP ASes. Moreover, we surveyed 245 network operators to understand why they would (not) join UTRS. Results show that threat and coping appraisal significantly influence the intention to participate in UTRS.
PlexinB1 Inactivation Reprograms Immune Cells in the Tumor Microenvironment, Inhibiting Breast Cancer Growth and Metastatic Dissemination
Authors: Franzolin Giulia , Brundu Serena , Cojocaru Carina F. , Curatolo Aurora , Ponzo Matteo , Mastrantonio Roberta , Mihara Emiko , Kumanogoh Atsushi , Suga Hiroaki , Takagi Junichi , Tamagnone Luca , Giraudo Enrico 
Published: June 2024

Abstract
Semaphorin–plexin signaling plays a major role in the tumor microenvironment (TME). In particular, Semaphorin 4D (SEMA4D) has been shown to promote tumor growth and metastasis; however, the role of its high-affinity receptor Plexin-B1 (PLXNB1), which is expressed in the TME, is poorly understood. In this study, we directly targeted PLXNB1 in the TME of triple-negative murine breast carcinoma to elucidate its relevance in cancer progression. We found that primary tumor growth and metastatic dissemination were strongly reduced in PLXNB1-deficient mice, which showed longer survival. PLXNB1 loss in the TME induced a switch in the polarization of tumor-associated macrophages (TAM) toward a pro-inflammatory M1 phenotype and enhanced the infiltration of CD8+ T lymphocytes both in primary tumors and in distant metastases. Moreover, PLXNB1 deficiency promoted a shift in the Th1/Th2 balance of the T-cell population and an antitumor gene signature, with the upregulation of Icos, Perforin-1, Stat3, and Ccl5 in tumor-infiltrating lymphocytes (TILs). We thus tested the translational relevance of TME reprogramming driven by PLXNB1 inactivation for responsiveness to immunotherapy. Indeed, in the absence of PLXNB1, the efficacy of anti-PD-1 blockade was strongly enhanced, efficiently reducing tumor growth and distant metastasis. Consistent with this, pharmacological PLXNB1 blockade by systemic treatment with a specific inhibitor significantly hampered breast cancer growth and enhanced the antitumor activity of the anti-PD-1 treatment in a preclinical model. Altogether, these data indicate that PLXNB1 signaling controls the antitumor immune response in the TME and highlight this receptor as a promising immune therapeutic target for metastatic breast cancers.
Knocking Out CD70 Rescues CD70-Specific NanoCAR T Cells from Antigen-Induced Exhaustion
Authors: De Munter Stijn , Buhl Juliane L. , De Cock Laurenz , Van Parys Alexander , Daneels Willem , Pascal Eva , Deseins Lucas , Ingels Joline , Goetgeluk Glenn , Jansen Hanne , Billiet Lore , Pille Melissa , Van Duyse Julie , Bonte Sarah , Vandamme Niels , Van Dorpe Jo , Offner Fritz , Leclercq Georges , Taghon Tom , Depla Erik , Tavernier Jan , Kerre Tessa , Drost Jarno , Vandekerckhove Bart 
Published: June 2024

Abstract
CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy for the treatment of both solid and liquid malignancies. However, the functionality of CD70-specific CAR T cells is modest. We optimized a CD70-specific VHH-based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T cells with malignant rhabdoid tumor organoids, and in vivo, using a diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although the nanoCAR T cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. We determined that fratricide was not causing this loss in efficacy but rather CD70 interaction in cis with the nanoCAR-induced exhaustion. Knocking out CD70 in nanoCAR T cells using CRISPR/Cas9 resulted in dramatically enhanced functionality in the diffuse large B-cell lymphoma PDX model. Through single-cell transcriptomics, we obtained evidence that CD70 knockout CD70-specific nanoCAR T cells were protected from antigen-induced exhaustion. In addition, we demonstrated that wild-type CD70-specific nanoCAR T cells already exhibited signs of exhaustion shortly after production. Their gene signature strongly overlapped with gene signatures of exhausted CAR T cells. Conversely, the gene signature of knockout CD70-specific nanoCAR T cells overlapped with the gene signature of CAR T-cell infusion products leading to complete responses in chronic lymphatic leukemia patients. Our data show that CARs targeting endogenous T-cell antigens negatively affect CAR T-cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target.
Human Resource Management Practices among Selected Hotels in Mandaue and Cebu Cities: A Phenomenological Study
Authors: Artes Alex B. , Cabatingan Albim Y. , Delantar Et al., 
Published: June 2024

This descriptive or Husserlian phenomenological study explored the lived experiences of the human resource management managers and supervisors among the selected hotels in Mandaue and Cebu cities. It also presented the meaning or the essence of the said lived experiences. These became the feeders for proposals for improvement. Using purposive sampling, ten (10) key informants who are managers in different hotels were selected as the source of information. The findings indicated that the human resources management components in planning, recruitment, maintenance development, and research were practiced with the guidance of HRM objectives. Moreover, some factors facilitated improving HR practices focused on managing human energy and capabilities to improve productivity. Further, there are challenges encountered by the organization that need to be addressed, for if unabated, it will have negative consequences. All the preceding became the basis for the crafting of recommendations for improvement. It was reflected that while the data generally lean toward the positive side, there is still room for further improvement. These opportunities for improvement are the take-off points for management to craft programs to further the practice of human resources management
Adequacy of Dialysis and Incidence of Atrial Fibrillation in Patients Undergoing Hemodialysis
Authors: Heo Ga Young , Park Jung Tak , Kim Hyo Jeong , Kim Kyung Won , Kwon Yong Uk , Kim Soo Hyun , Kim Gui Ok , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook , Kim Hyung Woo 
Published: June 2024

BACKGROUND:
Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality and has a greater prevalence in dialysis patients than in the general population. Several studies have suggested that uremic toxins may contribute to the development of AF. However, the association between dialysis adequacy and incident AF has not been well established.

METHODS:
In this retrospective nationwide cohort study, we analyzed data from the Korean National Periodic Hemodialysis Quality Assessment from 2013 to 2015 of patients who received outpatient maintenance hemodialysis 3× a week. The main exposure was single pooled Kt/V (spKt/V), which is the dialysis adequacy index, and the primary outcome was the development of AF. For the primary analysis, patients were categorized into quartiles according to baseline spKt/V. The lowest quartile, representing the lowest adequacy, was used as the reference group. Fine-Gray subdistribution hazard models were used, treating all-cause mortality as a competing risk.

RESULTS:
Of 25 173 patients, the mean age was 60 (51–69) years, and 14 772 (58.7%) were men. During a median follow-up of 5.7 years, incident AF occurred in a total of 3883 (15.4%) patients. Participants with a higher spKt/V tended to have lower AF incidence. In survival analysis, a graded association was observed between the risk of incident AF and spKt/V quartiles: subdistribution hazard ratios and 95% CIs for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.82–0.98), 0.84 (95% CI, 0.77–0.93), and 0.79 (95% CI, 0.72–0.88), respectively.

CONCLUSIONS:
This nationwide cohort study showed that a higher spKt/V is associated with a reduced risk of incident AF. These findings suggests that reducing uremic toxin burden through enhanced dialysis clearance may be associated with a lower risk of AF development in patients undergoing maintenance hemodialysis.
Weather-Based Disasters and Farming Communities in the Western Alps, 1650–1850
Authors: Dodgshon Robert 
Published: June 2024

Abstract
Because of the scale at which the key socio-cultural variables involved in climate-society interactions operate, analysis of such interactions benefits from a regional approach. Like all mountain regions, the western Alps possess a complex mosaic of topographically varied climates, or “topoclimates,” that can generate an array of damaging weather-based disasters, which impact residents at different scales. Cultural practices employed by Alpine farming communities in the latter period of the Little Ice Age (1650–1850) increased their vulnerability to such events, and their long-term stability relied on successful mitigation and coping strategies.
Unconscious Perception of Vernier Offsets
Authors: Amerio Pietro , Michel Matthias , Goerttler Stephan , Peters Megan A. K. , Cleeremans Axel 
Published: June 2024

Abstract
The comparison between conscious and unconscious perception is a cornerstone of consciousness science. However, most studies reporting above-chance discrimination of unseen stimuli do not control for criterion biases when assessing awareness. We tested whether observers can discriminate subjectively invisible offsets of Vernier stimuli when visibility is probed using a bias-free task. To reduce visibility, stimuli were either backward masked or presented for very brief durations (1–3 milliseconds) using a modern-day Tachistoscope. We found some behavioral indicators of perception without awareness, and yet, no conclusive evidence thereof. To seek more decisive proof, we simulated a series of Bayesian observer models, including some that produce visibility judgements alongside type-1 judgements. Our data are best accounted for by observers with slightly suboptimal conscious access to sensory evidence. Overall, the stimuli and visibility manipulations employed here induced mild instances of blindsight-like behavior, making them attractive candidates for future investigation of this phenomenon.
Organic Personality
Authors: Flowers Skyler R. 
Published: June 2024

Abstract
Bavinck’s critical appropriation of modern grammar in discussing Christian doctrine has led to his being described as a thinker who is “modern yet orthodox.” His appropriation of modern philosophy and psychology is clearly seen in his use of ‘personality’ in his doctrine of God and anthropology. This article argues that his use in these two areas demonstrates the organic ontology of creatures created in the image of their Creator. Thus, in understanding divine personality, human personality comes into focus, both theologically and psychologically. The article concludes with reflections on how the study of personality in Bavinck’s writings helps one to understand his entire project.
On the Harmony of Christ’s Wills
Authors: Johnson Randall K. 
Published: June 2024

Abstract
According to classical Christology, Christ’s human will was always in conformity with and never contrary to the divine will. Call this notion ‘volitional non-contrariety’ (VNC). But theologians disagree over how to explain VNC. In this article, I consider four models of VNC: the Parameter Model, the Beatific Vision Model, the Molinist Model, and the Causal Model. I argue that the Causal Model, coupled with a compatibilist account of freedom, is the best way to understand VNC because libertarian accounts of Christ’s human freedom inevitably fail to preserve some other element of classical Christology.
Prospects of using insects as alternative protein sources in broiler diets
Authors: Lee H.N. , Yeom G.L. , Kim Y.B. , Yum K.H. , Park J.Y. , Lee W.T. , Seo H.S. , Lee S.Y. , Kim J.H. 
Published: June 2024

Abstract
Insects are garnering attention as promising protein sources for broiler diets, presenting nutritional and environmental benefits comparable to plant-based protein sources. Various insects have been explored as broiler feed ingredients, including mealworm (Tenebrio molitor and Zophobas morio), cricket (Gryllidae), grasshopper (Acrididae), black soldier fly larvae (Hermetia illucens), silkworm pupae (Lepidoptera), bloodworm (Chironomidae), and housefly maggot (Musca domestica Linnaeus). We reviewed the literature involving these insects to assess their impact on broiler diets. Previous research has indicated that supplementing broiler diets with mealworm larvae meal (0.3 to 1.0% inclusion level) improved growth performance. Black soldier fly larvae meal (2.0 to 5.0% inclusion level) can replace protein sources. Similarly, dietary supplementation with silkworm pupae meal (1.5 to 5.0% inclusion level) can also replace protein sources, while including dietary supplementation with housefly maggot meal (1.6 to 4.0% inclusion level) enhanced growth performance in broiler chickens. However, few studies have focused on the effects of dried crickets, dried grasshoppers, and bloodworm supplementation on broiler performance and health. Despite the limitation that insects are more expensive compared to soybean meal or fishmeal, the short breeding period and the high nutritional content of insects make their use in broiler diets generally promising. Our meta-analysis of 28 studies on black soldier fly larvae supplementation found that it significantly decreased average daily feed intake and increased average daily gain with an optimal level of 15.3% determined through quadratic regression analysis. In conclusion, supplementing broiler diets with different insects has potential as a strategy to enhance the growth performance of broiler chickens without compromising overall health.