bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative analysis of sterol balance in a mouse model of hepatic lipid accumulation induced by cholesterol and cholic acid supplementation
Authors: Soma Hinata , Yoshida Ryo , Ishizuka Satoshi
Published: December 2024

The cholesterol balance and bile acid metabolism in a mouse model of hepatic lipid accumulation induced by a diet supplemented with cholesterol and cholic acid (CA) were quantitatively evaluated. The mice were fed diets supplemented with different levels of cholesterol (0, 3, or 6 g/kg of diet) and CA (0.5 g/kg of diet) for 6 weeks. Cholesterol supplementation doubled the hepatic triglyceride concentration, regardless of the supplementation level, without inflammation or gallstone formation. Both cholesterol supplementations enhanced fecal excretion of muricholic acid. Additionally, the higher cholesterol supplementation led to an increase in fecal cholesterol excretion, accompanied by elevated expression of hepatic cholesterol exporters and a reduction in fecal bile acid excretion. In this mouse study, supplementation with 3 g cholesterol/kg diet and 0.5 g CA/kg diet was sufficient to induce hepatic lipid accumulation.
Thermal biology of the endemic lizard Phymaturus verdugo: is it as conservative as we think?
Authors: Moreno Azocar Débora L , Vicenzi Nadia , Literas Sofía , Corbalán Valeria
Published: December 2024

Under the scenario of global climate change, understanding how animals cope with environmental changes might help to predict their future responses. The genus Phymaturus serves as a valuable model for studying thermal biology owing to its conservatism in thermal traits, despite its broad latitudinal distribution. By examining two geographically close populations of the lizard Phymaturus verdugo from the Andean mountains, we aimed to determine whether body mass, dorsal melanism, and microclimatic conditions influence their thermal biology. The species demonstrates moderate to good thermoregulation, with females increasing effectiveness in sites with lower thermal quality. Although their preferred temperature remained consistent across populations, significant differences in body temperature, effectiveness of thermoregulation, and heating times were observed. Melanism, proposed to enhance heating in cold environments, showed limited effects on thermoregulation, accelerating heating times only in specific conditions (males heating from 15°C to 35°C at the colder site). Instead, body mass emerged as the key factor that consistently slowed heating times. Our findings suggest that P. verdugo relies heavily on behavioural strategies for thermoregulation, allowing individuals to cope with immediate thermal variability, but the ability to adapt to future climate change remains uncertain, because these responses might provide short-term benefits but limit long-term physiological adaptation.
Estimating marginal treatment effect in cluster randomized trials with multi-level missing outcomes
Authors: Chang Chia-Rui , Wang Rui
Published: December 2024

Analyses of cluster randomized trials (CRTs) can be complicated by informative missing outcome data. Methods such as inverse probability weighted generalized estimating equations have been proposed to account for informative missingness by weighing the observed individual outcome data in each cluster. These existing methods have focused on settings where missingness occurs at the individual level and each cluster has partially or fully observed individual outcomes. In the presence of missing clusters, for example, all outcomes from a cluster are missing due to drop-out of the cluster, these approaches ignore this cluster-level missingness and can lead to biased inference if the cluster-level missingness is informative. Informative missingness at multiple levels can also occur in CRTs with a multi-level structure where study participants are nested in subclusters such as healthcare providers, and the subclusters are nested in clusters such as clinics. In this paper, we propose new estimators for estimating the marginal treatment effect in CRTs accounting for missing outcome data at multiple levels based on weighted generalized estimating equations. We show that the proposed multi-level multiply robust estimator is consistent and asymptotically normally distributed provided that one of the multiple propensity score models postulated at each clustering level is correctly specified. We evaluate the performance of the proposed method through extensive simulations and illustrate its use with a CRT evaluating a Malaria risk-reduction intervention in rural Madagascar.
Polyploids and geographic divergence blur species delimitation in the Paspalum stellatum complex (Poaceae: Paspaleae)
Authors: Bonasora Marisa G , López Méndez Alicia , Speranza Pablo R , Honfi Ana I , Rua Gabriel H
Published: December 2024

Paspalum stellatum comprises a diploid and several polyploid cytotypes. The widely distributed cytotype 2n = 32 is an amphidiploid, an outcome of hybridization between diploid P. stellatum (2n = 20) and the related species Paspalum schesslii (2n = 12). Several analyses were conducted upon a set of 24 accessions of P. stellatum and representatives of three related species. Multivariate analyses of morphological data discriminated between the two potentially sexual cytotypes, 2n = 20 and 2n = 32, but the putatively apomictic higher polyploids were interspersed between them. Instead, Iner Simple Sequence Repeat (ISSR) markers separate two main groups geographically, west and east from the Brazilian-Bolivian Pantanal. Both groups include diploid (2n = 20) and tetraploid (2n = 32) cytotypes, but higher polyploids belong exclusively to the eastern group. Considering that diploids and polyploids behave as different biological entities, we propose to treat the diploid (2n = 20) cytotype as a different species, for which the name Paspalum cujabense should be rehabilitated. Meanwhile, the name P. stellatum remains for a complex including the tetraploid and all polyploid cytotypes.
First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors
Authors: Schanz Moritz , Seikrit Claudia , Hohenstein Bernd , Zimmermann Aline , Kraft Leonie , Schricker Severin , Berger Susann , Schwab Andrea , Oberacker Tina , Latus Joerg
Published: December 2024

Background

Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.

Methods

A total of 23 patients with IgAN were treated with sparsentan via the Managed Access Programme between December 2023 and August 2024. The patients were stable on maximum tolerated doses of renin–angiotensin system (RAS) and SGLT2 inhibitors, with an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m² and a urine protein/creatinine ratio (UPCR) >0.75 g/g.

Results

In the 23 patients, median (IQR) baseline eGFR (CKD-EPI) was 42 mL/min/1.73 m2 (32–63) and median baseline UPCR was 1.5 g/g (0.9–1.8). After initiation of sparsentan, UPCR significantly decreased (P < 0.0001) to a median of 0.85 g/g (0.42–1.15) in the 2-week follow-up and further declined (P = 0.001) to a median of 0.60 g/g (0.32–0.82) after 14 weeks, equivalent to a relative reduction in proteinuria up to 62% (45–74). A similar significant reduction was observed for the urine albumin/creatinine ratio. No drug-related serious adverse events were reported.

Conclusions

In this real-world setting, sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already receiving SGLT2 inhibitors.
Admission control algorithm for visible light communication random access network under delay and jitter constraints
Authors: Sun Hongliang , Liu Zhihui , Wang Chao , Li Dan
Published: December 2024

This paper proposes a random access network admission control algorithm under delay and jitter constraints to efficiently guarantee the quality of service of a visible light communication system. The multi-packet reception technology is considered to enhance network service, and the interrupted Bernoulli process is used to model the arrival process of packets. The queuing model of the system is constructed from the perspective of a single transmission link, and this paper derives the probability of successful transmission for the terminals. The delay and jitter performance are evaluated according to the state transition matrix and Little’s law. The article set up the optimization problem with the goal of maximizing the throughput and the constraint of transmission probability. To solve the optimization problem better, we improve the tunicate swarm algorithm. Moreover, an admission control algorithm is designed under delay and jitter constraints. Simulation results demonstrate the influence of different parameters on the algorithm.
Internet of vehicles intrusion detection method based on CFS-COA feature selection and spatio-temporal feature extraction
Authors: Yang Zhongjun , Zhang Jixue , Su Beimin
Published: December 2024

With the rapid spread of the Internet of Vehicles (IoV) technology, vehicle network security is facing increasingly severe challenges. Intrusion detection technology has become a crucial tool for ensuring the information security of IoV. Since the traffic data of the IoV is large and has spatio-temporal characteristics, most previous studies are based on a single deep learning method to extract temporal or spatial features, which does not fully extract features of IoV data. To address the above issues, a spatio-temporal feature extraction model with feature selection is proposed. First, to solve the problem of long detection time with huge data traffic, a new feature selection method is proposed to screen the optimal feature subset by combining the correlation-based feature selection method with the crayfish optimization algorithm (CFS-COA). Second, the selected optimal features are used in a spatio-temporal feature extraction model that combines a Temporal Convolutional Network and a Bidirectional Gated Recurrent Unit (TCN-BiGRU) for classification. Finally, the performance of the model is evaluated using two types of datasets: the NSL-KDD and UNSW-NB15 datasets for external communications, and the Car-Hacking dataset for in-vehicle networks. The experimental results indicate that the proposed model demonstrates high classification performance and lightweight characteristics, achieving 100% accuracy on the Car-Hacking dataset.
The meaning of Mr. Tumnus: classical epic and the making of modern fantasy
Authors: Pogorzelski Randall
Published: December 2024

The faun Mr. Tumnus in C. S. Lewis’s The Lion, the Witch and the Wardrobe evokes a layering of pasts that both Lewis and J. R. R. Tolkien identify in their scholarly work as a key characteristic of Virgil’s Aeneid and of classical epic more generally. Tolkien discusses the epic layering of pasts as a shared feature of both Beowulf and the Aeneid, and he describes in letters his adoption of the literary technique of those poems in his fiction. Lewis treats the temporality of the Aeneid as a revolution in epic poetry in his Preface to Paradise Lost, and he less explicitly uses it in his Chronicles of Narnia. Fauns in Latin poetry are not simply Roman versions of Greek satyrs, but they represent a version of the same layering of pasts in epic that Lewis and Tolkien identify. By introducing both Lucy Pevensie and readers to Narnia with a faun, Lewis characterizes Narnia not only as a magical realm but also as an epic one.
Maxillary protraction anchored on miniplates versus miniscrews: three-dimensional dentoskeletal comparison
Authors: Miranda Felicia , Garib Daniela , Silva Ivan , Bastos José Carlos da Cunha , Aliaga-Del Castillo Aron , Yatabe Marilia , de Clerck Hugo , Cevidanes Lucia H S
Published: December 2024

Objective

This retrospective study aimed to compare the three-dimensional (3D) outcomes of the novel miniscrew-anchored maxillary protraction (MAMP) therapy and the bone-anchored maxillary protraction (BAMP) therapy.

Methods

The sample comprised growing patients with skeletal Class III malocclusion treated with two skeletal anchored maxillary protraction protocols. The MAMP group comprised 22 patients (9 female, 13 male; 10.9 ± 0.9 years of age at baseline) treated with Class III elastics anchored on a hybrid hyrax expander in the maxilla and two mandibular miniscrews distally to the permanent canines. The BAMP group comprised 24 patients (14 female, 10 male; 11.6 ± 1.1 years of age at baseline) treated with Class III elastic anchored in two titanium miniplates in the infra-zygomatic crest and two miniplates in the mesial of the mandibular permanent canines. Three-dimensional displacements were measured in the pre- and post-treatment cone-beam computed tomography scans superimposed on the cranial base using the Slicer Automated Dental Tools module of 3D Slicer software (www.slicer.org). Mean differences (MD) between groups and 95% confidence interval (CI) were obtained for all variables. Intergroup comparison was performed using the Analysis of Covariance (P < .05).

Results

Both groups showed improvements after treatment. The MAMP group showed a smaller anterior (MD: −1.09 mm; 95% CI, −2.07 to −0.56) and 3D (MD: −1.27 mm; 95% CI, −2.16 to −0.74) displacements of the maxilla after treatment when compared with BAMP. Both groups showed negligible and similar anteroposterior changes in the mandible (MD: 0.33 mm; 95% CI, −2.15 to 1.34). A greater increase in the nasal cavity width (MD of 2.36; 95% CI, 1.97–3.05) was observed in the MAMP group when compared with BAMP.

Limitations

The absence of an untreated control group to assess the possible growth impact in these findings is a limitation of this study.

Conclusion

Both BAMP and MAMP therapies showed adequate 3D outcomes after treatment. However, BAMP therapy produced a greater maxillary advancement with treatment, while MAMP therapy showed greater transversal increases in the nasal cavity.
How to prevent 3 million deaths worldwide: a systematic review of occupational accident research—a factor- and cost-based approach
Authors: Cañaveras Perea Rosa María , Tejada Ponce Ángel , Sánchez González María Pilar
Published: December 2024

Occupational accidents have emerged as a global concern, necessitating a comprehensive examination of their determinants and associated costs. This review aims to summarize, synthesize, and organize the factors and cost drivers of occupational accidents, exploring whether there is a gender perspective. Adhering to PRISMA guidelines, we performed a narrative synthesis to systematically review relevant literature. A systematic search was conducted in the electronic databases PubMed, Web of Science, and Scopus. Two researchers screened all records to eliminate any duplicates, and they selected the articles for full review. A third researcher was consulted to resolve discrepancies and reach a consensus. The analysis of 15 studies revealed diverse perspectives; in terms of determinants, studies on organizational aspects and the theory of human error were grouped together, while in cost drivers, the human capital model and willingness to pay were the most frequently used. Gender, meanwhile, is identified as a determinant variable for accident rate. Additionally, limitations such as data underestimation were noted in the existing literature. The review highlights the need for empirical studies capable of addressing both determinants and cost drivers. It also provides guidelines for researchers to design studies that are more comparable across different contexts, including the gender debate.
Metataxonomic analysis of halophilic archaea community in two geothermal oases in the southern Tunisian Sahara
Authors: Najjari Afef , Elmnasri Khaled , Cherif Hanene , Burleigh Stephen , Guesmi Amel , Mahjoubi Mouna , Linares-Pastén Javier A , Cherif Ameur , Ouzari Hadda-Imene
Published: December 2024

This study assesses halophilic archaea’s phylogenetic diversity in southern Tunisia’s geothermal water. In the arid southern regions, limited surface freshwater resources make geothermal waters a vital source for oases and greenhouse irrigation. Three samples, including water, sediment, and halite soil crust, were collected downstream of two geothermal springs of the Ksar Ghilane (KGH) and Zaouet Al Aness (ZAN) oases, Tunisia. The samples were subjected to 16S rRNA gene sequencing using the Illumina Miseq sequencing approach. Several haloarchaea were identified in the geothermal springs. The average taxonomic composition revealed that 20 out of 33 genera were shared between the two geothermal sources, with uneven distribution, where the Halogranum genus was the most represented genus with an abundance of 18.9% and 11.58% for ZAW and KGH, respectively. Several unique site-specific genera were observed: Halonotius, Halopelagius, Natronorubrum, and Haloarcula in ZAN, and Haloprofundus, Halomarina, Halovivax, Haloplanus, Natrinema, Halobium, Natronoarchaeum, and Haloterrigena in the KGH pool. Most genus members are typically found in low-salinity ecosystems. These findings suggest that haloarchaea can disperse downstream from geothermal sources and may survive temperature and chemical fluctuations in the runoff.
Intrafamilial relations between clergy and laity: the case of the Nemours family at the turn of the twelfth and thirteenth centuries
Authors: Casano-Skaghammar Sarah
Published: December 2024

Medieval theorists spilt much ink identifying the divisions within society, pitting the powers of the Church against those of the laity. However, by turning to documentary sources, historians have revealed a much more complex reality. This article contributes to this wider picture by bringing to light the intrafamilial relations between the clergy and laity of the house of Nemours around the turn of the twelfth and thirteenth centuries. This family provided numerous servants both to the Capetians and to the Church. These individuals managed to maintain harmonious relations with their relatives, notwithstanding the challenges and constraints of their respective roles.
A chromosome-level genome assembly of the Peruvian Algarrobo (Neltuma pallida) provides insights on its adaptation to its unique ecological niche
Authors: La Torre Renato , Hamilton John P , Saucedo-Bazalar Manuel , Caycho Esteban , Vaillancourt Brieanne , Wood Joshua C , Ramírez Manuel , Buell C Robin , Orjeda Gisella
Published: December 2024

The dry forests of northern Peru are dominated by the legumous tree Neltuma pallida which is adapted to hot arid and semiarid conditions in the tropics. Despite having been successfully introduced in multiple other areas around the world, N. pallida is currently threatened in its native area, where it is invaluable for the dry forest ecosystem and human subsistence. A major tool for enhancing ecosystem conservation and understanding the adaptive properties of N. pallida to dry forest ecosystems is the construction of a reference genome sequence. Here, we report on a high-quality reference genome for N. pallida. The final genome assembly size is 403.7 Mb, consisting of 14 pseudochromosomes and 63 scaffolds with an N50 size of 26.2 Mb and a 34.3% GC content. Use of Benchmarking Universal Single Copy Orthologs revealed 99.2% complete orthologs. Long terminal repeat elements dominated the repetitive sequence content which was 51.2%. Genes were annotated using N. pallida transcripts, plant protein sequences, and ab initio predictions resulting in 22,409 protein-coding genes encoding 24,607 gene models. Comparative genomic analysis showed evidence of rapidly evolving gene families related to disease resistance, transcription factors, and signaling pathways. The chromosome-scale N. pallida reference genome will be a useful resource for understanding plant evolution in extreme and highly variable environments.
GOplan: an R package for animal breeding program design via integrating Gene Flow and Bayesian optimization methods
Authors: Huang Qianqian , Zhou Lei , Xue Yahui , Du Heng , Zhuo Yue , Mao Ruihan , Liu Yaoxin , Yan Tiantian , Li Wanying , Wang Xiaofeng , Liu Jianfeng
Published: December 2024

The design of breeding programs is crucial for maximizing economic gains. Simulation provides the most efficient measures to test these programs, as real-world trials are often costly and time-consuming. We developed GOplan, a comprehensive and user-friendly R package designed to develop animal breeding programs considering pure-bred populations and crossbreeding systems. Compared with other traditional simulators, it has mainstream crossbreeding frameworks that streamline modeling and use Gene Flow and Bayesian optimization methods to enhance breeding program efficiency. GOplan includes 3 key functions: runCore() to evaluate the effects of nucleus breeding programs, runWhole() to predict economic outcomes and the production performance of crossbreeding systems, and runOpt() to optimize crossbreeding structures for greater profitability. These functions support breeders in better planning and accelerating breeding goals. Additionally, the application of Bayesian optimization algorithms in this study provides valuable insights for developing new optimization algorithms in the future. The software is available at https://github.com/CAU-TeamLiuJF/GOplan.
Selfing Shapes Fixation of a Mutant Allele Under Flux Equilibrium
Authors: Xiao Yu , Lv Yan-Wen , Wang Zi-Yun , Wu Chao , He Zi-Han , Hu Xin-Sheng
Published: December 2024

Sexual reproduction with alternative generations in a life cycle is an important feature in eukaryotic evolution. Partial selfing can regulate the efficacy of purging deleterious alleles in the gametophyte phase and the masking effect in heterozygotes in the sporophyte phase. Here, we develop a new theory to analyze how selfing shapes fixation of a mutant allele that is expressed in the gametophyte or the sporophyte phase only or in two phases. In an infinitely large population, we analyze a critical selfing rate beyond which the mutant allele tends to be fixed under equilibrium between irreversible mutation and selection effects. The critical selfing rate varies with genes expressed in alternative phases. In a finite population with partial self-fertilization, we apply Wright's method to calculate the fixation probability of the mutant allele under flux equilibrium among irreversible mutation, selection, and drift effects and compare it with the fixation probability derived from diffusion model under equilibrium between selection and drift effects. Selfing facilitates fixation of the deleterious allele expressed in the gametophyte phase only but impedes fixation of the deleterious allele expressed in the sporophyte phase only. Selfing facilitates or impedes fixation of the deleterious allele expressed in two phases, depending upon how phase variation in selection occurs in a life cycle. The overall results help to understand the adaptive strategy that sexual reproductive plant species evolve through the joint effects of partial selfing and alternative generations in a life cycle.
Home Ambient Temperature and Self-reported Attention in Community-Dwelling Older Adults
Authors: Baniassadi Amir , Yu Wanting , Travison Thomas , Day Ryan , Lipsitz Lewis , Manor Brad
Published: December 2024

Background

Climate change is expected to disrupt weather patterns across the world, exposing older adults to more intense and frequent periods of hot weather. Meanwhile, lab-based studies have established a causal relationship between ambient temperature and cognitive abilities, suggesting the expected rise in temperature may influence older adults’ cognitive functioning. Nevertheless, it is not clear whether, and to what extent, the temperature variations in older adults’ own homes - which unlike lab settings is under their control - influence their cognitive functioning. Our objective was to provide proof-of-concept that home ambient temperature influences self-reported ability to maintain attention in older adults.

Methods

We conducted a longitudinal observational study; continuously monitoring the home ambient temperature and self-reported difficulty keeping attention for 12 months in a cohort of community-dwelling older adults living in Boston, MA.

Participants

47 adults aged 65 and older.

Results

We observed a U-shaped relationship between home ambient temperature at the time of assessment and the odds ratio (OR) of reporting difficulty keeping attention such that the OR was lowest between 20 – 24 ˚C and doubled when moving away from this range by 4 ˚C in either direction.

Discussion

Our results suggest that even under the current climate a considerable portion of older adults encounter indoor temperatures detrimental to their cognitive abilities. Climate change may exacerbate this problem, particularly among low-income and underserved older adults. Addressing this issue in public health and housing policy is essential to building climate-resiliency in this vulnerable population.
The Relationship Between Subjective Cognitive Decline and Cognitive Leisure Activity Engagement: A Systematic Review
Authors: Akbayrak Emine , Powell Philip A , Tunc Neslihan , Barnes Sarah
Published: December 2024

Background and Objectives

Subjective cognitive decline (SCD) is a common experience of self-perceived decline without objective cognitive impairment. It has been theorized that SCD is associated with participation in cognitive leisure activities (CLAs), but the evidence base is multifarious and unclear. The purpose of this systematic review was to synthesize current evidence to determine the association between SCD and CLA engagement.

Research Design and Methods

Systematic searches were conducted in EMBASE, MEDLINE, PsycINFO, and Web of Science (last searched April 2023). Data were extracted against a priori inclusion criteria and synthesized narratively using Synthesis without Meta-Analysis guidelines. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) and Mixed Methods Appraisal Tool (MMAT). Reporting follows PRISMA guidelines.

Results

From 4,447 records, 11 articles were included. Due to study heterogeneity, evidence on SCD and CLA association is inconclusive. Although a modest correlation was found between greater engagement in CLA and fewer reports of SCD, the heterogeneity in study designs and outcomes, particularly in those addressing only perceived memory decline and CLA engagement, challenges definitive conclusions on this relationship. Evidence from mixed-method and qualitative studies indicated that perceived memory decline may cause negative feelings, such as shame and frustration, which may influence participating in CLA.

Discussion and Implications

These findings suggest that participation in CLA is moderately associated with, and may act protectively against, SCD. However, establishing a directional or causal relationship between CLA participation and SCD outcomes requires further investigation through longitudinal and/or interventional studies.
Advances in the Study of Senescence Mechanisms in the Genus Paeonia
Authors: Wang Yuxuan , Sun Miao , Zhu Wei , Chen Le , Zhu Shaocai , Zhao Jiageng , Teixeira da Silva Jaime A , Yu Xiaonan
Published: December 2024

Tree and herbaceous peony are considerably important ornamental plants within the genus Paeonia, and hold substantial horticultural value. This review summarizes the progress in research on the senescence mechanisms of tree and herbaceous peony flowers, focusing on the regulation of gene expression, hormonal interactions, and the influence of environmental factors on senescence. Using high-throughput sequencing technologies, key genes displaying differential expression during senescence have been identified, and these play central roles in hormone signaling and cellular senescence. The interactions among plant hormones, including ethylene, abscisic acid, gibberellins, cytokinins, and auxins, also play key roles in the regulation of senescence. Adjustments in antioxidant levels, as well as water and energy metabolism, are critical factors in the delay of senescence. Environmental factors, including light, temperature, drought, and salt stress, also significantly affect senescence. Additionally, this review proposes future research directions, including the expansion of the molecular regulatory network of senescence in Paeonia, the use of gene editing technologies like CRISPR/Cas9, multi-omics studies, and exploratory comparative research on spatial biology senescence mechanisms. These studies aim to deepen our understanding of the molecular mechanisms that underlie senescence in Paeonia, and provide a scientific basis for cultivar improvement and postharvest management of these ornamental commodities in the horticultural industry.
Is the Obligation Not to Refoule a Positive Obligation? An Intermediate Approach Toward the Classification Dilemma
Authors: Katsoni Spyridoula
Published: December 2024

Although the distinction of international obligations as positive or negative ones is well-established in international law, the classification of the obligation not to refoule has given rise to a disagreement in relevant academic writings. The present article contributes to this academic discussion by arguing for an intermediate position, whereby the obligation not to refoule is perceived as a mixed obligation, which is comprised of both negative and positive obligations. Doing so, the article outlines the series of positive and negative obligations that have been identified as stemming from non-refoulement and further evinces that the intermediate approach toward the obligation’s classification better corresponds to the recent scholarly and jurisprudential developments, embraces non-refoulement’s peremptory character, allows a consistent classification of the obligation in all fields of international law and enhances the overall protection that may be afforded to protection-seekers under non-refoulement by ‘hardening’ the obligations that are interpreted as stemming therefrom.
Anti-integrin αvβ6 Antibodies Predict Pouchitis in Patients With Ulcerative Colitis After Restorative Proctocolectomy With Ileal Pouch-Anal Anastomosis
Authors: Nakanishi Risa , Kuwada Takeshi , Shiokawa Masahiro , Nishikawa Yoshihiro , Ota Sakiko , Yamazaki Hajime , Yanaidani Takafumi , Sawada Kenji , Hirata Ayako , Yasuda Muneji , Takimoto Ikuhisa , Chikugo Koki , Yokode Masataka , Muramoto Yuya , Matsumoto Shimpei , Matsumori Tomoaki , Uza Norimitsu , Chiba Tsutomu , Seno Hiroshi
Published: December 2024

Background

Pouchitis is the most common complication of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We previously reported the presence of anti-integrin αvβ6 antibodies in the serum of patients with UC. This study investigated the association between anti-integrin αvβ6 antibodies and the development of pouchitis in patients with UC.

Methods

Serum levels of anti-integrin αvβ6 antibodies were measured by enzyme-linked immunosorbent assay in 16 patients with UC who underwent RPC with IPAA. Integrin αvβ6 expression in the colonic, terminal ileal, and pouch epithelium was examined using immunohistochemistry and western blot analysis.

Results

Anti-integrin αvβ6 antibody levels in patients with UC were significantly decreased at 3, 9, and 12 months after RPC (P < .05). However, in patients who developed pouchitis, antibody levels remained high. The antibody levels at the time of RPC were significantly higher in patients who developed pouchitis compared to those who did not. Kaplan-Meier analysis revealed a significantly higher incidence of pouchitis in patients with antibody levels above the cutoff at the time of RPC. Although integrin αvβ6 was not expressed in the terminal ileal epithelium at the time of RPC, expression became positive in the pouch epithelium of patients with pouchitis.

Conclusions

The anti-integrin αvβ6 antibody levels in patients with UC were decreased after RPC but remained high in patients who developed pouchitis. The antibody levels at the time of RPC may serve as a potential prognostic biomarker for predicting the risk of pouchitis in patients with UC.
Mediators of Filgotinib Treatment Effects in Ulcerative Colitis: Exploring Circulating Biomarkers in the Phase 2b/3 SELECTION Study
Authors: Nakase Hiroshi , Danese Silvio , Reinisch Walter , Ritter Timothy , Liang Yan , Wendt Emily , Levesque Barrett G , Yoon Oh Kyu , Tian Yuan , Zhuo Luting , Karouzakis Emmanuel , Bauer Yasmina , Oortwijn Alessandra , Kaise Toshihiko , Malkov Vladislav A , Hibi Toshifumi
Published: December 2024

Background

We utilized patient samples from the large, phase 2b/3 SELECTION trial to identify circulating biomarkers of ulcerative colitis (UC) and potential early mediators of filgotinib treatment effects.

Methods

Samples were collected at baseline and during the induction phase of the SELECTION trial. Evaluated biomarkers comprised serum and stool proteins (measured by enzyme-linked immunosorbent assay), whole-blood cell counts, and whole-blood RNA-seq-derived gene-expression factors identified via exploratory factor analysis. Biomarker levels were assessed by baseline disease severity (endoscopy/bleeding/stool and Mayo Clinic Score) and biologic status (naive vs experienced). Effects of filgotinib on biomarker levels, including week 4 biomarker changes that may mediate week 10 clinical improvements, were assessed.

Results

The biomarker analysis set included 598 biologic-naive patients and 592 biologic-experienced patients. Systemic inflammatory biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6], serum amyloid A [SAA], and platelet cell counts) had the strongest positive correlations with baseline UC disease severity. CRP, IL-6, SAA, and neutrophil activation biomarkers (including neutrophil gelatinase-associated lipocalin [NGAL], tumor necrosis factor ɑ, and oncostatin M [OSM]), as well as platelet, neutrophil, and monocyte cell counts were increased in biologic-experienced versus biologic-naive patients. Gene-expression-derived plasmablast and cell proliferation factors were positively correlated with disease severity; B cell, T-cell activation, and plasmacytoid dendritic cell factors were negatively correlated. Filgotinib reduced nearly all proinflammatory biomarkers correlated with baseline UC disease activity; reduced SAA, CRP, IL-6, NGAL, and OSM at week 4 were identified as mediators of improved week 10 clinical scores.

Conclusions

Filgotinib significantly impacted circulating biomarkers related to UC pathology. Several proinflammatory and neutrophil activation biomarkers may be early mediators of filgotinib treatment effects.

ClinicalTrials.gov identifier

NCT02914522
Providing solutions to mitigate, adapt, and build resilience to the effects of climate change
Authors: Robinson Carol , Sabine Christopher , Isensee Kirsten
Published: December 2024

This Quo Vadimus article is a summary of the Ocean Vision 2030 White Paper—Challenge 5: Unlock Ocean-based solutions to Climate Change (2024). We highlight the obstacles to harnessing the potential of ocean-based solutions to mitigate and adapt to the impacts of climate change. Recommendations to overcome these obstacles include (i) research into marine renewable energy, ways of reducing marine pollution and of expanding vegetated coastal ecosystems, (ii) controlled field testing of marine carbon dioxide removal co-designed with invested communities, (iii) improved co-designed governance and cooperation as well as capacity development, (iv) adaptive governance and management supported by decision support tools for the assessment of vulnerability and risk, and (v) prioritization of fairness and inclusivity in the execution of mitigation and adaptation measures to ensure all stakeholders benefit equitably.
Viral niche-partitioning: comparative genomics of giant viruses across environmental gradients in a high Arctic freshwater-saltwater lake
Authors: Pitot Thomas M , Girard Catherine , Rapp Josephine Z , Somerville Vincent , Culley Alexander I , Vincent Warwick F , Moineau Sylvain , Roux Simon
Published: December 2024

Giant viruses (GVs; Nucleocytoviricota) impact the biology and ecology of a wide range of eukaryotic hosts, with implications for global biogeochemical cycles. Here, we investigated GV niche separation in highly stratified Lake A at the northern coast of Ellesmere Island, Nunavut, Canada. This lake is composed of a layer of ice-covered freshwater that overlies saltwater derived from the ancient Arctic Ocean, and it therefore provides a broad gradient of environmental conditions and ecological habitats, each with a distinct protist community and rich assemblages of associated GVs. The upper layer (mixolimnion) had measurable light and oxygen, and contained diverse GVs linked to photosynthetic protists, indicating adaptation to surface biotic and abiotic conditions. In contrast, the saline lower layer (monimolimnion), lacking oxygen and light, hosted GVs associated with predicted heterotrophic protists, some of which are known for a predatory lifestyle, and with several viral genes suggesting adaptation to deep-water anaerobic conditions. Our observations underscore the coupling between physical and chemical gradients, microeukaryotes and their associated GVs in Lake A, and provide insight into the potential for GVs to directly and indirectly impact host metabolism. There were similarities between the genetic composition of GVs and the metabolic processes of their potential hosts, implying co-evolution and niche-adaptation within the lake habitats. Notably, we found a greater presence of viral rhodopsins in deeper water layers, suggesting an evolutionary relationship with potential hosts capable of supplementing their energetic needs to thrive in low energy, anoxic conditions.
IMF Lending Programs and Repression in Autocracies
Authors: Nelson Stephen C , Dinkel Christopher P
Published: December 2024

Do International Monetary Fund (IMF) lending programs increase repression in borrowing countries? We argue that repression worsens when autocratic governments enter conditional lending arrangements with the IMF. Autocracies are likelier than democracies to harshly crackdown during episodes of heightened protest and unrest triggered by IMF-mandated adjustment and structural reform programs. But harsh repression of anticipated spikes in dissent spurred by liberalization-oriented IMF conditions may also be used by autocrats to proactively signal their commitment to preserve regime insiders’ advantages. We present several tests of the arguments in the article. In the first test, we use a compound instrumental variable to estimate the conditional difference in human rights scores between IMF program participation and non-participation in both democratic and autocratic country-years (1975–2014). We do not find evidence for clear links between IMF program participation and human rights in developing democracies. In autocracies, however, the relationship between IMF lending programs and human rights respect is consistently negative and significant. In further tests, we isolate the impact of different types of IMF conditionality. Evidence suggests that IMF programs with more numerous structural reforms (namely, pro-privatization conditions) are associated with lower human rights protections in autocratic countries.
Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis
Authors: Hunter Cameron J , Marhoffer Elizabeth A , Holleck Jürgen L , Ein Alshaeba Samer , Grimshaw Alyssa A , Chou Andrew , Carey George B , Gunderson Craig G
Published: December 2024

Background

Empiric antibiotics active against Pseudomonas aeruginosa are recommended by professional societies for certain infections and are commonly prescribed for hospitalized patients. The effect of this practice on mortality is uncertain.

Methods

A systematic literature search was conducted using Embase, Medline, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from earliest entry through 9 October 2023. We included studies of patients hospitalized with P. aeruginosa infections that compared mortality rates depending on whether patients received active empiric antibiotics.

Results

We found 27 studies of 12 522 patients that reported adjusted OR of active empiric antibiotics on mortality. The pooled adjusted OR was 0.40 (95% CI, 0.32–0.50), favouring active empiric antibiotics. In practice, the mortality effect of empiric antibiotics against P. aeruginosa depends on the prevalence of P. aeruginosa and baseline mortality. The estimated absolute mortality benefit was 0.02% (95% CI, 0.02–0.02) for soft tissue infections, 0.12% (95% CI, 0.10–0.13) for urinary tract infections and community-acquired pneumonia, 0.3% (0.25–0.34) for sepsis without shock, 1.1% (95% CI, 0.9–1.4) for septic shock and 2.4% (95% CI, 1.9–2.8) for nosocomial pneumonia.

Conclusions

The mortality effect for empiric antibiotics against P. aeruginosa depends crucially on the prevalence of P. aeruginosa and baseline mortality by type of infection. For soft tissue infections, urinary tract infections and community-acquired pneumonia, the mortality benefit is low. Meaningful benefit of empiric antibiotics against P. aeruginosa is limited to patients with approximately 30% mortality and 5% prevalence of P. aeruginosa, which is largely limited to patients in intensive care settings.
Resilience of tigecycline heteroresistance phenotype in Acinetobacter baumannii
Authors: Jo Jeongwoo , Kim Sun Ju , Kwon Ki Tae , Ko Kwan Soo
Published: December 2024

Background

Heteroresistance, frequently observed in diverse bacterial species, imposes clinical challenges. For this study, we investigated the stability and resilience of tigecycline heteroresistance in Acinetobacter baumannii.

Methods

Four tigecycline-heteroresistant (HR) A. baumannii strains and resistant populations (RPs) obtained from them were subjected to laboratory evolution assays for 30 days in antibiotic-free media. The heteroresistance phenotype was determined using a population analysis. Bacterial growth curves and in vitro competitiveness were determined to investigate the fitness cost of heteroresistance. Tigecycline efficacy was evaluated using an in vitro time–killing assay. Genetic mutations were identified using whole genome sequencing, and expression of genes in the two-component systems was also evaluated.

Results

Tigecycline heteroresistance was preserved even in antibiotic-free media, and tigecycline-RPs reverted to heteroresistance during serial culture without tigecycline pressure. The tigecycline-RPs showed a higher fitness cost than their respective HR strains, and the HR strains exhibited a survival advantage upon tigecycline treatment. Although the AdeABC efflux pump was overexpressed in the tigecycline-RPs, it was down-regulated in the HR strains.

Conclusions

Our data indicate that tigecycline heteroresistance is a highly resilient phenotype in A. baumannii that gives a high fitness advantage to bacteria in terms of competitiveness and response to antibiotic pressure.
Politics, Techno-Science, and the Environment: The Late Twentieth-Century Challenges of Locust Control in Post-Colonial Southern Africa
Authors: Mseba Admire
Published: December 2024

This article tells the history of the management of invasive locust swarms in southern Africa in the 1970s and early 1980s. It examines the threats the pests posed to African livelihoods and the challenges in combating them. The article argues that in the 1970s, postcolonial southern African states’ attempts to manage the environment with the help of international organizations were intimately tied to the region’s experiences under colonial rule, their commitment to ensure the whole region’s independence, and the new realities of their dependence on international donor support. This support entrenched a reliance on techno-chemical interventions at a time when the global environmental movement against pesticides was particularly strong. Southern Africa’s international collaborators ultimately ignored this global movement, and locust control in the region continued to depend on the application of organochlorines. However, faith in techno-science failed to address the social, political, and ecological conditions that allowed locusts to flourish. Consequently, the pests remained a threat.
Furry, Feral, Foe: Temporalizing Heath and Invasion on an English Chalk Stream
Authors: Pearson Maddy
Published: December 2024

This article explores framings of life, death, health, and invasion on an English chalk stream. It focuses on the ways in which these notions have been put to work in recent history, in relation to each other, and in relation to particular species and spaces. By 2019, narratives of a chalk stream in South-East England as a dead river expanded beyond retort to intermittent waterlessness. The river’s death came to be framed as part of a wider ecology of chalk stream (ill)health, influenced by twenty-first century biodiversity conservation narratives and hauntological effects, which rendered deathly chalk stream futures present and requiring of human-action now. These narratives and effects conditioned a powerful sense of which non-human life belonged and counted, and which non-human life did not. Absent flagship chalk stream species, water voles, and efforts to resurrect them, were made synonymous with restoring the river itself to life and health. Contrarily, the ongoing presence of “invasive” American mink served as a continued reminder of the river’s demise and death as a chalk stream. The resurrection of chalk streams to health relied on their being dispatched. Once considered to belong as extracted “lively capital” dominating the fur industry and later tolerated as feral escapees in the wild of the UK, American mink had been resituated and their history progressively obscured. Humans became manager-come-saviors of chalk streams, whose lost health was agreed and rendered visible through the ghostly image of the water vole that must be saved from the invasive foe, American mink.
Challenging Practices of Victim-Centeredness in Consultations on Transitional Justice: Creating Space for the Voices of the Disappeared in Sri Lanka
Authors: Raheem Mirak
Published: December 2024

This article explores what it means to be victim-centered in a transitional justice (TJ) consultation process through the case study of the state-commissioned process in Sri Lanka in 2016. The author who was a member of the Consultation Task Force on Reconciliation Mechanisms (CTF) uses an insider perspective and the CTF reports to examine victim-centeredness. While noting the limited available literature on the specific issue of consultations in TJ processes, the article draws on work focused on victim participation in TJ and, more broadly, public participation in governance and development. This article attempts to unpick the concept of victim-centeredness through focusing on three key aspects, namely: representation, the listening to and integration of victims’ voices, and the role of experts. It highlights the need to examine the internal operations of TJ structures so as to better understand the factors that contribute to creating spaces for meaningful victim participation.