bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between pre-diagnostic plasma metabolites and biliary tract cancer risk in the prospective UK Biobank cohort
Authors: Gunchick Valerie , Jia Guochong , Wen Wanqing , Long Jirong , Shu Xiao-Ou , Zheng Wei
Published: October 2024

Biliary tract cancer (BTC) is potentially influenced by metabolic dysregulation yet previous metabolomic evaluations are limited. To address this gap, we prospectively investigated associations of blood metabolites and BTC risk in the UK biobank cohort study. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between 249 plasma metabolites per standard deviation and BTC risk in 232,781 participants. We implemented exploratory factor analyses and evaluated associations between factors and BTC risk. Associations at p-value<0.001 were considered statistically significant after multiple comparison adjustments. In a median follow-up of 11.8 years, we identified 268 first primary incident BTC cases. Of 49 biomarkers significantly associated with BTC risk, 12% were fatty acids, and 49%, 31%, and 8% were cholesterol, triglyceride, and phospholipid to total lipids ratios, respectively. Multiple cholesterol ratios were inversely associated with BTC with HRs (95% CIs) of 0.74 (0.65-0.84), p<6.0x10-6. Conversely, a triglyceride ratio was positively associated with BTC with an HR (95% CI) of 1.40 (1.22-1.61), p=2.5x10-6. Congruently, a factor high in cholesterol measures and low in triglyceride measures was inversely associated with BTC. Multiple metabolite biomarkers were associated with BTC risk, suggesting metabolism has a substantial role in BTC etiology.
Assessing the utilization of Current Procedural Terminology codes in pharmacists’ services using MarketScan data
Authors: Rawal Smita , Xu Jianing , Chen Xianyan , Hall Daniel B , Ricabal Lazara Cabrera , Young Henry N , Caballero Joshua
Published: October 2024

Purpose

The Medicare Prescription Drug, Improvement, and Modernization Act and Centers for Medicare and Medicaid Services affirmation enabled pharmacists to use Current Procedural Terminology (CPT) codes for documentation and billing of clinical services. Despite legislative support and potential availability of pharmacists’ clinical services, a gap may exist between the reported availability and actual prevalence of these services in real-world settings. The objective was to assess the prevalence of selected CPT codes (99605-99607, 98966-989968, and 99211-99215) in documenting and billing potential pharmacists’ clinical services using recent available data.

Methods

This retrospective study utilized the Merative MarketScan Medicare database from the period January 1, 2016, to December 31, 2020. The dataset included deidentified patient information and CPT codes. Patients with CPT codes for face-to-face medication therapy management (MTM) services (99605-99607), codes for telephonic assessment and management (A/M) services (98966-98968), and/or codes for evaluation and management (E/M) services (99211-99215) were identified from outpatient claims. Descriptive statistics, including prevalence rates, were calculated. This study was approved by an institutional review board and followed STROBE guidelines.

Results

There were claims data for 2,784,629 enrollees from 2016 through 2020. Prevalence rates varied during this period, with lower rates for MTM face-to-face CPT codes (0.06%) and telephonic A/M codes (0.58%), while E/M CPT codes showed higher prevalence rates (87%).

Conclusion

Study findings exhibited a limited adoption rate for MTM CPT codes for billing pharmacists’ clinical services. Future research may focus on assessing pharmacists’ perceptions and identifying facilitators and barriers to using CPT codes in billing clinical services.
scMGATGRN: a multiview graph attention network–based method for inferring gene regulatory networks from single-cell transcriptomic data
Authors: Yuan Lin , Zhao Ling , Jiang Yufeng , Shen Zhen , Zhang Qinhu , Zhang Ming , Zheng Chun-Hou , Huang De-Shuang
Published: October 2024

The gene regulatory network (GRN) plays a vital role in understanding the structure and dynamics of cellular systems, revealing complex regulatory relationships, and exploring disease mechanisms. Recently, deep learning (DL)–based methods have been proposed to infer GRNs from single-cell transcriptomic data and achieved impressive performance. However, these methods do not fully utilize graph topological information and high-order neighbor information from multiple receptive fields. To overcome those limitations, we propose a novel model based on multiview graph attention network, namely, scMGATGRN, to infer GRNs. scMGATGRN mainly consists of GAT, multiview, and view-level attention mechanism. GAT can extract essential features of the gene regulatory network. The multiview model can simultaneously utilize local feature information and high-order neighbor feature information of nodes in the gene regulatory network. The view-level attention mechanism dynamically adjusts the relative importance of node embedding representations and efficiently aggregates node embedding representations from two views. To verify the effectiveness of scMGATGRN, we compared its performance with 10 methods (five shallow learning algorithms and five state-of-the-art DL-based methods) on seven benchmark single-cell RNA sequencing (scRNA-seq) datasets from five cell lines (two in human and three in mouse) with four different kinds of ground-truth networks. The experimental results not only show that scMGATGRN outperforms competing methods but also demonstrate the potential of this model in inferring GRNs. The code and data of scMGATGRN are made freely available on GitHub (https://github.com/nathanyl/scMGATGRN).
Cyphellophora ludoviensis: a new causative species of tinea nigra
Authors: Son Chang Hyun , Jeong Sun Mun , Jung Jang Hwan , Kwon Do Ik , Seong Seol Hwa , Suh Kee Suck , Jang Min Soo
Published: October 2024

A case of tinea nigra caused by Cyphellophora ludoviensis.
Post-uterine artery embolization: 3-day MRI changes and their predictive value for therapeutic efficacy in symptomatic uterine fibroids
Authors: Chen Xuan-Yi , Zhang Ming-Zhao , Wang Jun-Kang , Li Bo , Qin Rong-Qing , Zhang Yu-Bo , Wan Chen-Yu , Hu Ruo-Chen , Zhu Jia-Yang , Zhou Bing
Published: October 2024

Objectives

To summarize and discuss 3-day MRI changes after uterine artery embolization (UAE) and their predictive value for efficacy.

Methods

From August 2016 to April 2023, 52 patients underwent enhanced MRI within 3 days post-embolization. We retrospectively analysed clinical and imaging data, focusing on MR characteristics at the 3-day mark, comparing pre- and post-embolization images. Patients were categorized based on 3-day MR findings into complete and incomplete necrosis groups, with clinical efficacy compared over 6 months.

Results

Our study included 30 cases of multiple leiomyomas and 22 of single leiomyomas. Postoperative MRI revealed complete necrosis in 31 tumours and incomplete necrosis in 21 tumours. At 3 days, MR ADC imaging showed increased signals in necrotic areas, mildly increased signals on T2-weighted images, and minimal changes on T1-weighted images. Six-month follow-up showed no significant difference in symptom improvement between groups (P = .524, P = .587, P = .615). However, a significant difference was found in leiomyoma volume reduction, with 70.63 ± 15.53% in the complete necrosis group and 51.36 ± 25.20% in the incomplete necrosis group (P < .001), highlighting the impact of necrosis extent on volumetric reduction.

Conclusion

Short-term MRI changes after UAE can reflect changes in blood supply to fibroids and normal uterine tissue, and have good predictive value for medium-term embolization efficacy.

Advances in knowledge

This study describes short-term MR manifestations of complete and incomplete embolism, aiding in predicting long-term outcome.
Genodermatoses
Authors: Agrawal Akriti , Beniwal Ranjana
Published: October 2024

A 20-year-old man presented with mildly pruritic, symmetrically distributed, erythematous, scaly plaques over the extensors, including elbows, knees and acral areas, with keratoderma of the palms; he had experienced this since childhood.
Disentangling gray matter atrophy and its neurotransmitter architecture in drug-naïve Parkinson’s disease: an atlas-based correlation analysis
Authors: Pang Huize , Li Xiaolu , Yu Ziyang , Yu Hongmei , Bu Shuting , Wang Juzhou , Zhao Mengwan , Liu Yu , Jiang Yueluan , Fan Guoguang
Published: October 2024

Parkinson’s disease is characterized by multiple neurotransmitter systems beyond the traditional dopaminergic pathway, yet their influence on volumetric alterations is not well comprehended. We included 72 de novo, drug-naïve Parkinson’s disease patients and 61 healthy controls. Voxel-wise gray matter volume was evaluated between Parkinson’s disease and healthy controls, as well as among Parkinson’s disease subgroups categorized by clinical manifestations. The Juspace toolbox was utilized to explore the spatial relationship between gray matter atrophy and neurotransmitter distribution. Parkinson’s disease patients exhibited widespread GM atrophy in the cerebral and cerebellar regions, with spatial correlations with various neurotransmitter receptors (FDR-P < 0.05). Cognitively impaired Parkinson’s disease patients showed gray matter atrophy in the left middle temporal atrophy, which is associated with serotoninergic, dopaminergic, cholinergic, and glutamatergic receptors (FDR-P < 0.05). Postural and gait disorder patients showed atrophy in the right precuneus, which is correlated with serotoninergic, dopaminergic, gamma-aminobutyric acid, and opioid receptors (FDR-P < 0.05). Patients with anxiety showed atrophy in the right superior orbital frontal region; those with depression showed atrophy in the left lingual and right inferior occipital regions. Both conditions were linked to serotoninergic and dopaminergic receptors (FDR-P < 0.05). Parkinson’s disease patients exhibited regional gray matter atrophy with a significant distribution of specific neurotransmitters, which might provide insights into the underlying pathophysiology of clinical manifestations and develop targeted intervention strategies.
Establishment of characteristic fingerprint of volatile components in Batocera horsfieldi (Coleoptera: Cerambycidae) host plants and correlation analysis with climatic factors
Authors: Wei Xinju , Xu Danping , Liu Zhiqian , Wu Junhao , Zhuo Zhihang
Published: October 2024

Batocera horsfieldi is the primary stemboring pest of timber forests and economic forests in China, belonging to the Coleoptera Cerambycidae. In this study, gas chromatography-mass spectrometry was used to analyze the volatile components in the supplementary feeding hosts and oviposition hosts of B. horsfieldi, and characteristic fingerprints were constructed. A total of 168 compounds were detected, primarily consisting of terpenes, hydrocarbons, and aldehydes, with 75, 23, and 14 compounds, respectively. Hierarchical cluster analysis and principal component analysis yielded consistent results. The similarity evaluation results showed that the similarity range between healthy poplar tree bark and healthy poplar leaves was the highest, reaching 0.953–0.98, and 10 common peaks were identified. The analysis of the correlation with climatic factors shows that most compounds are positively correlated with mean annual humidity, mean annual temperature, mean annual minimum temperature, and mean annual maximum temperature. Only caryophyllene and alpha-guaiene are negatively correlated with temperature-related climatic factors. Pathway analysis also reveals differences in the direct effects of different compounds. These analytical results provide a theoretical basis for further studying the selection mechanism of B. horsfieldi on hosts and offer theoretical guidance for identifying plant-derived attractants with biological activity.
Effects of temperature on the development of Rachiplusia nu (Lepidoptera: Noctuidae) and Chrysodeixis includens (Lepidoptera: Noctuidae) and implications on population growth in Brazil
Authors: Pasqualotto Larissa , Alves Juarez da Silva , Pedó Helene , de Souza Trombim Michele , de Souza Trombim Mireli , Soares Vanessa Nogueira , Horikoshi Renato Jun , Miraldo Leonardo , Ovejero Ramiro , Berger Geraldo , Bernardi Daniel
Published: October 2024

Temperature is an elementary component in mathematical models for predicting the biotic potential of insects. In this study, the objective was to evaluate the impact of different constant temperatures of 8, 10, 15, 20, 25, 30, and 32°C on the biological parameters, lower temperature thresholds (TT), and estimating the number of annual generations (NAG) of Rachiplusia nu and Chrysodeixis includens, both pests associated with the soybean crop in Brazil. There was no development of the immature stages of R. nu at 8°C, as was also found for C. includens at 8 and 10°C. However, at 10°C all stages of R. nu developed. In general, temperatures of 20 and 25°C were the most suitable for the development of R. nu and C. includens, providing egg to adult viability of over 60% and the highest total fecundities. However, the temperature of 32°C negatively affected the parameters of the fertility life table. Rachiplusia nu showed the lowest TT (eggs: 4.9°C; larvae: 10.8°C; pupa: 14.1°C; and egg to adult: 8.9°C) when compared with C. includens (eggs: 7.5°C; larvae: 15.3°C; pupa: 16.1°C; and egg to adult: 11.3°C). Based on TT values, the NAG varied from 3.9 in cold regions to 7.5 in warm regions. However, for C. includens, we can infer that the species can reach up to 8.8 generations in warm regions. The results of the present study are important for understanding the occurrence of R. nu and C. includens in field conditions and can help with the implications of management strategies.
Presentation and management of patients with adrenal masses: a large tertiary centre experience
Authors: Suntornlohanakul Onnicha , Mandal Sumedha , Saha Pratyusha , Saygili Emre S , Asia Miriam , Arlt Wiebke , Elhassan Yasir S , Prete Alessandro , Ronchi Cristina L
Published: October 2024

Background

Adrenal masses are found in up to 5%-7% of adults. The 2016 European guidelines on the management of adrenal incidentalomas have standardised the workup of these patients, but evidence of their impact on clinical practice is lacking.

Methods

Retrospective review of clinical presentation, radiological characteristics, and final diagnosis of a large cohort of patients with adrenal masses referred to a tertiary care centre 1998-2022. Sub-analysis compares outcomes before and after implementing the 2016 guidelines.

Results

A total of 1397 patients (55.7% women; median age 60 years [interquartile range {IQR}, 49-70]) were included. Incidental discovery was the most frequent mode of presentation (63.7%) and 30.6% of patients had masses ≥ 4 cm (median 2.9 cm [IQR, 1.9-4.7]). Unenhanced computed tomography Hounsfield units (HU) were available for 763 patients; of these, 32.9% had heterogeneous masses or >20 HU. The most common diagnoses were adrenocortical adenoma (56.0%), phaeochromocytoma (12.7%), adrenocortical carcinoma (10.6%), and metastases (5.7%). At multivariable analysis, significant predictors of malignancy included >20 HU or heterogeneous density (odds ratio [OR] 28.40), androgen excess (OR 27.67), detection during cancer surveillance (OR 11.34), size ≥ 4 cm (OR 6.11), and male sex (OR 3.06). After implementing the 2016 guidelines, the number of adrenalectomies decreased (6.1% pre-2016 vs 4.5% post-2016) and the number of patients discharged increased (4.4% pre-2016 vs 25.3% post-2016) for benign non-functioning adrenal masses.

Conclusion

Implementing the 2016 guidelines positively impacted clinical practice, reducing unnecessary surgeries and increasing the discharge rate for benign adrenal masses, thereby preserving healthcare resources and patient burden.
Life history in Caenorhabditis elegans: from molecular genetics to evolutionary ecology
Authors: Braendle Christian , Paaby Annalise
Published: October 2024

Life history is defined by traits that reflect key components of fitness, especially those relating to reproduction and survival. Research in life history seeks to unravel the relationships among these traits and understand how life history strategies evolve to maximize fitness. As such, life history research integrates the study of the genetic and developmental mechanisms underlying trait determination with the evolutionary and ecological context of Darwinian fitness. As a leading model organism for molecular and developmental genetics, Caenorhabditis elegans is unmatched in the characterization of life history-related processes, including developmental timing and plasticity, reproductive behaviors, sex determination, stress tolerance, and aging. Building on recent studies of natural populations and ecology, the combination of C. elegans’ historical research strengths with new insights into trait variation now positions it as a uniquely valuable model for life history research. In this review, we summarize the contributions of C. elegans and related species to life history and its evolution. We begin by reviewing the key characteristics of C. elegans life history, with an emphasis on its distinctive reproductive strategies and notable life cycle plasticity. Next, we explore intraspecific variation in life history traits and its underlying genetic architecture. Finally, we provide an overview of how C. elegans has guided research on major life history transitions both within the genus Caenorhabditis and across the broader phylum Nematoda. While C. elegans is relatively new to life history research, significant progress has been made by leveraging its distinctive biological traits, establishing it as a highly cross-disciplinary system for life history studies.
Centromere Landscapes Resolved from Hundreds of Human Genomes
Authors: Gao Shenghan , Zhang Yimeng , Bush Stephen J , Wang Bo , Yang Xiaofei , Ye Kai
Published: October 2024

High-fidelity (HiFi) sequencing has facilitated the assembly and analysis of the most repetitive region of the genome, the centromere. Nevertheless, our current understanding of human centromeres is based on a relatively small number of telomere-to-telomere assemblies, which have not yet captured its full diversity. In this study, we investigated the genomic diversity of human centromere higher order repeats (HORs) via both HiFi reads and haplotype-resolved assemblies from hundreds of samples drawn from ongoing pangenome-sequencing projects and reprocessed them via a novel HOR annotation pipeline, HiCAT-human. We used this wealth of data to provide a global survey of the centromeric HOR landscape; in particular, we found that 23 HORs presented significant copy number variability between populations. We detected three centromere genotypes with unbalanced population frequencies on chromosomes 5, 8, and 17. An inter-assembly comparison of HOR loci further revealed that while HOR array structures are diverse, they nevertheless tend to form a number of specific landscapes, each exhibiting different levels of HOR subunit expansion and possibly reflecting a cyclical evolutionary transition from homogeneous to nested structures and back.
Genomic selection and genetic architecture of agronomic traits during modern flowering Chinese cabbage breeding
Authors: Zhao Yahui , Li Guangguang , Zhu Zhangsheng , Hu Ming , Jiang Ding , Chen Muxi , Wang Juantao , Zhang Kexin , Zheng Yansong , Liao Yi , Chen Changming
Published: October 2024

Flowering Chinese cabbage is a type of leafy vegetable that belongs to the Brassica genus. Originally native to South China, it is now widely cultivated and consumed across the globe, particularly in Asian countries. The recent cultivation and regional expansion of flowering Chinese cabbage provides a valuable opportunity to elucidate the genomic basis underlying environmental adaptation and desired traits during a short-term artificial selection process. Here, we investigate the genetic variation, population structure, and diversity of a diverse germplasm collection of 403 flowering Chinese cabbage accessions. Our investigation seeks to elucidate the genomic basis that guides the selection of adaptability, yield, and pivotal agronomic traits. We further investigated breeding improvement associated with stem development by integrating transcriptome data. Genome-wide association analysis identified 642 loci and corresponding candidate genes associated with 11 essential agronomic traits, including plant architecture and yield. Furthermore, we uncovered a significant disparity in the allele frequency distribution of nonsynonymous mutations in these candidate genes throughout the improvement stages. Our results shed light on the genetic basis of improvement and crucial agronomic traits in flowering Chinese cabbage, offering invaluable resources for upcoming genomics-assisted breeding endeavors.
TOpClass Class 4 Perineal Crohn’s Disease: A Systematic Review and Meta-analysis of Perineal Wound Complication After Proctectomy in Crohn’s Patients
Authors: Alipouriani Ali , Erozkan Kamil , Schabl Lukas , Sancheti Himani , Sebastian Shaji , Wong Serre-Yu , Tozer Phil , Cohen Benjamin L , Holubar Stefan D
Published: October 2024

Background

Nonhealing perineal wounds have been reported to be common after proctectomy for Crohn’s disease (CD). We performed a systematic review and meta-analysis of perineal wound healing after proctectomy for CD and assessed the risk factors for nonhealing.

Methods

A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases from 2010 to 2023, and articles reporting perineal wound healing rates after proctectomy for CD were included. Data on study characteristics and proportion of healed wounds, and risk factors, were extracted. Random-effects meta-analysis was performed to estimate the pooled proportion and 95% CIs using the “meta” package in R. Heterogeneity was assessed using the I2 statistic.

Results

We identified 501 articles, of which 252 remained after de-duplication. After screening, 4 retrospective cohort studies involving 333 patients were included. Across the 4 studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%), and 70% (95% CI 60%-83%) at 12 months. Significant heterogeneity was found between studies (I2 = 86% at 6 months). Three studies examined risk factors for impaired healing after proctectomy. One study identified preoperative perineal sepsis as the only independent factor associated with impaired healing (P = .001) on multivariable analysis. In 1 study, male sex, shorter time from diversion to proctectomy, and higher preoperative C-reactive protein levels were all associated with delayed healing in univariate analysis. Another study found that close rectal dissection was associated with significantly lower healing rates than total mesorectal excision (P = .01). Prior use of tumor necrosis factor inhibitors was not associated with wound healing outcomes.

Conclusions

This meta-analysis revealed complete perineal healing in only 70% of patients 12 months after proctectomy for CD. This highlights knowledge gaps, including the identification of modifiable risk factors and methods for preventing or as rescue therapy, such as vacuum-assisted closure and flap reconstruction, for nonhealing perineal wounds after proctectomy for CD. Poor perineal wound healing outcomes are likely related to imperfectly understood underlying inflammatory dysregulation and systemically impaired wound healing in patients with CD.
Positive Ricci Curvature on Twisted Suspensions
Authors: Reiser Philipp
Published: October 2024

The twisted suspension of a manifold is obtained by surgery along the fibre of a principal circle bundle over the manifold. It generalizes the spinning operation for knots and preserves various topological properties. In this article, we show that Riemannian metrics of positive Ricci curvature can be lifted along twisted suspensions. As an application we show that the maximal symmetry rank of a closed, simply connected Riemannian manifold of positive Ricci curvature is $(n-2)$ in all dimensions $n\geq 4$. Further applications include simply connected 6-manifolds whose homology has torsion, (rational) homology spheres in all dimensions at least 4, and manifolds with prescribed third homology.
Ability Capitalism: Law’s Constitutive Role in Constructing Disability
Authors: Williams Clare
Published: October 2024

In proposing a theory of ability capitalism, this paper considers how, where, when, and why law plays a constitutive role in labour market constructions of disability. In problematising typical or mainstream accounts that see markets as ‘natural’ social orderings, the paper suggests a constitutive economic sociology of law lens that shifts beyond the embeddedness metaphor to focus on feedback loops. Such an approach can highlight the market’s legal priors as well as the ways in which economic and legal phenomena are iteratively re-co-constituted at market boundaries. It can also highlight the role of legal predistribution and processes of commodification in the construction of disability as a market rationality. Through the commodification of labour-power, the law makes visible standard employment relations whilst rendering non-standard relations, preferences, assumptions and norms—typically those reflecting disabled people’s experiences—invisible. Thus, the paper extends historical materialist accounts of the construction of disability, explaining how and why rights-based narratives are not, and cannot be the sole response to market-generated exclusions, disadvantages, and inequalities. A cornerstone of equality legislation, the reasonable adjustment, offers a case study of natural market narratives in action and how law demurs to underlying efficiency calculations that determine a disabled worker’s inclusion in labour markets. While mainstream, natural market narratives assume rights to be a function of efficiency, a constitutive lens reveals efficiency to be a function of (predistributed) rights. This indicates additional sites at which the law constructs disability disadvantage, suggesting alternative pathways to its challenge. The theoretical contributions set out here are explored in the light of the COVID-19 pandemic’s normalisation of remote working and the resulting radical inclusion gains for disabled communities. The paper queries whether shifts in background labour market norms—where and when work tasks are carried out—might adjust some of the assumptions that feed into the efficiency calculations underlying the reasonable adjustment of remote working. If so, the prefiguration of alternative market practices suggests an additional way of challenging entrenched inequalities such as the intractable disability employment and pay gaps.
A Phase 1 Study in Healthy Subjects to Evaluate the Safety and Pharmacokinetics of a Human Monoclonal Antibody (S315) Against Diphtheria Toxin
Authors: Sullivan-Bólyai John Z , Allen Larry B , Cannon Rebecca , Cohane Kenya P , Dunzo Elise , Goldwater Ronald , StCyr Kathleen , Wang Yang , Klempner Mark S
Published: October 2024

Background

Diphtheria is a recurrent threat with endemic still occurs in many parts of the world. The standard of care is horse serum–derived diphtheria antitoxin (eDAT), which is in critical short supply globally. S315 is a fully human, monoclonal immunoglobulin G1 neutralizing antibody, specific to the receptor-binding domain of diphtheria toxin. S315 is intended to be a safer, more readily available alternative to replace eDAT.

Methods

This first-in-human, randomized, double-blind, dose escalation study evaluated the safety, tolerability, and pharmacokinetics of S315 in healthy adults. Cohorts of study subjects received single intravenous infusions of S315 (480 mg, 960 mg, 1920 mg, 3840 mg, and 7680 mg) or matched placebo. Safety was assessed by standard clinical and laboratory evaluations. Serum S315 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and an in vitro diphtheria toxin neutralization assay, followed by pharmacokinetic analyses.

Results

Forty-one subjects were enrolled. S315 was safe and well tolerated. Most adverse events were mild or moderate. Peak mean serum concentrations ranged from 199 µg/mL to 2872 µg/mL (ELISA) and from 234 AU/mL to 1147 AU/mL (neutralization assay), with low variability. Mean serum half-life ranged from 12 to 27 days (ELISA) and from 17 to 22 days (neutralization assay).

Conclusions

S315 was generally safe and well tolerated by healthy subjects. Pharmacokinetic data suggest that S315 serum neutralizing activity is an order of magnitude greater than that attained by eDAT. The results of this study support continued development of S315 as a replacement for eDAT to address critical global supply issues.

Clinical Trials Registration. NCT04075175.
The evolving seascape of naval warfare: unmanned underwater vehicles and the challenges for international law
Authors: Ruhal Sanjeet
Published: October 2024

The rapid advancement of unmanned underwater vehicles (UUVs) has presented complex legal challenges in international maritime law. This article explores UUVs’ legal status and navigational rights in various maritime zones, analysing legal considerations related to innocent passage, and the potential for port access and sovereign immunity for UUVs. It contends that UUVs should be entitled to sovereign immunity when used for non-commercial government purposes. It also investigates the possibility of potential enforcement actions under the law of the sea against UUVs engaged in unauthorized activities. Additionally, it scrutinizes UUVs’ compliance with international standards, addressing security concerns and their role in international law of armed conflict. Subsequently, it touches upon the ongoing debate surrounding lethal autonomous weapons systems to provide a prospective outlook in a cursory manner. The conclusion underscores the necessity of proactive international initiatives to address the legal challenges posed by UUVs and proposes the recognition of UUVs as a distinct vessel category to ensure uniformity and predictability in their deployment.
The productivity effects of regional anchors on local firms in Swedish regions between 2007 and 2019—evidence from an expert-informed machine learning approach
Authors: Nilsson Magnus , Schubert Torben , Miörner Johan
Published: October 2024

The concept of regional anchor firms remains under-investigated. We analyse the mechanisms by which anchors affect other regional firms, disentangling effects resulting from scale/size vis-à-vis knowledge spillovers. Departing from previous idiographic research, we adopt a nomothetic research design and develop a stepwise expert-informed supervised machine learning approach to identify all anchor firms in Sweden between 2007 and 19. We find support for positive anchor effects on the productivity of dependent regional firms. This effect is driven by factors reflecting scale/size, while anchors’ R&D intensity as a measure for knowledge spillovers does not drive productivity gains.
‘The caliphate will last for thirty years’: polemic and political thought in the afterlife of a prophetic ḥadīth
Authors: Liew Han Hsien
Published: October 2024

The Prophetic ḥadīth ‘The caliphate will last for thirty years, then it will be kingship’ is one of the key proof texts for the Sunni doctrine of the ‘rightly guided caliphs’. While modern scholarship has examined its origins and transmission during the first two centuries of Islam, the political discussions that emerged from it after the crystallization of Sunnism in the third/ninth and fourth/tenth centuries have not received adequate attention. By examining ḥadīth compilations and commentaries, theological treatises, and historical chronicles, this article maps out the various ways in which Sunni Muslim scholars have engaged with the ḥadīth. It argues that in addition to employing the ḥadīth as a polemical tool against Shiʿi political claims, most Sunni scholars through the Mamluk period sought to circumvent its literal meaning out of reluctance to concede that a legitimate caliphate was limited to the first four caliphs. But in doing so, they were also hard-pressed to define what a true caliphate entailed. The ensuing discussions surrounding the ‘thirty-year ḥadīth’ often revolved around the political ideals of consensus, justice, and piety. They also shed light on the intricate connection between historiographical considerations and political thought in medieval Islam.
Statistical Predictions of Trading Strategies in Electronic Markets
Authors: Cartea Álvaro , Cohen Samuel N , Graumans Robert , Labyad Saad , Sánchez-Betancourt Leandro , van Veldhuijzen Leon
Published: October 2024

We build statistical models to describe how market participants choose the direction, price, and volume of orders. Our dataset, which spans 16 weeks for four shares traded in Euronext Amsterdam, contains all messages sent to the exchange and includes algorithm identification and member identification. We obtain reliable out-of-sample predictions and report the top features that predict direction, price, and volume of orders sent to the exchange. The coefficients from the fitted models are used to cluster trading behavior and we find that algorithms registered as Liquidity Providers exhibit the widest range of trading behavior among dealing capacities. In particular, for the most liquid share in our study, we identify three types of behavior that we call (i) directional trading, (ii) opportunistic trading, and (iii) market making, and we find that around one-third of Liquidity Providers behave as market markers.
Within the forest: a new species of Ctenomys (Rodentia: Ctenomyidae) from northwestern Patagonia
Authors: Brook Federico , González Baltazar , Tomasco Ivanna H , Verzi Diego H , Martin Gabriel M
Published: October 2024

The genus Ctenomys is represented by 68 species within at least 9 species groups. In Patagonia, there are 11 described species of Ctenomys in 3 phylogenetic species groups: (1) the sociabilis group; (2) the magellanicus group; and (3) the mendocinus group—added to this is C. maulinus, which is not clearly related to any species group. The magellanicus group is the most representative of Patagonia and includes 6 species, several unnamed forms, and has a widespread distribution from Río Negro and Neuquén provinces in the north of Patagonia to Tierra del Fuego province to the south. The magellanicus group is a highly supported clade and comprises 3 geographically defined lineages: the bidaui clade (northern clade) composed of C. bidaui, C. pulcer, and several undescribed forms; the polytypic haigi clade (central clade) comprising C. haigi, C. contrerasi, C. thalesi, C. sericeus, and Ctenomys cf. C. lentulus (sensu Teta and D’Elía 2020); and the monotypic magellanicus clade (southern clade) consisting of haplotypes assigned to C. magellanicus (including C. colburni). Ctenomys magellanicus (Magellanic Tuco-tuco) is widely distributed from southern Santa Cruz province in Argentina and central Aysén in Chile to Isla Grande de Tierra del Fuego in Argentina and Chile. Based on mitochondrial Cytochrome b DNA sequences and morphological assessment (qualitative and quantitative), we describe a new species of Ctenomys related to C. magellanicus from northwestern Chubut Province, Argentina. We provide anatomical comparisons between the new species and other species of Ctenomys from Patagonia, especially C. magellanicus, C. haigi, and C. plebiscitum. In addition, we recognize 2 groupings within C. magellanicus because of their morphometric differences, and report new localities for C. haigi and C. plebiscitum.
Tricolored Bat (Perimyotis subflavus) microsite use throughout hibernation
Authors: Brown Rebecca L , Loeb Susan C , Bridges William C , Rodriguez Shari L
Published: October 2024

White-nose syndrome (WNS) has caused dramatic population declines in several bat species, including the Tricolored Bat (Perimyotis subflavus). Several studies have documented bats using colder roosting temperatures after infection; however, this strategy may have costs such as increased freezing risks or greater predation risks and it is unknown when during hibernation bats begin to utilize these colder temperatures. Our aim was to examine Tricolored Bat roost locations in a WNS-positive site in relation to roost microclimate and other environmental conditions throughout the hibernation season. We conducted monthly censuses of tricolored bats across 2 hibernation seasons (November to March 2020 to 2021 and October to March 2021 to 2022) in a WNS-positive hibernaculum in northwestern South Carolina and recorded skin and adjacent wall temperature, tunnel section, and distance from the entrance for each bat species. We continuously measured hibernacula temperature and relative humidity during both hibernation seasons. Most bats roosted in the back part of the tunnel where temperatures were warmer and more stable, and vapor pressure deficit (VPD) and human disturbance were low. However, >20% of bats roosted in the front, where roost temperatures were significantly colder and VPD was higher but more variable; human disturbance was also higher in this section. The proportion of bats in each tunnel section did not vary among months and we did not find evidence of significant movement to the front section of the tunnel as hibernation progressed based on marked bats; however, bats in the front section roosted higher on the wall suggesting that they may be avoiding human disturbance or predators. Our results support the notion that no optimum hibernation temperature exists for tricolored bats and that high VPD and disturbance are likely important factors driving microsite use. Protection of Tricolored Bat hibernacula that offer a range of microclimates or a network of sites in close proximity that offer different microclimates may be helpful for recovery of this species.
Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis
Authors: Karlsson Per , Fyles Anthony , Chang S Laura , Arrick Bradley , Baehner Frederick L , Malmström Per , Fernö Mårtin , Holmberg Erik , Sjöström Martin , Liu Fei-Fei , Cameron David A , Williams Linda J , Bartlett John M S , Dunlop Joanna , Caldwell Jacqueline , Loane Joseph F , Mallon Elizabeth , Piper Tammy , Kunkler Ian , Feng Felix Y , Speers Corey W , Pierce Lori J , Bennett John P , Taylor Karen J
Published: October 2024

Background

There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates.

Methods

An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor–positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT.

Results

A total of 429 (69%) patients’ tumors had a high POLAR score, and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of locoregional recurrence (20%, 95% confidence interval [CI] = 15% to 26%, vs 5%, [CI] 2% to 11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT = 0.37, 95% CI = 0.23 to 0.60; P < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR = 0.92, 95% CI = 0.42 to 2.02; P = .832). The test for interaction between RT and POLAR was statistically significant (P = .022).

Conclusions

POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from RT in selected patients. Patients aged 50 years and older with estrogen receptor–positive and HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.
Sexual and reproductive health guidelines for Black girls: a call to action
Authors: Crooks Natasha , Sanker-Panchal Kimberly , Okafor Annette , Irving Di’Avionne , Singer Randi , Donenberg Geri
Published: October 2024

Objective

Black girls disproportionately face adverse sexual and reproductive health outcomes in their lifetime. In healthcare, Black girls experience racism and misogyny, which manifest as a combination of discriminatory practices and biases that result in their symptoms being dismissed or neglected, their voices silenced, inadequate treatment, and higher mortality rates. Pediatric providers are in an ideal position to influence, advocate, and strengthen Black girls’ sexual and reproductive health. The purpose of this topical review is to discuss current guidelines and provide recommendations to improve pediatric sexual and reproductive care for Black girls.

Methods

We examine current pediatric guidelines and recommendations for adolescent sexual and reproductive health.

Results

Current guidelines recommended by organizations and professional societies such as the Centers for Disease Control and Prevention, World Health Organization, Society of Adolescent Health Medicine, and American Academy of Pediatrics are inconsistent and insufficient for the unique needs of Black girls.

Conclusions

We offer three recommendations for pediatric providers to ensure the optimal sexual and reproductive health care for Black girls. These provider recommendations will aid in the protection of Black girls’ sexual and reproductive health.
Mature cystic teratoma originating in the broad ligament: a case report
Authors: Meng Tingzhu , Lu Xueliang , Teng Dan , Li Xin , Shi Jie
Published: October 2024

Teratomas are germ cell tumors, commonly affecting ovaries. Teratomas rarely affect extragonadal tissues. Few cases of teratomas occurring in extragonadal tissues have been reported in the past. However, no studies have reported cases of primary teratomas occurring in the broad ligament. In this study, we report a case of a sexually inactive young woman with a 3-day history of lower abdominal pain. B-ultrasound examination revealed an abnormal strong echogenicity mass in the left adnexal area. An exploratory laparotomy was performed on her. The surgery revealed normal size and appearance of both ovaries and uterus. However, a cyst was observed in the left broad ligament, which was diagnosed as benign mature teratoma based on pathology. In this study, we report a rare case of broad ligament teratoma. The clinical data enrich our understanding of teratomas and provide a reference for further studies.
Molecular epidemiology of seborrheic dermatitis/dandruff associated Malassezia species from northern India
Authors: Honnavar Prasanna , Chakrabarti Arunaloke , Joseph Jillwin , Thakur Sheetal , Dogra Sunil , Lakshmi P V M , Rudramurthy Shivaprakash M
Published: October 2024

Malassezia is a commensal that sometimes becomes pathogenic under the influence of diverse factors. Several species of Malassezia are difficult to culture, making traditional methods of identification challenging. The problem with molecular typing of Malassezia in association with seborrheic dermatitis/dandruff (SD/D) arises due to the unavailability of these fastidious yeast cultures. The aim of the study was to investigate the association between fluorescent amplified fragment length polymorphism (FAFLP) genotypes, disease state (SD/D), and the geographic distribution of M. globosa, M. restricta, and M. arunalokei. In total, 154 isolates representing M. globosa (n = 85), M. restricta (n = 55), and M. arunalokei (n = 14) from lesional/non-lesional areas of SD/D patients and healthy controls residing in the rural (n = 77) and urban (n = 77) areas of northern India were included. A strategy based on the FAFLP methodology was developed using two endonuclease enzymes (EcoRI and HindIII). M. globosa, M. restricta, and M. arunalokei formed 11, 3, and 2 FAFLP clusters, respectively. Disease-specific strains of M. restricta and M. arunalokei preferentially tend to cause SD/D. M. restricta and M. arunalokei showed less genetic variation. M.globosa showed higher genetic diversity. FAFLP clusters revealed the existence of geographically specific strains in M. restricta, M. arunalokei, and M. globosa. Our findings suggest that certain Malassezia strains are not only disease-specific but also geographically distinct.
Sequential formation of supermassive stars and heavy seed BHs through the interplay of cosmological cold accretion and stellar radiative feedback
Authors: Kiyuna Masaki , Hosokawa Takashi , Chon Sunmyon
Published: October 2024

Supermassive stars (SMSs) and heavy seed black holes, as their remnants, are promising candidates for supermassive black hole (SMBH) progenitors, especially for ones observed in the early universe $z\simeq 8.5-10$ by recent JWST observations. Expected cradles of SMSs are the atomic cooling haloes ($M_{\rm halo}\simeq 10^7\ \mathrm{M}_{\odot }$), where ‘cold accretion’ emerges and possibly forms SMSs. We perform a suit of cosmological radiation hydrodynamics simulations and investigate star formation after the emergence of cold accretion, solving radiative feedback from stars inside the halo. We follow the mass growth of the protostars for $\sim 3\ \mathrm{Myr}$, resolving the gas inflow down to $\sim 0.1\ \mathrm{pc}$ scales. We discover that, after cold accretion emerges, multiple SMSs of $m_{\star }\gtrsim 10^5\ \mathrm{M}_{\odot }$ form at the halo centre with the accretion rates maintained at $\dot{m}_{\star }\simeq 0.04\ \mathrm{M}_\odot \mathrm{yr}^{-1}$ for $\lesssim 3\ \mathrm{Myr}$. Cold accretion supplies gas at a rate of $\dot{M}_{\rm gas}\gtrsim 0.01-0.1\ \mathrm{M}_\odot \mathrm{yr}^{-1}$ from outside the halo virial radius to the central gas disc. Gravitational torques from spiral arms transport gas further inwards, which feeds the SMSs. Radiative feedback from stars suppresses $\mathrm{H}_2$ cooling and disc fragmentation, while photoevaporation is prevented by a dense envelope, which attenuates ionizing radiation. Our results suggest that cold accretion can bring efficient BH mass growth after seed formation in the later universe. Moreover, cold accretion and gas migration inside the central disc increase the mass concentration and provide a promising formation site for the extremely compact stellar clusters observed by JWST.