bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical considerations on the use of big data and artificial intelligence in kidney research from the ERA ethics committee
Authors: Van Biesen Wim , Ponikvar Jadranka Buturovic , Fontana Monica , Heering Peter , Sever Mehmet S , Sawhney Simon , Luyckx Valerie 
Published: November 2024

ABSTRACT
In the current paper, we will focus on requirements to ensure big data can advance the outcomes of our patients suffering from kidney disease. The associated ethical question is whether and how we as a nephrology community can and should encourage the collection of big data of our patients. We identify some ethical reflections on the use of big data, and their importance and relevance. Furthermore, we balance advantages and pitfalls and discuss requirements to make legitimate and ethical use of big data possible.
The collection, organization, and curation of data come upfront in the pipeline before any analyses. Great care must therefore be taken to ensure quality of the data at this stage, to avoid the ‘garbage in garbage out’ problem and suboptimal patient care as a consequence of such analyses.
Access to the data should be organized so that correct and efficient use of data is possible. This means that data must be stored safely, so that only those entitled to do so can access them. At the same time, those who are entitled to access the data should be able to do so in an efficient way, so as not to hinder relevant research.
Analysis of observational data is itself prone to many errors and biases. Each of these biases can finally result in provision of low-quality medical care. Secure platforms should therefore also ensure correct methodology is used to interpret the available data. This requires close collaboration of a skilled workforce of experts in medical research and data scientists. Only then will our patients be able to benefit fully from the potential of AI and big data.
Seasonal variations in the association between proteinuria and kidney failure
Authors: Kawaoka Takayuki , Sakaguchi Yusuke , Oka Tatsufumi , Asahina Yuta , Hattori Koki , Doi Yohei , Hashimoto Nobuhiro , Kusunoki Yasuo , Yamamoto Satoko , Yamato Masafumi , Yamamoto Ryohei , Matsui Isao , Mizui Masayuki , Kaimori Jun-Ya , Isaka Yoshitaka 
Published: November 2024

ABSTRACT

Background and hypothesis
Proteinuria exhibits seasonal fluctuations, decreasing in summer and increasing in winter. It is unknown whether the association between proteinuria and the risk of kidney failure varies by season.

Methods
The Osaka Consortium for Kidney Disease Research (OCKR) database contained retrospective data from 15 367 patients with estimated glomerular filtration rates of 10–60 mL/min/1.73 m2, who were referred to the Department of Nephrology at five clinical centers in Japan, between 2010 and 2021. Multivariate Cox models were used to examine the associations of urinary protein-to-creatinine ratio (UPCR) in summer (UPCRsummer) and winter (UPCRwinter), with kidney failure defined as initiation of kidney replacement therapy. LASSO was used to compare the strength of the association between UPCRsummer and UPCRwinter with respect to kidney failure. We also assessed whether seasonal fluctuations in UPCR were associated with kidney failure.

Results
The median (interquartile range) UPCRwinter was 0.89 (0.22, 2.69) g/gCre, 46% higher than UPCRsummer [0.61 (0.16, 1.87) g/gCre]. During a median follow-up of 3.0 years, 1585 patients developed kidney failure. In time-dependent Cox models, UPCRwinter showed a higher hazard of kidney failure [1.66 per 1-standard deviation (SD) increase; 95% confidence interval (CI) 1.60–1.73] than UPCRsummer (1.45 per 1-SD increase; 95% CI 1.41–1.48). LASSO identified that UPCRwinter was more strongly associated with kidney failure than UPCRsummer. Furthermore, higher percentage changes in UPCRwinter relative to UPCRsummer was associated with a higher hazard of kidney failure.

Conclusions
Proteinuria in winter exhibited stronger associations with kidney failure than that in summer. Seasonal fluctuations in UPCR should not be overlooked in the management of chronic kidney disease to make reasonable clinical decisions.
LTBK-01. PHASE 3 STELLAR STUDY SHOWS EFLORNITHINE IMPROVES OVERALL SURVIVAL (OS) AND PROGRESSION FREE SURVIVAL (PFS) IN PATIENTS WITH RECURRENT 2021 WHO ASTROCYTOMA, IDH-MUTANT GRADE 3
Authors: Colman Howard , Lombardi Giuseppe , Wong Eric , Walbert Tobias , Eoli Marica , Lassman Andrew , Peereboom David , Kizilbash Sani , Kamiya-Matsuoka Carlos , Pitz Marshall , Strowd Roy , Desjardins Annick , Kumthekar Priya , Mason Warren , Pellerino Alessia , Soffietti Ricardo , Butowski Nicholas , Forsyth Peter , Hamza Mohamed , Hau Peter , Lallana Enrico , Nabors Burt , Piccioni David , Uhlmann Erik , Welsh Liam , Wen Patrick , Dietrich Jorg , Levin Victor 
Published: November 2024

Abstract

BACKGROUND
Recurrent anaplastic astrocytoma (AA), a grade 3 brain cancer, remains an unmet medical need. STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone, originally for patients with recurrent AA. However, as the WHO definition of AA evolved during trial conduct (e.g., excluding IDH wild-type disease), we determined results in both the original ITT population and by revised molecularly defined WHO 2021 diagnoses in pre-planned analyses.

METHOD
Key eligibility: age ≥ 18, AA (2016 WHO criteria), first recurrence ≥ 6 months after radiation and temozolomide, KPS ≥ 70, no imaging findings consistent with grade 4 glioblastoma. Stratification: IDH, age, resection extent, and geography. Patients were randomized to Arm A: eflornithine (2.8 g/m2 TID Q 2/3 weeks) with lomustine (90 mg/m2 Q 6 weeks) or Arm B: lomustine (110 mg/m2 Q 6 weeks). Primary endpoint was OS. The pre-specified hazard ratio (HR) goal was 0.667 based on projected median OS (mOS) increase to 18 months from 12 months.

RESULTS
343 pts (172/171 Arms A/B) were randomized (105 sites, 8 countries). ITT analysis found no difference between arms (mOS 23.4 vs. 20.3 months, HR = 0.94). However, a pre-specified subset analysis in IDH mutant, 2021 WHO-defined grade 3 astrocytoma (n=194), showed significant improvement with eflornithine (mOS 34.9 vs. 23.5 months, HR = 0.64, log rank p = 0.016) and PFS (15.8 vs. 7.2 months, HR = 0.58, log rank p = 0.015). No difference was observed in the IDH wild-type subset. AEs were consistent with historic data.

CONCLUSION
There was no difference in OS between arms in the ITT analysis. However, medically meaningful and statistically significant OS and PFS benefits were observed with eflornithine in the pre-planned analysis of patients with molecularly defined 2021 WHO CNS grade 3 astrocytoma.
Catalytic mechanism underlying the regiospecificity of coumarin-substrate transmembrane prenyltransferases in Apiaceae
Authors: Han Junwen , Munakata Ryosuke , Takahashi Hironobu , Koeduka Takao , Kubota Mayumi , Moriyoshi Eiko , Hehn Alain , Sugiyama Akifumi , Yazaki Kazufumi 
Published: November 2024

Abstract
Plant membrane-bound prenyltransferases (PTs) catalyze the transfer of prenyl groups to acceptor substrates, phenols, using prenyl diphosphates as the donor substrate. The presence of prenyl residues in the reaction products, prenylated phenols, is key to the expression of a variety of physiological activities. Plant PTs generally exhibit high specificities for both substrate recognition and prenylation sites, while the molecular mechanism involved in these enzymatic properties is largely unknown. In this study, we performed a systematic biochemical analysis to elucidate the catalytic mechanism responsible for the reaction specificity of plant PTs. Using two representative PTs, PsPT1 and PsPT2, from parsnip (Pastinaca sativa, Apiaceae), which differ only in the regiospecificity of the prenylation site, we performed domain swapping and site-directed mutagenesis of these PTs, followed by detailed enzymatic analysis combined with 3D modeling. As a result, we discovered the domains that control prenylation site specificity and further defined key amino acid residues responsible for the catalytic mechanism. In addition, we showed that the control mechanism of prenylation specificity revealed here is also highly conserved among coumarin-substrate PTs. These data suggest that the regulatory domain revealed here is commonly involved in prenylation regiospecificity in Apiaceae PTs.
The Rhyolite Factory: Insights from Rhyolite-MELTS Geobarometry of Plutonic Rocks and Associated Volcanics
Authors: Gualda Guilherme A R , Miller Calvin F , Wallrich Blake M 
Published: November 2024

Abstract
Magmatic systems feed eruptions to the surface; lead to the formation of ore deposits; provide energy for geothermal systems; and are key to Earth’s differentiation. While it is commonly accepted that silicic magmatic systems span much of the crust, little direct evidence is available for their vertical continuity (or lack thereof), or for the spatial and temporal distribution of melt within them. In this work, we focus on Miocene plutonic and volcanic units exposed in the Colorado Extensional Corridor, SW USA. Plutonic units (Searchlight Pluton [SLP], Aztec Wash Pluton [AWP], and Spirit Mountain Batholith [SMB]) consist primarily of coarse-grained granitoids rich in feldspar that can be credibly considered cumulates. Marginal facies and fine-grained dikes and sills are interpreted to record melt compositions that fed the plutons. Leucogranite dikes and roof units were likely extracted from the crystallizing plutons. The nearby Upper Highland Range Volcanics record compositions that can be interpreted as extracted from the SLP system. We use whole-rock compositions of granitoids and rhyolites to calculate extraction pressures, and glass compositions from volcanic rocks to calculate pre-eruptive storage pressures using rhyolite-MELTS. We seek pressures consistent with assemblages containing quartz+2 feldspars±magnetite±ilmenite (Q2F or Q2FMI assemblages). We use the calculated pressures to assess the distribution of magma in silicic magmatic crustal columns. The dataset reveals three main clusters of compositions and pressures: 72–74.5 wt % SiO2, 450–370 MPa (Q2F extraction); 75.5–77 wt % SiO2, 300–185 MPa (Q2FMI extraction and pre-eruptive storage); 77.5–78 wt % SiO2, 180–120 MPa (Q2FMI extraction and pre-eruptive storage). Compositions attributed to cumulates (based on texture, major and trace-element compositions) do not typically yield extraction pressures, suggesting that rhyolite-MELTS can generally distinguish compositions of melts from those of cumulates. Our results show that magma distribution spanned from the middle crust to the surface, with well-defined gaps in pressure between the three groups. Magma mushes were located in the middle crust (~400 MPa, ~15 km depth), from which magmas that fed the shallow plutonic units were derived—there is no exposed record of these magma mushes, and they are inferred from extraction pressures for the less evolved fine-grained rocks. We infer two sets of discrete, shallower mush bodies that fed eruptions to the surface. The leucogranite roof zones represent bodies of melt-dominated magma that failed to erupt and instead solidified in the subsurface. Magma distribution was vertically discretized, rather than continuous as shown in most models—there were specific horizons within the crust where magma accumulation was favored, while much of the crust remained melt-free.
KNUCKLES regulates floral meristem termination by controlling auxin distribution and cytokinin activity
Authors: Wang Guangling , Wu Zhiyue , Sun Bo 
Published: November 2024

Abstract
The termination of floral meristem (FM) activity is essential for the normal development of reproductive floral organs. During this process, KNUCKLES (KNU), a C2H2-type zinc finger protein, crucially regulates FM termination by directly repressing the expression of both the stem cell identity gene WUSCHEL (WUS) and the stem cell marker gene CLAVATA3 (CLV3) to abolish the WUS-CLV3 feedback loop required for FM maintenance. In addition, phytohormones auxin and cytokinin are involved in FM regulation. However, whether KNU modulates auxin and cytokinin activities for FM determinacy control remains unclear. Here, we show that the auxin distribution and the cytokinin activity mediated by KNU in Arabidopsis (Arabidopsis thaliana) promote the termination of FM during stage 6 of flower development. Mutation of KNU leads to altered distribution of auxin and cytokinin in the FM of a stage 6 floral bud. Moreover, KNU directly represses the auxin transporter gene PIN-FORMED1 (PIN1) and the cytokinin biosynthesis gene ISOPENTENYLTRANSFERASE7 (IPT7) via mediating H3K27me3 deposition on these 2 loci to regulate auxin and cytokinin activities. Our study presents a molecular regulatory network that elucidates how the transcriptional repressor KNU integrates and modulates the activities of auxin and cytokinin, thus securing the timed FM termination.
Pummelo fruit extract (Citrus maxima) reduces oxidative damage in peripheral blood of obese patients
Authors: Nunes Vinícius Tejada , Gonçalves Itamar Luís , Schmitt Elizandra Gomes , Schreiner Gênifer Erminda , dos Santos Laura Smolski , de Moura Sarmento Silvia Muller , Pereira Camila Berny , da Costa Escobar Piccoli Jacqueline , Manfredini Vanusa , Denardin Cristiane Casagrande 
Published: November 2024

Abstract

Objectives
To verify the level of oxidation of biomolecules in the peripheral blood of obese patients before and after incubation with the pummelo pulp extract at 25 mg/mL.

Methods
This investigation included 241 individuals, distributed across the following groups: control (n = 69; 30 men and 39 women); pre-obesity (n = 78; 29 men and 49 women); level I obesity (n = 62; 20 men and 42 women); and level II or III obesity (n = 32; 11 men and 21 women).

Results
TBARS and MN levels were significantly altered by incubation with pummelo extract in both genders and in all the groups according to their obesity level. Another alteration in the antioxidant profile of the samples was a significant increase in vitamin C levels observed after incubation with pummelo extract in all experimental groups.

Conclusions
The aqueous extract of pummelo pulp showed in vitro biological activity against the oxidation of biomolecules, suggesting that its bioactive compounds may bring health benefits of obese patients.
Is therapeutic plasma exchange effective in leptospirosis-associated severe pulmonary haemorrhagic syndrome? A systematic review
Authors: Bandara J M R P , Rosairo A , Ranasinghe G S , De Silva T D , Gawarammana I B 
Published: November 2024

Abstract
Leptospirosis is a re-emerging zoonosis fast becoming a global burden. Pulmonary haemorrhages are a deadly complication, with case fatality rates &gt;50%. Systemic vasculitis is thought to be the pathological process responsible for pulmonary haemorrhages and therapeutic plasma exchange (TPE) is one of the treatments offered. This systematic review aims to evaluate the effectiveness of TPE in managing leptospirosis-associated severe pulmonary haemorrhagic syndrome (SPHS). A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol. The search used Medical Subject Headings in PubMed with keywords ‘Leptospirosis’ OR ‘Leptospira’ OR ‘Weil disease’ AND ‘plasmapheresis’ OR ‘plasma exchange’ AND ‘pulmonary haemorrhage’ OR ‘alveolar haemorrhage’. The search was widened to include the Google Scholar database. The review was confined to English-language articles and focused on primary research studies. Nineteen articles were considered for analysis. There were no randomized controlled trials. A non-randomized trial and a retrospective cohort documented recovery following adjuvant TPE treatment. Most case reports mention significant improvement and complete recovery following administration of TPE. One case reported the death of a patient despite treatment. However, this review revealed a lack of strong evidence endorsing the routine application of TPE as a therapeutic intervention for cases of SPHS. Thus we recommend the initiation of a well-structured randomized controlled trial to ensure an accurate assessment of the efficacy of TPE.
Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana
Authors: Choga Wonderful T , Gustani-Buss Emanuele , Tegally Houriiyah , Maruapula Dorcas , Yu Xiaoyu , Moir Monika , Zuze Boitumelo J L , James San Emmanuel , Ndlovu Nokuthula S , Seru Kedumetse , Motshosi Patience , Blenkinsop Alexandra , Gobe Irene , Baxter Cheryl , Manasa Justen , Lockman Shahin , Shapiro Roger , Makhema Joseph , Wilkinson Eduan , Blackard Jason T , Lemey Phillipe , Lessells Richard J , Martin Darren P , de Oliveira Tulio , Gaseitsiwe Simani , Moyo Sikhulile 
Published: November 2024

Abstract
Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.1.529.5.3.1.1.1.1.1.1.74.1 (alias FN.1, clade 22E). These genomes were sourced from both epidemiologically linked and unlinked samples collected in three close locations within the district of Greater Gaborone. In this study, we assessed the worldwide prevalence of the FN.1 lineage, evaluated its mutational profile, and conducted a phylogeographic analysis to reveal its global dispersal dynamics. Among approximately 16 million publicly available SARS-CoV-2 sequences generated by 30 September 2023, only 87 were of the FN.1 lineage, including 22 from Botswana, 6 from South Africa, and 59 from the UK. The estimated time to the most recent common ancestor of the 87 FN.1 sequences was 22 October 2022 [95% highest posterior density: 2 September 2022—24 November 2022], with the earliest of the 22 Botswana sequences having been sampled on 7 December 2022. Discrete trait reconstruction of FN.1 identified Botswana as the most probable place of origin. The FN.1 lineage is derived from the BQ.1.1 lineage and carries two missense variants in the spike protein, S:K182E in NTD and S:T478R in RDB. Among the over 90 SARS-CoV-2 lineages circulating in Botswana between September 2020 and July 2023, FN.1 was most closely related to BQ.1.1.74 based on maximum likelihood phylogenetic inference, differing only by the S:K182E mutation found in FN.1. Given the early detection of numerous novel variants from Botswana and its neighbouring countries, our study underscores the necessity of continuous surveillance to monitor the emergence of potential VOCs, integrating molecular and spatial data to identify dissemination patterns enhancing preparedness efforts.
Mathematical comparison of protocols for adapting a bacteriophage to a new host
Authors: Bull James J , Krone Stephen M 
Published: November 2024

Abstract
Interest in phage therapy—the use of bacterial viruses to treat infections—has increased recently because of the rise of infections with antibiotic-resistant bacteria and the failure to develop new antibiotics to treat those infections. Phages have shown therapeutic promise in recent work, and successful treatment minimally requires giving the patient a phage that will grow on their infecting bacterium. Although nature offers a bountiful and diverse supply of phages, there have been a surprising number of patient infections that could not be treated with phages because no suitable phage was found to kill the patient’s bacterium. Here, we develop computational models to analyze an alternative approach to obtaining phages with new host ranges—directed evolution via laboratory propagation of phages to select mutants that can grow on a new host. The models separately explore alternative directed evolution protocols for phage variants that overcome three types of bacterial blocks to phage growth: a block in adsorption, temperate phage immunity to superinfection, and abortive infection. Protocols assume serial transfer to amplify pre-existing, small-effect mutants that are initially rare. Best protocols are sensitive to the nature of the block, and the models provide several insights for enhancing success specific to each case. A common result is that low dilution rates between transfers are beneficial in reducing the mutant growth rate needed to ascend. Selection to overcome an adsorption block is insensitive to many protocol variations but benefits from long selection times between transfers. A temperate phage selected to grow on its lysogens can evolve in any of three phenotypes, but a common protocol favors the desired changes in all three. Abortive infection appears to be the least amenable to evolving phage growth because it is prone to select phages that avoid infection.
Adjusting adjustments: Using external data to estimate the impact of different confounder sets on published associations.
Authors: Ahern Thomas P. , Collin Lindsay J. , MacLehose Richard F. , Littenberg Benjamin , Haines Laura , Bonnett Michaela , Asmussen Fanny Børne , Chen Jennifer , Lash Timothy L. 
Published: November 2024

Background:
A 2013 meta-analysis observed a protective association between overweight BMI (versus normal BMI) and all-cause mortality that was particularly strong in people aged ≥65. Estimates informing this meta-analysis were highly heterogeneous, and critics raised insufficient or inappropriate confounder adjustment in many studies as an explanation for the protective summary association. Using this topic as an example, we demonstrate a novel approach for external adjustment of individual studies for a uniform and sufficient confounder set before meta-analysis.

Methods:
We abstracted summary data on the 33 associations comprising the age ≥65 stratum of the 2013 meta-analysis. Using an external dataset (NHANES III), we derived covariates used in each study’s multivariable model of the overweight–mortality association. We then calculated a bias factor to quantify the direction and magnitude of displacement of the ratio measure of association after changing from the original adjustment set to a sufficient adjustment set. After applying bias factors to adjust original associations, we compared summary results from random effects meta-analyses with and without such adjustment.

Results:
We reproduced the original meta-analysis of overweight–mortality estimates among older participants and found a protective association similar to that reported in 2013 (summary RR=0.88, 95% CI: 0.84, 0.92, I2=38.4%). After we simulated uniform adjustment of all 33 associations for a minimally sufficient confounder set (age, sex, and smoking status), the meta-analysis showed a similar summary association (summary RR=0.90, 95% CI: 0.86, 0.94), but with reduced heterogeneity (I2=34.6%).

Conclusion:
Simulated uniform adjustment for a sufficient confounder set may improve rigor and promote consensus in meta-analysis.