bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated microhematuria in potential kidney donors: evaluating kidney biopsy findings with dipstick urinalysis and urine microscopy results
Authors: Hammad Ehab A , Obeid Dalia A , Broering Dieter C , Shah Yaser Z , Brockmann Jens G , Marquez Kris A , Nazmi Ahmed M , Aleid Hassan A , AlManea Hadeel M , AlAbassi Amira M , Solomon Melba A , Jacob Nancy , Ali Tariq Z
Published: November 2024

Background

Isolated microhematuria (IMH) can signal hidden glomerular disease, necessitating detailed evaluations for potential kidney donors, including kidney biopsies. The optimal strategy for deciding on kidney biopsies remains unclear. While the British Transplant Society supports dipstick analysis, KDIGO focuses solely on urine microscopy. This study explored the correlation between kidney biopsy outcomes and results from dipstick urinalysis and urine microscopy in potential kidney donors.

Methods

This retrospective study encompassed all potential kidney donors who received kidney biopsies following a positive urine dipstick result for IMH, irrespective of whether red blood cells (RBCs) were found on urine microscopy. We performed sensitivity and specificity analyses to assess the effectiveness of microscopy and dipstick urinalysis in identifying histological abnormalities in the kidney biopsies.

Results

Approximately 49% of potential donors—133 out of 271—who had kidney biopsies due to positive dipstick tests showed negative results in urine microscopy for RBCs. In total, 168 donor candidates, or 62%, had abnormal findings in their biopsies, with nearly half of those diagnosed with immunoglobulin A nephropathy having negative urine microscopy results. Furthermore, 58% of potential donors with negative urine microscopy results—77 out of 133—also exhibited abnormal biopsy findings. The urine microscopy test displayed a sensitivity of 54.2% (95% confidence interval 46.6–61.5) and a specificity of 54.4% (95% confidence interval 44.8–63.7) for detecting abnormal biopsy results.

Conclusion

This study highlighted a significant presence of donors with IMH with underlying glomerular lesions. Using urine microscopy showed limited sensitivity and specificity in identifying abnormal histopathological results. Relying solely on urine microscopy may miss critical pathologies like IgAN in prospective kidney donors. The persistence of IMH during dipstick urinalysis calls for kidney biopsy in potential donors. These findings suggest that our results be incorporated into future global guideline formulations.
Impacts of intestinal fermentation on gastroesophageal reflux disease: can the tail wag the dog?
Authors: Quigley Eamonn M M
Published: November 2024

Communication between the foregut and the hindgut is amply illustrated by the gastro-colonic reflex and the impact of constipation on gastric function. Less well studied are the effects of the small intestinal or colonic microbiome and its metabolites on motor and secretory activities in the esophagus and stomach. In the study, the authors posit that small intestinal bacterial overgrowth promotes gastroesophageal and laryngo-pharyngeal reflux and in support of this hypothesis report an amelioration of related symptoms with antibiotic and dietary therapies. This editorial explores this hypothesis and also proposes an alternative one: changes in gastric and esophageal function consequent upon increased bacterial fermentation, not in the small intestine, but in the colon.
Collinearity-based Assembly Correction Tool GUI: Software for collinearity-based genome assembly correction
Authors: Zhang Shengcheng , Du Hejun , Zhang Xingtan , Wang Binzhong
Published: November 2024

Genome assembly errors can have a profound effect on downstream analyses. Collinearity-based Assembly Correction Tool GUI is designed to rectify these errors by leveraging collinearity information between the assembled genome and a reference genome. Collinearity-based Assembly Correction Tool GUI provides a user-friendly interface for visualizing and manually correcting assembly errors. It supports various operations such as insertion, deletion, inversion, and swapping of contigs and chromosomes. The software automatically reclusters, relabels, and redraws the assembly after each modification, ensuring that users can easily track changes. Collinearity-based Assembly Correction Tool GUI is a robust tool designed to efficiently correct large-scale assembly errors in polyploid genomes, featuring advanced collinearity detection capabilities.
Learning analysis of health system resilience
Authors: Thu Kyaw Myat , Bernays Sarah , Abimbola Seye
Published: November 2024

The emergence of ‘resilience’ as a concept for analysing health systems—especially in low- and middle-income countries—has been trailed by debates on whether ‘resilience’ is a process or an outcome. This debate poses a methodological challenge. What ‘health system resilience’ is interpreted to mean shapes the approach taken to its analysis. To address this methodological challenge, we propose ‘learning’ as a concept versatile enough to navigate the ‘process versus outcome’ tension. Learning—defined as ‘the development of insights, knowledge, and associations between past actions, the effectiveness of those actions, and future actions’—we argue, can animate features that tend to be silenced in analyses of resilience. As with learning, the processes involved in resilience are cyclical: from absorption to adaptation, to transformation, and then to anticipation of future disruption. Learning illuminates how resilience occurs—or fails to occur—interactively and iteratively within complex systems while acknowledging the contextual, cognitive, and behavioural capabilities of individuals, teams, and organizations that contribute to a system’s emergence from or evolution given shocks/stress. Learning analysis can help to resist the pull towards framing resilience as an outcome—as resilience is commonly used to mean or suggest a state or an attribute, rather than a process that unfolds, whether the outcomes are deemed positive or not. Analysing resilience as a learning process can help health systems researchers better systematically make sense of health system responses to present and future stress/shocks. In qualitative or quantitative analyses, seeing what is to be analysed as ‘learning’ rather than the more nebulous ‘resilience’ can refocus attention on what is to be measured, explained, and how—premised on the understanding that a health system with the ability to learn is the one with the ability to be resilient, regardless of the outcome of such a process.
Overcoming doubt: developing CDoH Essentials, a practical tool to introduce the commercial determinants of health
Authors: Brook Anna , Körner Katherine , van Schalkwyk May C I , Barnes Amy , Petticrew Mark
Published: November 2024

Despite growing awareness of the importance of commercial determinants of health (CDoH), there has been limited development or evaluation of educational and practice-focused support for public health professionals. This article reports findings from an action–research approach bringing together people with academic and practice expertise (n = 16) to co-create workshop materials (called ‘CDoH Essentials’), test and improve them through five trial workshops and explore their effects. Five English local public health teams co-facilitated the workshops in their organizations, with participants from public health teams and their internal partners (n = 94). Quantitative and qualitative data were collected throughout and analysed to understand: (1) whether the workshops met the expectations of participants, public health and academic observers, and (2) the effects of workshop participation on (a) participants’ knowledge, understanding and critical CDoH literacy, and (b) subsequent working practices and attitudes. The co-created CDoH Essentials appeared effective in meeting expectations, improving knowledge and critical CDoH literacy and promoting action on CDoH. The proportion of participants reporting ‘little’ or ‘no’ CDoH knowledge fell significantly following the workshop (55.4% vs 2.7%). Participants’ increased understanding supported reflection on the implications of the CDoH for their roles and for wider strategy and action. After 3 months, all five settings reported greater consideration of CDoH and had initiated or planned action. CDoH Essentials could be used to galvanize more effective public health action to tackle the CDoH in England and trialled in other public health contexts.
Birational Automorphism Groups of Severi–Brauer Surfaces Over the Field of Rational Numbers
Authors: Vikulova Anastasia V
Published: November 2024

We prove that the only non-trivial finite subgroups of birational automorphism group of non-trivial Severi–Brauer surfaces over the field of rational numbers are $\mathbb{Z}/3\mathbb{Z}$ and $(\mathbb{Z}/3\mathbb{Z})^{2}.$ Moreover, we show that $(\mathbb{Z}/3\mathbb{Z})^{2}$ is contained in $\textrm{Bir}(V)$ for any Severi–Brauer surface $V$ over a field of characteristic different from $2$ and $3$, and $(\mathbb{Z}/3\mathbb{Z})^{3}$ is contained in $\textrm{Bir}(V)$ for any Severi–Brauer surface $V$ over a field of characteristic different from $2$ and $3$, which contains a non-trivial cube root of unity.
Predicting mortality in hospitalized influenza patients: integration of deep learning-based chest X-ray severity score (FluDeep-XR) and clinical variables
Authors: Tsai Meng-Han , Ko Sung-Chu , Huang Amy Huaishiuan , Porta Lorenzo , Ferretti Cecilia , Longhi Clarissa , Hsu Wan-Ting , Chang Yung-Han , Hsiung Jo-Ching , Su Chin-Hua , Galbiati Filippo , Lee Chien-Chang
Published: November 2024

Objectives

To pioneer the first artificial intelligence system integrating radiological and objective clinical data, simulating the clinical reasoning process, for the early prediction of high-risk influenza patients.

Materials and Methods

Our system was developed using a cohort from National Taiwan University Hospital in Taiwan, with external validation data from ASST Grande Ospedale Metropolitano Niguarda in Italy. Convolutional neural networks pretrained on ImageNet were regressively trained using a 5-point scale to develop the influenza chest X-ray (CXR) severity scoring model, FluDeep-XR. Early, late, and joint fusion structures, incorporating varying weights of CXR severity with clinical data, were designed to predict 30-day mortality and compared with models using only CXR or clinical data. The best-performing model was designated as FluDeep. The explainability of FluDeep-XR and FluDeep was illustrated through activation maps and SHapley Additive exPlanations (SHAP).

Results

The Xception-based model, FluDeep-XR, achieved a mean square error of 0.738 in the external validation dataset. The Random Forest-based late fusion model, FluDeep, outperformed all the other models, achieving an area under the receiver operating curve of 0.818 and a sensitivity of 0.706 in the external dataset. Activation maps highlighted clear lung fields. Shapley additive explanations identified age, C-reactive protein, hematocrit, heart rate, and respiratory rate as the top 5 important clinical features.

Discussion

The integration of medical imaging with objective clinical data outperformed single-modality models to predict 30-day mortality in influenza patients. We ensured the explainability of our models aligned with clinical knowledge and validated its applicability across foreign institutions.

Conclusion

FluDeep highlights the potential of combining radiological and clinical information in late fusion design, enhancing diagnostic accuracy and offering an explainable, and generalizable decision support system.
Exploring the role of peripheral nerves in trauma-induced heterotopic ossification
Authors: Pereira Clifford T , Adams Sean H , Lloyd K C Kent , Knotts Trina A , James Aaron W , Price Theodore J , Levi Benjamin
Published: November 2024

Recent studies have linked pain and the resultant nociception-induced neural inflammation (NINI) to trauma-induced heterotopic ossification (THO). It is postulated that nociception at the injury site stimulates the transient receptor potential vanilloid-1 (the transient receptor potential cation channel subfamily V member 1) receptors on sensory nerves within the injured tissues resulting in the expression of neuroinflammatory peptides, substance P (SP), and calcitonin gene-related peptide (CGRP). Additionally, BMP-2 released from fractured bones and soft tissue injury also selectively activates TRVP1 receptors, resulting in the release of SP and CGRP and causing neuroinflammation and degranulation of mast cells causing the breakdown the blood-nerve barrier (BNB), leading to release of neural crest derived progenitor cells (NCDPCs) into the injured tissue. Parallel to this process BMP-2 initiates the NCDPCs toward osteogenic differentiation. CGRP has direct osteogenic effects on osteoprogenitor cells/mesenchymal stem cells, by activating BMP-2 via canonical Wnt/β-catenin signaling and cAMP-cAMP-response element binding protein signaling. BMP-2 binds to TGF-βRI and activates TGF-β-activated kinase 1 (TAK1) leading to phosphorylation of SMAD1/5/8, which binds to the co-activator SMAD4 and translocates to the nucleus to serve as transcription factor for BMP responsive genes critical in osteogenesis such as Runx2 and others. Thus, NINI phenotypes, and specifically CGRP induction, play a crucial role in THO initiation and progression through the activation of the BMP pathway, breakdown of the BNB, leading to the escape of NCDPCs, and the osteogenic differentiation of the latter.
Development of practical pheromone lures for Lygus hesperus and Lygus elisus (Heteroptera: Miridae)
Authors: Hall David R , Serrano Jacqueline , Yokota Glenn Y , Nieto Diego J , Farman Dudley I , McElfresh J Steven , Del Pozo-Valdivia Alejandro I , Millar Jocelyn G , Daane Kent M
Published: November 2024

The mirid bugs Lygus hesperus (Knight) and L. elisus (van Duzee) are key pests of forage, fiber, and fruit crops. Our goals were to identify pheromone components produced by females of both species and to develop practical pheromone dispensers for use in monitoring these pests. Volatiles collected from virgin female L. elisus contained (E)-2-hexenyl butyrate (E2HB) as the major component with lesser amounts of hexyl butyrate (HB) and (E)-4-oxo-2-hexenal (E4OH) (ratio 117.2:100:17.1, respectively), whereas volatiles and solvent extracts from L. hesperus contained HB and E4OH as major components, with only small amounts of E2HB (100:23.6:3.4, respectively in volatiles). Dispensers fabricated from pipette tips released the components at ~10 µg/d in a ratio similar to the loading ratio. These lures were used to optimize the pheromone blends in field studies from 2012 to 2017. Blends of E2HB and E4OH attracted L. elisus, and a 100:60 blend was optimal. Blends of HB and E4OH attracted L. hesperus, and a 100:60 blend was adopted as a base blend. The additions of possible minor components such as (Z)-3-hexenyl butyrate, (E)-2-hexenal, or 1-hexanol did not improve the attraction of L. hesperus. In trials in alfalfa and strawberry, traps baited with blends of HB:E4OH (100:60) were equally or more effective for monitoring L. hesperus than sweep or vacuum samples, with pipette tip dispensers lasting 2–3 weeks under field conditions. The numbers of L. hesperus captured were lower than expected as compared with reports of pheromone trapping for other Lygus spp. Some possible reasons were investigated.
Phosphine and phosphine plus ethyl formate for controlling papaya mealybug (Hemiptera: Pseudococcidae) on succulents
Authors: Zou Hang , Li Li , Li Baishu , Ren Yonglin , Liu Tao
Published: November 2024

The papaya mealybug, Paracoccus marginatus (Hemiptera: Pseudococcidae), poses a serious threat to global trade and is classified as a quarantine pest in some countries. Phosphine (PH3) is considered an alternative to methyl bromide for postharvest control of P. marginatus. However, reports addressing the impact of PH3 treatment to control P. marginatus on succulent plants are lacking. This study aims to investigate the effects of PH3 fumigation alone and in combination with ethyl formate (EF) on insecticidal activity across all developmental stages of P. marginatus and its influence on the quality of plant products. Tolerance tests showed that among all developmental stages, the egg stage of P. marginatus is the most tolerant to PH3 treatment. A concentration of 1 g m−3 PH3 for 8 h exposure at 25 °C achieved a 99.9968% (Probit-9) mortality rate for the eggs. Additionally, we examined the synergistic effects of combining EF with PH3. Combined fumigation with 0.5 g m−3 PH3 and 2 g m−3 EF for 8 h at 25 °C did not adversely affect the lifespan and quality of three succulent plant species, achieving an effective dose of 0.99991. These findings suggest that PH3 fumigation, with or without EF, are effective treatments for postharvest control of P. marginatus in succulent plants.
Transgenic αβ TCR tonic signaling is leukemogenic while strong stimulation is leukemia suppressive
Authors: Catarino Telmo A , Pacheco-Leyva Ivette , Baessa Marina , Pereira João L , R. dos Santos Nuno
Published: November 2024

The pre–T cell receptor (TCR) and TCR complexes are frequently expressed in T cell acute lymphoblastic leukemia (T-ALL), an aggressive T cell precursor malignancy. Although mutations in TCR components are infrequent in T-ALL, earlier research indicated that transgenic αβ TCR expression in mouse T cell precursors promoted T-ALL development. However, we recently found that stimulation of TCR signaling in T-ALL induced leukemic cell apoptosis and suppressed leukemia. Our aim was to elucidate if a given αβ TCR complex has a dual role in leukemogenesis depending on the nature of the stimulus. We demonstrate that transgenic expression of the Marilyn αβ TCR, specific for the H-Y male antigen presented by major histocompatibility complex class II, triggers T-ALL development exclusively in female mice. This T-ALL exhibited Notch1 mutations, Cdkn2a copy number loss, and immature immunophenotype, and infiltrated both lymphoid and nonlymphoid organs. Furthermore, leukemic cells expressed surface CD5, a marker of tonic TCR signaling. T-ALL efficiently developed in Rag2-deficient Marilyn transgenic females, indicating that Rag2-mediated recombination is not implicated in this T-ALL model. T-ALL development was also observed in the OT-I TCR transgenic mouse model, but it did not occur when major histocompatibility complex class I was abrogated through genetic inactivation of β2-microglobulin. Remarkably, exposure of Marilyn female T-ALL cells to endogenous agonist antigens in male recipient mice or exogenous peptides in female recipient mice resulted in T-ALL apoptosis and prolonged mouse survival. These findings underscore the dual role of the same αβ TCR complex in T-ALL, in which tonic stimulation is leukemogenic, while strong stimulation suppresses leukemia.
Trends in cancer mortality under age 50 in 15 upper-middle and high-income countries
Authors: Santucci Claudia , Mignozzi Silvia , Alicandro Gianfranco , Pizzato Margherita , Malvezzi Matteo , Negri Eva , Jha Prabhat , La Vecchia Carlo
Published: November 2024

Background

Rising cancer incidence, particularly for colorectal cancer, has been reported in young adults. This study examined whether this is related to an increase in mortality.

Methods

We analyzed World Health Organization mortality data among young adults aged 25-49 years in 15 most populous upper-middle and high-income countries from 1990 to 2021 with reliable data. Midyear populations were retrieved from the United Nations for the American Countries and from the World Health Organization for the other countries. We compared age-standardized mortality rates in 2019-2021 with those in 2009-2011 and performed joinpoint regression analysis for all cancers and selected most common cancer sites: colorectum, pancreas, lung, and breast.

Results

In 2019-2021, the highest age-standardized mortality rates (per 100 000) were in Romanian males (38.6) and Argentinian females (45.9), while the lowest ones were in Japanese males (16.3) and females (22.7). Age-standardized mortality rates for colorectal cancers increased in 2019-2021 compared with 2009-2011 in 9 countries among men and in 7 countries among women. The highest increases were in the United Kingdom (males: +26.1%; females: +33.7%), Canada (males: +25.3%), and Mexico (males: +33.5%; females: +29.7%). Long-term analysis over the last 3 decades showed declining trends in total cancer mortality in the majority of countries, in lung cancer mortality across all countries, and in breast cancer in all countries except in Latin America.

Conclusions

Although mortality from common cancers has generally decreased over the past 3 decades, mortality from colorectal cancer has increased in some countries. This highlights the need to control the obesity epidemic and implement targeted surveillance strategies in young populations.
Liver elastography-based risk score for predicting hepatocellular carcinoma risk
Authors: Tian Chan , Ye Chunyan , Guo Haiyan , Lu Kun , Yang Juan , Wang Xiao , Ge Xinyuan , Yu Chengxiao , Lu Jing , Jiang Longfeng , Zhang Qun , Song Ci
Published: November 2024

Background

Liver stiffness measurement (LSM) via vibration-controlled transient elastography accurately assesses fibrosis. We aimed to develop a universal risk score for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis.

Methods

We systematically selected predictors and developed the risk prediction model (HCC-LSM) in the hepatitis B virus (HBV) training cohort (n = 2251, median follow-up of 3.2 years). The HCC-LSM model was validated in an independent HBV validation cohort (n = 1191, median follow-up of 5.7 years) and a non-viral chronic liver disease (CLD) extrapolation cohort (n = 1189, median follow-up of 3.3 years). An HCC risk score was then constructed based on a nomogram. An online risk evaluation tool Liver Elastography-Based Hepatocellular Carcinoma Risk Score (LEBER) was developed using ChatGPT4.0.

Results

Eight routinely available predictors were identified, with LSM levels showing a significant dose-response relationship with HCC incidence (P < .001 by log-rank test). The HCC-LSM model exhibited excellent predictive performance in the HBV training cohort (C-index = 0.866) and the HBV validation cohort (C-index = 0.852), with good performance in the extrapolation CLD cohort (C-index = 0.769). The model demonstrated significantly superior discrimination compared to 6 previous models across the 3 cohorts. Cut-off values of 87.2 and 121.1 for the HCC-LSM score categorized participants into low-, medium-, and high-risk groups. An online public risk evaluation tool (LEBER; http://ccra.njmu.edu.cn/LEBER669.html) was developed to facilitate the use of HCC-LSM.

Conclusion

The accessible, reliable risk score based on LSM accurately predicted HCC development in patients with chronic hepatitis, providing an effective risk assessment tool for HCC surveillance strategies.
Utilization of Prognosis Assignment: A Cross-Sectional Survey of Military Periodontists
Authors: Sawaya Richard E , Dickens Noel E , Merchant Keith R , Wilson John H , Darcey Caitlin D
Published: November 2024

Introduction

Prognosis is a forecast of the likely course of a disease and its future implications on treatment outcomes. The significance of periodontal prognosis in clinical practice is evident by its influence on treatment planning, communication, and in the retrospective evaluation of treatment results. While there are multiple well-known prognosis systems reported in the periodontal dental literature, there is an absence of data on the actual use of prognosis assignment among practicing clinicians. The purpose of this study was to survey military periodontists regarding their utilization of periodontal prognosis and associated systems and to evaluate prognosis’ influence on treatment planning as well as its implications on operational dental readiness.

Methods

A 19-question internet survey was disseminated to military periodontists in the U.S. Air Force, Army, and Navy via their respective Periodontal Consultants to the Surgeon Generals. The survey inquired on provider-specific demographic information, the provider’s favored periodontal prognosis system, when and how prognosis is applied, and on the relationship between prognosis and operational dental readiness.

Results

Fifty-five percent (n = 65 out of 120) of eligible survey participants completed the survey. Army (94.4%, n = 17) and Air Force (72.2%, n = 13) respondents preferred utilizing the Kwok and Caton periodontal prognosis system compared to 37.9% (n = 11) of Navy periodontists. Most respondents assigned prognosis at multiple time points in a patient’s overall course of treatment (68%, n = 44), identified the severity of the periodontal presentation and the predictability of treatment outcomes as the most important factors involved in assigning a prognosis (82%, n = 55), and indicated that periodontal prognosis did not influence their dental readiness classification and vice versa.

Conclusions

Kwok and Caton and McGuire periodontal prognosis systems were utilized by the majority of respondents but differed in utilization by military service branch. Respondents considered periodontal presentation severity and treatment outcome predictability the most important factors when assigning a prognosis. There was minimal influence between operational dental readiness and periodontal prognosis. Future research will evaluate prognosis system utilization in a broader population and will assess the impact of system standardization in education and clinical practice.
Puzzling high-velocity calcium absorption features of type Ia supernovae
Authors: Zhao Xulin
Published: November 2024

Absorption features Ca ii NIR and Ca ii H&K of type Ia supernovae (SNe Ia) are characterized by their strong high-velocity features (HVFs). We find that, for these two features of calcium there is a puzzling anticorrelation between the line strengths of HVF and photospheric (PHO) components, and an unexpected positive correlation between the velocity difference and line strength ratio of HVF and PHO components. In comparison, HVFs of Si ii$\lambda$6355 and O i$\lambda$7773 show a positive correlation between the line strengths of HVF and PHO components, and no clear correlation between the velocity difference and line strength ratio of the two components. The differences may be associated with the fact that calcium was mostly synthesized in deeper layers than silicon and oxygen, and thus experienced much more serious blocking by substances in outer layers. These observations can shed light on the physics of HVFs.
emuflow: normalizing flows for joint cosmological analysis
Authors: Mootoovaloo Arrykrishna , García-García Carlos , Alonso David , Ruiz-Zapatero Jaime
Published: November 2024

Given the growth in the variety and precision of astronomical data sets of interest for cosmology, the best cosmological constraints are invariably obtained by combining data from different experiments. At the likelihood level, one complication in doing so is the need to marginalize over large-dimensional parameter models describing the data of each experiment. These include both the relatively small number of cosmological parameters of interest and a large number of ‘nuisance’ parameters. Sampling over the joint parameter space for multiple experiments can thus become a very computationally expensive operation. This can be significantly simplified if one could sample directly from the marginal cosmological posterior distribution of preceding experiments, depending only on the common set of cosmological parameters. We show that this can be achieved by emulating marginal posterior distributions via normalizing flows. The resulting trained normalizing flow models can be used to efficiently combine cosmological constraints from independent data sets without increasing the dimensionality of the parameter space under study. The method is able to accurately describe the posterior distribution of real cosmological data sets, as well as the joint distribution of different data sets, even when significant tension exists between experiments. The resulting joint constraints can be obtained in a fraction of the time it would take to combine the same data sets at the level of their likelihoods. We construct normalizing flow models for a set of public cosmological data sets of general interests and make them available, together with the software used to train them, and to exploit them in cosmological parameter inference.
Systematics in tests of general relativity using LISA massive black hole binaries
Authors: Garg Mudit , Sberna Laura , Speri Lorenzo , Duque Francisco , Gair Jonathan
Published: November 2024

Our current understanding is that an environment – mainly consisting of gas or stars – is required to bring massive black hole binaries (MBHBs) with total redshifted mass $M_z\sim [10^{4},10^7]~{\rm M}_{\odot }$ to the LISA band from parsec separation. Even in the gravitational wave (GW) dominated final inspiral, realistic environments can non-negligibly speed up or slow down the binary evolution, or leave residual, measurable eccentricity in the LISA band. Despite this fact, most of the literature does not consider environmental effects or orbital eccentricity in modelling GWs from near-equal mass MBHBs. Considering either a circular MBHB embedded in a circumbinary disc or a vacuum eccentric binary, we explore if ignoring either secular gas effects (migration and accretion) or eccentric corrections to the GW waveform can mimic a failure of general relativity (GR). We use inspiral-only aligned-spin 3.5 post-Newtonian (PN) waveforms, a complete LISA response model, and Bayesian inference to perform a parameterized test of GR. For a 4-yr LISA observation of an MBHB with $M_z=10^{5}~{\rm M}_{\odot }$, primary-to-secondary mass ratio $q=8$, and component BHs’ dimensionless spins $\chi _{1,2}=0.9$ at redshift $z=1$, even a moderate gas–disc imprint (Eddington ratio ${\it f}_{\rm Edd}\sim 0.1$) or low initial eccentricity ($e_0\sim 10^{-2.5}$) causes a false violation of GR in several PN orders. However, correctly modelling either effect can mitigate systematics while avoiding significant biases in vacuum circular systems. The adoption of LISA makes it urgent to consider gas imprints and eccentricity in waveform models to ensure accurate inference for MBHBs.
A coronal mass ejection encountered by four spacecraft within 1 au from the Sun: ensemble modelling of propagation and magnetic structure
Authors: Palmerio Erika , Kay Christina , Al-Haddad Nada , Lynch Benjamin J , Trotta Domenico , Yu Wenyuan , Ledvina Vincent E , Sánchez-Cano Beatriz , Riley Pete , Heyner Daniel , Schmid Daniel , Fischer David , Richter Ingo , Auster Hans-Ulrich
Published: November 2024

Understanding and predicting the structure and evolution of coronal mass ejections (CMEs) in the heliosphere remains one of the most sought-after goals in heliophysics and space weather research. A powerful tool for improving current knowledge and capabilities consists of multispacecraft observations of the same event, which take place when two or more spacecraft fortuitously find themselves in the path of a single CME. Multiprobe events can not only supply useful data to evaluate the large-scale of CMEs from 1D in situ trajectories, but also provide additional constraints and validation opportunities for CME propagation models. In this work, we analyse and simulate the coronal and heliospheric evolution of a slow, streamer-blowout CME that erupted on 2021 September 23 and was encountered in situ by four spacecraft approximately equally distributed in heliocentric distance between 0.4 and 1 au. We employ the Open Solar Physics Rapid Ensemble Information modelling suite in ensemble mode to predict the CME arrival and structure in a hindcast fashion and to compute the ‘best-fitting’ solutions at the different spacecraft individually and together. We find that the spread in the predicted quantities increases with heliocentric distance, suggesting that there may be a maximum (angular and radial) separation between an inner and an outer probe beyond which estimates of the in situ magnetic field orientation (parametrized by flux rope model geometry) increasingly diverge. We discuss the importance of these exceptional observations and the results of our investigation in the context of advancing our understanding of CME structure and evolution as well as improving space weather forecasts.
Tectonic and eustatic controls on the palaeobiogeographic distribution of Eocene bivalves
Authors: Mitra Aniket , Halder Kalyan
Published: November 2024

The Eocene epoch experienced important global events—a warming and transgression at the beginning, and a cooling and regression at the end. Crucial tectonic rearrangements were also taking place, such as the northward movement of the Indian plate and closure of the Tethys Sea. Here, the global palaeobiogeography of all Eocene bivalve genera is studied to see the effects of these tectonic and eustatic changes. We have established formal palaeobiogeographic provinces and explored their evolving relationships based on statistical analyses of global distribution data of all bivalve genera for each stage of the Eocene. The late Paleocene (Thanetian) and early Oligocene (Rupelian) stages have also been included to understand potential effects of climate and sea-level changes. Bivalve diversity increased at the beginning and fell at the end of the Eocene, apparently in response to opposite climatic and eustatic changes at these boundaries. The palaeobiogeographic provinces also expanded and shrank, respectively. The tropical and subtropical basins of northwestern Europe and eastern and western America accommodated maximum bivalve diversity and yielded temporally stable provinces. These provinces shared many bivalve genera. However, similarity of the western American fauna with that of eastern America dwindled with time as the Western Interior Seaway disappeared. The distribution sequence of shared diachronous genera between the provinces revealed that (1) the Western American Province later developed affinity to the Japan and Eastern Russian Province facilitated by the Alaska and Oyashio currents, (2) the Northern Equatorial Current and North Atlantic Gyre were primarily responsible for the similarity between the Tethyan and Atlantic provinces, and (3) the Tethys seaway was active until the middle Eocene, which allowed westward migration of the western Indian fauna leading to its similarity with the European and northern African faunas. This link was severed in the late Eocene.
The Natural Products Magnetic Resonance Database (NP-MRD) for 2025
Authors: Wishart David S , Sajed Tanvir , Pin Matthew , Poynton Ella F , Goel Bharat , Lee Brian L , Guo An Chi , Saha Sukanta , Sayeeda Zinat , Han Scott , Berjanskii Mark , Peters Harrison , Oler Eponine , Gautam Vasuk , Jordan Tamara , Kim Jonghyeok , Ledingham Benjamin , Tretter Zachary M , Koller James T , Shreffler Hailey A , Stillwell Lillian R , Jystad Amy M , Govind Niranjan , Bade Jessica L , Sumner Lloyd W , Linington Roger G , Cort John R
Published: November 2024

The Natural Products Magnetic Resonance Database (NP-MRD; https://np-mrd.org) is a comprehensive, freely accessible, web-based resource for the deposition, distribution, extraction, and retrieval of nuclear magnetic resonance (NMR) data on natural products (NPs). The NP-MRD was initially established to support compound de-replication and data dissemination for the NP community. However, that community has now grown to include many users from the metabolomics, microbiomics, foodomics, and nutrition science fields. Indeed, since its launch in 2022, the NP-MRD has expanded enormously in size, scope, and popularity. The current version of NP-MRD now contains nearly 7× more compounds (281 859 versus 40 908) and 7× more NMR spectra (5.5 million versus 817 278) than the first release. More specifically, an additional 4.6 million predicted spectra and another 11 000 spectra simulated from experimental chemical shifts were deposited into the database. Likewise, the number of NMR raw spectral data depositions has grown from 165 spectra per year to >10 000 per year. As a result of this expansion, the number of monthly webpage views has grown from 55 to 20 000 and the number of monthly visitors has increased from 7 to 2500. To address this growth and to better support the expanding needs of its diverse community of users, many additional improvements to the NP-MRD have been made. These include significant enhancements to the data submission process, notable updates to the database’s spectral search utilities and useful additions to support better NMR spectral analysis/prediction. Significant efforts have also been undertaken to remediate and update many of NP-MRD’s database entries. This manuscript describes these database improvements and expansion efforts, along with how they have been implemented and what future upgrades to the NP-MRD are planned.
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

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

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

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

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

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.